A CMC Professional At Sanofi Focuses On Collaborations (And The Right Questions)
By Louis Garguilo, Chief Editor, Outsourced Pharma
It may have been a first. A thoroughly entertaining discussion on CMC (chemistry, manufacturing and controls), and some (perhaps unintended) humor when discussing CDMOs.
For example, in the middle of our conversation, Manda Pasarkar, Global Regulatory Affairs, CMC Head, Sanofi, puts forth a seemingly incongruent self-assessment:
“I simply cannot stay on script,” she says. “When it comes to giving a talk or presentation, I do better speaking without the notes.”
A refreshing response from an experienced professional – by training and position detail-oriented, instruction-respecting, and process-disciplined.
She’s overseen multi-billion-dollar portfolios of products from early development to commercialization, and secured new-drug marketing approvals in the U.S., EU, Japan, China, Brazil, South Korea, and other international regulatory jurisdictions.
Another interesting moment in our conversation came when I asked her if personnel at CDMOs – given all those jurisdictions she’s been a part – is of a major concern.
“Luckily, managing their people is not my responsibility,” she says with a smile.
This is vital, because Pasakar believes “people are at the center of everything that has been planned and needs to be executed and delivered from a CDMO.”
Including at the sponsors themselves, our industry must have the “well-being, professional development opportunities, and appropriate compensation for employees to ensure execution and retention.”
Happy workers at home and external partners are the best CMC policy.
CDMO Collaborations
Staying true to her nuanced approach, Pasarkar is less likely than others to talk about outsourcing as relationships or partnerships, but more precisely as specific business "collaborations."
CDMO collaborations entail multiple aspects, she says; preeminent is ensuring the various arrangements making up those collaborations you require are set down on the right track, and stay on track.
This starts with detailed discussions prior to contracting, as an early codifying of exacting work requirements and specific delivery arrangements.
Contractual agreements with CDMOs include different sourcing strategies, and CMC professionals should assist in structuring well-defined clarifications and demarcations.
An example is when your CDMO is assigned “partial or functional responsibility for the procurement of materials.”
That arrangement then “plays a vital role in meeting expectations for having the necessary quality controls in place throughout the supply chain to satisfy the health authorities in the jurisdiction your marketing application is headed.”
Additionally, both parties to any outsourcing collaboration should understand what work came before, and what if any additive elements of process and formulation development is or should be ongoing.
“How is that all being discussed?” she asks. “Is there a ‘communication formula’ built into tech transfers, into the pilot plant at the CDMO, and also out of the CDMO to the sponsor, regarding the process or the formulation?”
Early consideration of such questions from a CMC standpoint – in terms of data generation, updates, and eventual practical needs to write up the CMC section in regulatory filings – helps ensure a smoother development and manufacturing pathway.
CMC Still Involved Too Late
What Pasarkar suggests next is surprising. I thought much of this problem had gone away by now.
Yet, still today, she avers, too often neither CMC staff nor CMC considerations are brought into play early enough to effectively impact those outsourcing arrangements Pasarkar wants sponsors to focus on in any collaboration.
This is detrimental to achieving optimal long-term effectiveness in filing with regulatory agencies.
If you are a biotech thinking it’s too early (or not worth the time) to seriously consider a clear commercial path, you are actively ensuring a bumpy road to any potential destination.
CMC should guide (and update) you in the present as to what the future may hold.
Pasarkar points to fundamentals of which both sponsor and provider organizations should be aware, including a heightened recognition of the different technologies used to advance new therapies or molecules.
“Are we talking about chemical synthesis utilizing highly advanced materials? Small molecules as large as some large molecules? Are we talking about being manufactured through an animal or microbial source – or different sources?
“All this plays an important role in process development, and the complexity of that development for the API,” she explains. “These factors should be researched and communicated.”
She does venture into the familiar nomenclature of relationships when she asks, “How is trust built to facilitate all this transparency?”
One answer is it starts with mutual defining, purposeful activation, and ongoing monitoring that make up the outsourcing objectives.
“In my different roles, I have seen all kinds of arrangements,” Pasarkar says.
These may have had various divergents, she explains, but no matter the contractual terms or how they are structured (i.e, who is responible for what), CMC cannot be considered a last piece of the development puzzle. You’ll end up with holes in your regulatory picture.
A fundamental example is the sudden realization you have not received key data from your CDMO. Or worse, you have not adequately generated that data at all.
This could have been avoided with CMC professionals asking the right questions regarding future needs.
In fact, we’ll end here with something Pasakar often says about CMC leadership that critically applies to outsourcing collaborations:
“The question is your best friend.”