The draft guidelines tell developers of cellular and gene therapies, therapeutic vaccines, xenotransplantation products and combined biologic-devices what preclinical information they need to provide to move their products into clinical trials.
Assessing the safety of such treatments – known collectively as CGT products – is a challenge according to the Center for Biologics Evaluation and Research (CBER), which said that standard preclinical testing methods used for small molecule drugs are often not appropriate.
Thomas Vihtelic, director and senior study director of experimental therapeutics at MPI Research welcomed the guidelines, telling Outsourcing-pharma.com that flexibility is important in a field of research that has evolved considerably since the previous recommendations were issued in 1998.
“As the science of these therapies has matured and been applied to new product development, it has undoubtedly influenced the content of these guidelines and the expectations of regulators,” he said, adding that “a science-driven approach for review of these products dictates there be flexibility in the guidelines.”
Vihtelic also suggested the recommendations will benefit contract research organisations (CRO) and customers, explaining that while they do not cut preclinical timelines their emphasis on discussing potential hurdles with regulators will help developers avoid extra studies.
“The more efficient use of resources directed to preclinical development as the result of the updated guidelines will not impact the trial cost. However, additional preclinical bridging studies may be required if, for example, manufacturing changes affecting the cellular product comparability to early studies are instituted during the clinical trial phase.”
He also predicted that the requirement that scientific justification for the selection of test animals species be provided “will facilitate our sponsor interactions and study design decisions, which will have a positive impact on our company.”
Addressing uncertainty
Raymond Donninger, programme manager, at Covance was similarly positive about the new recommendations, telling us that CGT development is in its infancy.
“The draft guidelines address a number of these questions, provide some structure for submissions and give insight into the FDA’s thinking in terms of the approach to the development of these unique products. The guidelines will certainly continue to develop as the field matures but this is a very welcome start.
“While the variability in the types of products and approaches makes it difficult to define highly specific guidance, the draft guidance goes far enough in terms of our current understanding to be useful in guiding development programs.”
More immunogenicity info
vivoPharm CEO Ralf Brandt also welcomed the guidelines. He told us they “support the role and importance of CROs and could eventually lead to more work and revenues. What effect this will have for drug development is hard to foresee, but maybe will require better selection for funding and therefore result in better drugs in shorter time.”
Despite this optimism, Brandt suggested that the guideline's discussion of toxicity testing needs to include more information about immunogenicity.
“The introduction of biologicals can lead to very unwanted effects caused by the immune system and this needs to be differentiated in short-term and long-term effect. The general wording covers this, but I suggest including an independent paragraph on immunogenicity.”