How to Choose the Right Biologics CDMO Partner

Introduction

Whether a biologic drug is being developed by a large multinational pharmaceutical company or is the first product for a virtual start-up, chances are that at least part of the supply chain is outsourced.?

By the time a biologic product progresses from discovery through development to commercialization, CMC-related expenses can exceed $100 million. Because the contract development and manufacturing organization (CDMO) vendor relationship is often one of the most significant partnerships and expenses for a biotechnology company choosing the right partner is a critical decision for a company.?

Often a CDMO partner is selected based on a single recommendation or after being approached by the CDMO’s business development person, but this choice has too much impact on a company’s success to be taken lightly. Instead, CDMO selection should be a thoughtful and pragmatic process to ensure the highest chances of selecting the best vendor to meet the company’s specific needs. This paper aims to outline one approach to selecting a biologics CDMO that is thoughtful, methodical, and allows the process to be documented.?

Create an Initial List of Candidates

An internet search is always a good place to start but also check industry forums and publications. Also ask colleagues and industry acquaintances for recommendations. If they have contracted similar CDMO services, ask whom they used and why. Also ask if they ran into any issues and what steps the CDMO took to resolve them. The CDMO space is rapidly evolving, and reputations go up and down, so a vendor who was good a year or two ago can have problems today. Vendors can also improve, so make sure you are working with up-to-date knowledge when making these initial assessments.

Next create a list of must have CDMO requirements. These requirements must include whether they have the required infrastructure for your product, have experience working with your type of product, and whether your required production scale fits in their facility.?

The CDMO must also have development, manufacturing, and analytical testing slots available in the timeframe needed to meet your timelines. The CDMO also needs to have the capacity to support your program with future follow-up batches. Therefore, a clear understanding of the lead times required for manufacturing and releasing future batches is also critical.?

Eliminate companies that do not meet these initial screening requirements. This can be accomplished by reviewing the company’s promotional materials, visiting the company website, and talking with the CDMO’s business development group. Nothing confidential should be discussed with any potential CDMO partner without a signed confidentiality agreement in place.?

Narrow Down the List?

Next create a spreadsheet to narrow down the list of candidates. This spreadsheet should include the CDMO name, business contact, required development competencies, available production scales, number of production suites, and analytical and stability study capabilities. This spreadsheet also needs to include whether the CDMO has dedicated project management support and a separate quality assurance department that reports directly to senior leadership. Also check whether each CDMO candidate has systems to protect customer confidentiality and intellectual property.?

Once the spreadsheet is populated, compare the information for each CDMO candidate to your program’s needs. Quality CDMOs will have systems to prevent using the client’s name in the production area. Documents should be transferred from a secure server, or if they are sent by email, they should be password protected with the password sent under a separate email. The project manager is usually the customers’ advocate once a contract is in place, so look for a well-established and integrated project management department that will serve as your advocate when issues arise.?

Finally, decide if you are looking for a larger one stop shop or a smaller CDMO that best fits your product’s unique needs. Going to a one stop shop can make managing the program easier but might not be the best fit for your program. Going to a smaller niche CDMO may be the best fit for your product, but it increases the complexity of the supply chain and management oversight responsibilities due to the need for handoffs between vendors.

Prepare a Request for Proposal (RFP)

At this point the candidate list should include at least three CDMOs. To directly compare time, cost, and deliverables between different CDMOs, the sponsor should draft a request for proposal or RFP that details the services being asked for.??

Sending each CDMO the same detailed RFP always provides the best mechanism for direct comparisons. The most informative proposals are received when the sponsor provides extensive details about the program. Providing extensive details always requires sharing confidential information. If a confidentiality agreement (CDA) still needs to be signed, now is the time to put one in place before any vendor receives an RFP.?

A good RFP always starts with a?product background followed by the scope of services being requested.?This is followed?by the deliverables section, which includes a list of deliverables the project requires.?

Specifically ask the CDMO to demonstrate in the RFP their ability to fit your process into the facility by defining the manufacturing process scale and any environmental controls, such as the ability to make an aseptic product or handle highly potent compounds. Also, ask for an estimated budget broken out by stage and as an aggregate that includes expected pass-through costs such as outsourced testing, raw materials, chromatography resins, and equipment such as column housings.?

Next, ask the CDMO about their ability to support your program in the future. List the program’s expected needs over the next few years to determine if the CDMO can continue supporting your program after the initial work is completed. Also, ask about the company’s economic viability and if the company will continue to be in business to support your program for the foreseeable future.

In the RFP request a regulatory inspection history and?a copy of the CDMO’s most recent inspection report. Also ask for several client references and a detailed timeline broken out by stage that shows the major deliverables and milestones.?

Last state how the CDMO should submit its proposal to the sponsor, including the format for the proposal and to whom it should be addressed. Finally give a deadline for when responses are due. If responses are not returned on time, chances are they will not be a responsive vendor.

A well written and comprehensive RFP will ensure that you are asking each potential CDMO for the same thing, which allows the quotes to be compared directly. If a vendor is unwilling to address each point in your RFP take this as a warning sign that they might not be a suitable partner.?

Review RFP Responses

When reviewing each of the responses, evaluate the overall soundness of their proposal, whether they supplied everything asked for in the RFP, and if there are any deal breakers. Also check whether the CDMO has made a case for long-term business viability. Finally review the regulatory inspection history and immediately disqualify and vendor with significant regulatory issues.

At this point, some of the vendors will have been disqualified for not submitting on time. Some will also have been disqualified because the proposal has some deal breaker that doesn’t support your needs. Some vendors will try to convince you they can support your program even if they don’t have appropriate capabilities. Disqualify these vendors immediately and move on.

Site Visits

The next step is to visit the remaining candidates. At this point, the list should be narrowed down to at least two candidates to provide a backup in case issues are uncovered during site visits or contract negotiations.?

When visiting each of the remaining candidates, tour their facility and meet the people who will be developing and manufacturing your product. This is usually the first chance to move beyond talking to the CDMO business development person and evaluate the team that would be making your product.?

Use this visit as a chance to gauge the depth of talent in the facility. Look for technical competence but also cultural fit with your team. Check if the facility is well-staffed, knowledgeable, well-trained, quality conscientious, and competent. For early-phase products, determine if the quality group is flexible enough to allow any changes needed to address CMC development and manufacturing issues or changes during early-phase clinical development.

During the visit confirm the capabilities outlined in the RFP response and if the CDMO site can actually support your product?in the future. Look for potential capacity issues, such as only having a single bioreactor train at your manufacturing scale, limited space for stability studies, limited analytical capabilities, or limited downstream processing capability.

Try to understand how well the facility is run and maintained.?When meeting with the site staff, ask about the person in plant policy. Quality CDMOs always welcome sponsors to be present on-site during critical manufacturing activities. Good CDMOs also have offices for the person in plant to work from when they are not watching critical operations.?

If the CDMO site only introduces you to a few members of the executive team and you do not see many of the site’s key employees, take this as a warning.?Finally try to get an idea of how they will be to work with. When problems arise, a strong and collaborative partnership is key.

Quality Audits

When evaluating CDMOs, it is important to perform a 1 to 2-day onsite quality systems audit. This needs to be led by an experienced QA auditor familiar with the services the CDMO site provides. An experienced QA auditor will come to the sites prepared and will spend the time reviewing the sites quality systems, quality manuals, document management systems, deviation and investigation procedures, corrective action and preventative action (CAPA) procedures, equipment maintenance and calibration programs, raw material sourcing procedures, and more. It is critical for the sponsor to carefully review the final quality audit report and understand any potential CDMO site quality issues before signing any contracts.

Reference Checks

The sponsor should have asked the CDMO for references in the RFP. If not, then ask the CDMO for references now. When talking to the references, look for gaps between what the CDMO promises and what was delivered. Also try to determine how the CDMO works with its customers. Developing biologics is complicated so issues will arise. What is important during the reference checks is to learn how the CDMO dealt with these issues. Immediately disqualify any CDMO that the references say is dishonest and lacks transparency. Quality CDMOs always communicate problems transparently and proactively.?

When checking references, look for signs of systemic quality issues, which can show themselves through frequent maintenance failures or product contamination. Also try to understand whether the CDMO staff is content or overworked. Finally try to understand the CDMO's flexibility when working with clients. The best CDMOs understand that issues can arise which affect the sponsor's needs. Like all partnerships, there must be give and take on all sides.

Negotiating Contracts

At least two vendors should remain going into contract negotiations. Having at least two vendors is important so the sponsor can walk away without starting the CDMO selection process over if unresolvable issues are found during negotiations.

In addition to negotiating the contract, it is critical to also negotiate the master services agreement and quality agreement. Review these carefully and look for deal breakers such as not having ownership of intellectual property, unfair payment terms, or onerous cancellation fees. The quality agreement template needs to be reviewed by a quality professional, preferably the same QA group that performed that quality site audit.?

Making the Decision

Review everything learned from the RFP responses, the site visits, quality audits, talking to references, and contract negotiations. Next weigh each CDMO site’s level of regulatory compliance, manufacturing record, facility fit, capabilities, supply chain complexity, and whether they have the flexibility and cultural fit to be an excellent strategic partner.?

The final decision always balances time, cost, and quality.?Balancing time and cost are often a personal decision that depends on the sponsor's circumstances. However, selecting based only on low price is often at the expense of quality which will eventually lead to problems and is not recommended.?

Once the final decision has been made, it is important to write a final report documenting the CDMO selection process and justifying why you chose this vendor. This document can be shared with company leadership, board members, and investors while providing a valuable reference for future programs.

Conclusion

This article provides a high-level overview of one way to select a CDMO for a biologic product. Following this process increases the chance of choosing a CDMO that is the best fit for your product and company needs. Selecting the right CDMO will not only help ensure the success of the CMC program but will also become a critical partner for your company's growth and long-term success. Contact the author with any questions.