Advancing RNA Covers the Session "Building an Approach to Rapid Sterility Testing of ATMPs” from the 2026 ISPE Aseptic Conference
During the 2026 ISPE Aseptic Conference, Jose Caraballo-Oramas, a biopharma executive and long-standing ISPE member, presented “Building an Approach to Rapid Sterility Testing of ATMPs.” Caraballo spoke with Advancing RNA ahead of the session to provide a candid assessment of how manufacturers must rethink contamination control and release strategies to protect both patient safety and product viability.
As highlighted throughout the 2026 ISPE Aseptic Conference, advanced therapy medicinal products (ATMPs), particularly autologous cell therapies, continue to challenge the boundaries of traditional sterility assurance frameworks. The industry is confronting a fundamental misalignment between the clinical realities of ultra‑short‑shelf‑life products and the long‑established 14‑day compendial sterility testing paradigm.
Caraballo emphasized that for many autologous ATMPs, releasing product before sterility results are complete has become an unavoidable operational baseline. This is not a preferred state, but a clinical necessity, as patients cannot wait two weeks for results when their personalized therapy may only remain viable for days. The consequence is a release paradigm that inherently carries risk, placing extraordinary pressure on contamination control systems, aseptic process design, and quality decision‑making frameworks. When a late sterility positive, whether true or false, emerges after infusion, organizations face a cascade of challenges: medical assessment, lot disposition, physician communication, pharmacovigilance, and potential erosion of trust with treatment centers.
While speed is the most visible advantage of rapid microbial methods, Caraballo underscored that their value extends far beyond turnaround time. Traditional growth‑based sterility tests can be confounded by the complex, opaque, and metabolically active matrices characteristic of cell‑based therapies. Rapid methods, by contrast, may use alternative detection principles such as metabolic markers, fluorescence, pressure changes, or nucleic acid‑based detection: these indicators are generally less affected by matrix interference. When validated appropriately, these methods improve interpretability, reduce ambiguity, and support more confident release decisions under compressed timelines.
ATMPs are often produced in extremely limited volumes, making traditional sampling strategies more challenging. Caraballo noted that rapid testing with risk‑based sampling should be part of a broader contamination control strategy that considers process design, container‑closure systems, and contamination‑prone points. The industry is also moving toward nondestructive or minimally invasive testing, not for convenience but out of necessity. The goal is to extract meaningful sterility‑related information from minimal sample volumes while preserving as much product as possible for the patient.
A recurring challenge arises when rapid sterility methods used successfully in early clinical phases fail to meet the more rigorous expectations of Phase 3 or Biologics License Application submissions. Caraballo observed that early‑phase programs often prioritize feasibility and speed, leaving gaps in validation, organism coverage, and lifecycle management. By late development, these gaps can complicate comparability assessments, especially if the product or process has evolved. The strongest programs treat rapid methods as integral to development from the outset rather than as late‑stage justifications.
The flexibility afforded by 21 CFR 610.12(h)(2) allows alternative sterility assurance approaches when they provide equal or greater safety. Caraballo views this not as a workaround but as an appropriate recognition that traditional frameworks do not always fit for ATMPs. Still, he acknowledged the value in more harmonized, explicit guidance—potentially a dedicated compendial chapter tailored or equivalent standard for ultra‑short‑life products. Such a standard could help align expectations around validation, sampling, and method performance across regulators and manufacturers.
With the US Food and Drug Administration signaling increased flexibility in chemistry, manufacturing, and control expectations for cell and gene therapies, Caraballo sees a shift toward greater reliance on process understanding, validated controls, and integrated evidence rather than a single end‑point sterility test. While classical parametric release may not be directly applicable due to product variability, the direction is clear: robust contamination control, in‑process monitoring, and strong process performance data must collectively support release decisions.
The insights shared at the 2026 ISPE Aseptic Conference by Caraballo and a variety of other life science experts reinforce the importance in industry‑wide collaboration to modernize sterility assurance frameworks. ATMPs demand a shift from static, test‑centric models to dynamic, risk‑based, and process‑integrated strategies. As the pharmaceutical industry rapidly evolves, ISPE will continue to champion innovation, community, and knowledge through conferences, guidance documents, trainings, webinars, and more.
Explore future ISPE conferences
About Advancing RNA
Advancing RNA functions as a specialized community within the larger Life Science Connect network, bringing together professionals with an interest in RNA‑based therapeutics. The publication serves as a hub for scientific exchange, practical guidance, and industry dialogue, all centered on the unique challenges and opportunities that come with developing RNA medicines.