Regulatory guidance documents

There are a number of FDA regulatory guidances that are associated with IVIVC development and validation, as well as the application of IVIVC to SUPAC. The specific IVIVC guidance for oral modified-release formulations was first published in September 1997 (1). There are several guidances on SUPAC, including those for both modified release (2) and immediate-release solid oral dosage forms (3). The recent 

The Committee for Proprietary Medicinal Products (CPMP) within the European Agency for the Evaluation of Medicinal Products (EMEA) has also issued a Note for Guidance on the pharmacokinetic and clinical evaluation of mod-ified-release oral products, which provides some information on the development and evaluation of an IVTVC (5). 

This chapter focuses primarily on the development and evaluation of IVIVC for ER oral products in accordance with the 1997 FDA Guidance. However, as the CPMP guidance provides almost identical information on these topics, the dis- 

ICH E14 provides recommendations to sponsors concerning the design, conduct, analysis and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization. Specifically, it calls for a clinical thorough QT/QTc study (typically conducted in healthy volunteers), which is intended to determine whether a drug has a threshold pharmacological effect on cardiac repolarization, as detected by QT/QTc interval prolongation. 

It is worth noting that, presently, in silico prediction of hERG liability is not considered in regulatory documents, although this is an area of intense investigation 

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It is important to remember that respiratory sensitization and asthma are related, but not identical, pathologies [31]. Asthma is a specific syndrome which appears to have genetic as well as environmental causes and there are numerous potential triggers which have been identified by immunotoxicologists [32], However, asthma is not the same disease as other respiratory hypersensitivity syndromes (sometimes referred to as chemical asthma, etc.) [33, 34], Various regulatory guidance documents have sought to deal with the latter disease entities to ensure that xenobiotics are assessed appropriately for their ability to induce immune-based pulmonary hypersensitivity reactions [35-37],... 

There are a number of examples in which histopathology and the functional immuno-toxicity tests recommended by regulatory guidance documents would not detect known... 

The following sections provide examples of approaches to assess drug effects on the cardiovascular, respiratory, and central nervous systems in compliance with the current and emerging regulatory guidance documents.25,42 45 60... 

This chapter focuses on approaches to the validation of high-performance liquid chromatography methods based on regulatory guidance documents and accepted industry practices. The information in this chapter gives a brief review of the reasons for performing method validation and the regulations that describe this activity. Individual validation parameters are discussed in relation to the type of method to be validated. Examples of typical validation conditions are presented with references to additional information on individual topics. This chapter was written to help analysts responsible for method validation. 

In addition to online resources, other texts and references have discussed the process of validation for methods used in the pharmaceutical industry in relation to the regulatory guidance documents. These guides include discussions on method development in relation to method validation, the validation of non-chromatographic methods and stability indicating methods. 

The SUPAC and other related regulatory guidance documents have, for the first time, provided an opportunity to reduce the regulatory constraints based on the pharmaceutical sciences. The FDA s participation in PQRI reflects its desire to enhance the scientific basis of its policies, thus creating numerous regulatory opportunities. It is hoped that the phannaceutical community wiU recognize these... 

Table 8 Validation Parameters Which Appear in Regulatory Guidance Documents...

TABLE 33.3 Key FDA regulatory guidance documents relating to cell-based therapies... 

A number of regulatory guidance documents touch on various aspects of the transition from preclinical to clinical study of a novel biopharmaceutical. The primary guidance documents describing the conduct and use of preclinical safety evaluation in supporting the initial clinical trials are as follows ... 

Regulatory guidance documents on the development of chiral drugs, mirroring... 

Interstate Technology Regulatory Council (ITRC), 2003. Technical and Regulatory Guidance Document for Constructed Treatment Wetlands. The Interstate Technology Regulatory Council Wetlands Team. 

Regulatory Guide 1.174 and Standard Review Plan Chapter 19 Regulatory guidance documents... 

As noted in Sect. 11.1, as we write this chapter there is not a regulatory landscape in place addressing the prospective exclusion of unacceptable blood pressure increases. It is legitimate, however, to speculate what questions a regulatory guidance document would address. Perhaps the following are reasonable possibilities. 

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