Boosting Pipeline Acceleration With A Strategic Pharma/CDMO Relationship

By Ralph Lambalot, Ph.D., independent consultant

Anyone who has driven down a mid-city avenue while running late for an important meeting knows the rush of relief that’s felt when all the traffic signals ahead are synchronized to green. It’s the same sensation a portfolio manager (PM) gets when all the bars in a Gantt chart fall into place to create an accelerated project timeline.¹ Achieving synchronicity in early development requires a high level of agility and coordination across multiple technical functions. Many cities strive to achieve this smooth continuous flow to their traffic patterns. “Traffic Signal Synchronization is a traffic engineering technique of matching the green light times for a series of intersections to enable the maximum number of vehicles to pass through, thereby reducing stops and delays experienced by motorists. Synchronizing traffic signals ensures a better flow of traffic and minimizes gas consumption and pollutant emissions.² PMs strive for the same level of coherence, coordination, and efficiency in driving the maximum number of programs toward the clinic in the shortest amount of time possible.

Availability of clinical manufacturing capacity can be a rate-limiting factor for early pipeline programs. Without diligent capacity utilization forecasting, scenario planning, and adherence to platform processes, pipelines can quickly become derailed by the often-turbulent dynamics of early development. Furthermore, to hedge against these dynamics, PMs will often stack pipelines with more and more candidates. While these factors present a challenge to internal resource and capacity management, they create an opportunity for PMs and CDMOs to seek more strategic modes of working together.

A recent Outsourced Pharma editorial by Louis Garguilo, “Big CDMOs Back on Emerging Biopharma Radar,” provided insight into how Deborah Choquette and Joanne Beck of Boston Pharmaceuticals made their selection of a strategic CDMO partner. Among the criteria mentioned in the article were the CDMO’s desire “to work with us in a real partnership scenario,” as well as having the needed capacity, resources, and project management capabilities. An earlier article, “Inflation Bites Biopharma in the Outsourcing Budget,” hit on another critical need for both small and large pharma alike – flexibility. Beck emphasized, “‘Penciling us in’ with a letter of intent versus a down payment is so incredibly helpful. I don't want to miss this point.” Flexibility is a critical differentiator in the topsy-turvy world of early phase portfolio management.

Whether centralized technical functions in a matrixed clinical development organization for big pharma or decentralized functions spanning a virtual development network of service providers for an emerging startup, each functional node is akin to a traffic signal along the development road. The PM’s aim is to keep all nodes engaged in the highest value activities in such an orchestrated way that no efforts are wasted, and all resources are aligned to the priorities of pipeline acceleration and, more importantly, pipeline advancement.

Each functional node along the clinical development continuum has its own rules that dictate its capacity to perform work. These nodes include cell line development, cell culture process development, purification process development, analytical methods development, formulation development, scale-up, tech transfer, GLP tox supply, GMP manufacturing, and clinical supply management. The rules include cycle time, number of concurrent projects that can be accommodated, and other node-specific constraints that limit throughput. In an ideal situation, all capacities would be matched and cycle times synchronized to enable a continuous flow of candidates through the development pipeline. In practice, this is rarely the case, and the workflow is subject to operating in fits-and-starts as portfolio dynamics take their toll and cause priorities to shift and work plans to change.

The crux of such a resource planning challenge might be an overabundance of seemingly good ideas to test in the clinic that outstrips the available capacity to accommodate such a workload. One obvious solution to this dilemma is ruthless prioritization to winnow the number of candidates down to what can best be accommodated by the available capacity. The dilemma persists when even the remaining highest priority programs simply outstrip capacity.

Balancing Operational Efficiency & Flexibility With Your CDMO

There is an inverse relationship between capacity utilization and flexibility. The more tightly scheduled a manufacturing line is, the less opportunity there is for shifting its schedule to accommodate an early phase asset. While operational efficiency dictates that capacity be fully utilized, the needs of clinical development are best served by the agility that comes with excess available capacity. Herein lies the opportunity for pharma/biotech PMs and CDMOs to work together more strategically and flexibly.

Pharma/CDMO relationships can range from the transactional-based contractual agreement for a single candidate to a strategic service level agreement that allows for greater levels of flexibility. Just as there is a need for internal client capacity management to leverage the benefits of platform processes, it is critical that a strategic CDMO position itself to become a like-for-like interchangeable option for its client partner. The major commercial CDMOs have become successful largely through operational excellence and efficiencies of scale. As mentioned in the articles cited above, some major CDMOs are adopting more flexible models to accommodate early pipelines. Smaller clinical phase CDMOs are also well positioned to achieve success through offering low-cost readily accessible capacity to augment a client’s internal process development and manufacturing capacity.

The benefits of a strategic pharma/CDMO relationship are numerous. The most critical factor of any such relationship is literally that – relationship. By leveraging a single partnership to meet the needs of early phase clinical development, the two partners can build trust and confidence in each other’s abilities to deliver on their promises. In making a shared commitment to each other’s clinical demand and manufacturing capacity, the joint team can open themselves up to dynamic forecasting and scenario planning to best anticipate sudden changes in clinical demand.

Cost management is always a key consideration. Here again, CDMOs have an opportunity to provide a cost competitive option in the make-versus-buy equation for their customers. Labor and capital are significant cost drivers. While large pharma is constrained by internal labor equity and facilities built to premium construction specifications, a CDMO can leverage phase appropriate investment in capital and serve as a training ground for early career talent. However, neither of these cost savings strategies can be allowed to compromise product quality or operational excellence. Indeed, when effectively managed, they can become enablers of both.

Establishing a truly strategic partnership requires that the pharma/biotech and CDMO work together to position the relationship to offer a strategic advantage to both parties. By augmenting a pharma’s internal clinical development capacity, a CDMO can greatly enable early phase pipeline acceleration. By being open and collaborative with a CDMO, PMs can secure a greater number of options in their quest toward synchronizing all the development stoplights to green.

By externalizing a portion of process development and manufacturing capacity management, the incremental cost of development for pharma shifts from a fixed cost with fixed capacity to a variable expense with scalable capacity. This type of hybrid internal/external capacity arrangement can enable PMs to absorb transient surges in clinical demand or achieve a greater balance of internal workload for resources that might be delivering beyond their designed capacity.

There are two dimensions to the traffic signal synchronization conundrum:

1. the volume of traffic, and
2. the management of the signals.

Extending the analogy further, the aim of the pharma/biotech PM is to put high-performance vehicles on the road, i.e., candidates in the pipeline that can effectively accelerate through the signals and make it to their pivotal trial destination. By working together in strategic partnership, PMs and CDMOs can better manage the flow of pipeline traffic, allowing a biopharma to flex its capacity needs with greater agility and get more candidates to their intended destinations in less time.

References/Notes

 

About The Author:

Prior to launching his independent consultancy, Ralph Lambalot, Ph.D., was head of the Biologics Development & Launch team for AbbVie Operations Science & Technology. Prior to AbbVie, he was director of protein biology at the Pfizer Research Technology center in Cambridge, MA. He earned his bachelor’s degree in chemistry from Cornell University and his doctorate in bio-organic chemistry from Brown University. He held a NIH Postdoctoral Fellowship in Enzymology at Harvard Medical School where he purified, cloned, and characterized the first phosphopantetheinlytransferase, a class of enzymes responsible for the activation of fatty acid and polyketide synthases and non-ribosomal peptide synthetases. Lambalot can be reached on LinkedIn or by email.