Cleaning specialists support safety-based detection limits

East Rutherford, NJ — Advancing automated cleaning or clean-in-place (CIP) technology and closer scrutiny from federal inspectors are prompting some validation specialists to encourage pharmaceutical makers to use safety-based methods to determine contamination detection limits during manufacturing.

“Form 483 observations (used by the Food and Drug Administration to cite deficiencies in good manufacturing practices) spark trends,” says Grant S. Hodgson, a validation and GMP compliance specialist at Raytheon Engineers & Constructors (Philadelphia, PA). “The FDA can only look at one area at a time, and (the agency) is now focusing on cleaning validation.”

Hodgson told attendees at the ISPE`s December seminar on cleaning technology and validation that as product manufacturers start to learn more and enhance their processes, FDA officials expect more. He says that requires making conservative choices to reduce chemical contamination in product batches.

At present, there are three primary methods for identifying limits or determining how much of a product can be detected in the next batch. Type 1 involves limits associated with the pharmacological properties of the active(s); Type 2 consists of limits associated with the percentage of contamination; and Type 3 encompasses process-capability limits, including visual and analytical detection levels.

“The trend is to get away from percent contamination and process capability-driven limits and move toward limits with safety factors,” Hodgson says, noting that he and his Raytheon associates are now suggesting that companies consider Type 1 when revalidating.

Type 1 provides a residual limits formula that considers the contaminant`s nature, dosage and patients` health, according to Hodgson. While the utilization of safety-based factors is not a regulatory requirement, he adds it is becoming the preferred method of limit detection.

Dan Dobrez of the Dober Group, a supplier of chemicals and CIP systems, concurs with Hodgson`s assessment. “With the trend from the FDA, I`ve seen more emphasis on Type 1,” he says. “It`s just common sense.”

However, he cautions that Type 3 also needs to be included in cleaning validations. “Visual inspection is always a good check even when you have a validated system. If something happens, like a pen falls in a tank, you can go in and see what happened or what the problem is. I think you need both.”