DRAFT GUIDANCE FOR INDUSTRY€¦ · l’industrie: Préparation de présentations électroniques destinées à la Direction des médicaments ... current scope will be considered as

DRAFT GUIDANCE FOR INDUSTRYPreparation of Electronic Submissions for the

Veterinary Drugs Directorate

Published by authority of theMinister of Health

Date Adopted 2011-11-01

Effective Date 2011-11-01

Health Products and Food Branch

Our mission is to help the people of Canada

maintain and improve their health.

Health Canada

HPFB’s Mandate is to take an integrated approach to the

management of the risks and benefits to health related to

health products and food by:

• Minimizing health risk factors to Canadians

while maximizing the safety provided by the

regulatory system for health products and food;

and,

• Promoting conditions that enable Canadians to

make healthy choices and providing information

so that they can make informed decisions about

their health.

Health Products and Food Branch

© Minister of Public Works and Government Services Canada 2006

Available in Canada throughHealth Canada–Publications

Brooke Claxton Building, A.L. #0913ATunney’s PastureOttawa, Ontario

K1A 0K9

Tel: (613) 954-5995Fax: (613) 941-5366

Également disponible en français sous le titre : Ligne directrice provisoire à l’intention del’industrie: Préparation de présentations électroniques destinées à la Direction des médicaments

vétérinaires

Health Canada Preparation of Electronic Submissions for the Veterinary Drugs Directorate

Draft Guidance for Industry

Effective Date: November 1, 2011 i

FOREWORD

Guidance documents are meant to provide assistance to industry and health care professionals onhow to comply with the policies and governing statutes and regulations. They also serve to

provide review and compliance guidance to staff, thereby ensuring that mandates areimplemented in a fair, consistent and effective manner.

Guidance documents are administrative instruments not having force of law and, as such, allowfor flexibility in approach. Alternate approaches to the principles and practices described in thisdocument may be acceptable provided they are supported by adequate scientific justification.

Alternate approaches should be discussed in advance with the relevant program area to avoid thepossible finding that applicable statutory or regulatory requirements have not been met.

As a corollary to the above, it is equally important to note that Health Canada reserves the rightto request information or material, or define conditions not specifically described in this

guidance, in order to allow the Department to adequately assess the safety, efficacy or quality ofa veterinary drug. Health Canada is committed to ensuring that such requests are justifiable and

that decisions are clearly documented.

This document should be read in conjunction with the accompanying notice and the relevantsections of other applicable guidances.



Effective Date: November 1, 2011 1

TABLE OF CONTENTS

1 INTRODUCTION...............................................................................................................2

2 PURPOSE AND SCOPE ....................................................................................................2

3 TECHNICAL REQUIREMENTS FOR ELECTRONIC DATA SUBMITTED WITHPAPER BASED SUBMISSIONS3.1 Media for Submitting Electronic Data ............................... ....................................33.2 Electronic Data Structure and Content

....................................................................33.2.1 General Requirements .................................................................................. 33.2.2 Files in Word Processed Format ...................................................................43.2.3 Files in Portable Document Format (PDF)...................................................4

3.3 File Structure ...........................................................................................................5

4 COMMON ELECTRONIC DATA REQUIREMENTS 4.1 Letter of Attestation ................................................................................................54.2 Cover Letter ............................................................................................................54.3 Drug Submission Application Form HC/SC 3011:

Drug Application for: Human, Veterinary, or Disinfectant Drugs and Clinical Trial Applications/Attestation ............................................................5

4.4 Veterinary Drug Submission Fee Application Form ..............................................5

Appendix A:

Electronic Folder Structure For Veterinary Drug Submissions ..........................................6

2

1 INTRODUCTION

This document provides guidance to assist sponsors in preparing the electronic components of adrug submission to the Veterinary Drugs Directorate (VDD). It also provides guidance on thestructure, content, format and media of electronic information.

The provision of as many sections of the submission as possible electronically has many benefitsfor both the VDD and sponsors and will ease the transition toward an electronic reviewenvironment. Electronic documents will be uploaded onto the Health Canada viewing tool,where they will be immediately accessible to all Health Canada staff involved with the review ofthe submission. Accessing the documents using the viewing tool will also contribute to goodrecord management by ensuring authenticity, integrity, availability, traceability and non-repudiation of the data.

It is important to note that the format for providing electronic data represents a work in progress.Future refinements to this guidance document will continue to be necessary as a result ofexperience gained.

2 PURPOSE AND SCOPE

The purpose of this guidance document is to communicate the general requirements for sponsorswishing to file part or all of their drug submission to the VDD electronically. Elements such asprocess, structure, content, format and media of electronic information are addressed within thisguidance document.

It should be noted that electronic filing is not a substitute for the paper submission at this time. Sponsors who choose to file part or all of their submission electronically are still required tosubmit the full paper copy, as the paper copy continues to be the legal copy. The electronicportion will serve to facilitate the review process and assist in the transition toward an eventualfully electronic environment.

At this time, the submission types for which electronic filing is being encouraged are New DrugSubmissions (NDSs), Supplemental New Drug Submissions (SNDSs), Abbreviated New DrugSubmissions (ANDSs) and Supplemental Abbreviated New Drug Submissions (SANDSs). Electronic filing is also encouraged for all submission-related documents submitted during thescreening and review of these submission types. Electronic filing for portions of othersubmission types may also be appropriate (e.g. Notifiable Changes). Further expansions to thecurrent scope will be considered as additional experience is gained.

3 TECHNICAL REQUIREMENTS FOR ELECTRONIC DATA SUBMITTED




WITH PAPER BASED SUBMISSIONS

3.1 Media for Submitting Electronic Data

The formats accepted at this time are CD-R conforming to the Joliet specification andDVD-RAM and DVD+R/-R recorded in the Universal Disk Format (UDF) standard. These are the formats currently supported by Health Canada. Sponsors may contactHealth Canada for other formats that may be acceptable at the time of filing.

Sponsors should fit all documents in as few CDs or DVDs as possible. Only the discsshould be labelled. Subsequent to burning the CD or DVD, sponsors should verify thatall files can be opened and that no files were corrupted during the writing of the disc.Only one copy of the electronic media should be submitted.

The labels on the discs should contain the following information:• Sponsor name and brand name;• Submission type;• Control number, if known;• “Protected B”;• Virus free certification, the software used for the virus check and the date of the

virus definition file or files;• Date of the submission; and• Disc number and total number of discs (e.g., Disc 1of 3)

3.2 Electronic Data Structure and Content

3.2.1 General Requirements

File names should be meaningful and kept as brief as possible, and all files shouldinclude the extension of the software used, in their name (i.e., MS Word: xxx.doc;WordPerfect: xxx.wpd; Portable Document Format: xxx.pdf; etc.)

Files submitted electronically should not be zipped nor should they be passwordprotected. File sizes should not exceed 100 MB.

Pages within a file or document should be numbered.

Chosen font sizes must be easily legible, and the use of black font isrecommended (blue font can be used for hyperlinks in PDF files). Sufficientmargins should be provided, e.g. minimum of 2.5 cm on the left side of eachpage.

3.2.2 Files in Word Processed Format

4

Sponsors are requested to submit original files in Microsoft Word 2003 or inCorel WordPerfect version 10.

3.2.3 Files in Portable Document Format (PDF)

Health Canada currently accepts files generated in PDF versions 1.7 and lower.PDF versions of documents should be generated from electronic sourcedocuments and not from scanned material, except where access to the sourceelectronic file is unavailable or where a signature is required. If scanned materialis to be submitted, sponsors must ensure that the material is clearly legible bothon the computer screen and when printed out.

It is also important that PDF documents be properly bookmarked.

The following are recommended as good bookmarking practices:

• Documents of ten pages or more should be bookmarked.• Bookmarks are equivalent to and should be organized like a

document table of contents and should not include the submissionlevel.

• Sections, subsections, tables, figures and appendices should all bebookmarked.

• Too many levels of bookmarks are inefficient; in most instances,three levels of bookmarks should be sufficient:

1 Heading1.1 Subheading

1.1.1 Sub-subheading• Health Canada recognizes that bookmarks are generated

automatically from document headings, but neverthelessrecommends they be kept concise.

PDF files must not contain:

• JavaScript• audio, video or special effects and animations• attachments• 3D content

If a file or item of information is submitted once but is referenced more than oncewithin the submission, a cross-reference or hyperlink is required. Hyperlinksimprove navigation efficiency through PDF documents. Relative paths - asopposed to absolute links that reference specific drives and root directories -should be used to create hyperlinks to minimize loss of functionality once thesubmission is loaded onto Health Canada’s network servers.

3.3 File Structure




The contents of the electronic media should be organized into folders, in accordance withthe structure outlined in Appendix V: Master Index of Health Canada’s Guidance forIndustry - Preparation of Veterinary New Drug Submissions dated March 2007. Emptyfolders within the electronic submission should be deleted as the folder structure shouldonly reflect what is actually submitted. The Table of Contents should identify thesesections as not applicable and therefore not included in the submitted folder structure. Inclusion of additional folders outside of the prescribed structure should be avoided.

See Appendix A for the prescribed electronic folder structure.

4 COMMON ELECTRONIC DATA REQUIREMENTS

4.1 Letter of Attestation

A Letter of Attestation should be provided in both paper and electronic (scanned PDF)format confirming that the content of the electronic documents are identical to that of thepaper submission. A Letter of Attestation is required for every submitted electronicdocument pertaining to a submission. The Letter of Attestation should be included inSection 1.3 - Submission Certification, and should be signed by the senior officer incharge of regulatory affairs or the official delegate.

4.2 Cover Letter

Submissions as well as additional information should be accompanied by anadministrative cover letter in both paper and electronic (PDF) format. The paper andelectronic cover letters should have identical content, and should indicate whether theinformation provided is a submission (e.g. NDS, SNDS, ANDS or SANDS) or additionalinformation concerning a submission.

4.3 Drug Submission Application Form HC/SC 3011: Drug Application for:Human, Veterinary, or Disinfectant Drugs and Clinical TrialApplications/Attestation

A completed, signed and scanned copy of the Drug Submission Application Form(HC/SC 3011) should be provided as a PDF file.

4.4 Veterinary Drug Submission Fee Application Form

A completed and scanned copy of the Veterinary Drug Submission Fee Application Formshould be provided as a PDF file.

6

Appendix A

ELECTRONIC FOLDER STRUCTURE FOR VETERINARY DRUG SUBMISSIONS

Part Section Headings Folder Structure

1 PART 1: REQUIREMENTS FOR MASTERVOLUME

\1 master volume\

1.1 Cover letter \1 master volume\1_1 cover

letter\

1.2 Table of Contents \1 m aster volum e\1_2 table

of contents\

1.3 Submission Certification \1 master volume\1_3

submission certification\

1.4 Authorization Letter \1 master volume\1_4

authorization letter\

1.4.1 Authorization to act as a regulatory agent onbehalf of the submission sponsor

\1 master volume\1_4

authorization letter\1_4_1

authorization regulatory

agent on behalf of sponsor\

1.4.2 Authorization to access information submittedby another company/sponsor



authorization access info

submitted by another

sponsor\

1.4.3 Authorization to share information with otheragencies



authorization share

information with other

agencies\

1.5 Drug Submission Application Form (HC/SC3011)

\1 master volume\1_5 drug

subm ission application form

-hc-sc 3011-\

1.6 Veterinary Drug Submission Fee ApplicationForm

\1 master volume\1_6 vet

drug submission fee

application form\

1.7 Animal Ingredient Form \1 master volume\1_7

animal ingredient form\

1.8 Draft Product Labels \1 master volume\1_8 draft

product labels\

1.9 Patent Forms/Documents \1 master volume\1_9

patent forms-documents\





1.10 GMP Status Information and EstablishmentLicence Information


gmp status info and

establishment licence info\

1.11 Prior Submissions \1 master volume\1_11

prior submissions\

1.12 Submission and Product Summary \1 master volume\1_12

submission and product

summary\

1.13 Summary of Batch Information \1 master volume\1_13

summ ary of batch

information\

1.13.1 For NDS and ABNDS \1 master volume\1_13

summ ary of batch

information\1_13_1 for nds

and abnds\

1.13.2 For SNDS, SABNDS and NC \1 master volume\1_13

summ ary of batch

information\1_13_2 for

snds-sabnds and nc\

1.14 Summary of Qualification for an ABNDS or aSABNDS Submission


qualification summ ary for

abnds or sabnds

submission\

1.15 Information Package for the Canadian FoodInspection Agency (CFIA)


information package for

cfia\

1.15.1 Drug Residue Monitoring Methods \1 master volume\1_15


cfia\1_15_1 drug residue

monitoring methods\

1.15.2 Drug Premix Products \1 master volume\1_15


cfia\1_15_2 drug premix

products\

1.16 Foreign Registration Information \1 master volume\1_16

foreign registration

information\

2 PART II: REQUIREMENTS FORMANUFACTURING AND QUALITYCONTROL

\2 quality\

2.1 Submission Type \2 quality\2_1 submission

type\

2.1.1 NDS and ABNDS \2 quality\2_1 submission

type\2_1_1 nds and abnds\


8

2.1.2 SNDS, SABNDS and NC \2 quality\2_1 submission

type\2_1_2 snds-sabnds

and nc\

2.2.S Drug Substance \2 quality\2_2__s DS\

2.2.S.1 General Information \2 quality\2_2__s

DS\2_2_s_1 general info\

2.2.S.1.1 Nomenclature \2 quality\2_2__s

DS\2_2_s_1 general

info\2_2_s_1_1

nomenclature\

2.2.S.1.2 Chemical Structure \2 quality\2_2__s

DS\2_2_s_1 general

info\2_2_s_1_2 chemical

structure\

2.2.S.1.3 Physicochemical Properties \2 quality\2_2__s

DS\2_2_s_1 general

info\2_2_s_1_3

physicochemical properties\

2.2.S.1.3.1 Physical Description \2 quality\2_2__s

DS\2_2_s_1 general

info\2_2_s_1_3

physicochemical

properties\2_2_s_1_3_1

physical description\

2.2.S.1.3.2 Solubilities/Quantitative Aqueous pH SolubilityProfile

\2 quality\2_2__s

DS\2_2_s_1 general

info\2_2_s_1_3

physicochemical


solubility-quantitative

profile\

2.2.S.1.3.3 Polymorphism \2 quality\2_2__s

DS\2_2_s_1 general

info\2_2_s_1_3

physicochemical


polymorphism\

2.2.S.1.3.4 Particle size distribution \2 quality\2_2__s

DS\2_2_s_1 general

info\2_2_s_1_3

physicochemical


particle size distribution\

2.2.S.2 Method of Manufacture \2 quality\2_2__s

DS\2_2_s_2 m ethod of m fr\





2.2.S.2.1 Manufacturer(s) \2 quality\2_2__s

DS\2_2_s_2 method of

mfr\2_2_s_2_1

manufacturers\

2.2.S.2.2 Description of Manufacturing Process andProcess Controls

\2 quality\2_2__s


mfr\2_2_s_2_2

manufacturing and process

controls\

2.2.S.2.3 Control of Materials \2 quality\2_2__s


mfr\2_2_s_2_3 control of

materials\

2.2.S.2.4 Controls of Critical Steps and IsolatedIntermediates (applied to the NDS)

\2 quality\2_2__s


mfr\2_2_s_2_4 critical

steps - isolated

intermediates controls -nds-

\

2.2.S.2.5 Process Validation and/or Evaluation (applied tothe NDS)

\2 quality\2_2__s


mfr\2_2_s_2_5 process

validation-evaluation -nds-\

2.2.S.2.6 Manufacturing Process Development (applied tothe NDS)

\2 quality\2_2__s


mfr\2_2_s_2_6

manufacturing process

development -nds-\

2.2.S.3 Structure Elucidation and Confirmation \2 quality\2_2__s

DS\2_2_s_3 struc eluc and

confirm\

2.2.S.3.1 Non-chiral drug substances \2 quality\2_2__s


confirm\2_2_s_3_1 non-

chiral drug substances\

2.2.S.3.2 Chiral Drug Substances \2 quality\2_2__s


confirm\2_2_s_3_2 chiral

drug substances\

2.2.S.4 Impurities \2 quality\2_2__s

DS\2_2_s_4 impurities\

2.2.S.4.1 Potential impurities \2 quality\2_2__s

DS\2_2_s_4

impurities\2_2_s_4_1

potential impurities\


10

2.2.S.4.2 Actual impurities detected \2 quality\2_2__s

DS\2_2_s_4

impurities\2_2_s_4_2

actual impurities detected\

2.2.S.4.3 Other Considerations \2 quality\2_2__s

DS\2_2_s_4

impurities\2_2_s_4_3 other

considerations\

2.2.S.5 Control of the Drug Substance \2 quality\2_2__s

DS\2_2_s_5 control of DS\

2.2.S.5.1 Specification \2 quality\2_2__s

DS\2_2_s_5 control of

DS\2_2_s_5_1

specification\

2.2.S.5.2 Analytical Procedures \2 quality\2_2__s


DS\2_2_s_5_2 analytical

procedures\

2.2.S.5.3 Validation of Analytical Procedures \2 quality\2_2__s


DS\2_2_s_5_3 validation of

analytical procedures\

2.2.S.5.4 Batch Analyses \2 quality\2_2__s


DS\2_2_s_5_4 batch

analyses\

2.2.S.5.5 Justification of Specification \2 quality\2_2__s


DS\2_2_s_5_5 justification

of specification\

2.2.S.6 Reference Standards \2 quality\2_2__s

DS\2_2_s_6 ref standards\

2.2.S.6.1 Primary Reference Standards \2 quality\2_2__s

DS\2_2_s_6 ref

standards\2_2_s_6_1

primary reference

standards\

2.2.S.6.2 Secondary Reference Standards \2 quality\2_2__s

DS\2_2_s_6 ref

standards\2_2_s_6_2

secondary reference

standards\

2.2.S.7 Packaging \2 quality\2_2__s

DS\2_2_s_7 packaging\

2.2.S.8 Stability \2 quality\2_2__s

DS\2_2_s_8 stability\





2.2.S.8.1 Forced Degradation (Stress) Studies \2 quality\2_2__s

DS\2_2_s_8

stability\2_2_s_8_1 forced

degradation studies\

2.2.S.8.2 Accelerated and Long Term Studies \2 quality\2_2__s

DS\2_2_s_8

stability\2_2_s_8_2

accelerated and long term

studies\

2.2.S.8.3 Proposed Storage Conditions and Re-test Period \2 quality\2_2__s

DS\2_2_s_8

stability\2_2_s_8_3

proposed storage

conditions - retest period\

2.2.P Drug Product \2 quality\2_2_p DP\

2.2.P.1 Description of the drug product \2 quality\2_2_p

DP\2_2_p_1 description of

DP\

2.2.P.2 Pharmaceutical Development \2 quality\2_2_p

DP\2_2_p_2 pharm dev\

2.2.P.3 Method of Manufacture \2 quality\2_2_p

DP\2_2_p_3 m ethod of m fr\

2.2.P.3.1 Manufacturer(s) \2 quality\2_2_p

DP\2_2_p_3 method of

mfr\2_2_p_3_1

manufacturers\

2.2.P.3.2 Formulae \2 quality\2_2_p


mfr\2_2_p_3_2 formulae\

2.2.P.3.2.1 Quantitative formula \2 quality\2_2_p


mfr\2_2_p_3_2

formulae\2_2_p_3_2_1

quantitative formula\

2.2.P.3.2.2 Batch formula \2 quality\2_2_p


mfr\2_2_p_3_2

formulae\2_2_p_3_2_2

batch formula\

2.2.P.3.3 Manufacturing Process \2 quality\2_2_p


mfr\2_2_p_3_3

manufacturing process\


12

2.2.P.3.3.1 Description \2 quality\2_2_p


mfr\2_2_p_3_3

manufacturing

process\2_2_p_3_3_1

description\

2.2.P.3.3.2 Master Production Documents \2 quality\2_2_p


mfr\2_2_p_3_3

manufacturing

process\2_2_p_3_3_2

master production docs\

2.2.P.3.3.3 Executed Production Documents \2 quality\2_2_p


mfr\2_2_p_3_3

manufacturing

process\2_2_p_3_3_3

executed production docs\

2.2.P.3.4 Process Validation \2 quality\2_2_p


mfr\2_2_p_3_4 process

validation\

2.2.P.3.4.1 Sterile Products \2 quality\2_2_p



validation\2_2_p_3_4_1

sterile products\

2.2.P.3.4.2 Non-sterile Products \2 quality\2_2_p



validation\2_2_p_3_4_2

non-sterile products\

2.2.P.3.5 Control of Excipients \2 quality\2_2_p


mfr\2_2_p_3_5 control of

excipients\

2.2.P.3.5.1 Specifications \2 quality\2_2_p



excipients\2_2_p_3_5_1

specifications\

2.2.P.3.5.2 Analytical Procedures and Validation \2 quality\2_2_p




analytical procedures and

validation\





2.2.P.3.5.3 Justification of specifications \2 quality\2_2_p




justification of

specifications\

2.2.P.3.5.4 Medicinal and Non-Medicinal Ingredients ofAnimal Origin

\2 quality\2_2_p




medicinal - non-medicinal

ingred anim al\

2.2.P.3.5.5 Novel Excipients \2 quality\2_2_p




novel excipients\

2.2.P.4 Control of the drug product \2 quality\2_2_p

DP\2_2_p_4 control of DP\

2.2.P.4.1 Specifications \2 quality\2_2_p

DP\2_2_p_4 control of

DP\2_2_p_4_1

specifications\

2.2.P.4.1.1 General requirements \2 quality\2_2_p


DP\2_2_p_4_1

specifications\2_2_p_4_1_

1 general requirements\

2.2.P.4.1.2 Tests applicable to all dosage forms \2 quality\2_2_p


DP\2_2_p_4_1


2 tests applicable to all

dosage forms\

2.2.P.4.1.3 Tests typically applicable for specific type ofdosage forms

\2 quality\2_2_p


DP\2_2_p_4_1


3 tests typically applicable

specific dosage forms\

2.2.P.4.2 Analytical Procedures \2 quality\2_2_p


DP\2_2_p_4_2 analytical

procedures\


14

2.2.P.4.3 Validation of Analytical Procedures \2 quality\2_2_p


DP\2_2_p_4_3 validation of

analytical procedures\

2.2.P.4.4 Batch Analyses \2 quality\2_2_p


DP\2_2_p_4_4 batch

analyses\

2.2.P.4.5 Justification of Specifications \2 quality\2_2_p


DP\2_2_p_4_5 justification

of specifications\

2.2.P.5 Packaging \2 quality\2_2_p

DP\2_2_p_5 packaging\

2.2.P.5.1 Description and specifications \2 quality\2_2_p

DP\2_2_p_5

packaging\2_2_p_5_1

description and

specifications\

2.2.P.5.2 Suitability \2 quality\2_2_p

DP\2_2_p_5

packaging\2_2_p_5_2

suitability\

2.2.P.6 Stability \2 quality\2_2_p

DP\2_2_p_6 stability\

2.2.P.6.1 Accelerated and Long Term Studies \2 quality\2_2_p

DP\2_2_p_6

stability\2_2_p_6_1

accelerated and long term

studies\

2.2.P.6.2 Proposed storage conditions and shelf life \2 quality\2_2_p

DP\2_2_p_6

stability\2_2_p_6_2

proposed storage

conditions - shelf life\

2.2.P.6.3 Stability Commitment \2 quality\2_2_p

DP\2_2_p_6

stability\2_2_p_6_3 stability

com mitment\

2.2.P.6.3.1 Primary Batch Stability \2 quality\2_2_p

DP\2_2_p_6


comm itment\2_2_p_6_3_1

primary batch stability\





2.2.P.6.3.2 Production scale batch stability \2 quality\2_2_p

DP\2_2_p_6



production scale batch

stability\

2.2.P.6.3.3 Continuing batch stability \2 quality\2_2_p

DP\2_2_p_6



continuing batch stability\

2.3 Additional Information for Drug Premixes \2 quality\2_3 additional

information for drug

premixes\

2.3.1 Stability of Medicated Feeds \2 quality\2_3 additional


premixes\2_3_1 stability of

medicated feeds\

2.3.2 Mixing Studies \2 quality\2_3 additional


premixes\2_3_2 mixing

studies\

2.3.3 Premixes Proposed for Concurrent Use \2 quality\2_3 additional


premixes\2_3_3 premixes

proposed concurrent use\

2.3.4 Feed Assay Validation \2 quality\2_3 additional


premixes\2_3_4 feed assay

validation\

2.3.5 Samples \2 quality\2_3 additional


premixes\2_3_5 samples\

2.4 Additional Information for Subsequent MarketEntry Drug Products

\2 quality\2_4 add info for

subsequent market entry

drug products\

3 PART III: REQUIREMENTS FORANIMAL SAFETY

\3 anim al safety\

3.1 Laboratory Animal Studies \3 animal safety\3_1

laboratory an imal\

3.1.1 Comprehensive Summary \3 animal safety\3_1

laboratory animal\3_1_1

comprehensive sum mary\


16

3.1.2 Sectional Reports \3 animal safety\3_1


sectional reports\

3.1.2.1 Acute Toxicity Studies \3 animal safety\3_1


sectional reports\3_1_2_1

acute toxicity\

3.1.2.2 Subchronic Toxicity Studies \3 animal safety\3_1



subchronic toxic ity\

3.1.2.3 Chronic Toxicity Studies \3 animal safety\3_1



chronic toxicity\

3.1.2.4 Irritation Studies \3 animal safety\3_1



irritation\

3.1.2.4.1 Dermal Sensitization Studies \3 animal safety\3_1



irritation\3_1_2_4_1 dermal

sensitization\

3.1.2.4.2 Primary Skin/Dermal Irritation Studies \3 animal safety\3_1



irritation\3_1_2_4_2

primary skin-dermal

irritation\

3.1.2.4.3 Primary Ocular Irritation Studies \3 animal safety\3_1



irritation\3_1_2_4_3

primary ocular irritation\

3.1.2.4.4 Tissue Irritation Studies \3 animal safety\3_1



irritation\3_1_2_4_4 tissue

irritation\

3.1.2.5 Reproduction and Teratogenicity Studies \3 animal safety\3_1



reproduction-teratogenicity\

3.1.2.6 Other Studies \3 animal safety\3_1



other\





3.1.3 Curriculum Vitae of Investigators \3 animal safety\3_1


curriculum vitae of

investigators\

3.2 Target Animal Safety Studies \3 animal safety\3_2 target

animal safety\

3.2.1 Comprehensive Summary \3 animal safety\3_2 target

animal safety\3_2_1


3.2.2 Sectional Reports \3 animal safety\3_2 target

animal safety\3_2_2

sectional reports\

3.2.2.1 Margin-of-Safety Studies \3 animal safety\3_2 target

animal safety\3_2_2


margin-of-safety\

3.2.2.2 Safety Under the Proposed Conditions of Use \3 animal safety\3_2 target

animal safety\3_2_2


safety under proposed

cond of use\

3.2.2.3 Topical Drug Studies \3 animal safety\3_2 target

animal safety\3_2_2


topical drug\

3.2.2.4 Inhalant Drug Studies \3 animal safety\3_2 target

animal safety\3_2_2


inhalant drug\

3.2.2.5 Tissue Irritation Studies \3 animal safety\3_2 target

animal safety\3_2_2


tissue irritation\

3.2.2.6 Udder Irritation Studies \3 animal safety\3_2 target

animal safety\3_2_2


udder irritation\

3.2.2.7 Reproductive Function Studies \3 animal safety\3_2 target

animal safety\3_2_2


reproductive function\

3.2.2.8 Clinical Safety Studies \3 animal safety\3_2 target

animal safety\3_2_2


clinical safety\


18

3.2.2.9 Pharmacovigilance Data \3 animal safety\3_2 target

animal safety\3_2_2


pharmacovigilance\

3.2.3 Curriculum Vitae of Investigators \3 animal safety\3_2 target

animal safety\3_2_3

curriculum vitae of

investigators\

4 PART IV: REQUIREMENTS FOREFFICACY

\4 efficacy\

4.1 Comprehensive Summary \4 efficacy\4_1


4.2 Sectional Reports \4 efficacy\4_2 sectional

reports\

4.2.1 Microbiology Studies \4 efficacy\4_2 sectional

reports\4_2_1 m icrobiology\

4.2.2 Laboratory Studies \4 efficacy\4_2 sectional

reports\4_2_2 laboratory\

4.2.3 Animal Model Efficacy Studies \4 efficacy\4_2 sectional

reports\4_2_3 animal

model efficacy\

4.2.4 Clinical Pharmacology Studies \4 efficacy\4_2 sectional

reports\4_2_4 clinical

pharmacology\

4.2.4.1 Pharmacokinetic Studies \4 efficacy\4_2 sectional


pharmacology\4_2_4_1

pharmacokinetic\

4.2.4.2 Bioavailability Studies \4 efficacy\4_2 sectional



bioavailability\

4.2.4.3 Pharmacodynamic Studies \4 efficacy\4_2 sectional



pharmacodynamic\

4.2.5 Dose Determination Studies \4 efficacy\4_2 sectional

reports\4_2_5 dose

determination\

4.2.5.1 Optimum Dose Studies \4 efficacy\4_2 sectional

reports\4_2_5 dose

determination\4_2_5_1

optimum dose\





4.2.5.2 Challenge Studies \4 efficacy\4_2 sectional

reports\4_2_5 dose

determination\4_2_5_2

challenge\

4.2.6 Dose Confirmation Studies \4 efficacy\4_2 sectional

reports\4_2_6 dose

confirmation\

4.2.6.1 Pivotal Studies \4 efficacy\4_2 sectional

reports\4_2_6 dose

confirmation\4_2_6_1

pivotal\

4.2.6.2 Clinical Studies \4 efficacy\4_2 sectional

reports\4_2_6 dose

confirmation\4_2_6_2

clinical\

4.2.7 Supplementary Supportive Efficacy Studies \4 efficacy\4_2 sectional

reports\4_2_7

supplem entary supportive

efficacy\

4.2.8 Pharmacovigilance Data \4 efficacy\4_2 sectional

reports\4_2_8

pharmacovigilance data\

4.3 Curriculum Vitae of Investigators \4 efficacy\4_3 curriculum

vitae of investigators\

5 PART V: REQUIREMENTS FOR HUMANSAFETY

\5 hum an safety\

5.1 Laboratory Animal Toxicity Studies \5 human safety\5_1

laboratory an imal toxic ity\

5.1.1 Comprehensive Summary \5 human safety\5_1

laboratory animal

toxicity\5_1_1


5.1.2 Sectional Reports \5 human safety\5_1

laboratory animal

toxicity\5_1_2 sectional

reports\

5.1.2.1 Subchronic Oral Toxicity Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_1

subchronic oral toxicity\


20

5.1.2.2 Chronic Toxicity Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_2 chronic

tox icity\

5.1.2.3 Carcinogenicity Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_3

carcinogenicity\

5.1.2.4 Combined Chronic Toxicity andCarcinogenicity Studies

\5 human safety\5_1

laboratory animal


reports\5_1_2_4 combined

chronic tox -

carcinogenicity\

5.1.2.5 Multigeneration Reproductive Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_5

multigeneration

reproductive\

5.1.2.6 Teratogenicity Testing \5 human safety\5_1

laboratory animal


reports\5_1_2_6

teratogenicity testing\

5.1.2.7 Short-term Tests for Genetic Toxicity Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_7 short-term

tests for genetic tox\

5.1.2.8 Pharmacological Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_8

pharmacological\

5.1.2.9 Immunotoxicity Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_9

immunotoxic ity\

5.1.2.10 Neurotoxicity Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_10

neurotoxic ity\





5.1.2.11 Hormonal Studies in Primates \5 human safety\5_1

laboratory animal


reports\5_1_2_11 hormonal

- primates\

5.1.2.12 Observations in Humans \5 human safety\5_1

laboratory animal


reports\5_1_2_12

observations in humans\

5.1.2.13 Other Studies \5 human safety\5_1

laboratory animal


reports\5_1_2_13 other

studies\

5.2 Microbiological Safety Studies \5 human safety\5_2 micro

safety\

5.2.1 Veterinary Antimicrobial Products \5 human safety\5_2 micro

safety\5_2_1 vet

antimicrobial products\

5.2.2 Sectional Reports \5 human safety\5_2 micro

safety\5_2_2 sectional

reports\

5.2.2.1 Information about the Antimicrobial \5 human safety\5_2 micro


reports\5_2_2_1 info about

antim icrobial\

5.2.2.2 Activity Spectrum of the Antimicrobial \5 human safety\5_2 micro


reports\5_2_2_2 activity

spectrum of antim icrobial\

5.2.2.3 Administration of the Antimicrobial \5 human safety\5_2 micro


reports\5_2_2_3

administration of

antim icrobial\

5.2.2.4 Antimicrobial Resistance Studies \5 human safety\5_2 micro


reports\5_2_2_4 antimicrob

resist\

5.2.2.4.1 Resistance Mechanism \5 human safety\5_2 micro



resist\5_2_2_4_1

resistance mechanism\


22

5.2.2.4.2 Transfer of Antimicrobial Resistance Genes \5 human safety\5_2 micro



resist\5_2_2_4_2 transfer

of antimicrob resist genes\

5.2.2.4.3 Cross-resistance \5 human safety\5_2 micro



resist\5_2_2_4_3 cross-

resistance\

5.2.2.4.4 Co-resistance \5 human safety\5_2 micro



resist\5_2_2_4_4 co-

resistance\

5.2.2.4.5 Resistance Development \5 human safety\5_2 micro



resist\5_2_2_4_5

resistance development\

5.2.2.5 Effect on the Animal Gut Microflora \5 human safety\5_2 micro


reports\5_2_2_5 effect on

the animal gut microflora\

5.2.2.6 Effect on Human Gut Microflora \5 human safety\5_2 micro


reports\5_2_2_6 effect on

human gut microflora\

5.2.2.7 Impact on Human Medicine \5 human safety\5_2 micro


reports\5_2_2_7 impact on

human m edicine\

5.2.2.8 Pharmacokinetics \5 human safety\5_2 micro


reports\5_2_2_8

pharmacokinetics\

5.2.2.9 Historical Information \5 human safety\5_2 micro


reports\5_2_2_9 historical

information\

5.2.2.10 Combination Antimicrobial Products \5 human safety\5_2 micro


reports\5_2_2_10

combination antimicrobial

products\





5.2.2.11 Post-approval Monitoring \5 human safety\5_2 micro


reports\5_2_2_11 post-

approval monitoring\

5.2.2.12 Global Harmonization \5 human safety\5_2 micro


reports\5_2_2_12 global

harmonization\

5.2.3 Direct-Fed Microbial and CompetitiveExclusion Products

\5 human safety\5_2 micro

safety\5_2_3 dir-fed microb

compet excl prod\

5.2.3.1 Sectional Reports \5 human safety\5_2 micro


compet excl prod\5_2_3_1

sectional reports\

5.2.3.1.1 Information about the Product \5 human safety\5_2 micro



sectional

reports\5_2_3_1_1 info

about product\

5.2.3.1.2 Antimicrobial Resistance Profile \5 human safety\5_2 micro



sectional

reports\5_2_3_1_2

antimicrob resist profile\

5.2.3.1.3 Effect on Animal and Human Gut Microflora \5 human safety\5_2 micro



sectional

reports\5_2_3_1_3 effect

animal hum an gut microfl\

5.3 Residue (Chemistry) Studies \5 human safety\5_3

residue chem\

5.3.1 Comprehensive Summary \5 human safety\5_3

residue chem\5_3_1


5.3.2 Sectional Reports \5 human safety\5_3

residue chem\5_3_2

sectional reports\

5.3.2.1 Pharmacokinetics \5 human safety\5_3

residue chem\5_3_2


pharmacokinetics\


24

5.3.2.1.1 Pharmacokinetic Studies in the Intended Species \5 human safety\5_3

residue chem\5_3_2


pharmacokinetics\5_3_2_1

_1 PK in intended species\

5.3.2.1.2 Metabolism Studies in the Intended Species \5 human safety\5_3

residue chem\5_3_2



_2 metabolism in intended

species\

5.3.2.1.3 Comparative Metabolism Studies in LaboratoryAnimals

\5 human safety\5_3

residue chem\5_3_2



_3 comp m etabolism in lab

animals\

5.3.2.2 Residue Studies \5 human safety\5_3

residue chem\5_3_2


residue\

5.3.2.2.1 Analytical Methodology \5 human safety\5_3

residue chem\5_3_2


residue\5_3_2_2_1

analytical m ethodology\

5.3.2.2.2 Validation of the Regulatory Method(s) for theDetection and Confirmation of Residues ofVeterinary Drug in Food

\5 human safety\5_3

residue chem\5_3_2


residue\5_3_2_2_2 valid

reg method detect-confirm

res vet drug in food\

5.3.2.2.3 Drug Residue Depletion Studies \5 human safety\5_3

residue chem\5_3_2


residue\5_3_2_2_3 drug

residue depletion\

5.3.2.2.4 Procedure for Establishing Maximum ResidueLimits

\5 human safety\5_3

residue chem\5_3_2


residue\5_3_2_2_4

procedure estab max

residue limits\

5.3.2.3 Drugs for Concurrent Use or in Combination \5 human safety\5_3

residue chem\5_3_2


drugs concurrent use-

combination\

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