By Anthony Grenier
Why does it take so much time between awarding a contract development and manufacturing organization (CDMO) contract and initiation of the first activities at the CDMO? During my consulting work, it is a question I am often asked by my sponsor company customers, who feel like they encounter numerous hurdles before finally seeing first activity at the CDMO.
Time lost at the beginning of the project can almost never be recovered down the road, so time saved when starting the activities is an immediate gain for your overall project timeline.
Delays between getting proposals back and starting a project are often sponsor-related. The number of people who need to approve the proposal, internal changes in project definition that require asking more questions of the CDMOs, negotiating the contract and/or a separate master service agreement (MSA), and developing the quality audit and the quality agreement (if either are a requirement prior to contract or project kickoff) are all mostly driven by the sponsor. They will all lead to delays in any project’s start time in the CDMOs’ proposals.
The sponsor can influence this process and shorten the time to having a final proposal approved by:
- having a predefined team of core team members reviewing the versions of the proposal/contract (e.g., project manager, TechOps, legal, quality review) and
- mapping the prerequisites for each step: what site visits or audits need to be performed and when, and what contractual or quality documents need to be in place and when.
Once a project is granted, there are activities you can perform before the traditional kickoff meeting and others that can be done at or after the kickoff meeting. The former will have the greatest effect on building a strong relationship with the CDMO, reducing misunderstandings and progressing the overall project timeline.
Prior To Kickoff Meeting
Some of the below-listed activities would probably be done at the kickoff meeting in other times but in the Zoom/Teams era, they might be done in advance. It is good to get as many logistics action items out of the way as possible while waiting for the kickoff meeting. That also allows the meeting to focus on specifics of the project.
- As necessary, update your request for proposal (RFP) and scope of work (SoW) before the kickoff meeting and recap all assumptions during that meeting. A few months may have passed since the RFP was initially sent and the proposal was revised, and meanwhile, the product development may have been continued by the sponsor, with more knowledge gained on the product/process. As a result, some assumptions may have changed. Likewise, some further internal discussions at the sponsor may have influenced the clinical development plan (including the number of doses and clinical batch size) or the market analysis (anticipated commercial batch size and forecasts of number of batches per year).
- Request the CDMO to clarify its onboarding process; it may be straightforward and very simple, or it could be stepwise with several forms to fill out (e.g., environmental, health, and safety forms, product description forms, etc.). The sooner you fill out these forms, the sooner your project will start. In addition, depending on the development stage and project plan, there may be procedures, test methods and reports, CoAs, reference standards, etc., required to be in place to initiate work. It is helpful to transfer this before the kickoff to help orient the project team.
- Ask to read the CDMO’s template for the quality agreement (QAg) and MSA (if not already signed by then). The QAg is often underestimated and, sometimes, can take several months to be agreed upon and approved by both parties before the first cGMP activities take place.
- Get to know your project manager (PM). If they have already been assigned, take time for a call to get to know her/him better; after all, they will be your key point of contact for months! Find out his/her working hours and the best time(s) and medium through which to contact him/her (phone, text message, email). Understand what your PM’s technical expertise is, what he/she is responsible for, and how influential he/she is (e.g., can they pull people into a room and make things happen? Do they understand when project activities start going away, etc.?).
- Clarify the CDMO’s process for accepting API or any material the sponsor will ship. Sometimes this exercise is not done until the kickoff meeting since the team may have some input into this. For example, if the analytical lab needs API from R&D inventory, it can easily be shipped and accepted by the CDMO; and it is separate from GMP inventory, which can't be accepted until certain forms or SOP steps are performed at the CDMO.
- Understand what the CDMO will request to accept API or materials on-site at the development stage (non-GMP activities) and then for GMP activities. While the requirements may be easy to meet for R&D work, they may become impenetrable for GMP activities, with multiple requirements to audit documents or test the API or materials supplied by the sponsor. Clarify as soon as possible the expected quantities of API for analytical development and a reference standard, if needed. Quantities are often limited for early-stage clinical projects, and it may take time to generate more, so plan it in advance and manage your inventory accordingly.
- Learn how the CDMO’s process for changes of scope and/or amendments works when new activities are added or changes are made to the initial proposal. Inquire if they maintain a spreadsheet they can share with you for budget tracking versus invoices (milestone payment schedule based on completion of activities). It is best to have this system in place at the beginning because it becomes very difficult and complex to track down all changes and additions to the original proposal.
- Ask the CDMO about their invoicing process. Let them also know how to bill your company (e.g., email address to forward invoices, process through a payment platform, share any vendor setup form). Basically, try to map the process to make sure it becomes as smooth and automated as possible later, without back and forth. Vendors have different patterns for invoicing; some systematically invoice as each project activity is completed, while others will invoice months after significant activities are delivered (e.g., upon release of the product). It is always good for the sponsor’s project manager to have visibility of incoming invoices to track the progress of invoicing versus the actual project budget. For this purpose, request to be copied on invoices sent by the CDMO or to be a first-line approver on the platform used by your accounts payable program (e.g., Bill.com).
- Request the CDMO to set up a shared site where all documents will be uploaded and stored for the project period. It is a great tool for reviewing and approving documents but is also useful for tracking down some source documents (e.g., materials specification or manufacturer’s brochure) after a few weeks or months have passed. Above all, it will avoid exchange of information through emails. It becomes challenging to retrieve information after months in your inbox.
- Plan an audit date to make sure you can have the dates matching your activities. Some CDMOs have long lead times to accommodate a sponsor’s audits. This might be a pre-contract closure issue, too.
During Or After The Kickoff Meeting
First, the kickoff meeting is always better in person, as far as possible. This will enable you to get to know the people you will interact with for months and sometimes years. It will also help you to understand the hierarchy, including influential people you hope never to have to contact but that, sometimes, you’ll have to contact to escalate major concerns with your project execution or management.
- The actual project team was likely not involved with the proposal itself and knows little about the project. Take time to prepare insightful and comprehensive slides with concise content but inclusive of all you know and all you don’t know about your process and product. This is, from my experience, a neglected step and it is worth investing some time to prepare them. It will greatly benefit the audience, adding to their knowledge and helping them start your project quicker and avoid making errors you may have already made. It is motivating for the project team to know what indication your drug will target and how your drug will make a difference in patients’ lives.
- Understand each person's role and their background. Nowadays, it is also insightful to know how long they've been with the company and in their position.
- Understand the internal processes at the CDMO by going step by step through the timeline. It will help you understand the flow of documents for issuance, review, and approval. It will also help you discuss with them and challenge the cycle times. Are they too generous with themselves for review time or not generous enough with you, or both?
- Understand how the CDMO works with subcontractors, including the flow of documents, proposals, and the timeline, as well as study documents (protocol, reports). CMOs must often seek expertise from external vendors for certain testing (e.g., container closure integrity testing, filter compatibility testing, and other filter validation studies) or equipment installation. In addition, with companies that have multiple sites, the sponsor should confirm if any activities might be carried out at another site.
Anticipating what’s coming next is key to saving some time at the beginning of your outsourcing project with a CDMO. Each CDMO has a different way of working, but the above listed points are practiced by many in the industry. Combined with good, proactive communications from the sponsor, they will make a difference in starting your next project faster.
The author would like to thank Susan Wollowitz, Ph.D., for her insightful review of and input to this article.
About The Author:
Anthony Grenier is an independent technology transfer and outsourcing consultant. A chemical engineer by training, he has completed over 60 technology transfers for both large, public multinational corporations and small specialty or virtual pharma companies spanning all major segments of the life sciences industry. He can be reached at firstname.lastname@example.org or on LinkedIn.