How have single-use systems advanced in recent years and what impact has this had on cleanroom environments?
Single-use systems have only recently been introduced into final-filling cleanroom environments. A key strength is their recognition
as “closed systems” by drug manufacturers and regulatory authorities. Many drug and vaccine manufacturers see this as a great
opportunity to work in non-classified or lower-classified areas (e.g., Grade C or D/Class 100,000/ISO 8), and some have already
applied this approach in new facilities and expansions. A key enabler of single-use systems in final-filling areas has been
the innovative development of sterile connectors, which enable sterile connections in nonclassified environments. These sterile
connectors are valued as providing higher assurance of containment than traditional aseptic connections that must be performed
under Grade A/Class 100/ISO 5 conditions. Although perhaps having minimal impact on existing cleanroom facilities, these advanced
capabilities are stimulating designers of new aseptic filling facilities to consider reduction in cleanroom spaces and classifications,
greatly reducing the potential cost to put up new aseptic filling suites.
When designing and building a new cleanroom facility, what consideration should be given to single-use systems?
Implementing single-use systems in a new cleanroom facility can enable reduction in the size of the cleanroom by allowing
for downgrades at every stage, working in grey areas for most of the process and limiting Class A (Grade 100, ISO 8) areas
to around the filling needles. This is further facilitated through the use of complementary technologies within cleanrooms,
for example, single-use port approaches on isolators that enable single-use system integration into Grade 100 areas. The primary
benefit of these technologies is a reduction in controlled environment class and areas, which can greatly decrease facility
build cost and time, as well as labour resources, time and the costs of environmental monitoring, maintenance and other ongoing
quality control activities.
How do single-use, closed systems help reduce or, in some cases, eliminate the need for classified cleanroom environments?
Closed systems eliminate the risk of external contamination—including chemical, microbial or particulate. Sterile connectors
have been shown to maintain sterile pathways even when externally contaminated with up to one million bacteria per unit and
in bacterial aerosols far higher than would occur even in an uncontrolled environment. Because clean sterile fluid pathways
are maintained independent of the environment, classified cleanroom conditions are only needed at points of filling. Conservative
practices and tradition may preclude complete elimination of controlled spaces, but single-use systems will enable manufacturing
in smaller and lower classification areas, greatly reducing facility construction and operating costs. Regulatory acceptance
of sterile connection technologies is increasing at the pace of single-use technology implementation, such that in the coming
years, both the user base and data for sterile connector technology will only further increase.