Clinical trial supplies

Peterson M, Byrom B, Dowlman N, Mcentegart D. Optimizing clinical trial supply requirements simulation of computer-controlled supply chain management. Clin Trials 2004 1.4 99-412. 

Contracting out of activities previously only conducted in-house is already becoming quite common and will probably continue to develop. In the past a so-called full-service pharmaceutical company took direct responsibility for all the activities required for the formulation, manufacture, quality control, and regulatory approval of its drug products. Nowadays the use of specialist contract houses to perform activities such as formulation, analytical methods development, manufacture of clinical trials supplies, supervision of the assembly of an NDA, postmarketing surveillance, and even troubleshooting may be contracted for even by some of the largest companies. 

Clinical trial supplies can be blinded using several techniques depending on the availability of resources and the consideration of competitor companies. The ideal situation is to produce a placebo or comparator product that looks and behaves in an identical fashion to its active test counterpart, for example, the same colour, weight, shape, size, markings, texture and... 

Apart from manufacturing placebo formulations, the company may need to approach the manufacturer of an already marketed product for clinical trial supplies if their medicine is chosen as a comparator. The precise requirements (such as similar size, colour and no identifying features) can be difficult to meet. Any approach may be met with some hesitation for valid reasons, but equally the reaction may be obstructive, asking for unreasonable access to information. It is customary to provide a copy of the protocol, or at the least an outline of it, with clear indication of the material needed and the timeframe for its supply. 

Synthesis of active ingredients Preclinical testing Formulations development Phase I, II, III, and IV clinical trials Clinical trials supplies manufacturing Clinical packaging... 

Category 4 vendors are sole-source API manufactures. First-time clinical trial supply manufacturers, offshore single pivotal trial clinical sites, and... 

Finally, on the introduction page to this section or in the cover letter, it is always a good idea to emphasize that the clinical trial supplies will not be shipped by the sponsor until there is documentation in hand to demonstrate IRB approval, and that the drug will not be shipped to the clinical trial site until after the 30-day review period of the initial IND filing. 

Subject Information Systems Data Management Clinical Trials Supplies Production Protocol Management... 

When the product in question is intended only for use in clinical trials, the fundamental purpose of the regulation, protection of patients from defective products, must still be of primary concern. However, the quantity of product at risk, and its limited distribution will impact the process of complaint investigation. For example, the generally smaller amount of product involved may make it difficult to identify low-level occurrences of manufacturing defects. The limited and more tightly controlled system of distribution of clinical trial supplies, however, will likely facilitate and limit the recall process should that be deemed necessary. 

Report writing and other document preparation. Clinical trial supply management. 

Dempster, M.A. Jones, J.A. Last, I.R. MacDonald, B.F. Near-infrared methods for the identification of tablets in clinical trial supplies. J. Pharm. Biomed. Anal. 1993, 11, 1087-1092. 

Clearance for Clinical trials is given by a No Objection Certificate (NOC). In addition a T Ficence (Test Ficence) for importation of Clinical Trial Supplies into India. These are then also free of customs duty. For further details, see Rule 122A of Drug and Cosmetics Rules. This T Licence is obtained by filling Form 12. 

Other possible downsides are the relative paucity of central laboratory facilities especially for assays, and that are accredited to International Standards and also both GLP and GCP compliant. Transport of clinical trial supplies, access of sites to monitoring visits may require days of rail transport rather than air with complications of humidity and temperature extremes on supplies and biological samples. Finally, sectarian violence can break out at any time causing disruption to monitoring of studies and possible danger to foreign monitors. 

This is a crucial area and one which should be given maximum attention during the planning process, as the length of time required to ensure adequate clinical trial supplies can never be underestimated. Inadequacy of clinical trial supplies can be a reason for delay in the execution of a clinical development programme. The explanation is likely to be threefold. 

Capsugel produce a range of specially sized opaque capsules specifically for the encapsulation of tablets for double blind clinical trial supplies. The capsules are wider than standardsized capsules to allow larger diameter tablets to be filled but have shorter bodies to retain patient acceptability/tolerability. 

Stability samples and any samples used in evaluation programmes (including clinical trial supplies) should be subjected to QC evaluation inspections ... 

Clinical trial supplies which include full QC and supporting stability studies to show that product-pack is satisfactory for issue (i.e. IND stage in the USA). See also (8) below, paying usual attention to GMP, effectiveness of standard operation procedures (SOPs), etc. 

Note that semi-automatic blister packaging employing large preformed trays which are filled by hand then lidded from reel or sheet, followed by punching-out or guillotining, can offer speeds of around 1,200 items per minute with two or three operators. Under such conditions prices can be reasonably competitive with more sophisticated automatic equipment, particularly if runs are relatively short and a variety of tray and product sizes are involved. This can be particularly useful for clinical trial supplies. 

The volume occupied by strip packs is invariably high. Some reduction can be achieved by preforming the pockets. Cartoning with the more flimsy materials may create difficulties. For single strips, envelope or catch covers are a useful alternative to cartons. They also make cartoning a much easier operation. Particularly useful for clinical trial supplies (Figure 13.10). 

Machinery—lister packs for Clinical Trial supplies—... 

---