Tips for Nonclinical Pharmacology and the Medical Writers that Draft Regulatory Submissions
by September Mihaly, Ph.D., RAC
Summarizing nonclinical studies in Module 2.6 of the common technical document (CTD) takes a unique skillset. These studies include pharmacology, pharmacokinetic, and toxicological studies conducted in vitro or in animals and are generally conduced prior to the administering the drug in humans.
Nonclinical studies are intended to show the efficacy and relative safety of the drug at this early stage. The pharmacology studies, in particular, are essential to supporting label claims and demonstrating that the drug works as expected. Medical writers drafting this portion of the new drug application (NDA) must have in-depth regulatory knowledge and a willingness to start work on a project that has already been in motion for several years.
By the time work for the nonclinical medical writer begins, a drug development pipeline will have narrowed significantly from its original list of leads. Once the team has pared it down to three or fewer compounds, nonclinical proof-of-principle studies are then conducted. Additionally, the sponsor may start with in vitro and in silica studies, and bring in a medical writer once in vivo nonclinical studies are underway.
Getting with the program
To get a handle on pharmacology, it is important for the medical writer to understand the entire drug development program, including any variations in indication and/or patient population. Understanding the chemistry of the drug and its mechanism of action is important, but knowing its regulatory history allows the medical writer to contribute fully to the entire drug development program.
When summarizing nonclinical studies, the medical writer will usually begin with a portion of reports that are in either final or draft form.
At times, later applications for a more rare indication or a small change to the molecule, for instance, can seem like just follow-up work. That is a myth. Deviations to the patient population, the indication, or the drug itself change how the medical writer focuses on drafting pharmacology sections of the NDA.
A case study
Take the marketing of prodrugs, for instance. A prodrug is a pharmacologically inactive form of a drug that is metabolized within the body to the active form. There have been cases where a prodrug is the initially marketed form, and the biologically active form of the drug is developed for a later application.
The role of a nonclinical pharmacology medical writer includes summarizing the mechanism of action for the drug, and providing a bridge between the original drug and the new drug. The writer may be able to use portions of the previous NDA submission as source material, as well as for comparison. In any case, it is important to keep in mind that the prodrug and active form can have markedly different efficacy and safety profiles.
Experts and writing tips
Medical writers should be subject matter experts of the regulatory guidance inside and out and have a good understanding of the drug under study. Additionally, getting to know the team and consulting with other experts is crucial.
When drafting summaries from the final nonclinical reports, it is generally a good idea to leave the conclusions as the study experts have originally written them. However, medical writers must know when to point out the mechanism of action, other effects that are not related to the desired effect, and any safety pharmacology concerns.
Bringing a drug to market is costly – around $2.9 billion according to a recent research. Ultimately, the nonclinical pharmacology summary will be the basis for detailing the therapeutic effect, making this section critical to get right the first time.
About the author
September Mihaly, Ph.D., RAC, is a Senior Medical Writer at MMS, based in Chapel Hill, North Carolina. She earned a Doctor of Philosophy in Toxicology from NC State University. Connect with her on LinkedIn.