When a Decision Decides the Outcome

When a Decision Decides the Outcome

Introduction to Chemistry, Manufacturing, and Controls (CMC) Regulatory Strategy
Introduction to Chemistry, Manufacturing, and Controls (CMC) Regulatory Strategy

Beginning with spring training through the dog days of summer to the stretch drive, every decision on and off the field can affect the postseason outcome.

In an analogous irony, by the end of Phase 2 clinical studies within the Biotech Industry, a Sponsor has devoted considerable time, expertise, skills, and expense to understanding the science of how the drug product works in humans and how to clinically administer the drug product to maximize its medical benefit and minimize its medical risks. But have similar resources been expended to understand the science of how the drug product can be manufactured consistently to yield the desired quality?

During the early clinical stages, regulatory authorities allow considerable flexibility in a company’s choice of development work. Up to this point, the product has been released for clinical trials using minimal data, which seemed perfectly fine to everyone, including the regulatory authority. Then, at the End-of-Phase 2 (EOP2) meeting, the company is frequently informed that the data may not be sufficient for Phase 3 trials or commercial production. Now that the company is entering late-stage clinical trials, regulatory authorities’ expectation for the program is much higher. Sponsors can take this regulatory authority input as bad news but should be thankful because the issue is now out in the open, and the resources needed to make the necessary changes or improvements can be completed in a timely fashion.

Want to avoid the error that decides the outcome of the season? Seek out regulatory authority advice. Sponsors need a reality check for their CMC regulatory compliance strategy at this transition from Phase 2 to Phase 3, and the regulatory authorities can provide it. Both the FDA and the EMA see the value of CMC-focused EOP2 meetings with companies. By having the issues identified at an EOP2 meeting, the company has adequate time to respond to concerns. Regulatory authorities do not expect a company to agree with them in every instance, but they do expect thoughtful consideration and a scientifically justified response. Sponsors don’t just wake up one morning and say, “I am going to ignore the CMC regulatory compliance requirements from now on.” The slippage occurs one step at a time: overlooking a manufacturing deficiency due to time constraints; looking the other way in a quality issue because of inventory pressures; not responding to a requirement because of financial constraints when a necessary process improvement has been identified. Don’t let one miscalculation decide the outcome.