By Ray Sison, xCell Strategic Consulting, LLC
A sense of accomplishment from problem-solving and discovery is why many of us do what we do in drug product development. However, formulations scientists, analytical chemists, and procurement specialists do not choose their projects. This choice is driven by corporate strategy. So when a new drug product is identified for development, it can be like Thanksgiving dinner — an enormous feast in the company of people with opinions and viewpoints that may be vastly different than your own. In organizations with an outsourcing model for drug product development, finding the right partner that can meet the collective needs of all stakeholders is critical to a successful outcome. There is no one-size-fits-all solution. If you've been following this series of articles, you already know utilizing a well-thought-out RFP is critical to CDMO selection because it places you at the head of the table when reaching out to vendors and helps you control the outcome.
RFPs for early formulation development (EFD) are different from tech transfers, clinical supplies, and other RFP strategies because the scope requirements need more flexibility to accommodate the unknowns of R&D. Going into the process, consider the following:
In each article of this RFP how-to series, we cover the rudimentary questions to ask to prime the CDMO proposal process.
What do you want?
During development of a product requirements specification (PRS), talk to the various stakeholders about their needs. Clinical drives performance requirements, regulatory sets the filing pathway, commercial communicates market needs, and legal may identify patents limiting your solution space. More than ever, “you” is plural, representing the needs of the collective stakeholders in your company. Moreover:
When do you want it?
It is important to communicate anticipated milestones to a CDMO so you can develop timelines that sync with cross-functional activities. Examples include: The clinical team has made commitments to begin studies, so drug product (DP) will be needed by a certain date. Regulatory and commercial will have expectations for filing and launch that must align with drug product development activities. Depending on variables such as timing, development stage, and budget, you or a CDMO may select one or all of the following EFD strategies.
Proof of concept (PoC)
Many refer to this as "quick and dirty,” implying a non-methodical, informed guess based on experience. While appealing to some for limiting time and budget, several conditions or scenarios must exist in order to ensure success:
Some EFD platforms can be utilized as shortcuts if they meet your needs and objectives:
a. solvent systems,
b. hot melt extrusion,
c. spray drying/particle engineering, or
d. functional excipient systems.
Project managers responsible for EFD know this means a comprehensive and methodical strategy to address each PRS line item. Key terms may include “design of experiment,” “quality by design,” and “characterization.” In the name of flexibility, refrain from insisting on a single approach, but in technical discussions encourage a dialogue to uncover what a CDMO development team has found works best for them.
In many cases, PoC or platform strategies will funnel to a full development program at the appropriate stage to determine the optimal drug product. If the target drug product or API falls into the following categories, there may be no choice but to implement a thorough developmental approach:
How much do you want?
If there are clinical commitments to provide materials, quantities must be communicated to the CDMO. The DP's intended use will also determine the level of quality (non-GMP versus GMP) needed, which impacts cost, controls, and timing. For EFD, typically the output is not inventoried product, but number of prototypes for evaluation, samples, and preliminary data.
Project scopes can be requested in various ways, but for EFD it may be beneficial to use open-ended language to encourage technical discussions. Here are some examples of such language: "Propose a formulation development strategy and testing to yield up to three viable formulations that meet the PRS." “Suggest various process strategies and unit operations appropriate for viable formulations, and point out any pros and cons associated with each approach.” “Propose a container closure system that meets the PRS, and comment on the scalability and/or machinability challenges we may encounter upon scale-up.” A comparison of the responses will differentiate the bidders.
The search for a CDMO partner for EFD starts with gaining alignment with your internal stakeholders and developing a product requirements specification you can share in the RFP process. You get what you give. It pays to share as much technical information about the physiochemical characteristics of the API and any previous development work that has been done to prime discussions with each vendor. This will save on cost, but for EFD be aware other criteria (operational, technical, analytical, etc.) may outweigh a direct comparison of vendors based solely on budget. Instead, focus on evaluating different approaches and understanding the expertise brought to the table by each team. Respect confidentiality when discussing among vendors, but use information to develop an overall comprehensive strategy. Find what works best for you and the project during the selection process, and build from there in subsequent requests.
About The Author:
Ray Sison is VP of Pharmaceutical Outsourcing and Tech Transfer at xCell Strategic Consulting. He began consulting in 2011 after recognizing a need for expertise in pharmaceutical outsourcing among the discovery- and clinical-stage pharma companies he served as a business development representative for Patheon and MDS Pharma Services. Based on his experience, Sison provides insight to the CMO’s business and operations, helping his clients negotiate and achieve better outcomes. Additionally, he has developed sound processes and templates to streamline CMO procurement to save time and cost. In this series of articles, as well as online webinars, he continues to share best practices and case studies, helping improve the outsourced business model. You can reach him at email@example.com or connect with him on LinkedIn.