Market trends and the biopharma evolution
The discovery of new biotherapeutics able to treat a wide range of diseases is increasing the demand for pharmaceutical process development and manufacturing capacity. Contract development and manufacturing organizations (CDMOs) are playing an essential role in global drug supply as they ramp up programs to meet this demand. Over the past two decades, CDMOs have adopted single-use technologies, making biomanufacturing processes more flexible, robust, and efficient in producing treatments for clinical trials.
Although capacity is expanding, there is currently a limited number of CDMOs with the expertise and availability required for unique and diverse molecules, such as cell and gene therapies. It can be challenging 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 produce enough drug product for hundreds? Process scale-out might be the only option for autologous therapies, as scale-up is not possible. In this scenario, working with a CDMO can be an appealing option — what factors should weigh into such a critical decision?
What, when, and why to outsource
It’s an exciting and busy time when your company identifies a promising drug candidate. You need to think about your time to market, milestones, available capacity, and the complexity of your molecule. For advanced cell and gene therapies, it can be challenging to find a CDMO with the specific experience or expertise your product needs. Should you do your own development and manufacturing, or are there parts you can outsource to a qualified supplier?
Opting to build in-house capabilities means you take on all expertise and expense requirements, making it important to consider the total cost of facility and equipment ownership. Alternatively, you could leverage a CDMO’s expertise and existing infrastructure, but you’ll be subject to their timelines and give up some control.
There’s a lot at stake when relying entirely on a CDMO to support your development and manufacturing, so you might consider taking a combined approach. You can work with a CDMO to develop your process while using internal resources to finesse product quality attributes. When everything comes together just right, these parallel activities merge to give you speed.
A solid understanding of your therapy is also critical before deciding if a CDMO partnership is the right choice. Be sure to answer the following key questions:
- Which cell line will I use?
- What’s the process that will be scaled up?
- What’s the volume of my terminal bioreactor?
- What will my downstream process and analytics be?
For clinical studies, it’s important to investigate your drug’s mechanism of action to define how it will work within patients. Consider the chemistry, manufacturing, and control (CMC) activities that are essential to regulatory approvals, as well.
How to choose a CDMO
The following criteria can help you choose a CDMO that meets your needs:
1. Specific capabilities and experience. Novel biotherapeutics often demand specialized equipment and pose unique obstacles. It can be hard to find a CDMO with the infrastructure and logistics necessary for these advanced therapies. In that case, it could be best to take efforts in-house. Experience with monoclonal antibody (mAb) process development and manufacturing, for example, might not equate to the specific and relevant expertise that’s vital to the success of your molecule.
2. Wait times and timelines. Consider available capacity and the complexity of your molecule, and ask CDMOs about wait times. There is currently limited CDMO capacity for viral vector manufacturing, for example, and we’re seeing some end users put in the queue for 6 months to 2 years. This delay is devastating to their drug programs. Modular options make it possible to avoid these delays and take manufacturing in-house. Instead of waiting 3 or 4 years on a stick-built, stainless steel site, a full manufacturing facility can be constructed in 1.5 to 2 years. With a box-in-box approach, you can have your own internal capacity in 10 to 12 months — but, you need to ensure you have the resources available to operate your own manufacturing facility.
3. Relationship. Open, transparent, and two-way communication is one of the biggest factors in a successful and trusted CDMO partnership. Accessibility to the CDMO’s staff is also key. Choose a CDMO that’s on board with a collaborative relationship, versus transactional.
4. Quality and compliance. Look for a CDMO with an established quality management system (QMS) and a proven track record with customers and regulators. Also check into their sourcing. There should be proof they are using qualified suppliers and they should allow you on-site to conduct quality audits. Call for the use of compliant materials at the process development stage, and make sure the CDMO staff understands GMP. Otherwise, they’re going to design something that isn’t scalable, isn’t compliant, or doesn’t come from a credible vendor.
5. Location. A CDMO that is closer can minimize travel time and help 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 a global CDMO operates with consistency 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 lot of drug product, 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. Consider the stage of your clinical program, as Preclinical, Phase 1, Phase 2, and Phase 3 studies will each have different requirements. If you’re still in the early stages, 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.
Commit to a shared mission
Whether or not to outsource some or all your activities is really an individual decision. If they have the necessary expertise, CDMOs can bring a lot of value in helping you to rapidly develop and manufacture your therapies.
When choosing a CDMO, make sure they are willing to be transparent and empower you. If you want to bring the process development or manufacturing setup in-house later on, your CDMO should be able to work with you, train you, and provide 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 couldn’t deliver on your process. Be sure to do your due diligence and select a partner who’s invested in your mission to deliver critical therapies to patients in need.
If you’re a biopharmaceutical manufacturer looking to increase process productivity, reduce cost, and bring your product to market faster, check out Cytiva’s Fast Trak™ Service Centers. And for more tips on getting your drug candidate to market efficiently, be sure to join the Biotech Makers group on LinkedIn!