Expedited Approval Pathways Increase Risk and Burden on CMC and Manufacturing: risk reduction strategies include…
At The Windshire Group, Chemistry Manufacturing and Controls (CMC) includes allied activities throughout the product lifecycle…
While I believe the term, Chemistry, Manufacturing and Controls (CMC) has become more familiar and ubiquitous over the years, I still come across folks in the industry who are not familiar with the acronym. Since The Windshire Group’s tagline is “Comprehensive CMC ConsultingSM”, we thought it was natural that our first blog address the meaning of the phrase. For us, it has two meanings, one specific to its use at U. S. Food and Drug Administration (FDA), and how we use it at The Windshire Group.
First, the term, is used by FDA mostly with respect to the part of the new pharmaceutical product application dossier in order to conduct a clinical trial or register a new product in the U.S. This part of the dossier covers those aspects that deal with the nature of the drug substance and drug product, the manner in which they were developed and are made, and the control aspects of the manufacturing process. This is distinguished from those parts of the dossier related to pre-clinical and clinical elements.
For us at The Windshire Group, CMC includes allied activities throughout the product lifecycle, such as operational excellence, program management, portfolio and EVA (economic value added) analysis and CMO selection and oversight. Thus, our catch phrase “Comprehensive CMC ConsultingSM”.
It is telling that the FDA renamed the category “Chemistry, Manufacturing, and Controls (CMC)” to “Pharmaceutical Quality/CMC” on its web page and (http://goo.gl/42nWFf ) listing CMC guidance, compliance and regulatory information. First, pharmaceutical quality is emphasized first and foremost. Not a surprise, given the FDA’s growing emphasis on quality throughout the product lifecycle (e.g., Quality by Design (QbD) and quality metrics). Second, “Chemistry, Manufacturing, and Controls” is shortened to just “CMC.”
Successful execution of CMC activities requires bright, experienced, persistent and hard-working professionals. That is, having the right person, at the right time, in the right place doing the right things. This can be invaluable to organizations in a number of ways.
First, if the people responsible for CMC activities are successful, CMC is kept off the critical path for clinical development and regulatory approval. Any unnecessary delays increase direct costs and can entail substantial opportunity costs, due to the time a product is not on the market.
Earlier in my career, I successfully defended a major investigation during PAI (Pre-Approval Inspection) for one of the most successful drugs in the world. The issue had been the subject of a Form 483 observation several years before at another site and had high potential to delay approval of the drug due to its recurrence. Alarm bells rang at corporate HQ. The investigation entailed two binders of information and documentation. The core of the defense was a clever, scientific rationale that incorporated a well-designed experiment, a simple mathematical model of the event and insights from both my biological and engineering background. It succeeded against one of the FDA’s most experienced and talented inspectors. It was the number one issue four of the five days of the PAI. Any delay in the approval for this drug would have entailed a loss of tens of millions of dollars.
Second, successful execution of CMC activities are major drivers for efficiency, which reduces cost; for avoidance of compliance issues, which can be expensive to remediate; and for avoidance of product stock-out and lost revenue.
Finally, CMC activities can increase the value of a drug product portfolio and of a company itself. I have seen investors walk away from a deal due to problems with CMC. While I don’t have a large, statistically valid data set, I believe there is a correlation between the strength of an organization’s CMC activities and the value of its drug products and portfolio.
Many organizations do not have all the expertise and resources they need in-house to meet their CMC goals avoid pot holes and speed bumps. Expert, experienced consultants can help these companies achieve their CMC goals by cost effectively providing “The right consultant, at the right place, at the right timeSM”.