International Conference on Harmonisation; guidance on Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs" (the ICH E2C guidance). The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). In the Federal Register of May 19, 1997 (62 FR 27470), FDA published the ICH E2C guidance, which recommends a unified standard for the format, content, and reporting frequency for postmarketing periodic safety update reports (PSURs) for drug and biological products. This guidance, an addendum to the ICH E2C guidance, provides additional information on the content and format of PSURs, including clarification of the objectives, general principles, and model for PSURs. This guidance is intended to help harmonize collection and submission of postmarketing clinical safety data.     

International Conference on Harmonisation; evaluation of stability data; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q1E Evaluation of Stability Data." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). This guidance is a supplement to an ICH guidance entitled "Q1A(R2) Stability Testing of New Drug Substances and Products," which was revised from Q1A(R) and published in the Federal Register of November 21, 2003 (68 FR 65717). It is intended to provide guidance on how to use stability data, generated in accordance with the principles outlined in Q1A(R2), to propose a retest period for the drug substance and a shelf life for the drug product.     

International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a process for the evaluation and recommendation by the ICH Q4B Expert Working Group (EWG) of selected pharmacopeial texts to facilitate their recognition by regulatory authorities for use as interchangeable in the ICH regions. Following favorable evaluations, ICH will issue topic-specific annexes with information about these texts and their implementation (the Q4B Outcomes). Implementation of the Q4B annexes is intended to avoid redundant testing by industry in favor of a common testing strategy in each ICH regulatory region.     

International Conference on Harmonisation; guidance on S7A safety pharmacology studies for human pharmaceuticals; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "S7A Safety Pharmacology Studies for Human Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides a definition, general principles, and recommendations for the nonclinical safety pharmacology studies. The guidance is intended to help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals, while avoiding unnecessary use of animals and other resources.     

International Conference on Harmonisation; guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin; availability--FDA. Notice

The Food and Drug Administration (FDA) is publishing a guidance entitled "Q5A Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes the testing and evaluation of the viral safety of biotechnology products derived from characterized cell lines of human or animal origin, and outlines data that should be submitted in marketing applications.     

International Conference on Harmonisation; Guidance on E2F Development Safety Update Report; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E2F Development Safety Update Report." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes the format, content, and timing of a development safety update report (DSUR) for an investigational drug. The DSUR will serve as a common standard for periodic reporting on drugs under development (including marketed drugs that are under further study) among the ICH regions. The DSUR can be submitted in the United States in place of an annual report for an investigational new drug application (IND). The harmonized DSUR is intended to promote a consistent approach to annual clinical safety reporting among the ICH regions and enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities.     

International Conference on Harmonisation; draft guidance on E2F Development Safety Update Report; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled "E2F Development Safety Update Report." The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The draft guidance describes the format, content, and timing of a development safety update report (DSUR) for an investigational drug. The DSUR would serve as a harmonized, annual clinical trial safety report that would be standard among the three ICH regions. The DSUR could be submitted in the United States in place of an annual report for an investigational new drug application (IND). The harmonized DSUR is intended to promote a consistent approach to annual clinical safety reporting among the ICH regions and enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities.     

International Conference on Harmonisation; Guidance on Q8 Pharmaceutical Development; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q8 Pharmaceutical Development." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes the suggested contents for the pharmaceutical development section of a regulatory submission in the ICH M4 Common Technical Document (CTD) format. The guidance also indicates areas where the provision of greater understanding of pharmaceutical and manufacturing sciences can create a basis for flexible regulatory approaches.     

International Conference on Harmonisation; guidance on data elements for transmission of individual case safety reports; availability. Notice. Food and Drug Administration,HHS

The Food and Drug Administration (FDA) is publishing a guidance entitled "E2B Data Elements for Transmission of Individual Case Safety Reports." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance is intended to facilitate the standardization of the data elements for the transmission of individual case safety reports for both preapproval and postapproval reporting periods.     

International Conference on Harmonisation; guidance on S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a nonclinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization and includes information concerning nonclinical assays and an integrated risk assessment. The guidance is intended to facilitate the nonclinical assessment of the effects of pharmaceuticals on ventricular repolarization and proarrhythmic risk.     

International Conference on Harmonisation; Guidance on S8 Immunotoxicity Studies for Human Pharmaceuticals; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "S8 Immunotoxicity Studies for Human Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides recommendations on nonclinical testing approaches to identify compounds that have the potential to be immunotoxic and guidance on a weight-of-evidence decision making approach for immunotoxicity testing. The guidance is intended to provide recommendations on nonclinical testing for immunotoxicity induced by human pharmaceuticals. The guidance applies to unintended immunosuppression and immunoenhancement, excluding allergenicity or drug-specific autoimmunity.     

International Conference on Harmonisation; guidance on S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals intended for Human Use; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled ``S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use' (ICH S2(R1)). This guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH S2(R1) combines and replaces two ICH guidances, "S2A Specific Aspects for Regulatory Genotoxicity Tests for Pharmaceuticals' and "S2B Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.' ICH S2(R1) provides guidance to drug sponsors on which tests should be performed to assess potential genotoxicity of pharmaceuticals. It also provides guidance on testing conditions, data interpretation, and followup strategies if a positive response is seen in in vitro assays. This guidance is intended to provide drug sponsors with recommendations to ensure that drugs are appropriately tested for potential to cause genetic damage and to ensure efficient development of new drugs.     

International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex on Residue on Ignition/Sulphated Ash General Chapter; Availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 1: Residue on Ignition/Sulphated Ash General Chapter.' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides the results of the ICH Q4B evaluation of the Residue on Ignition/Sulphated Ash General Chapter harmonized text from each of the three pharmacopeias (United States, European, and Japanese) represented by the Pharmacopoeial Discussion Group (PDG). The guidance conveys recognition of the three pharmacopeial methods by the three ICH regulatory regions and provides specific information regarding the recognition. The guidance is intended to recognize the interchangeability among these texts from the local regional pharmacopeias, thus avoiding redundant testing in favor of a common testing strategy in each regulatory region. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance on the Q4B process entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions."     

International Conference on Harmonisation; guidance on M4 common technical document; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of guidance entitled "M4 Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use" (M4CTD). The guidance was developed under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is being made available simultaneously in four parts (general organization, quality, safety, and efficacy), describes a harmonized format for new product applications (including applications for biotechnology-derived products) for submission to the regulatory authorities in the three ICH regions. The M4 CTD is intended to reduce the time and resources used to compile applications, ease the preparation of electronic submissions, facilitate regulatory reviews and communication with the applicant, and simplify the exchange of regulatory information among regulatory authorities.     

International Conference on Harmonisation; revised guidance on Q3B(R) Impurities in New Drug Products; Availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a revised guidance entitled "Q3B(R) Impurities in New Drug Products.' The revised guidance, which updates a guidance on the same topic published in the Federal Register of May 19, 1997 (the 1997 guidance), was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The revised guidance is intended to provide guidance to applicants for drug marketing registration on the content and qualification of impurities in new drug products produced by chemically synthesized new drug substances not previously registered in a country, region, or member State. The revised guidance clarifies the 1997 guidance, adds information, and provides consistency with more recently published ICH guidances. The revised guidance complements the ICH guidance entitled "Q3A(R) Impurities in New Drug Substances.'     

International Conference on Harmonisation: guidance on Q1D bracketing and matrixing designs for stability testing of new drug substances and products; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). This guidance is an annex to an ICH guidance entitled "Q1A(R) Stability Testing of New Drug Substances and Products" (66 FR 56332, November 7, 2001). It is intended to provide guidance on the application of reduced designs (i.e., bracketing and matrixing) for stability studies conducted in accordance with the principles outlined in ICH Q1A(R).     

International Conference on Harmonisation; guidance on good manufacturing practice for active pharmaceutical ingredients; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes current good manufacturing practice (CGMP) for manufacturing of active pharmaceutical ingredients (APIs). The guidance is intended to help ensure that all APIs meet the standards for quality and purity they purport or are represented to possess.     

International Conference on Harmonisation; guidance on Q9 Quality Risk Management; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q9 Quality Risk Management."' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides principles and examples of tools for quality risk management that can be applied to all aspects of pharmaceutical quality throughout the lifecycle of drug substances, drug products, and biological and biotechnological products. The guidance is intended to enable regulators and industry to make more effective and consistent risk-based decisions.     

International Conference on Harmonisation; guidance on electronic common technical document specification; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M2 eCTD: Electronic Common Technical Document Specification." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance defines the means for industry-to-agency transfer of regulatory information that will facilitate the creation, review, life cycle management, and archiving of the electronic submission. The guidance is intended to assist industry in transferring electronically their marketing applications for human drug and biological products to a regulatory authority.     

International Conference on Harmonisation; guidance on E2E Pharmacovigilance Planning; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E2E Pharmacovigilance Planning." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a method for summarizing the important potential and identified risks of a drug. It proposes a structure for a pharmacovigilance plan and sets out principles of good practice for the design and conduct of observational studies. The guidance is intended to aid in planning pharmacovigilance activities, especially in preparation for the early postmarketing period of a new drug.