10 firms piloting PAT, QbD, including 2 generics makers; March 2006 deadline imposed for participation.

SAN FRANCISCO -- About 10 companies, including two manufacturers of generic drugs, are participating in the Center for Drugs CMC pilot program, whereby "quality by design" (QbD) is to be achieved by companies disclosing early developmental data in an effort to accomplish "design space" for NDA reviews.

Office of New Drug Quality Assessment (ONDQA) Director Moheb Nast, Ph.D., told a California Separation Science Society (CaSSS) meeting here Jan. 24 that the pilot program's aims are to implement QbD, to evaluate elements of the new pharmaceutical quality assessment system (PQAS) approach, provide a mechanism for feedback from industry and the public, and to establish metrics for evaluating the quality of submissions and assessment.

He said FDA would like industry to make a request to participate by March 31, 2006, and to submit an NDA or supplemental NDA by the end of March 2007.

At the IFPAC meeting Feb. 22, it was revealed that 10 companies have signed up for the pilot, and that two are generic firms: Watson Labs and Alpharma.

Kevin Charrier, director of quality services at Watson, Corona, CA, said his firm decided to enter the pilot after trying internally to see if they could find failures in active pharmaceutical ingredients to meet specifications real-time controls on the manufacturing floor. Charrier said the hope was whether Watson could use this means to avoid having to "wait three weeks for the lab" to determine if the ingredients were in spec and use statistical process controls (SPC).

Watson used hardness and thickness as a measure, because that's what it could do on the floor.

The results did not provide anything meaningful, he said. "From our perspective, we don't think we're gathering the critical data on the floor to be able to a allow us to enter an SPC program of what we tried to do in first place, which is to put real controls on the manufacturing floor. Our existing, in-process measures are a poor indicator."

To make the program meaningful, Watson decided to enter the FDA pilot. Charrier said Watson is trying to establish a "continuous data-collection, monitoring stream around critical quality attributes and critical process attributes."

"We're not back at square one, but at least we know we have to go in a different direction," he said.

He said the assessment will be conducted by a team of "experienced reviewers with good understanding of the new PQAS and strong background" in pharmaceutical development and manufacturing processes. Nast said he, personally, will oversee the team reviews.

He sensed continued reluctance by firms to participate with FDA in the pilot due to the need to divulge details of manufacturing issues, some of which firms were never aware of before. Nast commented: "FDA is changing while industry is waiting!"

Nasr reminded the audience that PQAS will only impact the biotechnology NDAs submitted through CDER including chemically synthesized peptides and oligonucleotide hormone products, regardless of source. But products currently covered under BLA within CDER's Office of Biotechnology Products are not included.

These are: monoclonal antibodies for in vivo use; cytokines, growth factors, immunomodulators and thrombolytics; therapeutic proteins, extracted from animals or microorganisms, except clotting factors; other non-vaccine therapeutic immunotherapies; vaccines, cellular products, for transplantation or vaccination; and, blood, blood components and plasma-derived products.

By Mike Faden and Ken Reid

Validation Times Staff