FDA Withdraws Seven CMC and Stability Guidance Documents

June 2, 2006
Pharmaceutical Technology Editors

ePT--the Electronic Newsletter of Pharmaceutical Technology

The US Food and Drug Administration (Rockville, MD) is withdrawing seven guidance documents "because some of the principles in these guidances are inconsistent with the agency's initiative, Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century (CGMP Initiative) .

The US Food and Drug Administration (Rockville, MD, www.fda.gov) is withdrawing seven guidance documents "because some of the principles in these guidances are inconsistent with the agency's initiative, Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century (CGMP Initiative) ." The withdrawal was announced in a June 1 Federal Register announcement (1).

The FDA Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are withdrawing the following guidances, originally issued individually or jointly:

  • Format and Content of the Chemistry, Manufacturing, and Controls Section of an Application (CDER, February 1987);
  • Submitting Documentation for the Stability of Human Drugs and Biologics, (CDER/CBER February 1987);
  • Stability Testing of Drug Substances and Drug Products (Draft), (CDER/CBER, June 1998);
  • Drug Product: Chemistry, Manufacturing, and Controls Information (Draft) (CDER/CBER, January 2003);
  • Submission of Chemistry, Manufacturing and Controls Information for Synthetic Peptides, (CDER/CBER, November 1994);
  • BACPAC I: Intermediates in Drug Substance Synthesis; Bulk Actives Postapproval Changes: Chemistry, Manufacturing, and Controls Documentation (CDER/CBER, February 2001);
  • Drug Substance: Chemistry, Manufacturing, and Controls Information (Draft) (CDER/CBER January 2004).

(The Center for Veterinary Medicine is revising rather than withdrawing the last two documents listed; the revised guidances are available on http://www.fda.gov/cvm).

According to FDA's Federal Register notice, "the withdrawals are part of a continuing review of all FDA guidances. We will continue to review our guidances for their consistency with the CGMP Initiative and may withdraw or revise other guidances if they do not reflect our current thinking or to align them with the concepts of the CGMP Initiative, the Quality by Design Initiative, or Question-based Reviews." The agency is developing new guidance documents to conform with these initiatives. Until they arrive, FDA directs the human drug pharmaceutical industry to International Conference on Harmonization's (ICH) guidances, on FDA's Web site (2):

  • M4: Common Technical Document (CTD) for the Registration of Pharmaceuticals for Human Use (CTD) (October 2001);
  • M4: The CTD--Quality (August 2001);
  • Q1A(R2) Stability Testing of New Drug Substances and Products (November 2003);
  • Q1B Photostability Testing of New Drug Substances and Products (November 1996);
  • Q1C Stability Testing for New Dosage Forms (May 1997);
  • Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products (January 2003);

  • Q1E Evaluation of Stability Data (June 2004);
  • Q1F Stability Data Package for Registration Applications in Climatic Zones III and IV, Revision 1 (July 2004);
  • Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances (December 2000);
  • Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products (August 1999);
  • Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (August 2001);
  • Q8 Pharmaceutical Development (Draft) (February 2005);

References

1. US Food and Drug Administration, Guidance for Industry on Chemistry, Manufacturing, and Controls Information; Withdrawal and Revision of Seven Guidances,Federal Register71 (105), 31194-31195 (June 1, 2006). DOCID:fr01jn06-73. http://a257.g.akamaitech.net/7/257/2422/01jan20061800/edocket.access.gpo.gov/2006/E6-8417.htm

2. http://www.fda.gov/cder/guidance/index.htm.