Happi Staff09.23.20
The US Food and Drug Administration (FDA) has sent a warning letter to Dr. Vishnu Potini, president, HNC Products Inc, following an inspection of its manufacturing facility in Clinton, IL, from March 10 to 17, 2020. The warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, according to the agency.
FDA also said the inspection also revealed that your firm failed to fulfill its registration and listing obligations under section 510 of the FD&C Act, which is prohibited under section 301(p), 21 U.S.C. 360 and 331(p). As a result, your drugs are misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o).
During the inspection, investigators observed specific violations including, but not limited to, failure to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
According to FDA, the firm failed to thoroughly investigate an out-of-specification (OOS) assay test result, a critical product attribute, for one of your sunscreen drug products. FDA, in its letter stated: “Specifically, your investigation into the OOS result for (b)(4) batch (b)(4) lacked critical information in sufficient detail, such as sample and standard preparation, root cause analysis, conclusion of investigation, and corrective action and preventive action (CAPA).”
In addition, FDA said original data associated with the OOS result was overwritten and unavailable for review. FDA noted that the only information available in your investigation was that (b)(4) results were high and OOS. Your rationale for invalidating the test failure lacked a substantive scientific evaluation and did not follow your procedure for investigating OOS results.
Your response acknowledged that you did not have a formalized written review and investigation into the OOS result, and that your procedure lacked a requirement for root cause analysis and CAPA determination. You stated that you updated the (b)(4) method on the software to prevent deleting or overwriting results, although the quality control (QC) manager still retains the ability to do so.
Your response is inadequate because your revised procedure for OOS investigation provided in response to this violation continued to lack sufficient details on how your firm will meaningfully investigate OOS occurrences. We also note that your laboratory manager still retains the ability to delete and overwrite results, which is unacceptable. It is your fundamental GMP responsibility to ensure that laboratory records include complete data derived from all tests necessary to assure compliance with established specifications and standards.
The lack of control over the integrity of your data raises questions about the authenticity and reliability of your analytical data and the quality of your drug products, said FDA.
FDA also said the firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and your firm's quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).
FDA said the firm did not perform process validation studies for its sunscreen products. During the inspection, FDA said the firm was not able to provide documentation that process performance qualification (PPQ) studies had been conducted to establish that your processes are capable of consistently delivering quality product. Furthermore, FDA said the firm did not have an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.
The firm had sent a response that provided new procedure for its process validation, however FDA said the response is inadequate because it failed to include a detailed process performance protocol and actions to identify all sources of variability. Additionally, your response did not provide a timeline for completion of PPQ studies for each of your drug products.
FDA also said the firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).
FDA also said the inspection also revealed that your firm failed to fulfill its registration and listing obligations under section 510 of the FD&C Act, which is prohibited under section 301(p), 21 U.S.C. 360 and 331(p). As a result, your drugs are misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o).
During the inspection, investigators observed specific violations including, but not limited to, failure to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
According to FDA, the firm failed to thoroughly investigate an out-of-specification (OOS) assay test result, a critical product attribute, for one of your sunscreen drug products. FDA, in its letter stated: “Specifically, your investigation into the OOS result for (b)(4) batch (b)(4) lacked critical information in sufficient detail, such as sample and standard preparation, root cause analysis, conclusion of investigation, and corrective action and preventive action (CAPA).”
In addition, FDA said original data associated with the OOS result was overwritten and unavailable for review. FDA noted that the only information available in your investigation was that (b)(4) results were high and OOS. Your rationale for invalidating the test failure lacked a substantive scientific evaluation and did not follow your procedure for investigating OOS results.
Your response acknowledged that you did not have a formalized written review and investigation into the OOS result, and that your procedure lacked a requirement for root cause analysis and CAPA determination. You stated that you updated the (b)(4) method on the software to prevent deleting or overwriting results, although the quality control (QC) manager still retains the ability to do so.
Your response is inadequate because your revised procedure for OOS investigation provided in response to this violation continued to lack sufficient details on how your firm will meaningfully investigate OOS occurrences. We also note that your laboratory manager still retains the ability to delete and overwrite results, which is unacceptable. It is your fundamental GMP responsibility to ensure that laboratory records include complete data derived from all tests necessary to assure compliance with established specifications and standards.
The lack of control over the integrity of your data raises questions about the authenticity and reliability of your analytical data and the quality of your drug products, said FDA.
FDA also said the firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and your firm's quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).
FDA said the firm did not perform process validation studies for its sunscreen products. During the inspection, FDA said the firm was not able to provide documentation that process performance qualification (PPQ) studies had been conducted to establish that your processes are capable of consistently delivering quality product. Furthermore, FDA said the firm did not have an ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality.
The firm had sent a response that provided new procedure for its process validation, however FDA said the response is inadequate because it failed to include a detailed process performance protocol and actions to identify all sources of variability. Additionally, your response did not provide a timeline for completion of PPQ studies for each of your drug products.
FDA also said the firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).
