Introduction
Drug product manufacturing sterile fill and finish has frequently been in the pharmaceutical industry over the last few years. The focus of course was satisfying tens and hundreds of millions of doses for COVID vaccines and other rated therapies, which increased the pressure of access for ongoing clinical and commercial applications often leading to delays in trials and backlog for product.
Current Status on Sterile Fill and Finish
More recent news has highlighted large-scale production as demand for GLP-1 has skyrocketed consuming a significant portion of aseptic liquid filling from the accessible market and turning it captive. As expected, newer players are entering the market to fill that void, expanding their capabilities of sterile fill finish for biologics with aseptic vial filling, prefilled syringe capacity (PFS), and cartridge technology. So, for newer CDMOs, expanded capacity compliance is key.
- Getting Access – A deeper question for early-stage developers is how to access small-scale capacity for sterile injectables fill finish and ensure process and drug product compliance for early clinicals. For those small-scale needs identifying a compliant partner is not easy.
- Searching for Partners – Finding the sterile fill finish companies that encompasses years of experience, modern technology, ISO5 filing suites operating under cGMP conditions, to support human clinical trials in the US, EU, and APAC is a crucial sourcing action for procurement professionals in the external manufacturing arena.
Phase Appropriate Sourcing
For early clinical trials, Phase I and Phase I, II drug developers need access and options in drug product. Depending on the indication, safety and or safety plus efficacy studies, knowing that you can get a fill of 1,000 to 4,000 vials via an expert provider, in a timely manner can be a challenging endeavor. Those options include flexibility across multiple dimensions –semi-automated or fully automated filling technologies coupled with the ability to produce vials from 1 ml to 20ml in size (or greater).
- Quality Capabilities – From a quality perspective, also ensure that the provider has validated multiple volumes and has the quality systems in place to handle at a minimum PI and Phase II production. Ideally the provider can also support later stage production into commercial where, increasingly, small batch filling is required for certain indications such as orphan drug programs.
- Key Supplier Attributes or Focus – Seeking out those providers that focus on rapid access and available capacity, strong technology transfer, quality systems encompassing early clinical to commercial production is a way to ensure access reliability of supply, and above all else – high quality product.
- Capability Examples – For example, CDMOs providing semi-automated processes for aseptic vial filling should be using programmable pumps coupled with manual fill nozzle, to improve yields for small lot sizes and avoid line loss. Sourcing professions ascertain that fill checks are performed at logical points in the process and that operations are overseen and observed by quality personnel. Consistent environmental monitoring must also be included in the program. Stoppered and crimped completed vials must be checked for fill volume and seal integrity outside of the fill suite and monitored by quality personnel.
Compliance and Capability-ready
Automated fill systems such as the AST, must meet most worldwide regulatory agency requirements – FDA, Canadian and European Union regulatory authorities minimally. Look for Annex 1 of the EU’s cGMP guidelines. These smaller automated systems also support compliance by using ready-to-use components negating the need for in-line washing, sterilization, and de-pyrogenation – areas of risk during production preparation.
- New Age of Complex Large Molecules- Further check for sterile fill finish CDMO experience with some of the more exotic large molecules which also have a difficult time finding a home for drug product manufacturing.
- Complicated Tech Transfer – The CDMO should be accustomed to tech transfer of these more novel and challenging molecules such light-sensitive products, controlled (DEA-regulated) vaccine conjugates, exosomes, recombinant therapeutic proteins and enzymes, fragile multi-specific antibodies, antibody fusion proteins, and bio conjugated molecules (mAb or mAb-like structures conjugated to a linker/payload). That experience pays off in process and compliance knowledge and application.
- Formulation Considerations – As a majority of current programs are still mAbs and mAb derivatives and fusions, novel formulations, in particular higher concentration formulations for life-cycle management, stability, sub-cutaneous administration, are in development therefore CDMO drug product providers should also be capable of handling these higher viscosity fills.
Conclusion
Developers can sometimes struggle to find aseptic fill finish providers for their “smaller” but no less critical programs, so identifying those providers that meet the criteria identified here can be challenging. Capacity, robust tech transfer, strong quality systems, and focus on small batch production (5,000 vials or less) are important strengths of GBI Bio. GBI Bio strives to help clients with accelerated development capabilities from early process development and tech transfer to early-stage clinical trials, later stage clinical trials, PPQ and commercial production for drug substance and drug product.
Contact GBI Biomanufacturing Today about Your Sterile Fill and Finish Clinical & Commercial Manufacturing Needs!
