International Conference on Harmonisation; guidance on Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process." 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 purpose of the guidance is to provide principles for assessing the comparability of biotechnological/biological products before and after changes are made in the manufacturing process for the drug substance or drug product. The guidance is intended to assist in the collection of relevant technical information that serves as evidence that the manufacturing process changes will not have an adverse impact on the quality, safety, and efficacy of the drug product.     

International Conference on Harmonisation; guidance on E11 clinical investigation of medicinal products in the pediatric population; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E11 Clinical Investigation of Medicinal Products in the Pediatric Population." 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 sets forth critical issues in pediatric drug development and approaches to the safe, efficient, and ethical study of medicinal products in the pediatric population. The guidance is intended to encourage and facilitate the timely development of pediatric medicinal products internationally.     

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 Q6A specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. Notice

The Food and Drug Administration (FDA) is publishing a guidance entitled "Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances." 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 or provides recommendations concerning the selection of test procedures and the setting and justification of acceptance criteria for new chemical drug substances and new drug products produced from them. The guidance is intended to assist in the establishment of a single set of global specifications for new drug substances and new drug products.     

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.     

Draft guidance for industry on developing medical imaging drugs and biologics; availability--FDA. Availability of guidance

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled "Developing Medical Imaging Drugs and Biologics." This draft guidance is intended to assist developers of drug and biological products used for medical imaging, as well as radiopharmaceutical drugs used in disease diagnosis, in planning and coordinating the clinical investigations of, and submitting various types of applications for, such products. The draft guidance also provides information on how the agency will interpret and apply provisions in the proposed regulations for in vivo radiopharmaceuticals used for diagnosis and monitoring, which published in the Federal Register of May 22, 1998 (63 FR 28301).     

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 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; Guidance on E16 Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure, and Format of Qualification Submissions; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled ``E16 Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure, and Format of Qualification Submissions.' 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 recommendations regarding the context, structure, and format of qualification submissions for clinical and nonclinical genomic biomarkers related to development of drug or biotechnology products, including translational medicine approaches, pharmacokinetics, pharmacodynamics, and efficacy and safety aspects. The guidance is intended to create a harmonized recommended structure for biomarker qualification applications that will foster consistency of applications across regions and facilitate discussions with and among regulatory authorities.     

Current good manufacturing practice and investigational new drugs intended for use in clinical trials. Final rule

The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.     

Revocation of regulation on positron emission tomography drug products--FDA. Final rule; revocation

The Food and Drug Administration (FDA) is revoking a regulation on positron emission tomography (PET) radiopharmaceutical drug products. The regulation permits FDA to approve requests from manufacturers of PET drugs for exceptions or alternatives to provisions of the current good manufacturing practice (CGMP) regulations. FDA is taking this action in accordance with provisions of the Food and Drug Administration Modernization Act of 1997 (Modernization Act). Elsewhere in this issue of the Federal Register, FDA is publishing a notice revoking two notices concerning certain guidance documents on PET drugs and the guidance documents to which the notices relate.     

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.     

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.     

Natural rubber-containing medical devices; user labelling--FDA. Final rule; interpretation

The Food and Drug Administration (FDA) is providing notice that it does not intend to apply to combination products currently regulated under human drug or biologic labeling provisions its September 30, 1997, final rule requiring certain labeling statements for all medical devices that contain or have packaging that contains natural rubber that contacts humans. FDA is taking this action, in part, in response to a citizen petition and other communications from industry that the agency has received since the publication of the final rule. FDA intends to initiate a proceeding to propose natural rubber labeling requirements for drugs and biologics, including combination products that are currently regulated under drug and biologic labeling provisions. Such a proceeding may include a combination of rulemaking and guidance and will offer opportunity for public comment.     

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; choice of control group and related issues in clinical trials; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E10 Choice of Control Group and Related Issues in Clinical Trials." 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 sets forth general principles that are relevant to all controlled trials and are especially pertinent to the major clinical trials intended to demonstrate drug (including biological drug) efficacy. The guidance describes the principal types of control groups and discusses their appropriateness in particular situations. The guidance is intended to assist sponsors and investigators in the choice of control groups for clinical trials.     

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 E15 Pharmacogenomics Definitions and Sample Coding; Availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories." 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 contains definitions of key terms in the discipline of pharmacogenomics and pharmacogenetics, namely genomic biomarkers, pharmacogenomics, pharmacogenetics, and genomic data and sample coding categories. In the effort to develop harmonized approaches to drug regulation, it is important to ensure that consistent definitions of terminology are being applied across all constituents of the ICH. The guidance is intended to facilitate the integration of the discipline of pharmacogenomics and pharmacogenetics into global drug development and approval processes.     

International Conference on Harmonisation; guidance on E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs." 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 to sponsors concerning clinical studies to assess the potential of a new drug to cause cardiac arrhythmias, focusing on the assessment of changes in the QT/QTc interval on the electrocardiogram as a predictor of risk. The guidance is intended to encourage the assessment of drug effects on the QT/QTc interval as a standard part of drug development and to encourage the early discussion of this assessment with FDA.     

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.