Maintaining Harmony With Your CDMO Using 'The Middle Way'
By Steve Erb, Ph.D., Crown Point Biotech Consulting LLC
The soft skills we use to manage and cultivate our internal and external relationships are often overlooked or undervalued in biotech as we try to meet impossible deadlines with tight resources. Under those conditions, it is easy for tension to infiltrate our internal and external meetings, and we start dreading them for fear of disagreement. No one turns on their cameras, everyone is guarded, and the team's effectiveness and spirit of collaboration deteriorate. In turn, these circumstances precipitate missing milestones through ineffectual decision-making and unnecessary nitpicking.
So how do we avoid what seems, at times, an unavoidable fall into discomfort and ineffectiveness? I found an approach I call the “Middle Way” useful to meet the challenge of managing both a CDMO partner that is underperforming — struggling to meet deadlines and requiring heavy scrutiny — and retaining staff and a CDMO partner that exceeds expectations and is seemingly comfortable with their established systems, works problems, meets deliverables, and seems on autopilot.
If you want to play the guitar, your strings can't be too loose or too tight. It will sound flat or high, literally high-strung. You need to find the middle zone where you obtain balanced and harmonious resonance. This metaphor can be used as a guiding principle and for reflection while managing your CDMO and your internal stakeholders to ensure you are making harmonious music together.
Applicable to the seemingly stellar performer and challenging partner alike, being too loose with your CDMO or stakeholder will render you ineffectual but being too much of a hard-liner will cause resentment and degrade the relationship you are trying hard to cultivate and maintain. The Middle Way walks the tightrope between the extremes of being an overbearing micromanager and an ineffectual hands-free overseer and can be utilized by any project manager, quality representative, or technical lead for process development, manufacturing, and analytical development when engaging your external and internal partners.
While this concept is not breaking new ground, it is an opportunity to assess your current working relationships or, if you are just starting out, develop a consistent method of approaching all parties to maximize the return from your efforts. You can build and maintain the Middle Way by simultaneously evoking these tenets:
- Work for the patient.
- Use data to drive decisions.
- Find the win-win.
- Build a team mentality based on common decency.
At its core, when we first think about the CDMO-sponsor relationship, it is two companies coming from different structures, corporate cultures, and motivations where neither company can directly manage individuals across the company line. In effect, it is a relationship built for conflict, impasses, and a sense of lack of control by either side. It is the job of those managing the relationship to steer through these uncontrolled waters and find the common ground. When we keep the patient in mind as we perform our work and interact with each other, we are on common ground. When data is utilized to drive our discussions and decisions, we are on common ground. If we look for the win-win during our interactions, we are looking out for each other’s best interests and developing trust. And, lastly, when we feel part of a team and behave with common decency, we respect each other and will want to strive for the other’s success.
The common ground that no one in our industry can deny is that we are doing this for the patient. Everything you do in this industry should be motivated by this mantra, whether you are devising a product development strategy or pipetting cells from one tube to another for an analytical method. With this concept at the forefront of your mind, you can navigate discussions that become contentious. It allows you to keep a level head and stay calm, and, for all parties, it removes the sense of taking things personally.
The Incredible Leveling Power Of Patients
During a CMC meeting with a CDMO, we were discussing the need to include safety testing for batch release of a cell therapy product being manufactured in a GMP-like space to support an IND filing. The CDMO was adamant that these tests were unnecessary given it was not manufactured under true cGMP (they did not want to discover any issues they would need to mitigate), but we needed these data to demonstrate we could successfully manufacture and test for these parameters under our control strategy within a specific disposition window. We reached an impasse in the discussion and voices were getting loud, with increasing animosity. Seeing the temperature rise, I calmly stated that we acknowledged the stance of the CDMO but that, together, we needed to demonstrate our ability to manufacture clinical trial material and release it within a specific window to get the product back to patients during their treatment window. I leveled the field by stating we are doing this for the patient and doing it as a team. We jointly acknowledged the risks and liability in an “I see you, you see me, we are in this together and need to get this to patients” manner.
This seems like a trivial enough resolution; however, if we demanded the testing, full stop (hey, we are paying you!), the conversation would have continued on a sour note, the efforts of those completing the work would be laced with resentment, maybe mistakes, and subsequent interactions would have us appear as a dictator. On the contrasting side, if we conceded to forgo the testing, we would not have the data required for our regulatory submission and would not understand failure points in our short disposition time. Here, the CDMO realized our need was based on obtaining data to generate confidence in our process and systems, with a foundation on safety for the patient and, thus, we were able to move the conversation forward on common ground. By bringing the patient to the forefront, we are appealing to the basic reasons we are all working diligently in our positions at our companies.
A 'Middle Way' Through Common Sponsor/CDMO Pain Points
Challenges meeting product disposition timelines are ideal times to implement this strategy. Process deviations and out of specification events can be the most significant trials that test the relationship with your CDMO. For a struggling CDMO, some of the biggest disagreements and contentious moments are centered around deviations. There is a tendency to want to point out that you are paying hundreds of thousands of dollars for a quality product delivered within a certain time and, conversely, the CDMO may default to a narrow view and be quick to point to your process or your starting material variability as the root cause of failures.
Let’s be fair, deviations happen, and it is part of quality improvement, but the challenge is getting the teams to work together with transparency to move these investigations forward quickly. Putting both partners on common ground by reminding ourselves why we are doing this work sparks a different motivation. Simply mentioning the patient can decrease squabbling about whose fault it was (execution vs. batch record or process variability) and create a sense of urgency that decreases the time it takes deviation investigations and reports to reach your inbox for review and speeds up turnaround on comments and process documentation through quality management systems.
Couple this with a focus on working on the problem and using data to drive investigations keeps everyone on common ground and decreases defensiveness. There is no better time than during deviation and OOS discussions to remind all parties that every day past a deadline is another day a patient will not receive a treatment that could potentially alleviate their suffering; no one can argue against that. Working through the issues objectively using data gets to the root cause of investigations and it identifies areas for improvement that are advantageous to the CDMO and the client, i.e., lower deviation rates, decreased investigation times, and increased process and analytical testing robustness. What we often find when pursuing resolutions with a patient-first and data-driven mindset is that both entities benefit. We achieve a win-win for both parties and avoid emotional extremes during the discussions.
A 'Middle Way' To Managing Internal Team Disagreements
Bringing yourself back to the centering tenets also is applicable to conflicts that commonly occur internally between functions or different sites in larger companies. For example, during technology transfer of a method utilized for drug product release against specification to an internal laboratory, the receiving unit (an internal but different laboratory site) generated data for a reference standard with much greater variability compared to the sending unit.
A joint walkthrough of the protocol revealed the receiving unit was not following the pipetting procedure exactly, but they insisted their technique was sound, that it was not causing an issue, and they would not change what was considered their common practice. This left the sending unit’s transfer lead frustrated and willing to accept there would be a bias between labs or a higher level of variability for the assay at the new lab. With further advice, the transfer lead took a data-driven approach and pointed attention to previous work performed during method development. The sending unit was able to demonstrate objectively that their technique was required to reduce variability. The receiving unit had no argument against the data and understood in this instance the technique decreases variability and, therefore, product failure rates. Using data to drive the discussion, both teams were able to move past their conflict and achieve a win-win.
A 'Middle Way' To Optimize Complex Functions With High Performers
This approach is not limited to contentious relationships but was also effectively utilized during a complex technology transfer exercise of a new process and all of the analytics to a new CDMO. With careful business negotiations and diligent project management, the timeline for transfer was shortened from around 12 to 14 months to 10 months from the beginning of the transfer to start of the first clinical manufacturing run. As the analytical transfer lead, I managed the transfer of 20 different methods to support clinical trial manufacture. The aggressive timeline was constantly looming over our heads. However, together, we constantly reminded ourselves of the patients’ needs and that, for us to succeed, we needed to work together cohesively despite our disparate systems and ways of working.
During the transfer, the CDMO identified that an in-process method lacked specificity for certain days during the process that was resulting in batch failures. Instead of demanding an extension to the timeline and finger-pointing at the limitations of the assay, we jointly looked at the data, devised a strategy for mitigation, and developed an improved method of in-process testing within our timeline. The CDMO, to its credit, did not unreasonably charge us for additional work performed and was resolutely focused on achieving success. Together, we reached a solution to the problem that was acceptable to both.
Although the CDMO was considered a high performer and was capable of addressing the issue on its own, as the managing party we did not take a back seat; instead, we co-developed the strategy together, thus walking that Middle Way line and obtaining what we needed in return. This was one example of many touch points during this tech transfer that could have turned the relationship unpleasant but was progressively avoided by the openness and transparency of both companies, the focus on data to make decisions, and a general bond and team togetherness cultivated during each meeting and interaction between parties. It takes continuous effort by those forward-facing individuals between companies to reach and maintain this type of working relationship.
Mechanize Impasse Mitigation For Easier Conflict Resolution
Finally, it is up to everyone at the interface between companies (don’t forget your internal relationships, too!) to keep at the forefront common decency and an even keel. No one wants to hear anyone, from a new intern up to senior management, lose their cool and berate or disparage their colleagues. Taking an authoritative stance never achieves long term success; it builds resentment, decreases the confidence of staff, and stifles ideas by diminishing a safe space for ideas. No one is working in a one-person silo. The entire team is responsible for delivering, so keep interactions civilized to cultivate the healthy resolution of disagreements and perspectives. Everyone should have their say and can do so without inciting conflict.
In contrast, no one should rely solely on niceties or being completely hands-off to the point of negligence during interactions. If routine discourse cannot resolve issues that may impact meeting a milestone, mechanisms should be in place to address when an impasse, disagreement, or concern regarding execution presents itself with no obvious solution.
For example, these issues can be escalated to senior management to have further discussions at that level, which can alleviate the stress building on the technical teams. Team togetherness is not achieved on its own but is grown by every small deposit in the relationship bank. The glue for the Middle Way that compounds on working for the patient, using data to drive decisions, and seeking a win-win is common decency and calm discussion.
While this discussion focused on soft skills, it does not take away from the importance of having solid foundational tools that help dictate the working relationship. Having a mutually agreed upon quality agreement and clear statements of work, establishing communication and escalation plans, drafting meeting charters to facilitate technical meetings, and aligning on expectations and individual responsibilities all contribute to creating beautiful harmonies with your external and internal partners. While many of these things may seem like common sense, when we are in the thick of our projects and sweating over our deliverables, we can forget how simple relationship management can have a great impact on our effectiveness. Perhaps needed more than ever during this current time in the world is finding the path of the Middle Way, where two disparate teams can come together to solve problems for the greater good. The ability to stay calm, work on solving problems, and objectively collaborate with partners on your projects will yield results more consistently over the lifetime of your program. This is the way.
About The Author:
Steve Erb, Ph.D., is an independent consultant and founder of Crown Point Biotech Consulting with over 13 years of experience in CMC at small biotech and large pharma companies. He has significant experience managing CDMOs in analytical development, quality control, and technology transfer programs. During his time in CMC he has cultivated extensive experience leading drug product and in-process analytical method development and quality control programs, from utilizing analytical quality by design for method development and translation to QC, devising control strategies and determining specifications, and designing complex comparability studies to auditing executed quality control documents and quality event investigations for drug product disposition. He has authored numerous regulatory filings supporting IND CMC content, briefing books, annual reports, and amendments. Email him at steve.erb@crownpointbiotech.com or connect with him on LinkedIn.