Article inspired by a Tapas and TechTalks industry event in Cambridge, MA USA. Fast Trak services and upstream team members shared insights from customer collaborations.

Market trends and biopharma evolution

CDMOs are an essential contributor to global drug supply. A whole spectrum of molecules is increasing the demand for process development and manufacturing capacity. Contract development and manufacturing organizations (CDMOs) are ramping up their programs to meet that demand, addressing the needs of small biotech companies to major multinationals. In the past two decades, CDMOs have advanced rapidly with the adoption of single-use technologies for biomanufacturing, and most clinical trials use these technologies as they offer opportunities to rapidly develop robust and flexible biomanufacturing processes.

Although capacity is expanding, currently there are a limited number of CDMOs with the expertise and availability for unique and diverse molecules. Cell and gene therapies, which are very large and complex, still use a lot of traditional biomanufacturing equipment. It's challenging or impossible to achieve economy of scale for autologous cell therapies where one batch is produced for one patient. A clinical trial might have a handful of patients. How do you deal with hundreds of patients? Process scale-out might be the only option for autologous therapies, as process scale-up is not possible.

With all these factors influencing your therapeutic candidate, the fastest way to produce material for your next clinical trial may be to outsource to a qualified service provider. This allows you to delay critical decisions on adding capacity until you have more certainty over your molecule’s success. However, how do you ensure that a CDMO will be successful with your process and deliver within your timeline?

What, when, and why to outsource

It's a very exciting time at a company when you have a target that works and proof of concept. Much needs to happen. You need to think about your timeline to market or your next milestone. You must look at the available capacity and complexity of your molecule, both of which are quite relevant to cell and gene therapies. For these advanced therapies it can be challenging to find a CDMO with the specific experience or expertise. Should you do your own development and manufacturing, or are there parts you can outsource to a qualified supplier?

When you go to a CDMO, you're giving up some control. When you build in-house capabilities, you will take on the expense and expertise requirements. It’s important to consider the total cost of ownership if you are establishing a facility and all the infrastructure. On the other hand, when you go to a CDMO, you can leverage some of their experience, but you're on their timeline. There’s a lot at stake when you’re relying entirely on a CDMO to support your development and your manufacturing.

Hopefully, you can work concurrently with a contract development and manufacturing organization (CDMO) to help you develop your process. While that’s underway, you could use internal resources to finesse the product quality attributes. Ideally, all these parallel activities would merge to give you speed.

When you look at your target therapy, you first want to answer the basic questions: Which cell line will I use? What’s the process that will be scaled up? What’s the volume of my terminal bioreactor? And what will my downstream process be? After you have looked at your cell line and optimized your media, look at your downstream process and analytics. And from the clinical side, the patient, investigate the mechanism of how the drug works. There's also a lot to be done on the chemistry, manufacturing, and control (CMC) side.

Checklist to help you choose a CDMO

Checklist to help you choose a CDMO

Here are some of the key criteria to help you select the right CDMO for your needs.

  1. Specific capabilities and experience. Novel and emerging biotherapeutics often require specialized equipment and pose unique challenges. For example, cell therapies are living materials with chain of custody and identity requirements. For these advanced therapies you might not be able to find either the equipment to run it or an appropriate CDMO. In that case, you must take it in-house. A legacy in monoclonal antibody (mAb) process development and manufacturing is no substitute for specific and relevant experience in your novel molecule.

  2. Wait times and timelines. What’s your timeline to go to market or to your next milestone? You need to look at the available capacity and complexity of your molecule. Ask the CDMO about wait times and the timeline for project completion. There is limited CDMO capacity for viral vector manufacturing. We're seeing some end users put in the queue for 6 months to 2 years. This delay is devastating for their drug program.

    Because of delays at CDMOs, more people are taking manufacturing in-house. The modular trends are really making that possible, because you're not waiting 3 or 4 years on a stick-built, stainless steel site. With modular options, a full manufacturing facility takes 1.5 to 2 years to build. With a box in box approach, you can have your own internal capacity in 10 to 12 months. Of course, you need to consider whether you're ready to own and operate your own manufacturing facility.

  3. Relationship. Communication is one of the biggest factors to consider. You need to have open communication and accessibility to the CDMO’s staff. That’s what leads to successful relationship building. Consider whether your relationship will be collaborative or transactional. A trusted partnership will allow you to work in an open and transparent manner with two-way communication.

  4. Quality and compliance. Look for a CDMO with the appropriate quality management system (QMS) and a track record with customers and regulators. Also check into their sourcing. They should have proof they are using qualified suppliers and should allow you onsite to do your quality audits. Consider using compliant materials even at the process development stage, and make sure the process development staff at the CDMO understands GMP. Otherwise, they're going to design in something that isn’t scalable, isn’t compliant, or doesn’t come from a credible vendor.

  5. Location. Closer is better. Instead of putting your staff on a plane, you can put them in a car. That minimizes travel time and helps to ensure a smooth technical (tech) transfer. As distributed manufacturing (e.g., manufacturing capacity in the US, Europe, and China) becomes more common, it’s important that your global CDMO is consistent between facilities. Similar procedures, equipment, automation, and consumables are necessary if site-to-site tech transfer is desired.

  6. Size and scale. If you need a large quantity, a larger CDMO might be a good fit. But if you only need a small amount of product, you might get bumped by a larger customer coming in. Also look at the stage of the clinical program. Preclinical, Phase 1, Phase 2, and Phase 3 each will require slightly different selection criteria. If you're still at the early phases, make sure the CDMO has high-throughput process development (HTPD) capabilities. If your scale is larger or you're later in your program, check the facility fit.

Select a partner who shares your mission

Whether to outsource some or all your activities is really an individual decision for each company. CDMOs bring a lot of value. If they have the expertise, they can help you rapidly develop and manufacture your therapies.

If you go the CDMO route, choose one that's willing to be transparent and empower you. If you want to bring that process development or manufacturing setup in-house later on, your CDMO should be able to work with you, train you, and give you all the information you need to stand on your own and build internal expertise.

Ultimately, the value of experience and expertise can’t be underestimated. You don't want your batches to fail because you chose a CDMO that didn’t have the right expertise. Make sure to do your due diligence and select a partner who’s invested in your mission of serving patients.

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About Cytiva’s Fast Trak Services

Cytiva’s Fast Trak Service Centers are specifically designed to help biopharmaceutical manufacturers increase their process productivity, reduce cost, and enable them to bring their product to market faster through a comprehensive range of services including cGMP manufacturing, process development, and training.