FDA Highlights Aseptic Processing Pitfalls at PDA/FDA Conference

At the 2026 PDA/FDA Joint Regulatory Conference, Jason F. Chancey, PharmD, consumer safety officer in the Office of Manufacturing Quality within FDA's Center for Drug Evaluation and Research Office of Compliance, presented "Sterile Facility Trends: Insights and Modernization Opportunities," at which he paired core design principles for aseptic processing with real-world examples of facility and behavioral shortcomings the agency has observed during inspections.¹

What design principles guide modern aseptic processing facilities?

Dr Chancey outlined design principles for modern aseptic facilities, including optimizing cleanroom layout, operational space, air volume, and material and process flow; protecting the aseptic line with robust isolator or barrier technology to prevent ingress of lower-quality air into the ISO 5 (Class 100) area; minimizing exposure of sterile product components to contamination hazards; and limiting or eliminating manual manipulations through automation and integration.¹ He contrasted a 20th-century approach built on manually intensive unit operations and partial barriers with a 21st-century approach built around automation, integration, and physical separation.

The modern 21st century approach places emphasis on open-air laminar flow hoods and open and closed restricted-access barrier systems (RABS) as well as open and closed isolators. Dr Chancey noted that RABS represents "today's typical minimum level of separation" in current aseptic operations.¹^,² He also presented illustrative data suggesting process error rates can decline from roughly 2% toward 0% as automation increases, underscoring the rationale for automating manual steps wherever feasible.¹

What facility maintenance failures did FDA inspectors find?

Using inspection photographs to show how facility maintenance can undermine even well-designed barrier systems, Dr Chancey highlighted examples such as detached tape used to secure a diffusion membrane inside a barrier system and an inflatable isolator door gasket repaired with tape rather than replaced. Other maintenance examples included foam cuffs and tape found inside isolators, nonfunctional pressure-differential gauges observed during active batch manufacture, discoloration on a diffusion membrane directly above filling equipment, and silicone bellows found improperly positioned with unexplained discoloration.¹

Dr Chancey also flagged behavioral and design lapses on the line itself, including an operator reaching over an open vial-loading turntable and a mini-door retrofitted into a barrier system to enable manual interventions into the Grade A space, a modification that can compromise the separation the barrier was designed to provide.¹

What are common pitfalls in drop-in cleanrooms and airflow studies?

Turning to drop-in cleanrooms, prefabricated enclosures sometimes used to support aseptic processing, Dr Chancey emphasized a soft-walled cleanroom with a damaged, degraded ceiling and a horizontal flow hood presented as providing an ISO 5 environment despite visible imperfections.¹ He drew attention to airflow visualization, or smoke, studies used to confirm that unidirectional airflow protects critical processing areas.

He described 5 recurring deficiencies: tracer media lacking sufficient buoyancy or dissipating too quickly to be useful; tracer velocity too fast to represent actual conditions; tracer media not positioned near the intervention under evaluation; equipment or interventions not representative of commercial conditions; and airflow disturbances left unacknowledged in study conclusions. Examples included a tracer manifold positioned inches from the equipment being evaluated—with tracer media pooling on surfaces rather than demonstrating airflow; short circuit airflow moving from the Grade A space inside a barrier system directly into the surrounding Grade B space; and an unrecognized vortex forming and collapsing over a vibratory stopper bowl.¹

What did FDA's warning letter reveal about sterile manufacturing?

Dr Chancey closed with a case study drawn from a recent FDA warning letter spanning 4 categories of deficiencies. On microbiological contamination, the letter described extended water deadlegs used for equipment cleaning, which are known to cause stagnation and excessive microbial growth. Between June 2023 and September 2025, routine testing identified at least 47 microbial recoveries, including 14 exceeding the firm's action limit, with repeated recovery of gram-negative, biofilm-forming organisms, including Sphingomonas, Methylobacterium, Bradyrhizobium, and Ralstonia species, he noted. The firm's corrective action plans failed to address the underlying piping design, he added.¹

On equipment integrity testing, the letter described a program that permitted critical components to fail leak testing multiple times before requiring replacement, with retesting sometimes delayed to a later date rather than performed the same day. In one instance, a component failed testing on July 1, 2025, and did not pass a retest until July 19, 2025, an 18-day gap during which the firm's production schedule showed batches of drug product were manufactured using that component before its integrity was confirmed.¹

On material suitability, investigators observed fibers shedding from protective equipment covers inside critical aseptic filling areas, a recurring issue despite a prior customer complaint about a non-pharmaceutical-grade material, Dr Chancey pointed out.¹ On chemical decontamination, the letter cited a multiyear trend of positive biological indicator recoveries during decontamination cycle validation and acceptance criteria that inappropriately permitted multiple biological indicator survivors per cycle.¹

The PDA/FDA Joint Regulatory Conference 2026 is taking place September 14-16, 2026, in Washington, DC.

References

1. Chancey JF. Sterile facility trends: insights and modernization opportunities. Presented at: PDA/FDA Joint Regulatory Conference 2026; September 14-16, 2026; Washington, DC.
2. FDA. Guidance for Industry, sterile drug products produced by aseptic processing—current good manufacturing practice. (CDER, CBER, October 2024). Accessed September 16, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/sterile-drug-products-produced-aseptic-processing-current-good-manufacturing-practice