Clinical Trial Supplies vs. Commercial Drugs

Regulatory requirements for pharmaceutical clinical trial supplies differ from regulatory requirements for corresponding commercial drug products, especially in the early stages of clinical research (for example, Phase I and early Phase II.) As Phases III and IV are reached, the differences become fewer and more clearly defined. Although Dynamic DRUMBEAT^® for Pharmaceutical Clinical Trial Supplies addresses clinical trial supplies in Phases I through IV, Dynamic DRUMBEAT^® for Pharmaceutical Clinical Trial Supplies was developed chiefly for preparation of clinical trial supplies in the advanced phases of clinical research in the US. Regulations in most parts of the world resemble those in the US.

During early stages of clinical trials, manufacturing procedures and specifications may be subject to frequent changes and tend to be more general in scope. As clinical trials advance, procedures and specifications should become more detailed and specific as knowledge is gained regarding the process. Analytical test methods may also be refined, or different methods used in response, for example, to formulation changes that interfere with some methods.

When drug products are produced for clinical trials in humans or animals, compliance with GMPs is required. However, in early stages of clinical studies, such as Phase I, insufficient drug substance may be available to permit normal process validation practices; alternatives might include use of product and process analogs, data obtained from extensive in-process controls, and data from intensive product testing.

More comprehensive process validation will be conducted under replicated conditions as additional clinical trial supplies are made. Throughout this product life cycle, methods, facilities, and controls for producing clinical trial supplies evolve dynamically. As the drug candidate progresses into Phase III, increasingly larger batches are produced and all testing and operating measures approach those normally employed with commercial products. By the time of market launch, all lots involved should be in compliance with applicable GMP regulations.

Regulatory authorities expect written procedures to be available for sanitation, calibration and maintenance of equipment, and specific instructions for the use of the equipment and procedures used to manufacture the clinical trial supplies.

The application of GMP to the manufacture of clinical trial supplies helps to ensure that trial subjects are not placed at risk, and that the results of clinical trials are unaffected by, inadequate safety, quality, or efficacy due to unsatisfactory manufacturing practices. Compliance with applicable GMPs also helps to ensure that there is consistency between batches of the same clinical trial supplies used in the same or different clinical trials or that changes during the development of clinical trial supplies are adequately documented and justified.

Clinical trial supplies production involves added complexity in comparison to commercial products because of the lack of fixed routines, variety of clinical trial designs, randomization and blinding and increased risk of product cross-contamination and mix up. Furthermore there may be incomplete knowledge of the potency and toxicity of the product and a lack of full process validation, or marketed products may be used which have been re-packaged or modified in some way. Implementation and control of written SOPs can help to minimize risks to patients participating in the clinical trial.

Thus, prior to the time that commercial lots are produced, subjective, scientific judgments need to be made concerning how closely methods, facilities, and control need to match full-scale regulatory requirements. Dynamic DRUMBEAT^® for Pharmaceutical Clinical Trial Supplies cannot substitute for such supervisory judgment, but is designed to guide supervisors toward reaching correct decisions.

Unique exceptions to full GMP compliance are noted in Dynamic DRUMBEAT^® for Pharmaceutical Clinical Trial Supplies by the addition of “cs” to a DRUMBEAT^® Concept number. The “cs” indicates that the concept differs from the DRUMBEAT^® Concept for commercial pharmaceutical products.

To get started using Dynamic DRUMBEAT^® for Pharmaceutical Clinical Trial Supplies, follow the easy to use directions in the User Guide. If you are having difficulty using Dynamic DRUMBEAT^® for Pharmaceutical Clinical Trial Supplies, please contact Drumbeat Dimensions, Inc. for assistance.