Speaking as a representative of a global biopharmaceutical manufacturer, Hanania explored several considerations for identifying a suitable third-party manufacturer. Developers approach contract development/manufacturing organizations (CDMOs/CMOs) for different reasons. Biotechnology start-ups often lack internal capabilities for producing clinical-trial drug substance; thus, many such companies leverage CDMOs’ capacity and process-development expertise. Large, established pharmaceutical companies might work with contract partners to free up internal capacity for other products, advance multiple candidates simultaneously, or identify secondary manufacturing capabilities in case of supply-chain disruptions. Such companies might not require deep development activities and thus could save time, capital, and experimental effort by selecting a CMO rather than a CDMO. Regardless of company size, biologics developers should consider their process and product needs carefully before signing agreements with manufacturers.
Hanania reflected that developers big and small often confine their questions to production capacity and pricing. Those terms are vague, however, and answers to such queries differ according to production phase and scale. Before approaching potential manufacturers, sponsors must “do their homework” to ascertain how productive their current processes are, how much material they need to produce to reach a given milestone, and how much development work is needed to achieve that.
Drug companies also must understand that pricing accounts for quality systems and other critical features. When reviewing bids from potential contract partners, capabilities and offerings should be considered carefully to determine whether some high costs could reap significant value. One strategy, Hanania explained, is to check a CMO’s audit history, including records from customer and regulator inspections. Such documents will reveal the true value of a manufacturer’s quality system.
Hanania also recommended that developers evaluate CMOs/CDMOs as early as possible. Sponsors sometimes expect to sign an agreement, begin production shortly thereafter, and reach clinical/commercial milestones rapidly. But such thinking is unrealistic. Production timelines are phase dependent, especially if a process requires considerable development before it can reach a subsequent stage. Even if a drug company already has established a process for its biologic, effective technology transfer supported by thorough gap analysis can take time. Sponsors also should consider whether a manufacturer has sufficient analytical capabilities for product characterization, how long testing might take, and whether assays can be performed in a quality control (QC) environment after validation. Other factors include manufacturer access to raw materials. All those influences are interconnected, Hanania explained. Thus, timelines usually are measured not in weeks, but months. Sponsors must plan accordingly.
Special considerations can arise when a developer and manufacturer operate in different regions. For instance, sponsors should determine whether batch records will require translation into another language. Hanania highlighted the importance of ensuring that a selected CDMO has sufficient experience — or at least strong familiarity — with the sponsor’s regulatory framework.
Before summarizing his remarks as a checklist of CDMO selection criteria, Hanania emphasized that drug developers should seek out manufacturers with which they can establish long-term relationships: “Yes, you are looking for an entity to provide you with a service. But beyond that, you are looking for a partner.” Providing as much as information as possible to manufacturers during contract discussions helps in generating clear scope-of-work documents, realistic timelines, and accurate financial estimates.
Once agreements have been finalized, both parties must work together effectively and efficiently. Doing so requires trust, transparency, and a willingness to discuss “both the pluses and minuses” of a bioprocess. Hanania quipped, “Things will happen. You’re dealing with biologics. It’s important to have open dialogue” to address their inherent complexity.
Fill out the form below to view the full BPI Theater presentation.