The FDA regulatory methods validation program for new and abbreviated new drug applications

Pharmaceutical Technology

Volumn 24, Issue 1, 2000, Pages 30-42

  Layloff, T ^a   Nasr, M ^b   Baldwin, R ^a   Caphart, M ^a   Drew, H ^c   Hanig, J ^a   Hoiberg, C ^a   Koepke, S ^c,d   Lunn, G ^c   MacGregor, J T ^a   Mille, Y ^a   Murphy, E ^a   Ng, L ^e   Rajagopalan, R ^a   Sheinin, E ^c   Smela, M ^c   Welschenbach, M ^c   Winkle, H ^c   Williams, R ^f  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^b Div Test and Appl Analyt Devmt   (United States)

^c Office of Regional Affairs ^*

^d Division of New Drug Chemistry II

^e ONDC   (United States)

^f US Pharmacopeia   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANALYTIC METHOD; DRUG APPROVAL; DRUG RESEARCH; DRUG SCREENING; FOOD AND DRUG ADMINISTRATION; PRACTICE GUIDELINE; QUALITY CONTROL; REVIEW; STANDARD; VALIDATION PROCESS;

EID: 12944275545     PISSN: 01478087     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (27)

1. With the repeal of Section 507 of the Food, Drug, and Cosmetic Act, the antibiotic designations, which distinguished them from other drug products, have been eliminated. Methods validation approaches and issues for antibiotic drug products continue as those for all other new drugs currently approved under 505(b) and 505(j).
2. The United States Pharmacopeial Convention, 12601 Twinbrook Parkway, Rockville, MD 20852.
3. For example, see International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidance, "Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological and Biological Products," Federal Register 64 (159), 44928-44935 (1999).
4. Method validations generally are not performed for over-the-counter and certain drug efficacy study implementation-type products (post-1938 to pre-1962 approved products) and, not unexpectedly, inadequate methods are frequent and significant factors in a large number of regulatory actions for these products.
5. T. Layloff and P. Motise, "Selection and Validation of Legal Reference Methods of Analysis for Pharmaceutical Products in the United States," Pharm. Technol. 16 (9), 122-132 (1992).
6. Federal Food, Drug, and Cosmetic Act, Sec, 201.[321](g)(1) states that "The term drug means: (A) articles recognized in the official United States Pharmacopeia, official Homoeopathic Pharmacopeia of the United States, or official National Formulary, or any supplement to any of them."
7. 21 CFR 314.50(d)(1).
8. 21 CFR 314.50(e)(2)(i).
9. 21 CFA 211.165(e).
10. 21 CFR 211.194(a)(2).
11. See www.fda.gov/cder/guidance.
12. The ICH guidances are also available at www.fda.gov/cder/ guidance.
13. Available at www.fda.gov/cder/guidance/ameth.htm.
14. Available from the CDER FOIA Office.
15. The NDAs are classified: Type 1, new molecular entity; 2, new ester, salt, or other noncovalent derivative; 3, new formulation; 4, new combination; 5, new manufacturer; 6, new indication; or 7, drug already marketed but without an approved NDA. Types 1 and 4 require methods validation for both the new drug substance and the dosage form. Methods for Type 2 require validation only for the active moiety in the drug product but usually are as demanding as other categories.
16. 21 CFR 314.50(e)(1)(i).
17. 21 CFR 314.430.
18. 21 CFR 20.61.
19. 21 CFR 314.94(a)(8)(iv).
20. Verification demonstrates that the method is applicable to the product. This usually is accomplished by analyzing samples prepared by adding known quantities of the drug substance at the dosage levels to the excipient mixture to ensure there is no interference with this determination. Validation requires much more extensive evaluations that are described elsewhere in this article.
21. In the future, OGD review chemists will select an additional FDA laboratory to perform the methods validation so noncompendial ANDA analytical methods will occur in two FDA laboratories, as it does for noncompendial methods cited in an NDA.
22. See www.fda.gov/cder/mapp/5221-1.pdf.
23. 4 December 1981 memorandum from deputy director, Bureau of Drugs. Available from the FDA FOIA Office.
24. The ORA field laboratory personnel commitment probably exceeded this number.
25. 21 USC 377 states that "The Secretary, in carrying into effect the provisions of this chapter, is authorized hereafter to cooperate with associations and scientific societies in the revision of the United States Pharmacopeia and in the development of methods of analysis and mechanical and physical tests necessary to carry out the work of the Food and Drug Administration."
26. In the case of antibiotics, the submitted drug substance was formerly designated as the master standard for that product.
27. 21 CFR 314.430(e)(6) cites "After FDA sends an approval letter to the applicant, the following data and information ... are immediately available for public disclosure ... an assay method ..."