General September 2019
The next generation of medicines, ISPE Workshop hears how CAR-T cells are set to disrupt commercial manufacturing
Maurice Parlane recently co-chaired the successful two-day ISPE Process Validation (PV) Workshop in Boston with ISPE colleague Gretchen Allison from Pfizer. The event featured a wide range of delegates from industry, academia and the regulatory community.
Attendees joined to discuss existing and emerging challenges in process validation as well as an exciting new wave of breakthrough products such as cell and gene based products, including Chimeric Antigen Receptor T-cells (CAR-T) and Antibody Drug Conjugate (ADC) therapies.
Maurice said the medicinal applications of CAR-T cells are rapidly evolving into exciting commercial therapies; presenting some unique and disruptive challenges to scale up or scale out of commercial manufacture.
“This technology is individualised – a lot different to scaling up for mass production. The manufacturer is taking your cells and adding a molecule/cell or factor that turns them into super-soldiers that will go and kill cancer cells selectively and at the same time recruit your other cells to do the same,” he said.
“This will have a profound impact. The next generation of medicines!”
Participants also focused on the challenges of adopting science and risk based lifecycle validation approaches under emerging medicinal modalities and in an accelerated development program. What was apparent was the will of the regulators (FDA) to collaborate and expedite new products under a paradigm where process understanding is still developing while the products are being reviewed.
“The most challenging element is making commercial and compliant products based on limited data sets or developing process knowledge, and having a scalable process at the end of the expedited approval,” Maurice said.
There was keen debate over the tension between the traditionally conservative culture of typical biopharmaceutical manufacturing groups and the approaches needed for developing these new modalities.
Industry participants shared interesting case studies highlighting the challenges of process validation during product development programs, while also demonstrating useful skills and techniques that can be applied across the validation lifecycle.
Presenters from industry and the regulatory community gave informative talks about the challenges of introducing advanced technologies and analytics into biotech processes. Senior staff from both CBER and CDER shared their insights into their experiences with expedited approvals of BLAs, and outlined areas industry should focus on to ensure these significant products get to the patient in an expeditious and safe manner.
Maurice, a partner in CBE, also organised and facilitated interactive breakout session during the event with Catherine Giacolleti from Synolostats. During these sessions workshop attendees were presented with problem statements on some of the most challenging issues facing process validation professionals including:
- Managing the impacts of robustness of API manufacturing processes within PV programs
- Lifecycle PV challenges presented by limited datasets
- Validating resin & membrane life
- Legacy process validation prioritisation
- Validation of re-work and re-process requirements
Attendees worked in teams to refine the statement, discuss any roadblocks and identify possible solutions. Delegates bought their own experiences, expertise and opinions to the table, collaborating with each other to develop ideas and strategies to deal with these problems, which were then fed back to the wider meeting
The resin and membrane life validation strategies discussed will be further developed within the wider ISPE community with the objective to produce a discussion paper on this topic to be published under the auspices of ISPE. The practical challenges of working with limited data sets to produce compliant products also triggered lively discussions, with participants keen to share their experience and offer advice.
The success of the workshop motivated us to continue sharing ideas and working with each other to enhance our process understanding and improve outcomes for patients.
Maurice Parlane is the current chair of ISPE International’s Process Validation Team.
The ISPE Process Validation Team’s objectives are to:
- Assist industry in practical implementation of lifecycle approach to Process Validation (PV) with particular focus on unmet needs
- Increase understanding of the new paradigm for process validation by leveraging previously completed ISPE PQLI work as a foundation
The PV Team provides the following deliverables for ISPE:
- PV themed conferences, and workshops, as well as contribution to various educational sessions at other international events both for ISPE event and others
- Discussion papers - short and focused publications on targeted PV topics providing worked examples, benchmarking of best practices as well as decision making tools and processes
- Develops and maintains ISPE’s formal training program and provides the qualified instructors to deliver this [Maurice is one of the 7 international instructors on this topic]
- Development and maintenance of ISPE’s Good Practice Guide – the largest publication of its type at over 500 pages. [Maurice was a chapter author and one of the team responsible for final editing and review].