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As regulators balance pandemic tasks and rethink procedures, quality at manufacturing facilities is still a priority.
The pandemic created many challenges in 2021 for both pharmaceutical manufacturers and regulatory organizations. The quality of pharmaceutical products continued to be a focus, but many facility inspections were postponed in 2020, and FDA officials evaluated their inspection programs during the pandemic and issued guidance for remote monitoring and other virtual activities (1–3). From March 2020 through March 2021, FDA conducted 821 mission-critical inspections (49 for human drugs, 10 for biologics) and 777 prioritized domestic inspections (106 for human drugs, 53 for biologics) (4).
In Europe, there were fewer regulatory inspections in 2020 than in previous years (5). Siegfried Schmitt, vice president, Technical at Parexel, feels the limit on in-person inspections might have a long-term impact on the expertise of quality personnel. “The current pandemic limits the opportunities for in-person meetings, visits, and travel. These have proven to be important elements of professional development, particularly for budding quality professionals, as these allow learning and experiences that cannot be conveyed through virtual/electronic means. This may limit the pool of experienced and seasoned quality and compliance experts in years to come,” he says.
These challenges have made the already difficult task of inspecting facilities more problematic. Regulatory agencies, however, worked to get back on track in 2021 (6).
The pandemic created another complication for regulators: a flurry of companies claiming to sell products to treat or prevent COVID-19. A good number of FDA warning letters listed on FDA.gov in 2021 appeared to be directed at facilities manufacturing hand sanitizer or other COVID-19-related products that were adulterated (7). Quality problems occurring within these companies entering the market showcase some of the problems regulators see in quality departments, according to Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates. “I think many of the observations regarding insufficient quality are directed at this phenomena of companies producing products that are regulated and not understanding those regulations,” she says. Compounding pharmacies also got attention by the agency in 2021, with failures in aseptic and sterile manufacturing procedures a common notation on Form 483s (8–10). Some other common types of citations found in warning letters are listed in Table I.
Schniepp also sees the typical quality problems continuing in the future, including insufficient investigations, a lack of data integrity controls, not having adequate standard operating procedures (SOPs), and not following SOPs. “These issues have been responsible for the majority of observations in the past, and there is no reason to suspect that industry has solved these issues. I think one of the reasons for this situation is the industry doesn’t necessarily change their approach to certain key functions even as products and processes become more sophisticated and outpace a company’s ability to revise documents to keep pace with the product changes,” she says.
One of the common FDA observations in warning letters is the lack of adequate response to FDA 483 notices. “Effectively responding to a 483 and/or warning letter requires familiarity with processes, systems, and data because a proper response should address how you are going to fix the situation observed, how you are going to prevent the situation observed from recurring, and why the situation observed did not impact the patient safety/product quality of the product that was released before the situation was corrected,” says Schniepp. “I think many people forget to include this historical look back. Without this historical perspective, a response will never be sufficient.”
In Europe, Schmitt points to a lack of quality oversight as a quality issue at some facilities. “European agencies expect senior management to actively engage with the quality department and to drive quality and compliance in the company. To that end, a company must be able to demonstrate regular [documented] meetings between senior management and the quality department. In addition, quality and compliance key performance indicators should be in place,” he says.
As regulatory agencies work to combat COVID-19, facility inspections, either performed in-person or remotely, will continue to be one of the tools regulators use to ensure the safety of medicines. Inspections also provide pharmaceutical companies with the information they need to produce the most effective and safe products possible.
1. J. Wechsler, Pharm Tech 45 (11) (November 2021).
2. FDA, Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency, Guidance for Industry (FDA, April 2021).
3. K. Auchincloss, “FDA Inspections During COVID-19: A Brave New World,” PharmTech.com, April 14, 2021.
4. FDA, Resiliency Roadmap for FDA Inspectional Oversite, May 2021.
5. S. Ronninger, A. Kurz, F. Raya, “GMP/GDP Inspections: Challenges and Opportunities Revealed by the COVID-19 Pandemic,” PharmTech.com, Nov. 2, 2021.
6. R. Peters, Pharm Tech 45 (8) (August 2021).
7. FDA, Warning Letters, FDA.gov, accessed Dec. 13, 2021.
8. FDA, ORA FOIA Electronic Reading Room, FDA.gov, accessed Dec. 13, 2021.
9. FDA, Form FDA 483, Atlas Pharmaceuticals, issued June 11, 2021.
10. FDA, Form FDA 483, ACRX Specialty Pharmacy Inc, issued July 23, 2021.
Vol. 35, No. 1
When referring to this article, please cite it as S. Haigney, “Quality Still a Priority,” BioPharm International 35 (1) 38-39 (2022).