The crucial role of CMC in the drug development life cycle

A crucial building block, Chemistry, Manufacturing and Controls (CMC) procedures are key for maintaining quality, consistency and safety throughout the entire drug development lifecycle.?

Drug discovery and development is a critical job, impacting millions of people all across the planet. But if the process isn’t done correctly, and to the highest standards, there can be serious implications later down the line - which is where CMC comes in.?

Simply put, CMC professionals are key to keeping any medical advancements safe and quality controlled both in production and when the drug is on the market. So, what is the CMC role throughout the entire drug development cycle, and why are these processes so important??

What is CMC?

An acronym for Chemistry, Manufacturing and Controls, CMC aims to create a list of integral procedures and methods that must be followed at all times when developing any kind of new pharmaceutical product. It refers to various practices that under no circumstances should be overlooked.?

The primary goal of CMC is to ensure any drug product has a safe and reliable composition so that the formula that becomes commercially available is exactly the same as what was used in clinical trials. Essentially, it’s about defining a set of manufacturing practices and specifications (looking at the physical and chemical characteristics of drug products) to ensure consistency in batches.?

A lot of these guidelines come from Food and Drug Administration (FDA) regulations, which must be adhered to at all times to ensure product quality and compliance.

What is the CMC role in different stages of the drug development lifecycle??

Every single stage of the drug development life cycle will involve CMC practices, right from the drug’s very inception, all the way to manufacturing, licensing and marketing - the work doesn’t just come to a screeching halt once the drug hits the shelves.

Such a critical role and process calls for professionals in the field to assist at every stage, providing an in-depth knowledge of pharmaceuticals, as well as critical understanding and interpretation of the FDA regulations. Having these types of people to hand gives the drug candidate the best possible chance of being approved - critical when success rates are so low.

CMC is an umbrella term that encompasses all kinds of roles and responsibilities, from drug product development which includes sourcing API (active pharmaceutical ingredients) and excipients, manufacturing planning, distribution logistics, vendor and facility selection, risk assessments, reporting and more.?

A key responsibility when it comes to CMC is authoring. This entails the creation of critical CMC documentation for approval. For example, the CMC specialist needs specific scientific knowledge to be able to understand data concerning the API of drugs. Alongside this, they need to write clear instructions on how these drug substances are stored, in compliance with regulations.?

Other responsibilities include compiling and writing accurate information, such as composition of dosage form, the raw materials used to produce the product and much more, all so this can be clearly communicated in the drug’s Marketing Authorisation Application (MAA), Biologics License Agreement (BLA) and New Drug Application (NDA) documents.

Another key aspect of CMC is coordination, which involves collating and transferring documentation - whether that be from the laboratory or contract research organisations and partners. This documentation will help when it comes to creating the dossier licence application for submission of the drug.

But that’s not even half of it. CMC processes are essential at every stage of the process, way beyond when the drug reaches the market. Post-approval, the CMC continues to ensure the drug meets all the relevant criteria and regulations, maintaining the highest of standards for its entire lifetime.

Why is CMC so important?

As we know, CMC is integral to ensuring a drug product is safe and consistent, offering a blueprint to ensure all standards are met. The main goal is to assure the quality and efficacy of the finished product during every single phase of development.?

The entire drug development process takes a lot of time and money to complete, with only 10% of drugs actually making it beyond clinical trials. And without CMC there to detect issues at every stage of the drug development process, there’s the possibility of an issue arising at the very end, costing the organisation a devastating amount of time and money. CMC measures are in place to prevent this from happening, identifying issues with the process or molecule early on to ensure development doesn’t need to begin again from scratch.

If CMC practices fail to comply with the current regulatory requirements, the marketing authorisation will be withdrawn, leading to a hefty fine and possibly suspension. With that in mind, it’s clear that CMC guidelines are absolutely fundamental.?

And though a CMC strategy is mainly there to satisfy the requirements from regulatory agencies, developing a consistent CMC program can provide other benefits such as accelerating your entire development process, avoiding pointless delays and even reducing development costs overall.?

Challenges for CMC organisations

However, developing a proper CMC strategy is not always easy. FDA regulatory requirements are evolving as we speak, so it’s important to stay up to date to ensure you’re always compliant with the most recent guidelines.

Developing a CMC program that works for all your potential drug candidates is almost impossible, as each candidate has various unique characteristics, dosage forms and patient groups - so a generic, one-size-fits-all approach is likely impossible. This means you’ll have to set general parameters for your CMC program, but tailor it to suit, taking into account your current drug and the attributes it holds.

In addition, CMC organisations are under increasing pressure not only from changing FDA guidelines, but from the need to speed up product development, the increasing complexity of new advancements and even advancing technology which requires new, digitally-proficient staff.

Changing lives across the world

While the role of CMC might seem overshadowed in comparison to others within the drug discovery and development pipeline, their role is crucial for addressing patient needs all across the globe.?

All in all, CMC principles should always be at the very core of your process, never pushed to the sidelines.