Questions Answers Document

Now that ICH E14 Q A R3 has been released, the previous versions of this document are not posted on the ICH web site per se. However, the respective questions asked and answered in the original document and each of the three revisions can be identified within ICH E14 Q A R3 by looking at the Date of Approval column for each question and associated answer  

One of the questions in ICH E14 Q A R2 addressed the topic of exposure-response modeling. The relevant questions can be paraphrased as follows  

Exposure-response modeling can be an important component of a totality of evidence assessment of the risk of QTc prolongation. It can be evaluated in early-phase studies and as part of the conventiontil study of QTc prolongation, and may help inform further evaluation. There are many different types of models for the analysis of concentration-response data, including descriptive pharmacodynamic (PD) models and empirical models that link pharmacokinetic (PK) models (dose-concentration-response) with PD models. 

An understanding of the exposure-response relationship can help predict the QTc effects of doses, dosing regimens, routes of administration, or formulations that were not studied directly. Interpolation within the range of concentrations studied is considered more reliable than extrapolation above the range. 

If the results for the study drug me tunbiguous (e.g., QTc prolongation at lower dose but no prolongation at higher dose, or QTc prolongation at a single isolated time point), exposure-response analysis can help interpret the data. 

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EMEA in the Note for Guidance on the Investigation of Bioavailability and Bioequivalence (24) states that the 90% Cl for AUC and Cmax ratios should lie within an acceptance interval of 0.80 to 1.25. However, in certain cases a wider interval may be acceptable for Cmax (Fig. 1), provided that there are no safety or efficacy concerns. Some points of this statement were furthermore clarified in a Questions Answers document (33) as follows The possibility offered by the guideline to widen the acceptance range... 

Intentional Chemistry Example Documentation (All Questions Answered)... 

The facts of the case and question and answer documents should be prepared. Key members of such a team are therefore the medical director, or a designate, senior managers who are able to quickly implement actions, a legal adviser if appropriate, and a member of the public relations/communications department, who knows how to communicate the team s outputs effectively. 

The PEG has been transformed into Paediatric Working Party in relation to implementation of Regulation (EC) No 726/2004. On 29 September 2004, the EC released the first proposal for a Regulation on Medicinal Products for Paediatric Use together with an explanatory memorandum, the Extended Impact Assessment and questions and answers document. The proposal has now been presented to the Council of Ministers and the European Parliament and it will go through the co-decision procedure. The earliest that the proposal is likely to become law is late 2006. 

Regulation on Medicinal Products for Paediatric Use together with an explanatory memorandum, the Extended hnpad Assessment and questions and answers document http //pharmacos.eudra.org/ F2/Paediatrics / index.htm... 

The lack of full GLP compliance, particularly for preclinical studies collected early in a development program, does not inhibit data from being submitted and reviewed by regulatory agencies, provided that the sponsor adequately describes and justifies areas of noncompliance. The FDA in its 1981 Question and Answer Document [14] clearly indicates that even safety supporting preclinical studies with areas of noncompliance may be acceptable provided that the quality and integrity of the study has not been impacted [14] ... 

The Common Technical Document (CTD), including a Question Answer section... 

As an example of how to use metadata to get document dates, the current version of the EPA s Questions Answers for the New Chemicals Program is undated, and the EPA s Web site does not refer to version numbers, but the pdf document has useful data buried in it. If it is opened using Adobe Reader , the File pulldown menu will have a tab called Properties, and the document dates will be revealed by clicking on the tab labeled Properties. ... 

Questions Answers on Regulation (EC) No 1272/2008 on CLP of Substances and Mixtures, 2009, ECHA This document contains questions and answers on Regulation (EC) No 1272/2008 (CLP Regulation)... 

In addition to a variety of formal guidance documents, EEOC has developed a wide range of fact sheets, question-and-answer documents, and other publications to help employees and employers understand the complex issues surrounding disability discrimination. These titles include ... 

The Commission has also issued two question-and-answer documents on the final GINA regulations, ... 

ICH Implementation Working Group (2015) Guideline E14 questions answers (R3) document. Available at http //www.ich.org/fileadmin/Public Web Site/ICH Products/Guidelines/Efficacy/... 

The ICH E14 working group released a questions and answers document in 2008, which was expanded with additional questions and answers in a revised document issued in April 2012 and revised again in March 2014... 

The ICH E14 working group released the third revision of the questions and answers document associated with ICH Guideline E14 in December 2015 (ICH, 2015). This revision is triggering a major change in the cardiac safety regulatory landscape... 

International Support. As suggested before, the scientific audience is an international one, and the user has a right to expect local support whenever possible. This means getting search questions and software questions answered by a person who is not only knowledgeable about the problem, but also a speaker of the user s language and reachable without a transoceanic telephone call. The user in Germany, for example, should not be required to call the United States to ask about how to link up with the DATEX-P network. Many searching problems may in fact be domestic problems that are best answered locally. Similarly, if the user simply wants replacement copies of lost software or documentation, those items are best delivered by a nearby service center. We believe such support centers are key components of a truly international information service. 

C. Daniel, App/ications of Statistics to lndustria/Experimentation, ]oE Wiley Sons, Inc., New York, 1976. This book is based on the personal experiences and insights of the author, an eminent practitioner of industrial appHcations of experimental design. It provides extensive discussions and concepts, especially in the areas of factorial and fractional factorial designs. "The book should be of use to experimenters who have some knowledge of elementary statistics and to statisticians who want simple explanations, detailed examples, and a documentation of the variety of outcomes that may be encountered." Some of the unusual features are chapters on "Sequences of fractional repHcates" and "Trend-robust plans," and sections entided, "What is the answer (what is the question )," and "Conclusions and apologies."... 

PPIC uses the RCRA/Superfund and Small Business Ombudsman Hotlines as well as a PPIC technical assistance line to answer pollution-prevention questions, access information in the PPIC, and assist in document ordering and searches. To access PPIC by telephone, call ... 

Answers to each question on this sample assessment form should be noted when appropriate. Each question also includes two subsequent questions is a system (S) in place, which addresses the specific question and does documentation (D) exist for that system. In those instances where one or the other does not apply, the assessor will mark N/A for not applicable and no points will apply. 

In defining your inspection and test requirements it is necessary not only to specify what inspections and tests are required and when, but also to define the acceptance criteria and the frequency of inspection and test. Are the acceptance criteria those defined in the product specification or are the limits to be closed to gain better control over the process Is every product to be inspected or are the quantities so large that it would be economically unviable If sampling is to be performed what are the acceptance criteria Answers to these and other questions need to be provided by your documented inspection and testing requirements. 

Provide support materials to key people. Prepare a briefing document, drawn from the integration proposal and executive summary, that executives, colleagues, and staff can use in responding to internal or external enquiries or in crafting speeches and other presentations. This document is often framed in terms of providing answers to questions that employees or other interested parties may ask. Some sample questions and answers are provided at the end of this chapter. 

Once the complete title is known, the journal can easily be obtained if it is in the library customarily used by the chemist. If not, one must use another library, and the next step is to find out which libraries carry the journal. CASSI answers this question too, since it carries a list of some 360 libraries in the United States and other countries, and for each journal it tells which of these libraries carries it, and furthermore, if the holdings are incomplete, which volumes of that journal are carried by each library. It may be possible to visit the closest library personally. If not, a copy of the article can usually be obtained through interlibrary loan. The CASSI also includes lists of journal publishers, sales agents, and document depositories. Photocopies of most documents cited in CA can be obtained from chemical Abstracts Document Delivery Service, Customer Services, 2540 Olentangy River Road, Columbus OH, 43210, USA. Orders for documents can be placed by mail, telephone. Telex, fax, or online through STN or other services. 

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