“CMC topics are often taken a bit late in development. The biggest pitfall is not only it’s going to cost you more, but it’s going to cause delays to your programme. The more you push it, the bigger are the costs and potentially the delays.”
Marine Joly-Battaglini, CMC consultant and founder of PharmDev, specialises in CMC regulatory strategy for pharmaceutical companies at all stages of development. With a decade of experience in CMC development at Galderma and a master’s degree in regulatory affairs, she has built her career around preventing the costly mistakes that derail pharmaceutical development programmes.
In the latest PharmaSource podcast episode, Marine reveals the strategic framework that successful biotechs use to navigate manufacturing partnerships, avoid development pitfalls, and position their products for commercial success. Her approach challenges conventional wisdom about when to engage with CMC planning and demonstrates how early strategic thinking prevents expensive delays down the development pathway.
The Critical Development Timeline: When to Start CMC Planning
Most biotechs underestimate the complexity of transitioning from research-grade materials to commercial-scale manufacturing. Marine has identified the precise window when companies should begin engaging with CMC strategy to avoid costly delays later in development.
“While you’re in your preclinical studies, you’re fine more or less doing things on your own without necessarily having a CMC person on board. Initial phase one studies are still okay, but it’s while you are running your phase one study that is important to start thinking really about the CMC aspects.”
The strategic window between phase one and phase two represents the critical decision point for establishing manufacturing partnerships and CMC strategy. Marine explains why this timing is crucial:
“Phase two is between phase one and phase two—that’s the right time to start thinking about all that because usually phase one studies are relatively small. The more you advance in your development, the more you have to meet the GMP requirements and all the other regulatory requirements increase. Your studies are much bigger, so you’re going to need to be able to provide more products.”
The consequences of delaying this planning become increasingly severe as development progresses. “You’re going to be able to go into your phase one. You’re going to start really struggling when you enter phase two if you don’t have the proper partners in place, and then it becomes very difficult to fix once you enter phase three because authorities don’t like changes.”
Building the Virtual CMC Team: Consultant Strategy vs Internal Hiring
Marine advocates for a measured approach to building CMC capabilities that prioritises flexibility over premature hiring decisions. Her framework helps biotechs optimise resource allocation whilst maintaining access to critical expertise.
“As much as it is important to have a CMC representative on the team, I think there’s no rush in needing to hire someone. You can perfectly work with consultants. Maybe in an ideal scenario, try to hire at least one CMC person before your phase three.”
The timing for internal hiring depends largely on business strategy:
“Because while you’ll be running your phase three, you’re going to start preparing for the registration and slowly also start preparing for the launch. For companies and startups where the model will be more to sell the product after phase two, well, I would say don’t bother hiring CMC people. You can work with consultants.”
The ideal consultant arrangement requires someone who serves as a strategic bridge between technical teams and business leadership. “Someone who can speak the same CMC language as the CDMO and is capable of then translating this for the rest of the startup team. Maybe also help when reporting is needed, for example, for boards of investors or boards of directors.”
CDMO Partner Selection: The Complete Evaluation Framework
Marine has developed a comprehensive approach to CDMO selection that extends far beyond traditional cost and capability assessments. Her framework emphasises strategic fit and partnership potential over short-term savings.
Essential Capability Requirements: • Development capabilities alongside manufacturing capacity • Flexibility to adapt to changing project requirements
• GMP certifications appropriate for target markets • Scale-up expertise relevant to product type • Capacity to support entire development timeline
“If you’re working with small companies, very often it’s important to be selecting really a CDMO, so someone who has capacities also on the development side, because the resources on the pharmaceutical company side will be very limited on the CMC side.”
Partnership Success Factors: • Flexibility in project management and resource allocation • Transparent communication and honest problem-solving • Long-term strategic alignment with company goals • Geographic proximity to clinical trials and target markets • Proven track record in relevant therapeutic areas
Marine identifies flexibility as the most critical partnership ingredient: “One of the important key ingredients is flexibility because while you’re in development, it’s never a smooth path. We always encounter challenges. On the CDMO side, we need to have someone that has the possibility to adapt to all the potential changes that we can have.”
Trust and communication form the foundation of successful partnerships. “It’s really about building trust. Having proper communication between the pharmaceutical company and the CDMO, being honest and transparent about what is going on. If you work really as one team, well we can more or less overcome everything.”
Long-term Strategic Planning: Building Development Roadmaps
Marine emphasises the importance of establishing comprehensive development strategies that consider the entire pathway from early development through commercial manufacturing. This approach prevents costly transfers and provides strategic advantages for fundraising and partnership discussions.
“It’s trying to build with them what I would call a development proposal. So that would take into account all the required clinical phases. What is important there is first assess whether the CDMO that you’re about to select does have the capacities to support you all through development. Or will you have to transfer at some point?”
This long-term planning approach provides multiple strategic benefits:
“You’re giving also an indication to the CDMO that you’re not looking for a one-shop manufacturer, but you’re looking for someone to partner with on a midterm or even long-term. For the pharmaceutical company, when they go back to their different boards or when they’re looking for investors and money, well, at least they know from a CMC perspective more or less the amounts we are talking about.”
Geographic Risk Management and Supply Chain Strategy
With increasing geopolitical tensions affecting global supply chains, Marine advises companies to factor location and supply chain resilience into their CDMO selection process. Her approach balances cost efficiency with risk mitigation.
“Something I often recommend to my clients is try to have a CDMO that is not too far from where you’re planning at least to do your clinical studies or the countries where you would want to launch.”
Marine also recommends implementing a phased geographic strategy: “Another strategy could be first you select maybe someone that is a good compromise between price and location. Then you think about a strategy that would be more for lifecycle management, where you would add maybe a manufacturing site that’s closer to some of the countries where you would like to manufacture your product.”
This diversification approach provides essential risk mitigation: “It allows you to de-risk because if you have two manufacturers, if there’s something that goes wrong with one, well you have a backup.”
Avoiding Common CMC Pitfalls That Create Delays
Marine frequently encounters specific mistakes that create significant downstream complications and costly delays. These issues often stem from inadequate expertise during critical early decisions.
“Without working with the right subject matter experts on your formulation, you might have something that seems to be doable while you’re on small scale and you don’t have to manufacture much product, but you might encounter issues as you scale up.”
Common formulation development errors include:
“Maybe some of the raw materials you would like to work with are not so easily available. The scale up of the manufacturer doesn’t go as planned. I’ve seen formulations where people tell you each time you receive a new batch, you’re going to have to adapt your formulation. That’s typically something that doesn’t fly when you want to go to a CDMO.”
The fundamental requirement for commercial manufacturing success: “You have to have something that is robust, that is reproducible, and meets the GMP requirements.”
Due Diligence Framework for Investors
Marine frequently provides CMC expertise for due diligence activities where critical manufacturing questions aren’t being addressed. Her framework helps investors assess CMC risk appropriately.
“Some simple questions around the CMC part would be: who are your partners? Are you already working with companies capable of manufacturing for much later stages and have the right GMP certificates depending on when you plan on going?”
Critical assessment areas include product characteristics that impact commercial viability: “Things that are also important are the shelf life, the storage conditions of your product. Is the handling of your product easy or not? This has obvious implications at the pharmacy or in hospital, depending on how it will be distributed, but also for transportation.”
