Team, systems audits, Hazard Analysis Critical Control Point [HACCP] seen for drugs under Good Manufacturing Practices initiative.

Team inspections--fashioned after "Team Biologics" audits conducted by the Center for Biologics--could become the norm for makers of human and animal drugs, as well as biotech products, under FDA's "Pharmaceuticals for the 21st Century" initiative announced Aug. 21, but medical device quality system and Hazard Analysis Critical Control Point (HACCP) approaches could be in the offing, too.

The initiative, to be spearheaded primarily by the Center for Drugs (CDER), also is designed to update FDA's 24-year-old drug GMP rules (21 CFR Parts 210, 211), which were proposed for rewrite in May 1996, but never rendered final. The initiative comes in the aftermath of high-profile GMP-related problems at companies such as Abbott, Schering and Eli Lilly.

However, FDA hopes to reassess its inspection program too, and make inspections more focused on risk. The initiative calls, in part, for:

* Enhancing the scientific approach of GMPs to emphasize risk-based control point analysis and to facilitate the latest innovations in pharmaceutical engineering.

* Allowing certain changes in the manufacturing process without prior review/approval (e.g., comparability protocols).

* Having Centers provide a scientific and technical review of all drug GMP warning letters.

* Including product specialists, as needed, as a part of inspection teams.

* Evaluating optimal mechanisms to effectively and efficiently communicate deficiencies to industry, including content, consistency, disclosure and education.

* Developing a technical dispute resolution process that integrates technical experts from the Centers and addresses perceived inconsistencies between Centers.

* Emphasizing a risk-based approach in the work planning process.

* Improving operations of Team Biologics. While FDA will maintain the "systems based" approach that was piloted in 2001 and which is now the norm, CDER may create "specialized cadres" of expert field auditors to examine human and veterinary products, CDER Director Janet Woodcock, M.D., said in an interview.

She predicted that during the two-year GMP appraisal period--which expires in August 2004--CDER and the Center for Veterinary Medicine (CVM) will be "developing specially trained cadres of field inspectors."

While Woodcock said "we have to evaluate that," and acknowledged Team Biologics' value has not yet been determined by the agency, she said the approach of having a team of field-based experts involved in all drug GMP audits is being strongly considered for human and animal drugs.

Team Biologics was created in 1997 for plasma derivatives, source plasma, biotech and vaccines. The approach put inspections under the rubric of FDA's Office of Regulatory Affairs (ORA), rather than the Center for Biologics (CBER). ORA created a team of 17 field-based investigators who handled all the inspections, but with CBER staff and other specialists. As many as six FDAers have been involved in some audits, though CBER has cut that down in recent years due to industry complaints.

In January, CBER Deputy Director Mark Elengold said "the jury is still out" on whether Team Biologics was a success, yet Woodcock said CDER would consider emulating it for drugs.

Woodcock said "systems-based inspections" would be here to stay. "We're trying to get a more comprehensive idea of the state of compliance in a company, which is good," she said. "Everyone likes it. It's been very useful."

She also said the GMP reassessment would focus not so much on making a final cut on the May 1996 rewrite, but doing "benchmarking" on other approaches. Two, she mentioned, were the device Quality Systems (QS) regulation and the approach of preventing manufacturing quality problems via HACCP.

Woodcock said the agency would examine the applicability of HACCP, though she acknowledged "you just can't plop it down everywhere in the drug industry." There was initially resistance to HACCP when offered to device firms in 1998, but since that time, the device industry has taken great interest in this approach.

By and large, because the 1996 QS regulations mandate corrective and preventive actions (CAPA), management reviews, purchasing controls and a bevy of other rules that the 1978 GMPs do not have.

Carmen Medina, a former FDA inspector and now president of Precision Consultants, a San Diego, CA-based GMP consulting firm, said in an interview "it would be great to have the biologics and pharmaceutical regs catch up with the medical device regs."

Calling QS "the most enlightened regulation ever written," Medina said it would be wise for FDA to "codify these things and mandate the [drug and biologics] industry do things in a certain way."

Given advances in drug discovery technology and the increased use of contractors, Medina said the drug GMPs have no "muscle" for supplier and vendor qualification, management reviews or even much guidance on annual product reviews.

Woodcock noted that one major benefit of the QS approach is its stress on "management reviews" and making upper management responsible for a company's overall quality program.

"We agree that the focus on quality is the responsibility of upper management," she said, adding this is part of "corporate responsibility."

She said another rationale for moving to a risk-based and team approach toward auditing is that FDA consistently fails to meet its inspection targets. Despite a massive infusion of funds for bioterrorism this year, Woodcock said FDA might not carry out the inspections of drug firms it had hoped to do.

Part of the reason for moving away from rulemaking is to allow flexibility among drug firms and not to have a system where FDA dictates what constitutes compliance.

The proposed initiative and memos to FDA staff are $5 plus retrieval, Doc. 11850W.