Tuesday 2 October 2012

How to get a job in the field of Regulatory Affairs ?



This article is aimed at listing down the simple steps/facts, which I hope will help in solving the big riddle of getting a job in the field of regulatory affairs !

First of all, I would like to share my personal experiences in pursuit of job in the field of Regulatory Affairs. After my B.Pharmacy, I was pretty much sure that I wanted to get into RA., so I enrolled into the course offered by BII-Industry Program in RA, which was famous back then. I also enrolled into a short term industry oriented course for pharma graduates which included RA as one of the topics. I had also began researching regarding RA on the internet, but could get info in bits and pieces (This was the reason for me to start Regulatory One). 

After considerable time of enrolling into the above courses, I got a call for interview in my first company. I had few more freshers (beginners) for competition at the time of interview. I cleared the interview and got the job due to the fact that I had done suitable home work and my research study on DMF (Drug Master files), which was part of my course, was of great help. I am trying to state the fact that, if you want to get a job, you need to have special skills which are not there with your competitors!

The information which I learnt, while I worked on Regulatory One, helped  me to get my 2nd job.

Gaining Skills in Regulatory Affairs - 
  • If  you have done M.pharmacy (not in RA)- My suggestion would  be-do a diploma/PG diploma course related to RA through part-time/distance. My personally preferred course and institute is PG Diploma in Pharmaceutical Regulatory Affairs from  Jamia Hamdard University since it is accredited by NAAC in 'A' category and they have contact classes in major cities. The feed back I received regarding the course was that, its good.
  •  If  you are B. Pharmacy graduate and want to make a career in RA -I would recommend you to do M.Pharmacy in Pharmaceutical RA .
         The list of institutes offering M.Pharmacy in RA are given in the below link.
  •  Browse, through the websites of Regulatory Agencies like FDA, MHRA, CDSCO and try to gain as much knowledge as possible. In the below page of Regulatory One, Link to the updated news section in the websites of premier regulatory agencies of world is provided.       
         http://www.regulatoryone.com/p/updated-news.html
  • In FDA's website there are links like CDER learn , Educational Resources and Webinars which contain lots of useful information. Similarly there are training modules in MHRA' s website.Of course, all the above listed useful links are absolutely free to access !
  • Among all the ICH guidelines- M4 (and allied guidelines M4Q, M4S, M4S), Q1A , Q1E ,Q2Q3AQ3BQ3CQ6A are the most important references for RA professionals. Knowing them is very important. 
  • Go through all the articles, which I have written in Regulatory One. I personally believe that, if a beginner goes to the interview after reading the articles that I have written, they could easily clear the interview.
  • The below listed link is very useful at the time of interview, especially for beginners (freshers).            
         http://www.regulatoryone.com/p/regulatory-affairs-interview-questions.html

Writing Skills -
  • For a Regulatory Affairs professional, having good writing skills is very important, since he/she is involved in compilation of dossiers, responding to queries from regulatory agencies. 
Resume -  
  • Make sure that, you have a well formatted, unique resume which is different from others. If possible, get the resume reviewed by an expert. Ensure to highlight the course which you have done related to RA and specific skill with respect to RA.
  • Upload your resume in job websites like Monster and Naukri. Ensure to fill up all your details and have a complete profile.

Networking Networking is an important tool for getting to know about any openings in the field of Regulatory Affairs. In the professional Networking sites like Linkedin, having your complete profile is very important. The following things are to be considered/taken note of, while setting up your profile-
  • Have your detailed profile, with special emphasis on your educational qualification, skills related to regulatory affairs. 
  • Ensure that the information is given in a properly structured manner, without any grammatical errors.
  • Ensure that the photo which you have uploaded is a one in which you are in formal dress and definitely not the one, which you had taken during your vacation in a casual dress!
  • Join groups related to Regulatory Affairs like Drug Regulatory Affairs, Global Regulatory Affairs, Regulatory Affairs Job Opportunities etc and take active part in discussions in a relevant way.
  • Request people who are in senior positions in RA field to be part of your Networks. If they accept to be part of your network, send them an email,(in a properly structured manner, without any typo/grammatical errors) requesting them to let you know if there are any openings in their company. Respect their privacy, and do not ask them for their personal numbers. If they see your profile and they find you to be good enough, they may definitely let you know, if there are any openings.
General MisconceptionsI guess, some of you might have got the free advice- "Start of your career by working in Quality Control /Quality Assurance. Then you will have a better chance of getting a job in RA". This logic is absolute false. Why will a company prefer a person with experience in QC/QA over a person with experience in RA ?

Guys, a person who is a fresher (beginner) can get a job in RA. The best example is, myself !

Hope, the above article will help you in getting a job in the field of Regulatory Affairs. 

Best of Luck! 

P.S-
  • The above article is intended, mainly for the people from India, who are interested to make a career in the field of RA.
  • I am not in a position where I could refer/recommend for a job. So, kindly do not email me your resumes.




Friday 23 March 2012

GRASE, Grandfathered and DESI Drugs



GRASE Drugs-
  • The abbreviation of the term GRASE is -Generally Recognized as Safe and Effective
  • GRASE Drugs are certain old drugs that do not require prior approval from FDA in order to be marketed because they are generally recognized as safe and effective based on published scientific literature.
  • It is not an easy standard for a drug to qualify as GRASE. For a drug to qualify under the category of GRASE, it has to fulfill the following criteria-
  1. The Drug must have been subjected to adequate and well controlled clinical investigations that established its safety and effective.
  2. The Investigation results must be published in the scientific literature so that they are available to qualified experts.
  3. Experts must generally agree, based on those published studies, that the drug is safe and effective for its intended uses.
  • A product's general recognition as safe and effective must be demonstrated by at least the same quality and quantity of data necessary to support FDA approval for marketing.
  • It is unlikely that any currently marketed prescription drug is GRASE.
Note: The term GRAS (Generally Recognized as Safe) was used in 1938, Federal Food, Drug, and Cosmetic act.
The term GRASE (Generally Recognized as Safe and Effective) was used in 1962 amendment to the   Federal Food, Drug, and Cosmetic act.

Grandfathered Drugs
  • Drugs that entered the market before the passage of the 1938 act or the 1962 amendments to the act are often referred to as grandfathered drugs.
  • Under the 1962 grandfather clause, the FFDCA exempts a drug from the effectiveness requirements if its composition and labeling have not changed since 1962 and if, on the day before the 1962 amendments became effective, it was
  1.  Used or sold commercially in the United States
  2.   Not a new drug as defined by the act at that time
  3.   Not covered by an effective application
  • Many older drugs without FDA approval claim to be grandfathered; however, FDA believes that very few drugs are on the market that are actually entitled to grandfather status because the drugs currently on the market likely differ from the previous versions in some respect, such as formulation, dosage or strength, dosage form, route of administration, indications, labeling, or intended patient population.
DESI Drugs- 
  • The abbreviation of term DESI is- Drug Efficacy Study Implementation
  • Drugs that entered the US market between 1938 and 1962 and that were approved for safety but not effectiveness are referred to as DESI drugs.. Drugs that are IRS (Identical related or Similar )  to such drugs are also called DESI drugs.
Background-
  • “Safety” was the criteria for the approval of New Drugs between the passage of 1938, Federal Food, Drug, and Cosmetic act and its amendment in 1962 ( Kefauver-Harris amendment).
  • “Safety and Efficacy criteria“had to be met as per the Kefauver-Harris amendment for the approval of New Drugs.       
  • The Kefauver-Harris amendment also required that FDA evaluate the safety and the effectiveness of new drugs marketed between 1938 and 1962.
  • Drug Efficacy Study Implementation (DESI) was a program begun by the Food and Drug Administration (FDA) after the requirement by Kefauver-Harris amendment that all drugs marketed between 1938 and 1962 be safe and effective.
  • The DESI program was intended to classify all pre-1962 drugs that were already on the market as either effective, ineffective, or needing further study.
  • The Drug Efficacy Study Implementation (DESI) evaluated over 3000 separate products and over 16,000 therapeutic claims.
  • By 1984, final action had been completed on 3,443 products; of these, 2,225 were found to be effective, 1,051 were found not effective, and 167 were pending.
Keywords- Federal Food, Drug and Cosmetic act (FFDCA)-1938, Kefauver-Harris amendment-1962. 

References-


Thursday 8 March 2012

CEP




What is the Full form of abbreviation, CEP?
Certificate of Suitability to the monographs of the European Pharmacopoeia (or) Certificate of suitability of monographs of the European Pharmacopoeia (or) Certification of suitability of European Pharmacopoeia monographs
It is also informally referred to as Certificate of Suitability (COS)

What is a CEP?
It is the certificate which is issued by Certification of Substances Division of European Directorate for the Quality of Medicines (EDQM), when the manufacturer of a substance provides proof that the quality of the substance is suitably controlled by the relevant monographs of the European Pharmacopoeia.

For which substances, applications for the grant of CEPs can be submitted?
Applications for the grant of CEPs can be submitted to EDQM if monograph (general monograph and/or specific monograph) has been adopted by the European Pharmacopoeia for the following-
  • Organic or inorganic substances (active or excipients), manufactured or extracted.
  • Sterile Active Substances
  • Substances produced by fermentation as indirect gene products, which are metabolites of microorganisms, irrespective of whether or not the microorganisms have been modified by traditional procedures or r-DNA technology
  • Products with risk of transmitting agents of animal spongiform encephalopathies (TSE)
  • Herbal Drugs and Herbal Drug Preparations
For which substances CEP is not granted?
  • Direct gene products (proteins)
  • Products obtained from human tissues
  • Vaccines
  • Blood products and preparations.
What are the Legislations which describe certification Procedure?
Directives 2001/82/EC and 2001/83/EC, as amended, of the European Council and of the Parliament.
Guidelines to be referred for preparing Dossier to obtain a CEP 
Content of the Dossier for Chemical Purity and Microbiological Quality (PA/PH/CEP 04 1 4R)
Application form and template for QOS 
Link for Downloading Application form and template of QOS.
Note: Click on the hyperlinks in blue for application form and template of QOS to download them.
Online Database of Approved CEPs 
Link to Online Databases of Approved CEPs 
Registration Fees  
Registration fees for various New CEP Applications 

 Deficiencies
 Link to top 10 deficiencies in New Applications for grant of CEPs 

Recognition of CEPs- CEPs are recognised by all the member countries of the European Union and also   other Countries like Canada, Australia, New Zealand, Tunisia and Morocco. 
 
Advantages of CEPs-
  •  It is valid for 5 Years.
  • An API manufacturer need not file an ASMF/EDMF in all the member countries involved in DCP/MRP Procedures if the manufacturer has obtained CEP for that specific API. Sending a Copy of CEP will do.
  • Centralised evaluation of Dossier by only one agency i.e EDQM.
References-
Keywords: CEP, EDQM,  Resolution AP-CSP (07) 1, Directives 2001/82/EC and 2001/83/EC.

Monday 20 February 2012

Sample Quality Overall Summary



I am sure that, many of you may be interested to take a look at complete NDA/ANDA/Dossier/ASMF. Since, they contain confidential information, no company would like to share it in public domain. But guys! you could check out sample Quality Overall Summary (part of Module-2) of an ANDA submission. FDA has posted samples of Quality overall summary (QOS) in its website the links of which are provided below-


Module 2- It is part of  NDA/ANDA/Dossier/DMF/ASMF, where the summaries of Modules-3,4,5 are presented. It could  be correlated to an abstract of research article or trailer of a movie! The module-2 (Common Technical Document Summaries) consist of the following sections-

2.1 Common Technical Document Table of Contents (Modules 2-5)
2.2 CTD Introduction
2.3 Quality Overall Summary
2.4 Nonclinical Overview
2.5 Clinical Overview
2.6 Nonclinical Written and Tabulated Summaries
  • Pharmacology
  • Pharmacokinetics
  • Toxicology
2.7 Clinical Summary
  • Biopharmaceutic Studies and Associated Analytical Methods
  • Clinical Pharmacology Studies
  • Clinical Efficacy
  • Clinical Safety
  • Literature References
  • Synopses of Individual Studies

 As discussed by me earlier, you need to refer -M4 GuidelineM4Q GuidelineM4S GuidelineM4E Guideline to file a  NDA/ANDA/Dossier/DMF/ASMF in CTD format.

Reference-M4 Guideline

Keywords - Sample Quality Overall Summary, Module-2, M4 Guideline, FDA.

Tuesday 14 February 2012

Changes to an approved NDA or ANDA






In this post, I am going to discuss about the post approval changes and their reporting categories. After the approval of NDA or ANDA, the applicant may make post approval changes, provided the changes are reported to the FDA under the appropriate categories.

Section 506 A of the Federal Food, Drugs and Cosmetics act and 21 CFR 314.70 provide for 4 reporting categories of the post approval changes which are listed below-

1. Major Change                                                 
2. Moderate Change- It is categorized into 2 types-
 (a) The change requiring the submission of Supplement - Changes Being Effected in 30 Days
 (b) The change requiring the submission of Supplement - Changes Being Effected  
3. Minor Change        

1. Major Change-
  • A major change is a change that has a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product.                                                                                                                                                              
  • A major change requires the submission of a supplement and approval by FDA prior to distribution of the drug product made using the change. This type of supplement is called and should be clearly labeled as Prior approval supplement.

  • An applicant may ask FDA to expedite its review of a prior approval supplement for public health reasons like drug shortage or in case if there is a delay would impose an extraordinary hardship on the applicant.   
                                                                 
2. Moderate Change- A moderate change is a change that has a moderate potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product.

The moderate change is categorized into 2 types based on the type of supplement being filed -        
 a) Supplement - Changes Being Effected in 30 Days
  • This type of change requires submission of supplement to FDA at least 30 days before the distribution of drug product made using the change.  
  • This type of supplement is called, and should be clearly labeled, a Supplement - Changes being effected in 30 Days.
  • The drug product made using moderate changes cannot be distributed if the FDA informs the applicant to file a prior approval supplement for the changes made or if FDA informs that the information is missing or if FDA disapproves the changes being affected in 30 days.

   b) Supplement - Changes Being Effected
  • This type of supplement contains changes for which distribution can occur when FDA receives the supplement.
  • FDA may order the manufacturer to cease distribution of the drug products made using the disapproved change, If, after review, FDA disapproves a changes-being effected.
3. Minor change -A minor change is a change that has minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product.

 Assessing the effect of manufacturing changes

A. Assessment of the effects of the change-The applicant must assess the effects of the change before distributing a drug product made with a manufacturing change. Assessment should be made on the following-

1. Conformance to specifications- An assessment of the effects of a change on the identity, strength, quality, purity, and potency of the drug product should include a determination that the drug substance intermediates, drug substance, in-process materials, and/or drug product affected by the change conform to the approved specifications.

2. Additional Testing- 
  • Apart from checking for conformance to specifications, the applicant should perform additional testing, when appropriate, to assess whether the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product have been or will be affected.
  • The assessment should include, as appropriate, evaluation of any changes in the chemical, physical, microbiological, biological, bioavailability, and/or stability profiles.
  • This additional assessment could involve testing of the post change drug product itself or, if appropriate, the material directly affected by the change.
  • The type of additional testing that an applicant should perform would depend on the type of manufacturing change, the type of drug substance and/or drug product, and the effect of the change on the quality of the drug product.
For Example- Evaluation of the hardness or friability of a tablet after certain changes.

B. Equivalence- When testing is performed, the applicant should usually assess the extent to which the manufacturing change has affected the identity, strength, quality, purity, and potency of the drug product. Typically this is accomplished by comparing test results from pre- and post change material and determining if the test results are equivalent.

C. Adverse Effects- Some manufacturing changes have an adverse effect on the identity, strength, quality, purity, or potency of the drug product, which in most cases are not implemented by applicant. If an assessment indicates that a change has adversely affected the identity, strength, quality, purity, or potency of the drug product, FDA recommends that the change be submitted in a prior approval supplement regardless of the recommended reporting category for the change.

The reporting categories for the post approval changes are provided with respect to the following-

 (1) Components and composition
 (2) Manufacturing sites
 (3) Manufacturing process
 (4) Specifications
 (5) Container closure system
 (6) Labeling
 (7) Miscellaneous changes
 (8) Multiple related changes

(1) Components and composition-
  • Changes in the qualitative or quantitative formulation, including inactive ingredients, as provided in the approved application, are considered major changes requiring a prior approval supplement, unless exempted by regulation or guidance.
  • The deletion or reduction of an ingredient intended to affect only the color of the drug product may be reported in an annual report.
(2) Manufacturing sites

Example under reporting category of major change (Prior approval supplement)-
A move to a different manufacturing site, except one used to manufacture or process a drug substance intermediate, when the new manufacturing site has never been inspected by FDA for the type of operation that is being moved or the move results in a restart at the new manufacturing site of a type of operation that has been discontinued for more than two years.

Example under reporting category of moderate change (supplement changes being effected in 30 days)-
A move to a different manufacturing site for the primary packaging of (1) any drug product that is not otherwise listed as a major change and (2) modified-release solid oral dosage form drug products.

Example under reporting category of moderate change (supplement changes being effected)-
Move to a different manufacturing site for the manufacture or processing of the final intermediate.

Example under reporting category Minor Changes (Annual Report)
A move to a different manufacturing site for secondary packaging.

(3) Manufacturing process

Example under reporting category of major change (Prior approval supplement)-
Changes that may affect the controlled (or modified) release, metering or other characteristics (e.g., particle size) of the dose delivered to the patient, including the addition or deletion of a code imprint by embossing, debossing, or engraving on a modified-release solid oral dosage form.

Example under reporting category of moderate change (supplement changes being effected in 30 days)-  
For Drug substance, redefinition of an intermediate, excluding the final material, as the starting material.                                                                                                                                     
Example under reporting category of moderate change (supplement changes being effected)-
A change in methods or controls that provides increased assurance that the drug substance or drug product will have the characteristics of identity, strength, quality, purity, or potency that it purports or is represented to possess.

Example under reporting category of minor Changes (Annual Report)
A minor change in an existing code imprint for a dosage form. For example, changing from a numeric to alphanumeric code.

(4) Specifications

Example under reporting category of major change (Prior approval supplement)-
Establishing a new regulatory analytical procedure including designation of an alternative analytical procedure as a regulatory procedure.

Example under reporting category of moderate change (supplement changes being effected in 30 days)-
Relaxing an acceptance criterion or deleting a test to comply with an official compendium that is consistent with FDA statutory and regulatory requirements

Example under reporting category of moderate change (supplement changes being effected)-
An addition to a specification that provides increased assurance that the drug substance or drug product will have the characteristics of identity, strength, quality, purity, or potency that it purports or is represented to possess. For example, adding a new test and associated analytical procedure and acceptance criterion
.
Example under reporting category of minor Changes (Annual Report)
Tightening of acceptance criteria.

(5) Container closure system

Example under reporting category of major change (Prior approval supplement)-
A change in the primary packaging components for any drug product when the primary packaging components control the dose delivered to the patient (e.g., the valve or actuator of a metered-dose inhaler).

Example under reporting category of moderate change (supplement changes being effected in 30 days)- 
Changes in the size or shape of a container for a sterile drug substance.

Example under reporting category of moderate change (supplement changes being effected)-
A change in or addition or deletion of a desiccant.

Example under reporting category of minor Changes (Annual Report)
A change in the size and/or shape of a container for a nonsterile solid dosage form

(6) Labeling

Example under reporting category of major change (Prior approval supplement)-
Changes based on postmarketing study results, including, but not limited to, labeling changes associated with new indications and usage.

Example under reporting category of moderate change (supplement changes being effected)-
Addition of an adverse event due to information reported to the applicant or Agency.

Example under reporting category of minor Changes (Annual Report)
Labeling changes made to comply with an official compendium.

(7) Miscellaneous changes

Example under reporting category of major change (Prior approval supplement)-
Addition of a stability protocol or comparability protocol

Example under reporting category of moderate change (supplement changes being effected in 30 days)-
Reduction of an expiration dating period to provide increased assurance of the identity, strength,quality, purity, or potency of the drug product. Extension of an expiration date that has previously been reduced under this provision should be submitted in a changes-being-effected-in-30-days supplement even if the extension is based on data obtained under a protocol approved in the application.

Example under reporting category of moderate change (supplement changes being effected)- No changes have been identified.

Example under reporting category of minor Changes (Annual Report)
An extension of an expiration dating period based on full shelf life data on production batches obtained under a protocol approved in the application

(8) Multiple related changes

For multiple related changes where the recommended reporting categories for the individual changes differ, CDER recommends that the submission be in accordance with the most restrictive of the categories recommended for the individual changes. When the multiple related changes all have the same recommended reporting category, CDER recommends that the submission be in accordance with the reporting category for the individual changes.

Note- 
View the guidance-
Changes to an approved NDA or ANDA for categorization of all the possible changes.

Reference-
Further reading-
Changes to an approved NDA or ANDA Questions and Answers

Keywords: Changes to an approved NDA or ANDA, Section 506A,  21 CFR 314.70, Major Changes, Moderate Change, Supplement-Changes being effected in 30 Days, Supplement -Changes being effected, Minor Change.

Tuesday 24 January 2012

Abbreviated New Drug Application (ANDA)


What is an ANDA?

An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's Center for Drug Evaluation and Research (CDER), Office of Generic Drugs (OGD), provides for the review and ultimate approval of a generic drug product. Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public.

In simple words “It is an application which is filed with USFDA for generic drug approval of an existing licensed medication or approved drug.”

A generic drug product is one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use.

I. Important facts about generics and generic drug applications (ANDA)-
  • Generic drug applications are termed "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. 
  •  Generic applicants must scientifically demonstrate that their product is bioequivalent (i.e., performs in the same manner as the innovator drug). 
  • Bioequivalence is generally determined by measuring the time taken for generic drug to reach the bloodstream in 24 to 36 healthy, volunteers. This gives the rate of absorption, or bioavailability, of the generic drug, which can be compared to that of the innovator drug. 
  • The generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the innovator drug
  •  The basis for approving generic copies of drug products was established by the "Drug Price Competition and Patent Term Restoration Act of 1984," also known as the "Hatch -Waxman  Act". 

II. Facility and Drug Registration for filing an ANDA-
  •  The facility should be registered with FDA using form FDA 2656(Registration of Drug Establishment/Labeler Code Assignment form).
  • The product(s)/Drugs to be listed with FDA using form FDA 2657 (Drug listing form) .
Note: From June 1, 2009 FDA is accepting only electronic submissions of forms FDA 2656 and 2657.
III.Format and content of ANDA-
The FDA recommends ICH’s CTD for filing the ANDA.
Documents in each Module
Module
Information
1
Administrative and prescribing information (region specific)
2
Summaries and overview
3
Information on product quality
4
Nonclinical study reports
5
Clinical study reports


Module 1- Administrative and prescribing information

Documents should be organized in the order listed below. Generally, all of the documents in Module 1 can be provided in a single volume. Environmental assessments should be submitted separately.

1. Forms and cover letter-
  •       Cover letter

2. Comprehensive table of contents
The next document in Module 1 should be the comprehensive table of contents for the entire submission. Each ANDA submission is required to have a comprehensive table of contents or index for the entire submission (as per 21 CFR 314.94)

3. Administrative documents
a. Administrative documents
  • Appropriate administrative documents should be provided with the submission. Examples of administrative documents are listed below. 21 CFR 314.94  consists of details on the administrative documents needed for ANDA.
  • Field copy certification
  • Debarment certification
  • Financial Certification
  •  Patent information on any patent that claims the drug, if applicable
  • Patent certifications
  • Letters of authorization for reference to other applications or drug master files (if applicable)
  • US Agent Letter of Authorization
  • Proprietary name request (if applicable )
  • Basis of ANDA submission
  • Comparison between Generic Drug and RLD-505(j)(2)(A)
  • Request for waiver
  • Draft labeling
  • Listed drug labeling
  • Labeling requirements
  • Financial disclosure information
  • Waiver requests
  • Environmental assessment or request for categorical exclusion
  • Statements of claimed exclusivity and associated certifications
*Environmental assessment should be provided as a separate volume.
b.Prescribing information
All copies of the labels and all labeling for the product should be included. Examples are provided below-
  • Container and package labels
  • Package inserts
  • Draft labeling
  • Patient leaflets
  • Information sheets
  • Medication Guides
c. Labeling comparison
For the ANDA, the comparison of labeling should be provided that is described in 21 CFR 314.94(a)(8).
Module 2 – Common Technical Document Summaries
 Module 2 should include the summary documents. The documents for this module should be provided in the order as described below.
1. Overall CTD table of contents
For the first document in this module, a comprehensive table of Contents should be provided  listing all of the documents provided in the submission for modules 2 through 5.
2. Introduction to the summary documents
Introduction to the summary should be provided as described in the guidance document M4: Organization of the CTD as a one page document.
3. Overviews and summaries
Module 2 should contain the following additional documents as described in the appropriate guidance documents (M4Q: The CTD -QualityM4S:The CTD - SafetyM4E: The CTD – Efficacy):
  • Quality overall summary (2.3, Module 2, section 3)
  • Non clinical overview (2.4)
  • Clinical overview (2.5)
  • Nonclinical summary (2.6)
  • Clinical summary (2.7)
The nonclinical summary and the clinical summary should be provided in separate volumes for ease of use by reviewers.
Module 3 - Quality
Module 3 should include information on the drug and product that should be provided in the order described below

1. Module 3 table of contents
The first document in this module should be a table of contents listing all of the documents provided for module 3. See the guidance document M4Q: The CTD Quality for the headings and order to be used in the table of contents, including numbering of section headings.
2. Body of data
Each individual subsection related to the drug and product should be provided as an individual document either bound separately or divided by tab identifiers, depending on the size of the subsection. The documents should be presented in the order in which they are listed in the table of contents.
3. Literature References
Each literature reference should be provided as an individual document, separated from the others by tab identifiers.
Module 4 - Nonclinical Study Reports
For an ANDA submission Module 4 is not necessary.

Module 5 - Clinical Study Reports
Module 5 should contain clinical study reports and related information. The documents for this module should be provided in the order described below.

1. Module 5 table of contents
The first document in this module should be a table of contents listing all of the documents provided in Module 5. See the guidance to industry M4E: The CTD – Efficacy for the headings and order to be used in the table of contents, including numbering of section headings.

2. Study reports and related information
Each study report and each related document should be provided , such as tabular listings of all clinical studies, as an individual document separated from the other documents by binders or tab dividers. Tab identifiers be provided for each appendix in a study report. These documents should be presented in the order in which they are listed in the table of contents.

3. Literature References
Each literature reference should be provided as an individual document separated from the others by tab identifiers.
 For information in module 5 specific to an ANDA, refer -ANDA filing checklist.

V. Number of Copies of ANDA- The regulations requires archival, review, and field copies of ANDAs
1.Archival Copy- The archival copy is a complete copy of the application. It serves as the official archive of the application and may be used during the review of the application.
2. Review copy- It includes the information needed by each review discipline for its evaluation. These copies facilitate the concurrent review of the application by the different review disciplines. Review copies that may be necessary according to 21 CFR 314.94 for an individual submission include:
 Quality (Module 3),
 Clinical (Module 5) – Bioequivalence  documents
Copy of Modules 1 and 2 should be provided in each review copy. Each review copy should be labeled and bound separately.

3. Field copy-The field copy should be a separately bound copy of the Quality section (Module 3) for the ANDA.
VI. Paper size, font size, pagination, binder colors and mailing address-
Paper size-Standard U.S. letter size paper (8.5 x 11 inches) should be used for all submissions.
Font size-Narrative text be submitted in Times New Roman 12 point font. Font sizes 9 to10 points are considered acceptable in tables.
Pagination-Page numbering should be at the document level and not at the volume or module level. (The entire submission should never be numbered consecutively by page.) In general, all documents should have page numbers. Since the page numbering is at the document level, there should only be one set of page numbers for each document.
Binder Colors for ANDA Copies
copy
Binder color
Archival Copy
Blue
Review Copy
Red
Field Copy
Green



Mailing Address for Abbreviated New Drug Applications (ANDAs)
Office of Generic Drugs (HFD-600)
Center for Drug Evaluation and Research
Food and Drug Administration
Metro Park North VII
7620 Standish Place
Rockville, MD 20855