FDA is putting industry on notice that conventional aseptic processing lines not employing isolators or restricted access barrier systems (RABS) will get heightened scrutiny from agency investigators and that a convincing justification will have to be provided for their ability to consistently produce sterile product.
The agency has been making clear its concerns with the conventional lines during inspections and enforcement follow-up in the injectable arena and will soon be releasing a revision of its aseptic process inspection program to formalize this risk-based focus across its field operations.
During a discussion of regulatory concerns in the aseptic processing arena that capped the late February/early March ISPE Tampa meeting, Center For Drug Evaluation and Research (CDER) compliance official Richard Friedman explained that the forthcoming inspection program revision will direct field investigators to “spend more time on lines that have more contamination risks associated with them.”
Investigators will be directed to “scrutinize them more from a design control operational perspective, with the realization that our historical experience with those lines has been very sketchy,” Friedman commented.
The compliance official pointed out that a review of the recent warning letters reveals that the major aseptic processing observations FDA has been making involve the older lines.
Explaining that he has had the opportunity to participate in reviewing nearly all of the drug GMP warning letters that the agency has issued over the past eight years, Friedman noted that he does not remember “once seeing an isolator being cited as a line found to be non-compliant and out of a state of control. But what we are seeing is old conventional lines which are problematic. And as a result, for our risk-based approach we will require investigators…to focus most on those lines.”
Included on the FDA panel with Friedman to discuss the current aseptic processing regulatory issues and the advancing isolator and barrier technologies were Tara Gooen, who also works in the drug compliance office, and Destry Sillivan from CBER’s compliance office.
Gooen serves with Friedman in CDER’s Office of Manufacturing and Product Quality (OMPQ) and leads the team responsible for evaluating establishments named in applications and their preapproval inspection review. Sillivan serves a similar role in CBER’s DMPQ with responsibilities for preapproval and prelicensing inspections and review of post-licensure compliance actions, as well as development and implementation of regulatory policy.
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