Right now, pharmaceutical and biopharmaceutical manufacturers often rely on outdated best practices related to radiation sterilization and routine control of single-use systems. Fortunately, there is new industry guidance that will help streamline these processes.
AAMI has announced the release of, AAMI CR513:2024; Guidance on radiation sterilization validation and routine control of single-use systems used for pharmaceutical and biopharmaceutical manufacturing, a new guidance document that updates best practices for manufacturers of pharmaceuticals and biopharmaceuticals. The guidance outlines alternative, simplified approaches to radiation sterilization validation and routine control for single-use systems.
“This report addresses a real need to appropriately adapt our radiation sterilization validation methodologies to products that challenge the concept of what a medical device looks like,” explained Emily Craven, director, sterility assurance at Boston Scientific, who helped shape the document. “Single-use-systems used in bio-processes need to be sterile in order to manufacture products which will be safe for patient use, but they can be cumbersomely large, which becomes impractical when sampling for routine testing. The beauty of this consensus report is that it provides practical guidance on sampling methodologies and use of sample item portions for complex multi-component systems in order to provide an accurate picture of sterility assurance based on the use of the system.”
New Needs Arise with Size
Manufactured in a cleanroom, packaged, and sterilized by radiation or EtO sterilization methods, single-use technologies reduce product cross-contamination risks by eliminating the need for cleaning between batches. Seemingly the antithesis of an economic solution, these are drug delivery or biologic containment systems that are disposed of after their first use. However, proponents of single-use technologies will laud the fact that disposable systems – such as bags, filters, and sterile tubing – save health systems the time, money, and even the water that reprocessing traditional stainless-steel systems may require. Today, this technology has seen growing popularity in pharmaceutical and biopharmaceutical manufacturing, where difficult-to-maintain components of the drug-manufacturing process can be replaced with disposable systems.
“The single-use system industry continues to grow as these systems become better understood as a viable option for replacing the previous systems used for manufacturing pharmaceuticals and biopharmaceuticals,” explained Martell Winters, director of scientific competency at Nelson Laboratories, who helped develop the new guidance document.
According to Winters, older manufacturing systems usually included “meters and meters of stainless-steel pipes and large stainless steel vats, all which all of which needed to be cleaned and sterilized between each manufacturing batch. The use of single-use systems allows for great flexibility in carrying out the manufacturing process and increases patient safety by providing a process that has virtually no option for cross-contamination and in many cases is a completely closed or nearly closed system.”
However, as these systems have grown in size and complexity, new questions arose.
“The current practices as written for radiation sterilization validation and control testing can be difficult to implement for large, complicated single-use systems and are often cumbersome and can lead to contamination in the test vessels,” explained Kimberly Patton, sterilization staff engineer and auditor of the MedAccred Program at the Performance Review Institute. Some manufacturing practices may even be “overly conservative in some cases, where large equipment might not come into contact with the patient.”
Establishing An Industry Stopgap
AAMI CR513 is a Consensus Report (CR), a special class of AAMI guidance document that provides concise, prompt and practical guidance on narrowly focused topics of high importance to the health technology community. A CR is intended to respond to an urgent/immediate need for guidance while more robust data/information develops about emergent or changing technologies such as single-use systems.
CRs are traditionally developed by a small team of renowned industry experts. AAMI CR513 was produced by the AAMI Radiation Sterilization Working Group, a diverse team of sterility assurance and microbiological quality professionals, regulators and scientists. The group is co-chaired by Patton and Niki Fidopiastis, director of microbiology for global laboratory services at Medtronic.
AAMI CR513:2024 provides guidance on:
- Sterilization dose, addressing which products should be selected for testing, and best practices for testing.
- Sterile claim, providing guidance on estimating sterility assurance level and how to select sterile claims.
- Dose application, including information on the proper delivery of a verification dose and sterility testing.
- Risk assessment, establishing the correct components of risk assessment for single-use systems, considering the specific system and its needs.
- User verification, focusing on how to independently verify the sterility assurance level of a single-use system.
According to Fidopiastis, AAMI CR513 is a much-needed stopgap, and its “simplified approaches for validation and routine control of single-use systems” will provide manufacturers with the clear guidance they need. Patton added that the working group’s next step will be to monitor how the CR is used and whether a thorough Technical Information Report is desired by stakeholders.
The document can be accessed or purchased on AAMI ARRAY.
