7 CMC guidance documents withdrawn for non-conformity with FDA's GMP initiative.

WASHINGTON -- FDA is withdrawing seven guidance documents for chemistry, manufacturing and controls (CMC), which were drafted before the 2001 Pharmaceutical GMPs for the 21st Century Initiative because they are "not in line with our current thinking," a senior CDER official told the PDA-FDA joint regulatory conference Sept. 26.

Jon Clark, Associate Director for Policy Development and GMPs at the Office of Pharmaceutical Science (OPS), said the documents are:

* Stability (1987 and 1998 draft)

* Drug Product (1987 and 2003 draft)

* Drug Substance (DS) (2004 draft)

* DS Intermediates (2001 draft BACPAC1)

* Synthetic Peptides (1994)

Other changes under way within the agency have to do with the 21st Century Initiative, Clark added. "We still need to adopt an internal quality management system. The existing system relies only on the supervisory chain."

There also has been discussion about possible regulation changes, such as to 211 and GMP. Another possibility is 314.70 Application Supplements. "We want to encourage quality systems as change control."

The agency also is continuing its efforts to join the Pharmaceutical Inspection Cooperation Scheme (PIC/S). There are more similarities than differences with GMP, he noted. The PIC/S application has been submitted and membership is pending.

In new drugs, the CDER official stated that the following efforts are under way:

* Focus on critical pharmaceutical quality attributes and their relevance;

* Rely more on analysis from the applicant and less on reanalysis of raw data;

* New drug CMC implementing risk-based pharmaceutical quality assessment system;

* Encourage new technologies;

* Locate all New Drug CMC together;

* Unit dedicated to manufacturing science; and

* Unit dedicated to post approval changes.

Clark also discussed progress in comparability protocols. A public meeting on the issue was held in February and the following points were made:

* Demonstrate that you understand and know how to control variability in your product;

* Create a control strategy around this knowledge with rational criteria;

* Not manufacturing data; and

* Tell us when you implement the changed strategy.

Clark stressed that the guidance on comparability protocols is the top priority for OPS.

He also noted the difficulty in enacting change within FDA. "The great strength of bureaucratic structure is stability. Any change plan from inside the bureaucracy needs to account for this strength."

The best way to enact change, said Clark, is to form a committee to determine direction. Other than force of direct order, this is the only tool to use at FDA.

By Joseph Pickett

Managing Editor