Options for Food Substance without Regulatory Status

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Options for Food Substance without Regulatory Status

Any substance that is intentionally added to food is a “food additive” that is subject to pre-market review and approval unless it is GRAS

If substance is not listed as approved food additive at 21 CFR Part 172 or GRAS listed or affirmed at 21 CFR Parts 182, 184, and 186, then an appropriate regulatory status must be sought

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Options for Food Substance without Regulatory Status

Food Additive Petitions• FDA pre-market review and approval• Time and cost considerations• Codified in regulation • Only technical evidence of safety

Generally recognized as safe (GRAS)• No pre-market approval• Both technical evidence of safety and basis to

conclude this technical evidence of safety is known and accepted

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GRAS Status

Three conditions for GRAS status:(1) General recognition among experts that substance

is safe;(2) Experts must be qualified by scientific training and

experience; and(3) Experts must have based their safety judgment

either on scientific procedures or the fact that the substance was commonly used in foods prior to January 1, 1958.

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GRAS – Scientific Procedures

Same quality and quantity of evidence/safety data needed in food additive petition

“Key/Pivotal” safety data “ordinarily published” (e.g., in peer-reviewed scientific literature)

“General Recognition”/Consensus (e.g., use of GRAS Expert Panel)

• Conflict of interest issue

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GRAS Notifications

FDA started the GRAS Notification program because the prior GRAS Affirmation process was “broken”! • Over 100 pending GRAS Affirmation Petitions• FDA had insufficient resources to do a

complete review• Law does not require approval

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GRAS Notifications (con’t)

Submit GRAS Notifications/Notices to FDA• Positive response is not an “approval,” but simply a

statement that FDA does not object to the marketing of the ingredient for the condition and uses specified

• Majority include GRAS Panel Voluntary program in place since 1997

proposal As of May 2014, FDA completed 488

reviews out of 517 GRAS notices that have been submitted to FDA (rest either withdrawn or under review)

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GRAS Notifications (con’t)

Numbers alone indicate a successful program

15-20 withdrawn notices frequently reflect FDA raising questions about GRAS status

So there is a considered review of notices

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Self-Determined GRAS

Manufacturers may develop “self-determined” GRAS opinions without consulting FDA

Once GRAS determination has been reached, there is no requirement that FDA approve the conclusion

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Self-Determined GRAS (con’t)

Practical demands may dictate whether one takes self-determined or notification approach• What’s really happening!?• Are there really thousands of substances

being directly added to food based simply on “self-determined” GRAS?

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GRAS Under Attack

Feb. 2010: GAO report Nov. 2013: Capstone Report from PEW

Charitable Trust Feb. 2014: Center for Food Safety (CFS) files

Lawsuit to vacate FDA’s GRAS notification program

April 2014: National Resources Defense Council (NRDC) publishes “Generally Recognized as Secret: Chemicals Added to Food in the United States”

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GRAS Under Attack-GAO GAO 2010 Report:

• FDA’s oversight of GRAS food ingredients doesn’t ensure safety of new GRAS determinations

• Critical of number of GRAS substances not reviewed by FDA (e.g., nanomaterials can enter food supply as GRAS without FDA’s knowledge)

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GRAS Under Attack-GAO (con’t)

GAO recommends FDA• Finalize 1997 proposal*• Develop strategy to conduct reconsiderations• Monitor appropriateness of GRAS determinations

(e.g., random audits)• Develop way to avoid conflicts of interest* • Collect information on self-GRAS positions • Ensure nanomaterials not reviewed or approved for

use are safe and disclose if GRAS substance includes engineered nanomaterials*

*FDA is addressing/has addressed 15


GRAS Under Attack-GAO (con’t)

After GAO report, FDA reopened comment period on 1997 proposal in Dec. 2010• Addresses GAO recommendation that FDA

finalize proposal • Requests comments regarding the following

GAO recommendations– Nanomaterials– Conflict of interest – Guidance

• Comment period closed March 2011

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GRAS and Nanomaterials

June 2014 - FDA issued guidance that addresses use of GRAS approach for nanotech food substances

FDA’s current position regarding nanotech food substances• Questions the technical evidence of safety and

the general recognition of that safety for nanotech food substances

• Recommends premarket review and approval by FDA as opposed to GRAS approach


GRAS Under Attack-PEW

In PEW’s 2013 Report, Fixing the Oversight of Chemicals Added to Our Food, PEW alleges that:• FDA does not have sufficient information to assess the

safety of additives• FDA uses outdated science to evaluate the safety of

these additives• FDA's delayed implementation of the Food Safety

Modernization Act (FSMA) has impeded the agency's ability to identify food safety concerns

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GRAS Under Attack-PEW (con’t)

PEW says Congress should intervene • Suggests amendments to the Food Additives Amendments Act

of 1958 to require FDA review and approval of the first use of a new substance with subsequent applications going through GRAS Notification process

• Give FDA more legal and financial resources

Mandatory review-require manufacturers provide information to FDA

Conflict of interest restrictions User fees Are the PEW recommendations necessary or

practical?

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GRAS Under Attack-CFS Lawsuit

CFS Lawsuit to Vacate FDA’s GRAS Notification Program

At issue, FDA’s failure to finalize 1997 proposal to establish GRAS notification program and operation of GRAS program under proposal

Asks FDA to reinstate GRAS Affirmation Petition Process• Didn’t work pre-1997; why would it work now?• What happens to GRAS Notices that FDA has responded to?

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GRAS Under Attack-CFS Lawsuit (con’t)

FDA filed motion to dismiss • FDA says it plans to finalize 1997 rulemaking

no later than July 2016• Took issue with statute of limitations and lack

of final agency action FDA and CFS are working on a settlement

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GRAS Under Attack-NRDC

NRDC’s 2014 “Generally Recognized as Secret” report claims that chemical additives should not be GRAS if identity, chemical composition, and safety determination are not made public

Recommendations: • Congress get involved • Adopt recommendations in 2010 GAO, including:

– limit conflicts of interests – FDA be informed of all GRAS determinations– Make public FDA concerns with all notices it reviews,

even those that are withdrawn

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GRAS Under Attack-NRDC (con’t) NRDC actively attacking GRAS Notice

submissions by submitting letters to FDA• GRAS Notice 466

– PGPR for use as emulsifier in condiments, spreads, flavors, cheese powders and snacks

– NRDC took issue with cumulative estimated daily intake (EDI) being above acceptable daily intake (ADI) and uses that were not considered

– FDA issued “no questions” letter

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GRAS Under Attack-NRDC (con’t)

• GRAS Notice 471– Annatto seed extract, tocotrienols, as source of

vitamin E– NRDC took issue with recommended exposure and

hazard assessment research– FDA issued “no questions” letter

• GRAS Notice 474– BioPerine black pepper extract as flavoring– NRDC took issue with failure to address EFSA 2011

disagreement with JECFA safety evaluation-no expert consensus

– Company withdrew notice before NRDC letter

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GRAS Under Attack-PHOs

On November 8, 2013, FDA announced it has tentatively determined that partially hydrogenated oils (PHOs) are not GRAS under any conditions of use in food (See 78 Fed. Reg. 67169)

PHOs will be considered food additives that require pre-market approval

Issue: PHOs primary dietary source of trans fats, which are linked to health risks such as coronary heart disease

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GRAS Under Attack-PHOs (con’t)

FDA has tentatively concluded that there is no longer scientific consensus to support the safety of PHOs in food

21 CFR 170.38 gives FDA authority to publish notice when it determines a substance is not GRAS

Could be relevant to other substances of concern (e.g., sodium and caffeine)

Comment period closed March 8, 201425


GRAS Under Attack-PHOs (con’t)

FDA position on PHOs is unique In our view, strengthens integrity of the

GRAS program and demonstrates that the GRAS program works

If scientific information materializes after GRAS conclusion reached conclusion should be reassessed and GRAS position reversed, where necessary, but here, some would argue that data challenging GRAS position is weak

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Conclusions

In our view, the current GRAS system works• No reports of food safety issues raised by

substances that are marketed based on GRAS GRAS both supports food safety and

product innovation Attention on GRAS is diverting resources

from more important food safety issues

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Conclusions

FDA will likely finalize GRAS Notification program in the next couple of years

FDA will address concerns over conflict of interest in guidance

Anything further will require legislation

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Thank youMelvin S. Drozen

PartnerKeller and Heckman LLP

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[email protected]

Evangelia C. PelonisCounsel

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Suite 500 WestWashington, DC 20001

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Options for Food Substance without Regulatory Status