In my previous posting several weeks ago, I discuss a general overview of new drug
development 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 from September, 1990 up to
October, 2002. I am listing below a table of all CMC guidances 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 guidances. These guidances are available in the
Internet for everyone.
Below is a table of Chemistry, Manufacturing and Controls (CMC)
Guidances 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and Methods Validation (PDF - 91KB)1 Draft Guidance 08/30/00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Immunogenicity Testing of Therapeutic Proteins (PDF - 161KB)2 Draft
Guidance 12/04/09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
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Manufacturing Changes Reportable in Annual Reports (PDF - 78KB)8 Draft
Guidance 06/24/10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Draft Guidance 02/25/03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
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
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
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
Note: As a
Chemistry Team Leader, I need to be familiar with contents
of these 43 Guidances, so when representatives from the Pharmaceutical
firms ask me a question, I should be able to refer them to the
guidance. If I can answer their question without referring to the guidance, the firm's representative look at me
with high regard and respect.
It is therefore imperative that I know
most of the important requirements for an New Drug application (NDA)
submission as well as the post NDA requirements in the manufacture,
chemistry and controls of an Investigational New Drug (IND) or NDA. A
Guidance is not a Federal Regulation/Law. 21CFR (Code of Federal
Regulation), but gives FDA mandate to enforce drug and food laws in US.
Source: www.fda.gov