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Optimizing the use of partners for clinical trials depends on selecting the right contractor.
Significant resources are needed to bring new drugs to market. Companies that historically have not used third-party manufacturing may consider outsourcing rather than adding internal capabilities if their new product line requires specialized manufacturing equipment or expertise that are not available in-house. Virtual pharmaceutical companies, for example, which have no internal manufacturing capabilities, may use multiple contract manufacturing organizations (CMOs), contract development and manufacturing organizations (CDMOs), or contract research organizations (CROs).
Selecting the right manufacturing partner(s) and optimizing the use of those partners can include several key benefits, such as accelerated development and production timelines; reduced equipment costs and access to specialized equipment, both for production and analysis; and technical and regulatory expertise that can facilitate and expedite filing.
From a quality perspective, the sponsor and external service provider are responsible for the quality of the product, with the study sponsor ultimately being responsible for “approving or rejecting drug products manufactured by the contract facility” (1). This requirement has prompted some sponsors to choose an independent third-party laboratory to perform release and stability testing, a strategy that is particularly advantageous if a sponsor is using multiple manufacturing sites.
Utilizing a single CRO as the analytical testing site for all the sponsor’s manufacturing sites increases the consistency of the data because the same analysts, equipment, and methods are used to analyze samples from multiple manufacturing sites. Most CROs offer method development, method validation, and stability testing, although these same services may be offered by the CMO or CDMO. If an independent laboratory is used for release and stability analysis, then the sponsor or CDMO will often be approved as a backup testing site. CROs may offer services such as mass spectrometry, protein characterization, microbiology, extractible leachable testing, and impurity identification that may not be part of the service offering from a CDMO.
Several criteria should be considered when selecting a CRO, CDMO, or CMO for analytical services. These criteria include, but are not limited to, the following.
Understanding the legal framework that a CMO, CDMO, or CRO uses is important and especially so if the service provider is outside the United States. Contracts and quality agreements can help define these points but may not wholly mitigate issues with intellectual property. Ownership of methods, protocols, and data should be clearly defined as it can impact regulatory filings and method transfer.
One of the core principals of quality by design (QbD) is risk reduction. Selecting a service provider should include risk analysis. Effective
communication is critical to the success of any outsourced program, and the risk associated with managing the program should be evaluated as part of the contract and selection process. For example, if the service provider is in a different time zone or is in a country whose primary language is not the same, communication may be more difficult. Similarly, vendor location can impact audits and site visits. Management of the program may require more resources from the sponsor if the service provider has limited project management capabilities, is in a different time zone, or has limited program management resources.
Understanding the service provider’s past performance with projects of a similar scope, from companies with a similar size, and with similar management capabilities is information that should be gathered early in the process. Identifying the production and analytical capacity needed and assessing the ability of the service provider to deliver on time is also an important part of the analysis. One should identify critical manufacturing and analytical components and the levels of redundancy if failure should occur.
Outsourcing to either a contract manufacturing site or analytical laboratory means shipment of materials. If the service provider is overseas, then shipment of materials to the US may be required and, depending on the product, may require special handling due to temperature or safety restrictions. Early planning to ensure that sufficient material remains to support the clinical and analytical studies in the event of a shipping
failure is prudent.
Furthermore, temperature recording devices should be used in controlled-temperature shipments, and the CRO must be able to download the information. If multiple manufacturing sites are used, setting stability testing and performing release testing at a single analytical site can reduce or mitigate shipping risks.
Efficient utilization of CDMO, CMO, or CRO resources can significantly reduce the amount of capital investment in manufacturing and analytical equipment a sponsor must expend. The time needed to bring new products to market also may be reduced.
As with any internal project, if the sponsor uses a third-party service provider, the sponsor will be involved in day-to-day communications and operational decisions and should ensure that sufficient quality project management resources have been identified to support the program. This is particularly true if multiple CMOs or CDMOs are used to manufacture the product.
It is more efficient if a single CRO serves as the analytical laboratory for all the CMO or CDMO aspects of the program. Minimizing the number of external partners can reduce this program management workload, while using a single analytical lab can reduce risk and costs while resulting in improved quality.
1. FDA, Guidance for Industry, Contract Manufacturing Arrangements for Drugs: Quality Agreements Guidance for Industry (CDER, CBER, November 2016).
William Bakewell, PhD, is research fellow, GMP Lab, at PPD Clinical Research Services, Thermo Fisher Scientific.
Vol. 35, No. 3
When referring to this article, please cite it as W. Bakewell, “Selecting and Optimizing the Right Manufacturing Partner,” BioPharm International 35 (3) 35–37 (2022).