PHARMACEUTICALS
Strategies for biologics production
We have identified some of the strategies that can help firstly to accelerate the biologics production and scale-up processes and , secondly , to overcome the challenges associated with it .
Using established host cell lines for biopharmaceutical expression can significantly shorten manufacturing procedures and minimise risks in development . Established platforms are scalable , can accommodate a wide range of compounds , including difficult-to-express proteins , and have their own completely defined media systems .
They are intended to eliminate unpredictability , maximise yields and shorten development timelines dramatically . Furthermore , established cell lines will have a complete history and a track record of successful projects .
To accelerate downstream process development , established and proven expression vectors must be used when engineering novel cell lines . Efficient vector systems give a steady expression of the inserted genetic material without exhibiting any side effects on host cells .
Testing multiple platforms in parallel is another key strategy , especially when clients are unsure about the best host cell line platform to use . With many alternatives available , determining which platform would work best for a particular product is very difficult .
Therefore , many clients who understand the diversity of biologics and the unpredictability of biological systems choose the parallel testing of multiple platforms at the start of a programme . This strategy helps developers to mitigate the risk of failure and increase the odds of success in the very early stage of biologics development . 8
A comprehensive plan must be devised that describes the need and rationale for post-transfection investigations and assays . The protocols that will affect biologics from start to finish , including experiments and methodologies for small-scale characterisation and full-scale validation , must be included in the plan .
The plan must outline the efforts that will be made to execute and finish the different activities in accordance with cGMP . It must also guarantee that a well thought-out , justified and thorough process characterisation is achieved . The risks associated with various stages of process development ( such as minipool characterisation , single cell cloning , screening , etc .) must be rigorously evaluated at benchscale , since they can affect process features and product quality attributes . Critical product characteristics should be examined during analytical characterisation , depending on the risks recognised .
Using modern and high-throughput characterisation tools is critical for carrying out large screening operations and eliminating the possibility of human mistakes . Such tools help reduce both optimisation time and the use of reagents and consumables . The primary benefit of advanced technologies is that they are based on quality by design principles , and so are ideal for scaling and identifying hazards associated with the later phases of process development .
Figure 3 - Flow chart for delivering commercial-ready product
Advanced characterisation tools ensure that the testing methodologies are reliable . These procedures are critical for the analysis and characterisation of biologics , as well as guaranteeing the product ’ s safety , stability and efficacy at all stages of development . 9 These technologies are also essential for rapid clonality assurance to shorten cycle times for FDA submissions .
A second round of risk evaluations on the process parameters should be undertaken based on the analytical characterisation data . As a result , a list of critical and non-critical parameters is generated , as well as a prioritisation of the critical process parameters .
Automation allows for remote monitoring as well as shift production to maintain a socially separated safe atmosphere . It enables continuous production around the clock with less in-person supervision , as well as enhanced uniformity to aid in the conservation of critical components like adjuvants . Automation and digitisation also enable the collection of massive volumes of quality assurance data to create a comprehensive audit trail and develop predictive modelling initiatives . 10
Outsourcing cell line development packages is an important option . Before beginning a project , developers should carefully assess their capabilities for small- , pilot- and commercial-scale , GMP-compliant production . Where they are unsure , outsourcing the whole project or the most time-consuming or operationally difficult elements to well-established CROs with extensive domain experience might be the best alternative .
Established vendors who specialise in large molecule production and scale-up have experience of working with a wide range of molecules and thus understand the risks involved , as well as possible solutions . They also have all the modern technologies and expert manpower in place as well as solutions to a wide range of logistical and regulatory challenges .
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