Mock sheets and lack of stability data: US FDA hits two API makers with warnings

By Dan Stanton

- Last updated on GMT


Related tags High performance liquid chromatography

The US FDA has issued warning letters to two API makers found to have deviated from cGMP: Germany’s BBT Biotech and China’s Tai Heng Industry.

Following an inspection at BBT’s active pharmaceutical ingredient (API) facility in Baesweiler, Germany, last May, the US Food and Drug Administration (FDA) has issued the firm with a warning letter citing a number of significant deviations from current good manufacturing practice (CGMP).

Among the issues raised, the FDA said BBT failed to follow a documented, on-going stability testing program to monitor the stability characteristics of API, which could have had implications on the storage conditions of the APIs produced.

“For example, since January 2012, you shipped approximately (b)(4) batches of (b)(4) API to the United States for which you have no stability data to support your expiration dates,”the letter​ stated. “Without stability data for your API, you could not assure that your API met specifications when used by your customers.”

The Agency also noted the firm’s failure to establish and follow a change management system which it says could affect the quality of API.

“You did not provide change management documentation or any other documentation for these supplier changes. Without adequate evaluation for critical raw material changes, you could not assure the acceptability of your API manufactured using materials from different suppliers.”

Other deviations included BBT’s failure to adequately investigate out-of-specification in-process control testing results, and issues surrounding access to the firm’s computerised systems.

BBT was unable to provide comment about the warning to in-Pharmatechnologist at the time of going to press, as the firm is currently preparing for another regulatory inspection, a spokesman said.

But according to the FDA letter, BBT has already implemented some measures to address the problems, including the commitment to follow SOPs and perform required stability testing on future batches, and the hiring of a third-party expert to install audit trails and other controls to ensure data cannot be deleted from the firm’s electronic system.

Tai Heng Industry

The FDA has also published the warning letter​ sent to Shanghai, China-based API maker Tai Heng Industry, also subject to an inspection last May.

The Agency noted Tai Heng failed to investigate out-of-specification results with atypical results not being investigated or included in official laboratory control records.

Data issues were also high-lighted including failures in preventing unauthorised access or changes to data:

“Specifically, your Quality Control (QC) analysts used administrator privileges and passwords to manipulate your high performance liquid chromatography (HPLC) computer clock to alter the recorded chronology of laboratory testing events.”

Furthermore, the API maker was accused of using copies of the uncontrolled copy of the master production records – or ‘mock’ sheets - to capture and backdate critical manufacturing data.

“Our investigator noted discrepancies between the “mock” sheets and the complete batch production record that your firm represented as the official record for that lot. Because of your uncontrolled documentation practices, you could not produce evidence that your batch production records were accurate.”

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