CQV Best Practices for Single-Use Systems

Do you remember how difficult it used to be to find your way from one place to another? In high school and college, I drove around with a large paper map of my home state (which never did fold back into its original shape) and a United States atlas for interstate trips. Although cumbersome and not conducive to navigating while driving, large maps were a necessary part of travel in those days.

In the mid-1990s, I discovered MapQuest — a technological revelation at the time. I could dial up a blazing slow internet connection, enter a starting point and destination, and print out specific directions to guide me on my trip. It was a big step forward in navigation but still left a lot to be desired in terms of recent road changes, construction projects, and local landmarks. I often found myself missing turns and needing to turn around or find an alternate route on my own.

GPS devices again changed the game and made self-navigation easier and safer, until apps like Google Maps and Waze integrated with smartphones to provide traffic patterns, route details, intelligent rerouting, and user-submitted content.

When I began my career in biotech nearly 25 years ago, there was little industry guidance for navigating emerging technologies. I can remember conducting studies to determine how many times I could rinse and reuse 10” and 20” filters for media filtration at the animal vaccine company where I worked. The filters were expensive, and vaccine development for animals was not extremely profitable, so the pressure was on to maximize equipment use.

When I moved from USDA-governed animal products to FDA-governed human biologics, there were many new single-use technologies available. Small-scale filter capsules came pre-sterilized by gamma irradiation, large-scale single-use processing 2D bags came in volumes from 50 to 1600L, and later 3D bags for process volumes up to 3000L.

By the mid-1990s, biotech manufacturers began demanding prefabricated, single-use filter capsules with tubing and bags pre-attached to bio-containers. By the mid-2000s, these systems were gamma-irradiated and validated as sterile systems, and large-scale tube welders and sterile connectors enabled two sterilized fluid pathways while maintaining sterility of both.

The emergence of personalized medicine, improvements in cell culture processes, growth of biologics, and spread of CMOs have all driven the boom in single-use technologies. The industry guidance has evolved in parallel from sparse and often conflicting, to now more collaborative and definitive.

Increased collaboration among industry groups has provided clearer strategies for determining whether single-use components have been sufficiently and appropriately qualified. The following guides, templates, and reports can help you navigate the road to single-use technologies.

The Parenteral Drug Association (PDA) Technical Report No. 66 has dedicated chapters for key topic areas, including manufacturing strategies for multi-use versus single-use systems, an overview of the variety of single-use technologies, and a tutorial on business drivers influencing the selection of multi-use and single-use systems. The report also includes sections on qualification of assembled single-use products and implementation of single-use systems in a manufacturing process.

The Bio-Process Systems Alliance (BPSA) published its first component quality test matrices in 2007 to “help users when making their selections and facilitate qualification, validation, and the use of single-use products.” The 2015 update incorporates single-use sensors, chromatography column products, and common practices followed by single-use component and assembly providers.

The BPSA established a guide to address the concern for particles in single-use systems flow paths, especially those without inline filtration. The guide applies to non-filter sterilizable vaccines manufactured under aseptic sterile conditions, or simply downstream of sterilizing filters in single-use systems designed for filling of bulk or final dosage protein biopharmaceuticals and vaccines.

The BPSA Consensus Quality Agreement Template for Single-Use Biopharmaceutical Manufacturing Products provides a common structure for quality agreements between suppliers and end-users of single-use products.

BioPhorum Operations Group (BPOG) and BPSA collaborated to write An Industry Proposal for Change Notification Practices for Single-Use Biomanufacturing Systems to encourage better communication between suppliers and end-users. This paper aims to align all parties on a change notification process, term definitions, and responsibilities to facilitate industry-wide communication and process standardization.

BPSA developed the Guide to Irradiation and Sterilization Validation of Single-Use Bioprocess Systems to provide basic information and general recommendations on gamma irradiation for microbial control and sterilization of single-use disposable bioprocess systems applied to biopharmaceutical manufacturing.

The road to successfully implementing single-use technologies can be tedious and time-consuming if navigated without proper guidance. Our industry has graduated from paper maps but still needs work to reach Google Maps or Waze status. Fortunately, the resources mentioned in this post and others are helping industry professionals find their way.

If you need help navigating your road to manufacturing compliance and quality, we are here to help. Give us a call at 800-201-9871 to start a conversation.