News from the USA: BACPAC I now approved

GMP News No 105

GMP News
3 April 2001

Changes concerning active ingredients
News from the USA: BACPAC I now approved

The Guidance for Industry BACPAC I: Intermediates in Drug Substance Synthesis, Bulk Actives Post-approval Changes: Chemistry, Manufacturing, and Controls Documentation, published in draft form in November 1998, has now been approved in its final version by the Food and Drug Administration (FDA) and has been in effect since February of this year.

BACPAC I gives recommendations for dealing with changes of manufacturing site, batch size, equipment, specifications and manufacturing processes in the manufacture of synthetic active ingredients and for the synthetic manufacturing steps for active ingredients obtained by semi-synthetic means.

Any change in the manufacturing method of active ingredients harbors the risk that the quality of the final product may be changed, e.g. the physical properties of the active ingredients (e.g. polymorphy) or the contamination profile. The risk here that the quality of the final product will be influenced is greater the later in the manufacturing process that this change is made. The core of the BACPAC guide is the following decision tree, which defines the area of application of BACPAC.

(from: Guidance for Industry, BAPAC I: Intermediates in Drug Substance Synthesis, Attachment A: BACPAC I Decision Tree; February 2001)

BACPAC refers in its turn to the following additional guides:

  • Changes to an Approved NDA or ANDA, CDER, November 1999.

  • Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products, Center for Biologics Evaluation and Research (CBER) and CDER, July 1997.

  • Draft - Chemistry, Manufacturing and Controls Changes to an Approved NADA or ANADA, CVM, June 1999 (notice of availability published in the Federal Register on October 1, 1999 (64 FR 53281)).

  • Submitting Supporting Documentation in Drug Applications for the Manufacture of Drug Substances, CDER, February 1987.

BACPAC I applies to

  • NDAs (new drug applications)
  • ANDAs (abbreviated new drug applications)
  • NADAs (new animal drug applications)
  • ANADAs (abbreviated new animal drug applications)
  • DMFs (drug master files)
  • VMFs (veterinary master files).

and can be downloaded from the following address:

In view of other changes concerning active pharmaceutical ingredients we would like to draw your attention to this year's 4th APIC/CEFIC European Conference on Active Pharmaceutical Ingredients which is to take place in Vienna from September 26 - 28, 2001. This year's conference will include a GMP and a regulatory affairs segment.

From FDA Dr. Yuan-yuan Chiu has already agreed to speak on the topic of "New developments of post-approval changes". In addition to BACPAC, of course the GMP Guide ICH Q7 and TSE and falsification of active ingredients will be an important topic.

In this year too the European Chemical Industry Council (CEFIC/APIC) will be organizing this event and has invited both European and North American opinion-makers to Vienna. This year service providers will have the opportunity for the first time to take part to a limited extent in an integrated exhibition.

Click here to find out more.


Go back

GMP Conferences by Topics