Strategic CDMO Partnerships Begin By Unraveling The Complexities

By Life Science Connect Editorial Staff

Choosing the right CDMO partner is critical for pharmaceutical sponsors because the decision impacts product quality, timelines, and, ultimately, whether a program can deliver for patients. But the CDMO selection process can leave pharmaceutical sponsors feeling over- or underwhelmed by their options, especially when the most obvious attributes or metrics are not always the best indicators of whether the relationship will succeed. This guide is intended to provide direction to help sponsors quickly shortlist viable partners and avoid decision-making pitfalls.

Determine What Makes A Good CDMO

Capacity and technical capability are important attributes because they drive right-first-time performance and indicate whether a CDMO can support a product throughout development and commercialization. Understanding how a CDMO will respond to uncertainty is equally important, because programs and sponsor-CDMO relationships both evolve over time: for example, will midstream changes require contract renegotiation?

For more common drug-delivery technologies, it is advantageous to use a scoring matrix with criteria agreed upon and prioritized by the entire sponsor team, which can help eliminate bias stemming from team members’ differing experiences and preferences. The criteria will also differ based on the product’s development stage: for example, the amount of risk a sponsor is willing to accept, and thus the weight assigned to each criterion, is likely to change as a program advances. Additionally, the product’s nature, whether it is a novel biologic or a small-molecule combination product, can narrow the number of CDMOs with adequate knowledge and equipment to handle the program.

Lastly, is the CDMO in the collaboration for the long haul? A CDMO’s ownership structure can be indicative of the company’s financial health, the stability of its C-suite, and the business’s general health. CDMOs across all specialties and sizes are being acquired by private equity (PE), and the benefits or drawbacks depend on the objectives of each transaction. Often, the PE firm is simply acquiring a predictable revenue stream. Other times, they acquire the asset, learn more about its potential weaknesses, and decide to prioritize monetization over reinvestment.

So, sponsors need to understand the PE firm’s objective and its plans for the CDMO’s business model. If the focus is not on the CDMO’s core business, gaps and delays in the sponsor’s program(s) can result. One way to gauge the CDMO’s stability in this respect is to ask about its willingness to share long-term objectives, including its capital investment to date and revenue reinvestment plans moving forward.

Assess The CDMO’s Record For Quality And Delivery

Examining a CDMO’s record of FDA inspections and its response to findings can reveal insights into the organization’s capability and culture. For example, a company may have received a few Form 483 observations from the FDA, but took that opportunity to demonstrably refine its operations and strengthen its quality culture. The key quality metric is CAPA effectiveness, measured in on-time investigation and task completion, which tells the story of the CDMO’s commitment to continuous improvement.

Additionally, scrutinize the CDMO’s deviation-closure time and batch-record cycle time. Chronic failure to close deviations within the standard time window (i.e., frequent use of extensions) may indicate an under-resourced or under-experienced quality unit, or a poor overall quality culture. Prolonged batch record cycle times, meanwhile, can threaten clinical or commercial timelines by delaying batch release.

It is also prudent to understand the CDMO’s escalation pathway and to identify who determines an incident’s criticality: What events will be escalated, and to whom? Ensure that different individuals at the CDMO give the same answers, and ask the CDMO to provide an example of a project that encountered issues and explain the escalation process used. Confirm the process matches what you were told and pay attention to how the issue was resolved (e.g., collaboratively, in siloes, or with a lot of finger-pointing?). A CDMO that can clearly articulate its anticipated project governance is likely skilled at communication and maintaining established points of contact.

Sponsors should continue to monitor these metrics throughout the partnership and must be honest with themselves regarding their role in assessing and closing quality issues. For example, is the sponsor itself creating or exacerbating closure time problems by being under-resourced?

Vet CDMO Talent Early And Often

It can be difficult to identify the full team a CDMO will assign during the early stages of a partnership. The sponsor is often assigned a project manager and some primary, technical subject matter experts (SMEs), but few quality SMEs. It is a positive sign when individuals and teams that will be assigned to a program are in the room during prospecting. Their presence, particularly the PM, fosters early engagement and understanding. Even when working with a multinational partner, a sponsor’s experience will be local; rarely does the network’s power benefit the client or the innovator.

Additionally, it can be beneficial for a sponsor to request the CVs of those critical team members, enabling confirmation of their tenure with the CDMO and their experience relevant to the program’s modality. Examine the CDMO’s retention rates and ask how they ensure program continuity if members of the primary team need to leave the project. 

High turnover can be a red flag for quality, culture, and processes. Also, depending on the geographic location, high turnover rates may indicate that important positions are difficult to backfill. These conditions can lead to knowledge gaps, technical mistakes, and program delays, but they also can help guide the sponsor on when it may be appropriate to provide product-based training to new or onboarding CDMO employees. Using this information, a sponsor can amend the partnership contract to include personnel continuity clauses that help prevent major changeovers or “bait and switch” talent reassignments. 

Ongoing risk mitigation may also include placing a person in plant (PIP) during critical process steps to address potentially damaging knowledge gaps or troubleshooting. Knowledge management is vital amid turnover, so timely completion of reports and protocols is a must. This may sound obvious, but such paperwork is often deprioritized as a CDMO rushes through a program, stifling knowledge capture. It’s important to understand how the CDMO maintains product and process information, and how that data is transitioned when team members or the PM change. 

Eyes On The Prize. Always.

Sponsors cannot always be present at a CDMO plant, so setting up collaboration and communication standards at the outset of a partnership goes a long way toward building trust, establishing mutual risk transparency, and helping ensure that no one in the relationship feels unjustly challenged. If a challenging situation arises and the team cannot agree on a source of truth, it is in the sponsor’s best interest to review the raw data and notebooks to ascertain the most accurate source of information.

Additionally, quality audits are critical to determining data accuracy. Carry out one before selecting a CDMO and embed quality audits as a routine activity in the contract. Even more important are strong governance procedures: setting up governance meetings, establishing escalation pathways, and conducting continuous improvement reviews over time, letting a CDMO know where they stand in terms of communication strategies. Be patient but persistent in educating them about the standards you have found effective. 

With regard to remote oversight and data integrity, consider dashboards, electronic batch records (EBRs), and remote monitoring as a balancing act: verify some data before you trust all the data. For example, well-implemented EBRs feature controls to prevent operators from  proceeding to the next step if an OOS exists or a signature is missing, and   live video feeds can allow sponsors to observe critical steps when personnel are unable to be on-site. Inquire about the access a CDMO provides and how it “controls the controllables” relevant to engendering confidence in its use of digital tools.

Does The CDMO’s Supply Chain Have Weak Links?

In light of industry concerns over the BIOSECURE Act and geopolitical risk, many CDMOs position themselves as “Western” or “global,” but their supply chains still rely on restricted geographies for raw materials, filtration media, single-use assemblies, and more. Therefore, asking a CDMO deep questions about its raw and packaging material sources, deliveries, lead times, and risk-management strategies (e.g., dual sourcing or stockpiling) is in every sponsor’s best interest. Furthermore, contracts should include a mechanism to review any supply chain changes.

Viable Partners Love To Share

The CDMOs' sponsors want partners that want to earn the partnership. Adept CDMOs don’t stop at high-level slide decks and brochures highlighting their technical and equipment capabilities. They welcome site visits and face-to-face conversations with, say, manufacturing managers, as well as general observation of operations, which can provide a wealth of information not found in an RFP response. They offer SMEs, in person or virtually, who can answer the sponsor’s specific technical questions. They are typically proud of their knowledge, what they can deliver, and how they conduct business.

To learn more, watch the Outsourced Pharma virtual event, “The Unfiltered Truth About CDMO Selection,” on demand. Hosted by Outsourced Pharma Deputy Chief Editor Jeff Buguliskis, the event welcomed Jana Spes, CEO and co-founder of JT Biopharma Partners, and Christine Shaeffer, a manufacturing supply consultant and the former VP of Manufacturing and Supply for Spark Therapeutics, to share their expertise and experiences in the ever-evolving practice of identifying and partnering with the best CDMO for your needs.