FDA warns German OTC firm, Chinese API maker for lax cleaning practices, other GMP issues

Regulatory NewsRegulatory News | 28 September 2022 |  By 

A German manufacturer of OTC products and a Chinese supplier of active pharmaceutical ingredients (APIs) were told to adopt better equipment cleaning practices in recent warning letters from the US Food and Drug Administration (FDA). The letters, posted on 27 September, also identified a slew of other current good manufacturing practice (CGMP) violations.
 
The first warning letter, to System Kosmetik Produktionsgesellschaft fur kosmetische, located in Munster, Germany, found deficiencies in three areas: cleaning equipment, testing of incoming ingredients and computer access controls.
 
Investigators lambasted the firm for a shoddy approach to cleaning validation. “Your OTC drug products … are manufactured on the same equipment used to manufacture non-pharmaceutical products,” including ointments and other products, said FDA.
 
FDA warned that “it is unacceptable as a matter of CGMP to continue manufacturing drug products using the same equipment that you use to manufacture non-pharmaceutical products.”
 
The firm also failed to test incoming APIs used to manufacture drug products. “Our investigator observed that your firm released [redacted] API for use in manufacturing without an identification test for [redacted]. Identity testing is required for each component lot prior to use in drug product manufacturing, and you can only rely on a Certificate of Analysis (COA) for other component attributes though validation of the supplier’s test results at appropriate intervals,” FDA wrote.
 
The firm also failed to have adequate electronic controls in place, such as having unique usernames and passwords for each analyst accessing the Fourier Transform Infrared Spectrometer (FTIR) system.
 
In addition, the audit trail function was disabled, even though the FTIR system is routinely used for raw material and finished product testing.
 
FDA told the firm that failure to address the violations cited in the letter may result the agency withholding approval of new applications. The agency may re-inspect to verify that the corrective actions have been taken.
 
Similar cleaning problems found at Chinese API firm
 
Similar equipment cleaning lapses were observed by investigators in a warning letter to API maker Zhejiang Tianyu Pharmaceutical located in Taizhou City, China.
 
This company was one of the first worldwide to recall lots of valsartan due to the presence of nitrosamine impurities found in blood pressure medicines in 2018. (RELATED: EMA Warns of Impurity in Valsartan From Mylan, Regulatory Focus, 19, November 2018)


FDA investigators observed brownish rust like spots on the upper walls of product contact surfaces “with layers of thick black spots above the brownish spots.” Yet the equipment was deemed as ready to produce the next batch.
 
The company attributed the problem to “damaged or worn-out” equipment which caused metal to leach into products being synthesized.
 
FDA pointed out that this deficiency is a repeat deviation from an earlier inspection in 2019 when the firm failed to complete cleaning validation studies prior to releasing batches from 2021 to 2022.
 
The firm was also criticized for failing to establish an impurity profile for identified and unidentified impurities. For example, on 25 November 2021, there was a consumer complaint regarding an impurity found in the starting material. The company failed to identify the impurity as a by-product of the starting materials. It also “did not evaluate all [redacted] source impurities that may carryover from starting materials which could impact the efficacy or safety of the drug product.”
 
FDA observed that similar GMP observations were identified in an April 2019 inspection and that “repeated failures to address deficient operations demonstrate that executive management oversight and control is inadequate.”
 
Failure to address these violations may prompt the agency to withhold export certificates or withhold approval of new applications and supplements listing the firm as a manufacturer, FDA said. The firm was also advised to hire a GMP consultant.
 
Zhejiang Tianyu warning letter
 
System Kosmetik warning letter
 
 
 

 

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Tags: FDA, GMPs, letters, warning

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