PDA 2025: How Strategic CAPA Builds Anti-Fragile Manufacturing Compliance

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The issuance of an FDA Form 483 during an inspection represents a pivotal moment for biomanufacturing firms. These forms signal significant conditions that, in the judgment of an investigator, "are considered violations of the regulations and requirements." For experts in drug development and manufacturing, how a company addresses a Form 483 observation is critical; it establishes the "first impression" of how findings are handled and offers "an opportunity to visually demonstrate [a] site’s quality culture, [a] company's quality culture, and how seriously [the company] takes the findings,” Captain Tara Gooen Bizjak, associate director, GMP and Quality Standards, Office of Manufacturing Quality and Center for Drug Evaluation and Research Office of Compliance, FDA, and an engineering officer in the US Public Health Service, said at the Parenteral Drug Association (PDA) Regulatory Conference 2025 this week (1).

In her presentation, “Responding to Inspection Findings with Effective CAPA Strategy,” on Sept. 10, Gooen Bizjak emphasized that this response is a "core part of [FDA’s] evaluation" prior to case classification, helping the agency understand how problems are grasped and addressed (1).

The ultimate aim for companies involved with biopharmaceutical manufacturing should be to develop an "anti-fragile" quality system—one that gets stronger from stress and chaos, Gooen Bizjak noted. Having this approach in mind encourages manufacturers to view inspectional findings not as setbacks, but as catalysts for strengthening their operations, she explained.

Just as a "healthy immune system would get stronger after fighting infections", a robust quality organization can emerge stronger from problems identified through audits or inspections. This proactive stance provides a competitive advantage, transforming quality into a value driver rather than a mere cost center. Manufacturers must cultivate a "prevention-focused" approach that consistently yields compliance, moving beyond the reactive, inconsistent adherence seen in some operations, Gooen Bizjak stated.

How can manufacturers understand FDA 483 responses to establish their own strategic imperatives?

An effective Form 483 response is founded on strong leadership and a comprehensive corrective and preventive action (CAPA) strategy, Gooen Bizjak stressed in her talk. She pointed out that leadership must clearly demonstrate ownership of quality by actively engaging in understanding observations, allocating resources, and providing sustained support for remediation efforts. Establishing such ownership over quality necessitates an executive summary that showcases commitment coupled with a comprehensive risk assessment that considers patient and product impact. Such commitment translates to a deep understanding of the product, process, and systems, enabling a truly strategic approach that addresses deficiencies at their core, Gooen Bizjak said.

Furthermore, investigations must be methodical, minimizing bias and testing hypotheses scientifically to identify true root causes, not just symptoms. As Gooen Bizjak explained, a comprehensive scope means looking for related trends, system-wide implications, and considering quality culture improvements—moving beyond simple solutions such as retraining, as "it's never just retraining; there's always another element to it."

How can manufacturers optimize CAPA implementation in biopharma production processes?

Gooen Bizjak emphasized that the CAPA plan itself must directly "address true root causes, not just symptoms," with actions proportionate to identified risks, covering all affected areas, and incorporating interim protective measures with clear success metrics. Robust effectiveness monitoring is non-negotiable, she said, extending beyond routine testing to include performance trend analysis, process capability studies, and cultural assessment metrics.

Maintaining robust monitoring thus ensures the health of the CAPA system and contributes to sustained product quality, Gooen Bizjak pointed out. Such common pitfalls as minimizing scope, implementing "quick fixes," setting unrealistic timelines, or failing to provide evidence for commitments can lead to defects, regulatory actions, and business failures (2). As such, "less capable operations will continue to receive increased inspectional and compliance scrutiny," Gooen Bizjak stated.

How should leadership commit to accountability and compliance to drive quality excellence?

Management accountability is central to sustainable compliance, Gooen Bizjak stated as she explained that leaders must be engaged, understand all observations and risks, and provide sustained support for remediation. The individual signing the 483 or warning letter response must possess the authority to implement commitments. In instances of scientific or technical disagreements during an inspection, firms should seek clarification with the investigator, document discussions thoroughly, and engage respectfully.

In the formal response, Gooen Bizjak added, companies can clearly describe contested facts, provide scientific data, and reference applicable regulations and guidance. Ultimately, "the foundation of compliance is an ongoing commitment to quality assurance," she said. By evaluating current response capabilities, developing comprehensive procedures, training cross-functional teams, and implementing effectiveness monitoring, biopharmaceutical manufacturers can lead the way in building sustainable compliance and can transform challenges into opportunities for system strengthening and consistent delivery of high-quality drugs.

The PDA Regulatory Conference 2025 was held on Sept. 8–10 in Washington, D.C.

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References

1. Gooen Bizjak, T. Importance of the FDA-483 Response: Building Sustainable Compliance Through Strategic Communication. Presentation at the PDA Regulatory Conference 2025, Washington, D.C., Sept. 8–10, 2025. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://80a7ba3d04f8b71aa576-301909dc4570c350a1649a6d39e3ef3b.ssl.cf1.rackcdn.com//3176867-802448-001.pdf
2. The FDA Group. 5 Common Mistakes to Avoid in Your FDA 483 Response. Blog post, thefdagroup.com, March 25, 2016 (accessed Sept. 11, 2025).