Ensuring supply chain of cell therapy products during commercialization: easy reconstitution at the bedside

Snykers, S., P. Willemsen, et al.

Promethera   HepaStem  is the  company's  therapy  product  to  treat  serions metabolic liver disorders. An European  phase IIII  clinical trial is ongoing  to treat  Crigler-Najjar and  Urea  Cycle Disorders  in a pediatric setting. As  of today, 20 patients have been treated with HepaStem.  Cnrrently,  Promethera is preparing  its next clinical phases in US and Europe.  Th.e challenge is to provide  a  drug   product  easy-to-reconstitute  at  clinical  sites.  In  order   to guarantee  a flexible, highly quali tative, and economically sustainable supply chain  during  commercialization,   Promethera   has developed  a  ready-to-use off-the-shelf  product for direct reconstitution  at the hospitals. The  product preparation  is simply carried out  like conventional  reconstitution  of fi·eeze­ dried sterile  medicinal products (e.g. vaccine). The  challenge was to find an appropriate   final  container   (i)  compliant   to  liquid  nitrogen   storage,   (ii) allowing automated in-line filling and (iii) reconstitt1tion without changing the product  quality (safety/identity/purity/potency). The  Aseptic Technologies closed  vials perfectly  fit within  this concept. This  approach  does not  only simplify  the  preparation  procedure  and  operation  time, it also reduced  the storage  footprint  and  improved  the  product's  quality  in  terms  of viability, yield, content  uniformity and batch-to-batch  consistency. Shelf-life, the key­ bottleneck of most cell therapeutic  products, is substantially less critical. The idea for the upcoming clinical phases is to provide an ali-in-one  kit, including the cryopreserved cell tl1erapeutic product HepaStem  and all material needed for  reconstitution   (syringe/adaptor/uisinfectantlprefilled  vial with  reconsti­ tution   media).  In  conclusion,   Promethera   has  developed  a    ready-to-use product,   allowing  worldwide  availability  and   easy  reconstitution   at   the bedside. This technology guarantees a sustainable supply chain during commercialization  and offers opportunities  in the field of cell-based products with limited shelf-life.