Automating Release for Autologous Products
This is the third of a series of five blogs summarising key discussion points and outcomes from the latest automation Special Interest Group (SIG) sessions, held in June 2021.
This blog highlights the contributions of the third working group, focussed on ‘Automating Release for Autologous Products’.
Industrializing quality control processes for autologous products is an essential topic of discussion in the cell therapy industry.
As a first step, SIG participants discussed which standards are currently in place as well as which are needed, and explored what can be done to facilitate implementation of new standards. Upcoming sessions in September and December will focus on scalability, comparability and process automation.
Identifying Needed Standards
The group acknowledged the availability of well-established safety standards such those in place for testing for mycoplasma and stability. It is clear, however, that many areas remain in need of approaches applied across the industry in a consistent manner. Guidance continues to be provided by regulatory authorities and these documents highlight considerations for steps such as process development and characterization. This guidance needs to evolve into declarative statements in the spirit of ‘do this and have that read out’ and this process may require a series of incremental steps versus a quantum leap.
Areas in need of standards identified by the SIG participants include:
- Comparability assessments for gene therapies
- Characterization of T cell subsets and identification of the manufacturing composition which gives the most meaningful clinical outcome and facilitates comparability
- Potency measurement for cells to be administered to patients
Implementing New Standards
The ability to implement standards relies heavily on the flow of data. The working group noted that the flow of data from in-process control and release testing must be directly fed back to the manufacturing step so it can be acted upon. The question then becomes what manufacturers can do to facilitate this, across many different machines from many different vendors involved in such a production process.
Ideas to address this challenge include open collaboration, exchanging protocols and increased flexibility on the part of tool providers in order to reach a level of standardisation – in other words, offer less standardisation. This somewhat counterintuitive approach could possibly help industry reach the end goal for standardization sooner and would be applied at development stages, not to the end formulation which is much more stringent.
The benefit of having a ‘back-up plan’ was also explored in terms of what happens if the product needs to be held at some point in the process or if release criteria are not met. The example given was the case where cell number must be increased and the benefit of having a ‘plan B’ to accommodate for this type of situation.
In the effort to bridge the gap from the current state of minimal standards to broad implementation, the group identified several key areas for standards development:
- Comparability assessments for gene therapies. This aspect becomes more pressing with next generation cell therapies in development.
- Cell composition and characterization of T cell subsets and identification of the manufacturing composition which gives the most meaningful clinical outcome and facilitates comparability
- Potency measurement for cells to be administered to patients and whether there can be a standard to determine whether a therapy will be effective in respective patients.
The Automation Special Interest Group (SIG) was created by Phacilitate in 2017 to discuss and propose solutions to automation challenges presented by cell and gene therapy manufacturing. Since that time, we have advanced this mission by identifying key objectives, hosting meetings with industry experts to explore and address these objectives and releasing a report for the wider industry to use as guidance in their automation efforts. In 2021, we evolved the SIG into a parallel track of year-long working groups, each focused on a different area.
Catch up with what was discussed at the June 2021 meetings with this blog series:
1 – Manufacturing Digitisation in Advanced Therapies
2 – Vein-to-Vein Tracking and Supply Chain Digitisation
4 – Modularity and Flexibility in Closed Systems
5 – Aligning the Automation and Technology Roadmap to the Regulatory and Process Development Roadmap