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Regulatory Focus™ > News Articles > 2020 > 9 > FDA warns firm: Test batches before, not after release

FDA warns firm: Test batches before, not after release

Posted 08 September 2020 | By Kari Oakes 

FDA warns firm: Test batches before, not after release

An Indonesian firm was warned by the US Food and Drug Administration (FDA) for failures in product testing and method validation, among other breaches of current good manufacturing practice (CGMP).
In a November 2019 inspection of PT. MegaSura Mas, FDA inspectors found that some assays conducted for batch releases of an over-the-counter product were performed after the batches were released. “This discrepancy on batch release documents demonstrates a concern regarding the validity in your CGMP records,” wrote FDA in the warning letter dated 24 August 2020.
According to the warning letter, the firm also used an assay testing method for the active ingredient in the finished product that was not a US Pharmacopeia (USP) method, nor was it validated by high-performance liquid chromatography. The product produced by the firm was redacted in the letter.
Another shortcoming identified by the inspectors was a failure to conduct “at least one test to verify the identity of each component of a drug product;” instead, said FDA, PT. MegaSura Mas relied on certificates on analysis from suppliers of active pharmaceutical ingredients (APIs). Inspectors also found that the firm was using a cleaning program that had not undergone validation.
The quality unit maintained by PT. MegaSura Mas had multiple shortcomings, according to FDA inspectors. Mater Bath and batch records were lacking, as were laboratory controls for computerized systems; the unit also did not have procedures to evaluate discrepancies and out-of-specification results.
Finally, said FDA, the firm’s stability program lacked protocols for accelerated and long-term stability testing.
FDA noted that many of PT.MegaSura Mas’ responses to deficiencies identified in the inspection did not include plans for testing reserve samples to support the quality and purity of already-released batches. The agency recommended that the manufacturers retain a CGMP consultant to assist with formulation of corrective and preventive action (CAPA) plans.
In another warning letter, FDA cited California-based Calvin Scott & Company for deficiencies found during a March 2020 inspection of the firm’s Albuquerque, N.M. plant.
Calvin Scott & Company repackaged hydrochlorothiazide tablets into heat-sealed pouches with one transparent side. This was a problem, said FDA, because “Your firm does not have stability data to support the expiration dates you assigned to this repackaged drug product. The manufacturer’s container requires that the drug product be dispensed ‘in tight, light-resistant container as defined in the USP.’”
Though the firm agreed to discontinue using those particular heat-sealed pouches and test for light protection, as well as to conduct a recall of the products issued in the semi-transparent pouches, FDA termed this response inadequate. The agency is asking the firm to address “other vulnerabilities,” including moisture vapor and oxygen transmission, as well as compatibility of the container-closure system with the hydrochlorothiazide tablets.
The firm had not established a dedicated quality control unit, said FDA: "Multiple personnel in your manufacturing operation had the authority to perform quality control unit responsibilities, including release of drug products for distribution.
“However,” said the agency, “there is no assurance that you have appropriate separation of approval or rejection authority for final drug product release from personnel performing repackaging operations." 

Inspectors also turned up problems with cleaning and repackaging procedures that opened the possibility of cross-contamination.

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