By Brian James, Ph.D., SVP of operations, Rondaxe
The story is a common one. Your organization has just acquired a new asset and you are responsible for finding the custom development and manufacturing organization (CDMO) that is going to take you all the way to commercialization. The hard part is over, right? If only it were that simple. The process of selecting your partner is more than just drafting an agreement; it is a complex give and take that relies on clear expectations and communication.
Here are the critical questions you should ask yourself before you even approach a CDMO, let alone begin drafting that all-important request for proposal (RFP).
First, you need to be clear about your level of involvement with future project management. Although you may have the best intentions, brutal honesty is important. Are you going to be able to check on progress daily, weekly, biweekly? The less time you have, the more you will need to rely on the CDMO’s project managers. Clear lines of communication and regular updates foster trust between the innovator and the CDMO; trust that is necessary for success. Projects have failed, relationships have been destroyed, and companies have folded due to poor communication.
Know Your Risk Levels
Risk is inherent in every new venture, but it’s important to understand the level of risk you are taking on with a new project. Risk factors often center around three areas: time, budget, and region.
Time is always at a premium, and often there is extreme pressure to maintain a timeline. Capsules must be ready by a certain date to start your clinical trial. Can you afford a delay if problems arise? Will a month-long delay be catastrophic to the program?
Budget is another consideration, and depending on where your organization lands in the development cycle, the questions are different. In the early stages, providing proof-of-concept as quickly and cheaply as possible is the priority. As the scale increases, spending some development dollars to make process improvements begins to make more sense. Budget is also important when crafting your RFP. Can you afford multiple scope changes if you put out an incomplete request? It may take time to get it right, but that timeline is forefront in your thoughts.
The overall risk analysis should also include regional-based risk factors. When your project is located on the other side of the world you need to consider delays due to time zones. Your travel budget will need to be increased so you can visit the CDMO prior to selection and then as the project continues. You should also consider language issues. All batch records need to be written in the native language of the operators; do you have the time and budget to account for that?
Know Your Project
Once you have decided on the level of involvement and risk you can accept as an organization it is time to get serious about your project. After all, how can you create a short list of potential CDMOs if you don't match your project requirements against their strengths and weaknesses? When evaluating your project, are there any special technologies required, such as low temperature, high pressure, or unusually energetic chemistry? Maybe you need to be able to measure out very small doses for formulation. Are there special safety concerns, such as high-potency or dust explosion hazard?
What is the scale of your project now? Are you willing to perform a tech transfer later if you outgrow your first CDMO, or would you rather find one partner from start to finish? Trick question! Even if you partner with only one CDMO, there are likely to be multiple tech transfers within the organization.
Developing a clear and focused direction before you approach the CDMO will pay dividends in the end, maximizing your chance of a successful, smooth process.
Refine Your Approach
Companies have taken a variety of approaches in selecting companies to contact. Two of the most common approaches are calling on industry contacts and using the "shotgun" approach of cold calling.
Approach #1 – Personal Reference
I recently attended a panel presentation where one of the panelists told an all too common story. A small organization relied heavily on personal recommendations for its CDMO partners. After the project was awarded, disaster struck. The CDMO was a month late on meeting the delivery, then two months late, then all the material was destroyed in a fire. Eventually, the company was back at square one: no CDMO and no clinical material.
Partnering with a CDMO should be viewed as an important strategic and tactical decision. References are a part of the process, but should come after objective criteria have reduced the pool of candidates. Is the potential CDMO capable of handling your project from a safety and technological point of view? Is it a well-established CDMO with a documented regulatory history? How soon can you visit the facility to make your own assessment? These are questions that should be addressed early in the selection process.
Approach #2 – Shotgun
In the shotgun approach, you look at the companies listed in the latest trade show directory, eliminate several based on arbitrary criteria, and start the process of getting a CDA from 30 CDMOs. After getting the CDA in place and sending out the RFP, 10 of the companies may send you a polite “thanks but no thanks.” That still leaves the possibility of receiving 20 proposals. Over the next couple of weeks, you field a series of questions, often the same ones in different formats, from several of the candidates. Then five of them don't bother to submit a proposal in time, leaving you with 15 proposals to review and summarize. You are on the hot seat now as management wants to know who the new partner is. You shortlist a few and pick one, once again with less than desirable outcomes.
Approach #3 – Match Capability With Criteria
The above scenarios demonstrate the major pitfalls of two common approaches to vendor selection. So how do find the CDMO partner that has the best capacity, technology, resources, quality system, and financial match for your needs?
While there are a multitude of criteria that can be evaluated, identifying and avoiding the key mismatches will go a long way toward getting your project completed. Key questions need to address the following: quality systems, capacity, and technology.
Probably the most important question to ask of a potential CDMO is: Are the quality systems sufficient? If you need cGMP manufacturing, you can eliminate the ISO type contractors. Likewise, if you are looking at potential regulatory starting materials, why pay the premium for unnecessary cGMP production? Search the FDA database for warning letters to identify past quality problems. Reputable manufacturers will clearly outline their recent regulatory inspection history. This is not a substitute for a quality audit, but the goal at this early stage is to exclude potentially bad fits from your list.
Having reduced your pool based on quality information, the next step is to determine if potential CDMOs have the capacity to handle your project. This can get a little tricky at times, because you may only be able to determine if they have the reactors and equipment required, not their availability. If you are looking to prepare 10 MT of drug substance annually, you should avoid a smaller CDMO with limited capacity, or at the very least realize that you will likely need to transfer your project in the future.
The final step in determining who will receive your coveted RFP is to evaluate the CDMO technology needed for your project. A thorough understanding of your project requirements is a necessity at this point. For example, a highly potent compound requires specialized handling and equipment, necessitating a company that is an expert in the field. If you require energetic chemistry, cryogenic conditions, or lyophilization, the potential pool shrinks even further.
If you have directed your search for a CDMO using the guidelines above, you should be able to generate a list of five or six CDMOs that could potentially execute your vision, delivering high-quality product on time and under budget. These are the CDMOs that should be contacted to execute your confidentiality agreement and submit proposals. From there you can make comparisons, develop a short list, visit one or two, and then make your decision. Direct your search for the best CDMO for your project with the guidelines of quality systems, technology and capacity in mind and you will greatly increase the chances that your project is successful and on target.
About The Author:
Brian James, Ph.D., MBA, is the SVP of operations at Rondaxe, a pharmaceutical CMC consulting and software firm. Brian oversees project management, API synthesis design, and API/formulation sourcing support to Rondaxe clients. He manages and oversees projects ranging from pre-IND chemistry development to pre-launch validation and material sourcing for late-stage clinical trials. Prior to joining Rondaxe, he was with Bristol-Myers Squibb, where he honed his skills and expertise in API synthesis and sourcing strategies. Brian received his Ph.D. in chemistry from University of California and his MBA from Le Moyne College, and performed his post-doctoral fellowship at Colorado State University.