Speciality Chemicals Magazine MAR / APR 2023 | Page 18

PHARMACEUTICALS

Figure 4 – Biologics analytics at Aragen

Raw material quality should be one of the primary considerations for biologics manufacturing because impure reagents and consumables used in the initial phases of production might pose significant problems in the scale-up process . It will have an influence on performance metrics ( titres , PVCD ) and cause batch-tobatch variations .

The primary goal of scale-up is to enhance yield while preserving functional quality . The contaminants in the media affect post-translational modifications , such as glycosylation . Trace element analysis and adding supplements such as peptones , animal origin-free and / or chemically defined components can all be used to improve performance or maintain productivity at higher volumes .

Analysis of the cost of goods sold ( COGS ) associated with the scale-up process is critical . COGS fluctuates with the physiochemical features and scale of the biologics , so analysing it helps in making crucial choices , such as modifying process protocols or discontinuing development .

Efforts must be made to develop a scale-up procedure that is both costeffective and efficient . Single-use technologies , perfusion processes instead of fed-batch operations , continuous chromatography and endto-end continuous processes can all reduce COGS in bioprocessing .

Early optimisation of the formulations can likewise reduce the number of unsuccessful batches and the amount wasted material associated with process development . Process changes like moving from liquid to powder media to save on shipping expenses or switching to a perfusion procedure to boost bioreactor efficiency are another way .

The basic requirement for regulatory acceptance is the correct traceability of each component used in the formulation . Using approved and traceable reagents and consumables , delivered with full regulatory documentation , along with thorough product characterisation , helps to smooth the approval process .

Clinical trials demonstrating that the product is safe , effective and reproducible are an essential requirement of the FDA . cGMP regulations require all commercially produced biologics to meet stringent assay , quality and purity requirements . Regulations differ from country to country but all require a welloptimised product and a cost-effective , reproducible scale-up process .

Conclusion

The production and scale-up of biologics requires well-informed decision-making . There are numerous challenges and the upstream process development and scale-up methodologies come with various risks . Developers seek to design robust , reliable and reproducible protocols for cost-effectiveness and quick market access but the timelines and expenses budgeted are often idealistic .

To fast-track process optimisation , the correct decisions must be made early , which requires rapid access to high-quality data that can only be generated with established production platforms and advanced characterisation packages . Adopting modern and automated technologies from the inception of the project is necessary for identifying critical and non-critical factors influencing rapid , cost-effective market placement .

The large molecule industry is under extreme pressure , due to a huge number of competitors , limited budgets and tight timelines . One way to ensure successful delivery is to partner with an established vendor that has completed many projects and has experience with a range of biomolecules , including difficult-to-express proteins . Ultimately , taking informed decisions is critical to the successful production and scale-up of biologics , as well as the seamless delivery of the new therapy to the clinics . ●

* - The authors wish to acknowledge Drs Sufia Karim and Divya Khaitan of Aragen ’ s Department of Biologics for allowing the schematics to be used in this article and the formatting effort of the corporate communications team in India

18 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981