Effective March 12, 2004, FDA revised a long-standing policy document
regarding the validation of pharmaceutical manufacturing processes for
drugs that are subject to pre-market approval requirements. This policy
guide is now titled Process
Validation Requirements for Drug Products and Active Pharmaceutical
Ingredients Subject to Pre-Market Approval (formerly titled
Process Validation Requirements for Drug Products Subject to Pre-Market
Approval). Compliance Policy Guides (CPG) are intended for agency
staff and are for the purpose of consolidating agency compliance policy
decisions.
As with the previous version of this policy guide, the new version
reaffirms that agency drug product pre-market review units may approve
applications for marketing before a firm has manufactured one or more
conformance batches at commercial scale (also sometimes referred to as
"validation" batches). The revised CPG again recognizes certain
conditions under which a firm may market batches of drugs while gathering
data to confirm the validity of the manufacturing process.
New to this version is the recognition of the role of emerging advanced
engineering principles and control technologies in ensuring batch quality.
For drugs produced using these new principles and technologies, this CPG
provides for possible exceptions to the need for manufacturing multiple
conformance batches prior to initial marketing. This version also deletes
the previous reference to "three" validation (or conformance)
batches at commercial scale as adequate minimum proof of process validity
- a number is no longer suggested. Also, this version further clarifies
the importance of post-market information gathering especially for those
batches released to market concurrent with the manufacture of the initial
conformance batches. And, finally, this version adds a reference to the
currently recognized standard for CGMPs in the manufacture of active
pharmaceutical ingredients: Guidance for Industry, Q7A, GMP Guidance for
Active Pharmaceutical Ingredients, issued August 2001.
This is an important first step in the Agency's plan to address
the area of process validation. The next step will be to update the Guideline
on General Principles of Process Validation
(May 1987), to reflect modern manufacturing principles, technology,
and science. This update will be revised in accordance with the agency's
Good Guidance Practice procedures and include public notice and comment
before being finalized. The final step of this process will be addressing
the proposed revisions of the CGMPs, the Federal Register dated May
3,1996, Current Good Manufacturing Practice; Proposed Amendment of
Certain requirements for Finished Pharmaceuticals. This effort is
being taken in concert with FDA's initiative on the regulation of
pharmaceutical quality known as "Pharmaceutical cGMPs for the 21st
Century: A Risk-Based Approach." Progress on these issues will
be included in future announcements on the initiative.
