It’s no secret that money is not flowing as freely to biotechs as it once was. Between rough funding waters, inflation, and pressure to meet milestones, biotechs need to be as smart as ever when it comes to cash flow. That includes spending wisely in clinical manufacturing.
To spend wisely, however, a biotech doesn’t have to sacrifice quality or automatically select the contract development and manufacturing organization (CDMO) with the lowest initial bid (a choice that may cost more in the long run).
Instead, sponsors can partner with a CDMO to implement a strategic approach to process development and manufacturing that extends the cash runway. Lean clinical manufacturing, even at a U.S. biologics CDMO, is possible.
Lean clinical manufacturing is a phase-appropriate approach (sometimes called a stage-gated or milestone-based approach) to biopharmaceutical process development and manufacturing. In a lean strategy, the process development team leverages its understanding of regulatory requirements and performs only the work that is truly necessary for a given stage of clinical development — strategically waiting to optimize the manufacturing process until a therapeutic begins gaining success in the clinic.
Lean clinical manufacturing not only costs less; it also streamlines the path to phase I trials. For an emerging biotech company, time is the ultimate cost. If a startup has a cash burn rate of, say $250,000 a week, getting into the clinic a month—or two—sooner provides critical relief from financial pressures.
Then, once a therapeutic begins gaining success in clinical trials, funding organizations will have the confidence to provide more financing, which can be used to advance process development and optimization.
A good example of implementing lean manufacturing is to wait to carry out clonal selection—the process of identifying the best-growing and highest-producing clones—until after phase I. Instead, cell pool material, which is more heterogeneous but available earlier, can be used in early-stage development of downstream processing, formulation, and analytical methods.
Taking cell line development time off the critical path can reduce the time to the clinic by two to three months. This time savings has an enormous benefit for reducing cash burn.
Another element of lean clinical manufacturing is scaling efficiently. Two strategies can be applied.
The first is to use a scalable format for upstream process development, such as the Ambr 250 high-throughput bioreactor system. Data from this type of system can provide the confidence to skip intermediate-scale batches (25- or 50-L) and go directly to a pilot or demonstration batch at 100 or 200 L. This data-driven approach to accelerated scale-up could shave 8 to 10 weeks off the timeline to the clinic.
A second strategy for scaling efficiently is to produce a pilot batch in the process development laboratory instead of running an engineering batch in the GMP suite, where one incurs the costs of GMP suite maintenance and environmental monitoring. This option will cut the cost of this batch in half.
Of course, decisions to implement efficient scale-up strategies must be based on a careful risk assessment, conducted collaboratively by the subject-matter experts of both the biotech and the CDMO. In cases where the data are limited or not clear enough, more traditional approaches—such as running the intermediate-scale batches—might be chosen.
The risk assessments involved in lean clinical manufacturing must also consider protein complexity. Working with monoclonal antibodies (mAbs), with which the industry has extensive experience, will be simpler than dealing with other types of products, such as complex enzymes that are heavily glycosylated.
Protein expression for mAbs tends to be good, so even an un-optimized mAb process will likely provide plenty of material for initial development. A mAb process is also likely to scale well. These factors make it easier to adopt strategies like scaling up more aggressively. With a complex enzyme, on the other hand, the process development team may need intermediate-scale batches, to provide both sufficient material for development and confidence for scale-up.
With a mAb, one can also take advantage of established manufacturing platforms. An experienced biologics CDMO will have platformed workflows that serve as a starting point for mAb process development. With an enzyme, on the other hand, process development will likely start from scratch, involving more risk.
Biotechs can also save time in early clinical development by delaying full analytical method validation (AMV). Although many in the industry believe that AMV must be completed before phase 3 manufacturing, no such requirement appears in the regulations. For phases I, 2, and even 3, it is sufficient to qualify analytical methods, rather than to perform full AMV.
Further, rather than tying AMV to phase 3 manufacturing, biotechs should work with their CDMO to link the timing of AMV to process characterization. Process characterization provides extensive data that can be leveraged in analytical method development and validation.
In addition to adopting lean clinical manufacturing practices to accelerate time to the clinic, a biotech can also extend its cash runway by partnering with a biologics CDMO that has both the right capabilities and a flexible mindset.
Working with a biologics CDMO with in-house process development and in-house analytical development and testing capabilities saves money—by not having to outsource to a third party—and time—by eliminating the need to ship samples back and forth.
The right biologics CDMO partner can also ease the burden of cash burn through flexible invoicing. Large CDMOs may have set ways of doing business that require strict invoicing structures with large upfront payments. A smaller CDMO, with less overhead, may offer the flexibility to provide other arrangements.
A CDMO that is willing to consider the business risk of its clients—with approaches like lean clinical manufacturing and flexible invoicing that extend a biotech’s cash runway—is one that can serve as a true partner, rather than simply as a contract manufacturer.
Contact us to learn more
Contact Scorpius to discuss your next mammalian or microbial program and learn why a boutique biologics CDMO can provide the best outsourcing experience for small and emerging biotechs. Scorpius' business development and proposals teams are experts in lean clinical manufacturing, and can often provide an initial RFP response in less than 10 business days.