Pharmaceutical products clinical trials

Even on their own these are profound issues in the development of any product, but they have very particular implications for the difficult processes of formal pharmaceutical development, clinical trial, and marketing authorization of the full range of biopharmaceuticals. The answers will define major features of how the experimental work is done and the resources required to do it. 

The important differences between biotechnology products and conventional pharmaceuticals mean that the imthinking or routine application of standard safety tests could result in the release of biotechnologically-derived pharmaceuticals for clinical trials without adequate warning of possible adverse effects in humans. 

The purification of value-added pharmaceuticals in the past required multiple chromatographic steps for batch purification processes. The design and optimization of these processes were often cumbersome and the operations were fundamentally complex. Individual batch processes requires optimization between chromatographic efficiency and enantioselectivity, which results in major economic ramifications. An additional problem was the extremely short time for development of the purification process. Commercial constraints demand that the time interval between non-optimized laboratory bench purification and the first process-scale production for clinical trials are kept to a minimum. Therefore, rapid process design and optimization methods based on computer aided simulation of an SMB process will assist at this stage. 

In pharmaceutical and medical device development, clinical trials are classified into four main phases designated with Roman numerals 1,11, III and lY The various phases of development trials differ in purpose, length and number of subjects involved. Phase I trials are conducted to determine safe dose levels of a medication, treatment or product (National Institutes of Health, 2002). The main purpose is often to determine an acceptable single dosage - how much can be given without causing serious side-effects. Phase I trials will also involve studies of metabolism and bioavailabity (Pocock, 1983). The sample size of a Phase 1 clinical trial is usually small, ranging from 10-80 subjects (National Institutes of Health, 2002 Pocock, 1983). 

Some clinical trials can be completed with only a few visits. Others require more frequent contact with the study staff. As an example of the former, our clinic has conducted many studies intended to assess blood insulin and glucose responses to test products such as snack bars and beverages. These are usually conducted using a cross-over design and may require only three visits one for screening, one for consumption of the control product, and one for consumption of the active product. In contrast, we have also completed several trials to assess dietary and pharmaceutical interventions intended to promote weight loss. These usually require frequent clinic visits over a period of at least 12 weeks and sometimes as long as two years. 

WHO Guidelines for Good Clinical Practice for trials on pharmaceutical products. 

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. 

The company that applies for approval of the generic product must present full chemical and pharmaceutical documentation. If the new product does not fall within the definition of a generic medicinal product compared to the reference product the results of the appropriate pre-clinical tests or clinical trials should be provided (EU 2001 specific Article 10 (3)). It should be noted that the pharmaceutical and chemical quality is strictly regulated and includes all medications. 

Safety evaluation does not cease being an essential element in the success of the pharmaceutical industry once a product is on the market. It is also essential to support marketed products and ensure that their use is not only effective but also safe and unclouded by unfounded perceptions of safety problems. This requires not only that clinical trials be monitored during development (Spector et al., 1988), but also that experience in the marketplace be monitored. 

Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals Notice Stability testing of new drug substances and products Stability testing Stability testing... 

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