One result of the new European clinical trials directive 1 has been more outsourcing of the manufacturing of clinical trial materials. These materials must meet current Good Manufacturing Practice (cGMP) requirements, which leads one to use the services of a contract manufacturing organization (CMO). Choosing the CMO who will become your partner for clinical trials manufacturing can be a time-consuming process. Finding a CMO with the appropriate combination of experience, reliability, reputation, and skilled staff, who can accommodate your manufacturing requirements in terms of scale, schedule, and cost, can be a daunting task. This article is a guide to smooth the road to the clinic.
Mapping Your Route to the Clinic
The first critical step on the way to take a therapeutic candidate into clinical trials is to draw a road map. Even a simple Gantt chart will formulate a preliminary schedule for preparing cell and viral banks, followed by manufacture of the clinical trial material, leading to safety testing of that material, and ultimately, the delivery and administration of that material at the clinical trial site.
Firm up the schedule by considering the critical milestones within the various activities outlined. For example, funding of the clinical trial may be provided in a phased manner, and may be contingent on the success of the previous milestone. In a typical contract, funding may be available for the initial cGMP manufacture of the cell and viral banks, but the funding for the activities that come later in the schedule may not be released until those banks are fully tested and released by the CMO. Therefore, establishing which parts of the manufacturing program are on the critical path is an important exercise and should be performed early in the planning stages.
Work with your CMO to agree on the critical schedules and milestones. Make use of their project management skills, which will help both parties understand what must be done, and crucially, by what date to deliver material to the clinic.
Design of the Clinical Trial
Explore the following factors with the CMO to ensure that all regulatory, quality, and logistical implications are considered in the manufacturing of clinical trail material:
Taking each of these factors in turn will be instructive.
Size of the Clinical Trial
The size of the trial will have a bearing on the scale of manufacturing that will be required. This is probably the most important topic to discuss with your chosen CMO as early as possible in discussions about manufacturing. Consider the number of patients in the trial, the dose that each will receive (and how this dose is calculated), the number of doses that will be administered to each patient, and what overage needs to be built in (to allow for vial breakage during transit or in the hands of the clinician).
Once the CMO knows how many doses it must deliver for the actual trial, the project manager can factor in how much additional material must be manufactured to allow for product testing requirements. When the total volume required has been determined, the CMO can advise on the most suitable manufacturing strategy to deliver the requisite amount. At this stage, you should also discuss the placebo requirements for the clinical trial (as these must also be made according to cGMP guidelines).