Pharma Consulting Group International (PCGI)

Recently published Warning Letter to a foreign drug manufacturing facility provides a summary of signification cGMP violations. The letter starts by citing the failure of the Quality Unit to ensure reliability of the GMP data and that employees understand and adhere to data integrity principles. Specifically, during the inspection, torn batch production records were found in plastic bags in the rooftop and management admitted to “retrospectively” prepare batch production records for the investigators. Similarly, laboratory records lacked raw data to support testing of released drug products.??While the firm-initiated deviations and hired a third-party consultant, the agency found the response inadequate and requested (1) a comprehensive data integrity remediation program and (2) for Executive management to assess the operations to ensure systems, processes, and products conform to FDA requirements. At PCGI, we assist our clients with the implementation of data management programs to ensure the reliability and completeness of the GMP data. These programs include a periodic verification to ensure sustainability and to be inspection ready. Contact me today. www.pharmacgi.com #GMP, #FDA, #WL, #Dataintegrity, #Qualityunit

Recently published warning letter cited the 21 CFR 211.84 requirements for the testing and approval or rejection of components, drug product containers and closures.?Specifically; ? Each component shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a report of analysis (COA) may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer and ? the manufacturer must establish the reliability of the supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals. While the requirement to perform identity test for each lot of components is straight forward, the interval for the validation of the supplier test results is left to the manufacturer to define and implement.? In an absence of regulatory guidance, at PCGI, I suggest to clients to implement a process that is consistent with the principles of CGMP and risk management. Questions: Is your firm in full compliance with the 21 CFR 211.84 requirements? What is the approach and frequency for the verification of the supplier’s test results ?

A committee from the U.S. House of Representatives recently conducted an analysis of the FDA’s foreign drug inspection program, focusing on outcomes in India and China from 2014 to 2024. The findings revealed significant variation in inspection outcomes, indicating differing levels of inspector skill and thoroughness. There are concerns about possible bribery or fraud affecting these outcomes. The committee has requested the FDA to provide more information for evaluation. www.pharmacgi.com Feel free to share your thoughts on the letter and the issues raised. #FDA #DrugInspections #ForeignInspectionProgram #USHouseCommittee

USFDA has identified an increase in submissions containing unreliable data generated by third-party test labs resulting in rejection or delay on the approval of new devices or drug products. As registered firms, it's crucial to qualify third-party test labs and closely scrutinize all testing data that a firm does not perform itself, especially relating to biocompatibility and other performance testing, that are included in a submission to the FDA. While it may be difficult for firms to know if certain data have been compromised, the FDA expects firms to identify testing results that are improbable or impossible or do not seem consistent with known information about the product. PCGI can assist clients with the implementation of robust supplier management programs including 3rd party labs providing testing services. These programs include initial assessments followed by periodic reviews and on-site audits. Contact us today to ensure your submissions are reliable and approved. #FDA #suppliermanagement #thirdpartylabs

India’s Natco Pharma was hit with a USFDA Warning Letter resulting from an inspection of the Kothur facility in India back in October 2023.??The eight 483 observations centered on a lack of cleanliness of equipment and utensils to prevent contamination with inspectors referencing data that revealed the presence of different drug substances as high as up to about 800 times the acceptance limit and swab samples taken by inspectors showed the?potential for cross-contamination. Additional observations included not having written responsibilities and procedures for the quality control unit, lacking procedures to prevent microbiological contamination, failing to review unexplained discrepancies of batch failures and other record-keeping problems including the destruction of original records and raw data. https://lnkd.in/gck5HFFv ?? At PCGI we assist our clients with the implementation of comprehensive corrective actions to address 483 observations. Contact us today.??www.pharmacgi.com #USFDA #WL #483 #IndiaPharma

Tips to ensure responses to FDA 483 inspectional observations are complete to prevent a follow up Warning Letter (WL). ? (1) Ensure responses are complete with the necessary supportive documentation. If a procedure was updated, indicate what was updated and provide a copy of the revised procedure. If studies were conducted, provide a summary in the response and attach copies of the executed protocols and reports. ? (2) For corrective actions that will not be completed prior to the response submission, provide a justification and a timeline for completion. Submit periodic updates until the actions are completed. If possible, provide evidence the corrections were systemic in approach and effective. WL statement: The adequacy of your firm’s response cannot be determined at this time. The response notes that you have undertaken corrective actions however the response does not furnish specific information regarding the results or outcomes of these corrective actions as they are still ongoing. ? (3) Consider the observation's compliance and patient risk, ensure the proposed actions are aligned with the identified risk and take the proper market action when required. ? WL statement: Your response also states you have ceased purchasing syringes however, you have not acted sufficient to mitigate the risks for US consumers. For example, you have not committed to recalling and/or removing these violative syringes on the US market. Therefore, the proposed corrections are inadequate. ?? At PCGI we assist clients with the implementation of GMP regulatory compliance programs that include the analysis of enforcement actions for an effective inspection readiness strategy. Contact me today.?www.pharmacgi.com #FDA #WL #Enforcement #483response

A recently published FDA Warning letter cited the company for (1) failure to conduct at least one test to verify the identity of each component of a drug product and (2) failure to validate the reliability of the data provided by supplier.? ? Per 21CFR211.84 - each component batch must be tested for conformity with all appropriate specifications for identity, strength, quality, and purity. If relying in supplier’s Certificate of Analysis (COA), there must be a robust process in place to validate the reliability of the results provided by the supplier. Even when relying in the supplier COA, firm must conduct at least one specific identify test for each incoming component batch. ?? At PCGI, we assist clients with the implementation compliant processes for the evaluation of drug components. Contact me for further details. www.pharmacgi.com. #USFDA #Component #drug #Supplier

Complete testing of each batch of drug product before release is required to determine if the drug product meet appropriate specifications (reference 21 CFR 211.165.a). USFDA inspectors continue to identify CGMP violations during site inspections. ? A recent warning letter citation state .. Your Quality Unit (QU) approved drug products for distribution without complete finished product testing. For example, your firm shipped?(b)(4)?to your customer on September 11, 2023. However, the analytical and microbial test results were not reported in your batch record. Your QU approved the release of this batch on September 8, 2023. During the inspection, your firm could not provide the test results.? ?? At PCGI, we assist clients with the implementation of effective and compliant QMS. Contact me today. www.pharmacgi.com #fdacompliance #Warningletter #CGMP #Testing #Drugs #Release

The USFDA Warning Letter highlights the importance of contemporaneous entry of CGMP activities. Non-contemporaneous documentation on laboratory worksheets raises concerns about the validity and integrity of laboratory testing records. PCGI can assist clients in implementing effective strategies to manage data integrity risks. Learn more at www.pharmacgi.com. #dataintegrity #CGMP #ALCOA+ #pharma #manufacturing