By Nick Hutchinson
Therapeutic monoclonal antibodies (mAbs) have had a significant impact on both medicine and the biopharmaceutical industry. Oftentimes different mAb products will have similar properties to one another. In turn, this means companies can use similar production methods to produce multiple mAb treatments from their product portfolio or pipeline. I spoke to Dr Piranavan Thillaivinayagalingam, Director of Project Management from Alvotech Germany to learn more about the industry’s current approach to manufacturing mAbs with platform processes.
What does the phrase ‘platform process’ mean to you?
Platform processing, to me, means having a standardized approach to a range of activities required to develop and operate a biologics manufacturing process. These activities range from cell line development through to steps for the formulation of drug substance. Standardized activities allow drug developers to perform these steps in the fastest and most cost-effective way. In my role, platform processes are particularly important in getting products through to clinical phase I and II manufacturing as quickly as possible.
What are the other benefits of platform processes for mAbs?
A benefit of platform processes is their predictability. If a company develops and manufactures a new product using a standard platform, the outcome should be predictable because of the knowledge and data that has accumulated from running the platform with previous products. This prior experience will have shown that production technologies are safe to use and that they work effectively. It should be possible to predict approximately parameters such as viable cell densities and product titers using information from previous processes. This allows engineers to focus their activities on those process steps that need additional development.
Furthermore, firms may be able to leverage platform data in submissions to regulators during early stage process development to justify approaches to virus clearance studies. Similarly, where a firm is using the same bioprocess containers and films under similar process conditions it could consider leveraging platform extractables and leachables data.
A platform approach can help support facility fit and reduce complexity in operations. The explosion in firms applying single-use technology with disposable manifolds has led to many firms having to stock a large number of consumables and raw materials. A company can reduce the number of manifolds they hold in stock if they are able to use the same manifolds for different processes within the platform. This can increase operational flexibility and reduce dependency on supplier delivery times.
To what extent should process platforms for mAbs be flexible?
Some companies are using process platforms effectively and consequently are churning through phase I and phase II clinical trials very quickly. However, there will always be molecules that are not going to fit into the platform. These might be molecules with a greater propensity to aggregate or that are more difficult to separate from host cell proteins. Sometimes both of these scenarios occur.
To reduce the likelihood of mAb products not fitting the platform, engineers can develop flexibility into platforms and have some processing options available to draw upon in case the physico-chemical properties of a specific mAb differ greatly from other that the company has produced. Having a platform in which it is possible to interchange some of the processing steps will allow you to resolve these problems.
To what extent have mAb process platforms changed over the years and in what ways to you anticipate them changing in future?
The major change to the upstream part of mAb process platforms has been the advent of high-throughput process development technologies such as the ambr® microbioreactor systems. These are helping to speed up tasks such as cell line development and clone selection. They are helping process development scientists deliver more highly optimized and characterized cell culture processes during the early stage phase of biologics development. The consequence of this has been that titers in bioreactors have increased and upstream processes have become more productive. Unfortunately, during my career, the development of downstream technologies has not occurred at the same rate as upstream steps.
The next generation of mAb process platforms must incorporate continuous chromatography and processing to be able to handle this increased upstream productivity. To some extent, this implies the increased use of on-line process analytical technologies for taking process measurements and the use of on-line multivariate data analysis software to help gain a greater understanding of these processes. Continuous mAb platforms will be more automated and require fewer operator interventions. This will reduce the likelihood of operator errors and increase staffing flexibility in operations. Furthermore it should contribute to reduced cost of good especially with increasing product titres.
About the author: Nick Hutchinson is a Technical Content Marketing Manager at Sartorius Stedim Biotech.