Following the discovery of a novel biologic, a biomanufacturer must develop an efficient, reliable and consistent process to scale, test and optimise the molecule for regulatory approval and commercial production.
Biologics create new challenges, especially those for rare disease or personalised medicines, as they are often accompanied by expedited regulatory timelines.
To address these challenges, biomanufacturers must efficiently construct and execute a reliable chemistry, manufacturing and control (CMC) strategy.
A sound CMC strategy fully describes a molecule’s chemical properties, as well as how and where it is made, and how the manufacturer will ensure its proper and consistent production.
Manufacturers must begin by demonstrating a reliable and effective method to test their compound, including stability testing and forced degradation testing. Then, they must describe their manufacturing and support facilities’ design, qualification, operation and maintenance plan. Altogether, CMC involves dozens of steps and significant resources to develop and execute.
Many biomanufacturers seek to expedite their development timelines to safely and efficaciously bring the therapeutic to patients as soon as possible. This puts increased time pressure on biomanufacturers to consider and plan their CMC strategies as early as possible.
Producing a reliable CMC strategy
Small biopharmaceutical companies have fewer resources than larger ones; as a result, it’s harder for them to generate reliable and effective CMC strategies.
For instance, it takes experience and industry knowledge to understand the risks that accompany CMC strategy design. Large pharmaceutical companies can rely on their experience to develop a plan that accounts for all the necessary testing, optimisation and validation steps, whereas smaller companies need to determine how to collect the data with the resources they have available.
To make the process easier, many biomanufacturers repurpose parts of predesigned CMC plans among various product pipelines.
Furthermore, to meet expedited regulatory deadlines, biomanufacturers must demonstrate that their methods align with US FDA requirements early on during the drug development process.
The FDA will work with the biomanufacturer to make sure their CMC process is well defined, that the molecule and disease are fully understood and that the formulation is optimised.
But, biomanufacturers need to leave plenty of time to let this happen; the FDA might require the company to make extensive revisions to their CMC strategy to ensure it aligns with their expectations. If a biomanufacturer needs to make significant changes to its CMC strategy, it could hamper product quality and reduce the chance that its product will reach the market.
If the company is ultimately unable to comply with FDA requirements, the agency might withdraw its market authorisation, require that the manufacturer pause production and levy fines.
To streamline the process, biomanufacturers should consider several CMC strategies throughout product development and optimise their risk-mitigation approach to both satisfy regulators and meet the needs of patients.
The process should begin as early as target development and should continue throughout product formulation and clinical research. Constant vigilance will enable smaller companies to avoid surprises late in the development process that can derail production and threaten their chance of reaching the market.
How a biomanufacturer can enhance its CMC strategy
A strong CMC strategy is tailored to each compound and involves robust testing, rigorous monitoring and meticulous data collection. A company must monitor its development process and identify sources of potential risk.
It must also justify all its decisions on a scientific basis to remove risk from the workflow and optimise product development. Creating a CMC strategy is a complex process, but companies should not take any shortcuts without a risk mitigation plan; otherwise, this can lead to challenges with their Biologics License Application (BLA) and delay getting drug to patients.
To help them develop a streamlined strategy and avoid these issues, many smaller companies chose to partner with a contract development and manufacturing organisation (CDMO).
The greater role of innovative, agile and emerging biopharma companies in early drug and biologic development today means that the FDA might see more diversity in the BLAs it receives for novel drugs and biologics.
Experienced CDMOs can help these small companies to navigate their communication with the agency. CMDOs have not only seen a variety of applications, but they have also witnessed how the FDA responds — and this insight can help small biomanufacturers to develop a risk-based CMC strategy.
A biomanufacturer can benefit from a CDMO’s scientific, technical and regulatory knowledge. A CDMO can scientifically justify each component and product, the company’s analytical and validation methods, its stability data and the design and validation of product and process design. Overall, a CDMO’s guidance will help a company to satisfy FDA regulations.
Creating a CMC strategy is expensive and, without cost controls, the spending can become overbearing for a small company. CDMOs can help small companies to manage their costs.
A CDMO can calculate the cost of each CMC step and how each decision will impact the budget, which will make it easier for products to reach the market. Plus, with additional cost savings, a small company can begin other projects and diversify their portfolio to increase their chance of success.
A small biomanufacturer should not underestimate the complexity of a CMC strategy. As strong as a clinical trial may be, a biomanufacturer cannot reach the market without a robust CMC strategy.
Biomanufacturers, especially those who have not developed a product before, can benefit greatly from partnering with a CDMO that can assist them with the process. A strong partnership will help to bring products to market faster and offer some patients their only chance of finding relief.
