MM: Were procurement supply chain issues a consideration?
NB: The pandemic has clearly stretched the global supply of producers and manufacturers. Within our organization, there are strong
supply chain management groups with regular reviews and audits of suppliers. We have particularly rigorous controls in place
and also exchange a great deal with colleagues in the vaccines division who have many years experience with disposables selection
EJ: Our client voiced concern about single sourcing from Millipore. Millipore has met with several clients to review our strategy
around this critical area and is taking action such as developing specific bag holder systems that facilitate the deployment
of bags from alternate vendors.
MM: What did you see as the biggest challenges with single-use systems?
NB: The fact that we are contracting out the sterility assurance, cleanliness, particulates, and endotoxin control to a third
party requires careful auditing and supply agreements. We are of course concerned about the overall system integrity and the
perceived weakness of polymeric materials. We were concerned about the reliability of sterile connections in terms of mold
variation. Concerning the Bosch needles, we are concerned about ongoing control of the physical, chemical, and micro quality.
MM: One common concern when evaluating disposable technologies for final filling is the question of pre- and post-integrity
sterile filter and disposable system testing. How was this handled?
EJ: Pre-use system and filter integrity testing is performed by Millipore. Package validation testing by ISTA 2A drop and vibration
and post ISTA package integrity testing demonstrates that the system is integral pre-use.
NB: We then perform pre- and post-filter testing where appropriate.
MM: What do you see as the biggest limitations or risks when working with disposables in the context of final filling operations?
NB: Solvent-containing products are not ideal for disposables because of the potential for evaporative molecular loss through
tubing by permeation. We had two preserved multi-dose products that couldn't be filled in a single-use setup.
Having said all of this, I think the best proof of the fact that these systems are a sound solution is that we have now filled
85 million doses and we have had no integrity issues and no sterility failures.
MM: In terms of the benefits, have you been able to measure efficiency and productivity improvements and related cost savings
since implementing disposables?
NB: With the disposable setup, the amount of grade A intrusions for the wetted path assembly and strip down has been taken from
2 h to 0 using the Getinge La Calhene grade C to grade A door. This door has a disposable beta door that is premounted with
the disposable assembly, and is pre-gamma sterilized and prepared by the vendor with all the relevant documentation. Also,
with this arrangement there is no need for the operators to touch the needles, avoiding the need for SIP post-assembly. The
system is considerably simplified. The regulators have commented that it could reduce aseptic risk.
The overall time savings are significant. The system preparation time is minimal, the system build time is 30 minutes versus
2 hours for the stainless steel system, sterilization before filling is 0 versus 3.5 hours, operator training time is 2 days
versus 2 weeks, SIP qualification is 0 and no six-monthly requalification, the aseptic connections are 0 versus approximately
50 (which were SIP sterilized), and of course there is no cleaning validation. To sum it up, we previously required 36 hours
for a campaign fill and we are now down to 12 hours!
In addition, we had a stretch target to reduce energy. Since implementing disposable technologies for final filling, our site
energy usage has dropped, significantly reducing our carbon footprint. In addition, we have significantly reduced the carbon
footprint and increased capacity by 40%. Validation and routine SIP are key contributing factors, but of course there are
many other factors, as outlined earlier. We haven't yet carried out a full cost analysis, but again we expect the overall
impact to be significant in terms of less water usage and less chemical usage. And of course the increased capacity means
that the number of days gained in manufacturing capacity is huge.
MM: What are the key take home messages you have gained from this project?
NB: Disposables offer a platform-enabling simplification of many activities. The end-to-end solution will provide the biggest
benefits, including reducing assembly time, limiting aseptic intrusion, and enabling modular use of set-ups, allowing for
minimum hold and maximum flexibility. Consider all connections as highly critical, assume leakage will occur, and build in
security. Lastly, control suppliers through quality and supply chain agreements.
All of our forecasts indicate that there is going to be an explosion in the need for vaccines. Previously we were constrained
by capacity and now, thanks to disposable platforms, we can rapidly gear up to meet demand.