The Center for Biologics Evaluation and Research (CBER) released in June a revised version of its Compliance Program Guidance (CPG) 7345.848, “Inspection of Biological Drug Products,” which combines and replaces previous versions of CPGs covering related biological products and provides inspectional guidance to investigators for conducting biennial or for-cause inspections across the biologics spectrum.
The new umbrella CPG, which became effective on January 1, 2010, supersedes the CPGs for licensed allergenics (7345.001), licensed vaccines (7345.002), plasma derivatives (7342.006) and therapeutic drugs (7341.001).
The new compliance program clarifies that the firms it covers include:
● all licensed manufacturers of vaccines and related products, including source material manufacturers and licensed bulk manufacturers
● all licensed manufacturers of allergenic products (allergenic patch test manufacturers are not included)
● unlicensed source material suppliers
● all licensed manufacturers of fractionated products
● certain recombinant products, and certain human cell, tissue, and cellular and tissue-based products (HCT/Ps) regulated as drugs, and/or biological products.
A list of the 21 CFR regulations applicable to the products these firms manufacture is included.
The CPG provides inspectional guidance to investigators assigned to perform biennial or for cause inspections of the manufacturers covered and provides administrative/regulatory guidance for compliance officers and investigators.
General inspection information not new to this revised version is included – for example, regarding systems-based inspections and what key elements should be covered in each of the six systems when evaluating overall compliance.
Part V, “Regulatory/Administrative Strategy,” covers the decision-making process for recommendation of regulatory actions against noncompliant firms and factors that are unique to biologics to take into consideration.
This section of the document states that “because the number of manufacturers of biological drug products (vaccines, allergens, etc.) is often small, medical need and relative availability of the product(s), as well as the potential adverse effect of the CGMP deficiencies on the finished product(s) should be considered when determining the appropriate advisory, administrative or judicial action.” It further lists various types of deficiencies and the recommended resulting regulatory actions that should follow, ranging from a warning letter to license revocation or suspension, seizure, injunction, and prosecution.