Betting the Pharm: Determining Regulatory Expectations for Pharmacology Studies

02 Jun 2015

Are you generating sufficient pharmacology data and presenting the data effectively for your preclinical drug development program?

navigating the regulatory landscape and understanding how regulators work and what they expect is a difficult task for drug companies transitioning from a research-based drug discovery program to a formal development program.  the initial goal of an early development program is to generate relevant pharmacology, safety, and toxicology data on a candidate therapeutic with the goal of obtaining agreement from a regulatory agency that the information supports the conduct of first-in-human (fih) clinical trials.  while requirements for safety and toxicology studies are well described, pharmacology studies are only sparsely discussed in regulatory guidance documents.  as such, drug sponsors in their early development program commonly ask themselves how much pharmacology data are needed and how to present the generated pharmacology data for a successful initial application such as an investigational new drug (ind) submission in the united states or a clinical trial application (cta) in canada or in europe.

pharmacology studies are intended to assist with target validation, identify mechanism(s) of action (e.g. receptor binding, functional activity, and structure-activity relationship studies), provide proof of concept (e.g., efficacy in the proposed disease or disorder to be treated), and help determine efficacious dose levels and regimens that may be translated to the clinic.  in this regard, any study that demonstrates or supports the mechanism(s) of a potential clinical benefit of a candidate therapeutic (including information gathered from the published scientific literature) is valuable to the development program.  but how does this information fit into a regulatory review?

in an original cta or ind for a fih trial, companies are required to provide information on the safety and quality of the drug (or biologic) to support clinical studies, as the primary focus at this early stage is safety.  however, summaries of the available pharmacology data are also expected in regulatory submissions and are particularly useful for supporting the mechanism of action of biologics which are typically targeted to a single receptor, enzyme, or other specific target.  while the full "story" of the efficacy and mechanism of action of the drug might not yet be available, and further studies may be ongoing, this information assists with convincing regulators and clinicians that a drug candidate has the potential to benefit patients, which is not a small consideration.  as such, companies should be prepared to insist on well-designed, high-quality, and relevant pharmacology studies (e.g., always include a negative control group, try to use test material that is as close to the clinical material as possible, etc.) and to have reports available to provide to regulatory reviewers if requested.  early-stage companies may be accustomed to preparing poster presentations and slide deck summaries, but formal study reports containing methods, results, and conclusions are more informative and useful in the long run.  indeed, having well-designed studies that are summarized in an appropriate and detailed format has added benefit from an investment perspective.  potential investors will do their due diligence to ensure the scientific validity and robustness of a development program, and this process is facilitated when detailed pharmacology study reports are available.

what is the best path forward?  once a development plan is in place that includes details on your pharmacology and toxicology studies, consider requesting formal pre-submission meetings with regulatory agencies to get answers to pertinent questions regarding nonclinical, clinical, and manufacturing plans.  intertek has extensive experience helping clients transition from scientific concept to clinical development, and can help address your pharmacology and toxicology needs as well as assist with interactions with regulatory agencies.

for more information, please contact me at valentia.leebrotherton@intertek.com.