FDA/ICH guidelines

To use NIR spectroscopic methods as a release-testing tool, FDA/ICH guidelines that specifically address NIR applications or, at least, a validation guide for nonchromatographic techniques should be established. Until these exist, NIR methods must be validated using existing validation guidelines. 

The relevant regulations governing the conduct of clinical trials in the U S are shown in Table 5.4. As they also reflect the principles of GCP, they are quite similar in requirements to those of the E U. However, because they apply to a single jurisdiction, they are framed to provide more prescriptive detail than can be found in the equivalent EU directives. Similarly, they are supported by the ICH- and FDA-specific guidelines. As most of the practices are the same as discussed in the previous section, the chapter will now just examine some of the aspects that are unique to the US regulations. 

Just as there is an adverse event form, there is usually a serious adverse event (SAE) form. Note here that serious as defined by the FDA is different from severe on the adverse event form. A patient can have a severe headache that may not be considered serious. The ICH guideline (also in ICH E3) entitled Clinical Safety Data Management Definitions and Standards for Expedited Reporting defines serious adverse events as follows ... 

ICH Stage FDA Guidelines Great Britain and EEC Guidelines Japanese Guidelines EPA OPPTS, OECD and FDA Redbook Guidelines... 

Within the United States, the regulation of therapeutics is split on relatively arbitrary grounds. This is presented in Table 2.5 in Chapter 2. This chapter reflects both current FDA practices and the ICH guidelines. 

Some of the earliest guidelines were issued by the U.S. FDA.3 Several ICH guidelines now cover the performance of these studies, including amendments in 1995 to address possible effects on male reproduction.20,21... 

Generally speaking, the FDA will require placebo-controUed studies wherever possible to demonstrate efficacy at the dose to be marketed and these are termed pivotal studies. Pivotal studies do not have to be placebo controlled, however, and in some areas, such as depression, the ICH guidelines suggest a three-arm study, with both an active comparator and a placebo control. The Declaration of Helsinki, revised in 2000, suggested that in some disease areas, placebo-controlled studies are to be examined very carefuUy for their ethical content. This includes areas where conventional best therapy is generally acceptable. In this case, great care needs to be taken with the choice of active comparator. 

With respect to pharmaceuticals, the mouse is cited as an alternative species in the ICH S5(R2) guideline for the detection of toxicity to reproduction for medicinal products and toxicity to male fertility (2). Since the ICH guideline is also cited in other guidance documents (3, 4), it is clear that the mouse should be considered for teratology type (see Note 1) studies. In addition, although not specifically mentioned in other guidelines (OECD, FDA, EPA, etc.), the mouse may be an appropriate rodent model for products from the food and chemical industries if the choice is justified based on the available pharmacokinetic or metabolic information etc. (5-8). 

ICH guidelines are available at http /www.fda.gov/guidance ICH Q1B Photostability Testing of New Drug Substances and Products (November 1996)... 

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