CDMO Management for Sponsors — Part 1: Identify Partners and Nail Project Kickoff

By Life Science Connect Editorial Staff

At our second OP-Virtual, Outsourced Pharma Chief Editor Louis Garguilo invited individuals with professional experience at both CDMOs and biotechs to share advice and some best practices gleaned from working both sides of outsourcing partnerships.

The forum, moderated by Patty Seymour, featured contributors Lisa Wyman, VP of Technical Operations and Quality at Acceleron Pharma; Ken Baker, CMC Lead at Sage Therapeutics; Charlie Montgomery, Senior Director of CMC at Skyhawk Therapeutics; Bernhard Paul, President and Principal Consultant at Carinth Consulting; and Steve Collier, Executive Director of Process and Analytical Development at Sage Therapeutics.ⁱ

While outsourcing is ubiquitous in drug/therapy development and manufacturing, finding an appropriate CDMO partner — one that, for example, shares the sponsor’s values, meets its capability needs, and can deliver within the desired timeline — remains a project-by-project challenge. Per Collier, a successful CDMO partner exhibits five distinct qualities:

1. Strong process development
2. Robust analytical development
3. Flexible manufacturing
4. Quality assurance (QA) principles applied consistently across operations, underpinning all GMP activities
5. Adept project management that considers all elements impacting a project

Although some might profess otherwise, few CDMOs excel in all five areas, and their proficiency in a given area can fluctuate depending on which individuals from the CDMO are assigned to a program. Thus, issues tend to not only be inherent shortcomings with the CDMO, but often are circumstantial. Consider that CDMOs, particularly well-reputed organizations, take on a lot of work. As a result, they may lack the time or capacity to meet a given client’s needs (i.e., adhering to that project’s stated process development or analytical development timelines).

A common strategy to overcome this hurdle is to divide out work packages among specialized providers (e.g., use a secondary provider and then integrate that provider’s outputs back to the primary CDMO). An example could be impurity identification, wherein the secondary vendor explores impurity synthesis and those impurities’ effects on the process. In short, a portfolio of partners may be necessary to meet project outcomes, particularly within an aggressive timeline.

With respect to manufacturing, it is important to understand how scheduling works and how capacity is mapped — specifically, how far out a CDMO is booking and who controls that capacity. What kind of opportunities does that create? Potentially, a CDMO could reschedule a commercial batch (producing it sooner or delaying it, because they have visibility into the timing of its delivery) to allow another partner to squeeze in an API batch.

Innovator projects carry a lot of risk, and delays often are the result, creating a gap in the CDMO manufacturing schedule. The flexibility to bridge that gap is invaluable toward minimizing the impact not only on the CDMO, but on the client (versus paying for unused plant time). A CDMO that handles both innovative and commercial manufacturing also presents the possibility for expedited tech transfer (i.e., eliminating tech transfer processes between vendors).

Another manufacturing consideration is how the plant operates. Is the shift rotation 12-hour shifts, five days a week, or 24/7 operation? If the later, how is the plant staffed during less traditional hours? For example, if something goes wrong at 2 am on Saturday, will QC support be on-site? Understanding that staffing helps a sponsor plan when to complete certain activities: you don't want to run critical in-process control (IPC) for a validation process over the weekend unless appropriate staffing is on-hand to resolve any issues.

QA and project management are tougher skills to evaluate ahead of time — say, based on a CDMO’s past work or claims — since every project is different, circumstances change, and personnel may differ.

Set the Stage for a Successful Partnership

Effective, efficient startup activities have a massive impact on project outcomes, states Paul, who has experienced startup within CDMOs, biotechs, and as an independent consultant. For this reason, he advises a formal project kickoff meeting for every project, even those that might seem small or quick and easy. While a CDMO must execute a project, the sponsor is responsible for setting expectations and providing the framework for how it would like to operate.

Ideally, this meeting is conducted in person, but it can be conducted effectively through technology, as well. By no means a comprehensive list, these are a few important items for sponsors to cover during the project kickoff meeting:

• Provide a thorough overview of your company, the technology platform, the disease being targeted, and how your drug can help patients. This important and somewhat obvious step warrants mention because it can be so easy to forget. Everyone at the CDMO is just as interested in positively impacting patients’ lives as people at the sponsor, but it can be harder to do that at a CDMO because you feel a step removed.
  • Working at a biotech exposes personnel to regular meetings discussing the disease, as well as conversations with patients and advocates. Introducing that element to discussions with collaborative partners can greatly boost their level of engagement.
• Outline expectations and provide/revisit vital information. CDMO projects typically are prefaced by long lead times. The sponsor speaks to the CDMO’s business development unit multiple times, developing proposals and making revisions. Accordingly, it is natural to assume all the information the sponsor has shared throughout those discussions has been recorded and will be accurately transmitted to the CDMO’s project team.
  • However, parts of that information often are not tracked or passed on, and the sponsor goes on assuming everyone at the CDMO is familiar with what has been said, creating problems.  So, start at zero: the project history, the contract, the deliverable, etc.  This conversation also provides an opportunity to outline sponsor expectations about communication regarding project-specific items. Again, this step can seem redundant, but a 30-minute investment can spare each partner countless future meetings. 
• Provide project background and share context. Sponsors sometimes provide limited information about a problem that needs to be solved (i.e., sometimes due to IP-related concerns), leading to frustration for both partners. For example, an early-stage project might have confusion on both sides: why did the sponsor run this experiment and not that one? Why did the sponsor change this element of the process?
  • One solution to this issue is to hold, essentially, a kickoff meeting, even if the project began weeks ago — a reset to restate what the sponsor wants to accomplish and, perhaps, to examine regulatory constraints relevant to what has been filed. Consider how this approach is applied internally at a sponsor: if you tell a scientist to run an experiment, they will do so. But, if you tell that scientist the specific problem and why it is important to solve it, they generally are more effective. The same applies to working with a CDMO. 

Final Thoughts

Identifying an appropriate CDMO partner and establishing relationship structure/expectations early is an intrinsic part of leveraging the CDMO to provide the sponsor a competitive advantage. A good partner blurs the line between third-party service and extension of your company.

This article is the first in a two-part series. In Part 2, forum participants explore tenets of sound CDMO management and discuss how to avoid and/or overcome common challenges within those partnerships