17910 Federal Register /Vol. 62, No. 70/Friday, April 11 ... Federal Register/Vol. 62, No. 70/Friday, April 11, 1997/Rules and Regulations ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts

17910 Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

ENVIRONMENTAL PROTECTIONAGENCY

40 CFR Parts 700, 720, 721, 723, and725

[OPPTS–00049C; FRL–5577–2]

RIN 2070-AB61

Microbial Products of Biotechnology;Final Regulation Under the ToxicSubstances Control Act

AGENCY: Environmental ProtectionAgency (EPA).ACTION: Final rule.

SUMMARY: EPA is promulgating this finalrule under section 5 of the ToxicSubstances Control Act (TSCA), 15U.S.C 2604, to establish notificationprocedures for review of certain newmicroorganisms before they areintroduced into commerce. ‘‘New’’microorganisms are those formed bydeliberate combinations of geneticmaterial from organisms classified indifferent taxonomic genera. This reviewprocess is designed to preventunreasonable risk of injury to humanhealth and the environment withoutimposing unnecessary regulatoryburdens on the biotechnology industry.This final rule describes notificationprocedures and the microorganisms thatwould be exempt from notification.DATES: This rule will become effectiveJune 10, 1997. In accordance with 40CFR 23.5, this rule shall be promulgatedfor purposes of judicial review at 1 p.m.eastern daylight savings time on April27, 1997.FOR FURTHER INFORMATION CONTACT: Forgeneral information including copies ofthis document and related materials:Susan Hazen, Director, EnvironmentalAssistance Division (7408), Office of

Pollution Prevention and Toxics,Environmental Protection Agency, 401M St., SW., Washington, DC 20460,Telephone: (202-554-1404), TDD: (202-554-0551), e-mail address: [email protected].

For technical information regardingthis document: David Giamporcaro,Office of Pollution Prevention andToxics (7405), Environmental ProtectionAgency, 401 M St., SW., Washington,DC 20460. Telephone: (202-260-6362).SUPPLEMENTARY INFORMATION:Electronic Availability: Electroniccopies of this document and varioussupport documents are available fromthe EPA home page at theEnvironmental Sub-Set entry for thisdocument under ‘‘Regulations’’ (http://www.epa.gov/fedrgstr/). The final rulemay also be accessed at the Office ofPollution Prevention and ToxicsBiotechnology home page at http://www.epa.gov/opptintr/biotech/. Fax-On-Demand: Using a faxphone call 202–401–0527 and select item 3100 for anindex of available material andcorresponding item numbers related tothis document.

This rule establishes procedures forthe premanufacture review of certainnew microbial products ofbiotechnology that are comparable tothose for traditional chemicalsubstances but are tailored to addressthe specific characteristics of thesemicroorganisms. EPA published its finalTSCA section 5 premanufacturenotification (PMN) rule (40 CFR part720) on May 13, 1983 (48 FR 21722) andsubsequently amended certain parts ofthe rule on September 13, 1983 (48 FR41132), April 22, 1986 (51 FR 15096),and March 29, 1995 (60 FR 16298)(FRL–4921–8). In 1984, EPA discussedhow the PMN rule could be applied to

microorganisms in ‘‘Proposed PolicyRegarding Certain Microbial Products’’which was published as part of theFederal ‘‘Proposal for a CoordinatedFramework for Regulation ofBiotechnology; Notice’’ (‘‘1984 ProposedPolicy Statement’’) which waspublished by the Office of Science andTechnology Policy (OSTP) on December31, 1984 (49 FR 50856). In 1986, EPAstated how the PMN rule would beapplied to microorganisms in the‘‘Statement of Policy: MicrobialProducts Subject to the FederalInsecticide, Fungicide, and RodenticideAct and Toxic Substances Control Act’’(‘‘1986 Policy Statement’’), which waspublished as part of the Federal‘‘Coordinated Framework for Regulationof Biotechnology; Announcement ofPolicy and Notice for Public Comment’’which was published by OSTP on June26, 1986 (51 FR 23302). On September1, 1994, EPA published the proposedrule, ‘‘Microbial Products ofBiotechnology; Proposed RegulationUnder the Toxic Substances ControlAct,’’ which would, when finalized,fully implement its program formicroorganisms under TSCA section 5(59 FR 45526) (FRL–4778–4). Whilegeneral background information ispresented here, readers should alsoconsult the preambles of thosedocuments for further information onthe development of the biotechnologyprogram under TSCA section 5.Regulated Entities. Potentially regulatedentities are persons conductingcommercial research and developmentactivities or persons manufacturing,importing, or processing for commercialpurposes intergeneric microorganismsused for a TSCA purpose. Regulatedcategories and entities include:

Category Examples of Regulated Entities

Biotechnology research and development activities involving commer-cial funds

Persons conducting commercial research using intergeneric microorga-nisms for biofertilizers; biosensors; biotechnology reagents; commod-ity or specialty chemical production; energy applications; waste treat-ment or pollutant degradation; and other TSCA subject uses.

Commercial biotechnology products Persons manufacturing, importing or processing products for commer-cial purposes intergeneric microorganisms for biofertilizers; biosen-sors; biotechnology reagents; commodity or specialty chemical pro-duction; energy applications; waste treatment or pollutant degrada-tion; and other TSCA subject uses.

This table is not intended to beexhaustive, but rather provides a guidefor readers regarding entities likely to beregulated by this action. This table liststhe types of entities that EPA is nowaware could potentially be regulated by

this action. Other types of entities notlisted in the table could also beregulated. To determine whether yourintergeneric microorganism is regulatedby this action, you should carefullyexamine the list of substances excluded

by TSCA section (3)(2)(B), and therequirements for ‘‘persons who mustreport’’ in § 725.205 of the regulatorytext for research and developmentactivities using intergenericmicroorganisms and § 725.105 of the

17911Federal Register / Vol. 62, No. 70 / Friday, April 11, 1997 / Rules and Regulations

regulatory text for manufacturing,importing, and processing intergenericmicroorganisms. If you have questionsregarding the applicability of this actionto a particular entity, consult the personlisted in the preceding FOR FURTHERINFORMATION CONTACT UNIT.

I. Background

A. Statutory Authority

TSCA section 5(a)(1) requires thatpersons notify EPA at least 90 daysbefore they manufacture or import forcommercial purposes a ‘‘new’’ chemicalsubstance or manufacture, import, orprocess a chemical substance for a‘‘significant new use.’’ TSCA defines‘‘chemical substance’’ broadly and interms which cover microorganisms aswell as traditional chemicals. Therefore,for the purposes of TSCA, a ‘‘newmicroorganism,’’ like a ‘‘new chemicalsubstance,’’ is one that is not listed onthe TSCA Chemical SubstancesInventory compiled under TSCA section8(b). TSCA section 5(h)(3) exempts themanufacture or importation of smallquantities of chemical substancesproduced solely for research anddevelopment (R&D) from the section 5notification requirements if themanufacturer or importer notifiespersons engaged in R&D of any healthrisks that the company or EPA hasreason to believe may be associated withthe chemical substance. TSCA section5(h)(3) authorizes EPA to define by rulewhat constitutes small quantities and toprescribe the form and manner of risknotification. TSCA section 5(h)(4)authorizes EPA, upon application andby rule, to exempt the manufacturer orimporter of any new chemical substancefrom part or all of the provisions ofsection 5, if EPA determines that themanufacture, processing, distribution incommerce, use, or disposal of the newchemical substance will not present anunreasonable risk of injury to humanhealth or the environment.

B. History

This rule implements EPA’s programfor oversight of microorganisms, inaccordance with the 1986 PolicyStatement. Since its publication, EPAhas been operating its biotechnologyprogram under the 1986 PolicyStatement. Prior to the 1986 PolicyStatement, EPA issued the 1984Proposed Policy Statement. Subsequentto the 1986 Policy Statement, EPAissued a notice, entitled ‘‘Biotechnology;Request for Comment on RegulatoryApproach’’ on February 15, 1989 (54 FR7027), in order to solicit comments onthe direction of EPA’s biotechnologyprogram under TSCA. Comments on the

1984 and 1986 documents and theFebruary 15, 1989 Federal Registernotice are addressed, as appropriate, inthis preamble.

On September 7, 1990, EPA conveneda subcommittee of its BiotechnologyScience Advisory Committee(Subcommittee on Implementation ofScope) to comment on topics associatedwith the proposed rule. EPA againconvened a subcommittee, theSubcommittee on the ProposedBiotechnology Rule under TSCA, whichmet on July 22, 1991. Advice from bothof these subcommittees wasincorporated as appropriate in thepreamble to the proposed rules, andsummaries of subcommitteedeliberations were placed in the docketfor this rulemaking. On September 1,1994, EPA published the proposed rules‘‘Microbial Products of Biotechnology;Proposed Regulation Under the ToxicSubstances Control Act’’ (59 FR 45526).The final rule announced today isintended to describe implementation ofEPA’s program for regulation ofmicroorganisms under TSCA.

II. Summary of Proposed RuleEPA proposed to establish a new part

725 of Title 40 of the Code of FederalRegulations (CFR). EPA believed thatconsolidating all requirements andprocedures applicable to newmicroorganisms into one part of the CFRwas appropriate and justified because ofthe specific characteristics ofmicroorganisms. The consolidation wasexpected to benefit the public byproviding greater focus and enhancedclarity. Part 725 is devoted exclusivelyto the review of microorganisms undersection 5 of TSCA and is divided intoeight subparts. Subparts A, B, and Cconsolidated provisions primarilyadapted from parts 720 and 721.Subpart A, which includes definitionsthat are applicable throughout part 725,described general provisions andapplicability. Subpart B describedadministrative procedures that areapplicable to all submissions under part725. Subpart C described confidentialityprovisions that are applicable to allsubmissions under part 725.

Subpart D, which combined thegeneral PMN and significant new usenotice (SNUN) requirements adaptedfrom parts 720 and 721, described thereporting requirements and reviewprocess pertaining to microbialcommercial activity notices (MCANs).Subparts E, F, and G described thereporting requirements and reviewprocesses for applications forexemptions from full MCAN reporting.Subpart E, which was almost entirelynew, described a new reporting process

using the TSCA experimental releaseapplication (TERA) which wasdeveloped for reporting research anddevelopment (R&D) activities involvingrelease to the environment. Subpart Ealso described who would be eligible tosubmit a TERA or receive a TERA listexemption, and the criteria that must bemet to receive an exemption from EPAreview for certain types of R&Dactivities. Subpart F, which was anadaptation of § 720.38, described therequirements for a test marketingexemption for microorganisms. SubpartG, which was entirely new, describedthe criteria that must be met in order toqualify for Tier I or Tier II exemptionsfor certain microorganisms in generalcommercial use. Subpart L, which wasadapted from part 721, describedadditional procedures for reportingsignificant new uses of microorganisms.Although significant new use rules werenot being proposed, it was intended thatsubpart M would list microorganismsand specific significant new uses whenthey were promulgated.

In addition, EPA proposed to amendexisting regulations regarding thecollection of fees from submitters ofnotices under section 5 of TSCA (40CFR part 700), to reflect the fee structurefor the notices and applications thathave been developed by these proposedrules. Additional amendments to parts720, 721, and 723 were proposed toconsolidate TSCA section 5 review ofmicroorganisms into part 725.

III. Summary of Final Rule

This final rule establishes allreporting requirements under section 5of TSCA for manufacturers andprocessors of microorganisms subject toTSCA jurisdiction, that aremanufactured for commercial purposes,including research and development forcommercial purposes. The ruleestablishes a number of mechanisms forreporting to EPA, including a number ofspecific exemptions. Most of theexemptions create an alternativemechanism for reporting to EPA thatreduces the amount of information to bereported. Certain of the research anddevelopment exemptions establish theconditions under which no reportingwould be required.

Manufacturers are required to reportcertain information to EPA 90 daysbefore commencing the manufacture ofintergeneric microorganisms that are notlisted on the TSCA Inventory. The ruleestablishes the mechanism for reportingthis information. The rule also defines‘‘small quantities for research anddevelopment’’ for microorganisms; theeffect of which is to require section 5


reporting for certain research anddevelopment activities.

Any manufacturer, importer, orprocessor of a living microorganism,who is required to report under section5 of TSCA must file a MicrobialCommercial Activity Notice (MCAN)with EPA, unless the activity is eligiblefor one of the specific exemptions. Thegeneral procedures for filing MCANs aredescribed in subpart D of part 725 of theregulatory text.

TSCA section 5 only applies tomicroorganisms that are manufactured,imported, or processed for commercialpurposes. EPA has defined manufactureor process for commercial purposes as‘‘manufacture or process for purposes ofobtaining an immediate or eventualcommercial advantage.’’ Whether anactivity has an immediate or eventualcommercial advantage is determined byindicia of commercial intent. Researchand development activities are forcommercial purposes, and thus subjectto reporting, if tests are directly funded,in whole or in part by a commercialentity, when the researcher considersthere to be an immediate or eventualcommercial advantage. In addition, allpost R&D activities are consideredmanufacture or processing for acommercial purpose.

EPA has established two exemptionsfor new microorganisms, after the R&Ddevelopment stage, which are beingmanufactured for introduction intocommerce. In the Tier I exemption, ifthree criteria are met, manufacturers areonly required to notify EPA that they aremanufacturing a new microorganismthat qualifies for this exemption 10 daysbefore commencing manufacture, and tokeep certain records. A manufacturer isnot required to wait for EPA approvalbefore commencing manufacture. Toqualify for the Tier I exemption, amanufacturer must use one of the listedrecipient organisms and mustimplement specific physicalcontainment and control technologies.In addition, the DNA introduced intothe recipient microorganism must bewell-characterized, limited in size,poorly mobilizable, and free of certainsequences.

A manufacturer, who otherwise meetsthe conditions of the Tier I exemption,may modify the specified containmentrestrictions, but must submit a Tier IIexemption notice. The Tier II exemptionrequires manufacturers to submit anabbreviated notice describing themodified containment, and provides fora 45–day period, during which EPAwould review the proposedcontainment. The manufacturer may notproceed under this exemption until EPAapproves the exemption.

Rather than submitting a MCANduring research and development,manufacturers may qualify for one ofseveral exemptions, or may choose tosubmit to EPA a TSCA ExperimentalRelease Application.

If a manufacturer is conductingresearch and development activitiessolely within a contained structure, theresearch may qualify for one of twoexemptions. For contained researchconducted by researchers who arerequired to comply with the NIHguidelines, EPA has established acomplete exemption from EPA reviewand reporting and recordkeepingrequirements. For all othermanufacturers conducting containedresearch and development activitiesEPA has established a more limitedexemption. The exemption specifiesfactors which the technically qualifiedindividual must consider in selectingthe appropriate containment. Themanufacturer is required to keep recordsto document compliance with thecontainment requirements, but isexempt from all other TSCA section 5reporting requirements. See Unit V.C.5.of this preamble.

For researchers conducting small-scale field tests with Bradyrhizobiumjaponicum and Rhizobium meliloti, thefinal rule creates an exemption fromEPA review, providing certainconditions are met. The field testingmust occur on no more than 10terrestrial acres; the introduced geneticmaterial must comply with certainrestrictions, and appropriatecontainment measures must be selectedto limit dissemination.

If a manufacturer does not meet therequirements for one of the exemptionsdiscussed above, he or she may submita TERA. The TERA is essentially anabbreviated MCAN submission forindividual tests. EPA’s review period isreduced to 60 days, although EPA mayextend the period for good cause. EPAmust approve the test before theresearcher may proceed, even if the 60-day period expires. EPA’s approval islimited to the conditions outlined in theTERA notice or approval.

In addition, a manufacturer maysubmit a MCAN for any R&D activity.However, EPA expects that mostresearchers will instead choose tosubmit a TERA. In addition to the longerreview period, EPA expects that,because of the limited information at theR&D stage, the Agency would likelyissue a section 5(e) order to imposeconditions to address the uncertainties,which would need to be modified eachtime the manufacturer wanted to varythe terms of the order.

IV. Summary of Major Changes in FinalRule

The final rule adopts the provisions ofthe proposed rule with few revisions.EPA is adding to 40 CFR a new part 725,which applies TSCA section 5requirements specifically tomicroorganisms. Subpart A of part 725contains general provisions andapplicability. The final rule retains fromthe proposal the definition of ‘‘newmicroorganisms’’ that are subject toTSCA section 5 reporting. ‘‘Newmicroorganisms’’ are intergenericmicroorganisms that are not alreadylisted on the TSCA Inventory.‘‘Intergeneric microorganism’’ is definedat § 725.3. EPA has made some minorrevisions to definitions in § 725.3related to scope of oversight.

Subpart B of part 725 containsadministrative procedures that havebeen adapted with little change fromprovisions in 40 CFR parts 720 and 721.The provisions in the final rule havebeen adopted with minor changes fromthose proposed in 1994.

Subpart C of part 725 containsrequirements for claiming confidentialbusiness information (CBI). Theserequirements, which were adapted fromprovisions in part 720, have not beenchanged from the proposal, with theexception of the requirement relating toCBI claims in the TERA and other minorchanges. Section 725.94(a)(2) has beenmodified to eliminate the proposedrequirement for upfront substantiationof CBI claims in the TERA submission.

Subpart D establishes the reportingprogram for new microorganismsmanufactured or imported fordistribution into commerce and requiressubmission of a MCAN 90 days prior toinitiating manufacture or import of thenew microorganism. This subpartcodifies the requirements forinformation to be included in theMCAN at §§ 725.155 and 725.160 and ispromulgated with minor changes fromthe proposal.

Subpart E establishes the exemptionsfrom full MCAN reporting for R&Dactivities. At § 725.205(b), EPA defines‘‘commercial purposes’’ for R&Dactivities to include all R&D directlyfunded in whole or in part by acommercial entity, and all R&Dactivities, regardless of funding source,for which the researcher intends topursue immediate or eventualcommercial advantage.

Subpart E establishes, at § 725.232, acomplete exemption from TSCA section5 obligations for certain R&D activitiesconducted in contained structures andsubject to regulation by another Federalagency. EPA establishes another


exemption from reporting requirementsfor R&D activities in containedstructures which meet the requirementsof §§ 725.234 and 725.235.

Subpart E also establishes at§§ 725.238 and 725.239 the TERAexemption process for R&D activities,primarily those involving intentionalenvironmental release. EPA has revisedrequirements in § 725.239 to limit theantibiotic resistance markers that maybe used in the microorganisms eligiblefor the TERA exemption.

Subpart E codifies the requirementsfor information that must be included inthe TERA at §§ 725.255 and 725.260,and is promulgated with minor changesfrom the proposal. EPA has revised therequirements at §§ 725.238(b)(3)(ii) and725.255(e)(1)(vi) with regard tonotification of State and/or localauthorities.

Subpart F contains the requirementsfor exemptions for test marketingactivities. These requirements have beenadapted, with little change, fromprovisions in part 720 and have onlyminor changes from the 1994 proposedrule.

Subpart G establishes an exemptionfrom MCAN reporting for certainmicroorganisms and placesrequirements on the recipientmicroorganism, the introduced geneticmaterial, and the physical containment.Some changes have been made torequirements for specific eligibilitycriteria since the proposal. Section725.421 contains the requirements forthe introduced genetic material. Minorchanges have been made to § 725.421(d)to clarify the functional portions oftoxin-encoding sequences that cannot beincluded in the introduced geneticmaterial. Section 725.422 contains therequirements for physical containment.Section 725.422(b) has been revised torequire controlled access to thestructure. Section 725.422(e) has beenmodified to require submitters todocument the effectiveness of thefeatures used to minimize the microbialconcentrations in aerosols and exhaustgases released from the structure.

Subpart L establishes procedures forreporting significant new uses ofmicroorganisms. These requirementshave been adapted, with little change,from provisions in part 721 and haveonly minor changes since they wereproposed in 1994.

Subpart M is reserved forrequirements for significant new usesfor specific microorganisms; however,none are being promulgated in this rule.

The regulatory text also amendsexisting regulations regarding thecollection of fees from submitters ofnotices under section 5 of TSCA (40

CFR part 700), to reflect the fee structurefor the notices and applications thathave been developed by this rule.Additional amendments to parts 720,721, and 723 consolidate TSCA section5 review of microorganisms into part725.

V. Discussion of Final Rule andResponse to Comments

In response to the proposed rule, EPAreceived 40 letters from the publicduring the comment period. Commentswere received from industry, academia,professional and trade associations,government agencies, public interestgroups, and individuals. While allcommenters raised issues about specificaspects of the rule, several commentersindicated that they generally supportedit. Some commenters had majorconcerns about the rule and suggestedmodifications that would havesignificantly changed the nature of therule as it was proposed. EPA reviewedand considered all comments receivedon the proposed rule and prepareddetailed responses to the comments.Copies of all comments received alongwith EPA’s ‘‘Summary of PublicComments and EPA’s Response’’ areavailable in the public docket for thisrulemaking. A discussion of the finalrule, including a summary of significantcomments and EPA’s responses follows.

A. Coverage of Microorganisms underTSCA

EPA continues to believe that theTSCA section 3(2) definition of‘‘chemical substance’’ gives EPAauthority to review microorganismsunder TSCA. EPA is retaining itsinterpretation of ‘‘new’’ microorganismsas stated in the 1986 statement policyand the proposed rule. Under thatinterpretation, microorganisms resultingfrom deliberate combinations of geneticmaterial from organisms classified indifferent genera constitute ‘‘new’’microorganisms subject to section 5reporting requirements. EPA terms suchmicroorganisms intergeneric. For thepurposes of this rule, EPA will treatmobile genetic elements, those elementsof genetic material that have the abilityto move genetic material within andbetween organisms, as follows: The term‘‘intergeneric microorganism’’ includesa microorganism which contains amobile genetic element which wasoriginally isolated from amicroorganism in a genus different fromthe recipient microorganism. Excludedfrom the definition of ‘‘intergenericmicroorganism’’ are microorganismswhich contain introduced geneticmaterial consisting solely of well-characterized, non-coding regulatory

regions from organisms in anothergenus. These terms are defined at§ 725.3.

1. Intergeneric scope. EPA hasdecided to define ‘‘newmicroorganisms’’ as thosemicroorganisms resulting from thedeliberate combination of geneticmaterial originally isolated fromorganisms classified in different generabecause of the degree of humanintervention involved, the significantlikelihood of creating new combinationsof traits, and the greater uncertaintyregarding the effects of suchmicroorganisms on human health andthe environment. This approach, basedon a taxonomic standard, both identifiesa group of microorganisms whosebehavior in the environment posessignificant uncertainty, which thereforewarrant regulatory review under TSCAsection 5, and provides a way ofdefining ‘‘new’’ microorganisms underTSCA section 5.

TSCA section 5 requires allmanufacturers of new chemicalsubstances to submit information toEPA 90 days before commencingcommercial manufacture, to permit EPAto examine whether they may present anunreasonable risk of injury to health andthe environment. As discussed at greaterlength in Unit II. of the Response toComments Document, the rationale forthe requirement was to have EPAattempt to resolve the uncertaintiessurrounding the class of new chemicalsubstances--specifically, whether theywere likely to cause unreasonable risksbefore they were introduced into theenvironment.

When considering the variousapproaches that could be used to definea ‘‘new’’ microorganism for TSCApurposes, one important factor EPA tookinto account was the regulatoryprecedents established in compiling theinventory of existing chemicalsubstances under section 8(b) of TSCA.Any chemical substance not on theInventory is ‘‘new’’ under section 5(a) ofTSCA and is therefore subject topremanufacture reporting. Naturallyoccurring substances and substancesderived from nature with limited humanintervention are considered to beautomatically included on theInventory, and thus are not ‘‘new.’’ EPAconcluded that microorganisms foundin nature could also be considered notnew because they occur naturally,without human intervention, andtherefore, ‘‘naturally occurringmicroorganisms’’ are automaticallylisted on the TSCA Inventory, and arenot subject to this rule.

Second, EPA considered that modernbiotechnology techniques permit genetic


material to be intentionally movedbetween and combined in disparateorganisms. On occasion the geneticmaterial combined would not be geneticmaterial expressing traits possessed byboth the donors of the genetic materialand the recipients. In other words, thegenetic material encoding these traitswould not be commonly shared betweenthe donor and recipient organisms.Microorganisms formed from geneticmaterial not commonly shared bydonors and recipients would have asignificantly higher probability ofexhibiting new traits or newcombinations of traits compared tonaturally occurring microorganisms.Some of the microorganisms developedthrough modern biotechnology mayexhibit new or altered traits affecting,for example, their survivability, hostrange, substrate utilization,competitiveness with other organisms,or protein or polysaccharide production.The behavior of organisms expressing anew trait or new combinations of traitsis thus less predictable and theirprobable behavior less certain. EPAchose to focus particular regulatoryattention on microorganisms that have ahigher potential for exhibiting a newtrait or combinations of traits.

EPA decided that a standard based onthe taxonomic taxon of genus defined aclass of sufficiently high probability ofexhibiting a new trait or newcombinations of traits to warrant review.Taxonomy is a system of orderlyclassification of organisms according totheir presumed natural relationships.Since the organisms contributinggenetic material to intergenericmicroorganisms are, in general, moredistantly related than themicroorganisms contributing geneticmaterial to intrageneric microorganisms(and thus less likely to have traits incommon), intergeneric microorganismshave a higher probability of exhibitinga new trait or new combinations of traitsand their behavior is thereforesignificantly less predictable thanintrageneric microorganisms.

A scope based on a taxonomicstandard such as intergeneric hascertain advantages. A taxonomy basedscope relates directly to the potential ofthe resulting new microorganism todisplay a new trait or new combinationsof traits, since organisms that share aclose evolutionary ancestry are morelikely to have traits in common thanthose that are more distantly related. Inaddition, the taxonomy standard isindependent of the technology used tocreate the microorganism. A number oftechniques may be used to produceintergeneric microorganisms. Anyintergeneric microorganisms created by

techniques developed in the futurewould also be subject to this final rule.

Taxonomy reflects current scientificobservations about phenotypic, and to acertain extent, genotypic, differencesbetween organisms. Although subject toperiodic revision within the scientificcommunity, taxonomy is a commonlanguage used by scientists. Basing thestandard for interpreting ‘‘new’’ formicroorganisms on an existing systemfor categorizing organisms obviates theneed to create another system fordetermining if a microorganism issubject to reporting under TSCA section5. Taxonomy is understood by theregulated community and its useimposes little, if any, additional burdento determine whether a microorganismis new.

For circumscribing what is new forTSCA section 5, microbial taxonomy isa relatively clear and objective criterionfor scope of oversight and thus providesclarity for both the regulated communityand the Agency for enforcementpurposes. Taxonomic designationsprovide a widely available standard andpoint of reference. It is reasonable toexpect a manufacturer to use thetaxonomic literature and/or taxonomiststo determine currently accepted namesof organisms they wish to utilize. Oncea manufacturer knows the genus of amicroorganism, he or she can readilydetermine whether a microorganism isintergeneric and thus whether it is‘‘new’’ within the section 5 context.

EPA recognizes that taxonomy,particularly microbial taxonomy, issubject to change and that newinformation concerning organisms’properties and relationships could altertaxonomic designations. In recent years,new tools have become available tomicrobial taxonomists which haveallowed them to clarify phylogenicrelationships among microorganisms.Some microbial genera are highlydefined and consist of closely relatedmembers which are likely to sharecommon information in their geneticmaterial. However, other microbialgenera may consist of members moreclosely related to microorganismsclassified in other genera than to eachother. While reorganizations couldresult in changes in taxonomicdesignations for some microorganismsin the short term, it should result ingreater stability in the various taxa inthe long term. EPA anticipates that asreclassifications occur in the scientificcommunity, the intergeneric standardwill become a better reflection of theprobability of new traits or newcombination of traits resulting from thedeliberate combining of geneticmaterial. However, even under current

taxonomic designations, gene exchangeis generally less likely to occur naturallyamong members of different microbialgenera than among members of the samegenus, and this suggests a new trait ornew combinations of traits are morelikely to occur when genetic materialfrom microorganisms in differenttaxonomic genera are combined.Moreover, the probability of a new traitor new combination of traits occurringincreases when the organismscombining genetic material are moredistantly related; e.g., even among themicroorganisms, bacteria classified indifferent genera are more likely to sharecommon traits than bacteria and fungi,and bacteria classified in differentgenera are more likely to share traitsthan bacteria with plants and animals.While taxonomic reorganizations couldaffect the status, for TSCA purposes, ofsome microorganisms formed bycombining genetic material from somerelatively closely relatedmicroorganisms, the TSCA section 5status of microorganisms formed bycombining genetic material of moredistantly related organisms is unlikelyto be affected. These considerationssuggest that while taxonomy may not bea perfect standard, its use is likely tocapture for review thosemicroorganisms with a higherprobability of displaying new traits ornew combinations of traits. EPAdiscusses in other parts of this preambleand in the Response to Commentsdocument how it will accommodatewithin its regulatory structurereclassifications of microorganisms intonew or different taxa.

EPA believes that on whole, theintergeneric definition generallycaptures for review microorganismswith a higher potential for displaying anew trait or new combination of traits.While this approach does have somedrawbacks, EPA believes that itsprocedures are sufficiently flexible toaccommodate these drawbacks, and thatthe advantages to using the intergenericdefinition outweigh the disadvantages.

EPA includes the phrase ‘‘originallyisolated’’ in the definition ofintergeneric to clarify that geneticmaterial belongs to the genus fromwhich it was originally isolated ororiginally observed. For example, if asequence of genetic material wasoriginally introduced frommicroorganism A into microorganism B,subsequently reisolated frommicroorganism B to be combined inmicroorganism C, the manufacturer ordeveloper must consider the genera ofmicroorganisms A and C in determiningthe status of the microorganism


resulting from the second combiningevent described above.

2. Mobile genetic elements. In theproposal (59 FR 45528), EPA alsodiscussed mobile genetic elements(MGEs) and how it would apply its MGEpolicy to the interpretation of ‘‘new’’microorganisms for the purposes ofTSCA section 5. EPA has retained thepolicy and incorporated it in itsdefinition of intergenericmicroorganism. MGEs, which areelements of genetic material such asplasmids and transposons, may innature move within or among organismsand may carry with them and transfergenetic material in addition to theirown. MGEs, which are used as vectorsfor moving genetic material amongorganisms, may move across taxonomicboundaries and therefore are not aconstant part of the genome of oneparticular taxonomic group or another.

After publication of the 1986 policystatement describing EPA’s intergenericinterpretation, several producers ofmicroorganisms inquired about thestatus under TSCA of microorganismscontaining MGE material. Therefore, itwas necessary for EPA to develop anapproach for addressing MGEs underthe intergeneric interpretation. Inkeeping with its intergeneric definitionwhich focused on the origin of theintroduced genetic material, EPAdecided that microorganisms would beconsidered intergeneric if theycontained an MGE first identified in amicroorganism in a genus different fromthe recipient microorganism genus.Microorganisms would be consideredintrageneric, and not new, if theliterature indicates the MGE was firstidentified in a microorganism in thesame genus as the recipient. EPA hascontinued to use this policy regardingMGEs to assist in determining whethera microorganism is intergeneric.

The issue of whether the MGE may beindigenous to the recipient genus is notconsidered in EPA’s approach todetermining whether the finalmicroorganism is inter- or intrageneric.The major consideration is the source ofthe organism in which the MGE wasfirst identified. The source of theorganism in which the MGE was firstidentified may be determined by asearch of relevant published scientificliterature or by reviewing available databases such as GENBANK. Such aliterature or data base reference is oftenthe first to name, and possibly describe,the MGE. Subsequent referencespostdating this first reference arefrequently not relevant for determiningthe intergeneric status of the MGE, sinceafter isolation an MGE is oftentransferred to a different taxon where it

can be more easily maintained andstudied. Although EPA recognizes thatMGEs may occur in more than onegenus in nature, EPA believes that forthe moment, use of the source of theorganism in which the MGE was firstidentified for classifying MGEs providesthe most straightforward regulatoryapproach under its intergenericdefinition. EPA will continue to use thisapproach until it can reevaluate thestatus of MGEs within an intergenericstandard in a future rulemaking. EPAhas included a statement about MGEs inits definition of intergenericmicroorganisms in this final rule.

3. Well-characterized, non-codingregulatory regions. In the 1986 policystatement and in the proposed rule, EPAexcluded from the definition ofintergeneric microorganisms, thosemicroorganisms that resulted from theaddition of intergeneric material that iswell-characterized and contains onlynon-coding regulatory regions such asoperators, promoters, origins ofreplication, terminators, and ribosome-binding regions. Where only regulatorymaterial is transferred, no distinctlynew combinations of traits areintroduced. Instead, quantitativechanges in existing traits in therecipient microorganisms may occur.EPA recognizes that insertion of well-characterized, noncoding regulatoryregions may result in expression ofpreviously cryptic regions. However, thegenetic material in cryptic regions ispresent in the population and could beexpressed in some members of themicrobial population at any timenaturally. A microorganism expressingsuch material as a consequence ofinsertion of non-coding regulatoryregions would thus not be new underTSCA. Therefore, EPA believes thatmicroorganisms formed throughintergeneric transfer of well-characterized, non-coding regulatoryregions should not be considered ‘‘new’’microorganisms under TSCA section 5.EPA emphasizes that this exclusionapplies only to intergenericmicroorganisms that have resultedsolely from the addition of well-characterized, non-coding, regulatoryregions. If the final microorganismcontains any regions from organisms ofother genera that do not meet thisrestriction, such as coding regulatoryregions or any poorly characterizedregions, the microorganism isconsidered new and is not eligible forthe exclusion.

In response to comments, EPA hasrevised some of its definitions at § 725.3relating to the intergeneric scope toprovide greater clarity for the regulatedcommunity. The word ‘‘introduced’’ has

been added to the second sentence inthe definition of ‘‘intergenericmicroorganism’’ to clarify thatmicroorganisms which containintroduced genetic material consistingonly of well-characterized, non-codingregulatory regions from another genusare not considered intergeneric for thepurposes of TSCA section 5. EPA agreeswith a commenter who suggested thatthe regulations should have a singledefinition of well-characterized and thatthe definitions of ‘‘well-characterized’’at §§ 725.3 and 725.421(b) should beidentical. To achieve this end, thephrase ‘‘well-characterized, non-codingregulatory region’’ would be deletedfrom §§ 725.3 and ‘‘well-characterized’’and ‘‘non-coding regulatory region’’would be separately defined. Therefore,the definition of ‘‘well-characterized,non-coding regulatory region’’ is beingdeleted and definitions of ‘‘non-codingregulatory region’’ and ‘‘well-characterized’’ are being added to§ 725.3. EPA agreed with thecommenter’s suggestion to use thelanguage in § 725.421(b) to define ‘‘well-characterized.’’ EPA developed thedefinition of ‘‘non-coding regulatoryregion’’ based on language pertinent tothe non-coding aspect of the definitionof ‘‘well-characterized, non-codingregulatory region.’’ EPA believes that itis necessary to specifically require thatthe regulatory regions be non-coding. Asstated in the 1986 policy statement andin the proposed rule, EPA excludedfrom the definition of intergenericmicroorganisms, those microorganismsthat solely contained intergenericregulatory regions that are well-characterized and non-coding. Suchintergeneric material would notintroduce distinctly new combinationsof traits. Instead, only the level ofexpression of existing traits in therecipient microorganisms may bealtered. By also including a restrictionthat the flanking sequences be non-coding, EPA is ensuring that personswill consider the nature of the flankingsequences associated with regulatoryregions when determining theireligibility for the well-characterized,non-coding regulatory region exclusion.

In the proposed rule, EPA indicatedthat it may choose to reconsider itsinterpretation of ‘‘new’’ microorganismat a later time and in a separaterulemaking. Of the 17 commentsreceived on scope of oversight, only 4commenters strongly opposed theintergeneric scope and supportedanother approach, while 13 commentersexpressed some level of support forintergeneric, albeit with somemodifications. EPA believes that while


the intergeneric scope is not perfect, asone commenter noted, ‘‘no one hasproposed a clearly superior scope,despite years of discussion and debate.’’Therefore, EPA is retaining theintergeneric interpretation for the finalrule. However, EPA appreciates themany useful suggestions made bycommenters for refinement of theintergeneric interpretation and plans toconsider at a later time modifications tothe intergeneric interpretation,including issues related to the exclusionof well-characterized, non-codingregulatory regions and to the MGEpolicy. TSCA applicability and scope ofoversight are discussed in detail in theproposed rule and in the Response toComments document in Unit II.

B. Reporting General Commercial Use ofMicroorganisms

1. MCAN and SNUR. The final ruleincorporates many procedures that wereoriginally developed for the TSCAsection 5 program for traditionalchemicals. Procedures from parts 720(premanufacture notification (PMN))and 721 (significant new usenotification SNUN)) are being placed inthe new part 725 with the minormodifications necessary toaccommodate the specificcharacteristics of microorganisms. Inlieu of the PMN or SNUN described inparts 720 and 721, respectively, EPA isincluding in part 725 a requirement forsubmission of a MCAN by persons whointend to manufacture or import newliving microorganisms, and by personswho intend to manufacture, import, orprocess microorganisms for a significantnew use. Subpart D of part 725, whichcontains the MCAN requirements, isbeing promulgated without substantiverevision. The MCAN process isdiscussed in the proposed rule and inthe Response to Comments document inUnit III.A.

EPA received general comments aboutthe process, as well as specificcomments about contractmanufacturing, certain informationrequirements for the MCAN process,and the inclusion of requirements forbyproducts. EPA is providing additionalexplanations and clarifications toaddress these concerns. Both thecomments and EPA’s responses arediscussed in detail in the Response toComments document in Unit III.A.

In response to the commenters whostated that the information required tobe submitted in the MCAN wasconfusing, burdensome, and open-ended, EPA notes that both theproposed and final rule requiresubmission only of the information thatis explicitly required to be submitted by

TSCA section 5(b) and 5(d)(1). Thepurpose of the MCAN is to supply EPAwith information necessary to identifyand list the new microorganism on theTSCA Inventory and to determinewhether the microorganism and theassociated activities would pose anunreasonable risk of injury to humanhealth or the environment. The MCANinformation requirements closelyparallel those for PMNs and differ onlyto the extent necessary to accommodatethe specific characteristics of livingmicroorganisms. Therefore, theintroductory paragraphs in § 725.155have been revised to more closelyparallel the introductory language in§ 720.45, which contains theinformation requirements for the PMN.EPA has also revised § 725.155(b) toexplicitly include the statement that thesubmitter should include all reasonablyascertainable information that willpermit EPA to make a reasonedevaluation of the health andenvironmental effects of themicroorganism. EPA believes that theaddition of the statement in § 725.155(b)also addresses the commenter whorequested that EPA relate theinformation requested to the datanecessary to assess potential risk tohuman health and the environment.

The proposed subpart L of part 725incorporated the Significant New UseRule (SNUR) provisions from part 721with minor modifications toaccommodate the specificcharacteristics of living microorganisms.EPA is promulgating subpart L in thefinal rule with minor revisions,primarily to clarify the relationship ofsubpart L to the other subparts in part725. EPA has not yet proposed a SNURfor a specific microorganism. EPA hasclarified its approach to microorganismSNURs in response to commenters. TheSNUR for microorganisms is discussedin the proposed rule (59 FR 45552-53)and in the Response to Commentsdocument in Unit III.B.

2. Tiered exemption. EPA isestablishing under TSCA section 5(h)(4),the Tier I and Tier II exemptions forcertain microorganisms meeting certaincriteria. The criteria defining eligibilityfor the Tier I exemption address: (1) Therecipient microorganism; (2) theintroduced genetic material; and (3)physical containment conditions tominimize the numbers ofmicroorganisms emitted from themanufacturing facility. For the Tier IIexemption, only the first two of the TierI criteria must be met. Manufacturerswould select containment appropriate tominimize release of the microorganisms.EPA would review the appropriatenessof the containment for the

microorganisms in an expedited 45–dayreview. The requirements for the tieredexemptions are found in subpart G ofpart 725. In response to comments, EPAhas made certain revisions torequirements for the introduced geneticmaterial at § 725.421 and for physicalcontainment at § 725.422. These arediscussed below. The tiered exemptionis discussed in detail in the proposedrule (59 FR 45545-50) and in theResponse to Comments document inUnit III.C.

a. General comments. EPA receivedcomments on issues related to theoverall approach to the tieredexemption. While EPA did not makesubstantive changes to the process forthe Tier I and Tier II exemptions, EPAdid make minor changes in §§ 725.424through 725.470 to further clarifyexemption requirements. In Unit III.C.of the Response to Commentsdocument, EPA provided additionalexplanation of its rationale fordevelopment of the tiered approach.

Some commenters indicated that it is‘‘excessive and unwarranted’’ to requirethe submitter for a tiered exemption tocertify that test data are being submittedas stated in § 725.25(b). Anothercommenter stated that a 30–day reviewwas not necessary and that companiesworking with organisms eligible for theTier I exemption should simplydocument their eligibility in theirrecords.

EPA wishes to clarify how thecertification statement at § 725.25(b)applies to the tiered exemption. Thefirst two sentences, where the companyindicates that it intends to manufacturethe microorganism identified in thesubmission and that all information iscomplete and truthful, are applicable toall submitters. However, the lastsentence is only relevant to personspreparing either the MCAN whichincludes information requirements at§ 725.160 or the TERA which includesinformation requirements at § 725.260.To reduce confusion, EPA has added aclarification to § 725.424(b)(5). EPAinadvertently neglected in the proposedregulatory text, although the proposedpreamble clearly describes procedures,to include the requirements at§ 725.424(b)(4) and (5) as requirementsfor the Tier II exemption at § 725.455.Therefore, EPA has added thoserequirements as § 725.455(e) and (f) inthe final rule. Although § 725.25(b)states that persons submittingexemption requests must submit thecertification statement, EPA hasrepeated the requirement at§§ 725.424(b)(5) and 725.455(f) for theconvenience of submitters. Therequirement at § 725.455(e) was


inadvertently left out of the proposedrule; however, EPA does not believe thatthis requirement adds an additionalburden, because submitters shouldalready have information about wastedisposal of the microorganisms.

EPA agrees that EPA review is notrequired for the Tier I exemption, asEPA has already made the nounreasonable risk finding formicroorganisms meeting the conditionsof the exemption. EPA has structuredthe Tier I exemption such that EPAreceives a one-time certification alertingEPA to the application of the exemptionand to demonstrate that the submitter iscomplying with the criteria set out forthe exemption. The certificationcontains no data for EPA to review.Once a person has sent in thecertification required by § 725.424,subsequent uses of the same recipientdo not require additional certificationunder § 725.424, as long as themanufacturer is continuing to complywith the introduced genetic materialrequirements of § 725.421 and thecontainment requirements of § 725.422.While EPA does not believe that an EPAreview is necessary, EPA does believethat it is appropriate for EPA to benotified of which manufacturers areeligible for and utilizing the exemption.However, EPA also has decided thatsince the purpose of the certification issolely to inform EPA that persons areusing the Tier I exemption, suchnotification is not needed 30 days inadvance, and 10 days in advance ofmanufacture or import is sufficient.Therefore, EPA has revised therequirement at § 725.424(a)(4) to requiresubmission of the certification to EPA atleast 10 days before commencing initialmanufacture or import of a newmicroorganism.

b. Recipient microorganism. EPAreceived no substantive commentschallenging EPA’s approach to selectingrecipient microorganisms for listing orquestioning the eligibility of the 10candidates proposed for listing.Therefore, EPA has not madesubstantive changes to its approach toselecting recipient microorganisms.Section 725.420 continues to list the 10microorganisms as eligible for use in thetiered exemption. Although EPAexplained in detail in the proposal (59FR 45545-47) the considerations itevaluated in selecting candidatemicroorganisms for listing at § 725.420,EPA provided commenters withadditional explanation as to how sixcriteria are used together to determine amicroorganism’s eligibility for listing at§ 725.420. The recipient microorganismcriteria are discussed in detail in theproposed rule (59 FR 45545-47) and in

the Response to Comments document inUnit III.C.2.

Some commenters were concernedabout the effect of potential changes inmicrobial taxonomy on themicroorganisms listed at § 725.420. Therisk assessments that EPA prepared forthe 10 microorganisms listed at§ 725.420 evaluated the hazards of themicroorganisms as they wereappropriately designated taxonomicallyin 1994. Therefore, EPA believes that ifin the future the name is changed forany of the 10 microorganisms currentlylisted in § 725.420, persons would needto document that their microorganismswould have been classified in 1994under the name listed in § 725.420.

EPA proposed the petition process at§ 725.67 to provide a mechanism for thepublic to propose additional candidatesand provide the appropriate supportinginformation. As a general matter, EPAexpects that petitions to add specificrecipient microorganisms to the list at§ 725.420 will ideally be preceded byseveral MCANs before the necessaryexperience with and information on themicroorganism have been accumulatedto provide EPA with a starting point fordetermining whether the recipientshould be listed as a candidate for thetiered exemption. EPA has revised theregulatory text for the petition process at§ 725.67 generally to clarify that theinformation required to be submitted ina petition will mirror the informationrequirements for the provision forwhich the exemption is being sought.With regard to the tiered exemption,EPA has indicated at § 725.67(a)(3)(iii)that when applying to list a recipientmicroorganism for the tiered exemptionunder § 725.420, persons should includeinformation addressing the six criteria,which EPA will use to evaluate themicroorganism for listing. EPA made thegeneric revision, because the petitionprocess was designed to be used byanyone seeking to apply for a section5(h)(4) exemption from full MCANreporting under TSCA section 5.

One commenter asked EPA to clarifywhether the microorganism Bacillusamyloliquefaciens would be considereda variant of the listed candidate Bacillussubtilis and thus eligible for the tieredexemption. EPA does not believe thatBacillus amyloliquefaciens can besubsumed under the exemption forBacillus subtilis. B. amyloliquefaciensmay have been considered a variant ofB. subtilis in the past; however, by thetime the risk assessment for B. subtiliswas developed in 1994, B.amyloliquefaciens had been givenseparate species status (Ref. 1).Therefore, B. amyloliquefaciens is notsynonymous with B. subtilis, and EPA is

not including the former under theexemption for the latter.

Another commenter asked that EPAadd Pseudomonas fluorescens to the listat § 725.420. After review of theinformation supplied by the commenter,and other information referenced in theResponse to Comments Document inUnit III.C.2.b., EPA has concluded thatthe species P. fluorescens is not eligiblefor listing as a recipient microorganismunder § 725.420 at this time for thefollowing reasons: its confusingtaxonomic status; its lack of history ofsafe commercial use; and the potentialof some strains currently classified as P.fluorescens to cause adverse effects onhuman health and the environment,particularly in relation to plantpathogenicity. EPA’s review does notrepresent a full consideration of thespecies P. fluorescens, becausesufficient information was notsubmitted. Thus EPA responds to thecommenter’s request as a rule commentand not a formal petition.

c. Introduced genetic material. For theintroduced genetic material, EPAidentified four requirements in§ 725.421 which must be met to qualifyfor the Tier I or Tier II exemptions: thegenetic material must be (a) limited insize, (b) well-characterized, (c) poorlymobilizable, and (d) free of certainsequences. EPA responds to commentson the criteria for the introduced geneticmaterial within the context of theintergeneric scope. The terms in thefinal regulatory text for the tieredexemption refer to ‘‘introduced geneticmaterial’’ and only the intergenericportions of the introduced geneticmaterial must meet the requirements at§ 725.421. Therefore, the requirementsin § 725.421 refer solely to theintroduced genetic material which isderived from an organism classified ina different genus from the recipientmicroorganism. The introduced geneticmaterial criteria are discussed in detailin the proposed rule (59 FR 45547-48)and in the Response to Commentsdocument in Unit III.C.3.

(i) Limited in size. The requirementsfor the ‘‘limited in size’’ criterion are setforth at § 725.421(a), which states thatthe introduced genetic material mustconsist only of the following: (1) Thestructural gene(s) of interest; (2) theregulatory sequences permitting theexpression of solely the gene(s) ofinterest; (3) associated nucleotidesequences needed to move geneticmaterial, including linkers,homopolymers, adaptors, transposons,insertion sequences, and restrictionenzyme sites; (4) nucleotide sequencesneeded for vector transfer; and (5)nucleotide sequences needed for vector


maintenance. EPA discussed itsrationale supporting the limited in sizecriterion in the preamble to theproposed rule (59 FR 45547).

EPA is providing additional guidancefor interpreting the ‘‘limited in size’’requirements in this preamble and inthe Response to Comments document inUnit III.C.3.a., but is not making changesto the regulatory text at § 725.421(a).Commenters generally requested thatEPA clarify which vector sequenceswould meet the criterion, including thestatus of certain sequences found inwell-known, frequently used plasmids.In response, EPA is clarifying that itinterprets requirement (3) above toallow the introduced DNA to containvector material necessary formaintenance in and/or transfer tointermediate hosts, provided this vectormaterial is not expressed in theintergeneric microorganism that will bemanufactured under the tieredexemption. Such nonexpressed vectormaterial should not change the behaviorof the intergeneric microorganism. EPAalso indicates that certain plasmid andphage vectors listed in Appendices Eand I of the National Institutes of HealthGuidelines for Research InvolvingRecombinant DNA Molecules (NIHGuidelines (59 FR 34496, July 5, 1994)(FR Doc. 94–16200)) (Ref. 2) would meetthe introduced genetic material criteriaincluding the limited in size criterion.

(ii) Well-characterized. Therequirements for the ‘‘well-characterized’’ criterion are set forth at§ 725.421(b) which states that wellcharacterized means that the followinghave been determined for theintroduced genetic material: (1) Thefunction of all of the products expressedfrom the structural gene(s); (2) thefunction of sequences that participate inthe regulation of expression of thestructural gene(s); and (3) the presenceor absence of associated nucleotidesequences where associated nucleotidesequences are defined as those ‘‘neededto move genetic material, includinglinkers, homopolymers, adaptors,transposons, insertion sequences, andrestriction enzyme sites.’’ EPAdiscussed its rationale supporting thewell-characterized criterion in thepreamble to the proposed rule (59 FR45547).

EPA is providing additional guidancefor interpreting the ‘‘well characterized’’requirements in this preamble and inthe Response to Comments document inUnit III.C.3.b., but is not makingchanges to the regulatory text at§ 725.421(b). Commenters expressedconcerns about what it means to knowthe functions of all products expressedby the structural genes, how to address

open reading frames (ORFs) present inthe introduced genetic material, whatinformation is needed to determinewhether upstream activator sequencesmeet the ‘‘well-characterized’’ criterion,and whether complete genomicsequencing of the final construct isnecessary to meet the well-characterizeddefinition.

EPA’s intent in developing the ‘‘well-characterized’’ criterion was to ensurethat the functions introduced with thegenetic material were sufficientlyunderstood to predict the likelybehavior of the resulting microorganism.Because EPA defined a ‘‘new’’microorganism as an intergenericmicroorganism, it is the predicted effectof the intergeneric sequences on thephenotype of the recipientmicroorganism that must be evaluated.With regard to the functions of productsexpressed by introduced structuralgenes, manufacturers could rely, forexample, on peer-reviewed literature onproducts of structural genes and/or theresults of protein expression assays tocharacterize the function(s) of a geneproduct.

Manufacturers must ensure, byevaluating ORFs and multiple readingframes, that unanticipated novel traitsare not expressed by the intergenericmicroorganism. ORFs must be assessedto determine whether a product otherthan the anticipated, desired product islikely to be expressed and to predictwhether such a product(s), if expressed,would have an effect on the phenotypeof the intergeneric microorganism.

In determining the status of upstreamactivator sequences (UASs) with regardto the exemption at § 725.421,manufacturers must first considerwhether introduction of the UAS wouldcreate an intergeneric microorganism.For a UAS isolated from an organism ina different genus from the recipientmicroorganism, manufacturers shoulddetermine whether their UAS meets therequirements in the definitions at§ 725.3 for ‘‘non-coding regulatoryregion’’ and for ‘‘well-characterized.’’Microorganisms developed through theintroduction of only UAS geneticmaterial that is isolated from anorganism in a different genus and thatmeets the above-noted definitions at§ 725.3, are excluded from the definitionof ‘‘intergeneric microorganism’’ andtherefore are not subject to therequirements of TSCA section 5.

Manufacturers who wish to utilize thetiered exemption for microorganismsthat contain both a UAS(s) and othergenetic material isolated from anorganism(s) in a different genus than therecipient, must, to meet the exemptionrequirements: (1) Ensure that the UAS

meets the definitions of ‘‘non-codingregulatory region’’ and ‘‘well-characterized’’ at § 725.3; (2) ensure thatthe other introduced genetic materialmeets the requirements at § 725.421(b);and (3) ensure that the otherrequirements of the Tier I or Tier IIexemption are met.

(iii) Poorly mobilizable. Therequirements for the ‘‘poorlymobilizable’’ criterion are set forth at§ 725.421(c) which states that theprobability that the introduced geneticmaterial would be transferred to othermicroorganisms must be low, with afrequency of transfer of less than 10-8

transfer events per recipient. EPAdiscussed its rationale supporting thepoorly mobilizable criterion in thepreamble to the proposed rule (59 FR45547-48).

EPA is providing additional guidancefor interpreting the ‘‘poorlymobilizable’’ requirements in thispreamble and in the Response toComments document in Unit III.C.3.c.,but is not making changes to theregulatory text at § 725.421(c). Somecommenters requested clarification onthe conditions under which the 10-8

criterion should be measured. They alsorequested that EPA clarify the statuswith regard to the ‘‘poorly mobilizable’’criterion of introduced genetic materiallocated on the chromosome.

EPA believes the 10-8 criterion, whichis a standard established by NIH in itsGuidelines (Ref. 2) and an importantfeature of the Good Industrial Large-Scale Practices (GILSP) criteriadeveloped by the Organization ofEconomic Cooperation andDevelopment (OECD) (Ref. 3), should beapplied to the introduced geneticmaterial under § 725.421, because EPAis not restricting (aside from that under§ 725.421(d)) the source and function ofthe introduced genetic material.Therefore, EPA in order to make thefinding that organisms meeting the othercriteria at § 725.400 present low risk, the‘‘poorly mobilizable’’ standard must beincluded in the criteria at § 725.421.EPA believes that manufacturers canreadily determine whether theintroduced genetic material will meetthe 10-8 criterion. For many bacteria,most sequences introduced bytransduction and transformation will apriori meet the 10-8 criterion. Therefore,a single mechanism of gene exchange,conjugation, will need to be consideredand the introduced genetic materialconstructed to meet the 10-8 standard forthat mechanism. EPA also clarifies thatgenetic material stably integrated intothe chromosome with no functionaltransposons is likely to meet the 10-8

criterion.


(iv) Free of certain sequences. Therequirements for the ‘‘free of certainsequences’’ criterion were set forth atproposed § 725.421(d) which indicatedthat the introduced genetic materialmust not contain any part of thenucleotide sequences that encodecertain listed toxins, which arepolypeptides of relatively high potency.EPA discussed its rationale supportingthe ‘‘free of certain sequences’’ criterionin the preamble to the proposed rule (59FR 45547).

A commenter noted that the languagein proposed § 725.421(d), if takenliterally, would ‘‘preclude the use ofDNA that codes for a pair of amino acids(or even a single one) if that sequencealso occurs in any of these toxins.’’ Inorder to clarify this point, thecommenter suggested that the languagebe altered to state that the introducedgenetic material must not contain asequence ‘‘encoding any active moietyof a toxin’’ listed in § 725.421(d).

EPA is providing additional guidancefor interpreting the ‘‘free of certainsequences’’ requirements in itsResponse to Comments document inUnit III.C.3.d., and is modifying theregulatory text at § 725.421(d) to clarifyits intentions. The introductory text of§ 725.421(d) has been modified toinclude the term ‘‘functional portion ofa toxin-encoding sequence.’’ To assistsubmitters in interpreting the term‘‘functional portion’’ of a toxin-encodingsequence described at § 725.421(d), EPAprovides a discussion of sequences thatdirectly or indirectly contribute to toxiceffects in human cells. For toxins thataffect a cell’s cytoplasmic functions,nucleic acid sequences that encode the‘‘functional portion’’ of a toxin are thosewhich encode either functional receptorbinding or toxic domains of the toxin.For toxins that affect a cell’s membrane,nucleic acid sequences that shall not beincluded in the introduced geneticmaterial are those which encode thefunctional portion that allows target cellmembrane disruption.

EPA did not intend for the restrictionon toxin-encoding sequences to beinterpreted to mean that the presence ofa nucleotide found in a toxin genesequence on the list at § 725.421(d)would preclude introduced geneticmaterial containing that nucleotide fromqualifying for the tiered exemption. EPAbelieves the likelihood of any significantrisk resulting from incorporation ofnonfunctional portions of a toxin geneinto a recipient listed at § 725.420 islow. EPA is also modifying thedefinition to emphasize that EPA isexcluding specific toxin sequences andnot source organisms, which are listedat § 725.421(d) to identify the toxins.

d. Physical containment. Theproposal included the followingcontainment requirements at § 725.422for the Tier I exemption: (1) Thestructure is designed and operated tocontain the microorganism, (2) limitentry only to those persons whosepresence is critical to the reliability orsafety of the activity, (3) providewritten, published, and implementedprocedures for the safety of personneland control of hygiene, (4) provide anddocument effectiveness of inactivationprocedures to reduce microbialconcentrations by at least 6 logs inliquid and solid wastes, (5) provide anddocument effectiveness of features toreduce microbial concentration by atleast 2 logs in aerosols and exhaustgases released from the structure, (6)include and document systems forcontrolling dissemination of themicroorganisms through other routes,(7) have in place emergency clean-upprocedures. Most of the commentsfocussed either on (2), the limited entryrequirement, or (4) and (5), theinactivation requirements. The physicalcontainment criteria are discussed indetail in the proposed rule (59 FR45548-49) and in the Response toComments document in Unit III.C.4.

(i) Limited entry requirement. Somecommenters indicated that the limitedentry requirement was too restrictive,given the low potential hazards posedby microorganisms used under the TierI exemption criteria. Specifically, theystated that under that requirement,managers may be precluded fromallowing administrative personnel,customers, school and other educationaltours into the facility. It was not EPA’sintention to constrain facility managersto this extent. Consequently, EPArecognizes that language at proposed§ 725.422(b) may have been stricter thanwas necessary. Neither the NIHGuidelines (Ref. 2) nor the OECD GILSPcriteria (Ref. 3) have specific limitedentry requirements for large scale usesof comparable microorganisms.Additionally, EPA’s review of PMNsreceived for intergenericmicroorganisms indicated that restrictedentry was not common industry practice(Ref. 4). EPA agrees with thecommenters who stated that given thelow risk posed by the microorganismseligible for the exemption, managersshould have the discretion to allowadministrative personnel, customers,and school and other educational toursinto the facility. However, EPA alsoexpects that managers will maintainappropriate containment, therebycontrolling access and avoidinginadvertent exposure. Modification of

the language of this requirement doesnot alter EPA’s original determinationthat microorganisms that are eligible forand used under the conditions of theTier I exemption will not present anunreasonable risk of injury to humanhealth and the environment. Therefore,EPA has revised § 725.422(b) to read‘‘Control access to the structure.’’

(ii) Inactivation requirements. Somecommenters indicated that with thelimitations placed on the recipientmicroorganism and the introducedgenetic material, quantitation ofinactivation procedures was notnecessary. The commenters stated that itwould be necessary to modify existingequipment to sample off-gas as requiredand that an additional sample portwould increase the potential forcontamination and worker exposure.The commenters suggested that insteadof numerical requirements, language besubstituted that more generally requiredreduction of microorganisms in liquidand solid wastes and aerosols andexhaust gases. Other commenters statedthat the numerical requirements for theinactivation procedures are too lenient.These commenters suggested that gasesbe vented through a HEPA filter orincinerated. They also recommendedthat the containment criteria becoordinated with the containment levelsset out in the NIH Guidelines (Ref. 2).

After considering comments regardingits inactivation requirements atproposed § 725.422(d) and (e), EPAreviewed information submitted onphysical containment and controltechnologies in PMNs it has received forintergeneric microorganisms between1986 and 1995 (Ref. 4). On the basis ofthat review, EPA has made thefollowing determinations. EPA hasdecided to retain § 725.422(d) whichrequires the use of inactivationprocedures that reduce microbialconcentrations by at least 6 logs inliquid and solid wastes. However, EPAhas determined that it is appropriate torevise § 725.422(e) to read ‘‘Provide anddocument effectiveness of features tominimize viable microbial populationsin aerosols and exhaust gases releasedfrom the structure.’’ The physicalcontainment criteria are discussed indetail in the Response to Commentsdocument in Unit III.C.4.

As indicated in the preamble to theproposed rule (59 FR 45548-49), EPAbelieved that it was appropriate toprescribe standards for minimizing thenumber of microorganisms emittedthrough the disposal of wastes, becausea wide range of behaviors could bedisplayed by microorganisms eligiblefor the exemption and because EPAwould not be reviewing MCANs on


microorganisms eligible for the Tier Iexemption. EPA believes that therequirement for a 6-log reduction in thenumber of microorganisms is reasonablefor inactivation of liquid and solidwastes and well within current industrypractices. The 6-log reduction criterionrepresents a level of inactivation whichcan be validated. This standard gives adecrease in viable microbial populationsso that at least 99.9999 percent of theorganisms resulting from thefermentation will be killed. EPAdiscusses the application of thisstandard under normal industrypractices in the proposed rule (59 FR45548-49) and in the Response toComments document in unit III.C.4.b.An examination of PMNs forintergeneric microorganisms (Ref. 4)revealed that this criterion is readilyachievable by manufacturers. Thereview of these PMNs also indicatedthat in the several cases wheremonitoring was conducted there wereno detectable viable microorganisms inliquid and solid wastes afterinactivation (Ref. 4). EPA believes thatthe 6-log reduction in viable microbialnumbers in the liquid and solid wastesis a reasonable and demonstrableperformance criterion ensuring anappropriate level of containment for thelow risk microorganisms which wouldbe eligible for the tiered exemption.

As indicated in the preamble to theproposed rule (59 FR 45548-49), EPAbelieved that it was appropriate torequire manufacturers to minimize thenumber of microorganisms emittedthrough the venting of gases. A widerange of behaviors could be displayedby microorganisms eligible for theexemption, and EPA would not bereviewing MCANs for microorganismseligible for the Tier I exemption. In theproposal EPA indicated that a 2-logreduction in viable microorganisms percubic foot of air between the headspaceand the actual vent port was theappropriate standard. EPA chose thisnumber based on an estimate of thenumbers of microorganisms likely to bein the exhaust from an uncontrolledfermentor and common industrypractice. EPA discusses the applicationof this standard under normal industrypractices in the proposed rule (59 FR45549) and in the Response toComments document in unit III.C.4.b.Additionally, the 2-log reductionrepresented a somewhat less restrictivenumber than the reduction obtainedwith HEPA filter filtration (thereduction level required for the NIHGuidelines BL1-LS level (NIH,Appendix K, 1995) (Ref. 2).

However, EPA received severalcomments pointing out the technical

problems associated with the proposed2-log reduction performance criterion.EPA agrees with the commenters thatcompanies should not have to modify/retrofit their existing equipment norjeopardize the sterility of theirfermentations in order to validate thatthe number of microorganisms beingreleased in the exhaust has beenreduced by at least 2 logs relative to themicrobial numbers in the fermentorgases in the headspace. EPA did notintend that retrofitting or any otherburdensome engineering modificationswould be necessary for those whowished to utilize the Tier I exemption.Rather, EPA had intended to developrequirements for this exemption thatwould impose performance standardsfor equipment already commonly used.In light of comments received, EPA hassought to modify its requirement toachieve its goal of having submittersdemonstrate that the equipment orfeatures normally employed infermentation systems are effective inreducing numbers of viablemicroorganisms being vented in exhaustgases.

As stated in the preamble and notedby commenters, industrial fermentationsare not routinely run in an uncontrolledfashion, and thus the number ofmicroorganisms potentially releasedinto the gas phase and unrecovered iscontrolled. Additionally, anexamination of PMNs for intergenericmicroorganisms (Ref. 4) showed that allof the fermentations, which wereoperating under standard industrypractices, were utilizing features whichminimize the number ofmicroorganisms released in the off-gases.

For fermentations to operateoptimally, vapor recovery systems areused to maintain the correct growthconditions for the microorganisms, e.g.,correct molality in the fermentationbroth must be maintained. Vaporrecovery systems, by their nature, helpto minimize the number ofmicroorganisms exhausted from thefacilities. EPA believes that it shouldallow some flexibility in the type offeatures manufacturers employ tominimize microbial releases as aerosols.A variety of fermentor equipment orfeatures are commonly used by theindustry such as demisters, wetscrubbers, cyclone separators,coalescing filters, and HEPA filters.These types of equipment reduce thenumber of microorganisms ventedthrough exhaust gases from thefermentor. Moreover, as stated in thepreamble (59 FR 45549), even ifmicroorganisms are exhausted from thefermentor, their survival is likely to be

limited due to the stress conditions ofaerosolization, including shear forces,desiccation, and UV light exposure.

Given the comments received on thefeasibility of this requirement and thevariety of methods used by PMNsubmitters to reduce microbial numbersin aerosols, EPA believes that a specificnumerical performance standard is lessappropriate for inactivation of aerosolsthan it is for inactivation of liquid andsolid wastes. EPA agrees withcommenters who asserted that themajority of microorganisms potentiallyreleased from the fermentation facilitywould be found in the liquid and solidwastes. EPA has prescribed a specificviable microorganism reductionstandard for these materials. Therefore,EPA believes that if the newmicroorganism meets all of the otherrequirements of the Tier I exemption, itis sufficient to require use of validatedmethods for minimizing release ofmicrobial concentrations in aerosols andexhaust gases without prescribing aspecific numerical reduction innumbers. If manufacturers areconducting their quality assurance/quality control (QA/QC) monitoring toensure proper performance of theirfermentation equipment, EPA believesthat the facilities would be meeting therequirement of § 725.422(e). EPA hasrevised § 725.422(e) to read: ‘‘Provideand document effectiveness of featuresto minimize viable microbialpopulations in aerosols and exhaustgases released from the structure.’’Based on the above points and theresults of the review of EPA’s PMNexperience, EPA believes that thisrequirement will ensure that the numberof microorganisms released in fermentoroff-gases will be negligible and allowEPA to make the ‘‘no unreasonable risk’’finding of section 5(h)(4).

EPA does not agree with commenterswho stated that a 2-log reduction foraerosols is too lenient. As discussed inthe proposed rule (59 FR 45549), evenif small numbers of microorganisms arereleased in fermentor exhaust gases,aerosolization is a stressful conditiondecreasing the survival of mostmicroorganisms. Aerosolized bacterialcells are weakened by shear forces, andare subject to desiccation and exposureto UV light. Therefore, survival ofaerosolized microorganisms is expectedto be limited. Since organisms whichare eligible as recipient microorganismsfor the Tier I exemption are low risk,EPA does not believe it is necessary toimpose more stringent conditions than arequirement that manufacturersminimize the numbers ofmicroorganisms in fermentor off-gases.


Several commenters suggested thatEPA coordinate its containment criteriawith those specified in the NIHGuidelines (Ref. 2). EPA considered useof the NIH Guidelines when it wasdeveloping the tiered exemption butfound such an approach to beproblematic. In particular, the NIHGuidelines may change through aprocess independent of EPA activitiessuch that the Guidelines would nolonger provide the appropriate criteriato support a TSCA section 5(h)(4)exemption. EPA has developed anapproach at § 725.422 based, in largepart, on standards set forth in the NIHGuidelines and the OECD GILSP thatallow EPA to make the finding that isrequired under TSCA section 5(h)(4).However, in considering the specificcontainment requirements of the currentNIH Guidelines (Ref. 2), EPA could notfind one level in Appendix K that EPAbelieved would be appropriate for theTier I exemption. The NIH Good LargeScale Practice (GLSP) criteria thatwould be applicable to some, but notall, of the microorganisms listed at§ 725.420, do not require minimizationof the numbers of microorganismsreleased in off-gasses. Biosafety Level 1-Large Scale (BL1-LS) criteria require theuse of HEPA filters or their equivalent,a 3-log reduction, and therefore aremore restrictive than EPA’s original 2-log reduction requirement.

In reconsidering its originalrequirement, EPA believes that the costsof retrofitting existing equipment aswell as the increase in potentialcontamination and worker exposure thatwould accompany sample collectionnecessary to validate the 2-log reductionrequirement are not justified for the lowrisk microorganisms eligible for theexemption. EPA has attempted to makeits approach compatible with goodpractice in industry. Most of therequirements of § 725.422 are analogousto NIH Guidelines requirements. Inparticular, companies who are in fullcompliance with the NIH BL1-LSrequirements would also be incompliance with § 725.422(e), althoughthe use of HEPA filters or theirequivalent is a more stringentrequirement than § 725.422(e).

C. Reporting R&D Activities ofMicroorganisms

As discussed earlier in this preambleand in the proposed rule, TSCA section5 generally requires notification to EPAat least 90 days prior to the manufactureand importation of new chemicalsubstances and 90 days prior to themanufacture, importation, andprocessing of designated chemicalsubstances for significant new uses.

TSCA section 5(i) makes clear that onlymanufacturing, importing, andprocessing ‘‘for commercial purposes’’are subject to section 5 notification.TSCA section 5(h)(3) exempts entirelyfrom notification under section 5 themanufacturing, importing, andprocessing of chemical substances ‘‘onlyin small quantities (as defined by theAdministrator)’’ for R&D, subject only tothe manufacturer, importer, or processornotifying (as prescribed by EPA) thepersons involved in the R&D activity ofany risks to health associated with thesubstance.

As discussed in more detail below, fortraditional chemical substances, EPAhas defined ‘‘small quantities’’ for R&Dto be those quantities ‘‘not greater thanreasonably necessary’’ for the R&Dpurposes. However, EPA is adopting adifferent definition of ‘‘small quantities’’for R&D for microorganisms, becauseliving microorganisms may reproduceand increase their own volume oramount. The definition adopted in thisfinal rule limits the section 5(h)(3)exemption from section 5 MCANrequirements to R&D activities that areadequately contained as set forth in§ 725.234.

This narrower definition of ‘‘smallquantities’’ means that R&D activitiesconducted outside the prescribedcontainment (including field tests) donot qualify for the section 5(h)(3)exemption and are subject to the MCANrequirement. However, EPA has created,under authority of TSCA section 5(h)(4),other exemptions that will reduce thereporting burden for persons conductingcertain R&D activities that do notqualify for the complete exemption insection 5(h)(3). These activities arediscussed below.

Researchers, including those inacademic institutions, may be subject toTSCA section 5 jurisdiction because, bycreating or reproducing microorganismsin their R&D activities, they are‘‘manufacturing’’ or ‘‘processing’’ suchmicroorganisms. Since many such R&Dactivities involving microorganisms willnot qualify for the section 5(h)(3)exemption from MCAN reporting, it isimportant for researchers, includingthose in academic institutions, todetermine whether their activities fitwithin the definition of ‘‘commercialpurposes’’ and, thus, are subject toTSCA section 5 and the MCANrequirements at all. Because of thenature of microorganism R&D and thebroad definition of ‘‘commercialpurposes’’ discussed below, it is likelythat many researchers, including somein academic institutions, will be subjectto TSCA section 5 jurisdiction for thefirst time and will want to utilize the

TERA and other exemption provisionsto reduce the reporting burdensinvolved in their R&D activities.

Each of the exemptions for R&Dactivities applies to specific types ofactivities. At the beginning of R&D,while the research is taking place in alaboratory subject to appropriatecontainment, the R&D activity may befully exempt under the section 5(h)(3)exemption if the researcher complieswith the conditions set out in the rule.Once the researcher decides to conductresearch outside the contained setting,such as field tests, the researcher willneed to utilize a different exemption,such as the TERA.

1. TSCA jurisdiction. EPA did notpropose any provisions that would alterthe jurisdictional scope of section 5, i.e.,whether the use or potential use of amicroorganism would be subject toTSCA. However, EPA receivedcomments asking for clarificationregarding TSCA section 5 coverage ofR&D activities with microorganisms. Acommenter requested clarification ofEPA’s statement that ‘‘EPA wouldconsider that R&D activities involvingnew microorganisms where researchersare unsure of the final use would besubject to TSCA section 5.’’ Somecommenters requested that EPA confirmthat researchers working with newmicroorganisms for the purposes ofdeveloping products such as drugs andfoods would not be subject to TSCAsection 5.

EPA did not intend to imply thatresearchers using microorganismswould automatically be subject tosection 5 requirements, withoutconsideration of whether the researchwas conducted for a commercialpurpose. The commenters apparentlymisunderstood EPA’s proposedpreamble discussion, which wasintended only to explain the analyticalsteps to follow in determining whetherresearchers would be required to file aTERA notice.

Researchers attempting to determinepotential TSCA section 5 obligations forR&D activities would first ascertainwhether the use or potential use of themicroorganism is specifically excludedfrom TSCA section 5. Uses that are notspecifically excluded are subject toTSCA. EPA anticipates that much R&Dactivity with microorganisms will not besubject to TSCA. If the research isconducted with the intention ofdeveloping a product, the use of whichwould be subject solely to the FederalFood, Drug, and Cosmetic Act (FFDCA),the research would not be subject toTSCA. For example, with regard tobiotechnology companies engaged indevelopment of drugs, TSCA


specifically excludes substances used inthe production of foods, drugs,cosmetics and medical devices fromTSCA jurisdiction. Microorganismsused in the production of foods, drugs,cosmetics and medical devices aresimilarly excluded from TSCA.However, researchers unsure of the finaluse or potential use, or who intend todevelop a product, a use of which couldbe subject to either FIFRA or TSCA, willneed to consider whether they aresubject to TSCA. Further discussion ofthe comments and EPA’s responses canbe found in the Response to Commentdocument at Unit IV.A. If the researchis subject to TSCA, researchers may beeligible for one of the exemptionsdiscussed in Units IV.C. and E. of theResponse to Comments document.

2. Commercial R&D. The mostsubstantial decision made in developingthe final rule was selection of thedefinition of commercial purposes forR&D activities. This issue is discussedin detail in the proposed rule (59 FR45537-39) and in the Response toComments document in Unit IV.B.

TSCA section 5(i) limits all section 5screening to activities for commercialpurposes. Research on traditionalchemicals is not generally affected bythe commercial purposes limitation,because EPA’s current regulatorydefinition of small quantities for R&Dusing traditional chemicals (anyamounts reasonably necessary forresearch) at § 720.3 effectively exemptsmost research with these chemicalsfrom section 5 review. However,because of the ability of microorganismsto reproduce, disseminate and spread,EPA believed that it was necessary toreview these products at an earlier stageand therefore proposed an interpretationto address testing with microorganisms.Consequently, EPA developed adifferent small quantities definition formicroorganisms and is imposingreporting and recordkeepingrequirements on certain R&D activities.Researchers utilizing microorganisms,therefore, will need to consider whethertheir R&D activities would beconsidered commercial, and thereforesubject to TSCA section 5 requirements.

During development of regulations onbiotechnology over the past severalyears, EPA has received numerouspublic comments that differsubstantially on how the Agency shouldapply the commercial purposesdefinition to research. Of particularconcern has been the appropriateness ofan EPA oversight system based on thestatus of an activity as commercial ornoncommercial rather than on potentialrisk. Because of the past difference inpublic opinion, EPA proposed three

approaches to defining what constitutescommercial activities: (1) Using indiciato determine commercial purposes; (2)presuming all environmental testing iscommercial; and (3) presuming that allenvironmental research is commercialbut offering an opportunity forresearchers to rebut the presumption.Rather than indicating a preference,EPA discussed in the preamble theadvantages and disadvantages of eachapproach and asked for public commenton which approach would beappropriate.

Comments received on the proposedrule produced no prevailing opinion onhow EPA should define ‘‘commercialpurposes’’ for R&D. In considering thisissue, EPA turned to its experience overthe past several years responding toresearchers who inquired about thestatus of their field tests under TSCA.EPA based its responses to thoseinquiries, in part, on its approach totraditional chemicals under TSCA.Under the TSCA section 5 program fortraditional chemicals, EPA determineswhether an activity is for a commercialpurpose based on whether the purposeof the activity is to have an immediateor eventual commercial advantage. EPAfound that determining the commercialstatus of research microorganisms basedon indicia similar to those used fortraditional chemicals functionedadequately. Therefore, EPA has decidedthat for this final rule when determiningwhether their R&D activities withmicroorganisms would be ‘‘forcommercial purposes,’’ researchers willneed to consider the indicia listed in§ 725.205(b).

The indicia approach applies to R&Din laboratories and other containedstructures as well as to intentionaltesting in the environment and isdiscussed in more detail below.

Researchers who are attempting todetermine whether their research wouldbe for ‘‘commercial purposes’’ shouldconsult § 725.205(b). Under§ 725.205(b)(1) researchers would firstconsider whether any of the funding forthe proposed research comes directlyfrom a commercial source. Any directindustry involvement in or directfunding of an activity at anoncommercial institution is forcommercial purposes. This wouldinclude the use of company funds todevelop the microorganisms or the useof a company-provided microorganismin the research. If any portion of theresearch is funded directly by acommercial source, then the research is‘‘for commercial purposes.’’ Thus, if anypart of the research is funded bycontract, joint venture, or other financialarrangement, with the purpose of

eventually producing a commercialproduct, the research is subject to therequirements of section 5. For example,laboratory work or field tests conductedunder a research contract between acompany and a university or aresearcher where patent rights or tradesecrets are held by the company, wouldbe considered commercial R&D.

If researchers do not fall under§ 725.205(b)(1), they should nextconsider potential indirect indicators ofcommercial intent as reflected in§ 725.205(b)(2). They would need toconsider, for example, whether theresearch is directed towards developinga commercially viable improvement of aproduct already on the market, orwhether they are seeking commercialfunding or a patent.

If researchers do not fall within thescope of § 725.205(b)(1) or (b)(2), theirresearch may be considerednoncommercial. For example, anoutright gift from a company to auniversity or a researcher without thecompany directing or otherwisecontrolling the research for which thefunds are to be used or the use to bemade of the results of the researchconducted, would not be considereddirect funding under § 725.205(b)(1). Assuch, the research conducted using sucha gift would be considerednoncommercial R&D, assuming theresearcher also does not believe themicroorganism has the potential to bedeveloped as a commercial product inthe future or intend to obtain animmediate or eventual commercialadvantage as described under§ 725.205(b)(2). Therefore, if aresearcher is planning to conductlaboratory work or field tests or otherenvironmental testing using fundswhich were part of an outright gift froma company to the university with nostrings attached, that research would beconsidered noncommercial R&D.

If none of the funding or support forthe laboratory work or field test or otherenvironmental testing, includingdevelopment of the microorganism,comes from a commercial source, thenthe researcher must consider whether heor she intends to pursue thedevelopment of the new microorganismas a commercial product in the future,should testing show potentialcommercial viability. The researcher isresponsible for judging whencommercial intent exists for his or herparticular research project. EPArecognizes that in the initial stage ofresearch projects, researchers may notenvision an eventual commercialpurpose for their microorganisms.However, if, during the course of theirinvestigations, researchers determine


that their microorganism has a potentialcommercial use which they intend topursue, they then become subject to therequirements of TSCA section 5 and thisrule, and their further research activitiesmust be in compliance with this rule.EPA has provided examples of researchthat has an immediate or eventualcommercial advantage in the regulatorytext at § 725.205(b)(2)(i) through (iv). Anexample of ‘‘other evidence’’ of acommercial application cited under§ 725.205(b)(2)(iv) would be if theresearcher has engaged in seriousdiscussions with a company concerningmarketing or commercializing themicroorganism if initial research issuccessful. If researchers have difficultydeciding whether their research is forcommercial purposes, they areencouraged to consult EPA.

The above approach represents amodified version of the indicia ofcommercial purposes approachdiscussed in the preamble to theproposed rule. EPA has adopted thismodified version for the followingreasons. All research conducted directlyby a commercial entity is clearly forcommercial purposes, as the courtdecided in The Dow Chemical Companyv. EPA, 605 F.2d 673 (3d Cir. 1979).Consequently, if a business directlyfunds a research activity for potentialproduct development, the activity is forcommercial purposes, even if theresearch activity is conducted at anacademic institution. EPA has chosen tofocus on the source of funding for thespecific laboratory work or field test orother environmental testing as theappropriate indicator of commercialintent, because EPA recognizes that itcan be difficult to trace sources offunding at the institutional level andagrees with the commenter who statedthat ‘‘there is no logical basis for theassertion that commercial support ofone narrowly defined project changesthe fundamental academic nature ofevery other activity conductedelsewhere in the institution.’’

EPA’s definition of commercialpurposes is consistent with the currentregulations for traditional chemicals,which define a commercial activity asone undertaken with the purpose ofobtaining an immediate or eventualcommercial advantage. For example,this is the definition in § 720.3(r), whichdefines ‘‘manufacture or import forcommercial purposes,’’ and § 721.3,which defines ‘‘process for commercialpurposes.’’ Consequently, EPA hasadopted the idea in § 725.3, whichdefines for microorganisms‘‘manufacture, import, or process forcommercial purposes.’’ Similarly,§ 720.30(i) provides that ‘‘non-

commercial research and development’’consists of activities conducted byacademic, government, or independentnot-for-profit organizations ‘‘unless theactivity is for eventual commercialpurposes.’’ EPA has developed acomparable exclusion for non-commercial R&D uses ofmicroorganisms by including adefinition of ‘‘commercial purposes forresearch and development activities’’ at§ 725.205(b). As noted above, thiscommercial indicia approach applies toR&D in laboratories and other containedstructures, as well as to intentionaltesting in the environment.

EPA’s experience over the past severalyears responding to researchersinquiring about the status of theirenvironmental research under TSCAindicates the following points. All of theresearchers identified the sources oftheir funding for the particularexperiments. Generally they were ableto readily indicate whether theybelieved there was a future commercialapplication for the microorganismwhich they intended to pursue. In mostcases where a company was directlyfunding field tests to be conducted atuniversity sites, the company contactedEPA directly and took responsibility forpreparation of the PMN. In one case,researchers were being funded byFederal agencies but were usingcompany-owned microorganismssubject to a TSCA section 5(e) consentorder. The company asked EPA tomodify the consent order to allow thecompany to give the microorganisms tothe researchers for use in their fieldtests. Although the company made theoriginal request, the researcherssubmitted information about their fieldtests to EPA. Therefore, researchersshould contact EPA if they are planningfield tests involving intergenericmicroorganisms supplied by a company.In most cases, a TERA would berequired.

In several cases where researcherscontacted EPA regarding the status oftheir field tests, EPA found that fieldtests using intergeneric microorganismswere not subject to TSCA, because thefield tests were being funded by otherFederal agencies and the researchers didnot foresee future commercial uses fortheir microorganisms. Finding that thesefield tests did not constitute commercialR&D under TSCA, EPA directed theresearchers to the Federal agencieswhich were the primary funding sourcesfor the field tests and suggested thatresearchers should, at a minimum,obtain reviews from these agenciesunder relevant authorities, includingmeeting the National Environmental

Policy Act (NEPA) responsibilities ofthese other agencies.

Although EPA has chosen in this finalrule to follow an approach for‘‘commercial purposes’’ similar to itsapproach for traditional chemicals, EPArecognizes that there are no differencesin risk depending on funding source.EPA takes seriously its responsibilitiesto address risk and intends to pursueapproaches laid out in the CoordinatedFramework for Regulation ofBiotechnology (51 FR 23302, June 26,1986) to ensure an adequate network ofoversight of R&D activities. To this end,EPA will work closely with otheragencies, particularly NIH.

3. Microorganisms eligible for theR&D small quantities exemption. TSCAsection 5(h)(3) exempts from section 5screening, chemical substancesmanufactured or processed in smallquantities solely for R&D and directsEPA to define small quantities by rule.EPA’s regulations for traditionalchemicals at § 720.3(cc) define ‘‘smallquantities solely for R&D’’ as thosequantities that are ‘‘not greater thanreasonably necessary for ...[R&D]purposes.’’ This definition of smallquantities for R&D has been appropriatefor traditional chemical substances,because these chemicals do not have theability to increase their own volume oramount. However, livingmicroorganisms may reproduce andincrease beyond the number initiallyintroduced, may establish in theenvironment, and may spread beyondthe test site. Once they are released intothe environment or are no longercontained, there is no longer anassurance they will remain ‘‘smallquantities.’’

Therefore, EPA’s definition at § 725.3of ‘‘small quantities’’ formicroorganisms is restricted tomicroorganisms used under conditionsthat meet the requirements of § 725.234,which are designed to reduce theprobability of establishment by reducingthe number and frequency of viablemicroorganisms emitted from a facility.The small quantities exemption formicroorganisms is also referred to as the‘‘contained structures’’ exemption,because § 725.234(c) limits theexemption to R&D activities incontained structures.

Most of the comments EPA receivedon its application of the section 5(h)(3)exemption to R&D activities withmicroorganisms in contained structuresrequested clarification with regard tothe use of research microorganisms incommerce, the use of genetic libraries,and coordination with the NIHGuidelines. None of the commentersprovided EPA with new information


that would cause EPA to reconsider orchange the basis for its decision torestrict the section 5(h)(3) exemption tomicroorganisms used under conditionsmeeting the requirements of § 725.234.Consequently EPA has adopted theproposed regulatory text for thisexemption with some revisions. Therequirements for this exemption arefound in the regulatory text in§§ 725.232, 725.234 and 725.235. Theseissues are discussed in the proposedrule (59 FR 45539-42) and in theResponse to Comments document inUnit IV.C.

For purposes of clarification, EPA hasmodified requirements originallyincluded in proposed § 725.235. Most ofthe proposed language was adapted,with little revision, from the smallquantities exemption for traditionalchemicals at § 720.36. Upon furtherreflection, EPA has determined thatsome of that language is not appropriatefor microorganisms. Therefore, EPA hasdeleted proposed § 725.235(a)(2), whichprovided an exemption from the smallquantities notification requirements forR&D in a laboratory, and proposed§ 725.235(e), which related to impuritiesand articles. Additionally, therequirements at proposed § 725.235(c),(d), and (f) have been moved to§ 725.205(d), (e), and (f), respectively, asthese requirements apply to all R&Dactivities under subpart E. EPA hasfurther revised § 725.205(f) tospecifically exclude microbialpesticides by referring to the microbialpesticide notification requirements thatwere promulgated in September 1994(59 FR 45612).

EPA disagrees with the commenterwho stated that EPA had not justifiedthe ‘‘wholesale removal of the R&Dexemption provided by Congress.’’TSCA section 5(h)(3) does not providea complete exemption for all R&D, norhas EPA removed the statutoryexemption wholesale. Rather, TSCAsection 5(h)(3) exempts from section 5reporting chemical substancesmanufactured or processed in smallquantities for R&D and specificallydirects EPA to define ‘‘small quantities’’by rule. EPA has determined that thedefinition of ‘‘small quantities’’ appliedat § 720.3 to traditional chemicalsubstances cannot be applied to all R&Dactivities involving microorganisms forthe reasons discussed in the proposedrule (59 FR 45539-40).

4. R&D subject to TSCA and anotherFederal agency. In the proposed rule,EPA discussed situations where R&Dactivities might be subject to both TSCAand another Federal authority. EPAsuggested different approaches todealing with overlapping jurisdiction,

depending on whether the R&Dactivities were conducted in a containedstructure or involved intentionalenvironmental testing.

EPA proposed a complete exemptionfrom EPA-specific reporting underTSCA section 5(h)(4) for research onnew microorganisms in containedstructures, if the research is regulated orfunded by a Federal agency which hasagreed to abide by the NIH Guidelines.

In the proposed rule (59 FR 45542-43), EPA discussed exempting fromTSCA section 5 requirements theintentional environmental testing ofnew microorganisms, when anotherFederal agency has clear regulatoryauthority and EPA determines that theother Federal agency’s review addressescriteria equivalent to those which wouldbe evaluated under TSCA section 5.Specifically, EPA indicated that it wasworking with USDA/APHIS to developan exemption from TSCA section 5requirements for R&D field testsreviewed by APHIS under the FederalPlant Pest Act and the Plant QuarantineAct.

Several commenters supported theproposal to exempt from EPArequirements those researchers whomandatorily comply with the NIHGuidelines. Some commenters statedthat researchers who voluntarily complywith the NIH Guidelines should also beexempt from the TSCA section 5(h)(3)requirements. Some commentersspecifically supported EPA’s discussionof potentially deferring to otheragencies’ reviews and determinations,when appropriate, for intentionalenvironmental testing of newmicroorganisms. It was requested thatEPA clarify its relationship with USDA/APHIS. Some commenters suggestedextension of EPA’s proposal to defer toother Federal agencies.

EPA has retained at § 725.232(b) itscomplete exemption from TSCA section5 obligations for research on newmicroorganisms in contained structures,if the researcher is receiving funds fromanother Federal agency which requirescompliance with the NIH Guidelines.This includes all research, whetherdirectly funded by an agency or not, ata university or institution that adheresto the NIH Guidelines on an institution-wide basis as a condition of receivingFederal funds. EPA developed thisexemption to avoid duplicativeoversight with other Federal authorities.Researchers who are complying with theNIH Guidelines voluntarily or throughvehicles such as contracts or localregulations, will not be eligible for theexemption at § 725.232, because theirresearch is not being overseen byanother Federal agency. However, as

discussed further below, EPA believesthat anyone who is complying with theNIH Guidelines should be able to meetthe requirements of §§ 725.234 and725.235 with little difficulty.

EPA agrees in principle withcommenters who believe that, whenconsistent with the requirements of thestatutes involved, products subject toanother statute as well as to TSCA needonly be regulated by one of thoseagencies. Presently, EPA has identifiedthe Plant Pest Act and Plant QuarantineAct administered by USDA/APHIS aspresenting some degree of overlappingjurisdiction with TSCA formicroorganisms. At this time EPA andUSDA do not know of any productssubject to overlapping jurisdiction.Should such a situation arise, EPA willwork with APHIS to develop a proposedexemption from TSCA section 5requirements for R&D field tests subjectto overlapping jurisdiction. In thefuture, should other cases of duplicativeoversight arise, EPA will work with theother agencies involved to develop anappropriate solution. These issues arediscussed in the Response to Commentsdocument in Unit IV.D.

5. Requirements for small quantities/contained R&D exemption. EPAindicated in the proposed rule (59 FR45540) that for those researchers whoare voluntarily complying with, but arenot subject to, the NIH Guidelines, therequirements of the R&D smallquantities exemption at § 725.234 couldbe met by having the principalinvestigator (PI) serve as the technicallyqualified individual (TQI) required by§ 725.234(b) and keep records indicatingthat they abide by and are following theNIH Guidelines for the specific TSCA-subject R&D activities. However, EPAproposed to rely on the experience andjudgement of the TQI to selectcontainment and inactivation controlsappropriate to the microorganism(s)being utilized. In some cases, the TQIcould find it appropriate to use NIHGuidelines, and in others, the TQI mightnot. EPA took this position, becauseEPA recognized that many differentkinds of microorganisms displaying awide range of characteristics couldpotentially be used in research and thatthe type of controls appropriate for onemicroorganism might have limitedrelevance to other microorganisms. Thisissue is discussed in the Response toComments document in Unit IV.E.

Several commenters indicatedsupport for use of the NIH Guidelinesand requested clarification and/or madesuggestions concerning the relationshipof the NIH Guidelines to the R&D smallquantities exemption. While EPAconsiders the NIH Guidelines to provide


the primary standard for laboratoryresearch, EPA continues to believe thatit is appropriate to allow TQIs to havethe option of relying on their experienceand judgement in selecting appropriatecontainment as opposed to being forcedto rely solely on the NIH Guidelines. Inaddition, not all TSCA-subjectmicroorganisms will also be subject tothe NIH Guidelines, since theGuidelines focus on research involvingrecombinant DNA (rDNA) moleculesand EPA focuses on intergenericmicroorganisms as ‘‘new.’’ Therefore,some researchers will need to rely forsome activities on EPA’s criteria at§ 725.234, since their activities will notbe covered by the NIH Guidelines. Instructuring its approach, EPA believes ithas provided an appropriate measure offlexibility to researchers. Additionally,EPA believes that those researchers whocurrently comply with the NIHGuidelines, but are not eligible for theexemption under § 725.232,nevertheless can comply with therequirements of §§ 725.234 and 725.235with little additional burden beyondthat imposed by the NIH Guidelines.

With respect to the requirement at§ 725.234(d)(2) for certification by anauthorized official, EPA recognized inthe proposal (59 FR 45540) thatInstitutional Biosafety Committees(IBCs) and similar committees arecharged with assessing the containmentselected by researchers. EPA encouragesthe active use of such committees andagrees that an authorized official may bean IBC chair. EPA also evaluated thecomments on the burden imposed byrecordkeeping for the R&D smallquantities exemption. As EPA noted inthe proposal, EPA believes that personsfollowing the NIH Guidelines wouldkeep records as part of normalprocedures at an institution where IBCsare responsible for ensuring the safety ofresearch. Such records are likely to beadequate for meeting the provisions at§ 725.234(d)(3). This issue is discussedin more detail in the Response toComments document in Unit IV.E.,which also provides a comparison of theNIH Guidelines and the requirements of§§ 725.234 and 725.235.

Several commenters suggested thatEPA adopt the NIH Guidelines as arequirement for the R&D smallquantities exemption. As discussedpreviously, EPA believes that it is moreappropriate to show researchers how theuse of the NIH Guidelines can fulfill therequirements of the R&D smallquantities exemption and has includeda comparison discussion in theResponse to Comments document inUnit IV.E.1. In general, EPA expects thatcompanies currently complying with

the NIH Guidelines will also be able tosatisfy the requirements of the R&Dsmall quantities exemption. Althoughthe NIH Guidelines do not explicitlystate that documentation of thenotification is required, the requirementfor such documentation can be readilyinferred in section IV. of the NIHGuidelines. Because TSCA explicitlyrequires such notification, researchersmay still need to verify that thedocumentation maintained pursuant tothe NIH Guidelines includesdocumentation of the notification asspecified in § 725.235(c)(1).

Like the NIH Guidelines, EPA’sregulations cannot anticipate everyresearch situation. Therefore, using thecomparison of the NIH Guidelines andthe requirements of §§ 725.234 and725.235 as guidance, researchers subjectto TSCA section 5 and complying withthe NIH Guidelines should evaluatetheir specific research situation todetermine whether their use of theGuidelines also fulfills the requirementsof §§ 725.234 and 725.235.

6. Exemptions from TERA reportingfor certain R&D activities conductedoutside a structure. In the proposedrule, EPA discussed a process forexempting small-scale field tests ofcertain microorganisms from TERAreporting. To qualify for the exemption,certain criteria regarding the recipientmicroorganisms, the source(s) andcharacteristics of the introduced geneticmaterial, and the conditions of usewould need to be met. EPA proposedcertain strains of Bradyrhizobiumjaponicum and Rhizobium meliloti ascandidates for exemption from TERAreporting, based on EPA reviews ofvoluntary PMNs for thesemicroorganisms submitted under the1986 Policy Statement and field testdata generated in these field trials. Inresponse to comments, EPA hasmodified some of the specificconditions for the exemption. Somecommenters expressed concern aboutEPA’s proposal to exempt strainscontaining antibiotic resistance markersfrom any source. EPA has determinedthat for the exemption described at§ 725.239, it will follow the conservativecourse of only allowing use in B.japonicum and R. meliloti of thosemarkers EPA has reviewed for use inthese microorganisms. This approachwould ensure that the probability ofpresenting unreasonable risk would below for each antibiotic resistancemarker. The regulatory text at§§ 725.239(a)(2)(ii)(A)(1) and725.239(b)(2)(ii)(A)(1) has beenmodified to limit structural genesencoding marker sequences to thoseencoding resistance to the aadH gene,

which confers resistance tostreptomycin and spectinomycin, inthese microorganisms. Based on EPA’sanalysis of use of this marker inrhizobia, and including consideration ofthe advice of the January 4, 1995 BSACSubcommittee, the use of streptomycinand/or spectinomycin resistancemarkers in B. japonicum and R. meliloticurrently meets this requirement of theexemption.

EPA recognizes that the exemption at§ 725.239 is narrow and may only applyto very few research projects. It may bethe case in the early years of the TERAprogram that TERA exemptions arenarrowly written to apply to specificmicroorganisms that have completedTERA review. However, EPA hopes thatin the longer term as EPA gains greaterexperience reviewing intergenericmicroorganisms for environmental uses,broader exemptions can be written. Tothat end, EPA has placed generalrequirements for the TERA exemptionin § 725.238 and will use § 725.239 tolist certain microorganisms for theexemption and the specific conditionsof use as needed.

7. TERA reporting process. Undersection 5(h)(4), EPA proposed toconditionally exempt from MCANnotification certain R&D activitiesinvolving new microorganisms. Theexemption is conditional, sinceresearchers must submit a TERA, anabbreviated notification. Due to theavailability of other exemptions for R&Dactivities discussed in this preamble,EPA expects that the TERA will be usedprimarily for environmental research. Inthe proposed rule (59 FR 45535), EPAindicated that its goal was to reviewTERAs in 60 days, but that for goodcause, EPA could extend the initialTERA review period by an additional 60days, for a total of 120 days. Thiscondition, the information requirementsfor submitters, and the TERA approvalprocess have not been changed from theproposed rule. This exemption isdiscussed in the proposed rule (59 FR45535-36, 45543-44) and in theResponse to Comments document inUnit IV.G.

EPA received some commentssupporting the TERA process. Othercommenters who opposed the use of theTERA process and stated that some ofthe information requirements were tooextensive, also stated that specificmonitoring data should be required.EPA has made minor revisions to theTERA requirements at §§ 725.250through 725.288. Issues raised aboutstate coordination are discussed in thenext section.

EPA believes that it is necessary toestablish a review and approval process


specifically for R&D activities involvingenvironmental release. While manyfield tests of new microorganisms willbe determined to pose low risks, thisassumption cannot be made for fieldtests in general, and thus EPA findssome type of review is warranted.However, EPA recognizes that fullMCAN reporting also may not bewarranted. Therefore, EPA has chosento develop a review and approvalprocess specifically tailored to addressR&D.

EPA believes that the informationrequirements proposed for the TERA areappropriate. EPA must have sufficientinformation to evaluate the health andenvironmental effects of a planned fieldtest. However, because a variety ofmicroorganisms are potentially subjectto TSCA, the requirements indicated in§ 725.255 are necessarily broad. Not allof the requirements are equallyapplicable to all microorganisms.Submitters are encouraged to consultwith EPA prior to preparing TERAs, sothat appropriate information needs andconcerns may be identified.

EPA has made minor changes to theregulatory text at § 725.270 to clarifythat EPA is approving or denying theTERA. Therefore, the term ‘‘TERAagreement’’ which was used in theproposed rule has been changed to‘‘TERA approval.’’ In addition toapproving or denying the TERA, EPAmay provide, in the TERA approval,conditions under which the R&Dactivity described in the TERA must beconducted in order for EPA to make theTSCA section 5(h)(4) finding that theR&D activity will not present anunreasonable risk to health or theenvironment. During the TERA reviewperiod, EPA may identify issues thatneed further information before EPA cangive its approval for the R&D activity toproceed. EPA or the submitter maysuspend the review period, if necessary.When EPA approves a TERA, thesubmitter must conduct the R&Dactivity only as described in the TERA,and any amendments to the TERA, andunder any conditions specified by EPAin its approval of the TERA.

8. Options for oversight of R&Dactivities. As discussed above, EPAproposed an approach for oversight ofR&D activities which included a varietyof exemptions from the full 90-dayreporting process required for generalcommercial use activities. EPA’s goalwas to provide a flexible process whichtailored oversight to the level of risk.EPA asked for comment on its R&Dexemptions, all of which have beendiscussed above, and indicated that thepublic could suggest other options forconsideration. Options for oversight

suggested by the commenters arediscussed in the Response to Commentsdocument in Unit IV.H. For a variety ofreasons, EPA concluded that thealternatives suggested would notadequately permit EPA to fulfill itsstatutory duties under TSCA section 5.

Some commenters, while indicatingthat the R&D exemptions werecomprehensible, did not believe thatlevel of oversight correlated to level ofrisk. EPA disagrees with comments thatthe level of oversight imposed in itsR&D exemptions is not correlated tolevel of risk. EPA discusses its view ofthe relationship between risk and theTSCA definition of ‘‘newmicroorganism’’ in Unit II.D. of theResponse to Comments document. EPAhas chosen to implement its R&Doversight in a manner whichdistinguishes between R&D activities incontained structures and R&D activitiesinvolving intentional release to theenvironment because of the greateroverall potential in the latter case forsurvival, dissemination, and exposure tothe microorganisms. Within this broadstructure, EPA has developed severalexemptions which recognize thediffering risk potentials presented bydifferent settings and organisms. Theseexemptions have been discussed aboveand are discussed in greater detail inUnits IV.C. through G. of the Responseto Comments document.

In the proposed rule (59 FR 45536-37), EPA briefly discussed an alternativeexemption for certain R&D releases.This alternative would containrequirements for documentation andrecordkeeping by a TQI and certificationby an authorized official. EPA is notfinalizing this option at this time.However, EPA plans to propose anexemption along these lines at a laterdate to allow the public an opportunityto comment on the new information onwhich EPA is relying to support theexemption.

D. Other Issues1. Microorganism definition. In the

proposed rule (59 FR 45550-51), EPAdefined ‘‘microorganisms’’ in § 725.3 asthose organisms classified under the 5-kingdom system of Whittacker (Ref. 5)in the kingdoms Monera (orProcaryotae), Protista, and Fungi, theChlorophyta and the Rhodophyta of thePlantae, and viruses and virus-likeparticles. Therefore, this definitionincludes, but is not limited to, bacteria,protozoa, fungi, mycoplasmas,mycoplasma-like organisms,spiroplasmas, microphytoplanktons,green and red algae, viruses, and virus-like particles (e.g., viroids, satellites,and virusoids). Should new categories

of organisms within the Monera,Protista, Fungi and the Chlorophyta andRhodophyta of the Plantae be identified,these would also be consideredmicroorganisms under this definition.

EPA proposed to treat viruses of othermicroorganisms (also termed phages) asMGEs. EPA’s MGE policy is discussedin the proposed rule (59 FR 45528) andin Unit II.D. of the Response toComments document. In the proposedrule, EPA indicated that it was not ableto identify uses of viruses ofmacroorganisms that might be subject toTSCA. EPA asked if it was appropriateto apply the intergeneric interpretationto viruses of macroorganisms if TSCAuses for such viruses were identified.

Commenters thought the proposeddefinition of ‘‘microorganism’’ wasreasonable and included the appropriateorganisms. Thus, EPA will retain thedefinition of ‘‘microorganism’’ asdiscussed in the proposed rule andfound in the regulatory text in § 725.3.EPA has modified the definition toclearly indicate in the regulatory textthat EPA is using the 5-kingdomclassification of Whittacker.Additionally, as discussed in theproposal, EPA will treat phages asMGEs. No commenters identifiedcurrent or imminent TSCA uses ofviruses of macroorganisms. Therefore,EPA believes the best use of limitedresources would be to develop anapproach under TSCA for viruses ofmacroorganisms in the future if TSCAuses are identified. The definition ofmicroorganism is discussed in theResponse to Comments document inUnit V.A.

2. TSCA Inventory. EPA described inthe proposed rule (59 FR 45551-52) howit planned to explicitly listmicroorganisms on the TSCA Inventoryand the rationale for the proposedlisting. EPA proposed to identifymicroorganisms on the Inventory usinga taxonomic designation and aconsistent set of supplementalinformation on phenotypic andgenotypic traits necessary to identify themicroorganism as precisely as possible.Additionally, EPA indicated that it wasconsidering requiring thatmicroorganisms listed on the Inventorybe deposited in a recognized culturecollection.

In the proposed rule, EPA advisedmanufacturers and importers of any ofthe 192 microorganisms reported in1978 for the initial TSCA Inventory thatEPA planned to remove from theInventory the explicit listing of thesemicroorganisms. EPA believed that mostof these microorganisms are notintergeneric; therefore they would beautomatically included on the Inventory


and do not need to be explicitly listed.EPA asked manufacturers and importersof these microorganisms to inform EPAif any of the microorganisms wereintergeneric and should not be removedfrom the Inventory.

In response to EPA’s request forcomments on developing a requirementfor culture collection deposit, severalcommenters strongly opposed thedevelopment of any requirement fordeposit of a microorganism in a culturecollection. One commenter wasconcerned about the effect that an EPArequirement would have on patentprotection. Others believed that such arequirement would be unnecessary andonerous at the R&D stage. EPA hasconsidered the concerns raised bycommenters who oppose the culturecollection requirement and has decidedthat deposit of new microorganisms inrecognized culture collections is notnecessary. Therefore, EPA has not madethis a requirement for microorganismssubject to TSCA section 5 reporting.

Commenters asked that EPA clarifythe type of taxonomic designation to beused for Inventory listing and indicatehow revisions to taxonomy would beaccommodated on the Inventory. Othersasked EPA to clarify what is ‘‘new’’under TSCA, particularly with respectto minor changes made during strainimprovement of microorganisms alreadylisted on the Inventory. EPA agrees thatInventory listing for intergenericmicroorganisms is more complex thanlisting for most traditional chemicals.As indicated above, EPA plans toconsider modifications andclarifications to its intergenericinterpretation in the future. Futuremodifications to the intergenericinterpretation will also affect howmicroorganisms are listed on theInventory. A subcommittee of EPA’sBSAC, which met on July 22, 1991,when questioned on EPA’s proposedapproach to Inventory listing formicroorganisms, suggested that EPAcontinue on a case-by-case basis andgain additional experience beforefinalizing its requirements for Inventorylisting. Therefore, EPA believes itprudent to defer a fuller development ofInventory listing for microorganismsuntil it has considered modifications tothe intergeneric interpretation and gainsadditional experience. Meanwhile, EPAwill use a case-by-case approach toInventory listing for newmicroorganisms. Inventory issues arediscussed in the Response to Commentsdocument in Unit V.B. EPA hasprovided some clarification regardinguse of taxonomy in the Response toComments document in Unit II.D.Additional guidance on Inventory

listing may also be found in theproposed rule preamble (59 FR 45551-52).

Commenters requested that EPAprovide a ‘‘grandfather’’ period byopening up the Inventory for 1 year afterthe final rule is published to allowproducts currently in commerce to belisted. One commenter requested thatintergeneric products currently incommerce be automatically placed onthe Inventory. EPA disagrees with thecommenters who believe that a‘‘grandfather’’ period is necessary. Sincethe publication of the 1986 PolicyStatement in June 1986, EPA hasrequired PMN reporting for generalcommercial use of intergenericmicroorganisms subject to TSCA.Although different scopes of oversighthave been discussed in the interveningyears, the Policy Statement hasremained in effect all that time.Therefore, EPA believes that the publichas had sufficient notice of its programand that intergeneric microorganismscurrently in commerce and being usedfor TSCA purposes should already havebeen reported to EPA.

In response to the EPA proposal todelist 192 microorganisms currentlylisted on the Inventory by genus andspecies only, commenters discussedtheir concerns. One commenter statedthat there was no information about thephenotypic characteristics of thesestrains or about any introduced DNA.EPA wishes to clarify its position onmicroorganisms currently listed on theInventory. These microorganisms can bedivided into two groups: (1) Thosereported to the initial Inventory in thelate 1970s, and (2) those listed afterEPA’s review of PMNs and receipt ofNotices of Commencement tomanufacture. EPA has no concernsabout the Inventory status of the secondgroup, because these microorganismswere all reported to EPA under the 1986Policy Statement and therefore areintergeneric and are appropriatelyexplicitly listed. The listings for thesemicroorganisms include descriptiveinformation to specifically identify thembeyond the genus and speciesdesignations.

Such is not the case for the firstgroup, the 192 microorganisms reportedfor the initial Inventory in the late1970s. As one commenter noted, thesemicroorganisms are primarily listed bygenus and species. EPA believes thatmost of these microorganisms arenaturally occurring or have beenmodified by methods that do notinvolve the introduction of DNA froman organism in another genus and thusin many cases would not need to beexplicitly listed. To confirm this

assumption, EPA requested commentfrom persons manufacturing orimporting any of the 192microorganisms. No comments werereceived on the status of thesemicroorganisms. EPA wishes to ensurethat all microorganisms which areexplicitly listed on the Inventory areintergeneric and are described in aconsistent manner. Therefore, EPA hasconcluded that the 192 microorganismsare not intergeneric and, thus, areautomatically on the Inventory under§ 725.8(b). EPA will remove the explicitlistings from the Inventory in a separateaction under the authority of TSCAsection 8(b).

3. Confidential Business Information.EPA proposed to require upfrontsubstantiation of confidential businessinformation (CBI) claims in allsubmissions for general commercialuses of microorganisms. Under theproposal, anyone submitting a MCAN, aTest Marketing Exemption (TME), Tier Icertification, or a Tier II exemptionrequest would be required tosubstantiate CBI claims at the time ofsubmission. With respect to upfrontsubstantiation for TERAs, EPA proposedtwo options and asked for publiccomments on both. Option 1 wouldhave required upfront substantiation ofall CBI claims in TERAs. Option 2would not have required upfrontsubstantiation of CBI claims in TERAs,but would only require CBIsubstantiation after EPA received aFreedom of Information (FOIA) request.

One commenter asked for additionalclarification of EPA’s CBI policy formicroorganism submissions. Twocommenters supported EPA’s proposalto require upfront substantiation of CBIclaims for submissions for both researchand general commercial use. However,most commenters opposed upfrontsubstantiation of CBI claims in R&Dsubmissions, indicating that therequirement was too burdensome forR&D, especially because it wasimportant to have proprietary protectionfor R&D activities. Some commentersspecifically opposed upfrontsubstantiation of CBI claims insubmissions for R&D submissions only.Others opposed upfront substantiationof CBI claims in any microorganismsubmission, arguing that EPA’sapproach to substantiation of CBI claimsin microorganism submissions shouldnot differ from EPA’s approach tosubstantiation of CBI claims intraditional chemical submissions.

Considering the competing interestsin the comments received and theburden imposed on industry, EPA hasdecided not to require upfrontsubstantiation of CBI claims in TERAs


but will retain the upfrontsubstantiation requirement for CBIclaims in MCANs, TMEs, Tier Icertifications, and Tier II exemptionrequests. In the past several years,submitters of voluntary PMNs for fieldtests of new microorganisms haveclaimed very little, if any, CBI.However, if, in the future, EPA findsthat CBI claims have increased inTERAs and that insufficient informationis available to the public during theshorter TERA review period, EPA mayfind it necessary to reconsider thedecision not to require upfrontsubstantiation of CBI claims in TERAs.At this time, EPA has revised theregulatory text at § 725.94(a)(2) to deletethe requirement for upfront CBIsubstantiation. In the case of generalcommercial use submissions, EPAbelieves that the upfront substantiationrequirement for CBI claims will imposelittle burden on submitters of MCANs,TMEs, Tier I certifications, and Tier IIexemption requests. Because personspreparing these submissions are readyto put their products on the market, theywill have a greater understanding of theproducts and any CBI issues and,therefore, should be able to justify whyit will continue to be necessary to keepcertain information confidential. Inaddition, given the shorter reviewperiod for TMEs and Tier II exemptionrequests, sufficient information may notbe made available to the public ifupfront substantiation of CBI claims isnot required. In particular, EPA may notbe able to comply with all deadlines ifa FOIA request is received.

4. Antibiotic resistance markers. EPAdid not establish a general policy foraddressing antibiotic resistance markersas part of its proposed rule. Use ofantibiotic resistance markers was onlydiscussed as part of the exemption fromTERA reporting proposed for certainmodified strains of Bradyrhizobiumjaponicum and Rhizobium meliloti atproposed § 725.239. Although EPA onlydiscussed the use of antibioticresistance markers as part of its proposalfor exempting two specificmicroorganisms from TERA reporting,EPA also received comments addressingmore generally the use of antibioticresistance markers. As discussed above,EPA has responded to comments on theTERA exemption, including revising theregulatory text at § 725.239 regardinguse of antibiotic resistance markers inthose microorganisms. The generaldiscussion of antibiotic resistancemarkers can be found in the Responseto Comments document in Unit V.E.

EPA recognizes that many factorsaffect the health and safety evaluation ofuse of antibiotic resistance markers. The

use of antibiotic resistance markers is acomplicated issue which hasramifications for products beyond thescope of TSCA. Because of thecomplexity, EPA will not issue a generalpolicy on the use of antibiotic resistancemarkers, but will continue to evaluatetheir use in specific microorganisms ona case-by-case basis as submissions arereceived. EPA plans to pursue this issuein consultation with other Federalagencies who have an interest in thisissue.

5. State coordination. The proposedrule discussed EPA’s procedures underthe 1986 Policy Statement forcoordinating reviews and sharingscientific information with appropriateState and local authorities (59 FR45531). EPA proposed to requirepersons preparing TERA submissionsfor R&D activities involving release tothe environment to provide evidence ofhaving notified appropriate Stateauthorities. This issue is discussed inthe Response to Comments document inUnit V.F.

Although one commenter supportedEPA’s proposed requirement for Statecoordination, several commentersopposed the requirement. EPA hasdeveloped comprehensive procedures tocoordinate reviews of submissions andto share scientific information withappropriate State and local authoritiesto the fullest extent possible withoutviolating TSCA CBI requirements.Comments and concerns raised by theState(s) are given careful attentionduring the review process. Statepersonnel receive a copy of anydocument which addresses theconditions under which the R&Dactivity, generally a field test, can beperformed.

EPA’s coordination procedures wouldmake researcher notification redundant.Consequently, EPA has revised§§ 725.238(b)(3)(ii) and 725.255(e)(1)(vi)to remove the requirement thatsubmitters include evidence that Stateauthorities have been notified in theTERA exemption certification andTERA submission, respectively. EPAwill continue to encourage submitters toadvise State and local authorities oftheir field test plans, although this willnot be a requirement. In cases wheresubmitters have informed State andlocal authorities of their test plans, EPAbelieves that it is appropriate to requirethat submitters inform EPA of thisnotification as part of their submissions.

VI. Economic Analysis

A. Introduction

EPA has prepared a Regulatory ImpactAnalysis (RIA) assessing the costs,

benefits, and associated impacts ofregulating new microorganisms underTSCA as set forth in this final rule. Asummary of key findings and estimatesis presented below.

B. Regulated CommunityAlthough unable to quantify the exact

magnitude of activity in biotechnologysectors affected by this rulemaking, theAgency believes that activities involvingmicroorganisms falling within the scopeof the final rule comprise a modestshare of overall activity. EPA estimatesthat approximately 130 firms may beinvolved in commercial R&D or ingeneral commercial use of potentiallyregulated microorganisms. In terms ofrevenue, the potentially affecteduniverse appears to be divided sharplybetween large and small firms. EPAestimates roughly one-half of thecompanies potentially affected to haveannual sales of $40 million or more,while most of those remaining areestimated to have sales under $10million. For many of these firms,however, revenue generated fromactivities subject to this rule is believedto represent only a small portion ofreported sales. At proposal, EPA alsoestimated that approximately 300universities could be affected by therulemaking. However, in the final rule,because of its implementation of adefinition of commercial purposes atR&D based on financial indicia, EPAbelieves substantially fewer universitieswill be affected.

C. Costs to SubmittersDue to data limitations and the

uncertainties associated with projectingfuture product development activities inbiotechnology application areas subjectto the final rule, EPA’s estimates of thecosts of compliance associated with thisrulemaking action have been onlypartially quantified. In cases where theAgency was able to generate quantifiedestimates of compliance costs,information which would havepermitted the development of moreaccurate estimates was frequentlyunavailable; in such cases, the bestavailable information was used, and theestimates are believed to represent areasonable approximation of actualcosts attributable to the rule. Asummary of EPA’s quantitative costestimates follows.

In assessing the potential cost impactof the final rule, EPA focussed on twoimpact years, ‘‘Year 1’’ and ‘‘Year 5.’’Year 1 costs are based on the expectedcosts associated with biotechnologyproducts in the early stage of regulation,while year 5 costs are based on aprojection of conditions following some


industry growth, subsequent to rulepromulgation. This approach was usedbecause of the relative immaturity of thebiotechnology sectors potentiallysubject to the rule, and the difficulty inattempting to forecast long-termtechnological and marketingdevelopments. It is emphasized,however, that estimated costs could besignificantly higher in the long-term,owing to continued industry expansion.

Four major cost areas were identified,based on an analysis of the requirementsof the rule. These areas were: costsincurred in preparing various types ofnotification submissions ordocumentation; costs incurred incomplying with any post reviewrequirements for monitoring or controlsthat may be imposed by EPA as a resultof risk concerns and uncertainties; costsincurred in substantiating CBI claims;and one-time costs attributable to rulefamiliarization.

Incremental costs to industry(industry-wide costs net requirementsunder current policy), estimated basedon prevailing wage rates for 1987, wereestimated to fall between $890,000 to$2.2 million in year 1 and between$70,000 to $510,000 in year 5. (Year 5costs account for rule familiarizationonly in the case of new firms enteringthe affected market areas, and thereforeare much less than year 1 costs, whererule familiarization costs were summedover all affected entities.) Adjusted toreflect current rates (1995 dollars),estimated incremental costs range from$1.2 million to $3.0 million in year 1and from $95,000 to $690,000 in year 5.

Cost impacts on individual productswill vary, depending on applicationarea. Submitters qualifying for full orpartial exemptions in connection withmicroorganisms intended for generalcommercial use will realize net savingsrelative to current reportingrequirements, while submitters filing inconnection with field experiments mayrealize an increase in regulatory burdenunder the rule.

D. Costs to the Federal GovernmentEPA estimated the potential costs to

government associated with the finalrule. These costs arise in connectionwith the Agency’s processing ofindividual notification submissions.

In estimating government costimpacts, EPA included costs estimatedto be incurred in reviewing eachsubmittal. EPA professionals andmembers of the Biotechnology ScienceAdvisory Committee were assumed tobe involved in such review. In the eventthat post-review restrictions are placedon a specific activity, such asmonitoring during a field test,

additional costs attributable to thedrawing up of regulatory documentationwould be incurred.

Incremental costs to the governmentwere estimated, using 1987 as the baseyear for valuing compensation, to fallbetween $115,000 to $122,000 in year 1,while year 5 costs were estimated to fallbetween -$105,000 (a net savings) to$4,000. Using 1995 as base year forcompensation, estimated incrementalcosts range from $156,000 to $165,000in year 1 and from -$143,000 to $5,300in year 5. Savings arise in connectionwith the substantial number of fullreviews that will be avoided due to theexemption provisions of the rule.

E. Benefits of the RuleEPA’s regulation of new

microorganisms under TSCA providesbenefits to society through reduction ofthe potential for adverse impacts onhealth and the environment resultingfrom the use of such organisms. Thisbenefit is achieved by screening newmicroorganisms and, when appropriate,imposing controls on microorganismuse to protect society from costly andpossibly irreversible damages.

For microorganisms in generalcommercial use, risk reductionattributable strictly to the notificationrequirements of the final rule would bemarginal, as these requirements arebased on current policy. However, therule enhances and contributes to theoverall risk reduction potential of theAgency’s program under TSCA byproviding for a more efficient regulatorystrategy relative to current policy,focussing society’s resources on thosenew microorganisms of greatestconcern.

For microorganisms in commercialR&D, a greater proportion of overall riskreduction can be attributed to the rule,since reporting in connection with fieldexperiments has been voluntary since1986. Though the Agency has receivedvoluntary submittals, it is uncertainwhether this practice is universal, orwhether those filing voluntarily wouldcontinue to do so in the absence of theserules.

Over the long-term, regulation is alsolikely to encourage development ofadditional information concerning fateand effects of new microorganisms, toencourage the development ofmicroorganisms which pose lowconcern for effects on human health andthe environment, and to encouragepublic input into decisions concerningthe use of new microorganisms.

Benefits may also be realized throughthe rule’s potential impact on the paceof product development. A lessuncertain regulatory climate could

stimulate business activity, as could amore reassured public. The rule mayalso reduce the possibility of continuedregulatory activity at the State and locallevel. A national system of potentiallyuncoordinated rulemaking initiativescould lead to market distortion andhamper competitiveness.

F. Effects of the Rule on InnovativeActivity

As a result of this final rule, membersof the regulated community may findproduct development strategies inconnection with certain products torequire reassessment. Since impacts ofthis nature could influence the degree ofemphasis a firm places on innovativeactivity, the potential for innovationimpacts was investigated.

Though great uncertainty regardingregulatory costs and the potential for aparticular product’s commercial successmake it impossible to estimateinnovation impacts quantitatively, theeffects of added regulatory costs anddelays on a product’s lifetime cash-flowwas examined. More specifically, anumber of plausible productdevelopment scenarios were modeledincorporating assumptions regardingexpenditures and returns over thecourse of a product’s useful life (fromresearch to obsolescence). Regulatoryburdens were then factored into themodels, and profit impacts observed.

Impacts realized when total regulatorycosts were assumed to reach the upper-bound of EPA’s estimated range couldresult in severe profit reductions insome cases; however, in general, EPA’sanalysis indicated that impacts shouldnot be prohibitive, particularly whenincremental costs are considered.Factors such as length of delay relatedto regulatory review, return rate, andobsolescence rate all play importantroles in determining the impact of EPA’sprogram on innovative activity, andthese factors are expected to be highlyvariable and product-specific.

G. Impacts on Small BusinessEPA survey data suggest 42 percent of

companies potentially affected by therule may be small businesses. Thoughdata were not available allowing theAgency to employ standard criteria forassessing the magnitude of smallbusiness impacts, the finding of asubstantial portion of the regulatedcommunity to be small businessesprompted EPA to propose options toprovide relief to such businesses. Theoptions considered included reducingCBI substantiation requirements and theelimination of the $100 filing fee.

Comments were submitted indicatingconcern for the rules impacts on


products of low-value or limited use,and for cost impacts on smallcompanies. Comments were alsoreceived on the Agency’s proposedalternatives for substantiation of CBIclaims in connection with TERAsubmissions.

With regard to comments regardingsmaller-scale product development andcost impacts on small business, EPAfinds that, because smaller scale projectswould most likely be exempt or involvea relatively limited set of use andexposure scenarios, burdens due toregulatory review would be expected tobe minimal; thus, the impacts of greatestconcern to smaller institutions ororganizations could be frequentlymitigated. In considering commentsregarding CBI substantiation, EPA hasdecided not to require upfront CBIsubstantiation in connection with TERAsubmissions, as most commentersgenerally indicated upfrontsubstantiation to be overly burdensomefor R&D. Since the Agency consideredreducing up-front CBI substantiationrequirements for small businessessubmitting TERAs in its IRFA, EPAviews the CBI substantiationrequirements contained in the final ruleas providing important burden relief tosmall businesses (or any business)conducting R&D.

VII. Public RecordEPA has established a public record

for this rulemaking (docket controlnumber OPPTS–00049C). The recordincludes all information considered byEPA in developing this final rule. Thisincludes all information in the docket,as well as information referenced indocuments in the docket. A publicversion of the record without anyconfidential information is available inthe TSCA Public Docket Office fromnoon to 4 p.m., Monday through Friday,except legal holidays. The TSCA PublicDocket Office is located in Rm. NE-G607, Northeast Mall, 401 M St., SW.,Washington, DC.

EPA has also made this final rule andcertain support documents availableelectronically. They may be accessedthrough the Internet at: gopher.epa.govor the Office of Pollution Preventionand Toxics Biotechnology home page athttp://www.epa.gov/opptintr/biotech/.

The record now includes thefollowing items:

1. All prior Federal Register Notices,and supporting public dockets, relatingto the regulation of microbial productsof biotechnology under TSCA. Theseinclude:

a. The 1984 Proposed PolicyStatement (49 FR 50856, December 31,1984).

b. The 1986 Policy Statement (51 FR23302, June 26, 1986).

c. ‘‘Biotechnology; Request forComment on Regulatory Approach,’’ 54FR 7027, February 15, 1989).

2. Public comments submitted inresponse to each of the above Notices,including the comments received at theSeptember 1989 Meeting which washeld to discuss TSCA regulatory optionsfor oversight of R&D.

3. ‘‘Principles for Federal Oversight ofBiotechnology: Planned IntroductionInto the Environment of OrganismsWith Modified Hereditary Traits,’’Office of Science and TechnologyPolicy, 55 FR 31118, July 31, 1990.

4. Reports of all BSAC meetingspertaining to the development of thisfinal rule.

5. The Regulatory Impact Analysis forthis final rule.

6. Support documents and reports.7. Records of all communications

between EPA personnel and personsoutside EPA pertaining to thedevelopment of this final rule. (Thisdoes not include any inter- or intra-agency memoranda, unless specificallynoted in the Index of this docket.)

8. The docket also includes publishedliterature that is cited in this document.

9. The Response to Commentsdocument responding to the publiccomments received on the September1994 proposed rule, and all referencescited therein.

VIII. References

The following books, articles, andreports were used in preparing this finalrule and were cited in this notice by thenumber indicated below:

1. Priest, F. G., M. Goodfellow, L.A.Shute, R.C.W. Berkeley. 1987. ‘‘Bacillusamyloliquefaciens. sp. nov., nom.rev.’’Internat. J. Syst. Bacteriol. 37:69-71.

2. U.S. Department of Health HumanServices, National Institutes of Health(NIH). 1994. ‘‘Guidelines for ResearchInvolving Recombinant DNA Molecules(NIH Guidelines)’’ (59 FR 34496, July 5,1994).

3. OECD. 1988. ‘‘Recombinant DNASafety Considerations.’’ OECD, Paris.

4. Radian Corporation. 1996. ‘‘Reviewof past premanufacture notices forpotential containment criteria for the5(h)(4) exemptions in the proposedbiotechnology rule.’’ U.S.Environmental Protection Agency,Office of Pollution Prevention andToxics, Chemical Engineering Branch,unpublished. Washington, D.C.

5. Atlas, R. and Bartha. R. 1987.‘‘Microbial Ecology.’’ Chapter 2 ‘‘Surveyof Microorganisms,’’ pg. 19-60.Benjamin/Cummings PublishingCompany, Inc. Menlo Park, CA.

6. Battelle. 1988. ‘‘Final Report onBiosafety in Large-Scale rDNAProcessing Facilities.’’ 4 volume set.U.S. EPA, Risk Reduction EngineeringLaboratory, Cincinnati, OH.

IX. Regulatory AssessmentRequirements

A. Executive Order 12866

Under Executive Order 12866 (58 FR51735, October 4, 1993), it has beendetermined that this rule is‘‘significant’’ because it may raise novelpolicy issues arising out of legalmandates. As such, this action wassubmitted to OMB for review, and anycomments or changes made in responseto OMB suggestions orrecommendations have beendocumented in the public record.

B. Regulatory Flexibility Act

Pursuant to section 605(b) of theRegulatory Flexibility Act (RFA) (5U.S.C. 601 et seq), the Agency herebycertifies that this final rule will not havea significant adverse economic impacton a substantial number of smallentities. The factual basis for thisdetermination is contained in the smallbusiness regulatory flexibility analysis,which is included as part of the RIAaccompanying this final rule, and issummarized in Unit V. of this preamble.In sum, EPA believes that themechanisms outlined in the final rulewill minimize economic impacts onsmall businesses as much as possible,and has determined that the rule shouldnot unduly burden small entities, norhinder the industry as a whole frompursuing a full range of productapplications.

Information relating to thisdetermination has been included in thedocket for this rule, and will beprovided to the Chief Counsel forAdvocacy of the Small BusinessAdministration upon request.

C. Paperwork Reduction Act

The Office of Management and Budget(OMB) has approved the informationcollection requirements contained inthis rule under the provisions of thePaperwork Reduction Act, 44 U.S.C.3501 et seq. and has assigned OMBcontrol number 2070-0012 (EPA ICR No.574).

This request is for an amendment toan existing ICR covering EPA’sPremanufacture Notice (PMN) reviewprogram as is necessary to: (1) Collectinformation on new microorganismsmanufactured or imported forcommercial use, and certain newmicroorganisms used for research anddevelopment (R&D); (2) reduce reporting


requirements for certain categories ofnew microorganisms; and (3) requirerecordkeeping demonstratingcompliance with conditions of certainexemptions for new microorganisms.

Section 5 of TSCA gives EPAauthority to review chemical substancesprior to their manufacture, importation,or processing in the U.S. in order todetermine whether such substances maypresent an unreasonable risk of injury tohealth or the environment. As explainedin the preamble to the proposed ruleand affirmed in Unit IV. earlier in thispreamble, the Agency has determinedsuch chemical substances to includemicroorganisms. To make a reasonedevaluation of the risk associated withnew microorganisms, EPA needs dataon each microorganism’s genetic make-up; physical, chemical, genetic orphenotypic properties; manufacturingprocess; worker exposure;environmental release; productionvolume; potential industrial,commercial, and consumer use; andrelated test data. The submission ofsuch data is mandatory, pursuant tosection 5(a)(1) of TSCA, 15 U.S.C. 2604,and is to be submitted 90 days beforemanufacture or import begins. Theconfidentiality of collected informationwill be maintained pursuant to theprovisions of TSCA, 15 U.S.C. 2613.

The projected annual incremental costto private parties associated with therule is $1.2 million, with an associatedburden of 41,000 hours. Annualincremental costs may be broken downinto two components - initialization orstart-up costs (rule familiarization),estimated to be $575,000, and costs forinformation disclosure and maintenanceof records, estimated to be $600,000.Annual burden is estimated to bedistributed among 218 responses,averaging 188 hours per response. Thenumber of potential respondents isestimated to be about 400 (not everypossible respondent is expected to fileeach year).

Burden means the total time, effort, orfinancial resources expended by personsto generate, maintain, retain, or discloseor provide information to or for aFederal agency. This includes the timeneeded to review instructions; develop,acquire, install, and utilize technologyand systems for the purposes ofcollecting, validating, and verifyinginformation, processing andmaintaining information, and disclosingand providing information; adjust theexisting ways to comply with anypreviously applicable instructions andrequirements; train personnel to be ableto respond to a collection ofinformation; search data sources;complete and review the collection of

information; and transmit or otherwisedisclose the information.

An Agency may not conduct orsponsor, and a person is not required torespond to a collection of informationunless it displays a currently valid OMBcontrol number.

D. Unfunded Mandates Reform Act andExecutive Order 12875

Pursuant to Title II of the UnfundedMandates Reform Act of 1995 (UMRA)(Pub. L. 104-4), EPA has determinedthat this action does not contain aFederal mandate that may result inexpenditures of $100 million or morefor State, local, and tribal governments,in the aggregate, or the private sector inany 1 year. The costs associated withthis action which are described in theExecutive Order 12866 section above arewell below $100 million for the privatesector. This rule does not impose anyduties upon States and localgovernment. Therefore, this action is notsubject to the requirements of sections202 and 205 of the UMRA.

E. Executive Order 12898Pursuant to Executive Order 12898

(59 FR 7629, February 16, 1994),entitled Federal Actions to AddressEnvironmental Justice in MinorityPopulations and Low-IncomePopulations, the Agency has consideredenvironmental justice related issueswith regard to the potential impacts ofthis action on the environmental andhealth conditions in low-income andminority communities. The Agency hasdetermined that nothing in thesenotification procedures shall contributeto disproportionately high and adversehuman health or environmental effectson such communities. This final ruledescribes informational requirementsprior to manufacture, process, or importof new microorganisms based only onsuch microorganisms’ geneticcharacteristics and, as such, shall nothave the effect of excluding populationsfrom participation in, denyingpopulations the benefits of, orsubjecting populations to discriminationbecause of their race, color, or nationalorigin.

F. Submission to Congress and theGeneral Accounting Office

Under 5 U.S.C. 801(a)(1)(A) of theAdministrative Procedure Act (APA) asamended by the Small BusinessRegulatory Enforcement Fairness Act of1996 (Title II of Pub. L. 104-121, 110Stat. 847), EPA submitted a reportcontaining this rule and other requiredinformation to the U.S. Senate, the U.S.House of Representatives and theComptroller General of the General

Accounting Office prior to publicationof the rule in today’s Federal Register.This rule is not a ‘‘major rule’’ asdefined by 5 U.S.C. 804(2) of the APAas amended.

List of Subjects in 40 CFR Parts 700,720, 721, 723, and 725

Environmental protection,Administrative practice and procedure,Biotechnology, Chemicals, Hazardoussubstances, Imports, Labeling,Microorganisms, Occupational safetyand health, Reporting andrecordkeeping requirements, Significantnew use rule.

Dated: March 26, 1997.Carol M. Browner,Administrator.

Therefore, 40 CFR Chapter I isamended as follows:

PART 700—[AMENDED]

1. In part 700:a. The authority citation for part 700

continues to read as follows:Authority: 15 U.S.C. 2625.

b. In § 700.43, by revising theintroductory text and the definition of‘‘Section 5 notice’’ and adding twodefinitions to read as follows:

§ 700.43 Definitions.Definitions in section 3 of the Act (15

U.S.C. 2602), as well as definitionscontained in §§ 704.3, 720.3, and 725.3of this chapter, apply to this subpartunless otherwise specified in thissection. In addition, the followingdefinitions apply:

Consolidated microbial commercialactivity notice or consolidated MCANmeans any MCAN submitted to EPAthat covers more than onemicroorganism (each being assigned aseparate MCAN number by EPA) as aresult of a prenotice agreement withEPA.

* * * * *Microbial commercial activity notice

or MCAN means any notice formicroorganisms submitted to EPApursuant to section 5(a)(1) of the Act inaccordance with subpart D of part 725of this chapter.

* * * * *Section 5 notice means any PMN,

consolidated PMN, intermediate PMN,significant new use notice, exemptionnotice, exemption application, anyMCAN or consolidated MCANsubmitted under section 5 of the Act.

* * * * *c. In § 700.45 by adding paragraphs

(b)(2)(vi), (e)(4)(iv), (e)(5)(iv), (f)(4), andrevising paragraphs (c) and (f)(3) to readas follows:


§ 700.45 Fee payments.* * * * *(b) * * *(2) * * *(vi) MCAN and consolidated MCAN.

Persons shall remit a fee of $2,500 foreach MCAN or consolidated MCANsubmitted.

(c) No fee required. Persons areexempt from remitting any fee forsubmissions under §§ 720.38, 723.50,and subparts E, F, and G of part 725 ofthis chapter.

* * * * *(e) * * *(4) * * *(iv) Each person who remits the fee

identified in paragraph (b)(1) of thissection for a MCAN for a microorganismshall include the words, ‘‘The companyidentified in this notice is a smallbusiness concern under 40 CFR 700.43and has remitted a fee of $100 inaccordance with 40 CFR 700.45(d),’’ inthe certification required in § 725.25(b)of this chapter.

(5) * * *(iv) Each person who remits a fee

identified in paragraph (b)(2) of thissection for a MCAN for a microorganismshall include the words, ‘‘The companyidentified in this notice has remitted thefee specified in 40 CFR 700.45(b),’’ inthe certification required in § 725.25(b)of this chapter.

(f) * * *(3) The notice is incomplete under

either § 720.65(c) or 725.33, of thischapter.

(4) That as of the date of submissionof the notice: the microorganism that isthe subject of a MCAN is not a newmicroorganism; nor is the use involvingthe microorganism a significant newuse.

d. By revising § 700.49 to read asfollows:

§ 700.49 Failure to remit fees.EPA will not consider a section 5

notice to be complete unless theappropriate certification under§ 700.45(e) is included and until theappropriate remittance under§ 700.45(b) has been sent to EPA asprovided in § 700.45(e) and received byEPA. EPA will notify the submitter thatthe section 5 notice is incomplete inaccordance with §§ 720.65(c) and 725.33of this chapter.



continues to read as follows:Authority: 15 U.S.C. 2604, 2607, and 2613.

b. In § 720.1, by revising the firstsentence and adding a sentence to readas follows:

§ 720.1 Scope.This part establishes procedures for

the reporting of new chemicalsubstances by manufacturers andimporters under section 5 of the ToxicSubstances Control Act, 15 U.S.C. 2604.This part applies to microorganismsonly to the extent provided by part 725of this chapter. * * *



continues to read as follows:Authority: 15 U.S.C. 2604, 2607, and

2625(c).

b. In § 721.1(a), by revising the firstsentence to read as follows:

§ 721.1 Scope and applicability.This part identifies uses of chemical

substances, except for microorganismsregulated under part 725 of this chapter,which EPA has determined aresignificant new uses under the authorityof section 5(a)(2) of the ToxicSubstances Control Act. * * *



continues to read as follows:Authority: 15 U.S.C. 2604.

b. In § 723.50, by revising the sectionheading and adding paragraph (a)(3) toread as follows:

§ 723.50 Chemical substancesmanufactured in quantities of 10,000kilograms or less per year, and chemicalsubstances with low environmentalreleases and human exposures.

(a) * * *(3) This section does not apply to

microorganisms subject to part 725 ofthis chapter.

* * * * *c. In § 723.175, by revising paragraph

(a)(1) to read as follows:

§ 723.175 Chemical substances used in orfor the manufacture or processing ofinstant photographic and peel-apart filmarticles.

(a) Purpose and scope. (1) Thissection grants an exemption from thepremanufacture notice requirements ofsection 5(a)(1)(A) of the ToxicSubstances Control Act (15 U.S.C.2604(a)(1)(A)) for the manufacture andprocessing of new chemical substancesused in or for the manufacture orprocessing of instant photographic andpeel-apart film articles. This sectiondoes not apply to microorganismssubject to part 725 of this chapter.

* * * * *d. In § 723.250, by revising paragraph

(a)(1) to read as follows:

§ 723.250 Polymers.

(a) Purpose and scope. (1) Thissection grants an exemption fromcertain of the premanufacture noticerequirements of section 5(a)(1)(A) of theToxic Substances Control Act (15 U.S.C.2604(a)(1)(A)) for the manufacture ofcertain polymers. This section does notapply to microorganisms subject to part725 of this chapter.

* * * * *5. Part 725 is added to read as follows:

PART 725—REPORTINGREQUIREMENTS AND REVIEWPROCESSES FOR MICROORGANISMS

Subpart A—General Provisions andApplicability

Sec.

725.1 Scope and purpose.725.3 Definitions.725.8 Coverage of this part.725.12 Identification of microorganisms forInventory and other listing purposes.725.15 Determining applicability whenmicroorganism identity or use is confidentialor uncertain.725.17 Consultation with EPA.

Subpart B—Administrative Procedures

725.20 Scope and purpose.725.25 General administrativerequirements.725.27 Submissions.725.28 Notice that submission is notrequired.725.29 EPA acknowledgement of receipt ofsubmission.725.32 Errors in the submission.725.33 Incomplete submissions.725.36 New information.725.40 Notice in the Federal Register.725.50 EPA review.725.54 Suspension of the review period.725.56 Extension of the review period.725.60 Withdrawal of submission by thesubmitter.725.65 Recordkeeping.725.67 Applications to exempt newmicroorganisms from this part.725.70 Compliance.725.75 Inspections.

Subpart C—Confidentiality and PublicAccess to Information

725.80 General provisions forconfidentiality claims.725.85 Microorganism identity.725.88 Uses of a microorganism.725.92 Data from health and safety studiesof microorganisms.725.94 Substantiation requirements.725.95 Public file.

Subpart D—Microbial Commercial ActivitiesNotification Requirements

725.100 Scope and purpose.725.105 Persons who must report.725.110 Persons not subject to this subpart.725.150 Procedural requirements for thissubpart.725.155 Information to be included in theMCAN.


725.160 Submission of health andenvironmental effects data.725.170 EPA review of the MCAN.725.190 Notice of commencement ofmanufacture or import.

Subpart E—Exemptions for Research andDevelopment Activities

725.200 Scope and purpose.725.205 Persons who may report under thissubpart.725.232 Activities subject to thejurisdiction of other Federal programs oragencies.725.234 Activities conducted inside astructure.725.235 Conditions of exemption foractivities conducted inside a structure.725.238 Activities conducted outside astructure.725.239 Use of specific microorganisms inactivities conducted outside a structure.725.250 Procedural requirements for theTERA.725.255 Information to be included in theTERA.725.260 Submission of health andenvironmental effects data.725.270 EPA review of the TERA.725.288 Revocation or modification ofTERA approval.

Subpart F—Exemptions for Test Marketing725.300 Scope and purpose.725.305 Persons who may apply under thissubpart.725.350 Procedural requirements for thissubpart.725.355 Information to be included in theTME application.725.370 EPA review of the TMEapplication.

Subpart G—General Exemptions for NewMicroorganisms

725.400 Scope and purpose.725.420 Recipient microorganisms.725.421 Introduced genetic material.725.422 Physical containment and controltechnologies.725.424 Requirements for the Tier Iexemption.725.426 Applicability of the Tier Iexemption.725.428 Requirements for the Tier IIexemption.725.450 Procedural requirements for theTier II exemption.725.455 Information to be included in theTier II exemption request.725.470 EPA review of the Tier IIexemption request.

Subparts H—K [Reserved]

Subpart L—Additional Procedures forReporting on Significant New Uses ofMicroorganisms

725.900 Scope and purpose.725.910 Persons excluded from reportingsignificant new uses.725.912 Exemptions.725.920 Exports and imports.725.950 Additional recordkeepingrequirements.725.975 EPA approval of alternative controlmeasures.

725.980 Expedited procedures for issuingsignificant new use rules for microorganismssubject to section 5(e) orders.725.984 Modification or revocation ofcertain notification requirements.

Subpart M—Significant New Uses forSpecific Microorganisms725.1000 Scope.

Authority: 15 U.S.C. 2604, 2607, 2613, and2625.

Subpart A—General Provisions andApplicability

§ 725.1 Scope and purpose.(a) This part establishes all reporting

requirements under section 5 of TSCAfor manufacturers, importers, andprocessors of microorganisms subject toTSCA jurisdiction for commercialpurposes, including research anddevelopment for commercial purposes.New microorganisms for whichmanufacturers and importers arerequired to report under section5(a)(1)(A) of TSCA are those that areintergeneric. In addition, under section5(a)(1)(B) of TSCA, manufacturers,importers, and processors may berequired to report for anymicroorganism that EPA determines byrule is being manufactured, imported, orprocessed for a significant new use.

(b) Any manufacturer, importer, orprocessor required to report undersection 5 of TSCA (see § 725.100 fornew microorganisms and § 725.900 forsignificant new uses) must file aMicrobial Commercial Activity Notice(MCAN) with EPA, unless the activity iseligible for a specific exemption asdescribed in this part. The generalprocedures for filing MCANs aredescribed in subpart D of this part. Theexemptions from the requirement to filea MCAN are for certain kinds ofcontained activities (see §§ 725.424 and725.428), test marketing activities (see§ 725.300), and research anddevelopment activities described inparagraph (c) of this section.

(c) Any manufacturer, importer, orprocessor required to file a MCAN forresearch and development (R&D)activities may instead file a TSCAExperimental Release Application(TERA) for a specific test (see§ 725.250). A TERA is not required forcertain R&D activities; however a TERAexemption does not extend beyond theresearch and development stage, togeneral commercial use of themicroorganism, for which compliancewith MCAN requirements is required.The TERA exemptions are for R&Dactivities subject to other Federalagencies or programs (see § 725.232),certain kinds of contained R&Dactivities (see § 725.234), and R&D

activities using certain listedmicroorganisms (see § 725.238).

(d) New microorganisms will beadded to the Inventory establishedunder section 8 of TSCA once a MCANhas been received, the MCAN reviewperiod has expired, and EPA receives aNotice of Commencement (NOC)indicating that manufacture orimportation has actually begun. Newmicroorganisms approved for use undera TERA will not be added to theInventory until a MCAN has beenreceived, the MCAN review period hasexpired, and EPA has received an NOC.

§ 725.3 Definitions.Definitions in section 3 of the Act (15

U.S.C. 2602), as well as definitionscontained in §§ 704.3, 720.3, and 721.3of this chapter, apply to this part unlessotherwise specified in this section. Inaddition, the following definitionsapply to this part:

Consolidated microbial commercialactivity notice or consolidated MCANmeans any MCAN submitted to EPAthat covers more than onemicroorganism (each being assigned aseparate MCAN number by EPA) as aresult of a prenotice agreement withEPA.

Containment and/or inactivationcontrols means any combination ofengineering, mechanical, procedural, orbiological controls designed andoperated to restrict environmentalrelease of viable microorganisms from astructure.

Director means the Director of theEPA Office of Pollution Prevention andToxics.

Exemption request means anyapplication submitted to EPA undersubparts E, F, or G of this part.

General commercial use means usefor commercial purposes other thanresearch and development.

Genome means the sum total ofchromosomal and extrachromosomalgenetic material of an isolate and anydescendants derived under pure cultureconditions from that isolate.

Health and safety study of amicroorganism or health and safetystudy means any study of any effect ofa microorganism or microbial mixtureon health or the environment or onboth, including underlying data andepidemiological studies, studies ofoccupational exposure to amicroorganism or microbial mixture,toxicological, clinical, and ecological, orother studies of a microorganism ormicrobial mixture, and any testperformed under the Act.Microorganism identity is always part ofa health and safety study of amicroorganism.


(1) It is intended that the term ‘‘healthand safety study of a microorganism’’ beinterpreted broadly. Not only isinformation which arises as a result ofa formal, disciplined study included,but other information relating to theeffects of a microorganism or microbialmixture on health or the environment isalso included. Any data that bear on theeffects of a microorganism on health orthe environment would be included.

(2) Examples include:(i) Tests for ecological or other

environmental effects on invertebrates,fish, or other animals, and plants,including: Acute toxicity tests, chronictoxicity tests, critical life stage tests,behavioral tests, algal growth tests, seedgermination tests, plant growth ordamage tests, microbial function tests,bioconcentration or bioaccumulationtests, and model ecosystem (microcosm)studies.

(ii) Long- and short-term tests ofmutagenicity, carcinogenicity, orteratogenicity; dermatoxicity;cumulative, additive, and synergisticeffects; and acute, subchronic, andchronic effects.

(iii) Assessments of human andenvironmental exposure, includingworkplace exposure, and impacts of aparticular microorganism or microbialmixture on the environment, includingsurveys, tests, and studies of: Survivaland transport in air, water, and soil;ability to exchange genetic material withother microorganisms, ability tocolonize human or animal guts, andability to colonize plants.

(iv) Monitoring data, when they havebeen aggregated and analyzed tomeasure the exposure of humans or theenvironment to a microorganism.

(v) Any assessments of risk to healthand the environment resulting from themanufacture, processing, distribution incommerce, use, or disposal of themicroorganism.

Inactivation means that livingmicroorganisms are rendered nonviable.

Institutional Biosafety Committeemeans the committees described in theNIH Guidelines in section IV.B.2.

Intergeneric microorganism means amicroorganism that is formed by thedeliberate combination of geneticmaterial originally isolated fromorganisms of different taxonomicgenera.

(1) The term ‘‘intergenericmicroorganism’’ includes amicroorganism which contains a mobilegenetic element which was firstidentified in a microorganism in a genusdifferent from the recipientmicroorganism.

(2) The term ‘‘intergenericmicroorganism’’ does not include a

microorganism which containsintroduced genetic material consistingof only well-characterized, non-codingregulatory regions from another genus.

Introduced genetic material meansgenetic material that is added to, andremains as a component of, the genomeof the recipient.

Manufacture, import, or process forcommercial purposes means:

(1) To import, produce, manufacture,or process with the purpose of obtainingan immediate or eventual commercialadvantage for the manufacturer,importer, or processor, and includes,among other things, ‘‘manufacture’’ or‘‘processing’’ of any amount of amicroorganism or microbial mixture:

(i) For commercial distribution,including for test marketing.

(ii) For use by the manufacturer,including use for product research anddevelopment or as an intermediate.

(2) The term also applies tosubstances that are producedcoincidentally during the manufacture,processing, use, or disposal of anothermicroorganism or microbial mixture,including byproducts that are separatedfrom that other microorganism ormicrobial mixture and impurities thatremain in that microorganism ormicrobial mixture. Byproducts andimpurities without separate commercialvalue are nonetheless produced for thepurpose of obtaining a commercialadvantage, since they are part of themanufacture or processing of amicroorganism for commercialpurposes.

Microbial commercial activity noticeor MCAN means a notice formicroorganisms submitted to EPApursuant to section 5(a)(1) of the Act inaccordance with subpart D of this part.

Microbial mixture means anycombination of microorganisms ormicroorganisms and other chemicalsubstances, if the combination does notoccur in nature and is not an article.

Microorganism means an organismclassified, using the 5-kingdomclassification system of Whittacker, inthe kingdoms Monera (or Procaryotae),Protista, Fungi, and the Chlorophytaand the Rhodophyta of the Plantae, anda virus or virus-like particle.

Mobile genetic element or MGE meansan element of genetic material that hasthe ability to move genetic materialwithin and between organisms. ‘‘Mobilegenetic elements’’ include all plasmids,viruses, transposons, insertionsequences, and other classes of elementswith these general properties.

New microorganism means amicroorganism not included on theInventory.

NIH Guidelines means the NationalInstitutes of Health (NIH) ‘‘Guidelinesfor Research Involving RecombinantDNA Molecules’’ (July 5, 1994).

Non-coding regulatory region means asegment of introduced genetic materialfor which:

(1) The regulatory region and anyinserted flanking nucleotides do notcode for protein, peptide, or functionalribonucleic acid molecules.

(2) The regulatory region solelycontrols the activity of other regions thatcode for protein or peptide molecules oract as recognition sites for the initiationof nucleic acid or protein synthesis.

Small quantities solely for researchand development (or ‘‘small quantitiessolely for purposes of scientificexperimentation or analysis or researchon, or analysis of, such substance oranother substance, including suchresearch or analysis for development ofa product’’) means quantities of amicroorganism manufactured, imported,or processed or proposed to bemanufactured, imported, or processedsolely for research and developmentthat meet the requirements of § 725.234.

Structure means a building or vesselwhich effectively surrounds andencloses the microorganism andincludes features designed to restrict themicroorganism from leaving.

Submission means any MCAN orexemption request submitted to EPAunder this part.

Technically qualified individualmeans a person or persons:

(1) Who, because of education,training, or experience, or acombination of these factors, is capableof understanding the health andenvironmental risks associated with themicroorganism which is used under hisor her supervision,

(2) Who is responsible for enforcingappropriate methods of conductingscientific experimentation, analysis, ormicrobiological research to minimizesuch risks, and

(3) Who is responsible for the safetyassessments and clearances related tothe procurement, storage, use, anddisposal of the microorganism as may beappropriate or required within the scopeof conducting a research anddevelopment activity.

TSCA Experimental ReleaseApplication or TERA means anexemption request for a research anddevelopment activity, which is noteligible for a full exemption fromreporting under § 725.232, 725.234, or725.238, submitted to EPA inaccordance with subpart E of this part.

Well-characterized for introducedgenetic material means that thefollowing have been determined:


(1) The function of all of the productsexpressed from the structural gene(s).

(2) The function of sequences thatparticipate in the regulation ofexpression of the structural gene(s).

(3) The presence or absence ofassociated nucleotide sequences andtheir associated functions, whereassociated nucleotide sequences arethose sequences needed to move geneticmaterial including linkers,homopolymers, adaptors, transposons,insertion sequences, and restrictionenzyme sites.

§ 725.8 Coverage of this part.(a) Microorganisms subject to this

part. Only microorganisms which aremanufactured, imported, or processedfor commercial purposes, as defined in§ 725.3, are subject to the requirementsof this part.

(b) Microorganisms automaticallyincluded on the Inventory.Microorganisms that are not intergenericare automatically included on theInventory.

(c) Microorganisms not subject to thispart. The following microorganisms arenot subject to this part, either becausethey are not subject to jurisdictionunder the Act or are not subject toreporting under section 5 of the Act.

(1) Any microorganism which wouldbe excluded from the definition of‘‘chemical substance’’ in section 3 of theAct and § 720.3(e) of this chapter.

(2) Any microbial mixture as definedin § 725.3. This exclusion applies onlyto a microbial mixture as a whole andnot to any microorganisms and otherchemical substances which are part ofthe microbial mixture.

(3) Any microorganism that ismanufactured and processed solely forexport if the following conditions aremet:

(i) The microorganism is labeled inaccordance with section 12(a)(1)(B) ofthe Act, when the microorganism isdistributed in commerce.

(ii) The manufacturer and processorcan document at the commencement ofmanufacturing or processing that theperson to whom the microorganism willbe distributed intends to export it orprocess it solely for export as defined in§ 721.3 of this chapter.

§ 725.12 Identification of microorganismsfor Inventory and other listing purposes.

To identify and list microorganismson the Inventory, both taxonomicdesignations and supplementalinformation will be used. Thesupplemental information required inparagraph (b) of this section will beused to specifically describe anindividual microorganism on the

Inventory. Submitters must provide thesupplemental information required byparagraph (b) of this section to theextent necessary to enable amicroorganism to be accurately andunambiguously identified on theInventory.

(a) Taxonomic designation. Thetaxonomic designation of amicroorganism must be provided for thedonor organism and the recipientmicroorganism to the level of strain, asappropriate. These designations must besubstantiated by a letter from a culturecollection, literature references, or theresults of tests conducted for thepurpose of taxonomic classification.Upon EPA’s request to the submitter,data supporting the taxonomicdesignation must be provided to EPA.The genetic history of the recipientmicroorganism should be documentedback to the isolate from which it wasderived.

(b) Supplemental information. Thesupplemental information described inparagraphs (b)(1) and (b)(2) of thissection is required to the extent that itenables a microorganism to beaccurately and unambiguouslyidentified.

(1) Phenotypic information.Phenotypic information means pertinenttraits that result from the interaction ofa microorganism’s genotype and theenvironment in which it is intended tobe used and may include intentionallyadded biochemical and physiologicaltraits.

(2) Genotypic information. Genotypicinformation means the pertinent anddistinguishing genotypic characteristicsof a microorganism, such as the identityof the introduced genetic material andthe methods used to construct thereported microorganism. This also mayinclude information on the vectorconstruct, the cellular location, and thenumber of copies of the introducedgenetic material.

§ 725.15 Determining applicability whenmicroorganism identity or use isconfidential or uncertain.

(a) Consulting EPA. Persons intendingto conduct activities involvingmicroorganisms may determine theirobligations under this part by consultingthe Inventory or the microorganismsand uses specified in § 725.239 or insubpart M of this part. This sectionestablishes procedures for EPA to assistpersons in determining whether themicroorganism or the use is listed onthe Inventory, in § 725.239 or in subpartM of this part.

(1) Confidential identity or use. Insome cases it may not be possible todirectly determine if a specific

microorganism is listed, becauseportions of that entry may containgeneric information to protectconfidential business information (CBI).If any portion of the microorganism’sidentity or use has been claimed as CBI,that portion does not appear on thepublic version of the Inventory, in§ 725.239 or in subpart M of this part.Instead, it is contained in a confidentialversion held in EPA’s ConfidentialBusiness Information Center (CBIC). Thepublic versions contain genericinformation which masks theconfidential business information. Aperson who intends to conduct anactivity involving a microorganism oruse whose entry is described withgeneric information will need to inquireof EPA whether the unreportedmicroorganism or use is on theconfidential version.

(2) Uncertain microorganism identity.The current state of scientificknowledge leads to some imprecision indescribing a microorganism. As the stateof knowledge increases, EPA will bedeveloping policies to determinewhether one microorganism isequivalent to another. Persons intendingto conduct activities involvingmicroorganisms may inquire of EPAwhether the microorganisms they intendto manufacture, import, or process areequivalent to specific microorganismsdescribed on the Inventory, in§ 725.239, or in subpart M of this part.

(b) Requirement of bona fide intent.(1) EPA will answer the inquiriesdescribed in paragraph (a) of thissection only if the Agency determinesthat the person has a bona fide intent toconduct the activity for which reportingis required or for which any exemptionmay apply.

(2) To establish a bona fide intent tomanufacture, import, or process amicroorganism, the person who intendsto manufacture, import, or process themicroorganism must submit thefollowing information in writing to theOffice of Pollution Prevention andToxics, Document Control Officer, 7407,401 M St., SW., Washington, DC 20460,ATTN: BIOTECH bona fide submission.

(i) Taxonomic designations andsupplemental information required by§ 725.12.

(ii) A signed statement certifying thatthe submitter intends to manufacture,import, or process the microorganismfor commercial purposes.

(iii) A description of research anddevelopment activities conducted withthe microorganism to date,demonstration of the submitter’s abilityto produce or obtain the microorganismfrom a foreign manufacturer, and thepurpose for which the person will


manufacture, import, or process themicroorganism.

(iv) An indication of whether a relatedmicroorganism was previously reviewedby EPA to the extent known by thesubmitter.

(v) A specific description of the majorintended application or use of themicroorganism.

(c) If an importer or processor cannotprovide all the information required byparagraph (b) of this section, because itis claimed as confidential businessinformation by its foreign manufactureror supplier, the foreign manufacturer orsupplier may supply the informationdirectly to EPA.

(d) EPA will review the informationsubmitted by the manufacturer,importer, or processor under thisparagraph to determine whether thatperson has shown a bona fide intent tomanufacture, import, or process themicroorganism. If necessary, EPA willcompare this information to theinformation requested for theconfidential microorganism under§ 725.85(b)(3)(iii).

(e) In order for EPA to make aconclusive determination of themicroorganism’s status, the proposedmanufacturer, importer, or processormust show a bona fide intent tomanufacture, import, or process themicroorganism and must providesufficient information to establishidentity unambiguously. After sufficientinformation has been provided, EPAwill inform the manufacturer, importer,or processor whether the microorganismis subject to this part and if so, whichsections of this part apply.

(f) If the microorganism is found onthe confidential version of theInventory, in § 725.239 or in subpart Mof this part, EPA will notify theperson(s) who originally reported themicroorganism that another person(whose identity will remainconfidential, if so requested) hasdemonstrated a bona fide intent tomanufacture, import, or process themicroorganism and therefore was toldthat the microorganism is on theInventory, in § 725.239, or in subpart Mof this part.

(g) A disclosure to a person with abona fide intent to manufacture, import,or process a particular microorganismthat the microorganism is on theInventory, in § 725.239, or in subpart Mof this part will not be considered apublic disclosure of confidentialbusiness information under section 14of the Act.

(h) EPA will answer an inquiry onwhether a particular microorganism issubject to this part within 30 days after

receipt of a complete submission underparagraph (b) of this section.

§ 725.17 Consultation with EPA.Persons may consult with EPA, either

in writing or by telephone, about theirobligations under this part. Writtenconsultation is preferred. Writteninquiries should be sent to the followingaddress: Environmental AssistanceDivision (7408), Office of PollutionPrevention and Toxics, U.S.Environmental Protection Agency, 401M St., SW., Washington, DC 20460,ATTN: Biotechnology NoticeConsultation. Persons wishing toconsult with EPA by telephone shouldcall (202) 554–1404; hearing impairedTDD (202) 554–0551 or e-mail: [email protected].

Subpart B—Administrative Procedures

§ 725.20 Scope and purpose.This subpart describes general

administrative procedures applicable toall persons who submit MCANs andexemption requests to EPA undersection 5 of the Act for microorganisms.

§ 725.25 General administrativerequirements.

(a) General. (1) Each person who issubject to the notification provisions ofthis part must complete, sign, andsubmit a MCAN or exemption requestcontaining the information as requiredfor the appropriate submission underthis part. Except as otherwise provided,each submission must include allreferenced attachments. All informationin the submission (unless certainattachments appear in the openscientific literature) must be in English.All information submitted must be trueand correct.

(2) In addition to specific informationrequired, the submitter should submitall information known to or reasonablyascertainable by the submitter thatwould permit EPA to make a reasonedevaluation of the human health andenvironmental effects of themicroorganism and any microbialmixture or article that may contain themicroorganism.

(b) Certification. Persons submittingMCANs and exemption requests to EPAunder this part, and material related totheir reporting obligations under thispart, must attach the followingstatement to any information submittedto EPA. This statement must be signedand dated by an authorized official ofthe submitter:

I certify that to the best of my knowledgeand belief: The company named in thissubmission intends to manufacture, import,or process for a commercial purpose, otherthan in small quantities solely for research

and development, the microorganismidentified in this submission. All informationprovided in this submission is complete andtruthful as of the date of submission. I amincluding with this submission all test datain my possession or control and a descriptionof all other data known to or reasonablyascertainable by me as required by 40 CFR725.160 or 725.260.

(c) Where to submit informationunder this part. Persons submittingMCANs and exemption requests to EPAunder this part, and material related totheir reporting obligations under thispart, must send them to: TSCADocument Processing Center (7407),Rm. L–100, Office of PollutionPrevention and Toxics, U.S.Environmental Protection Agency, 401M St., SW., Washington, DC 20460.

(d) General requirements forsubmission of data. (1) Submissionsunder this part must include theinformation described in § 725.155,725.255, 725.355, or 725.455, asappropriate, to the extent suchinformation is known to or reasonablyascertainable by the submitter.

(2) In accordance with § 725.160 or725.260, as appropriate, the submissionmust also include any test data in thesubmitter’s possession or control anddescriptions of other data which areknown to or reasonably ascertainable bythe submitter and which concern thehealth and environmental effects of themicroorganism.

(e) Agency or joint submissions. (1) Amanufacturer or importer may designatean agent to submit the MCAN orexemption request. Both themanufacturer or importer and the agentmust sign the certification required inparagraph (b) of this section.

(2) A manufacturer or importer mayauthorize another person (e.g., a foreignmanufacturer or supplier, or a tollmanufacturer) to report some of theinformation required in the MCAN orexemption request to EPA on its behalf.If separate portions of a joint submissionare not submitted together, thesubmitter must indicate whichinformation will be supplied by anotherperson and identify that person. Themanufacturer or importer and any otherperson supplying the information mustsign the certification required byparagraph (b) of this section.

(3) If EPA receives a submissionwhich does not include the informationrequired, which the submitter indicatesthat it has authorized another person toprovide, the review period will notbegin until EPA receives all of therequired information.

(f) Microorganisms subject to a section4 test rule. (1) Except as provided inparagraph (f)(3) of this section, if a


person intends to manufacture or importa new microorganism which is subjectto the notification requirements of thispart, and the microorganism is subjectto a test rule promulgated under section4 of the Act before the notice issubmitted, section 5(b)(1) of the Actrequires the person to submit the testdata required by the testing rule withthe notice. The person must submit thedata in the form and manner specifiedin the test rule and in accordance with§ 725.160. If the person does not submitthe test data, the submission isincomplete and EPA will follow theprocedures in § 725.33.

(2) If EPA has granted the submitteran exemption under section 4(c) of theAct from the requirement to conducttests and submit data, the person maynot file a MCAN or TERA until EPAreceives the test data.

(3) If EPA has granted the submitteran exemption under section 4(c) of theAct and if another person previouslyhas submitted the test data to EPA, theexempted person may either submit thetest data or provide the followinginformation as part of the notice:

(i) The name, title, and address of theperson who submitted the test data toEPA.

(ii) The date the test data weresubmitted to EPA.

(iii) A citation for the test rule.(iv) A description of the exemption

and a reference identifying it.(g) Microorganisms subject to a

section 5(b)(4) rule. (1) If a person:(i) Intends to manufacture or import a

microorganism which is subject to thenotification requirements of this partand which is subject to a rule issuedunder section 5(b)(4) of the Act; and

(ii) Is not required by a rule issuedunder section 4 of the Act to submit testdata for the microorganism before thefiling of a submission, the person mustsubmit to EPA data described inparagraph (g)(2) of this section at thetime the submission is filed.

(2) Data submitted under paragraph(g)(1) of this section must be data whichthe person submitting the noticebelieves show that the manufacture,processing, distribution in commerce,use, and disposal of the microorganism,or any combination of such activities,will not present an unreasonable risk ofinjury to health or the environment.

(h) Data that need not be submitted.Specific data requirements are listed insubparts D, E, F, G, and L of this part.The following is a list of data that neednot be submitted under this part:

(1) Data previously submitted to EPA.(i) A person need not submit any datapreviously submitted to EPA with noclaims of confidentiality if the new

submission includes: the office orperson to whom the data weresubmitted; the date of submission; and,if appropriate, a standard literaturecitation as specified in§ 725.160(a)(3)(ii).

(ii) For data previously submitted toEPA with a claim of confidentiality, theperson must resubmit the data with thenew submission and any claim ofconfidentiality, under § 725.80.

(2) Efficacy data. This part does notrequire submission of any data relatedsolely to product efficacy. However,including efficacy data will improveEPA’s ability to assess the benefits of theuse of the microorganism. This does notexempt a person from submitting any ofthe data specified in § 725.160 or725.260.

(3) Non-U.S. exposure data. This partdoes not require submission of any datawhich relates only to exposure ofhumans or the environment outside theUnited States. This does not excludenonexposure data such as data on healtheffects (including epidemiologicalstudies), ecological effects, physical andchemical properties, or environmentalfate characteristics.

§ 725.27 Submissions.

Each person who is required tosubmit information under this part mustsubmit the information in the form andmanner set forth in the appropriatesubpart.

(a) Requirements specific to MCANsare described in §§ 725.150 through725.160.

(b) Requirements specific to TERAsare described in §§ 725.250 through725.260.

(c) Requirements specific to testmarketing exemptions (TMEs) aredescribed in §§ 725.350 and 725.355.

(d) Requirements specific to Tier I andTier II exemptions for certain generalcommercial uses are described in§§ 725.424 through 725.470.

(e) Additional requirements specificto significant new uses formicroorganisms are described at§ 725.950.

§ 725.28 Notice that submission is notrequired.

When EPA receives a MCAN orexemption request, EPA will review it todetermine whether the microorganism issubject to the requirements of this part.If EPA determines that themicroorganism is not subject to theserequirements, EPA will notify thesubmitter that section 5 of the Act doesnot prevent the manufacture, import, orprocessing of the microorganism andthat the submission is not needed.

§ 725.29 EPA acknowledgement of receiptof submission.

(a) EPA will acknowledge receipt ofeach submission by sending thesubmitter a letter that identifies thenumber assigned to each MCAN orexemption request and the date onwhich the review period begins. Thereview period will begin on the date theMCAN or exemption request is receivedby the Office of Pollution Preventionand Toxics Document Control Officer.

(b) The acknowledgement does notconstitute a finding by EPA that thesubmission is in compliance with thispart.

§ 725.32 Errors in the submission.(a) Within 30 days of receipt of the

submission, EPA may request that thesubmitter remedy errors in thesubmission. The following are examplesof such errors:

(1) Failure to date the submission.(2) Typographical errors that cause

data to be misleading or answers to anyquestions to be unclear.

(3) Contradictory information.(4) Ambiguous statements or

information.(b) In the request to correct the

submission, EPA will explain the actionwhich the submitter must take to correctthe submission.

(c) If the submitter fails to correct thesubmission within 15 days of receipt ofthe request, EPA may extend the reviewperiod.

§ 725.33 Incomplete submissions.(a) A submission under this part is not

complete, and the review period doesnot begin, if:

(1) The wrong person files thesubmission.

(2) The submitter does not attach andsign the certification statement asrequired by § 725.25(b).

(3) Some or all of the information inthe submission or any attachments arenot in English, except for publishedscientific literature.

(4) The submitter does not provideinformation that is required by sections5(d)(1)(B) and (C) of the Act and§ 725.160 or 725.260, as appropriate.

(5) The submitter does not provideinformation required by § 725.25,725.155, 725.255, 725.355, or 725.455,as appropriate, or indicate that it is notknown to or reasonably ascertainable bythe submitter.

(6) The submitter has assertedconfidentiality claims and has failed to:

(i) Submit a second copy of thesubmission with all confidentialinformation deleted for the public file,as required by § 725.80(b)(2).

(ii) Comply with the substantiationrequirements as described in § 725.94.


(7) The submitter does not includeany information required by section5(b)(1) of the Act and pursuant to a rulepromulgated under section 4 of the Act,as required by § 725.25(f).

(8) The submitter does not submitdata which the submitter believes showthat the microorganism will not presentan unreasonable risk of injury to healthor the environment, if EPA has listedthe microorganism under section 5(b)(4)of the Act, as required in § 725.25(g).

(9) For MCANs, the submitter doesnot remit the fees required by§ 700.45(b)(1) or (b)(2)(vi) of thischapter.

(b)(1) If EPA receives an incompletesubmission under this part, the Director,or a designee, will notify the submitterwithin 30 days of receipt that thesubmission is incomplete and that thereview period will not begin until EPAreceives a complete submission.

(2) If EPA obtains additionalinformation during the review periodfor any submission that indicates theoriginal submission was incomplete, theDirector, or a designee, may declare thesubmission incomplete within 30 daysafter EPA obtains the additionalinformation and so notify the submitter.

(c) The notification that a submissionis incomplete under paragraph (b) ofthis section will include:

(1) A statement of the basis of EPA’sdetermination that the submission isincomplete.

(2) The requirements for correctingthe incomplete submission.

(3) Information on procedures underparagraph (d) of this section for filingobjections to the determination orrequesting modification of therequirements for completing thesubmission.

(d) Within 10 days after receipt ofnotification by EPA that a submission isincomplete, the submitter may filewritten objections requesting that EPAaccept the submission as complete ormodify the requirements necessary tocomplete the submission.

(e)(1) EPA will consider the objectionsfiled by the submitter. The Director, ora designee, will determine whether thesubmission was complete orincomplete, or whether to modify therequirements for completing thesubmission. EPA will notify thesubmitter in writing of EPA’s responsewithin 10 days of receiving theobjections.

(2) If the Director, or a designee,determines, in response to the objection,that the submission was complete, thereview period will be deemedsuspended on the date EPA declared thesubmission incomplete, and will resumeon the date that the submission is

declared complete. The submitter neednot correct the submission as EPAoriginally requested. If EPA cancomplete its review within the reviewperiod beginning on the date of thesubmission, the Director, or a designee,may inform the submitter that therunning of the review period willresume on the date EPA originallydeclared it incomplete.

(3) If the Director, or a designee,modifies the requirements forcompleting the submission or concurswith EPA’s original determination, thereview period will begin when EPAreceives a complete submission.

(f) If EPA discovers at any time thata person submitted materially false ormisleading statements in informationsubmitted under this part, EPA may findthat the submission was incompletefrom the date it was submitted, and takeany other appropriate action.

§ 725.36 New information.(a) During the review period, if a

submitter possesses, controls, or knowsof new information that materially addsto, changes, or otherwise makessignificantly more complete theinformation included in the MCAN orexemption request, the submitter mustsend that information to the addresslisted in § 725.25(c) within 10 days ofreceiving the new information, but nolater than 5 days before the end of thereview period.

(b) The new submission must clearlyidentify the submitter, the MCAN orexemption request to which the newinformation is related, and the numberassigned to that submission by EPA, ifknown to the submitter.

(c) If the new information becomesavailable during the last 5 days of thereview period, the submitter mustimmediately inform the EPA contact forthat submission by telephone of the newinformation.

§ 725.40 Notice in the Federal Register.(a) Filing of Federal Register notice.

After EPA receives a MCAN or anexemption request under this part, EPAwill issue a notice in the FederalRegister including the informationspecified in paragraph (b) of thissection.

(b) Contents of notice. (1) In thepublic interest, the specificmicroorganism identity listed in thesubmission will be published in theFederal Register unless the submitterhas claimed the microorganism identityconfidential. If the submitter claimsconfidentiality, a generic name will bepublished in accordance with § 725.85.

(2) The categories of use of themicroorganism will be published as

reported in the submission unless thisinformation is claimed confidential. Ifconfidentiality is claimed, the genericinformation which is submitted under§ 725.88 will be published.

(3) A list of information submitted inaccordance with § 725.160(a), 725.255,725.260, 725.355, or 725.455, asappropriate, will be published.

(4) The submitter’s identity will bepublished, unless the submitter hasclaimed it confidential.

(c) Publication of exemptiondecisions. Following the expiration ofthe appropriate review period for theexemption request, EPA will issue anotice in the Federal Register indicatingwhether the request has been approvedor denied and the reasons for thedecision.

§ 725.50 EPA review.(a) MCANs. The review period

specified in section 5(a) of the Act forMCANs runs for 90 days from the datethe Document Control Officer receives acomplete submission, or the date EPAdetermines the submission is completeunder § 725.33, unless the Agencyextends the review period under section5(c) of the Act and § 725.56.

(b) Exemption requests. The reviewperiod starts on the date the DocumentControl Officer receives a completeexemption request, or the date EPAdetermines the request is completeunder § 725.33, unless the Agencyextends the review period under§ 725.56. The review periods forexemption requests run as follows:

(1) TERAs. The review period forTERAs is 60 days.

(2) TMEs. The review period for TMEsis 45 days.

(3) Tier II exemption requests. Thereview period for Tier II exemptionrequests is 45 days.

§ 725.54 Suspension of the review period.(a) A submitter may voluntarily

suspend the running of the reviewperiod if the Director, or a designee,agrees. If the Director does not agree, thereview period will continue to run, andEPA will notify the submitter. Asubmitter may request a suspension atany time during the review period. Thesuspension must be for a specifiedperiod of time.

(b) A request for suspension may bemade in writing to the address listed in§ 725.25(c). The suspension also may bemade orally, including by telephone, tothe submitter’s EPA contact for thatsubmission. EPA will send thesubmitter a written confirmation thatthe suspension has been granted.

(1) An oral request may be granted forno longer than 15 days. To obtain a


longer suspension, the DocumentControl Officer for the Office ofPollution Prevention and Toxics mustreceive written confirmation of the oralrequest. The review period is suspendedas of the date of the oral request.

(2) If the submitter has not made aprevious oral request, the running of thereview period is suspended as of thedate of receipt of the written request bythe Document Control Officer for theOffice of Pollution Prevention andToxics.

§ 725.56 Extension of the review period.(a) At any time during the review

period, EPA may unilaterally determinethat good cause exists to extend thereview period specified for MCANs, orthe exemption requests.

(b) If EPA makes such adetermination, EPA:

(1) Will notify the submitter that EPAis extending the review period for aspecified length of time and state thereasons for the extension.

(2) For MCANs, EPA may issue anotice for publication in the FederalRegister which states that EPA isextending the review period and givesthe reasons for the extension.

(c) The total period of the extensionmay be for a period of up to the samelength of time as specified for each typeof submission in § 725.50. If the initialextension is for less than the total timeallowed, EPA may make additionalextensions. However, the sum of theextensions may not exceed the totalallowed.

(d) The following are examples ofsituations in which EPA may find thatgood cause exists for extending thereview period:

(1) EPA has reviewed the submissionand is seeking additional information.

(2) EPA has received significantadditional information during thereview period.

(3) The submitter has failed to correcta submission after receiving EPA’srequest under § 725.32.

(4) EPA has reviewed the submissionand determined that there is asignificant possibility that themicroorganism will be regulated undersection 5(e) or section 5(f) of the Act,but EPA is unable to initiate regulatoryaction within the initial review period.

§ 725.60 Withdrawal of submission by thesubmitter.

(a) A submitter may withdraw asubmission during the review period. Astatement of withdrawal must be madein writing to the address listed in§ 725.25(c). The withdrawal is effectiveupon receipt of the statement by theDocument Control Officer.

(b) If a manufacturer, importer, orprocessor who withdrew a submissionlater resubmits a submission for thesame microorganism, a new reviewperiod begins.

§ 725.65 Recordkeeping.(a) General provisions. (1) Any person

who submits a notice under this partmust retain documentation ofinformation in the submission,including:

(i) Any data in the submitter’spossession or control; and

(ii) Records of production volume forthe first 3 years of manufacture, import,or processing.

(2) Any person who submits a noticeunder this part must retaindocumentation of the date ofcommencement of testing, manufacture,import, or processing.

(3) Any person who is exempt fromsome or all of the reportingrequirements of this part must retaindocumentation that supports theexemption.

(4) All information required by thissection must be retained for 3 yearsfrom the date of commencement of eachactivity for which records are requiredunder this part.

(b) Specific requirements. In additionto the requirements of paragraph (a) ofthis section, specific recordkeepingrequirements included in certainsubparts must also be followed.

(1) Additional recordkeepingrequirements for activities conductedinside a structure are set forth in§ 725.235(h).

(2) Additional recordkeepingrequirements for TERAs are set forth in§ 725.250(f).

(3) Additional recordkeepingrequirements for TMEs are set forth in§ 725.350(c).

(4) Additional recordkeepingrequirements for Tier I exemptionsunder subpart G of this part are set forthin § 725.424(a)(5).

(5) Additional recordkeepingrequirements for Tier II exemptionsunder subpart G of this part are set forthin § 725.450(d).

(6) Additional recordkeepingrequirements for significant new uses ofmicroorganisms reported under subpartL of this part are set forth in § 725.850.Recordkeeping requirements may alsobe included when a microorganism andsignificant new use are added to subpartM of this part.

§ 725.67 Applications to exempt newmicroorganisms from this part.

(a) Submission. (1) Any manufactureror importer of a new microorganismmay request, under section 5(h)(4) of the

Act, an exemption, in whole or in part,from this part by sending a Letter ofApplication to the Chief, NewChemicals Branch, Chemical ControlDivision, Office of Pollution Preventionand Toxics, U.S. EnvironmentalProtection Agency, 401 M St., SW.,Washington, DC 20460.

(2) General provisions. The Letter ofApplication should provide informationto show that any activities affected bythe requested exemption will notpresent an unreasonable risk of injury tohealth or the environment. Thisinformation should include datadescribed in the following paragraphs.

(i) The effects of the newmicroorganism on health and theenvironment.

(ii) The magnitude of exposure ofhuman beings and the environment tothe new microorganism.

(iii) The benefits of the newmicroorganism for various uses and theavailability of substitutes for such uses.

(iv) The reasonably ascertainableeconomic consequences of granting ordenying the exemption, includingeffects on the national economy, smallbusiness, and technological innovation.

(3) Specific requirements. In additionto the requirements of paragraph (a)(2)of this section, the specific informationrequirements of the relevant subpartunder which the exemption is soughtshould be met.

(i) Exemption from MCAN reportingunder subpart D. Informationrequirements are set forth in §§ 725.155and 725.160.

(ii) Exemption from TERA reportingunder subpart E. Informationrequirements are set forth in §§ 725.255and 725.260.

(iii) Listing a recipient microorganismas eligible for exemption under subpartG. Information regarding the followingcriteria should be addressed in anapplication to list a recipientmicroorganism under § 725.420:

(A) Identification and classification ofthe microorganism using availablegenotypic and phenotypic information;

(B) Information to evaluate therelationship of the microorganism toany other closely relatedmicroorganisms which have a potentialfor adverse effects on health or theenvironment;

(C) A history of safe commercial usefor the microorganism;

(D) Commercial uses indicating thatthe microorganism products might besubject to TSCA;

(E) Studies which indicate thepotential for the microorganism to causeadverse effects to health or theenvironment; and


(F) Studies which indicate thesurvival characteristics of themicroorganism in the environment.

(b) Processing of the Letter ofApplication by EPA—(1) Grant of theApplication. If, after consideration ofthe Letter of Application and any otherrelevant information available to EPA,the Assistant Administrator forPrevention, Pesticides and ToxicSubstances makes a preliminarydetermination that the newmicroorganism will not present anunreasonable risk of injury to health orthe environment, the AssistantAdministrator will propose a rule togrant the exemption using theapplicable procedures in part 750 of thischapter.

(2) Denial of the application. If theAssistant Administrator decides that thepreliminary determination described inparagraph (b)(1) of this section cannotbe made, the application will be deniedby sending the applicant a writtenstatement with the AssistantAdministrator’s reasons for denial.

(c) Processing of the exemption—(1)Unreasonable risk standard. Granting asection 5(h)(4) exemption requires adetermination that the activities will notpresent an unreasonable risk of injury tohealth or the environment.

(i) An unreasonable riskdetermination under the Act is anadministrative judgment that requiresbalancing of the harm to health or theenvironment that a chemical substancemay cause and the magnitude andseverity of that harm, against the socialand economic effects on society of EPAaction to reduce that harm.

(ii) A determination of unreasonablerisk under section 5(h)(4) of the Act willexamine the reasonably ascertainableeconomic and social consequences ofgranting or denying the exemption afterconsideration of the effect on thenational economy, small business,technological innovation, theenvironment, and public health.

(2) Grant of the exemption. Theexemption will be granted if theAssistant Administrator determines,after consideration of all relevantevidence presented in the rulemakingproceeding described in paragraph (b)(1)of this section, that the newmicroorganism will not present anunreasonable risk of injury to health orthe environment.

(3) Denial of the exemption. Theexemption will be denied if theAssistant Administrator determines,after consideration of all relevantevidence presented in the rulemakingproceeding described in paragraph (b)(1)of this section, that the determinationdescribed in paragraph (c)(2) of this

section cannot be made. A final decisionterminating the rulemaking proceedingwill be published in the FederalRegister.

§ 725.70 Compliance.(a) Failure to comply with any

provision of this part is a violation ofsection 15 of the Act (15 U.S.C. 2614).

(b) A person who manufactures orimports a microorganism before aMCAN is submitted and the MCANreview period expires is in violation ofsection 15 of the Act even if that personwas not required to submit the MCANunder § 725.105.

(c) Using a microorganism which aperson knew or had reason to know wasmanufactured, processed, or distributedin commerce in violation of section 5 ofthe Act or this part is a violation ofsection 15 of the Act (15 U.S.C. 2614).

(d) Failure or refusal to establish andmaintain records or to permit access toor copying of records, as required by theAct, is a violation of section 15 of theAct (15 U.S.C. 2614).

(e) Failure or refusal to permit entryor inspection as required by section 11of the Act is a violation of section 15 ofthe Act (15 U.S.C. 2614).

(f) Violators may be subject to thecivil and criminal penalties in section16 of the Act (15 U.S.C. 2615) for eachviolation. Persons who submitmaterially misleading or falseinformation in connection with therequirements of any provision of thispart may be subject to penaltiescalculated as if they never filed theirsubmissions.

(g) EPA may seek to enjoin themanufacture or processing of amicroorganism in violation of this partor act to seize any microorganismmanufactured or processed in violationof this part or take other actions underthe authority of section 7 of the Act (15U.S.C. 2606) or section 17 of the Act (15U.S.C. 2616).

§ 725.75 Inspections.EPA will conduct inspections under

section 11 of the Act to assurecompliance with section 5 of the Actand this part, to verify that informationrequired by EPA under this part is trueand correct, and to audit data submittedto EPA under this part.

Subpart C—Confidentiality and PublicAccess to Information

§ 725.80 General provisions forconfidentiality claims.

(a) A person may assert a claim ofconfidentiality for any informationsubmitted to EPA under this part.However,

(1) Any person who asserts a claim ofconfidentiality for portions of the

specific microorganism identity mustprovide the information as described in§ 725.85.

(2) Any person who asserts a claim ofconfidentiality for a use of amicroorganism must provide theinformation as described in § 725.88.

(3) Any person who asserts a claim ofconfidentiality for informationcontained in a health and safety studyof a microorganism must provide theinformation described in § 725.92.

(b) Any claim of confidentiality mustaccompany the information when it issubmitted to EPA.

(1) When a person submits anyinformation under this part, includingany attachments, for which claims ofconfidentiality are made, the claim(s)must be asserted by circling the specificinformation which is claimed andmarking the page on which thatinformation appears with an appropriatedesignation such as ‘‘trade secret,’’‘‘TSCA CBI,’’ or ‘‘confidential businessinformation.’’

(2) If any information is claimedconfidential, the person must submittwo copies of the document includingthe claimed information.

(i) One copy of the document must becomplete. In that copy, the submittermust mark the information which isclaimed as confidential in the mannerprescribed in paragraph (b)(1) of thissection.

(ii) The second copy must becomplete except that all informationclaimed as confidential in the first copymust be deleted. EPA will place thesecond copy in the public file.

(iii) If the submitter does not providethe second copy, the submission isincomplete and the review period doesnot begin to run until EPA receives thesecond copy, in accordance with§ 725.33.

(iv) Any information contained withinthe copy submitted under paragraph(b)(2)(ii) of this section which has beenin the public file for more than 30 dayswill be presumed to be in the publicdomain, notwithstanding any assertionof confidentiality made under thissection.

(3) A person who submits informationto EPA under this part must reassert aclaim of confidentiality and substantiatethe claim each time the information issubmitted to EPA.

(c) Any person asserting a claim ofconfidentiality under this part mustsubstantiate each claim in accordancewith the requirements in § 725.94.

(d) EPA will disclose information thatis subject to a claim of confidentialityasserted under this section only to theextent permitted by the Act, thissubpart, and part 2 of this title.


(e) If a submitter does not assert aclaim of confidentiality for informationat the time it is submitted to EPA, EPAmay make the information public andplace it in the public file without furthernotice to the submitter.

§ 725.85 Microorganism identity.(a) Claims applicable to the period

prior to commencement of manufactureor import for general commercial use—(1) When to make a claim. (i) A personwho submits information to EPA underthis part may assert a claim ofconfidentiality for portions of thespecific microorganism identity at thetime of submission of the information.This claim will apply only to the periodprior to the commencement ofmanufacture or import for generalcommercial use.

(ii) A person who submits informationto EPA under this part must reassert aclaim of confidentiality and substantiatethe claim each time the information issubmitted to EPA. For example, if aperson claims certain informationconfidential in a TERA submission andwishes the same information to remainconfidential in a subsequent TERA orMCAN submission, the person mustreassert and resubstantiate the claim inthe subsequent submission.

(2) Assertion of claim. (i) A submittermay assert a claim of confidentialityonly if the submitter believes that publicdisclosure prior to commencement ofmanufacture or import for generalcommercial use of the fact that anyoneis initiating research and developmentactivities pertaining to the specificmicroorganism or intends tomanufacture or import the specificmicroorganism for general commercialuse would reveal confidential businessinformation. Claims must besubstantiated in accordance with therequirements of § 725.94(a).

(ii) If the submission includes a healthand safety study concerning themicroorganism and if the claim forconfidentiality with respect to thespecific identity is denied in accordancewith § 725.92(c), EPA will deny a claimasserted under paragraph (a) of thissection.

(3) Development of generic name. Anyperson who asserts a claim ofconfidentiality for portions of thespecific microorganism identity underthis paragraph must provide one of thefollowing items at the time thesubmission is filed:

(i) The generic name which wasaccepted by EPA in the prenoticeconsultation conducted underparagraph (a)(4) of this section.

(ii) One generic name that is only asgeneric as necessary to protect the

confidential identity of the particularmicroorganism. The name should revealthe specific identity to the maximumextent possible. The generic name willbe subject to EPA review and approval.

(4) Determination by EPA. (i) Anyperson who intends to assert a claim ofconfidentiality for the specific identityof a new microorganism may seek adetermination by EPA of an appropriategeneric name for the microorganismbefore filing a submission. For thispurpose, the person should submit toEPA:

(A) The specific identity of themicroorganism.

(B) A proposed generic name(s) whichis only as generic as necessary to protectthe confidential identity of the newmicroorganism. The name(s) shouldreveal the specific identity of themicroorganism to the maximum extentpossible.

(ii) Within 30 days, EPA will informthe submitter either that one of theproposed generic names is adequate orthat none is adequate and furtherconsultation is necessary.

(5) Use of generic name. If a submitterclaims microorganism identity asconfidential under paragraph (a) of thissection, and if the submitter complieswith paragraph (a)(2) of this section,EPA will issue for publication in theFederal Register notice described in§ 725.40 the generic name proposed bythe submitter or one agreed upon byEPA and the submitter.

(b) Claims applicable to the periodafter commencement of manufacture orimport for general commercial use—(1)Maintaining claim. Any claim ofconfidentiality under paragraph (a) ofthis section is applicable only until themicroorganism is manufactured orimported for general commercial useand becomes eligible for inclusion onthe Inventory. To maintain theconfidential status of the microorganismidentity when the microorganism isadded to the Inventory, a submittermust reassert the confidentiality claimand substantiate the claim in the noticeof commencement of manufacturerequired under § 725.190.

(i) A submitter may not claim themicroorganism identity confidential forthe period after commencement ofmanufacture or import for generalcommercial use unless the submitterclaimed the microorganism identityconfidential under paragraph (a) of thissection in the MCAN submitted for themicroorganism.

(ii) A submitter may claim themicroorganism identity confidential forthe period after commencement ofmanufacture or import for generalcommercial use if the submitter did not

claim the microorganism identityconfidential under paragraph (a) of thissection in any TERA submitted for themicroorganism, but subsequently didclaim microorganism identityconfidential in the MCAN submitted forthe microorganism.

(2) Assertion of claim. (i) A personwho believes that public disclosure ofthe fact that anyone manufactures orimports the microorganism for generalcommercial use would revealconfidential business information mayassert a claim of confidentiality underparagraph (b) of this section.

(ii) If the notice includes a health andsafety study concerning the newmicroorganism, and if the claim forconfidentiality with respect to themicroorganism identity is denied inaccordance with § 725.92(c), EPA willdeny a claim asserted under paragraph(b) of this section.

(3) Requirements for assertion. Anyperson who asserts a confidentialityclaim for microorganism identity must:

(i) Comply with the requirements ofparagraph (a)(3) of this section regardingsubmission of a generic name.

(ii) Agree that EPA may disclose to aperson with a bona fide intent tomanufacture or import themicroorganism the fact that theparticular microorganism is included onthe confidential Inventory for purposesof notification under section 5(a)(1)(A)of the Act.

(iii) Have available and agree tofurnish to EPA upon request thetaxonomic designations andsupplemental information required by§ 725.12.

(iv) Provide a detailed writtensubstantiation of the claim, inaccordance with the requirements of§ 725.94(b).

(4) Denial of claim. If the submitterdoes not meet the requirements ofparagraph (b) of this section, EPA willdeny the claim of confidentiality.

(5) Acceptance of claim. (i) EPA willpublish a generic name on the publicInventory if:

(A) The submitter asserts a claim ofconfidentiality in accordance with thisparagraph.

(B) No claim for confidentiality of themicroorganism identity as part of ahealth and safety study has been deniedin accordance with part 2 of this title or§ 725.92.

(ii) Publication of a generic name onthe public Inventory does not create acategory for purposes of the Inventory.Any person who has a bona fide intentto manufacture or import amicroorganism which is described by ageneric name on the public Inventorymay submit an inquiry to EPA under


§ 725.15(b) to determine whether theparticular microorganism is included onthe confidential Inventory.

(iii) Upon receipt of a requestdescribed in § 725.15(b), EPA mayrequire the submitter who originallyasserted confidentiality for amicroorganism to submit to EPA theinformation listed in paragraph(b)(3)(iii) of this section.

(iv) Failure to submit any of theinformation required under paragraph(b)(3)(iii) of this section within 10calendar days of receipt of a request byEPA under paragraph (b) of this sectionwill constitute a waiver of the originalsubmitter’s confidentiality claim. In thisevent, EPA may place the specificmicroorganism identity on the publicInventory without further notice to theoriginal submitter.

(6) Use of generic name on the publicInventory. If a submitter asserts a claimof confidentiality under paragraph (b) ofthis section, EPA will examine thegeneric microorganism name proposedby the submitter.

(i) If EPA determines that the genericname proposed by the submitter is onlyas generic as necessary to protect theconfidential identity of the particularmicroorganism, EPA will place thatgeneric name on the public Inventory.

(ii) If EPA determines that the genericname proposed by the submitter is moregeneric than necessary to protect theconfidential identity, EPA will proposein writing, for review by the submitter,an alternative generic name that willreveal the identity of the microorganismto the maximum extent possible.

(iii) If the generic name proposed byEPA is acceptable to the submitter, EPAwill place that generic name on thepublic Inventory.

(iv) If the generic name proposed byEPA is not acceptable to the submitter,the submitter must explain in detailwhy disclosure of that generic namewould reveal confidential businessinformation and propose anothergeneric name which is only as genericas necessary to protect the confidentialidentity of the microorganism. If EPAdoes not receive a response from thesubmitter within 30 days after thesubmitter receives the proposed name,EPA will place EPA’s chosen genericname on the public Inventory. If thesubmitter does provide the informationrequested, EPA will review theresponse. If the submitter’s proposedgeneric name is acceptable, EPA willpublish that generic name on the publicInventory. If the submitter’s proposedgeneric name is not acceptable, EPAwill notify the submitter of EPA’s choiceof a generic name. Thirty days after this

notification, EPA will place the chosengeneric name on the public Inventory.

§ 725.88 Uses of a microorganism.(a) Assertion of claim. A person who

submits information to EPA under thispart on the categories or proposedcategories of use of a microorganismmay assert a claim of confidentiality forthis information.

(b) Requirements for claim. Asubmitter that asserts such a claim must:

(1) Report the categories or proposedcategories of use of the microorganism.

(2) Provide, in nonconfidential form,a description of the uses that is only asgeneric as necessary to protect theconfidential business information. Thegeneric use description will be includedin the Federal Register notice describedin § 725.40.

(c) Generic use description. Theperson must submit the informationrequired by paragraph (b) of this sectionby describing the uses as precisely aspossible, without revealing theinformation which is claimedconfidential, to disclose as much aspossible how the use may result inhuman exposure to the microorganismor its release to the environment.

§ 725.92 Data from health and safetystudies of microorganisms.

(a) Information other than specificmicroorganism identity. Except asprovided in paragraph (b) of thissection, EPA will deny any claim ofconfidentiality with respect toinformation included in a health andsafety study of a microorganism, unlessthe information would discloseconfidential business informationconcerning:

(1) Processes used in the manufactureor processing of a microorganism.

(2) Information which is not in anyway related to the effects of amicroorganism on health or theenvironment, such as, the name of thesubmitting company, cost or otherfinancial data, product development ormarketing plans, and advertising plans,for which the person submits a claim ofconfidentiality in accordance with§ 725.80.

(b) Microorganism identity—(1)Claims applicable to the period prior tocommencement of manufacture orimport for general commercial use. Aclaim of confidentiality for the periodprior to commencement of manufactureor import for general commercial use forthe specific identity of a microorganismfor which a health and safety study wassubmitted must be asserted inconjunction with a claim asserted under§ 725.85(a). The submitter mustsubstantiate each claim in accordancewith the requirements of § 725.94(a).

(2) Claims applicable to the periodafter commencement of manufacture orimport for general commercial use. Tomaintain the confidential status of thespecific identity of a microorganism forwhich a health and safety study wassubmitted after commencement ofmanufacture or import for generalcommercial use, the claim must bereasserted and substantiated inconjunction with a claim under§ 725.85(b). The submitter mustsubstantiate each claim in accordancewith the requirements of § 725.94(b).

(c) Denial of confidentiality claim.EPA will deny a claim of confidentialityfor microorganism identity underparagraph (b) of this section, unless:

(1) The information would discloseprocesses used in the manufacture orprocessing of a microorganism.

(2) The microorganism identity is notnecessary to interpret a health andsafety study.

(d) Use of generic names. When EPAdiscloses a health and safety studycontaining a microorganism identity,which the submitter has claimedconfidential, and if the Agency has notdenied the claim under paragraph (c) ofthis section, EPA will identify themicroorganism by the generic nameselected under § 725.85.

§ 725.94 Substantiation requirements.(a) Claims applicable to the period

prior to commencement of manufactureor import for general commercial use—(1) MCAN, TME, Tier I certification, andTier II exemption request requirements.Any person who submits a MCAN,TME, Tier I certification, or Tier IIexemption request should strictly limitconfidentiality claims to thatinformation which is confidential andproprietary to the business.

(i) If any information in thesubmission is claimed as confidentialbusiness information, the submittermust substantiate each claim bysubmitting written answers to thequestions in paragraphs (c), (d), and (e)of this section at the time the personsubmits the information.

(ii) If the submitter does not providewritten substantiation as required inparagraph (a)(1)(i) of this section, thesubmission will be consideredincomplete and the review period willnot begin in accordance with § 725.33.

(2) TERA requirements. Any personwho submits a TERA, should strictlylimit confidentiality claims to thatinformation which is confidential andproprietary to the business. If anyinformation in such a submission isclaimed as confidential businessinformation, the submitter must haveavailable for each of those claims, and


agree to furnish to EPA upon request,written answers to the questions inparagraphs (d) and (e) of this section.

(b) Claims applicable to the periodafter commencement of manufacture orimport for general commercial use. (1) Ifa submitter claimed portions of themicroorganism identity confidential inthe MCAN and wants the identity to belisted on the confidential Inventory, theclaim must be reasserted andsubstantiated at the time the Notice ofCommencement (NOC) is submittedunder § 725.190. Otherwise, EPA willlist the specific microorganism identityon the public Inventory.

(2) The submitter must substantiatethe claim for confidentiality of themicroorganism identity by answering allof the questions in paragraphs (c), (d),and (e) in this section. In addition, thefollowing questions must be answered:

(i) What harmful effects to thecompany’s or institution’s competitiveposition, if any, would result if EPApublishes on the Inventory the identityof the microorganism? How could acompetitor use such information giventhe fact that the identity of themicroorganism otherwise would appearon the TSCA Inventory with no linkbetween the microorganism and thecompany or institution? Howsubstantial would the harmful effects ofdisclosure be? What is the causalrelationship between the disclosure andthe harmful effects?

(ii) Has the identity of themicroorganism been kept confidential tothe extent that competitors do not knowit is being manufactured or imported forgeneral commercial use by anyone?

(c) General questions. The followingquestions must be answered in detail foreach confidentiality claim:

(1) For what period of time is a claimof confidentiality being asserted? If theclaim is to extend until a certain eventor point in time, indicate that event ortime period. Explain why theinformation should remain confidentialuntil such point.

(2) Briefly describe any physical orprocedural restrictions within thecompany or institution relating to theuse and storage of the informationclaimed as confidential. What othersteps, if any, apply to use or furtherdisclosure of the information?

(3) Has the information claimed asconfidential been disclosed toindividuals outside of the company orinstitution? Will it be disclosed to suchpersons in the future? If so, whatrestrictions, if any, apply to use orfurther disclosure of the information?

(4) Does the information claimed asconfidential appear, or is it referred to,in any of the following questions? If the

answer is yes to any of these questions,indicate where the information appearsand explain why it should nonethelessbe treated as confidential.

(i) Advertising or promotionalmaterials for the microorganism or theresulting end product?

(ii) Material safety data sheets or othersimilar materials for the microorganismor the resulting end product?

(iii) Professional or tradepublications?

(iv) Any other media available to thepublic or to competitors?

(v) Patents?(vi) Local, State, or Federal agency

public files?(5) Has EPA, another Federal agency,

a Federal court, or a State made anyconfidentiality determination regardingthe information claimed as confidential?If so, provide copies of suchdeterminations.

(6) For each type of informationclaimed confidential, describe the harmto the company’s or institution’scompetitive position that would result ifthis information were disclosed. Whywould this harm be substantial? Howcould a competitor use suchinformation? What is the causalconnection between the disclosure andharm?

(7) If EPA disclosed to the public theinformation claimed as confidential,how difficult would it be for thecompetitor to enter the market for theresulting product? Consider suchconstraints as capital and marketingcost, specialized technical expertise, orunusual processes.

(d) Microorganism identity andproduction method. If confidentialityclaims are asserted for the identity ofthe microorganism or information onhow the microorganism is produced, thefollowing questions must be answered:

(1) Has the microorganism or methodof production been patented in the U.S.or elsewhere? If so, why isconfidentiality necessary?

(2) Does the microorganism leave thesite of production or testing in a formwhich is accessible to the public or tocompetitors? What is the cost to acompetitor, in time and money, todevelop appropriate use conditions?What factors facilitate or impedeproduct analysis?

(3) For each additional type ofinformation claimed as confidential,explain what harm would result fromdisclosure of each type of information ifthe identity of the microorganism wereto remain confidential.

(e) Health and safety studies ofmicroorganisms. If confidentialityclaims are asserted for information in ahealth or safety study of a

microorganism, the following questionsmust be answered:

(1) Would the disclosure of theinformation claimed confidential reveal:confidential process information, orinformation unrelated to the effects ofthe microorganism on health and theenvironment. Describe the causalconnection between the disclosure andharm.

(2) Does the company or institutionassert that disclosure of themicroorganism identity is not necessaryto interpret any health and safetystudies which have been submitted? Ifso, explain how a less specific identitywould be sufficient to interpret thestudies.

§ 725.95 Public file.

All information submitted, includingany health and safety study of amicroorganism and other supportingdocumentation, will become part of thepublic file for that submission, unlesssuch materials are claimed confidential.In addition, EPA may add materials tothe public file, unless such materials areclaimed confidential. Any of thenonconfidential material described inthis subpart will be available for publicinspection in the TSCA Public DocketOffice, Rm. NE–B607, 401 M St., SW.,Washington, DC, between the hours ofnoon to 4 p.m., Monday through Friday,excluding legal holidays.

Subpart D—Microbial Commercial ActivitiesNotification Requirements

§ 725.100 Scope and purpose.

(a) This subpart establishesprocedures for submission of a notice toEPA under section 5(a) of the Act forpersons who manufacture, import, orprocess microorganisms for commercialpurposes. This notice is called aMicrobial Commercial Activity Notice(MCAN). It is expected that MCANs willin general only be submitted formicroorganisms intended for generalcommercial use. Persons whomanufacture, import, or process amicroorganism in small quantitiessolely for research and development asdefined in § 725.3 are not required tosubmit a notice to EPA. Persons whomanufacture, import, or process amicroorganism for research anddevelopment activities that do not fitthe definition of small quantities solelyfor research and development maynonetheless qualify for more limitedreporting requirements in Subpart E,including the TERA which can be usedfor review of research and developmentinvolving environmental release.

(b) Persons subject to MCANsubmission are described in § 725.105.


(c) Exclusions and exemptionsspecific to MCAN submissions aredescribed in § 725.110.

(d) Submission requirementsapplicable specifically to MCANs aredescribed at § 725.150.

(e) Data requirements for MCANs areset forth in §§ 725.155 and 725.160.

(f) EPA review procedures specific toMCANs are set forth in § 725.170.

(g) Subparts A through C of this partapply to any MCAN submitted underthis subpart.

§ 725.105 Persons who must report.(a) Manufacturers of new

microorganisms. (1) MCAN submissionis required for any person who intendsto manufacture for commercial purposesin the United States a newmicroorganism. Exclusions aredescribed in § 725.110.

(2) If a person contracts with amanufacturer to produce or process anew microorganism and themanufacturer produces or processes themicroorganism exclusively for thatperson, and that person specifies theidentity of the microorganism, andcontrols the total amount produced andthe basic technology for the plantprocess, then that person must submitthe MCAN. If it is unclear who mustreport, EPA should be contacted todetermine who must submit the MCAN.

(3) Only manufacturers that areincorporated, licensed, or doingbusiness in the United States maysubmit a MCAN.

(b) Importers of new microorganisms.(1) MCAN submission is required for aperson who intends to import into theUnited States for commercial purposesa new microorganism. Exclusions aredescribed in § 725.110.

(2) When several persons are involvedin an import transaction, the MCANmust be submitted by the principalimporter. If no one person fits theprincipal importer definition in aparticular transaction, the importershould contact EPA to determine whomust submit the MCAN for thattransaction.

(3) Except as otherwise provided inparagraph (b)(4) of this section, theprovisions of this subpart D apply toeach person who submits a MCAN fora new microorganism which suchperson intends to import for acommercial purpose. In addition, eachimporter must comply with paragraph(b)(4) of this section.

(4) EPA will hold the principalimporter, or the importer that EPAdetermines must submit the MCANwhen there is no principal importerunder paragraph (b)(2) of this section,liable for complying with this part, for

completing the MCAN, and for thecompleteness and truthfulness of allinformation which it submits.

(c) Manufacturers, importers, orprocessors of microorganisms for asignificant new use. MCAN submissionis required for any person who intendsto manufacture, import, or process forcommercial purposes a microorganismidentified as having one or moresignificant new uses in subpart M of thispart, and who intends either to engagein a designated significant new use ofthe microorganism or intends todistribute it in commerce. Personsexcluded from reporting on significantnew uses of microorganisms andadditional procedures for reporting aredescribed in subpart L of this part.

§ 725.110 Persons not subject to thissubpart.

Persons are not subject to therequirements of this subpart for thefollowing activities:

(a) Manufacturing, importing, orprocessing solely for research anddevelopment microorganisms that meetthe requirements for an exemptionunder subpart E of this part.

(b) Manufacturing, importing, orprocessing microorganisms for testmarketing activities which have beengranted an exemption under subpart Fof this part.

(c) Manufacturing or importing newmicroorganisms under the conditions ofa Tier I or Tier II exemption undersubpart G of this part.

§ 725.150 Procedural requirements for thissubpart.

General requirements for all MCANsunder this part are contained insubparts A through C of this part. Inaddition, the following requirementsapply to MCANs submitted under thissubpart:

(a) When to submit a MCAN. A MCANmust be submitted at least 90 calendardays prior to manufacturing orimporting a new microorganism and atleast 90 calendar days prior tomanufacturing, importing, or processinga microorganism for a significant newuse.

(b) Section 5(b) of the Act. Thesubmitter must comply with anyapplicable requirement of section 5(b) ofthe Act for the submission of test data.

(c) Contents of a MCAN. Each personwho submits a MCAN under thissubpart must provide the informationand test data described in §§ 725.155and 725.160.

(d) Recordkeeping. Each person whosubmits a MCAN under this subpartmust comply with the recordkeepingrequirements of § 725.65.

§ 725.155 Information to be included in theMCAN.

(a) Each person who is required bythis part to submit a MCAN mustinclude the information specified inparagraphs (c) through (h) of thissection, to the extent it is known to orreasonably ascertainable by that person.However, no person is required toinclude information which relates solelyto exposure of humans or ecologicalpopulations outside of the UnitedStates.

(b) Each person should also submit, inwriting, all other information known toor reasonably ascertainable by thatperson that would permit EPA to makea reasoned evaluation of the health andenvironmental effects of themicroorganism, or any microbialmixture or article, includinginformation on its effects on humans,animals, plants, and othermicroorganisms, and in theenvironment. The information to besubmitted under this subpart includesthe information listed in paragraphs (c)through (h) of this section relating to themanufacture, processing, distribution incommerce, use, and disposal of the newmicroorganism.

(c) Submitter identification. (1) Thename and headquarters address of thesubmitter.

(2) The name, address, and officetelephone number (including area code)of the principal technical contactrepresenting the submitter.

(d) Microorganism identityinformation. Persons must submitsufficient information to allow themicroorganism to be accurately andunambiguously identified for listingpurposes as required by § 725.12.

(1) Description of the recipientmicroorganism and the newmicroorganism. (i) Data substantiatingthe taxonomy of the recipientmicroorganism and the newmicroorganism to the level of strain, asappropriate. In lieu of data, EPA willaccept a letter from a culture collectionsubstantiating taxonomy, provided EPA,upon request to the submitter, may haveaccess to the data supporting thetaxonomic designation.

(ii) Information on the morphologicaland physiological features of the newmicroorganism.

(iii) Other specific data by which thenew microorganism may be uniquelyidentified for Inventory purposes.

(2) Genetic construction of the newmicroorganism. (i) Data substantiatingthe taxonomy of the donor organism(s).In lieu of data, EPA will accept a letterfrom a culture collection substantiatingtaxonomy, provided EPA, upon requestto the submitter, may have access to the


data supporting the taxonomicdesignation.

(ii) Description of the traits for whichthe new microorganism has beenselected or developed and other traitsknown to have been added or modified.

(iii) A detailed description of thegenetic construction of the newmicroorganism, including the techniqueused to modify the microorganism (e.g.,fusion of cells, injection of DNA,electroporation or chemical poration, ormethods used for induced mutation andselection). The description shouldinclude, for example, a description ofthe introduced genetic material,including any regulatory sequences andstructural genes and the products ofthose genes; how the introduced geneticmaterial is expected to affect behavior ofthe recipient; expression, alteration, andstability of the introduced geneticmaterial; methods for vectorconstruction and introduction; and adescription of the regulatory andstructural genes that are components ofthe introduced genetic material,including genetic maps of theintroduced sequences.

(3) Phenotypic and ecologicalcharacteristics. (i) Habitat, geographicaldistribution, and source of the recipientmicroorganism.

(ii) Survival and dissemination underrelevant environmental conditionsincluding a description of methods fordetecting the new or recipientmicroorganism(s) in the environmentand the sensitivity limit of detection forthese techniques.

(iii) A description of anticipatedbiological interactions with and effectson target organisms and other organismssuch as competitors, prey, hosts,symbionts, parasites, and pathogens; adescription of host range; a descriptionof pathogenicity, infectivity, toxicity,virulence, or action as a vector ofpathogens; and capacity for genetictransfer under laboratory and relevantenvironmental conditions.

(iv) A description of anticipatedinvolvement in biogeochemical orbiological cycling processes,involvement in rate limiting steps inmineral or nutrient cycling, orinvolvement in inorganic compoundscycling (such as possible sequestrationor transformation of heavy metals).

(e) Byproducts. A description of thebyproducts resulting from themanufacture, processing, use, anddisposal of the new microorganism.

(f) Total production volume. Theestimated maximum amount of the newmicroorganism intended to bemanufactured or imported during thefirst year of production and theestimated maximum amount to be

manufactured or imported during anyconsecutive 12–month period duringthe first 3 years of production. Thisestimate may be by weight or volumeand should include an estimation ofviability (i.e., viable cells per unitvolume or colony forming units per unitdry weight).

(g) Use information. A description ofintended categories of use by functionand application, the estimated percentof production volume devoted to eachcategory of use, and the percent of thenew microorganism in the formulationfor each commercial or consumer use.

(h) Worker exposure andenvironmental release. (1) For sitescontrolled by the submitter:

(i) The identity of sites where the newmicroorganism will be manufactured,processed, or used. For purposes of thissection, the site for a person whoimports a new microorganism is the siteof the operating unit within the person’sorganization which is directlyresponsible for importing the newmicroorganism and which controls theimport transaction. The import site mayin some cases be the organization’sheadquarters office in the United States.

(ii) A process description of eachmanufacture, processing, and useoperation, which includes a diagram ofthe major unit operations andconversions, the identity and entrypoint of all feedstocks, and the identityof any possible points of release of thenew microorganism from the process,including a description of all controls,including engineering controls, used toprevent such releases.

(iii) Worker exposure information,including worker activities, physicalform of process streams which containthe new microorganism to whichworkers may be exposed, the number ofworkers, and the duration of activities.

(iv) Information on release of the newmicroorganism to the environment,including the quantity and media ofrelease and type of control technologyused.

(v) A narrative description of theintended transport of the newmicroorganism, including the means oftransport, containment methods to beused during transport, and emergencycontainment procedures to be followedin case of accidental release.

(vi) Procedures for disposal of anyarticles, waste, clothing, or otherequipment involved in the activity,including procedures for inactivation ofthe new microorganism, containment,disinfection, and disposal ofcontaminated items.

(2) For sites not controlled by thesubmitter, a description of each type ofprocessing and use operation involving

the new microorganism, includingidentification of the estimated numberof processing or use sites, situations inwhich worker exposure to and/orenvironmental release of the newmicroorganism will occur, the numberof workers exposed and the duration ofexposure; procedures for transport ofthe new microorganism and fordisposal, including procedures forinactivation of the new microorganism;and control measures which limitworker exposure and environmentalrelease.

§ 725.160 Submission of health andenvironmental effects data.

(a) Test data on the newmicroorganism in the possession orcontrol of the submitter. (1) Except asprovided in § 725.25(h), and in additionto the information required by§ 725.155(d)(3), each MCAN mustcontain all test data in the submitter’spossession or control which are relatedto the effects on health or theenvironment of any manufacture,processing, distribution in commerce,use, or disposal of the newmicroorganism or any microbial mixtureor article containing the newmicroorganism, or any combination ofsuch activities. This includes test dataconcerning the new microorganism in apure culture or formulated form as usedor as intended to be used in one of theactivities listed above.

(2) A full report or standard literaturecitation must be submitted for thefollowing types of test data:

(i) Health effects data.(ii) Ecological effects data.(iii) Physical and chemical properties

data.(iv) Environmental fate

characteristics.(v) Monitoring data and other test data

related to human exposure to orenvironmental release of the newmicroorganism.

(3)(i) If the data do not appear in theopen scientific literature, the submittermust provide a full report. A full reportincludes the experimental methods andmaterials, results, discussion and dataanalysis, conclusions, references, andthe name and address of the laboratorythat developed the data.

(ii) If the data appear in the openscientific literature, the submitter needonly provide a standard literaturecitation. A standard literature citationincludes author, title, periodical name,date of publication, volume, and pagenumbers.

(4)(i) If a study, report, or test isincomplete when a person submits aMCAN, the submitter must identify thenature and purpose of the study; name


and address of the laboratorydeveloping the data; progress to date;types of data collected, significantpreliminary results; and anticipatedcompletion date.

(ii) If a test or experiment iscompleted before the MCAN reviewperiod ends, the person must submit thestudy, report, or test, as specified inparagraph (a)(3)(i) of this section, to theaddress listed in § 725.25(c) within 10days of receiving it, but no later than 5days before the end of the reviewperiod. If the test or experiment iscompleted during the last 5 days of thereview period, the submitter mustimmediately inform its EPA contact forthat submission by telephone.

(5) For test data in the submitter’spossession or control which are notlisted in paragraph (a)(2) of this section,a person is not required to submit acomplete report. The person mustsubmit a summary of the data. If EPA sorequests, the person must submit a fullreport within 10 days of the request, butno later than 5 days before the end ofthe review period.

(6) All test data described underparagraph (a) of this section are subjectto these requirements, regardless of theirage, quality, or results.

(b) Other data concerning the healthand environmental effects of the newmicroorganism that are known to orreasonably ascertainable by thesubmitter. (1) Except as provided in§ 725.25(h), and in addition to theinformation required by § 725.155(c)(3),any person who submits a MCAN mustdescribe the following data, includingany data from a health and safety studyof a microorganism, if the data arerelated to effects on health or theenvironment of any manufacture,processing, distribution in commerce,use, or disposal of the microorganism, ofany microbial mixture or articlecontaining the new microorganism, or ofany combination of such activities:

(i) Any data, other than test data, inthe submitter’s possession or control.

(ii) Any data, including test data,which are not in the submitter’spossession or control, but which areknown to or reasonably ascertainable bythe submitter. For the purposes of thissection, data are known to or reasonablyascertainable by the submitter if the dataare known to any of its employees orother agents who are associated with theresearch and development, testmarketing, or commercial marketing ofthe microorganism.

(2) Data that must be describedinclude data concerning the newmicroorganism in a pure culture orformulated form as used or as intended

to be used in one of the activities listedin paragraph (b)(1) of this section.

(3) The description of data reportedunder paragraph (b) of this section mustinclude:

(i) If the data appear in the openscientific literature, a standard literaturecitation, which includes the author,title, periodical name, date ofpublication, volume, and pages.

(ii) If the data are not available in theopen scientific literature, a descriptionof the type of data and summary of theresults, if available, and the names andaddresses of persons the submitterbelieves may have possession or controlof the data.

(4) All data described in paragraph (b)of this section are subject to theserequirements, regardless of their age,quality, or results; and regardless ofwhether they are complete at the timethe MCAN is submitted.

§ 725.170 EPA review of the MCAN.General procedures for review of all

submissions under this part arecontained in §§ 725.28 through 725.60.In addition, the following proceduresapply to EPA review of MCANssubmitted under this subpart:

(a) Length of the review period. TheMCAN review period specified insection 5(a) of the Act runs for 90 daysfrom the date the Document ControlOfficer for the Office of PollutionPrevention and Toxics receives acomplete MCAN, or the date EPAdetermines the MCAN is completeunder § 725.33, unless the Agencyextends the period under section 5(c) ofthe Act and § 725.56.

(b) Notice of expiration of MCANreview period. (1) EPA will notify thesubmitter that the MCAN review periodhas expired or that EPA has completedits review of the MCAN. Expiration ofthe review period does not constituteEPA approval or certification of the newmicroorganism, and does not mean thatEPA may not take regulatory actionagainst the microorganism in the future.

(2) After expiration of the MCANreview period, in the absence ofregulatory action by EPA under section5(e), 5(f), or 6(a) of the Act, thesubmitter may manufacture or importthe microorganism even if the submitterhas not received notice of expiration.

(3) Early notification that EPA hascompleted its review does not permitcommencement of manufacture orimport prior to the expiration of the 90–day MCAN review period.

(c) No person submitting a MCAN inresponse to the requirements of thissubpart may manufacture, import, orprocess a microorganism subject to thissubpart until the review period,

including all extensions andsuspensions, has expired.

§ 725.190 Notice of commencement ofmanufacture or import.

(a) Applicability. Any person whocommences the manufacture or importof a new microorganism for nonexempt,commercial purposes for which thatperson previously submitted a section5(a) notice under this part must submita notice of commencement (NOC) ofmanufacture or import.

(b) When to report. (1) If manufactureor import for nonexempt, commercialpurposes begins on or after May 27,1997, the submitter must submit theNOC to EPA no later than 30 calendardays after the first day of suchmanufacture or import.

(2) If manufacture or import fornonexempt, commercial purposes beganor will begin before May 27, 1997, thesubmitter must submit the NOC by May27, 1997.

(3) Submission of an NOC prior to thecommencement of manufacture orimport is a violation of section 15 of theAct.

(c) Information to be reported. TheNOC must contain the followinginformation: Specific microorganismidentity, MCAN number, and the datewhen manufacture or importcommences. If the person claimedmicroorganism identity confidential inthe MCAN, and wants the identity to belisted on the confidential Inventory, theclaim must be reasserted andresubstantiated in accordance with§ 725.85(b). Otherwise, EPA will list thespecific microorganism identity on thepublic Inventory.

(d) Where to submit. NOCs should besubmitted to the address listed in§ 725.25(c).

Subpart E—Exemptions for Research andDevelopment Activities

§ 725.200 Scope and purpose.(a) This subpart describes exemptions

from the reporting requirements undersubpart D of this part for research anddevelopment activities involvingmicroorganisms.

(b) In lieu of complying with subpartD of this part, persons described in§ 725.205 may submit a TSCAExperimental Release Application(TERA) for research and developmentactivities involving microorganisms orotherwise comply with this subpart.

(c) Exemptions from part 725 areprovided at §§ 725.232, 725.234, and725.238.

(d) Submission requirements specificfor TERAs are described at § 725.250.

(e) Data requirements for TERAs areset forth in §§ 725.255 and 725.260.


(f) EPA review procedures specific forTERAs are set forth in §§ 725.270 and725.288.

(g) Subparts A through C of this partapply to any submission under thissubpart.

§ 725.205 Persons who may report underthis subpart.

(a) Commercial research anddevelopment activities involving newmicroorganisms or significant new usesof microorganisms are subject toreporting under this part unless theyqualify for an exemption under thispart.

(b) Commercial purposes for researchand development means that theactivities are conducted with thepurpose of obtaining an immediate oreventual commercial advantage for theresearcher and would include:

(1) All research and developmentactivities which are funded directly, inwhole or in part, by a commercial entityregardless of who is actually conductingthe research. Indications that theresearch and development activities arefunded directly, in whole or in part,may include, but are not limited to:

(i) Situations in which a commercialentity contracts directly with auniversity or researcher; or

(ii) Situations in which a commercialentity gives a conditional grant wherethe commercial entity holds patentrights, or establishes a joint venturewhere the commercial entity holdspatent or licensing rights; or

(iii) Any other situation in which thecommercial entity intends to obtain animmediate or eventual commercialadvantage for the commercial entityand/or the researcher.

(2) Research and developmentactivities that are not funded directly bya commercial entity, if the researcherintends to obtain an immediate oreventual commercial advantage.Indications that the researcher intendsto obtain an immediate or eventualcommercial advantage may include, butare not limited to:

(i) The research is directed towarddeveloping a commercially viableimprovement of a product already onthe market; or

(ii) The researcher has sought or isseeking commercial funding for thepurpose of developing a commercialapplication; or

(iii) The researcher or university hassought or is seeking a patent to protecta commercial application which theresearch is developing; or

(iv) Other evidence that the researcheris aware of a commercial application forthe research and has directed theresearch toward developing thatapplication.

(c) Certain research and developmentactivities involving microorganismssubject to jurisdiction under the Act areexempt from reporting under this part.A person conducting research anddevelopment activities which meet theconditions for the exemptions describedin §§ 725.232, 725.234, or 725.238 isexempt from TERA reporting under thissubpart.

(d) A microorganism is not exemptfrom reporting under subpart D of thispart if any amount of themicroorganism, including as part of amixture, is processed, distributed incommerce, or used, for any commercialpurpose other than research anddevelopment.

(e) Quantities of the inactivatedmicroorganism, or mixtures or articlescontaining the inactivatedmicroorganism, remaining aftercompletion of research anddevelopment activities may be disposedof as a waste in accordance withapplicable Federal, State, and localregulations.

(f) A person who manufactures,imports, or processes a microorganismsolely for research and development isnot required to comply with therequirements of this section if:

(1) The person is manufacturing amicrobial pesticide identified in§ 172.45(c), or

(2) The person is manufacturing amicrobial pesticide for which anExperimental Use Permit is required,pursuant to § 172.3; or

(3) The person is manufacturing amicrobial pesticide for which anotification or an Experimental UsePermit is not required to be submitted.

§ 725.232 Activities subject to thejurisdiction of other Federal programs oragencies.

This part does not apply to anyresearch and development activity thatmeets all of the following conditions.

(a) The microorganism ismanufactured, imported, or processedsolely for research and developmentactivities.

(b) There is no intentional testing ofa microorganism outside of a structure,as structure is defined in § 725.3.

(c)(1) The person receives researchfunds from another Federal agency, andthe funds are awarded on the conditionthat the research will be conducted inaccordance with the relevant portions ofthe NIH Guidelines, or

(2) A Federal agency or programotherwise imposes the legally bindingrequirement that the research is to beconducted in accordance with relevantportions of the NIH Guidelines.

§ 725.234 Activities conducted inside astructure.

A person who manufactures, imports,or processes a microorganism is notsubject to the reporting requirementsunder subpart D of this part if all of thefollowing conditions are met:

(a) The microorganism ismanufactured, imported, or processedsolely for research and developmentactivities.

(b) The microorganism is used by, ordirectly under the supervision of, atechnically qualified individual, asdefined in § 725.3. The technicallyqualified individual must maintaindocumentation of the proceduresselected to comply with paragraph (d) ofthis section and must ensure that theprocedures are used.

(c) There is no intentional testing ofa microorganism outside of a structure,as structure is defined in § 725.3.

(d) Containment and/or inactivationcontrols. (1) Selection and use ofcontainment and/or inactivationcontrols inside a structure for aparticular microorganism shall take intoaccount the following:

(i) Factors relevant to the organism’sability to survive in the environment.

(ii) Potential routes of release in air,solids and liquids; in or on wastematerials and equipment; in or onpeople, including maintenance andcustodial personnel; and in or on otherorganisms, such as insects and rodents.

(iii) Procedures for transfer ofmaterials between facilities.

(2) The technically qualifiedindividual’s selection of containmentand/or inactivation controls shall beapproved and certified by an authorizedofficial (other than the TQI) of theinstitution that is conducting the testprior to the commencement of the test.

(3) Records shall be developed andmaintained describing the selection anduse of containment and/or inactivationcontrols, as specified in § 725.235(c).These records, which must bemaintained at the location where theresearch and development activity isbeing conducted, shall be submitted toEPA upon written request and withinthe time frame specified in EPA’srequest.

(4) Subsequent to EPA review ofrecords in accordance with paragraph(d)(3) of this section, changes to thecontainment/inactivation controlsselected under paragraph (d)(1) of thissection must be made upon EPA order.Failure to comply with EPA’s ordershall result in automatic loss ofeligibility for an exemption under thissection.

(e) The manufacturer, importer, orprocessor notifies all persons in its


employ or to whom it directlydistributes the microorganism, who areengaged in experimentation, research, oranalysis on the microorganism,including the manufacture, processing,use, transport, storage, and disposal ofthe microorganism associated withresearch and development activities, ofany risk to health, identified under§ 725.235(a), which may be associatedwith the microorganism. Thenotification must be made in accordancewith § 725.235(b).

§ 725.235 Conditions of exemption foractivities conducted inside a structure.

(a) Determination of risks. Todetermine whether notification under§ 725.234(e) is required, themanufacturer, importer, or processormust do one of the following:

(1) For research conducted inaccordance with the NIH Guidelines,the manufacturer, importer, or processormust meet the conditions laid out at IV-B-4-d of the NIH Guidelines; or

(2) For all other research conducted inaccordance with § 725.234, themanufacturer, importer, or processormust review and evaluate the followinginformation to determine whether thereis reason to believe there is any risk tohealth which may be associated withthe microorganism:

(i) Information in its possession orcontrol concerning any significantadverse reaction of persons exposed tothe microorganism which mayreasonably be associated with suchexposure.

(ii) Information provided to themanufacturer, importer, or processor bya supplier or any other personconcerning a health risk believed to beassociated with the microorganism.

(iii) Health and environmental effectsdata in its possession or controlconcerning the microorganism.

(iv) Information on health effectswhich accompanies any EPA rule ororder issued under TSCA section 4, 5,or 6 of the Act that applies to themicroorganism and of which themanufacturer, importer, or processorhas knowledge.

(b) Notification to employees andothers. (1) The manufacturer, importer,or processor must notify the personsidentified in § 725.234(e) by means of acontainer labeling system, conspicuousplacement of notices in areas whereexposure may occur, writtennotification to each person potentiallyexposed, or any other method ofnotification which adequately informspersons of health risks which themanufacturer, importer, or processorhas reason to believe may be associated

with the microorganism, as determinedunder paragraph (a) of this section.

(2) If the manufacturer, importer, orprocessor distributes a microorganismmanufactured, imported, or processedunder this section to persons not in itsemploy, the manufacturer, importer, orprocessor must in written form:

(i) Notify those persons that themicroorganism is to be used only forresearch and development purposes andthe requirements of § 725.234 are to bemet.

(ii) Provide the notice of health risksspecified in paragraph (b)(1) of thissection.

(3) The adequacy of any notificationunder this section is the responsibilityof the manufacturer, importer, orprocessor.

(c) Recordkeeping. (1) For researchconducted in accordance with the NIHGuidelines, a person who manufactures,imports, or processes a microorganismunder this section must retain thefollowing records:

(i) Documentation that the NIHGuidelines have been adhered to. Suchdocumentation shall include:

(A) For experiments subject toInstitutional Biosafety Committeereview, or notification simultaneouswith initiation of the experiment, theinformation submitted for review ornotification, along with standardlaboratory records, shall satisfy therecordkeeping requirements specified in§ 725.234(d)(3).

(B) For experiments exempt fromInstitutional Biosafety Committeereview or notification simultaneouswith initiation of the experiment,documentation of the exemption, alongwith standard laboratory records, shallsatisfy the recordkeeping requirementspecified in § 725.234(d)(3).

(ii) Documentation of how thefollowing requirements are satisfiedunder the NIH Guidelines:

(A) Copies or citations to informationreviewed and evaluated to determinethe need to make any notification ofrisk.

(B) Documentation of the nature andmethod of notification of risk, includingcopies of any labels or written noticesused.

(C) The names and addresses of anypersons other than the manufacturer,importer, or processor to whom thesubstance is distributed, the identity ofthe microorganism, the amountdistributed, and copies of thenotifications required.

(2) For all other research conducted inaccordance with § 725.234, a personwho manufacturers, imports, orprocesses a microorganism under this

section, must maintain the followingrecords:

(i) Records describing selection anduse of containment and/or inactivationcontrols required by § 725.234(d)(3) andcertification by an authorized officialrequired by § 725.234(d)(2) for eachmicroorganism.

(ii) Copies or citations to informationreviewed and evaluated underparagraph (a) of this section todetermine the need to make anynotification of risk.

(iii) Documentation of the nature andmethod of notification under paragraph(b)(1) of this section, including copies ofany labels or written notices used.

(iv) The names and addresses of anypersons other than the manufacturer,importer, or processor to whom thesubstance is distributed, the identity ofthe microorganism, the amountdistributed, and copies of thenotifications required under paragraph(b)(2) of this section.

§ 725.238 Activities conducted outside astructure.

(a) Exemption. (1) Research anddevelopment activities involvingintentional testing in the environment ofcertain microorganisms listed in§ 725.239 may be conducted withoutprior review by EPA if all of theconditions of this section and § 725.239are met.

(2) The research and developmentactivity involving a microorganismlisted in § 725.239 must be conductedby, or directly under the supervision of,a technically qualified individual, asdefined in § 725.3.

(b) Certification. To be eligible for theexemption under this section, amanufacturer or importer must submitto EPA prior to initiation of the activitya document signed by an authorizedofficial containing the followinginformation:

(1) Name, address, and telephonenumber of the manufacturer or importer.

(2) Location, estimated duration, andplanned start date of the test.

(3) Certification of the following:(i) Compliance with the conditions of

the exemption specified for themicroorganism in § 725.239.

(ii) If state and/or local authoritieshave been notified of the activity,evidence of notification.

(c) Recordkeeping. Persons whoconduct research and developmentactivities under this section mustcomply with the recordkeepingrequirements of § 725.65 and retaindocumentation that supports theircompliance with the requirements ofthis section and the specificrequirements for the microorganismlisted in § 725.239.


§ 725.239 Use of specific microorganismsin activities conducted outside a structure.

(a) Bradyrhizobium japonicum. Toqualify for an exemption under thissection, all of the following conditionsmust be met for a test involvingBradyrhizobium japonicum:

(1) Characteristics of recipientmicroorganism. The recipientmicroorganism is limited to strains ofBradyrhizobium japonicum.

(2) Modification of traits. (i) Theintroduced genetic material must meetthe criteria for poorly mobilizable listedin § 725.421(c).

(ii) The introduced genetic materialmust consist only of the followingcomponents:

(A) The structural gene(s) of interest,which have the following limitations:

(1) For structural genes encodingmarker sequences, the gene is limited tothe aadH gene, which confers resistanceto the antibiotics streptomycin andspectinomycin.

(2) For traits other than antibioticresistance, the structural gene must belimited to the genera Bradyrhizobiumand Rhizobium.

(B) The regulatory sequencespermitting the expression of solely thegene(s) of interest.

(C) Associated nucleotide sequencesneeded to move genetic material,including linkers, homopolymers,adaptors, transposons, insertionsequences, and restriction enzyme sites.

(D) The vector nucleotide sequencesneeded for vector transfer.

(E) The vector nucleotide sequencesneeded for vector maintenance.

(3) Limitations on exposure. (i) Thetest site area must be no more than 10terrestrial acres.

(ii) The technically qualifiedindividual must select appropriatemethods to limit the dissemination ofmodified Bradyrhizobium japonicum.

(b) Rhizobium meliloti. To qualify foran exemption under this section, all ofthe following conditions must be metfor a test involving Rhizobium meliloti:

(1) Characteristics of recipientmicroorganism. The recipientmicroorganism is limited to strains ofRhizobium meliloti.

(2) Modification of traits. (i) Theintroduced genetic material must meetthe criteria for poorly mobilizable listedin § 725.421(c) of this part.

(ii) The introduced genetic materialmust consist only of the followingcomponents:

(A) The structural gene(s) of interest,which have the following limitations:

(1) For structural genes encodingmarker sequences, the gene is limited tothe aadH gene, which confers resistanceto the antibiotics streptomycin andspectinomycin.

(2) For traits other than antibioticresistance, the structural gene must belimited to the genera Bradyrhizobiumand Rhizobium.

(B) The regulatory sequencespermitting the expression of solely thegene(s) of interest.

(C) Associated nucleotide sequencesneeded to move genetic material,including linkers, homopolymers,adaptors, transposons, insertionsequences, and restriction enzyme sites.

(D) The vector nucleotide sequencesneeded for vector transfer.

(E) The vector nucleotide sequencesneeded for vector maintenance.

(3) Limitations on exposure. (i) Thetest site area must be no more than 10terrestrial acres.

(ii) The technically qualifiedindividual must select appropriatemethods to limit the dissemination ofmodified Rhizobium meliloti.

§ 725.250 Procedural requirements for theTERA.

General requirements for allsubmissions under this part arecontained in subparts A through C ofthis part. In addition, the followingrequirements apply to TERAs submittedunder this subpart:

(a) When to submit the TERA. Eachperson who is eligible to submit a TERAunder this subpart must submit theTERA at least 60 calendar days beforethe person intends to initiate theproposed research and developmentactivity.

(b) Contents of the TERA. Each personwho submits a TERA under this subpartmust provide the information and testdata described in §§ 725.255 and725.260. In addition, the submitter mustsupply sufficient information to enableEPA to evaluate the effects of allactivities for which approval isrequested.

(c) A person may submit a TERA forone or more microorganisms and one ormore research and developmentactivities, including a research program.

(d) EPA will either approve the TERA,with or without conditions, ordisapprove it under proceduresestablished in this subpart.

(e) The manufacturer, importer, orprocessor who receives a TERAapproval must comply with all terms ofthe approval, as well as conditionsdescribed in the TERA, and remainsliable for compliance with all terms andconditions, regardless of who conductsthe research and development activity.Any person conducting the research anddevelopment activity approved underthe TERA must comply with all termsof the TERA approval, as well as theconditions described in the TERA.

(f) Recordkeeping. Persons submittinga TERA must comply with therecordkeeping requirements of § 725.65.In addition, the following requirementsapply to TERAs:

(1) Each person submitting a TERAunder this part must retaindocumentation of information containedin the TERA for a period of 3 years fromthe date that the results of the study aresubmitted to the Agency.

(2) Summaries of all data,conclusions, and reports resulting fromthe conduct of the research anddevelopment activity under the TERAmust be submitted to the EPA addressidentified in § 725.25(c) within 1 year ofthe termination of the activity.

§ 725.255 Information to be included in theTERA.

(a) To review a TERA, EPA must havesufficient information to permit areasoned evaluation of the health andenvironmental effects of the plannedtest in the environment. The personseeking EPA approval must submit allinformation known to or reasonablyascertainable by the submitter on themicroorganism(s) and the research anddevelopment activity, includinginformation not listed in paragraphs (c),(d), and (e) of this section that theperson believes will be useful for EPA’srisk assessment. The TERA must be inwriting and must include at least theinformation described in the followingparagraphs.

(b) When specific information is notsubmitted, an explanation of why suchinformation is not available or notapplicable must be included.

(c) Persons applying for a TERA, mustinclude the submitter identification andmicroorganism identity informationrequired for MCANs in § 725.155(c),(d)(1), and (d)(2).

(d) Persons applying for a TERA mustsubmit phenotypic and ecologicalcharacteristics information required in§ 725.155(d)(3) as it relates directly tothe conditions of the proposed researchand development activity.

(e) Persons applying for a TERA mustalso submit the following informationabout the proposed research anddevelopment activity:

(1) A detailed description of theproposed research and developmentactivity. (i) The objectives andsignificance of the activity and arationale for testing the microorganismsin the environment.

(ii) Number of microorganismsreleased (including viability per volumeif applicable) and the method(s) ofapplication or release.

(iii) Characteristics of the test site(s),including location, geographical,


physical, chemical, and biologicalfeatures, proximity to human habitationor activity, and description of sitecharacteristics that would influencedispersal or confinement.

(iv) Target organisms (if themicroorganism(s) to be tested has anintended target), includingidentification of each target organismand anticipated mechanism and resultof interaction.

(v) Planned start date and duration ofeach activity.

(vi) If State and/or local authoritieshave been notified of the activity,evidence of notification.

(2) Information on monitoring,confinement, mitigation, and emergencytermination procedures. (i) Confinementprocedures for the activity, access andsecurity measures, and procedures forroutine termination of the activity.

(ii) Mitigation and emergencyprocedures.

(iii) Measures to detect and controlpotential adverse effects.

(iv) Name of principal investigatorand chief of site personnel responsiblefor emergency procedures.

(v) Personal protective equipment,engineering controls, and procedures tobe followed to minimize dispersion ofthe microorganism(s) by people,machinery, or equipment.

(vi) Procedures for disposal of anyarticles, waste, clothing, machinery, orother equipment involved in theexperimental release, includingmethods for inactivation of themicroorganism(s), containment,disinfection, and disposal ofcontaminated items.

§ 725.260 Submission of health andenvironmental effects data.

Each TERA must contain all availabledata concerning actual or potentialeffects on health or the environment ofthe new microorganism that are in thepossession or control of the submitterand a description of other data knownto or reasonably ascertainable by thesubmitter that will permit a reasonedevaluation of the planned test in theenvironment. The data must be reportedin the manner described in§ 725.160(a)(3) and (b)(3).

§ 725.270 EPA review of the TERA.General procedures for review of all

submissions under this part arecontained in §§ 725.28 through 725.60.In addition, the following proceduresapply to EPA review of applicationssubmitted under this subpart:

(a) Length of the review period. (1)The review period for the TERA will be60 days from the date the DocumentControl Officer for the Office of

Pollution Prevention and Toxicsreceives a complete TERA, or the dateEPA determines the TERA is completeunder § 725.33, unless EPA finds goodcause for an extension under § 725.56.

(2) A submitter shall not proceed withthe research and development activitydescribed in the TERA unless and untilEPA provides written approval of theTERA. A submitter may receive earlyapproval if a review is completed in lessthan 60 days.

(b) EPA decision regarding proposedTERA activity. (1) A decisionconcerning a TERA under this subpartwill be made by the Administrator, or adesignee.

(2) If EPA determines that theproposed research and developmentactivity for the microorganism does notpresent an unreasonable risk of injury tohealth or the environment, EPA willnotify the submitter that the TERA isapproved and that the submitter canproceed with the proposed research anddevelopment activity described in theTERA.

(3) EPA may include requirementsand conditions in its approval of theTERA that would be stated in the TERAapproval under paragraph (c) of thissection.

(4) If EPA concludes that it cannotdetermine that the proposed researchand development activity described inthe TERA will not present anunreasonable risk of injury to health orthe environment, EPA will deny theTERA and will provide reasons for thedenial in writing.

(c) TERA approval. (1) A TERAapproval issued by EPA under thissection is legally binding on the TERAsubmitter.

(2) When EPA approves a TERA, thesubmitter must conduct the researchand development activity only asdescribed in the TERA and inaccordance with any requirements andconditions prescribed by EPA in itsapproval of the TERA.

(3) Any person who fails to conductthe research and development activityas described in the TERA and inaccordance with any requirements andconditions prescribed by EPA in itsapproval of the TERA under thissection, shall be in violation of sections5 and 15 of the Act and be subject tocivil and criminal penalties undersection 16 of the Act.

§ 725.288 Revocation or modification ofTERA approval.

(a) Significant questions about risk.(1) If, after approval of a TERA underthis subpart, EPA receives informationwhich raises significant questions aboutEPA’s determination that the activity

does not present an unreasonable risk ofinjury to health or the environment,EPA will notify the submitter in writingof those questions.

(2) The submitter may, within 10 daysof receipt of EPA’s notice, provide inwriting additional information orarguments concerning the significanceof the questions and whether EPAshould modify or revoke the approval ofthe TERA.

(3) After considering any suchinformation and arguments, EPA willdecide whether to change itsdetermination regarding approval of theTERA.

(i) If EPA determines that the activitywill not present an unreasonable risk ofinjury to health or the environment, itwill notify the submitter in writing. Tomake this finding, EPA may prescribeadditional conditions which must befollowed by the submitter.

(ii) If EPA determines that it can nolonger conclude that the activity willnot present an unreasonable risk ofinjury to health or the environment, itwill notify the submitter in writing thatEPA is revoking its approval and stateits reasons. In that event, the submittermust terminate the research anddevelopment activity within 48 hours ofreceipt of the notice in accordance withdirections provided by EPA in thenotice.

(b) Evidence of unreasonable risk. (1)If, after approval of a TERA under thissubpart, EPA determines that theproposed research and developmentactivity will present an unreasonablerisk of injury to health or theenvironment, EPA will notify thesubmitter in writing and state itsreasons.

(2) In the notice, EPA may prescribeadditional safeguards to address orreduce the risk, or may instruct thesubmitter to suspend the research anddevelopment activities.

(3) Within 48 hours, the submittermust implement the instructionscontained in the notice. The submittermay then submit additional informationor arguments concerning the mattersraised by EPA and whether EPA shouldmodify or revoke the approval of theTERA in accordance with paragraph(a)(2) of this section.

(4) EPA will consider the informationand arguments in accordance withparagraph (a)(3) of this section.

(5) Following consideration of theinformation and arguments underparagraph (a)(3) of this section, if EPAnotifies the submitter that the R&Dactivity must be suspended orterminted, the submitter may resumethe activity only upon written noticefrom EPA that EPA has approved


resumption of the activity. In approvingresumption of an activity, EPA mayprescribe additional conditions whichmust be followed by the submitter.

(c) Modifications. If, after approval ofa TERA under this subpart, thesubmitter concludes that it is necessaryto alter the conduct of the research anddevelopment activity in a manner whichwould result in the activity beingdifferent from that described in theTERA agreement and any conditionsEPA prescribed in its approval, thesubmitter must inform the EPA contactfor the TERA and may not modify theactivity without the approval of EPA.

Subpart F—Exemptions for Test Marketing


from the reporting requirements undersubpart D of this part for test marketingactivities involving microorganisms.

(b) In lieu of complying with subpartD of this part, persons described in§ 725.305 may submit an application fora test marketing exemption (TME).

(c) Submission requirements specificfor TME applications are described at§ 725.350.

(d) Data requirements for TMEapplications are set forth in § 725.355.

(e) EPA review procedures specific forTMEs are set forth in § 725.370.

(f) Subparts A through C of this partapply to any submission under thissubpart.

§ 725.305 Persons who may apply underthis subpart.

A person identified in this sectionmay apply for a test marketingexemption. EPA may grant theexemption if the person demonstratesthat the microorganism will not presentan unreasonable risk of injury to healthor the environment as a result of the testmarketing. A person may apply underthis subpart for the following testmarketing activities:

(a) A person who intends tomanufacture or import for commercialpurposes a new microorganism.

(b) A person who intends tomanufacture, import, or process forcommercial purposes a microorganismidentified in subpart M of this part fora significant new use.

§ 725.350 Procedural requirements for thissubpart.

General requirements for allsubmissions under this part arecontained in subparts A through C ofthis part. In addition, the followingrequirements apply to applicationssubmitted under this subpart:

(a) Prenotice consultation. EPAstrongly suggests that for a TME, the

applicant contact EPA for a prenoticeconsultation regarding eligibility for aTME.

(b) When to submit a TMEapplication. Each person who is eligibleto apply for a TME under this subpartmust submit the application at least 45calendar days before the person intendsto commence the test marketing activity.

(c) Recordkeeping. Each person whois granted a TME must comply with therecordkeeping requirements of § 725.65.In addition, any person who obtains aTME must retain documentation ofcompliance with any restrictionsimposed by EPA when it grants theTME. This information must be retainedfor 3 years from the final date ofmanufacture or import under theexemption.

§ 725.355 Information to be included in theTME application.

(a) To review a TME application, EPAmust have sufficient information topermit a reasoned evaluation of thehealth and environmental effects of theplanned test marketing activity. Theperson seeking EPA approval mustsubmit all information known to orreasonably ascertainable by the personon the microorganism and the testmarketing activity, includinginformation not listed in paragraphs (c),(d), and (e) of this section that theperson believes will demonstrate thatthe microorganism will not present anunreasonable risk of injury to health orthe environment as a result of the testmarketing. The TME application mustbe in writing and must include at leastthe information described in paragraphs(b), (c), (d), and (e) of this section.

(b) When specific information is notsubmitted, an explanation of why suchinformation is not available or notapplicable must be included.

(c) Persons applying for a TME mustsubmit the submitter identification andmicroorganism identity informationrequired for MCANs in § 725.155(c),(d)(1), and (d)(2).

(d) Persons applying for a TME mustsubmit phenotypic and ecologicalcharacteristics information required in§ 725.155(d)(3) as it relates directly tothe conditions of the proposed testmarketing activity.

(e) Persons applying for a TME mustalso submit the following informationabout the proposed test marketingactivity:

(1) Proposed test marketing activity.(i) The maximum quantity of themicroorganism which the applicant willmanufacture or import for testmarketing.

(ii) The maximum number of personswho may be provided themicroorganism during test marketing.

(iii) The maximum number of personswho may be exposed to themicroorganism as a result of testmarketing, including informationregarding duration and route of suchexposures.

(iv) A description of the testmarketing activity, including itsduration and how it can bedistinguished from full-scalecommercial production and researchand development activities.

(2) Health and environmental effectsdata. All existing data regarding healthand environmental effects of themicroorganism must be reported inaccordance with § 725.160.

§ 725.370 EPA review of the TMEapplication.

General procedures for review of allsubmissions under this part arecontained in §§ 725.28 through 725.60.In addition, the following proceduresapply to EPA review of TMEapplications submitted under thissubpart:

(a) No later than 45 days after EPAreceives a TME, the Agency will eitherapprove or deny the application.

(b) A submitter may only proceedwith test marketing activities afterreceipt of EPA approval.

(c) In approving a TME application,EPA may impose any restrictionsnecessary to ensure that themicroorganism will not present anunreasonable risk of injury to health andthe environment as a result of testmarketing.

Subpart G—General Exemptions for NewMicroorganisms


from reporting under subpart D of thispart, and from review under this partaltogether, for manufacturing andimporting of certain newmicroorganisms for commercialpurposes.

(b) Recipient microorganisms eligiblefor the tiered exemption from reviewunder this part are listed in § 725.420.

(c) Criteria for the introduced geneticmaterial contained in the newmicroorganisms are described in§ 725.421.

(d) Physical containment and controltechnologies are described in § 725.422.

(e) The conditions for the Tier Iexemption are listed in § 725.424.

(f) In lieu of complying with subpartD of this part, persons using recipientmicroorganisms eligible for the tieredexemption may submit a Tier II


exemption request. The limitedreporting requirements for the Tier IIexemption, including datarequirements, are described in§§ 725.450 and 725.455.

(g) EPA review procedures for the TierII exemption are set forth in § 725.470.

(h) Subparts A through C of this partapply to any submission under thissubpart.

§ 725.420 Recipient microorganisms.The following recipient

microorganisms are eligible for eitherexemption under this subpart:

(a) Acetobacter aceti.(b) Aspergillus niger.(c) Aspergillus oryzae.(d) Bacillus licheniformis.(e) Bacillus subtilis.(f) Clostridium acetobutylicum.(g) Escherichia coli K-12.(h) Penicillium roqueforti.(i) Saccharomyces cerevisiae.(j) Saccharomyces uvarum.

§ 725.421 Introduced genetic material.For a new microorganism to qualify

for either exemption under this subpart,introduced genetic material must meetall of the criteria listed in this section.

(a) Limited in size. The introducedgenetic material must consist only of thefollowing:

(1) The structural gene(s) of interest.(2) The regulatory sequences

permitting the expression of solely thegene(s) of interest.

(3) Associated nucleotide sequencesneeded to move genetic material,including linkers, homopolymers,adaptors, transposons, insertionsequences, and restriction enzyme sites.

(4) The nucleotide sequences neededfor vector transfer.

(5) The nucleotide sequences neededfor vector maintenance.

(b) Well-characterized. For introducedgenetic material, well-characterizedmeans that the following have beendetermined:

(1) The function of all of the productsexpressed from the structural gene(s).

(2) The function of sequences thatparticipate in the regulation ofexpression of the structural gene(s).

(3) The presence or absence ofassociated nucleotide sequences andtheir associated functions, whereassociated nucleotide sequences arethose sequences needed to move geneticmaterial including linkers,homopolymers, adaptors, transposons,insertion sequences, and restrictionenzyme sites.

(c) Poorly mobilizable. The ability ofthe introduced genetic material to betransferred and mobilized is inactivated,with a resulting frequency of transfer of

less than 10-8 transfer events perrecipient.

(d) Free of certain sequences. (1) Theintroduced genetic material must notcontain a functional portion of any ofthe toxin-encoding sequences describedin this paragraph (d).

(i) For the purposes of this section, afunctional portion of a toxin-encodingsequence means any sequence whichcodes for a polypeptide that has one ofthe following effects:

(A) It directly or indirectly contributesto toxic effects in humans. Directlycontributes to toxic effects in humansmeans those sequences encodingpolypeptides that have direct toxicity totarget cells. An example of a sequencewhich directly contributes to toxiceffects in humans is one which encodesthe portion of diphtheria toxin, listed inparagraph (d)(2) of this section, capableof interacting with elongation factor 2,leading to inhibition of proteinsynthesis in target respiratory, heart,kidney, and nerve tissues. Indirectlycontributes to toxic effects in humansmeans a sequence whose encodedpolypeptide is not directly toxic totarget cells, yet still adversely affectshumans. An example of a sequencewhich indirectly contributes to toxiceffects is the sequence which encodesthe portion of the botulinum toxin,listed in paragraph (d)(3) of this section,capable of blocking the release ofacetylcholine from gangliosides.Botulinum toxin affects neuromuscularjunctions by its blockage ofacetylcholine release, leading toirreversible relaxation of muscles andrespiratory arrest.

(B) It binds a toxin or toxin precursorto target human cells.

(C) It facilitates intracellular transportof a toxin in target human cells.

(ii) While these toxins are listed (withsynonyms in parentheses) in paragraphs(d)(2) through (d)(7) of this sectionaccording to the source organism, it isuse of the nucleotide sequences thatencode the toxins that is being restrictedand not the use of the source organisms.The source organisms are listed toprovide specificity in identification ofsequences whose use is restricted.Although similar or identical sequencesmay be isolated from organisms otherthan those listed below in paragraphs(d)(2) through (d)(7) of this section,these comparable toxin sequences,regardless of the organism from whichthey are derived, must not be includedin the introduced genetic material.

(2) Sequences for protein synthesisinhibitor.

Sequence Source Toxin Name

Corynebacteriumdiphtheriae & C.ulcerans

Diphtheria toxin

Pseudomonasaeruginosa

Exotoxin A

Shigella dysenteriae Shigella toxin (Shigatoxin, Shigelladysenteriae type Itoxin, Vero celltoxin)

Abrus precatorius,seeds

Abrin

Ricinus communis,seeds

Ricin

(3) Sequences for neurotoxins.


Clostridium botulinum Neurotoxins A, B, C1,D, E, F, G(Botulinum toxins,botulinal toxins)

Clostridium tetani Tetanus toxin(tetanospasmin)

Proteus mirabilis NeurotoxinStaphylococcus

aureusAlpha toxin (alpha

lysin)Yersinia pestis Murine toxin

Snake toxinsBungarus caeruleus CaeruleotoxinBungarus multicinctus Beta-bungarotoxin

(phospholipase)Crotalus spp. Crotoxin

(phospholipase)Dendroaspis viridis NeurotoxinNaja naja varieties NeurotoxinNotechia scutatus Notexin

(phospholipase)Oxyuranus scutellatus Taipoxin

Invertebrate toxinsChironex fleckeri NeurotoxinAndroctnus australis NeurotoxinCentruroides

sculpturatusNeurotoxin

(4) Sequences for oxygen labilecytolysins.


Bacillus alve AlveolysinBacillus cereus CereolysinBacillus laterosporus LaterosporolysinBacillus thuringiensis ThuringiolysinClostridium

bifermentansLysin

Clostridium botulinum LysinClostridium caproicum LysinClostridium chauvoei Delta-toxinClostridium

histolyticumEpsilon-toxin

Clostridium novyi Gamma-toxinClostridium

oedematiensDelta-toxin



Clostridiumperfringens

Theta-toxin(Perfringolysin)

Clostridium septicum Delta-toxinClostridium sordellii LysinClostridium tetani TetanolysinListeria

monocytogenesListeriolysin (A B)

Streptococcuspneumoniae

Pneumolysin

Streptococcuspyogene

Streptolysin O (SLO)

(5) Sequences for toxins affectingmembrane function.


Bacillus anthracis Edema factor (Fac-tors I II); Lethal fac-tor (Factors II III)

Bacillus cereus Enterotoxin(diarrheagenictoxin, mouse lethalfactor)

Bordetella pertussis Adenylate cyclase(Heat-labile factor);Pertussigen (per-tussis toxin, isletactivating factor,histamine sensitiz-ing factor,lymphocytosis pro-moting factor)

Clostridium botulinum C2 toxinClostridium difficile Enterotoxin (toxin A)Clostridium

perfringensBeta-toxin; Delta-

toxinEscherichia coli &

otherEnterobacteriaceaespp.

Heat-labileenterotoxins (LT);Heat-stableenterotoxins (STa,ST1 subtypesST1a ST1b; alsoSTb, STII)

Legionellapneumophila

Cytolysin

Vibrio cholerae &Vibrio mimicus

Cholera toxin(choleragen)

(6) Sequences that affect membraneintegrity.


Clostridiumbifermentans &other Clostridiumspp

Lecithinase

Clostridiumperfringens

Alpha-toxin(phospholipase C,lecithinase);Enterotoxin

Corynebacteriumpyogenes & otherCorynebacteriumspp.

Cytolysin(phospholipase C),Ovis toxin(sphingomyelinaseD)


Staphylococcusaureus

Beta-lysin (beta toxin)

(7) Sequences that are generalcytotoxins.


Adenia digitata ModeccinAeromonas

hydrophilaAerolysin (beta-lysin,

cytotoxic lysin)Clostridium difficile Cytotoxin (toxin B)Clostridium

perfringensBeta-toxin; Epsilon-

toxin; Kappa-toxinEscherichia coli &

otherEnterobacteriaceaespp.

Cytotoxin (Shiga-liketoxin, Vero celltoxin)

Pseudomonasaeruginosa

Proteases

Staphylococcusaureus

Gamma lysin(Gamma toxin);Enterotoxins (SEA,SEB, SEC, SEDSEE); Pyrogenicexotoxins A B;Toxic shock syn-drome toxins(TSST-1)

Staphylococcusaureus &Pseudomonasaeruginosa

Leucocidin(leukocidin,cytotoxin)

Streptococcuspyogenes

Streptolysin S (SLS);Erythrogenic toxins(scarlet fever tox-ins, pyrogenicexotoxins)

Yersinia enterocolitica Heat-stableenterotoxins (ST)

§ 725.422 Physical containment andcontrol technologies.

The manufacturer must meet all of thefollowing criteria for physicalcontainment and control technologiesfor any facility in which the newmicroorganism will be used for a Tier Iexemption; these criteria also serve asguidance for a Tier II exemption.

(a) Use a structure that is designedand operated to contain the newmicroorganism.

(b) Control access to the structure.(c) Provide written, published, and

implemented procedures for the safetyof personnel and control of hygiene.

(d) Use inactivation proceduresdemonstrated and documented to beeffective against the new microorganismcontained in liquid and solid wastesprior to disposal of the wastes. Theinactivation procedures must reduceviable microbial populations by at least6 logs in liquid and solid wastes.

(e) Use features known to be effectivein minimizing viable microbialpopulations in aerosols and exhaust

gases released from the structure, anddocument use of such features.

(f) Use systems for controllingdissemination of the newmicroorganism through other routes,and document use of such features.

(g) Have in place emergency clean-upprocedures.

§ 725.424 Requirements for the Tier Iexemption.

(a) Conditions of exemption. Themanufacture or import of a newmicroorganism for commercial purposesis not subject to review under this partif all of the following conditions are metfor all activities involving the newmicroorganism:

(1) The recipient microorganism islisted in and meets any requirementsspecified in § 725.420.

(2) The introduced genetic materialmeets the criteria under § 725.421.

(3) The physical containment andcontrol technologies of any facility inwhich the microorganism will bemanufactured, processed, or used meetthe criteria under § 725.422.

(4) The manufacturer or importersubmits a certification described inparagraph (b) of this section to EPA atleast 10 days before commencing initialmanufacture or import of a newmicroorganism derived from a recipientmicroorganism listed in § 725.420.

(5) The manufacturer or importercomplies with the recordkeepingrequirements of § 725.65 and maintainsrecords for the initial and subsequentuses of the new microorganism thatverify compliance with the following:

(i) The certifications made inparagraph (b) of this section.

(ii) All the eligibility criteria for theTier I exemption including the criteriafor the recipient microorganism, theintroduced genetic material, thephysical containment and controltechnologies.

(b) Certification. To be eligible for theTier I exemption under this subpart, themanufacturer or importer must submitto EPA a document signed by aresponsible company official containingthe information listed in this paragraph.

(1) Name and address of manufactureror importer.

(2) Date when manufacture or importis expected to begin.

(3) The identification (genus, species)of the recipient microorganism listed in§ 725.420 which is being used to createthe new microorganism which will beused under the conditions of the Tier Iexemption.

(4) Certification of the following:(i) Compliance with the introduced

genetic material criteria described in§ 725.421.


(ii) Compliance with the containmentrequirements described in § 725.422,including the provision in paragraph(a)(3) of this section.

(5) The site of waste disposal and thetype of permits for disposal, the permitnumbers and the institutions issuing thepermits.

(6) The certification statementrequired in § 725.25(b). Certification ofsubmission of test data is not requiredfor the Tier I exemption.

§ 725.426 Applicability of the Tier Iexemption.

The Tier I exemption under § 725.424applies only to a manufacturer orimporter of a new microorganism thatcertifies that the microorganism will beused in all cases in compliance with§§ 725.420, 725.421, and 725.422.

§ 725.428 Requirements for the Tier IIexemption.

The manufacturer or importer of anew microorganism for commercialpurposes may submit to EPA a Tier IIexemption request in lieu of a MCANunder subpart D of this part if all of thefollowing conditions are met:

(a) The recipient microorganism islisted in and meets any requirementsspecified in § 725.420.

(b) The introduced genetic materialmeets the criteria under § 725.421.

(c) Adequate physical containmentand control technologies are used. Thecriteria listed under § 725.422 forphysical containment and controltechnologies of facilities should be usedas guidance to satisfy the Tier IIexemption request data requirementslisted at § 725.455(d). EPA will reviewproposed process and containmentprocedures as part of the submission fora Tier II exemption under this section.

§ 725.450 Procedural requirements for theTier II exemption.

General requirements for allsubmissions under this part arecontained in § 725.25. In addition, thefollowing requirements apply torequests submitted under this subpart:

(a) Prenotice consultation. EPAstrongly suggests that for a Tier IIexemption, the submitter contact theAgency for a prenotice consultationregarding eligibility for the exemption.

(b) When to submit the Tier IIexemption request. Each person who iseligible to submit a Tier II exemptionrequest under this subpart must submitthe request at least 45 calendar daysbefore the person intends to commencemanufacture or import.

(c) Contents of the Tier II exemptionrequest. Each person who submits arequest under this subpart must providethe information described in §§ 725.428

and 725.455, as well as informationknown to or reasonably ascertainable bythe person that would permit EPA todetermine that use of themicroorganism, under the conditionsspecified in the request, will not presentan unreasonable risk of injury to healthor the environment.

(d) Recordkeeping. Each person whosubmits a request under this subpartmust comply with the recordkeepingrequirements of § 725.65. In addition,the submitter should maintain recordswhich contain information that verifiescompliance with the following:

(1) The certifications made in therequest.

(2) All the eligibility criteria for theTier II exemption request including thecriteria for the recipient microorganism,the introduced genetic material, thephysical containment and controltechnologies.

§ 725.455 Information to be included in theTier II exemption request.

The submitter must indicate clearlythat the submission is a Tier IIexemption request for a microorganisminstead of the MCAN under subpart Dof this part and must submit thefollowing information:

(a) Submitter identification. (1) Thename and headquarters address of thesubmitter.

(2) The name, address, and officetelephone number (including area code)of the principal technical contactrepresenting the submitter.

(b) Microorganism identityinformation. (1) Identification (genus,species, and strain) of the recipientmicroorganism. Genus, speciesdesignation should be substantiated bya letter from a culture collection or abrief summary of the results of testsconducted for taxonomic identification.

(2) Type of genetic modification andthe function of the introduced geneticmaterial.

(3) Site of insertion.(4) Certification of compliance with

the introduced genetic material criteriadescribed in § 725.421.

(c) Production volume. Productionvolume, including total liters per year,and the maximum cell concentrationachieved during the production process.

(d) Process and containmentinformation. (1) A description of theprocess including the following:

(i) Identity and location of themanufacturing site(s).

(ii) Process flow diagram illustratingthe production process, includingdownstream separations, and indicatingthe containment envelope around theappropriate equipment.

(iii) Identities and quantities offeedstocks.

(iv) Sources and quantities ofpotential releases to both the workplaceand environment, and a description ofengineering controls, inactivationprocedures, and other measures whichwill reduce worker exposure andenvironmental releases.

(v) A description of procedures whichwill be undertaken to prevent fugitiveemissions, i.e. leak detection and repairprogram.

(vi) A description of procedures/safeguards to prevent and mitigateaccidental releases to the workplace andthe environment.

(2) Certification of those elements ofthe containment criteria described in§ 725.422 with which the manufactureris in compliance, including stating bynumber the elements with which themanufacturer is in full compliance.

(e) The site of waste disposal and thetype of permits for disposal, the permitnumbers and the institutions issuing thepermits.

(f) The certification statementrequired in § 725.25(b). Certification ofsubmission of test data is not requiredfor the Tier II exemption.

§ 725.470 EPA review of the Tier IIexemption request.

General procedures for review of allsubmissions under this part arecontained in §§ 725.28 through 725.60.In addition, the following proceduresapply to EPA review of Tier IIexemption requests submitted underthis subpart:

(a) Length of the review period. Thereview period for the request will be 45days from the date the DocumentControl Officer for the Office ofPollution Prevention and Toxicsreceives a complete request, or the dateEPA determines the request is completeunder § 725.33, unless the Agencyextends the review period for goodcause under § 725.56.

(b) Criteria for review. EPA willreview the request to determine that thenew microorganism complies with§ 725.428 and that its manufacture,processing, use, and disposal asdescribed in the request will not presentan unreasonable risk of injury to healthor the environment.

(c) EPA decision regarding the Tier IIexemption request. A decisionconcerning a request under this subpartwill be made by the Administrator, or adesignee.

(d) Determination that themicroorganism is ineligible for a Tier IIreview. (1) EPA may determine that themanufacturer or importer is not eligiblefor Tier II review, because themicroorganism does not meet thecriteria under § 725.428 or the


Administrator, or a designee, decidesthat there is insufficient information todetermine that the conditions ofmanufacture, processing, use, ordisposal of the microorganism asdescribed in the request will not presentan unreasonable risk to health or theenvironment.

(2) If the Agency makes thisdetermination, the Administrator, or adesignee will notify the manufacturer orimporter by telephone, followed by aletter, that the request has been denied.The letter will explain reasons for thedenial.

(3) If the request is denied, themanufacturer or importer may submitthe information necessary to constitutea MCAN under subpart D of this part.

(e) Approval or denial of the Tier IIexemption request. (1) No later than 45days after EPA receives a request, theAgency will either approve or deny therequest.

(2) In approving a request, EPA mayimpose any restrictions necessary toensure that the microorganism will notpresent an unreasonable risk of injury tohealth and the environment as a resultof general commercial use.

(f) EPA may seek to enjoin themanufacture or import of amicroorganism in violation of thissubpart, or act to seize anymicroorganism manufactured orimported in violation of this section ortake other actions under the authority ofsections 7 or 17 of the Act.

(g) A manufacturer or importer mayonly proceed after receipt of EPAapproval.

Subparts H–K—[Reserved]

Subpart L—Additional Procedures forReporting on Significant New Uses ofMicroorganisms

§ 725.900 Scope and purpose.(a) This subpart describes additional

provisions governing submission ofMCANs for microorganisms subject tosignificant new use rules identified insubpart M of this part.

(b) Manufacturers, importers, andprocessors described in § 725.105(c)must submit a MCAN under subpart Dof this part for significant new uses ofmicroorganisms described in subpart Mof this part, unless they are excludedunder §§ 725.910 or 725.912.

(c) Section 725.920 discusses exportsand imports.

(d) Additional recordkeepingrequirements specific to significant newuses of microorganisms are described in§ 725.950.

(e) Section 725.975 describes howEPA will approve alternative means ofcomplying with significant new use

requirements designated in subpart M ofthis part.

(f) Expedited procedures forpromulgating significant new userequirements under subpart M of thispart for microorganisms subject tosection 5(e) orders are discussed in§§ 725.980 and 725.984.

(g) This subpart L contains provisionsgoverning submission and review ofnotices for the microorganisms andsignificant new uses identified insubpart M of this part. The provisionsof this subpart L apply to themicroorganisms and significant newuses identified in subpart M of this part,except to the extent that they arespecifically modified or supplanted byspecific requirements in subpart M ofthis part. In the event of a conflictbetween the provisions of this subpart Land the provisions of subpart M of thispart, the provisions of subpart M of thispart shall govern.

(h) The provisions of subparts Athrough F of this part also apply tosubparts L and M of this part. Forpurposes of subparts L and M of thispart, wherever the words‘‘microorganism’’ or ‘‘newmicroorganism’’ appear in subparts Athrough F of this part, it shall mean themicroorganism subject to subparts L andM of this part. In the event of a conflictbetween the provisions of subparts Athrough F and the provisions of subpartsL and M of this part, the provisions ofsubparts L and M of this part shallgovern.

§ 725.910 Persons excluded fromreporting significant new uses.

(a) A person who intends tomanufacture, import, or process amicroorganism identified in subpart Mof this part and who intends todistribute it in commerce is not requiredto submit a MCAN under subpart D ofthis part, if that person can documentone or more of the following as to eachrecipient of the microorganism from thatperson:

(1) That the person has notified therecipient, in writing, of the specificsection in subpart M of this part whichidentifies the microorganism and itsdesignated significant new uses, or

(2) That the recipient has knowledgeof the specific section in subpart M ofthis part which identifies themicroorganism and its designatedsignificant new uses, or

(3) That the recipient cannotundertake any significant new usedescribed in the specific section insubpart M of this part.

(b) The manufacturer, importer, orprocessor described in paragraph (a) ofthis section must submit a MCAN under

subpart D of this part, if such person hasknowledge at the time of commercialdistribution of the microorganismidentified in the specific section insubpart M of this part that a recipientintends to engage in a designatedsignificant new use of thatmicroorganism without submitting aMCAN under this part.

(c) A person who processes amicroorganism identified in a specificsection in subpart M of this part for asignificant new use of thatmicroorganism is not required to submita MCAN if that person can documenteach of the following:

(1) That the person does not know thespecific microorganism identity of themicroorganism being processed, and

(2) That the person is processing themicroorganism without knowledge thatthe microorganism is identified insubpart M of this part.

(d)(1) If at any time after commencingdistribution in commerce of amicroorganism identified in a specificsection in subpart M of this part, aperson who manufactures, imports, orprocesses a microorganism described insubpart M of this part and distributes itin commerce has knowledge that arecipient of the microorganism isengaging in a significant new use of thatmicroorganism designated in thatsection without submitting a MCANunder this part, the person is requiredto cease supplying the microorganism tothat recipient and to submit a MCAN forthat microorganism and significant newuse, unless the person is able todocument each of the following:

(i) That the person has notified therecipient and EPA enforcementauthorities (at the address in paragraph(d)(1)(iii) of this section), in writingwithin 15 working days of the time theperson develops knowledge that therecipient is engaging in a significantnew use, that the recipient is engagingin a significant new use withoutsubmitting a MCAN.

(ii) That, within 15 working days ofnotifying the recipient as described inparagraph (d)(1)(i) of this section, theperson received from the recipient, inwriting, a statement of assurance thatthe recipient is aware of the terms of theapplicable section in subpart M of thispart and will not engage in thesignificant new use.

(iii) That the person has promptlyprovided EPA enforcement authoritieswith a copy of the recipient’s statementof assurance described in paragraph(d)(1)(ii) of this section. The copy mustbe sent to the Director, Office ofCompliance (2221A), EnvironmentalProtection Agency, 401 M St., SW.,Washington, DC 20460.


(2) If EPA notifies the manufacturer,importer, or processor that the recipientis engaging in a significant new use afterproviding the statement of assurancedescribed in paragraph (d)(1)(ii) of thissection and without submitting a MCANunder this part, the manufacturer,importer, or processor shallimmediately cease distribution to thatrecipient until the manufacturer,importer, or processor or the recipienthas submitted a MCAN under this partand the MCAN review period hasended.

(3) If, after receiving a statement ofassurance from a recipient underparagraph (d)(1)(ii) of this section, amanufacturer, importer, or processorhas knowledge that the recipient isengaging in a significant new usewithout submitting a MCAN under thispart, the manufacturer, importer, orprocessor must immediately ceasedistributing the microorganism to thatrecipient and notify EPA enforcementauthorities at the address identified inparagraph (d)(1)(iii) of this section. Themanufacturer, importer, or processormay not resume distribution to thatrecipient until any one of the followinghas occurred:

(i) The manufacturer, importer, orprocessor has submitted a MCAN underthis part and the MCAN review periodhas ended.

(ii) The recipient has submitted aMCAN under this part and the MCANreview period has ended.

(iii) The manufacturer, importer, orprocessor has received notice from EPAenforcement authorities that it mayresume distribution to that recipient.

§ 725.912 Exemptions.Persons identified in § 725.105(c) are

not required to submit a MCAN undersubpart D of this part for amicroorganism identified in subpart Mof this part, unless otherwise specifiedin a specific section in subpart M, if:

(a) The person submits a MCAN forthe microorganism prior to thepromulgation date of the section insubpart M of this part which identifiesthe microorganism, and the personreceives written notification ofcompliance from EPA prior to theeffective date of such section. TheMCAN submitter must comply with anyapplicable requirement of section 5(b) ofthe Act. The MCAN must include theinformation and test data specified insection 5(d)(1) of the Act. For purposesof this exemption, the specific section insubpart M of this part which identifiesthe microorganism and §§ 725.3, 725.15,725.65, 725.70, 725.75, 725.100, and725.900 apply; after the effective date ofthe section in subpart M of this part

which identifies the microorganism,§§ 725.105 and 725.910 apply and§ 725.920 continues to apply. EPA willprovide the MCAN submitter withwritten notification of compliance onlyif one of the following occurs:

(1) EPA is unable to make the findingthat the activities described in theMCAN will or may present anunreasonable risk of injury to health orthe environment under reasonablyforeseeable circumstances, or

(2) EPA and the person negotiate aconsent order under section 5(e) of theAct, such order to take effect on theeffective date of the section in subpartM of this part which identifies themicroorganism.

(b) The person is operating under theterms of a consent order issued undersection 5(e) of the Act applicable to thatperson. If a provision of such section5(e) order is inconsistent with a specificsignificant new use identified in subpartM of this part, abiding by the provisionof the section 5(e) order exempts theperson from submitting a MCAN for thatspecific significant new use.

§ 725.920 Exports and imports.

(a) Exports. Persons who intend toexport a microorganism identified insubpart M of this part, or in anyproposed rule which would amendsubpart M of this part, are subject to theexport notification provisions of section12(b) of the Act. The regulations thatinterpret section 12(b) appear at part707 of this chapter.

(b) Imports. Persons who import asubstance identified in a specific sectionin subpart M of this part are subject tothe import certification requirementsunder section 13 of the Act, which arecodified at 19 CFR §§ 12.118 through12.127 and 127.28(i). The EPA policy insupport of the import certificationrequirements appears at part 707 of thischapter.

§ 725.950 Additional recordkeepingrequirements.

Persons submitting a MCAN for asignificant new use of a microorganismmust comply with the recordkeepingrequirements of § 725.65. In addition,the following requirements apply:

(a) At the time EPA adds amicroorganism to subpart M of this part,EPA may specify appropriaterecordkeeping requirements. Eachmanufacturer, importer, and processorof the microorganism shall maintain therecords for 3 years from the date of theircreation.

(b) The records required to bemaintained under this section mayinclude the following:

(1) Records documenting theinformation contained in the MCANsubmitted to EPA.

(2) Records documenting themanufacture and importation volume ofthe microorganism and thecorresponding dates of manufacture andimport.

(3) Records documenting volumes ofthe microorganism purchaseddomestically by processors of themicroorganism, names and addresses ofsuppliers and corresponding dates ofpurchase.

(4) Records documenting the namesand addresses (including shipmentdestination address, if different) of allpersons outside the site of manufactureor import to whom the manufacturer,importer, or processor directly sells ortransfers the microorganism, the date ofeach sale or transfer, and the quantity ofthe microorganism sold or transferredon such date.

§ 725.975 EPA approval of alternativecontrol measures.

(a) In certain sections of subpart M ofthis part, significant new uses for theidentified microorganisms are describedas the failure to establish andimplement programs providing for theuse of either: specific measures tocontrol worker exposure to or release ofmicroorganisms which are identified insuch sections, or alternative measures tocontrol worker exposure orenvironmental release which EPA hasdetermined provide substantially thesame degree of protection as thespecified control measures. Persons whomanufacture, import, or process amicroorganism identified in suchsections and who intend to employalternative measures to control workerexposure or environmental release mustsubmit a request to EPA for adetermination of equivalency beforecommencing manufacture, import, orprocessing involving the alternativecontrol measures.

(b) A request for a determination ofequivalency must be submitted inwriting to the Office of PollutionPrevention and Toxics, DocumentControl Officer, 7407, 401 M St., SW.,Washington, DC 20460: ATTN: SNUREquivalency Determination, and mustcontain:

(1) The name of the submitter.(2) The specific identity of the

microorganism.(3) The citation for the specific

section in subpart M of this part whichpertains to the microorganism for whichthe request is being submitted.

(4) A detailed description of theactivities involved.


(5) The specifications of thealternative worker exposure controlmeasures or environmental releasecontrol measures.

(6) A detailed analysis explainingwhy such alternative control measuresprovide substantially the same degree ofprotection as the specific controlmeasures identified in the specificsection in subpart M of this part whichpertains to the microorganism for whichthe request is being submitted.

(7) The data and informationdescribed in §§ 725.155 and 725.160. Ifsuch data and information have alreadybeen submitted to EPA’s Office ofPollution Prevention and Toxics, thesubmitter need only document that itwas previously submitted, to whom,and the date it was submitted.

(c) Requests for determinations ofequivalency will be reviewed by EPAwithin 45 days. Determinations underthis paragraph will be made by theDirector, or a designee. Notice of theresults of such determinations will bemailed to the submitter.

(d) If EPA notifies the submitter underparagraph (c) of this section that EPAhas determined that the alternativecontrol measures provide substantiallythe same degree of protection as thespecified control measures identified inthe specific section of subpart M of thispart which pertains to themicroorganism for which the request isbeing submitted, the submitter maycommence manufacture, import, orprocessing in accordance with thespecifications for alternative workerexposure control measures orenvironmental release control measuresidentified in the submitter’s request,and may alter any correspondingnotification to workers to reflect suchalternative controls. Deviations from theactivities described in the EPAnotification constitute a significant newuse and are subject to the requirementsof this part.

§ 725.980 Expedited procedures forissuing significant new use rules formicroorganisms subject to section 5(e)orders.

(a) Selection of microorganisms. (1) Inaccordance with the expedited processspecified in this section, EPA will issuesignificant new use notificationrequirements for each newmicroorganism that, after MCAN reviewunder subpart D of this part, becomessubject to a final order issued undersection 5(e) of the Act, except for anorder that prohibits manufacture andimport of the microorganism, unlessEPA determines that significant new usenotification requirements are notneeded for the microorganism.

(2) If EPA determines that significantnew use notifications requirements arenot needed for a microorganism that issubject to a final order issued undersection 5(e) of the Act, EPA will issuea notice in the Federal Registerexplaining why the significant new userequirements are not needed.

(b) Designation of requirements. (1)The significant new use notification andother specific requirements will bebased on and be consistent with theprovisions included in the final orderissued for the microorganism undersection 5(e) of the Act. EPA may alsodesignate additional activities assignificant new uses which will besubject to notification.

(2) Significant new use requirementsand other specific requirementsdesignated under this section will belisted in subpart M of this part. For eachmicroorganism, subpart M of this partwill identify:

(i) The microorganism name.(ii) The activities designated as

significant new uses.(iii) Other specific requirements

applicable to the microorganism,including recordkeeping requirementsor any other requirements included inthe final section 5(e) order.

(c) Procedures for issuing significantnew use rules. (1) Possible processes.EPA will issue significant new use rules(SNURs) under this section by one ofthe following three processes: directfinal rulemaking, interim finalrulemaking, or notice and commentrulemaking. EPA will use the directfinal rulemaking process to issuesignificant new use rules unless itdetermines that, in a particular case, oneof the other processes is moreappropriate.

(2) Notice in the Federal Register.Federal Register documents issued topropose or establish significant newuses under this section will contain thefollowing:

(i) The microorganism identity or, ifits specific identity is claimedconfidential, an appropriate genericmicroorganism name and an accessionnumber assigned by EPA.

(ii) The MCAN number.(iii) A summary of EPA’s findings

under section 5(e)(1)(A) of the Act forthe final order issued under section 5(e).

(iv) Designation of the significant newuses subject to, or proposed to besubject to, notification and any otherapplicable requirements.

(v) Any modification of subpart L ofthis part applicable to the specificmicroorganism and significant newuses.

(vi) If the Federal Register documentestablishes a final rule, or notifies the

public that a final rule will not beissued after public comment has beenreceived, the document will describecomments received and EPA’s response.

(3) Direct final rulemaking. (i) EPAwill use direct final rulemaking to issuea significant new use rule, whenspecific requirements will be based onand be consistent with the provisionsincluded in the final order issued for themicroorganism under section 5(e) of theAct. EPA will issue a final rule in theFederal Register following its decisionto develop a significant new use ruleunder this section for a specific newmicroorganism.

(ii) The Federal Register documentwill state that, unless written notice isreceived by EPA within 30 days ofpublication that someone wishes tosubmit adverse or critical comments, therule will be effective 60 days from thedate of publication. The written noticeof intent to submit adverse or criticalcomments should state which SNUR(s)will be the subject of the adverse orcritical comments, if several SNURs areestablished through the direct final rule.If notice is received within 30 days thatsomeone wishes to submit adverse orcritical comments, the section(s) of thedirect final rule containing the SNUR(s)for which a notice of intent to commentwas received will be withdrawn by EPAissuing a document in the final rulesection of the Federal Register, and aproposal will be published in theproposed rule section of the FederalRegister. The proposal will establish a30–day comment period.

(iii) If EPA, having considered anytimely comments submitted in responseto the proposal, decides to establishnotification requirements under thissection, EPA will issue a final ruleadding the microorganism to subpart Mof this part and designating thesignificant new uses subject tonotification.

(4) Interim final rulemaking. (i) EPAwill use the interim final rulemakingprocedure to issue a significant new userule, when specific requirements will bebased on and be consistent with theprovisions included in the final orderissued for the microorganism undersection 5(e) of the Act. The Agency willissue an interim final rule in the FederalRegister following its decision todevelop a significant new use rule for aspecific new microorganism. Thedocument will state EPA’s reasons forusing the interim final rulemakingprocedure.

(A) The significant new use rule willtake effect on the date of publication.

(B) Persons will be given 30 days fromthe date of publication to submitcomments.


(ii) Interim final rules issued underthis section shall cease to be in effect180 days after publication unless,within the 180–day period, EPA issuesa final rule in the Federal Registerresponding to any written commentsreceived during the 30–day commentperiod specified in paragraph (c)(4)(i)(B)of this section and promulgating finalsignificant new use notificationrequirements and other requirements forthe microorganism.

(5) Notice and comment rulemaking.(i) EPA will use a notice and commentprocedure to issue a significant new userule, when EPA is designatingadditional activities which are notprovisions included in the final orderissued for the microorganism undersection 5(e) of the Act as significant newuses which will be subject tonotification. EPA will issue a proposalin the Federal Register following itsdecision to develop a significant newuse rule under this section for a specificnew microorganism. Persons will begiven 30 days to comment on whetherEPA should establish notificationrequirements for the microorganismunder this part.

(ii) If EPA, having considered anytimely comments, decides to establishnotification requirements under thissection, EPA will issue a final ruleadding the microorganism to subpart Mof this part and designating thesignificant new uses subject tonotification.

(d) Schedule for issuing significantnew use rules. (1) Unless EPAdetermines that a significant new userule should not be issued under thissection, EPA will issue a proposed rule,a direct final rule, or an interim finalrule within 180 days of receipt of a validnotice of commencement under§ 725.190.

(2) If EPA receives adverse or criticalsignificant comments followingpublication of a proposed or interimfinal rule, EPA will either withdraw therule or issue a final rule addressing thecomments received.

§ 725.984 Modification or revocation ofcertain notification requirements.

(a) Criteria for modification orrevocation. EPA may at any time modifyor revoke significant new usenotification requirements for amicroorganism which has been added tosubpart M of this part using theprocedures of § 725.980. Such actionmay be taken under this section if EPAmakes one of the followingdeterminations, unless otherinformation shows that therequirements should be retained:

(1) Test data or other informationobtained by EPA provide a reasonablebasis for concluding that activitiesdesignated as significant new uses of themicroorganism will not present anunreasonable risk of injury to health orthe environment.

(2) EPA has promulgated a rule undersection 4 or 6 of the Act, or EPA oranother agency has taken action underanother law, for the microorganism thateliminates the need for significant newuse notification under section 5(a)(2) ofthe Act.

(3) EPA has received MCANs for someor all of the activities designated assignificant new uses of themicroorganism and, after reviewingsuch MCANs, concluded that there is noneed to require additional notice frompersons who propose to engage inidentical or similar activities.

(4) EPA has examined newinformation, or has reexamined the testdata or other information supporting itsfinding under section 5(e)(1)(A)(ii)(I) ofthe Act and has concluded that arational basis no longer exists for thefindings that activities involving themicroorganism may present anunreasonable risk of injury to health orthe environment required under section5(e)(1)(A) of the Act.

(5) Certain activities involving themicroorganism have been designated assignificant new uses pending thecompletion of testing, and adequate testdata developed in accordance withapplicable procedures and criteria havebeen submitted to EPA.

(b) Procedures for limitation orrevocation. Modification or revocation

of significant new use notificationrequirements for a microorganism thathas been added to subpart M of this partusing the procedures described in§ 725.980 may occur either at EPA’sinitiative or in response to a writtenrequest.

(1) Any affected person may requestmodification or revocation of significantnew use notification requirements for amicroorganism that has been added tosubpart M of this part using theprocedures described in § 725.980 bywriting to the Director, or a designee,and stating the basis for such request.The request must be accompanied byinformation sufficient to support therequest. All requests should be sent tothe TSCA Document Processing Center(7407), Room L–100, U.S.Environmental Protection Agency, 401M St., SW., Washington, DC 20460,ATTN: Request to amend SNUR.

(2) The Director, or a designee, willconsider the request, make adetermination whether to initiaterulemaking to modify the requirements,and notify the requester of thatdetermination by certified letter. If therequest is denied, the letter will explainwhy EPA has concluded that thesignificant new use notificationrequirements for that microorganismshould remain in effect.

(3) If EPA concludes that significantnew use notification requirements for amicroorganism should be limited orrevoked, EPA will propose the changesin a notice in the Federal Register,briefly describe the grounds for theaction, and provide interested parties anopportunity to comment.

Subpart M—Significant New Uses forSpecific Microorganisms

§ 725.1000 Scope.

This subpart identifies uses ofmicroorganisms which EPA hasdetermined to be significant new usesunder the authority of section 5(a)(2) ofthe Toxic Substances Control Act.

[FR Doc. 97–8669 Filed 4–10–97; 8:45 am]BILLING CODE 6560–50–F

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