Aligning the Automation and Technology Roadmap to the Regulatory and Process Development Roadmap
This is the final post in 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 fifth working group, focussed on ‘Aligning the Automation and Technology Roadmap to the Regulatory and Process Development Roadmap’.
The June kick-off meeting of this Automation Special Interest Group (SIG) brought lively discussion on aligning roadmaps for automation and technology with regulatory and process development. This session, which brought together a diverse set of stakeholders from cell and gene therapy companies, research organisations and technology providers, established the foundation for defining and implementing regulatory-compliant automation plans.
Session chair Sean Werner, CEO of Sexton Biotechnologies, described the ultimate goal of the group as:
“the development of best practices and guidance on the ways people can think about integrating automation into their processes, when to start thinking about automation, how to do it and how to avoid major pitfalls.”
As a first step, the group defined what automation means in the context of cell and gene therapy. Among the key characteristics are removal of operators, reduction of touchpoints, integration of machine learning for process optimization and decision making, scalability, modularity, and interoperability of processes.
With these definitions in hand, breakout sessions explored key questions:
- What are the regulatory challenges to implementing automation and strategies for addressing them?
- How should developers understand GMP requirements and how does automation fit within a GMP system?
- How should developers and suppliers communicate with regulators about automation?
Defining Regulatory Challenges
The nature of cell and gene therapy processes and automation of these processes present several regulatory challenges. Among the most pressing challenges identified by the group is the need to identify and understand key process parameters, product characterisation and quality to satisfy regulatory authorities. Additionally, comparability to open processes must be assessed and the impact that variation of donors and starting materials has on the process should also be taken into consideration. With extensive variability in starting materials and process, validation of automated systems becomes critical.
Participants in the session then identified several possible strategies for addressing these challenges. A critical factor for success will be standardization of analytical testing methods, documentation and batch records and collection procedures for starting materials. The group highlighted the fact that standardisation of some of the smallest common denominators such as cell washing and fill finish could help the entire industry reduce cost and timelines for product development.
In addition, access to educational materials and processes designed to help industry understand the ease and benefits of communicating with regulators early and often in the process would be beneficial.
Understanding GMP Requirements
The group emphasised that automation is part of a GMP system and cell and gene therapy developers must understand GMP requirements. A GMP automation system is qualified with a required level of documentation and includes QA, materials management, training, qualification, documentation and data records.
While the vendor is responsible for ensuring equipment meets specifications and performs safely and as intended, the sponsor is ultimately responsible to repeat qualification with their specific process and under their own quality system.
Ensuring Effective Communication
The cell and gene therapy industries are evolving rapidly, and this demands timely and proactive communication between developers and suppliers with regulators. A key first step in ensuring robust communications is to understand expectations at national, regional and local levels and importantly, that these expectations are continually evolving. Publicly available information such as guidance documents can be a great resource to keep up with regulatory expectations and what has been acceptable to authorities.
When possible, it is advisable for developers to include technology providers in preparation for discussions with regulatory agencies. Additionally, providers should include plans for master file submission where available and support regulatory submissions directly or through regulatory agencies bodies where they are not. Use of robust risk management tools (FMEA, Assurance cases, etc.) will help ensure acceptability.
While meetings with regulators are readily available for therapeutic developers, this dialogue is more difficult for technology providers to arrange. A productive strategy is to proactively educate regulators about technology products and processes rather than seeking acceptability.
While regulatory expectations evolve and become more defined, communication between therapy developers, technology providers, and regulators will limit late-stage challenges regarding the acceptability of automated systems in meeting expectations of cGMP inspections. Developers and technology providers should also understand that cGMP manufacturing is dependent on the whole of the manufacturing system, and both parties have responsibilities specific to their respective role in the system.
The next steps for this working group should include drafting recommendations for regulatory guidelines and communication pathways which will help stakeholders develop implementation strategies for automation that are compliant with cGMP expectations.
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
3 – Automating Release for Autologous Products
4 – Modularity and Flexibility in Closed Systems