Taking Your API to the Next Level: Three Steps to Consider Before Outsourcing

11月 19, 2020 By Laura Chamberlain (10 minute read)

With outsourcing API development becoming more common, we see a rise of multiple competing Contract Development Manufacturing Organizations (CDMOs) as potential development partners. This allows small/virtual companies the ability to take their concept to clinic at a much lower cost versus building, renting, or buying lab space at a facility.

More accessible drug development for small, emerging, and virtual companies should mean more opportunities for research and faster development/approvals for medicines to change the world. After researchers make it past preclinical toxicology, they often don’t know where to go and the idea of engaging with a large CDMO can be intimidating. Researchers have put their heart and soul into their small molecule API, and the thought of handing their “baby” off to a stranger opens a myriad of concerns and considerations.

If you and your team are thinking about outsourcing your API’s clinical development, it’s important to ask yourself:

• Can the CDMO get our API to the clinic as soon as possible?
• Does the CDMO have the expertise to mitigate risks at both the chemistry and regulatory levels?
• Can the CDMO create a robust and efficient synthetic route?
• Can the CDMO effectively solve complex chemistry/potency challenges?
• Does the CDMO have the capacity, expertise, and experience to scaleup to support the future of the molecule?

Though these questions just scratch the surface of what capabilities the right CDMO should possess, they are the foundation of the criteria in selecting one. The right CDMO should be a partner who not only values your API, but one that guides you through the quoting and selection process—especially if it’s your first-time outsourcing.

The timing, prep, and process of engaging with a CDMO is often unclear, and the growing network of possible vendors can be daunting. A savvy CDMO should be able to provide flexible drug development to small, virtual companies, university spinouts, and bench-top chemists. Whether your molecule requires basic or complex synthesis, or containment, a CDMO should make you feel confident in their ability to deliver high yields, optimize synthetic routes, and mitigate risk in the manufacturing process.

To make an informed decision on a CDMO, consider these three steps:

Step One: Determining When to Engage

Determining the right time to engage a potential CDMO is the first step and is often a challenging decision. Many new and emerging biotech/pharma companies get stuck on timing and funding, which can make them hesitate in engaging with a potential CDMO.

Engage Earlier Than You Think

The time it takes to evaluate, select, and initiate activity with a CDMO can be a lot longer than you may think. It’s important to engage a potential CDMO earlier rather than later to discuss the development and/or manufacturing of your molecule. The average time to a select a CDMO—from first conversation to initiation—takes approximately three months. By engaging earlier, you give yourself ample time to get a better understanding of your own needs and what the right CDMO looks like for you and your molecule.

There Will Never Be a “Perfect Time” to Engage

For new and emerging biotech/pharma companies, funding is a typical roadblock and compiling a full RFP is time consuming. If you find yourself facing either of these challenges, it’s important to remember that early engagement is a balancing act, and you may never find yourself in the “sweet spot” with the required funding and a complete RFP for use in CDMO discussions. This makes having transparent conversations sooner rather than later even more critical, as you can use them to refine and make decisions faster in the future. When engaging with a CDMO in the early days, be sure to ask them:

• What amount of process development work will be required?
• What are the lead times for raw materials?
• How do you—the CDMO—plan to approach scale-up manufacturing?

The best information often comes through discussion and cannot be put into a technical package. Asking these questions up front can be used to craft a more thorough RFP.

Ask the Potential CDMO to Show and Tell

While many companies don’t require the assistance of a CDMO until they need GMP material, that does not necessarily mean they need to wait to engage a potential CDMO. As early as lead candidate selection, engage the potential CDMO for non-GMP material for late-stage toxicology studies. Utilizing a CDMO for late-stage tox material may cost you slightly more upfront than a CRO or non-GMP shop, but it’s worth it, because:

• It develops rapport between you and the potential CDMO.
• It encourages adherence to communication, timelines, quality, and delivery.
• It weeds out CMDOs who aren’t as hands-on and willing to get their hands “dirty” with the chemistry.
• It helps you start evaluating for potential future developments.
• It can be done separately and won’t bind you to a CDMO—if the studies are poor, you can find a different CDMO with more experience.

Step Two: Preparing for Conversations With a CDMO

It is helpful to a potential CDMO to have a formal RFP detailing your needs, goals, and the technical information your team has generated so far on the API. A common challenge for small and virtual pharma/biotech companies is they do not always have the workforce or bandwidth to compile an RFP. If compiling the “perfect” RFP is standing in the way of beginning your vendor search, the right CDMO will have a team who can review, discuss, and confirm the scope of your project to help move the process forward. The more you prepare for your conversations with prospective CDMOs, the more confident you’ll feel through the process. There are some key elements that are crucial to develop a proposal for your project. Gathering and sharing this information up front will allow for more detailed discussions as to how the potential CDMO fits into your specific program.

• SDS/Safety information
  Safety is often a top priority for many CDMOs and understanding the handling requirements for your API will be critical to determining if and how the CDMO could work on your molecule. The right CDMO will be able to preliminarily determine the proper handling specific to their site through available data and/or guided, specific questions.
• Timeline delivery, deadlines/goals, and trial goals
  Timing needs are a critical factor to the success of your program and should be communicated to a potential CDMO. Everything from filing deadlines to corporate goals—this will help them determine resource availability as it relates to your needs. Your CDMO’s proposal should include a detailed timeline that can then be discussed further during conversations.
• Budget or funding situation
  It’s very helpful for both parties if you are transparent about your current funding situation and your goals for engaging with the CDMO. Regardless of your funding situation, transparency should make sure neither party’s time is wasted and will help the CDMO tailor a solution that fits your needs.
• Quantity
  The amount of API you’ll need expands beyond just what you will need for clinical trials—it is important to consider material for formulation development, stability studies, and testing contingencies. The right CDMO will be able to help you estimate additional material needs, but make sure you communicate what you intend the quantity to cover.
• Indication
  A potential future partner should be interested in better understanding what drives your company and the program. The right CDMO will ask about the product indication and care to learn more about the product—be prepared to share your passion and tell your story.
• Phase of development
  There are certain service aspects that vary based on the phase of development, such as analytical methods, which are developed to be “phase appropriate.” Be transparent if you are looking for only what is needed for your specific phase, or if you are forward-thinking and preparing your program long-term.
• Clinical approach
  Be open with the CDMO about your clinical plans. While it is up to you to tell your CDMO the services you need, a strong partner may recommend services often needed based on your regulatory approach. If nothing else, it will allow your CDMO to align on your company’s goals.
• Technical information
  The meat of the discussion will be focused on the technical aspects of your program. The more information you share, the more accurately a CDMO will be able to provide a proposal for development and manufacturing specific to your program needs. At a minimum, be prepared to provide your current API structure, synthetic scheme, and experimental procedures. If you have developed methods and specifications, it is valuable for your CDMO to reference these, as well.
• Multiple vendors/integrated offering
  An integrated offering is the combination of multiple drug development services within the same CDMO partner. These often include drug substance, formulation, drug product, packaging, and clinical trial distribution needs. Take some time to learn more about the CDMO’s ability to support additional services and begin to consider the pros/cons of working with multiple CDMOs or combining multiple services at a single vendor.

Step Three: Vendor Scorecard and Meaningful Conversations

Once you’ve outlined your goals and commercial aspirations, it’s important to develop selection criteria. Rank each criterion by level of importance and “score” each vendor as you move through the selection process. Common criteria include:

1. Capability, technology, and expertise—does the CDMO possess the technological capabilities and scientific expertise to develop and optimize a robust and scalable API process?
2. Capacity and timing—does the CDMO have the production resources to meet your timing and delivery needs?
3. Regulatory history and quality—does the CDMO have a successful track record with local and global regulatory agencies and adhere to strict quality standards?
4. Partnerships and relationships—does the CDMO have a vast network of esteemed partners who can vouch for their performance?
5. Location and geographical reach—does the CDMO have a large geographical network of internal labs and support locations?
6. Integrated offering—does the CDMO provide an end-to-end sourcing solution and can they work on multiple aspects of your drug development needs?
7. Security of supply—does the CDMO’s vast network of partners include vendors who can continually provide the raw materials necessary for production?
8. Financial security and business continuity—does the CDMO have a history of strong financial performance and internal processes/procedures to ensure business continuity?

Next Steps for Selection

Once you prepare for conversations and develop your vendor scorecard, it’s equally as important to come up with selection requirements. These are the actions you intend to take during the vendor screening process and prior to moving forward with a CDMO. This is where you really get to know a prospective CDMO. Potential CDMOs should show you: their facilities and how they work at the ground level, how they approach terms and their flexibility with things like licensing and contracts, and how they interact with your internal stakeholders. Some common considerations are explained, but only your team can determine what you need to know from a potential partner before moving forward.

• Site visit
  Your only contact shouldn’t be with a sales representative. The right CDMO will introduce you to the site team at the ground level to show you how they manage their work. This also allows you to get an idea of their culture—an often overlooked but very important aspect of working together. Culture is huge, and the right CDMO will showcase theirs and ask about yours and should indicate where both cultures can work collaboratively as one. Due to current, COVID-19 travel limitations, if a physical site visit is not possible, the right CDMO should have a robust means of showing you their site virtually.
• Contractual terms
  Often not discussed until later in the selection process, the contractual terms are a critical piece to selecting your CDMO. Whether it’s Terms & Conditions listed in a proposal or an overarching agreement that will also govern future scopes of work, the right CDMO should be flexible and willing to work with you at all levels of contract negotiation. This is where you and the potential CDMO can also establish expectations and turnaround times on both sides.
• Initiation
  During this phase, it is crucial to engage your own internal stakeholders as you discover your shortlist of potential CDMOs. The approval process after you select a CDMO can take longer and be more challenging than you may think. Considering stakeholder buy-in—in advance—will help you in the long-run. Do your university, board of directors, and/or investors need to be involved to select a CDMO? Most likely, yes. Engage them early and update them on conversations with potential CDMOs as you have them. The right CDMO will be open to direct conversations or connecting with management to prove their capability.

Engaging in Purposeful and Meaningful Conversation

Developing all of this will ultimately prepare you for each conversation with a potential CDMO. The more you put into having purposeful and meaningful conversations, the more you’ll get out of them. As you engage in these types of conversations, be sure to:

• Ask the hard questions
  The right CDMO should not only be able to answer them but give you confidence in their expertise and capabilities. Make them work to build rapport with you.
• Uncover their passion
  Find a CDMO that is passionate about their work and most of all, patients—this type of vendor will engage in fulfilling conversations when addressing your specific interests.
• Notice how they tailor the conversation
  Many vendors can talk about their site all day, but they might not be telling you what you really want to know—this is where your questions and engagement allow CDMOs to tailor the conversation to you and your API.

Making the Most Informed Choice

By following these steps, your team will be able to make the most informed choice of which CDMO is best for you. The right CDMO should always take a consultative approach, but if your team is new to drug development, it is wise to engage a CMC consultant for additional support. A CDMO isn’t there to make decisions for you. They are there to be your partner who can help make recommendations on their experience, but also allow you to have the power and ownership to make final decisions regarding your program. The right CDMO will act as your commercial accelerator who can take your API to the next level.

For more information on the criticality of API CDMO selection, please download this case study.

Download Case Study »