Euro Convergence: Academic clinics should establish risk management programs for ATMP development

Regulatory NewsRegulatory News
| 17 May 2021 | By Joanne S. Eglovitch 

Academic centers should establish risk management programs to successfully commercialize cell and gene therapy products and to be a viable partner with contract research organizations (CROs) and manufacturers in developing these therapies.
So asserted Lutz Uharek, a professor of internal medicine and founder and CEO of Xencura, at RAPS Euro Convergence 2021 on 12 May in discussing some of the challenges and opportunities for academic centers in developing cell and gene therapies. Uharek is a hematologist and cell and gene therapy specialist at Berlin’s Charité Hospital.
Uharek described how his company used these risk management principles in developing a blood cancer treatment which has now been commercialized.
Historical origins
Uharek noted that development of cell and gene therapies had its historical origins in academic clinics and laboratories. Now these entities are being increasingly sought out to develop these therapies as more applications are being explored, especially with the “groundbreaking results” of these trials in the oncology areas.
He said that last year, more than 1,000 personalized cell and gene therapeutics were in clinical trials worldwide, and over 80% of these were for treating oncological diseases. With this explosive growth, “the need for clinical testing and application facilities is growing steadily,” said Uharek.
This means that academic centers have to become capable of many of the activities that pharmaceutical companies ordinarily perform, such as validating starting materials used in these therapies. Some of these activities, though mean that centers must have risk management programs in place.

ATMP risk management not easy
“Requiring a quality assurance system for risk management is not within the scope of these academic institutions” and is not an easy task, said Uharek.
While risk analysis is typically conducted in “highly standardized” pharmaceutical manufacturing operations, the nature of cell based ATMP manufacturing does not lend itself to a standardized process. Cell therapy manufacturing is characterized by a high degree of flexibility, is dependent on human intervention, uses poorly automated processes and is affected by the variability of reagents.
Uharek noted that current regulatory guidance also provides little direction on how to conduct risk management for ATMP production.
To address this gap, the German Cancer Consortium (DKRK) and the Paul-Ehrlich Institute held a 2016 workshop on designing risk-based approaches for ATMP manufacturing in academic clinical trials.
The learnings from the workshop were that centers should form quality risk management working groups to explore the risk of these compounds. The group should be led by a designated team leader, and their activities should be aligned with the principles established in the International Council for Harmonization’s Q9 guidelline on risk management.
These risk models can look at the risk of transmission of infectious agents to therapies and the risk of induction of autoimmune reactions.
At an academic center as elsewhere, risk assessment should take into consideration the severity of these risks and the probability of the risks occurring; then the risk management group should assign a priority score according to whether the risk is high or low.
Risk management activities should be extended to choosing vendors and materials, in-process controls and conducting process validation activities.
Uharek said that academic institutions should also take their cues from manufacturers, and therapies with greater complexity should be manufactured in a centralized production area while those with a lower level of complexity can be manufactured in decentralized locations.

Euro Convergence Programme




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