The document discusses the requirements and procedures for submitting an Abbreviated New Drug Application (ANDA) under Paragraph IV certification, which allows generic drugs to be marketed before the expiration of brand-name patents. It outlines the necessary modules, submission formats, and regulatory hurdles faced by applicants, especially with the shift to electronic submissions only. The conclusion emphasizes the increasing challenges since 2000, despite the growing number of companies entering the Paragraph IV market.

1. By Richa Trivedi
Rollno: 10
MRA SEM III

17. PARAGRAPH IV- PATENT CERTIFICATIONS
• FDAAPPROVAL TO MARKET A GENERIC DRUG BEFORE THE EXPIRATION OF PATENTS RELATED TO
THE BRAND-NAME DRUG THAT THE GENERIC SEEKS TO COPY.
• TO SEEK THIS APPROVAL, A GENERIC APPLICANT MUST PROVIDE IN ITS APPLICATION A
"CERTIFICATION" THAT A PATENT SUBMITTED TO FDA BY THE BRAND-NAME DRUG'S SPONSOR AND
LISTED IN FDA'S APPROVED DRUG PRODUCTS WITH THERAPEUTIC EQUIVALENCE EVALUATIONS (THE
ORANGE BOOK IS, IN THE GENERIC APPLICANT'S OPINION AND TO THE BEST OF ITS KNOWLEDGE,
INVALID, UNENFORCEABLE, OR WILL NOT BE INFRINGED BY THE GENERIC PRODUCT
• THE FIRST COMPANY OR COMPANIES TO SUBMIT AN APPLICATION THAT IS DETERMINED BY THE
AGENCY TO BE "SUBSTANTIALLY COMPLETE" UPON SUBMISSION AND CONTAINS A PARAGRAPH IV
CERTIFICATION TO AT LEAST ONE OF THE PATENTS LISTED IN THE ORANGE BOOK IS GENERALLY
ELIGIBLE FOR THE EXCLUSIVE RIGHT TO MARKET THE GENERIC DRUG FOR 180 DAY

20. PATENT CHALLENGE SUCCESSFUL
• AWARD OF 180-DAY EXCLUSIVITY PERIOD
• AWARDED TO FIRST ANDA HOLDER TO FILE A COMPLETE APPLICATION WITH PATENT
CHALLENGE
• PROTECTION FROM OTHER GENERIC COMPETITION – BLOCKS APPROVAL OF
SUBSEQUENT ANDAS
• PROTECTION TRIGGERED BY: FIRST COMMERCIAL MARKETING FORFEITURE
PROVISIONS

26. FOLLOWING INFORMATION ARE REQUIRED IN 5 MODULES OF CTD
FOR SUBMITTING ANDAAPPLICATION
• MODULE 1 SHALL CONTAIN:
• COVER LETTER REQUESTING THE REVIEW AND MARKETING AUTHORIZATION FOR THE PRODUCT APPLIED.
• INFORMATION ON THE PRODUCT IN FORM 2657 (DOWNLOADABLE FROM FDA SITE).
• INFORMATION ON MANUFACTURING FACILITY IN FORM 2656 (DOWNLOADABLE FROM FDA SITE).
• INFORMATION AS PER FDA FORM 356H AND FORM 3674 (DOWNLOADABLE FROM FDA SITE).
• FIELD COPY CERTIFICATION
• DEBARMENT CERTIFICATION
• FINANCIAL CERTIFICATION
• PATENT INFORMATION
• PATENT CERTIFICATIONS

27. • 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 FOR BA/BE STUDIES, IF ANY
• DRAFT LABELING , PACKAGE INSERT , PATIENT INFORMATION , MEDICATION GUIDE,
LABELING COMPARISON WITH APPROVED PRODUCT (SPL FORMAT).
• FINANCIAL DISCLOSURE INFORMATION
• ENVIRONMENTAL ASSESSMENT OR REQUEST FOR CATEGORICAL EXCLUSION.
• STATEMENTS OF CLAIMED EXCLUSIVITYAND ASSOCIATED CERTIFICATIONS.

28. • CTD MODULE 2 SHALL CONTAIN: OVERVIEWS AND SUMMARIES RELATED TO
QUALITY AND BA/BE STUDIES.
• CTD MODULE 3: IT SHALL CONTAINS DETAILED QUALITY INFORMATION ON API AND
DOSAGE FORM.
• CTD MODULE 4: THIS MODULE IS NORMALLY NOT REQUIRED FOR ANDA.
• CTD MODULE 5: THIS MODULE ONLY REQUIRES BA/BE STUDY DETAILS.

30. • THE ENTIRE SET OF INFORMATION SHALL BE SUBMITTED IN TRIPLICATE AS PER BELOW:
• ARCHIVAL COPY- THE ARCHIVAL COPY IS A COMPLETE SET OF THE INFORMATION FILED WITH ANDA
APPLICATION. IT SERVES AS THE OFFICIALARCHIVE OF THE APPLICATION AND MAY BE USED DURING
THE REVIEW OF THE APPLICATION. IT SHALL HAVE BLUE COLOR BINDER.
• REVIEW COPY- IT IS MEANT FOR EVALUATION OF THE CONTENTS BY DIFFERENT REVIEWERS. IT
SHALL HAVE RED COLOR.
• FIELD COPY- IT CONTAINS ONLY QUALITY SECTION (MODULE 3). IT SHALL HAVE GREEN COLOR
• THE FAILURE TO PROVIDE ANY ONE OF THESE COPIES WILL INDUCT “REFUSE TO FILE” LETTER
FROM FDA
• STANDARD U.S. LETTER SIZE PAPER (8.5 X 11 INCHES) SHOULD BE USED FOR ALL SUBMISSIONS.
• FURTHER, THE NARRATIVE TEXT SHALL BE IN TIMES NEW ROMAN 12 POINT FONT. FONT SIZES 9
TO10 SHALL BE CONSIDERED FOR TABLES
• ALL DOCUMENTS SHOULD HAVE PAGE NUMBERS

31. • THE APPLICATION FOR ANDA IS REQUIRED TO BE ADDRESSED TO:
CENTER FOR DRUG EVALUATION AND RESEARCH FOOD AND DRUG ADMINISTRATION
DOCUMENT AND RECORDS SECTION 5901-B AMMENDALE RD BELTSVILLE, MD. 20705-1266

32. SUBMITTING ANDA
• ANDA IS A REGULATORY SUBMISSION FOR AUTHORIZATION OF GENERIC VERSION
OF NEW DRUGS AFTER EXPIRY OF ITS PATENT PERIOD. CURRENTLY, FILING ANDA
IS NOT AS SIMPLE AS IT WAS BEFORE. THE DAY BY DAY HURDLES ARE
MULTIPLYING. CURRENTLY FDA HAS STOPPED ACCEPTING PAPER
SUBMISSIONS AND ONLY ELECTRONIC FILINGS IN THE FORM ECTD ARE
ENTERTAINED. FOLLOWINGS ARE CRITICAL STEPS FOR INITIAL FILING AND
REVIEW OF ANDA.

33. ELECTRONIC SUBMISSIONS:
• THIS IS CTD STRUCTURE WHICH IS SUBMITTED IN THE ECTD IN THE ANDA
SUBMISSION FOR FDA THIS IS PREPARED AS FOLLOWING THE ICH GUIDELINE.
ECTD COMPOSED OF TWO TYPES OF SPECIFICATION
• CONTENT SPECIFICATION – AS DEFINED BY ICH
• TECHNICAL SPECIFICATION – ELECTRONIC SOFTWARES

35. THE FDA WILL TENTATIVELY APPROVE A TWO YEAR
EXPIRATION DATE FOR A PRODUCT IF SATISFACTORY DATA
REFLECTING AT LEAST 3 MONTHS STORAGE UNDER
ACCELERATED CONDITIONS IS SUBMITTED.
THE SPONSOR IS ALSO EXPECTED TO PROVIDE A COMMITMENT
TO CONTINUE TO MONITOR THE STABILITY OF THE PRODUCT
PERIODICALLY REPORT THE RESULTS TO FDA, AND TO REMOVE
FROM MARKET ANY BATCHES FAILING TO MEET
SPECIFICATIONS PRIOR TO PRODUCT’S LABELED EXPIRATION
PERIOD.
35

36. CONCLUSION
• FROM THE STUDY IT WAS FOUND THAT (ANDA) SUBMISSION UNDER THE
PARAGRAPH IV CERTIFICATION IS VERY CHALLENGING,
• AS CONCLUSION THAT PARA - IV CERTIFICATION APPLICANT HAS TO FACE A LOT
OF PROBLEM TO GET THE BENEFITS, SINCE 2000, MANY COMPANIES HAVE
ENTERED THE P-IV MARKET AND THERE HAS BEEN A STEADY UPTICK IN P-IV
CASES (PER PARAGRAPHFOUR.COM RESEARCH).

37. REFRENCES
• M, S. K., J. D. KATAMREDDY, AND J. R. P. “A REVIEW ON ANDA SUBMISSION
REQUIREMENTS FOR GENERIC DRUGS: ‘PARAGRAPH IV CERTIFICATION’AS
PER FDA CDER GUIDELINES”. INTERNATIONAL JOURNAL OF DRUG
REGULATORY AFFAIRS, VOL. 6, NO. 3, SEPT. 2018, PP. 5-12,
DOI:10.22270/IJDRA.V6I3.260.
• GUPTA RAJKUMAR “ INSIDE STORY FOR REVIEW OF AN ABBREVIATED NEW DRUG
APPLICATION” INTERNATIONAL JOURNAL OF DRUG REGULATORY AFFAIRS; 2014,
2(1), 29-31 ISSN: 2321 - 6794