4 Things to Consider about Pharmaceutical CMC

“A robust and tailored CMC strategy enables an efficient development program, prevents information gaps that will delay key regulatory filings, reduces the number of rate-limiting CMC activities, and increases the chances of a successful outcome: approval”.

?- Andrea Pless,?Principal Consultant and CMC expert at NDA Group.

?What is CMC?

CMC (Chemistry, Manufacturing, and Controls), also referred to as pharmaceutical Quality, refers to the various procedures used to make and assess the material characteristics of pharmaceutical drug products as well as their components. CMC is regulated by administrative law across the entire product development life cycle: from first-in-human studies to post-approval. CMC regulations are foundational as they guarantee the identity, strength, quality, and purity of the product—which is necessary to demonstrate and maintain pharmaceutical safety and efficacy. CMC regulations apply not only to the final product but to everything involved in making it. The regulatory authorities require pharmaceutical companies to define the composition (chemistry), and how it is made (manufacturing), as well as procedures & testing (controls) to ensure consistency.

?Why CMC?

Information regarding CMC for drugs is a legal requirement to begin first-in-human clinical studies to ensure the safety of the clinical subjects. To sell a pharmaceutical product, the manufacturing practices, materials, and product specifications must be defined and ensured by independent quality oversight. The development process involves studies to establish controls appropriate for the current use of the material while also providing relevant drug product for pre-clinical and clinical studies. To ease the process for drug-developing companies, both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have issued guidance regarding quality requirements and participate in global guidance harmonization through the International Council for Harmonization (ICH) and the World Health Organization (WHO). However, application of guidance to a specific product at a particular stage of development can be ambiguous. “For various reasons, government agencies won’t tell companies exactly what to do, which is why agencies recommend help from expert consultants when they are needing direction”, says Quin Christensen, Senior consultant at NDA.

?CMC Strategy

It is expected that the characterization of a product with respect to its critical quality attributes will be ongoing during development to meet the increasing Quality requirements on the way to final approval. Creating a CMC development plan early in the development process helps to avoid future roadblocks. “The benefit is the potential for a streamlined and efficient development program that optimizes the use of available resources. ”, Quin explains. According to Andrea, CMC can easily become rate-limiting to getting a product approved. “Always start CMC planning early. Many times, the drug developer is quick to get a clinical study started and CMC is not given ample time to ‘catch up’ to positive clinical study outcomes. Incorporating quality and control into drug development programs is a very time-consuming and rigorous process and should not be short-changed”.

CMC for Success

CMC cannot be approached in a one-size-fits-all fashion. There are opportunities to consider early in development that can have a big impact later. “A robust potency assay is not a regulatory requirement for early biologics but investing in this, or an appropriate experimental system for a small molecule, ensures early development results remain relevant”, Quin says. Similarly, having a phase-appropriate characterization strategy is key to avoid having to repeat studies. “Many times, methods are developed and qualified using material that is not representative of what is being used in a study”, Andrea explains. Understanding opportunities and requirements for pre-clinical material characterization is key because it must be relevant to what will be proposed for clinical studies. CMC consultants are specialists that can develop an appropriate CMC strategy and facilitate interactions of technical personnel and with regulatory authorities to de-risk drug development.

The role of a regulatory CMC professional is critical in facilitating non-clinical and clinical studies, and in expediting the time it takes for products to reach the market. In our next newsletter, our CMC expert and senior consultant, Quin Christensen, will provide invaluable insights into the daily work of a regulatory CMC professional. Through his expert lens, readers will gain a deeper understanding of this important role and the impact it has on the drug development process.

NDAs team of development experts can support development of a robust and tailored CMC program early in the development process, paving a road to approval. To future-proof your pharmaceutical development program, talk to our team at?[email protected] or visit?www.ndareg.com.?