Guidance documents, overview

The approach of deriving a tolerable intake by dividing the N/LOAEL, or alternatively a BMD for the critical effect(s) by an assessment factor has been described and discussed extensively in the scientihc literature. It is beyond the scope of this book to review all these references. This chapter presents an overview of pubhshed extrapolation methods for the derivation of a tolerable intake based on the assessment factor approach, i.e., limited to address effects with threshold characteristics, and is not meant to be exhaustive. The main focus is on the rationale for and the use of the assessment factors. Pertinent guidance documents and reviews for the issues addressed in this chapter include WHO/IPCS (1994, 1996, 1999), US-EPA (2002, 2004), IGHRC (2003), ECETOC (2003), KEMI (2003), Kalberlah and Schneider (1998), Vermeire et al. (1999), and Nielsen et al. (2005). 

The reader is also referred to the OECD Guidance Document No. 43 on Reproductive Toxicity Testing and Assessment (13), which will form the basis for the methodological points discussed below. More information can also be found in the IPGS paper on principles for evaluating health risks to reproduction associated with exposure to chemicals (14) as well as in an overview paper by Buschmann (15). 

The summary should provide each FDA reviewer an overview of the entire NDA. It should be organized according to the guidance document (1), and... 

This section will not provide an all-encompassing overview of all requirements of Part 11. It will focus on those requirements where the current interpretation of Part 11 has changed in the light of the Guidance document. 

This chapter does not aim to provide an extensive overview of monitoring provisions and their interpretation, which are largely described in guidance documents developed... 

The CTD format allows other, regional specific information, to be provided in a separate section of the application. The requirements for this section are often described in detail in the individual agency guidance documents. The CTD format also specifies sections for inclusion of references and attachments, as appropriate. Additionally, the CTD includes a quality overall summary (QOS) of the more detailed information provided in the application. The contents of the QOS related to API are fully described in ICH M4Q, and represent a brief overview of the main API section. The QOS may be used during the review of the application by other reviewing disciplines (e.g., clinical, pharm/tox, etc.). The QOS in essence has eliminated the need for a specific expert opinion report and summary tables in the EU however, it is expected that the contents of the document submitted to the EU have been reviewed and accepted by an appropriate quality expert, and that this expert is suitably identified in the application. 

An excellent overview of the problem, particularly as it affects bioanalytical data and information submitted to the US FDA, was published by the Society for Quality Assurance (SQA 2000). The relevant regulatory documents on electronic documents and signatures are found as Part 11 of the US Code of Federal Regulations (CFR21 2003) and an FDA Guidance document is available (FDA 2003a). (Note that the FDA interprets the word equipment to include hardware and software as well as instrumentation.) The review of qualification of anal54ical instrumentation (Bansal 2004) includes a section on software validation and the same phases (DQ, IQ, OQ and PQ, see Section 9.5.1a) apply. 

The FDA Guidance document (FDA 2001) provides a good model for analytical reports in general. Flowever, since the publication of that document additional details are commonly addressed (Viswanathan 2007). Table 10.8 was drawn from these publications and although the documents specifically address reporting requirements for bioanalyt-ical analysis in support of drug development studies, they provide an excellent overview of the requirements for a analytical report in general. 

Guidance on the content of the Nonclinical Overview (NCO) is given in ICH M4S, Common Technical Document for the Registration of Pharmaceuticals for Human Use—Safety, CHMP/ ICH/2887/99 Rev 1 Safety. This guideline also gives information on the structure and content of the narrative and tabular summaries that contain the more detailed information. 

An overview of the elements of validation mentioned or being dealt within some major official guidance validation documents is shown in Table 4. Empty circles are used for topics that have been mentioned without further explanation, while filled circles indicate topics that give more room. 

Present an overview of the ICH clinical safety and efficacy documents and facilitate the user s access to guidance pertinent to clinical trials within these documents. 

Module 2 - Summaries in addition to a table of contents and a one-page introduction, this module contains the Quality Overall Summary, the Non-clinical Overview, and the Clinical Overview these are followed by the Non-clinical Written Summaries, the Non-clinical Tabulated Summaries, and the Clinical Summary separate documents (M4Q, M4S, and M4E) give guidance on the format and content of the summaries)... 

As discussed in the Appendix Overview, each issue is composed of four parts (1) a ISSUE statement section, which describes the safety concern, (2) a ACCEPTANCE CRITERIA section which discusses the applicable NRC guidance and regulations and industry codes, standards and/or other relevant requirements, (3) a RESOLUTION section which describes the technical bases for the resolution of the issue considering the System 80+ Standard Design, as described within CESSAR-DC or other relevant documentation (e.g., special technical reports) and finally, (4) a REFERENCES section which lists the references used in the formulation of the Issue Statement, Acceptance Criteria, and Resolution sections of the issue. 

This document provides an overview of the OEMS, our standard approach for achieving world class performance. It includes general guidance for the implementation and operation of the OEMS. More detailed guidance can be found on the Operational Excellence Website and within OE documentation, the Leader s Guide to the OEMS and in the online OE Certification modules. 

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