Selecting a CDMO: Part ONE: Defining Requirements

Many firms jump right into the process of CDMO selection without taking the time to fully understand their own requirements. Without identifying the cross-functional needs of all internal stakeholders, it is difficult if not impossible to write a meaningful Request for Proposal (RFP). The RFP is a critical document that serves to source candidate companies as well as to assess their bids against objective criteria (more on that in the next blog).

Ideally, cross-functional requirements should be driven by internal procedures or policies but can also be identified outside a formal framework. The CMC leader or project manager should spearhead the collection of requirements through interviews and document the output in writing. Examples (this is not an exhaustive list) of the sort of information to be collected include:

Clinical Operations: an assessment of product needs to support planned clinical trials. These demand estimates are often necessarily uncertain as detailed clinical protocols or even study schema have probably not yet been written. Nevertheless, the overall product demand estimate is a critical piece of information, as it will ultimately drive the production scale (batch size) and campaign duration (batch number). Information about the expected dosage form is also important, as this will drive drug product process development.

Process and Analytical Sciences: the production processes for drug substance, drug product and finished drug product may not be well established for a pre-IND drug candidate. Even established processes will need to be transferred and established in the facilities of the new CDMO. The technical capabilities of the vendor must be thoroughly vetted by SMEs who have detailed knowledge down to the unit operation level. Often, production is transferred or established at a variety of scales. Initial production may often be performed at the benchtop in a non-GMP environment. This is useful for building process understanding, for providing an environment for troubleshooting and process optimization and, thinking down the road, as a platform for performing process characterization studies needed to support future marketing applications.

Production at pilot-scale is often also performed to gain additional process knowledge and to provide enough non-GMP material to perform additional product characterization work and to provide working standards for the development of analytical methods. In addition, sufficiently qualified pilot-scale process data can be used to support regulatory submissions and stability programs, subject to approval from Regulatory Affairs function.

Finally, Process Sciences often has specific requirements for the transfer of process information gained from bench and pilot scale studies. Reports may be formalized to a varying degree and like QC, often must be accompanied by raw data files.

Quality Assurance: the CDMO, like all 3rd party suppliers of GMP products, must be qualified by the Quality Unit according to internal procedures. The CDMO must be able to meet these requirements, with any exceptions understood and accepted in writing by the Quality Unit. Often these requirements are specified in a questionnaire or survey the CDMO completes and submits as part of their Proposal submission. Any selection is almost always preceded by a thorough on-site audit by Quality and technical staff.

In addition to compliance requirements, the CDMO quality systems for production, lot disposition, deviation management, change control and many other aspects of GMP manufacturing must be understood in order to allow the Quality Unit to inform the CDMO selection process.

Quality Control: as the CDMO will almost certainly provide GMP analytical services in addition to manufacturing, analytical methods must be developed or transferred and qualified for use. Quality Control must specify their requirements for each of these activities to sign off on the final approved suite of analytical methods.

A key QC deliverable that is often missed during the sourcing process is that of data acquisition. Often CDMOs will provide a final Certificate of Testing or Analysis to support batch release. Occasionally, copies of completed test records are also available. These are often insufficient, however, for QC to fully understand analytical results. Chromatographic data for example, in the form of electronic files for each run, are needed to ensure that the stated results align with the raw data. QC should endeavor to state their data requirements for each analytical method used in the process.

In addition to overseeing testing, Quality Control is usually responsible for the product Stability program and will need to work in conjunction with the CDMO to implement the program using approved procedures and protocols. Their input at an early stage will help ensure the CDMO stability program standards are acceptable. It is worth noting that the material requirements of the stability program are often considerable and will impact the total product demand.

Project Management: Project Management is the function which ties all the pieces together. In addition to leading the project in terms of collection of functional requirements, PM often has its own requirements as well. Considerations include the logistics of company-company interaction, establishing a document transfer system and document repository, building a project governance process with senior management from both companies and finally, defining key milestones and deliverables upon which to base payments.

Regulatory Affairs: RA often can help inform vendor decisions by providing insight into prior regulatory history with global health authorities. It is good practice to consult with RA to understand their requirements as well as gain information on specific vendors from their previous regulatory track record.

Finance: Like any contract, the CDMO agreements require careful scrutiny by the Finance unit. Satisfactory terms and conditions must be negotiated, which include payment terms, incentives and penalties and liability conditions. Although Finance will play a large role once the final proposal is under negotiation, it is wise to bring them in early to ensure any critical requirements are made clear to prospective vendors.

Next Time: Part TWO: Writing and Distributing the RFP