Validation drug guidelines

Some internationally harmonized guidelines regarding specifications and tests, impurities and validation of analytical methods have particular relevance to the development of chiral drugs and are discussed below. In addition, the impact of work on the common technical document is considered. 

Guidance on specifications is divided into universal tests/criteria which are considered generally applicable to all new substances/products and specific tests/criteria which may need to be addressed on a case-by-case basis when they have an impact on the quality for batch control. Tests are expected to follow the ICH guideline on analytical validation (Section 13.5.4). Identification of the drug substance is included in the universal category, and such a test must be able discriminate between compounds of closely related structure which are likely to be present. It is acknowledged here that optically active substances may need specific identification testing or performance of a chiral assay in addition to this requirement. 

The guideline states that the objective of validation is to demonstrate that an analytical method is fit for its purpose and summarizes the characteristics required of tests for identification, control of impurities and assay procedures (Table 13-2). As such, it applies to chiral drug substances as to any other active ingredients. Requirements for other analytical procedures may be added in due course. 

Netherlands drug regulation now follow European Union rules. For example, GMP inspection is based on the 1983 European Union guidelines for GMP. Since 1 January 1995, a European procedure for registration has operated in the Netherlands. Now two types of trade licences exist a European licence and a national licence. Products with a European licence may be sold throughout the whole European Union, while the national licences are only valid for the country in which the licence was issued by means of the national registration procedure. 

Nowadays most trials of psychotropic drugs are multicentric, and an increasing number of them are carried out in different regions of the world. However, ethnic variations in response to the tested drugs are rarely a focus of attention in these trials. Moreover, treatment guidelines produced in North America and Europe are often regarded as universally valid, and rarely adapted to other regional contexts. This is still partly due to some reluctance to accept the concept of ethnic variability,... 

Guideline for Submitting Samples and Analytical Data for Methods Validation, February 1987, Center for Drugs and Biologies, Food and Drug Administration, Rockville, MD. 

Validation of analytical procedures methodology Guideline on Impurities in New Drug Substances Guideline on Impurities in New Drug Products Availability Notice... 

The current guidelines for IVIVC development and validation state that studies for IVIVC development should be performed with enough subjects to adequately characterize the performance of the drug product under study. Acceptable data sets have ranged from 6 to 36 subjects. 

Toxicokinetics has become a critically important component of any nonclinical program (see discussion in Section 14.10). Current ICH guidelines require the determination of animal pharmacokinetics at all dose levels administered on at least 2 days (beginning and end) during a nonclinical toxicology study.5 Similarly, this requires the development of a validated analytical method for the determination of parent drug (and possible major metabolites). 

TABLE 6 ICH Guidelines Affecting the Analytical Testing of Drug Substances and Drug Products Valid as of November 2005... 

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