Chemistry, Manufacturing and Control for Biologic Development

There is no question that the process of bringing biologics to market is not easy. Besides testing their safety and efficacy in ever-increasing numbers of volunteers over a decade or more, biopharmaceutical companies must also design a protocol for scaling and manufacturing the drug for regulatory approval and commercial use. Furthermore, many biologics in development today address high unmet needs, giving biomanufacturers an impetus to expedite their development timelines and bring their biologics to market as quickly as possible while ensuring their molecule’s safety and efficacy. As a result, biomanufacturers are under immense pressure to expeditiously develop streamlined chemistry, manufacturing and control (CMC) strategies.

But pharmaceutical companies do not have to go at it alone. With the help of a contract development and manufacturing organization (CDMO), a company can optimize the CMC process, for efficient and reliable biological production and release.

A CMC strategy incorporates many elements that a biomanufacturer must plan to ensure a controlled and consistent product. These elements include reliable and effective tests that characterize their biologic’s chemical properties, including its stability. A CMC strategy also includes descriptions of how and where the biologic is manufactured, including the details of the process qualification, operation and maintenance plan. Finally, biomanufacturers need to describe their plans for how to ensure the biologic’s proper and consistent quality attributes at product release and while it’s on stability. In the end, a CMC strategy incorporates many steps and requires a dedicated effort to develop it and execute it according to plan.

CMC design challenges for small biopharmas

Companies must understand the risks associated with CMC, and in this area, large pharmaceutical companies can benefit from their experience and industry knowledge. These companies have everything they need to test their molecules as well as optimize and validate their manufacturing protocols. In contrast, small biopharmaceutical companies, such as virtual companies, face additional challenges, as they possess fewer of the resources they need to design, optimize and execute a CMC strategy. To make the process more efficient, many companies will recycle portions of pre-designed CMC plans for various products. Yet, they must still keep their end goal, regulatory approval, in mind from the beginning.

To maximize their molecule’s chance of regulatory success amidst expedited timelines, companies must address how their CMC strategy will work to satisfy FDA requirements as the program progresses. The FDA works with biomanufacturers to ensure their CMC strategy is sufficiently defined, that the molecule and its target indication are fully understood and that the formulation is optimized. However, biomanufacturers need to build in extra time to respond to FDA feedback, as the Agency might require extensive revisions. If the company has trouble aligning its strategy with FDA guidelines, this could ultimately impact the quality of the product and lower its chances of reaching the market. The FDA might withdraw its market authorization, pause production and levy fines if the company cannot ultimately meet the FDA’s expectations.

The factors that make a strong CMC strategy

To prevent complications with the FDA, biomanufacturers should consider more than one CMC strategy throughout product development and perform continuous improvement to optimize their approach. This will help them mitigate the risks and satisfy regulators to bring much-needed relief to patients.

Successful CMC strategies share many common elements. For example, a strong strategy includes robust testing, rigorous monitoring and meticulous data collection. A successful manufacturer will monitor its development process to identify potential sources of risk. To reduce risk, the CMC plan should be stage-gated, and scientific justification must be provided for all important decisions made from process development to product release and expiry dating. 

The complexity of CMC design may tempt companies to take shortcuts without a risk mitigation plan, but this can lead to challenges with their Biologics License Application (BLA) and cause delays in regulatory approval. Instead, companies should begin designing their CMC strategy as early as a disease target is developed and should continue refining it through the entire development process. Small companies should remain vigilant to avoid surprises late in the process that can slow production and reduce the chance that their molecule will reach the market. Often, companies seeking to avoid these issues and optimize CMC strategy development will partner with a CDMO.

Enlisting the help of a CDMO

As smaller biopharmaceutical companies play a bigger role in early drug development, CDMOs become a more integral part of the biopharmaceutical industry. CDMOs have experience working with biopharmaceutical companies and the FDA to bring biologics to market and can lend this experience to smaller companies in need of guidance. CDMOs understand how to develop risk-based and scientifically justified CMC strategies that the FDA may favor.

CDMOs also bring scientific, technical and regulatory knowledge to the table. These companies can offer the scientific justification that biopharmaceutical companies need as they establish their production, analysis and validation plans. Their guidance will increase the chance of regulatory success without too much do-over.

CDMOs can also reduce costs. Without cost controls, a small biopharmaceutical company will face financial challenges as development progresses. CDMOs can help small companies understand the cost of each CMC step and how their decisions will impact the budget, making it easier to keep costs down while increasing the chance of reaching the market.

No pharmaceutical company should take CMC for granted, especially smaller companies who lack experience in biologic CMC development. Even if a biologic shows success in clinical testing, it will not find success in the market without robust CMC strategy. By partnering with a CDMO, biomanufacturers with limited experience bring their products to market faster to meet the needs of patients more quickly.