By: Deb Quick, Ph.D.
Senior Consultant
Everyone knows that good aseptic technique is crucial when handling biological products, particularly in fill and finish operations. But for cellular therapies, good aseptic technique is essential throughout the entire process to prevent product contamination and to provide a safe product to the patient. These cellular therapies cannot be sterile-filtered, and thus the only way to prevent contamination is to ensure that all processing is performed aseptically. Product safety thus relies on the operators’ ability to perform the open processing tasks with good aseptic technique.
One approach to reducing the dependence on the individual’s technique is to improve the cleanliness of the processing environment. Many factors affect the cleanliness of the processing environment, including effective disinfection of the processing environment and the processing materials before they enter the processing environment.
The approach that is highly favored by the FDA and the EMA to ensure a clean processing environment is to use an isolator for open processing steps, instead of performing such tasks in a biological safety cabinet or BSC (see Appendix 1 of FDA Guidance for Sterile Drug Products and EU Annex 1).
Isolators significantly reduce the bioburden present on materials used for open processing and on the gloves used for processing. By having a sterile processing environment and by using a decontamination cycle for transferring in the processing materials, the risk of contamination is reduced, and the resulting product safety is less dependent on the operator’s technique.
Although fill and finish tasks are commonly performed in isolators, cell processing steps are historically more commonly performed in a BSC. Cell processing often requires dexterity and manual manipulations that are difficult to perform with bulky isolator gloves inside an isolator. In addition to the difficulties associated with isolator gloves, some cell therapies rely on microscopes for in-process tests and microscopic-scale manipulations of the cells during the process. Most microscopes aren’t compatible with isolator environments.
But there are advancements in the isolator industry that are making them better suited to producing cellular therapies.
- There are thinner gloves available that provide greater dexterity, like neoprene and nitrile. While neoprene gloves have shorter lifetimes in the isolator environment due to their vulnerability to repeated peroxide decontaminations inside the isolator, nitrile gloves provide a good alternative to the standard bulky CSM (chlorosulfonated polyethylene material) gloves.
- Most microscopes aren’t compatible with the peroxide decontamination cycles required in an isolator, but there are options for encapsulating the microscope within a protective shell while still being able to view slides and dishes.
Despite the difficulties associated with processing in isolators, it is in the manufacturer’s best interest to develop their cell therapy process so that it can be performed in an isolator, since the isolator environment significantly reduces the contamination risk, which improves product safety and increases the chance of regulatory approval.
Syner-G BioPharma Group is ready to help you develop a cell therapy process that’s compatible with isolators and guide you to select the isolator accessories and/or modifications that may be needed to get your cell therapy to market.