The Day Your Inadequate Quality Control Systems Passed An FDA Audit
May 25th, 2025 // 2:49 pm @ jmpickett
A terrible day for a QA manager is to receive an FDA 483 for inadequate quality control (QC) systems. The Code of Federal Regulations (CFR) Title 21, Part 211.22 states requirements for quality control systems in pharmaceutical manufacturing. Violating this important cGMP regulation means bad news for your company.
Lack of Independent QC Unit
FDA nails pharmaceutical companies regularly for subpar QC systems. For example, my 2024 review of FDA 483s discovered ‘lack of independent quality control unit’ as a regular complaint. One 483 I reviewed stated that the drug faciilty didn’t have a dedicated Quality Control Unit with the authority to approve or reject drug products or APIs. Rather, the production personnel made vital quality decisions without oversight. Such a potential conflict of interest puts that company in FDA’s crosshairs.
Lack of an independent QC unit violates 21 CFR 211.22(a). The regulation requires a QC unit with enough independence to ensure objective quality decisions. Without independence, contaminated or defective products can reach the market.
Optikem International Slammed With FDA Warning Letter in June 2024
A 21 CFR 211(a) violation can lead to more than a 483 – the dreaded warning letter. In June 2024, FDA sent a warning letter to Optikem International, Inc. for major cGMP violations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).
The warning letter states that Optikem did not establish an adequate QC unit with the responsibility/authority to approve/reject all drug product containers, components, in-process materials, closures, packaging materials, labeling, and drug products, and the authority to review production records to assure there were no errors.
The warning letter continues that the QC unit did not use its authorities and responsibilties to implement effective QC procedures and oversight. For example, Optikem’s QC unit did not make sure that data was legible, recorded, original and accurate. The FDA inspector discovered missing original data in the firm’s lab and production violations (21 CFR 211.194 & 211.100).
FDA also found the company did not ensure an adequate stability program was created to support its claimed three-year expiry for ophtalmic drug products (21 CFR 211.166).
Optikem Reponds, But FDA Still Displeased
Optikem responded to the warning letter, but FDA wasn’t happy. The agency stated that the response was inadequate. Here’s why: The company did not provide enough details to ensure data integrity and document control. The response did not have changes to batch record documentation, data management and procedures for qualifying aseptic processing operatings, and with sufficient training.
Solutions
Violations of (CFR) Title 21, Part 211.22 are no joke. But you can avoid FDA 483s and warning letters for QC problems by establishing a truly independent quality control unit. Create a dedicated QC department with strong authority to approve/reject materials, products, and processes. Make sure the quality control unit reports directly to senior managers – not product – to avoid a conflict of interest.
Define the quality control unit’s roles and duties in a written charger, then assign qualified employees with cGMP and quality assurance expertise to the unit. Empower your QC unit to stop drug product or reject batches if the facility fails to meet quality standards.
Inadequate QC systems under 21 CFR 211.22 can trigger serious FDA 483s and warning letters. You can address them by reorganizing your organization, implementing robust QC procedures, and strong oversight.
