How Do You Manage Corporate Risk in Drug Substance Manufacturing?

When dealing with New Chemical Entities (NCEs) and manufacturing novel Active Pharmaceutical Ingredients (APIs), it’s no wonder that risk management is a serious concern. Today’s Contract Development & Manufacturing Organizations (CDMOs) are being asked to do things that have never been done before, which involves a tremendous amount of uncertainty.  It’s no wonder that according to an article in Pharmaceutical Technology, “about nine out of 10 drug candidates fail to win approval.” The same article indicates that this comes at a cost just below $2.6B for each drug approved, according to the Tufts Center for the Study of Drug Development (CSDD).

Despite the best intentions, many factors can impact risk. The quality or availability of raw materials; the relevant experience of the CDMO team; the methodology utilized; or the regulatory requirements imposed. Any one of these issues can put your project at risk of going over-budget, failing to reach commercialization or resulting in the loss of millions of dollars and unhappy investors. 

Yet, despite the inherently risky drug substance manufacturing environment, there are ways to effectively lessen its impact on the product side, through diligent research into the right CDMO for the job, carefully vetted suppliers, robust methods and testing processes and other best practices. Ultimately the goals is to manage over-runs in cost, time or investment of resources. 

To minimize these concerns, below are four best practices to consider.

1. Plan a realistic regulatory strategy. The most important thing is to develop a clear and realistic regulatory strategy that will guide the scope and lifecycle of the project, as well as its associated costs.  A good way to accomplish this is to hire a consultant who has done this before and who knows all the latest requirements. You can also request a meeting with the FDA and their professionals can guide you. Once you have your regulatory strategy in place, the key is to share it with your CDMO in order to accurately execute  chemical development process. This is the single most important thing you can do and cost-control will follow.
2. Pick the right CDMO for the job. Since each project is unique when it comes to API development,  it would be impossible to have a CDMO that has the precise experience working with the chemical entity.  It pays, however, to take your time choosing the right one with extensive experience working with a variety of similar projects, SOPs and insights that can be applied to improve your project’s success rate.  The key to reducing risk is keeping open lines of communication between you and your CDMO so it’s important to pick one that you can trust and feel comfortable collaborating with.
3. Shop around for suppliers. Quality raw materials can make or break your project, so it’s important to work with CDMOs that have good relationships with reputable suppliers. The more impurities are found in stability testing, the longer the project will be delayed, and often, there’s no way to eliminate them at all. Starting your project out on the right foot with quality materials can minimize the risk of failed projects because of the levels of impurities.
4. Determine when and when not to skimp. Cutting corners without a good understanding of the potential consequences never saves you money, but can make the project significantly more expensive in the long-run.  Given this, it’s important to evaluate everything you do with an idea toward the benefit of saving money versus the risk of cost-cutting putting the project in jeopardy.  An experienced CDMO or a consultant often has a  good understanding of what will and will not pass muster with the FDA, so it’s important to work closely to determine where savings can and cannot be generated. One place not to skimp is in Phase 3 clinical trials, which have a more than 50-percent chance of success.  At that point, there are clear clinical results, leading to solid funding and a good chance you are on the right path to commercialization. Yet, this stage of the process also means greater scrutiny by the FDA and better odds of losing a huge investment if any problems occur this late in the game.

Pre-clinical and Phase 1 stages are often where cost-savings can be implemented the most, since at these stages there has been less investment yet in time and resources, as well as less regulatory scrutiny, since many projects do not make it out of this stage.

Managing risk in API development and manufacturing is an ongoing battle for sponsors and CDMOs alike.  While there’s no way to prevent it, by understanding your regulatory strategy, vetting the right CDMOs and wisely managing costs and resources, you can minimize risk and ensure that you’ve done all you can to put your project on the road to successful commercialization.

What are some other ways to reduce risk in API manufacturing? We’d love to hear from you. Contact us at 978-462-5555.

About the Author

Ed is President & CEO of SEQENS North America (formerly PCI Synthesis). He serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA)...

Do you have questions? Talk to Ed.