Published on Nov 07, 2024
In the wake of the recently finalized FDA guidance, further clarifying expectations and processes, what is on the global horizon? Before the joint guidances by FDA, EMA, and Health Canada were released in 2023, in a panel discussion including both regulators and industry, the industry consensus was that 5-10 years would be needed to achieve compliance with forthcoming nitrosamine limits.
A rapid increase in knowledge and product understanding is needed before the broader industry can fully comply with the global regulations.
There are many ways in which the regulatory agencies have acted in unison. It is more frequent, though, that each guidance is missing details from others. For example, when looking at the regulated nitrosamines, there are glaring additions and subtractions in most lists; common drugs listed as a risk by one agency and not mentioned by others.
On the other hand, agencies are in lock step concerning the overall plan.
Over the coming months, each company must close the gap between where they are and regulatory requirements. An unfortunate number of companies are still grappling with understanding the guidelines and what APIs and resultant products are at risk. They may not have direct access to the instrumentation necessary to complete this work. Thankfully, many other manufacturers are in a much better position. Some are already implementing their control strategies.
It is fair to extrapolate that most of the industry will be fully compliant. Their risk assessments and confirmatory testing will be complete. Control strategies and most reformulation will be completed. If, as expected and communicated, bioequivalence requirements are loosened, many at risk products will be compliant, following the limits and regulations without issue.
However, not all of industry will be compliant. This will be due to a number of factors including over reliance on a mitigation strategy that does not work for the specific drug product; this may be use of inhibitors or reduced nitrite excipients. Some nitrosamine standards may not be available in the necessary quantities. This will be a particular issue for the nitrosamines formed from impurities.
Lastly, an expedient mitigation technique may not be currently identified for all drug product issues. Some APIs will not be amenable to the addition of antioxidants to the formulation. While other techniques are available, none are as effective and have been granted an abbreviated change management process.
It will be incumbent upon industry and regulators to work together, developing interim controls and unique solutions to ensure that the drug supply is not interrupted. Without dialogue, unnecessary recalls and product discontinuation will occur. Industry teams and leaders must fully understand what is expected of them and the tools available that will lead them to compliance.
To learn more about the year ahead for Nitrosamines, our course, led by Jason Brown, a renowned expert on nitrosamines, will take you through the latest regulations. Reserve your place today.
Published on Nov 07, 2024 by Jason Brown