Chemistry, Manufacturing and Control Requirements for New Drug Application

In my previous posting, I discussed the general overview of new drug development in the US and FDA's role in the process. In this article I am focusing on the Chemistry portion of a New Drug Application (NDA) which was my expertise when I was still working for FDA. I worked for FDA from September, 1990 up to October, 2002. Twelve productive years of my professional career.

I am listing below a table of all Chemistry, Manufacturing and Control(CMC) guidance both in draft and final form. As a former Chemistry team leader in one of the divisions in the Center of New Drugs, I have some input on the contents of a few of these guidance. These guidance are available in the Internet for everyone.

Below is a table of Chemistry, Manufacturing and Controls (CMC) Guidance showing,
category, title status( draft or final) and date.

1. Chemistry, Manufacturing, and Controls (CMC) Analytical Procedures and Methods Validation (PDF - 91KB)1 Draft Guidance 08/30/00

2. Chemistry, Manufacturing, and Controls (CMC) Assay Development for Immunogenicity Testing of Therapeutic Proteins (PDF - 161KB)2 Draft Guidance 12/04/09

3. Chemistry, Manufacturing, and Controls (CMC) Botanical Drug Products (PDF - 437KB)3 Final Guidance 06/01/04

Taken at My Retirement Party-FDA Colleagues-2002

4. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products (PDF - 33KB)4 Final Guidance 07/01/97

5. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved NDA or ANDA (PDF - 108KB)5 Final Guidance 04/01/04

6. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved NDA or ANDA: Questions and Answers (PDF - 35KB)6 Final Guidance 01/01/01

7. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved NDA or ANDA; Specifications – Use of Enforcement Discretion for Compendial Changes (PDF - 18KB)7 Final Guidance 11/19/04

8. Chemistry, Manufacturing, and Controls (CMC) CMC Postapproval Manufacturing Changes Reportable in Annual Reports (PDF - 78KB)8 Draft Guidance 06/24/10

9. Chemistry, Manufacturing, and Controls (CMC) Comparability Protocols -- Chemistry, Manufacturing, and Controls Information (PDF - 240KB)9 Draft Guidance 02/25/03

10. Chemistry, Manufacturing, and Controls (CMC) Container Closure Systems for Packaging Human Drugs and Biologics (PDF - 164KB)10 Final Guidance 05/01/99

11.Chemistry, Manufacturing, and Controls (CMC) Container Closure Systems for
Packaging Human Drugs and Biologics -- Questions and Answers (PDF - 15KB)11 Final Guidance 05/01/02

12. Chemistry, Manufacturing, and Controls (CMC) Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products12 Final Guidance 04/01/96

13, Chemistry, Manufacturing, and Controls (CMC) Development of New Stereoisomeric Drugs13 Final Guidance 05/01/92

14. Chemistry, Manufacturing and Controls (CMC) Drug Master Files (DMFs)14 Additional Information regarding DMF's

Letter of Appreciation from the CEO and President of Bristol Myers-Sion Boney,1997

15. Chemistry, Manufacturing, and Controls (CMC) Drug Master Files for Bulk Antibiotic Drug Substances (PDF - 23KB)15 Final Guidance 11/01/99

16. Chemistry, Manufacturing, and Controls (CMC) Drugs, Biologics, and Medical Devices Derived from Bioengineered Plants for Use in Humans and Animals (PDF - 88KB) Draft Guidance 09/11/02

17. Chemistry, Manufacturing, and Controls (CMC) Environmental Assessment of Human Drug and Biologics Applications (PDF - 188KB)17 Final Guidance 07/01/98

18. Chemistry, Manufacturing, and Controls (CMC) Format and Content for the CMC Section of an Annual Report (PDF - 29KB)18 Final Guidance 09/01/94

19. Chemistry, Manufacturing, and Controls (CMC) Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting (PDF - 79KB)19 Draft Guidance 07/14/09

20. Chemistry, Manufacturing, and Controls (CMC) INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information (PDF - 193KB)20 Final Guidance 05/20/03

21. Chemistry, Manufacturing, and Controls (CMC) IND Meetings for Human Drugs and Biologics Chemistry, Manufacturing, and Controls Information (PDF - 30KB)21 Final Guidance 05/01/01

Ceremony during my Equal Employment Opportunity Award(EE0)

22. Guidance for Industry: Interpreting Sameness of Monoclonal Antibody Products Under the Orphan Drug Regulations (PDF - 26KB)22

23. Chemistry, Manufacturing, and Controls (CMC) Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation (PDF - 45KB)23 Draft Guidance 08/21/02

24. Chemistry, Manufacturing, and Controls (CMC) Monoclonal Antibodies Used as Reagents in Drug Manufacturing (PDF - 29KB)24 Final Guidance 03/01/01

25. Chemistry, Manufacturing, and Controls (CMC) Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products (PDF - 361KB)25 Draft Guidance 11/19/98

26. Chemistry, Manufacturing, and Controls (CMC) Nasal Spray and Inhalation Solution, Suspension, and Drug Products (PDF - 116KB)26 Final Guidance 07/01/02

27. Chemistry, Manufacturing, and Controls (CMC) NDAs: Impurities in Drug Substances (PDF - 11KB)27 Final Guidance 02/01/00

28. Chemistry, Manufacturing, and Controls (CMC) Orally Disintegrating Tablets (PDF - 52KB)28 Final Guidance 12/17/08

29. Chemistry, Manufacturing, and Controls (CMC) PAC-ATLS: Postapproval Changes - Analytical Testing Laboratory Sites (PDF - 76KB)29 Final Guidance 04/28/98

Some of My FDA Awards

30. Chemistry, Manufacturing, and Controls (CMC) Residual Drug in Transdermal and Related Drug Delivery Systems (PDF - 44KB)30 Draft Guidance 08/02/10

31. Chemistry, Manufacturing, and Controls (CMC) Residual Solvents in Drug Products Marketed in the United States (PDF - 52KB)31 Final Guidance 11/24/09

32. Chemistry, Manufacturing, and Controls (CMC) Reviewer Guidance, Validation of Chromatographic Methods (PDF - 703KB)32 Final Guidance 11/01/94

33. Chemistry, Manufacturing, and Controls (CMC) Size of Beads in Drug Products Labeled for Sprinkle (PDF - 43KB)33 Draft Guidance 01/18/11

34. Chemistry, Manufacturing, and Controls (CMC) Submitting Documentation for the Manufacturing of and Controls for Drug Products (PDF - 1048KB)34 Final Guidance 02/01/87

35. Chemistry, Manufacturing, and Controls (CMC) Guidelines for Submitting Samples and Analytical Data for Methods Validation Final Guidance 02/01/87

36. Chemistry, Manufacturing, and Controls (CMC) Submitting Supporting Documentation in Drug Applications for the Manufacture of Drug Substances (PDF - 94KB)36 Final Guidance 02/01/87

37. Chemistry, Manufacturing, and Controls (CMC) SUPAC-IR: Immediate-Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation (PDF - 60KB)37 Final Guidance 11/01/95

38. Chemistry, Manufacturing, and Controls (CMC) SUPAC-IR Questions and Answers about SUPAC-IR Guidance38 Final Guidance 02/18/97

39. Chemistry, Manufacturing, and Controls (CMC) SUPAC-IR/MR: Immediate Release and Modified Release Solid Oral Dosage Forms Manufacturing Equipment Addendum (PDF - 117KB)39 Final Guidance 01/01/99

40. Chemistry, Manufacturing, and Controls (CMC) SUPAC-MR: Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation (PDF - 215KB)40 Final Guidance 10/06/97

41. Chemistry, Manufacturing, and Controls (CMC) SUPAC-SS: Nonsterile Semisolid Dosage Forms Manufacturing Equipment Addendum (PDF - 61KB)41 Draft Guidance 12/01/98

42. Chemistry, Manufacturing, and Controls (CMC) SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation (PDF - 118KB)42 Final Guidance 05/01/97

43. Guidance for Industry - The Sourcing and Processing of Gelatin to Reduce the Potential Risk Posed by Bovine Spongiform Encephalopathy (BSE) in FDA-Regulated Products for Human Use The Sourcing and Processing of Gelatin to Reduce the Potential Risk Posed by Bovine Spongiform Encephalopathy (BSE) in FDA-Regulated Products for Human Use 09/01/97

My election to the United States Pharmacopeia Council of Experts is one of the highlight of my career with FDA

As a Chemistry Team Leader, you need to be familiar with contents of these 43 guidances, so when representatives from the Pharmaceutical firms ask you a question, you should be able to refer them to the guidance. If you can answer their question without referring to the guidance, the firm's representative look at you with high regard and respect. It is therefore imperative that you know most of the important requirements for an NDA submission as well as the post NDA requirements in the manufacture, chemistry and controls of an IND or NDA. A Guidance is not a Federal Regulation/Law. 21CFR (Code of Federal Regulation), gives FDA mandate to enforce drug and food laws in US. Source: www.fda.gov

My twelve years in FDA was the happiest and most productive years of my professional life. Macrine and my involvement with the Filipino-American community in the tristate area will also be memories that we will never forget.