Speciality Chemicals Magazine MAR / APR 2023 | Page 16

challenge . Biologics made up of several monomeric components have complicated structures , mechanisms of expression , post-translational modifications and transport within the cell to be functionally active . 5

A one-size-fits-all approach is unsuitable . The appropriate platform should express the molecule in its fully functional form , and be simple to handle ( transfection ) and scalable . Some elements for CLD success include a traceable and thoroughly recorded history , legal needs , growth characteristics and cell culture conditions .

Identifying a better performing clone is difficult and time-consuming . Screening procedures require substantial time , considerable optimisation of many assays and testing using purified chemicals . Expert professionals will be involved in clone selection and checking its performance at various bioreactor levels .

There are many challenges in analytical characterisation . The chosen clone must be amplified and thoroughly characterised . To ensure safety and efficacy , orthogonal

characterisation methodologies should be used . 6 Comprehensive characterisation of biologics is feasible using a variety of assays , each of which is required in order to obtain information about the product ’ s physicochemical qualities . Performing these assays demands the use of modern equipment and established protocols .

Establishing a high throughput analytical laboratory is costly . Handling this equipment and carrying out the procedures necessitates experienced scientific staff with competence across numerous disciplines , which is challenging for small businesses to procure . Furthermore , analytical characterisation is prone to manual errors , which must be corrected by qualified technicians .

There are also challenges in process development to address . Commercial-scale biologic production is only possible when bench-scale prototypes are scalable to pilotscale and high-volume bioreactors . 7 Parameters should be established both at the shaker flask scale and at the larger-scale reactors to avoid wasting valuable resources and time .

Therefore , it is critical to establish the production parameters following rigorous experimental design and the verification of as many variables as feasible . Process development must also include parameter testing at various bioreactor volumes , which is expensive and can cause considerable delays .

Besides technological problems , biologics manufacturing has several logistical challenges . To mitigate these challenges , a client needs to make sure that a CRO will be able to complete the entire process in-house from beginning to end . In addition , a GMP-compliant facility and a committed scientific workforce with robust project management skills are essential .

One way to reduce time-to-market is to outsource production to established CROs and CDMOs that specialise in large molecules and have the appropriate competence . Another , which requires significant capex , is to develop in-house capabilities , such as investing in some of the most modern technology and characterisation services in commercial biologics manufacturing .

16 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981