Guest Column | November 11, 2024

CDMO Selection: 7 Steps To Find Your Best Fit

By Jim Morris, IQS Consulting, and Don DeRoo, independent consultant

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It was in the late 1990s that I (Jim Morris) remember the head of Pfizer U.S. Manufacturing announcing at a townhall meeting that over 50% of the company’s manufacturing capacity would be outsourced to contract manufacturers. I also remember that the reaction in the room was basically stunned silence. At the time, Pfizer was well integrated with API manufacturing facilities in several strategic locations and downstream finishing facilities across the globe. Most anything could be done in-house. The new approach to manufacturing was realized over the subsequent decade, with Pfizer Global Manufacturing becoming Pfizer Global Supply.

Contract development and manufacturing organizations (CMDOs) have clearly become integral players in pharmaceutical product development and supply. Specialization by dosage form or package type offers a strategic advantage. Why build when there is existing capacity and expertise at small and large-scale CDMOs, which in many cases offer a global footprint with extensive capabilities — the proverbial CDMO one-stop-shop? However, selecting the right CDMO for your project is essential. The following points will ensure you inject sufficient rigor into your selection process.

1. Decide: In house Vs. Outsource?

This is the first question you should ask. If your technology or therapeutic is unique and there is no existing CDMO platform, then you should consider building in house capability. Only outsource those activities where there is existing capability and knowledge. This might mean manufacturing in-house and testing externally or vice versa. It may mean working with one CDMO through Phase 1/2 and transferring to a CMO for late-stage development and commercialization. Many virtual companies simply cannot afford to build and staff a GMP-compliant manufacturing facility or do not have the functional expertise (analytical, regulatory, quality, etc.); therefore, they will need to lean on CDMOs to move their projects from bench to commercial scale.

Caution: There is a natural sense of increased risk in outsourcing key activities, whether in development or commercialization, and a sense of losing control of your timeline and project. That feeling is very real but given the evolution and maturity of the CDMO ecosystem, chances are you do not need to reinvent, and you can leverage existing expertise. That is why the CDMO selection process is so fundamentally important.

2. Survey The CDMO Landscape.

Once the decision is taken to outsource the entire program or part of your program, the next step is to survey the CDMO landscape. A lot of information can be obtained online and by attending industry conferences. This is a good starting point to develop a preliminary list of candidate CDMOs.

Caution: Leveraging CDMO relationships your company may already have will make a lot of sense, but this should not short circuit your vetting process. Ensure your vetting process is rigorous irrespective of how you were introduced to a prospective CDMO.

3. Narrow The Field.

As noted, much can be learned about a CDMO online or by asking questions of each prospective company. A well-developed CDMO questionnaire will help narrow the field by providing information on applicable licenses, certifications, and basic considerations such as the size of the organization and facility, company history, regulatory history, manufacturing and analytical capabilities, etc. This step will ultimately reduce the amount of time required on-site and serve to document your due diligence activities.

Caution: Don’t rely too heavily on the questionnaire. It is a starting point and should help your vetting process, but the questionnaire should not preclude an on-site assessment. Bottom line, you want to know whether the prospective CDMO has a track record of experience and success that fits your project.

4. Issue A Request For Proposal.

The RFP process will help to further narrow the field of candidates. Ensure your RFP process reflects the criteria your internal team considers to be project “critical”, “important”, or in the “nice to have” category. Include sufficient detail in your RFP to ensure that CDMOs have an accurate picture of the project scope, timeline, challenges, and deliverables. As with a validation exercise, agree to your acceptance criteria in advance; this way, you can compare proposals on much more than price alone.

Caution: There is a tendency to scroll to the price tag of a service and quickly arrive at a conclusion. Populate a grid with your selection criteria to compare each prospect.

5. Conduct On-Site Evaluation.

There is nothing more important than an on-site visit and face-to-face discussion. While on-site, you should be able to assess the capabilities and experience of the leadership team and technical personnel, manufacturing and testing facilities, compliance history, quality system maturity, etc. Use of an experienced third-party auditor will ensure an unbiased, fact-based review of the candidate operation. If a prospective CDMO is reluctant to permit an on-site audit, it is likely not the right fit. If the CDMO says it was recently audited by XYZ agency, that does not matter. It is certainly important information; however, you want to be certain they are the right fit for your project.

Caution: Ensure that if you choose to use an independent auditor, they understand your short-term and long-term needs from a technical and regulatory perspective. For instance, if cGMP manufacturing is essential, the auditor will need to confirm, among many considerations, the maturity of the CDMO’s pharmaceutical quality system.

6. Think Ahead To Commercial Launch.

While product licensure, including a pre-approval inspection, may be a long way off, consider whether the CDMO will be able to work toward that objective successfully. Do they have a track record of success in helping to bring similar products to market? Will they meet the FDA Pre-Approval Inspection criteria and be capable of achieving the level of development required to support regulatory submissions? ICH guidelines (Q8 through Q12) encourage a quality by design approach to product development in which the identification of established conditions will offer regulatory flexibility post approval. Will the CDMO be capable of supporting this approach if it is one of your company’s objectives?

Caution: It’s inevitable that issues will arise given the “unknowns” about a new product and manufacturing process. Variation in inputs, equipment, process conditions, and analytical conditions will warrant study. Ensure you structure your CDMO agreement properly by thinking ahead to manage any additional activities or studies required to support your submission. If every study requires a new contract or statement of work, your finance and legal personnel will be busier than your bench scientists.

7. Make A Final Decision.

You will have collected a lot of data during your evaluation of candidate CDMOs. There may be some red flags or showstoppers that will help you eliminate a candidate. The red flags may relate to the technical capability or perhaps the infrastructure of the facility. They could also relate to quality system weaknesses at a CDMO, such as concerns related to their documentation system and data integrity.

You may decide to select a CDMO that has weaknesses in certain areas but meets nearly all of your other criteria. At one point, a client we worked with turned away from a CDMO that did not have internal analytical capability but was technically the strongest candidate for sterile manufacturing. In hindsight, that may have been the wrong decision. The analytical gap could have been bridged.

Final Word Of Caution

It’s important to select a CDMO that has the right “culture” to quickly and efficiently drive your project to a successful result. Some CDMOs simply see themselves as service providers, while others act as true partners, working side by side with client technical and quality teams to solve the inevitable problems as they arise. It’s not always easy to get an accurate picture of a CDMO’s culture, but this should be a focus during site visits and audits. Networking contacts also can be a good source of information on CDMO delivery and quality.

At the end of the day, your satisfaction with a CDMO will be initially due to the robustness of your selection process. Time invested up front will minimize the chances that you end up having to identify a different CDMO when you are midway through your development program.

About The Authors:

Jim Morris is founder and principal consultant at IQS Consulting. Previously, he was vice president of NSF’s Pharma-Biotech Consulting practice.

 

 

 

Don DeRoo is a pharmaceutical quality and regulatory consultant. Previously, he was site head of quality at Lonza Portsmouth NH and has served as global head of quality (biologics) and head of cell therapy operations.