Regulatory Guidance

Guidance Documents

2010

FDA Draft Guidance on Abuse Liability

2006

EU Guidance on Abuse Liability Assessment

Guidance for Industry: S8 Immunotoxicity Studies for Human Pharmaceuticals—The objectives of this guidance are to provide (1) recommendations on nonclinical testing approaches to identify compounds that have the potential to be immunotoxic and (2) guidance on a weight-of-evidence decisionmaking approach for immunotoxicity testing. Immunotoxicity is, for the purpose of this guidance, defined as unintended immunosuppression or enhancement. Drug-induced hypersensitivity and autoimmunity are excluded.

2005

Guidance for Industry: E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs—This guidance provides recommendations to sponsors concerning the design, conduct, analysis, and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization. This assessment should include testing the effects of new agents on the QT/QTc interval as well as the collection of cardiovascular adverse events. The investigational approach used for a particular drug should be individualized, depending on the pharmacodynamic, pharmacokinetic, and safety characteristics of the product, as well as on its proposed clinical use. The assessment of the effects of drugs on cardiac repolarization is the subject of active investigation. When additional data (nonclinical and clinical) are accumulated in the future, this document may be reevaluated and revised.

Guidance for Industry: S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals—This guidance describes a nonclinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization. The guidance includes information concerning nonclinical assays and integrated risk assessments. The assessment of the effects of pharmaceuticals on ventricular repolarization and proarrhythmic risk is the subject of active investigation. When additional data (nonclinical and clinical) are accumulated in the future, they will be evaluated and this guidance might be revised.

2002

Public Health Service Policy on Humane Care and Use of Laboratory Animals—This 2002 reprint of the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals reflects the August 7, 2002 PHS Policy amendment permitting institutions with PHS Animal Welfare Assurances to submit verification of Institutional Animal Care and Use Committee (IACUC) approval for competing applications or proposals subsequent to peer review but prior to award (67 FR 51289). New footnotes (6 and 12) are incorporated to provide institutions with the option of coding the names of IACUC members in materials routinely submitted to the Office of Laboratory Animal Welfare (OLAW). Citations and addresses are also updated in this reprint, and language specifying that information be submitted on institutional letterhead or in letter form is eliminated to allow for electronic submission of information to OLAW in the future.

2001

Guidance for Industry: S7A Safety Pharmacology Studies for Human Pharmaceuticals—This guidance was developed 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. This guidance provides a definition, general principles, and recommendations for safety pharmacology studies.

Regulatory Agencies and Nonprofit Organizations

Dutch Ministry of Health, Welfare and Sport (Dutch)

European Union Food Safety
Consumer confidence in the safety of food products has sometimes been shaken in recent years by food-related health crises. Responding to the challenge, the European Union has put in place a comprehensive strategy to restore people’s belief in the safety of their food “from the farm to the fork.” This is based on a combination of high standards for food, animal health and welfare, and plant health. These standards apply both to food produced inside the EU and food imports. Find out more...

Institut De Veille Santitaire (French)

German Federal Ministry for Health (German)

Health Canada
Health Canada is the Federal department responsible for helping Canadians maintain and improve their health, while respecting individual choices and circumstances.

ILSI Health and Environmental Sciences Institute (HESI)
The Health and Environmental Sciences Institute (HESI) is a nonprofit institution whose mission is to stimulate and support scientific research and educational programs that contribute to the identification and resolution of health and environmental issues of concern to the public, scientific community, government agencies, and industry. HESI’s programs bring together scientists from around the world from academia, industry, regulatory agencies, and other governmental institutions to address and reach consensus on scientific questions that have the potential to be resolved through creative application of intellectual and financial resources. This “tripartite” approach forms the core of every HESI scientific endeavor. As a nonprofit organization, HESI provides a unique, objective forum for initiating dialogue among scientists with different perspectives and expertise. Industry members provide primary financial support for HESI programs, but HESI also receives financial and in-kind support from a variety of US and international government agencies.

International Conference on Harmonisation: Safety Guidelines
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a unique project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration. The purpose is to make recommendations on ways to achieve greater harmonisation in the interpretation and application of technical guidelines and requirements for product registration in order to reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines. The objective of such harmonisation is a more economical use of human, animal and material resources, and the elimination of unnecessary delay in the global development and availability of new medicines whilst maintaining safeguards on quality, safety and efficacy, and regulatory obligations to protect public health. This Mission is embodied in the Terms of Reference of ICH.

International Life Sciences Institute
Founded in 1978, the International Life Sciences Institute (ILSI) is a nonprofit, worldwide foundation that seeks to improve the well-being of the general public through the advancement of science. Its goal is to further the understanding of scientific issues relating to nutrition, food safety, toxicology, risk assessment, and the environment by bringing together scientists from academia, government, and industry. ILSI’s work is guided by its Code of Ethics and Organizational Standards of Conduct. An organization chart showing the structure and reporting relationships of the ILSI Entities is available on this site.

Japanese National Institute of Health Services
The National Institute of Health Sciences (NIHS) conducts testing, research, and studies toward the proper evaluation of the quality, safety, and efficacy of pharmaceutical products, foods, and the numerous chemicals in the living environment.

Ministry of Health, Labour and Welfare

National Center for Complementary and Alternative Medicine
The National Center for Complementary and Alternative Medicine (NCCAM) is the Federal Government’s lead agency for scientific research on complementary and alternative medicine (CAM). We are 1 of the 27 institutes and centers that make up the National Institutes of Health (NIH) within the US Department of Health and Human Services. The mission of NCCAM is to: Explore complementary and alternative healing practices in the context of rigorous science., train complementary and alternative medicine researchers., and disseminate authoritative information to the public and professionals.

Office of Laboratory Animal Welfare- Policies and Laws

Organization for Economic and Co-Operation and Development
Established in 1961, the OECD brings together the governments of countries committed to democracy and the market economy from around the world to: Support sustainable economic growth, boost employment, raise living standards, maintain financial stability, Assist other countries’ economic development, and contribute to growth in world trade. The OECD also shares expertise and exchanges views with more than 100 other countries and economies, from Brazil, China, and Russia to the least developed countries in Africa.

Pharmaceutical Information Services
Phorum is a Pharmaceutical Information Portal founded in 1999 by West Point Pharmaceutical Consulting President Dr. Joe Patterson.

UK Department of Health
The aim of the Department of Health (DH) is to improve the health and wellbeing of people in England. About us explains DH’s work, structure and responsibilities.

US Department of Health & Human Services
Office of Extramural Reearch- Extramural grants account for approximately 84 percent of NIH’s $29 billion budget. These are awarded to investigators throughout the US and abroad. Approximately 10 percent of the NIH budget supports NIH intramural investigators, NIH staff who conduct research

US Food and Drug Administration

The US FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The US FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health. US FDA is the federal agency responsible for ensuring that foods are safe, wholesome and sanitary; human and veterinary drugs, biological products, and medical devices are safe and effective; cosmetics are safe; and electronic products that emit radiation are safe. US FDA also ensures that these products are honestly, accurately and informatively represented to the public. Some of the agency’s specific responsibilities include:

National Institute of Health

Public Health Service Policy on Humane Care and Use of Laboratory Animals

Frequently Asked Question

SEND (Standard for Exchange of Nonclinical Data)—Safety Pharmacology

Implementation of the CDISC SEND (Standard for Exchange of Nonclinical Data) standard by sponsors and CROs has picked up significant momentum following draft guidance issued by the FDA in December 2014.  This guidance mandates SEND readiness for general toxicology and carcinogenicity studies based on the SEND Implementation Guide 3.0 starting in December 2016 for NDA submissions.  Details regarding the FDA’s guidance can be found at http://www.fda.gov/forindustry/datastandards/studydatastandards/default.htm. The PMDA in Japan is also implementing CDISC standards, starting first with SDTM data for clinical trials to be followed by nonclinical studies based on the SEND model.   

CDISC recently released for public comment Version 3.1 of the SEND Implementation Guide which supports the reporting of respiratory and cardiovascular data from safety pharmacology studies.  Once the standard is published, the FDA is expected to commence a piloting process including test submissions followed by an update to its regulatory submission requirements.

Adoption of SEND offers significant benefits to our industry as it will enable all of us to exchange data (the individual animal data we currently find is the final export from our data software packages in Microsoft Excel files) in a form which we can reconstruct, store and visualize data in a format of our choice without the need to share exactly the same data acquisition software. This will ease the process of exchanging data with Contract Resource Organizations into in-house data repositories as well as streamline the integration of data during the process of in-licensing.  This will require a greater evolution and testing of the model to be able to uniquely identify the preparations vs. the subject/animal currently used. The software we will eventually use has not yet been fully refined but ToxVision (by PointCross Life Sciences) is the current visualization and analysis tool used by FDA reviewers. For more information on this data standard and to provide feedback on the SEND 3.1 Guide, read more at www.cdisc.org/send.