Michaela Sharpe, Head of Cell Safety at Pfizer, delivered an interesting presentation last week at the World Stem Cells & Regenerative Medicine Congress aboutÂ the development and implementation of innovative safety strategies in the context of the pharmaceutical industry. Considering how, for example, disease models be harnessed in pivotal safety studies and the regulatory requirements for drug safety data in a stem cell context.
She began by drawing a comparison between different medicinal products.Â At one extreme, there is the small molecule, such a 21 atom “bicycle”.Â Complex biological products come next, but at the other extreme sits an entire cell,- an astronomically larger and more complex entity.Â The opportunities for things to go wrong are obviously considerable, so safety is plainly paramount.
So, what should safety studies be like?Â Michaela answered the question: they should be rational, designed to solve problems, assessed using the best technologies and methodologies, data driven and make judicious use of animals.
Studies should therefore recommend safe starting clinical dose levels, a biologically plausible dosage escalation scheme (where applicable) and uninterrupted clinical development: a feature which highlights how important it is to have a plan at the outset.
As noted above, the choice of animal for toxicity studies is important.Â Michaela emphasised the importance of ensuring that the cells endure or act in the chosen animal model as they would do in humans.Â Similarly, researchers might have a requirement specific to a particular disease or injury, to a micro-environment for differentiation or for engraftment.Â Immunosuppression is also a key issue.Â The use of disease/injury models,- in particular, the importance in obtaining best data-, were particularly stressed.
Considering whether the pivotal nonclinical data should be GLP, or not, Michaela Sharpe raised the question whether the safety study should be performed in a healthy, or in an immune-compromised, animal. If not, then GLP compliancy may be reached. If not, however, if the animal disease model is transferable to a GLP facility, GLP compliancy may again be reached. If the data is not GLP compliant, you have to ask “why not?”
Turning to the regulatory framework, Michaela reminded delegates that if the product falls to be classified as a gene therapy medicinal product, it will be essential to comply with the relevant guidelines and requirements for this ATMP subclass.Â Discussion with regulators is essential.
Michaela concluded that nonclinical safety strategy needs to be adapted for a given product, that (although different to conventional drugs) the same principles of toxicityÂ assessment apply, that it is important to select appropriate animal models and to seek clinical trials.
Check back here in a couple of days for the full presentation. Excellent presentation Michaela!