International Cooperation on Harmonisation of Technical requirements for Approval of Veterinary Medicinal Products (VICH); final guidance on " Safety studies for veterinary drug residues in human food: reproduction toxicity testing" (VICH GL22); availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a final guidance for industry (#115) entitled "Safety Studies for Veterinary Drug Residues in Human Food: Reproduction Toxicity Testing"(VICH GL22). This final guidance has been adapted for veterinary use by the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) from a guidance regarding pharmaceuticals for human use, which was adopted by the International Conference on Harmonisation of Technical Requirements for Approval of Pharmaceuticals for Human Use (ICH). This final VICH guidance document recommends a basic battery of tests that can be used to evaluate the reproduction safety of veterinary drug residues in human food.     

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 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 testing for carcinogenicity of pharmaceuticals. Notice. Food and Drug Administration,HHS

The Food and Drug Administration (FDA) is publishing a guidance entitled "S1B Testing for Carcinogenicity of 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 outlines experimental approaches to evaluating the carcinogenic potential of pharmaceuticals to humans that may obviate the necessity for the routine conduct of two long-term rodent carcinogenicity studies     

Immunotoxicity testing guidance; availability. Food and Drug Administration, HHS. Notice

The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled "Immunotoxicity Testing Guidance." This guidance is intended to provide FDA reviewers and manufacturers with a coherent strategy for assessing whether testing for potential adverse effects involving medical devices or constituent materials and the immune system is needed. The guidance is also intended to aid in developing a systematic approach to such testing.     

International Conference on Harmonisation; guidance on Q1A stability testing of new drug substances and products; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a revised guidance entitled "Q1A(R) Stability Testing of New Drug Substances and Products." The revised 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 sets forth recommendations on the information to be submitted in the stability data package for a new drug substance or drug product for a registration application within the three regions of the European Union (EU), Japan, and the United States. The purpose of there vision is to add information to certain sections and to provide clarification to other sections of the guidance.     

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; 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.     

Draft guidance for industry; container and closure integrity testing in lieu of sterility testing as a component of the stability protocol for sterile products; availability--FDA. Notice

The Food and Drug Administration (FDA) is announcing the availability of the draft guidance entitled "Guidance for Industry: Container and Closure Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products." The draft guidance is intended to provide recommendations and offer alternative methods for sterility testing to confirm the integrity of container and closure systems for sterile biological products, human and veterinary drugs, and medical devices. The draft guidance applies only to the replacement of the sterility test with an appropriate container and closure integrity test in the stability protocol, and it is not offered as a replacement for sterility testing for product release.     

International Cooperation on Harmonisation of Technical Requirements for Approval of Veterinary Medicinal Products (VICH); final guidance for industry on "studies to evaluate the safety of residues of veterinary drugs in human food: genotoxicity testing" (VICH GL23); availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a final guidance for industry (116) entitled "Studies to Evaluate the Safety of Residues of Veterinary Drugs in Human Food:Genotoxicity Testing" (VICH GL23). This final guidance has been adapted for veterinary use by the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products(VICH) from a guidance regarding pharmaceuticals for human use, which was adopted by the International Conference on Harmonisation of Technical Requirements for Approval of Pharmaceuticals for Human Use (ICH). This final VICH guidance document recommends a basic battery of tests that can be used to evaluate the genotoxicity of veterinary drug residues in human food in the European Union, Japan, and the United States     

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; Stability Data Package for Registration Applications in Climatic Zones III and IV; Stability Testing of New Drug Substances and Products; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of two guidances prepared under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The first is a guidance entitled "Q1F Stability Data Package for Registration Applications in Climatic Zones III and IV' (the Q1F guidance). The second is a revised guidance entitled "Q1A(R2) Stability Testing of New Drug Substances and Products' (the Q1A guidance). The Q1F guidance, which is an annex to the Q1A guidance, defines an approach for broader use of the Q1A guidance for territories in climatic zones III and IV. The revised Q1A guidance incorporates relevant Q1F recommendations.     

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; 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 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 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; 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; revised guidance on Q3A impurities in new drug substances; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a revised guidance entitled "Q3A(R) Impurities in New Drug Substances." The revised guidance, which updates a guidance on the same topic published in the Federal Register of January 4, 1996 (the 1996 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 clarifies the 1996 guidance, adds information, and provides consistency with more recently published ICH guidances. The revised guidance is intended to provide guidance to applicants for drug marketing registration on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a country, region, or member State.     

International Conference on Harmonisation; addendum to International Conference on Harmonisation Guidance on S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "S6 Addendum to Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals' (S6 addendum). The S6 addendum was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The S6 addendum is intended to incorporate new knowledge and experience gained since the implementation of the ICH guidance entitled "S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals' (ICH S6) and to clarify and provide greater detail to enable the development of safe and effective biopharmaceuticals.