A Day In The Life Of A CMC Professional
By Louis Garguilo, Chief Editor, Outsourced Pharma
Consider the 25-employee biotech, located in the continental U.S., with limited R&D labs, and which outsources all development and manufacturing.
The company has achieved an FDA-approved drug, and is pursuing a pipeline with candidates currently in phase one and two.
The professional in charge of CMC (chemistry, manufacturing, and controls) at this biotech has, shall we say, been here before.
He’s worked in the industry and at biotechs – big and small – for decades, and headed up CMC operations at some of those positions.
Like most all outsourcing professionals at any organization, he spends a good deal of time (during manufacturing campaigns, even more) thinking about and interacting with his CDMOs.
Ineluctably, this experienced CMC professional knows that some form of challenge will arise at the CDMO, for example out-of-spec tolerances or filtration issues.
This particular biotech employs CDMOs in various geographies, potentially widening and complicating the CMC challenges.
The global reach is necessary, due to some specific know-how and equipment requirements, and a philosophic approach to selecting the best CDMOs, no matter where they are located.
Our CMC head handles some decisions more-or-less on his own, but typically he’ll involve a number of cross-functional team members.
Some of those decisions are momentous, such as:
Should a production be put on hold to enter full investigation mode regarding a perceived issue with a current batch?
If multiple batches are in queue for manufacture at the busy CDMO, do you start the next batch while the current investigation is ongoing?
It becomes a matter of informed risk assessment and mitigation. The stakes are high. Economic and other considerations play a role.
And that is only the manufacturing end of things.
On the analytical and quality control side, for example, considerations are also underway.
If there are investigations ongoing – and typically there is something in play – the CMC professional and his analytical team members will be interacting with the CDMOs' team, plowing through all the data being generated.
On this front, and at times, our CMC professional and colleagues may opt to contract a separate analytical-testing organization for third-party analysis and assistance.
There’s the necessity to dig into the deepest level of the data generated, and all that data is critical to the “other” job the CMC head is responsible for.
The at times massive amount of documentation that must be reviewed on a continual basis, and eventually submitted in the CMC sections of an IND,NDA, BLA or PMA.
The CMC sections (Module 3) of the IND and NDA must be thorough, accurate, and again, data-driven.
Data and analysis in the IND for Drug Substance, include manufacturer and preparation method (CDMO-related information); characterization data, including analytical methods and reference standards; control of the drug substance, including specifications and analytical procedures; stability data; etc.
For Drug Product, the list is similar.
And that all goes for the similar sections in a regulatory submission.
If nothing else, then, the CMC professional must be the keeper of the various data and information, and the one, by the way, who also gets to explain things to the CEO, the board, and perhaps investors.
Oh, and he is often responsible for coordinating if not directly answering questions raised by a regulatory authority.
Our seasoned CMC professional knows, that in a word, it all begins and ends with regulatory.
What’s New
But let’s not forget about the other drug candidates in the pipeline at the biotech.
There is active planning and management of new studies to be put in place to support these new programs, and coordination with the CROs and CDMOs regarding timing, further development and processing activities.
Looking at the chemistry to evaluate and optimize organic synthetic routes for new chemicals to make these materials is one of those important jobs.
Our CMC professional can, though, handle all the above. Like we said, he's been here before.
But execution depends on the team surrounding him, the specific subject matter experts in the different areas; his quality and analytical staff; biologists and chemists; regulatory professionals ... and at further extension, executive management, scientific board members, and even investors.
And of course, his external partners.
Because our CMC has learned to work hand-in-hand with them, and not hold information back from them, their advice and expertise can be sought after.
It’s a cornucopia of professionals convening dynamic discussions. At, we might add, what we often call a "virtual biotech."
Fortunately for this biotech, the CMC professional has extensive experience in the writing of INDs, NDAs, BLAs, and other submissions.
In fact, he sometimes jokes, that on days he needs to focus on that element of his duties, he lays red pens out on his desk, and might even wear something red to mentally prepare for the careful crafting and editing he needs to perform.
Who Shall Be CMC?
I ask him one more question on the CMC function:
Who should gain the position as head of CMC at a biotech?
His reply:
“I would say it does require a professional with some sort of relevant scientific degree, whether it's a PhD or master's as a foundation. In my case, it happens to be a PhD in analytical chemistry, which, if I may, is a pretty good start.
“But it could be a background in chemical engineering; pharmaceutical science is another degree, because CMC is broad, as we’ve documented.
“Finding someone who has at least dipped their toes into several areas is optimal, perhaps best is a professional with hands-on pharmaceutical manufacturing experience.
"People skills and project management experience is essential as well.
“I'd also mention current quality professionals who have interacted with regulatory authorities, and been in the middle of a grilling by agencies and auditors.
“You need someone, so to speak, who has a a sense of what flies and what does not, and has an ability to ‘connect the dots.’”