Non-clinical safety testing

Kasper P, Oliver G, Lima BS, Singer T, Tweats D. Joint EFPIA/CHMP SWP workshop The emerging use of omic technologies for regulatory non-clinical safety testing. Pharmacogenomics 2005 6(2) 181 1. 

First of all, there is the scope of GLP as it is defined in the OECD Principles, and which states that GLP encompasses the non-clinical safety testing of test items contained in pharmaceutical products, pesticide products, cosmetic products, veterinary drugs as well as food additives, feed additives, and industrial chemicals. These test items are frequently synthetic chemicals, but may be of natural or biological origin and, in some circumstances, may be living organisms. The purpose of testing these test items is to obtain data on their properties and/or their safety with respect to human health and/or the environment. (OECD, 1998). GLP is thus applicable to safety studies in two major areas Effects on human health and on the environment. These two areas may share some types of studies that have to be conducted in order to test the safety of the respective test item, but other study types may exclusively be required for one or the other area. 

Pre-clinical Enabling non-clinical safety testing (ICH M3) and formulation development to support Phase I 100s g-fewkg... 

Griffiths SA, Ashton GA and Lumley CE (1995). Non-clinical Safety Testing of Products of Biotechnology Issues of Concern. CMR International Report, CMR95-63R, December 1995. 

Predictive Value of Non-Clinical Safety Pharmacology Testing to Humans. .270... 

In this section, a brief summary of the nature, frequency, and consequences of adverse drug reactions (ADRs) in two clinical situations is presented. There are ADRs experienced by healthy volunteers and patients participating in clinical studies with potential new medicines and those experienced by patients who are prescribed licensed medicines. A review of these two situations points to areas of success with the current practices for non-clinical safety pharmacology testing but also identifies some areas where further research might lead to new or better safety pharmacology tests. Prior to reviewing the literature, some... 

Characterization of the vector batch used in non-clinical safety studies is also performed in compliance with GLPs. Care should be taken to ensure that adequate and appropriate processes are used to produce the batch(es) required, and the production process should be similar to that proposed for production of the vector for human clinical trials, or at least performed in such a way that adequate documentation of the production methods is available for comparative purposes. The GLP regulations state that the identity, purity, and composition of the vector batch (test article) used in a safety study must be known and documented. In addition, the stability of the vector preparation in the specific container used for the study must also be known prior to initiation of the study or acquired concomitantly with the study itself. These test article characterization experiments require that the researcher produce additional amounts of vector identical to the material used in... 

Cavero, I. and Crumb, W. (2005) ICH S7B draft guideline on the non-clinical strategy for testing delayed cardiac repolarisation risk of drugs a critical analysis. Expert Opinion on Drug Safety, 4, 509-530. 

Regulatory guidance for non-clinical cardiovascular safety pharmacology testing is given in the ICH S7A and B.25,42 The effects of an NCE on blood pressure, heart rate, and the ECG should be evaluated. Furthermore, in vivo, in vitro, and ex vivo evaluations, including methods for (assessing) repolarization and conductance abnormalities, should... 

Good Laboratory Practice is a qnahty system concerned with the organisation of the test facility and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported. This is the GLP Decalogue stating the basic principles that the laboratory must follow. 

Good Laboratory Practice is a quality system that is tailored to the needs of the modem laboratories. Its principles are very close to the principles of the modem quality management systems like ISO 9000 and ISO 17025. However, GLP is specific to the non-clinical health and environmental safety studies, it covers physical and chemical test systems, and gives emphasis to biological test systems. It is of utmost importance to note that GLP principles were set out by the Organization for Economic Cooperation and Development (OECD) and after being modified they were adopted by the Emopean Union and are now the Commission Directive 1999/11/EC. 

The NDA. After the sponsor has completed all non-clinical and clinical testing necessary to demonstrate the safety and effectiveness of the drug, the test results must be compiled in an NDA for submission to FDA. As with the IND, the content and format of the NDA are set forth in the FDA regulations and must be followed in detail. The NDA must begin with a sum-ma ry, to be followed by technica 1 sections relating to (1) chemistry, manufacturing and controls,... 

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