Bringing a drug candidate through clinical trials is a challenging and high-risk process, since only 10% of candidates actually reach final approval. Both established pharma companies and small startups are often faced with this dilemma: they want to delay capital investment in manufacturing infrastructure on an investigational therapy until there is greater certainty of safety and efficacy, and ultimately approval. However, at the same time they must also plan for success to avoid delaying market entry for the successful candidate. Fortunately, external resources can help you maintain small-batch manufacturing in parallel with clinical trials, develop commercial-scale processes, build physical capacity and upskill internal teams. In this article, I offer tips on how to leverage outside resources to help you cost-effectively and strategically prepare for clinical or commercial manufacturing while you move a new therapy through clinical trials.
TIP #1: Plan for success from the outset
The first, most immediate manufacturing challenge is securing sufficient supply, or sufficient capacity, for the clinical trials. This may also entail process development work to scale up from lab-scale to small-batch manufacturing. At this point, rather than scale up internal resources, drug developers will often turn to external partners such as contract development and manufacturing organizations (CDMOs) for supplemental capabilities and capacity. As clinical trials progress through Phases II and III, biopharma companies will need increasingly large quantities of the drug. A CDMO has built flexibility for this into their business model and their physical facility and has worked through this process many times.
Particularly for a young company that does not have established partnerships in place, selection of a CDMO will be one of the most critical decisions they have yet faced. While your immediate objective is to obtain a supply of your drug candidate for clinical trials, keep an eye to the future, as well. If your drug candidate is successful, the journey from clinical trials to market will be lengthy, and your needs will evolve along the way. Using the best-case scenario when selecting your CDMO can help you avoid costly stops-and-starts and mis-matches down the road. Ideally, a CDMO is not just a service provider, but a partner and collaborator in the clinical trial journey.
TIP #2: Work in parallel with a CDMO to delay capital investment
As Phase III clinical trials progress, and there are good indications of efficacy, the probability of regulatory approval increases. This triggers some of the trickiest and most critical timing decisions: when and how to proceed to commercial-scale manufacturing. Process development to scale up the manufacture is itself a major project with significant cost, but the bet-your-business decision is when and how to invest in manufacturing capacity.
Most companies do not have idle capacity, and they will want to delay this major investment as long as possible. Trial results and regulatory approval provide certainty as well as a clearer picture of the market, making it easier to secure financing for the capital investment required to build manufacturing capacity. Delaying investment, however, can also delay market entry, which can result in smaller market share in a competitive market. Again, a CDMO can fill the gap with biomanufacturing capabilities, enabling a biopharma organization to enter the market while building out manufacturing capacity in parallel.
TIP #3: Capacity isn’t just about capacity. Pay attention to the HOW.
If your CDMO can reliably supply your clinical trials, and can scale up quickly when regulatory approval is achieved, does it matter how they do it? In a word, yes.
Shepherding a drug through clinical trials and bringing
it to market involves several complex transitions before a steady state is achieved. There are at least two process development steps along the way: the first when scaling up from laboratory scale to small-batch manufacturing, and the second when scaling up to commercial manufacturing. One way to drive risk and complexity out of these transitions is to use the same type of equipment across the manufacturing environment, from small batch to commercial scale. While cells may notoriously behave differently at different scale, even in a similar type of bioreactor, utilizing similar equipment will nevertheless minimize the variations and complexity.
TIP #4: Align manufacturing methods and systems
The final, and perhaps most sensitive, transition will be bringing your manufacturing operations in-house. This transition will be much easier if you have planned in advance for infrastructure alignment and staff training.
Matching your biomanufacturing equipment to that of your CDMO’s plant will save both time and money by eliminating a process development step. While you will still need to validate your new process train, you can be confident that the process itself can be transferred one-to-one. Working with a CDMO that can train up your staff will further facilitate a smooth transfer. Failure to plan for this from the outset can add time, cost and unnecessary risk to your manufacturing operations start-up. Alignment of manufacturing methods and systems with your CDMO will have an additional benefit: potential supplemental manufacturing capacity should the need arise.
TIP #5: Leverage industry knowledge and experience to navigate global markets and requirements
When initiating clinical trials you may be focused on pilot studies that are locally implemented, but as the likelihood of approval increases you will also want to take into account global considerations. A supplier or CDMO with a global presence can be invaluable, helping ensure that your process is up to snuff on regulatory requirements in your intended markets. For example, China, a large and rapidly emerging market, has very specific requirements regarding data from foreign clinical trials. Though they have recently streamlined their approval process in order to accelerate new drug approvals, the devil is in the details. A supplier or partner with a local presence can bring to the table. A supplier or partner with a local facility can bring to the table not only knowledge of regulatory requirements and processes, but also local contacts, language, and familiarity with local administrative procedures.
When hiring an external partner, you will have a list of capabilities and services that you require, but, just as when hiring an employee, don’t forget the “soft skills.” Trust is paramount. If your drug candidate is successful, you will be working with that partner for years. You will be sharing your most closely-held scientific discoveries and collaborating on multiple technology transfers. As you move into commercial manufacturing, you may lean on that external partner to train your in-house staff and work closely with you as you plan, build and start up a new manufacturing facility or process. The right organization can facilitate these complex transitions and position you for ongoing manufacturing success.