ABSTRACT
The long-term nature of outsourcing biologics process development and GMP manufacturing over the course of clinical trial
development can involve unforeseeable events that could be a source of conflict between the sponsor and the CMO. In this article,
we present the CMO's perspective on various potential sources of sponsor–CMO conflicts, preventive actions to circumvent conflicts
before they occur, and strategies for resolving conflicts as related to process transfer, development, and GMP manufacturing
of biologics.
A successfully outsourced GMP manufacturing program is built upon a common goal and the management of numerous factors in
the complex collaboration between the sponsor and contract manufacturing organization (CMO). The successful collaboration
involves a synergistic exchange of each party's knowledge and experience, combining detailed understanding of the product's
intrinsic properties, experience in process development and manufacturing, and GMP regulatory requirements for manufacturing,
toxicology, and clinical trials. In this article, the authors will present potential sources of sponsor–CMO conflicts, preventive
actions to circumvent conflicts before they occur, and strategies for resolving conflicts as related to process transfer and
development, and GMP manufacturing of bulk biologics.
Conflict prevention in CMO selection
Figure 1. Sponsor-CMO conflict management for clinical phrase biologics
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Numerous articles have already been published reviewing best practices in CMO selection (1–3). It is clear that the selection
of a suitable CMO is the first step in the prevention of conflicts. Mid-project changes in the service provider will only
incur losses of time and money. As a rule, sponsor–CMO conflicts arise when a delivery gap is created in terms of product
quality, quantity, cost, and timelines (see Figure 1). When the sponsor and the CMO first meet to discuss the potential partnership,
it is important that the CMO not overpromise and that the sponsor not overexpect; aligning expectations is the first step
toward minimizing a delivery gap. The interaction must be open, must highlight technical difficulties and pain points of the
project, resource bottlenecks, and specify gaps in expertise of each party. A clear articulation of the project's scope, deliverables,
and timelines should lead to the mutual acknowledgement of constraints related to the project. It should also bring about
a mutual understanding of what the resources required to complete the project are.
At this stage, the CMO is responsible for accurately identifying the process steps that are incompatible with its existing
facility or incompatible with the level of expertise required for the project. Doing so will ensure that the CMO avoids underperforming.
For its part, the sponsor should have a total awareness of what is and is not known about the product to be developed and
should be transparent about the state of development of the process, analytics, scales of previous runs, yields for each step,
purpose of each process step, which process steps are problematic, and the behavior of the molecule during the process and
under storage conditions. The desired quantities of material should be based on requirements for preclinical, clinical, future
market needs, technical considerations, such as scale and process performance, characterization, and stability studies; the
evaluation of these will require the intervention of both parties. Should incompatibilities exist, the two parties should
brainstorm alternative approaches to meet the sponsor's expectations. This often has the added benefit of building trust between
the two parties.
