CONTRACT & TOLL MANUFACTURING
acetate can maintain pre-defined purification conditions , provide stability and protect the biologics from co-precipitants .
preclinical CGT assets . The reason is simple : large biopharma companies tend to focus on developing therapies in specific disease areas , not on developing the technology platforms .
Most technology platform work is performed in academic settings and , once proven , they are spun out as small biotech start-ups . By their very nature , these venture-fund-backed new companies need to operate leaner , with a laser focus on continuing to optimise their technology or potential drug candidates . Outsourcing for these CGT upstarts across necessary but non-core activities is a commonplace practice .
There are unique challenges related to CGTs based on the instability of living cells . Manufacturing of cell therapies must take place occur before the cells expire and , since they cannot be sterilised , an aseptic environment is needed .
Actylis ’ newest facility at Eugene , Oregon
Gene therapies also frequently require an aseptic manufacturing environment as they cannot be sterile-filtered . The proteins tend to be sticky , requiring segregation of the materials and frequent cleaning of the manufacturing lines to prevent cross contamination .
GMP-grade buffers are thus essential in CGTs . Buffers in the upstream process need to maintain a very tight pH window for the culture material in order to preserve therapeutic characteristics . TRIS , MES and guanidine hydrochloride , among others , can ensure the efficacy of upstream processes while also complying with global regulatory requirements .
Buffers for downstream processes , meanwhile , need to provide for the very specific conditions under which CGTs will remain stable . Suitable ones , such as phosphate , citrate and
Choosing a supplier
Since the beginning of the pandemic , supply chain issues have come into sharp focus . When it comes to choosing a custom buffer supplier , the due diligence of biopharma companies should include understanding how robust its supply chain is and their ability to maintain a steady on-time , in-full stream . In addition , it is essential to know the company ’ s warehousing capabilities , and whether it meets all the quality requirements and provides the documentation needed .
A facility visit is a good step to see first-hand how a supplier operates , the quality systems it has in place and its ability to serve each client ’ s specific needs . Equally important is introducing the teams of each company that would be assigned to the project to allow for a better understanding of how each works , to outline the requirements of the project , and share information that can improve buffer design .
In addition to outsourcing of buffers and associated processing ingredients , outsourcing of custom process intermediates and regulatory starting materials ( RSMs ) is a critical component of the drug substance supply chain . Regulatory requirements with respect to the auditing and qualification of manufacturers of these key raw materials have , though , become increasingly more stringent .
As a result , the practice of outsourcing manufacture of process intermediates for drug substance production has grown much more challenging from a regulatory perspective . Contracting the manufacture of process intermediates outside of the US and Europe has been heavily leveraged in the recent past , primarily for economic reasons . However , there are significant difficulties when attempting to qualify manufacturers in the current regulatory environment .
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