FDA

Regulatory Research Agencies

FDA

Last updated: February 16, 2016

Overview:
The Food and Drug Administration (FDA) is a regulatory and research agency within the US Department of Health and Human Services that is responsible for “protecting the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products [for humans], medical devices, our nation’s food supply [including dietary supplements], cosmetics, and products that emit radiation.” FDA’s broad statutory authority stems from the Federal Food, Drug, and Cosmetic Act of 1938 (FFDCA), as amended. The Tobacco Control Act of 2009 expanded the FDA’s regulatory authority to cover the manufacture, distribution, and marketing of tobacco products.

FDA’s programs are organized into a number of centers and offices, each with its own regulatory, research, and/or enforcement mandate. In the context of regulatory toxicology, the primary divisions overseeing animal use and/or testing requirements at FDA are:

  • Center for Biologics Evaluation and Research (CBER): regulates the licensing of vaccines, blood products, animal-to-human xenotransplants, and other human biologics
  • Center for Devices and Radiological Health (CDRH):responsible for pre-market approval of new medical devices and radiation-emitting electronic products
  • Center for Drug Evaluation and Research (CDER):regulates the licensing and labeling of human pharmaceuticals
  • Center for Food Safety and Applied Nutrition (CFSAN): monitors the safety and labeling of cosmetics, food additives, domestically produced and imported foods, and shellfish
  • Center for Tobacco Products (CTP): responsible for implementation of the Family Smoking Prevention and Tobacco Control Act
  • Center for Veterinary Medicine (CVM): regulates veterinary drugs and devices, pet foods, and livestock feeds
  • National Center for Toxicological Research (NCTR): conducts intramural R&D and provides scientific support to other FDA centers and offices

Laws, Regulations, Guidance:
FDA regulations carry “the full force of the law.”  The agency’s regulatory authority is defined primarily by the following US laws:

The FDA regulates the following technologies, materials, and products:
Foods
Drugs
Biologics
Medical Devices
Radiation-Emitting Products
Cosmetics
Animal & Veterinary
Tobacco Products

Foods

Through the Center for Food Safety and Applied Nutrition (CFSAN), the FDA works to “assure that the food supply is safe, sanitary, wholesome, and honestly labeled.” The agency establishes performance standards and toxicity testing protocols for assuring the safety of food additives and nutritional supplements, and the absence of contaminants.

Food Additives

The Federal Food, Drug, and Cosmetic Act requires that manufacturers and packagers of processed foods demonstrate the safety (i.e., “reasonable certainty of no harm”) of all chemical additives and/or other materials that come into contact with food prior to marketing. The Office of Food Additive Safety within FDA’s Center for Food Safety and Applied Nutrition provides pre-market review of the safety of food/color additives and food contact materials.

FDA guidance for the toxicological assessment of food ingredients (also referred to as the Redbook) prescribes often extensive toxicological testing based on “concern levels” as determined by chemical structure and cumulative human exposure. Commonly required study types include the following:

  • Acute oral toxicity
  • Short-term (28 day) toxicity in rodents and nonrodents
  • Subchronic (90 day) toxicity in rodents and nonrodents
  • Chronic (1-2 year) toxicity in rodents and nonrodents
  • Mutagenicity and genotoxicity
  • Carcinogenicity (including possible in utero exposure phase)
  • Reproductive toxicity
  • Developmental toxicity
  • Neurotoxicity
  • Immunotoxicity
  • Metabolism and pharmacokinetics
  • Human clinical and/or epidemiology

Exceptions to the above testing requirements are provided under a 1958 amendment to the FFDCA for two broad groups of substances:

  • Substances that FDA or the US Department of Agriculture had determined safe for use in food prior to 1958
  • Ingredients generally recognized as safe (GRAS) based on a long history of use and/or published scientific evidence

Nutritional Supplements

Vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites are regulated under the Dietary Supplement Health and Education Act of 1994 (DSHEA) by FDA’s Office of Nutritional Products, Labeling, and Dietary Supplements, a division of the Center for Food Safety and Applied Nutrition. In contrast to most other products regulated by FDA, nutritional supplements are not subject to specific safety/efficacy testing requirements or pre-market approval by the agency. Responsibility for ensuring that a nutritional supplement is safe rests with the manufacturer, who is only obligated to notify FDA prior to marketing a supplement containing a new dietary ingredient. FDA is responsible for: (1) monitoring the market for potentially unsafe products and/or those that make false or misleading label claims; (2) investigating reports of adverse effects; and where appropriate, (3) taking action to remove unsafe products from the market.

Foodborne Illness

Foods of animal or plant origin may present intrinsic hazards due to microbiological contamination (e.g., Salmonella); for these the FDA’s Center for Food Safety and Applied Nutrition has developed general analytical methods. Separate methodologies have also been established for testing of oysters, scallops, and other shellfish for toxins that can cause sickness ranging from indigestion to paralysis and death. Current FDA standards generally prescribe the use of often-lethal animal tests to detect three different classes of shellfish toxins (paralytic, amnesiac, and diarrhetic), yet also permit the use of validated, non-animal techniques such as the Lawrence method of high performance liquid chromatography under certain circumstances.

Guidance Documents:

Drugs

The Federal Food, Drug, and Cosmetic Act provides for an extensive pre-market approval process for all pharmaceutical products––including generic, over-the-counter, and prescription drugs––to ensure their safety and effectiveness for human use. Responsibility for the regulation of human pharmaceuticals in the US rests with FDA’s Center for Drug Evaluation and Research.

US regulations and guidance for pharmaceutical safety assessments have been harmonized with those of other major pharmaceuticals markets (i.e., Europe and Japan) under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Harmonized ICH guidelines for the safety assessment of human medicines call for a wide array of pre-clinical (animal) studies before a drug candidate is deemed safe for human clinical trials. Commonly required animal tests include the following:

  • Toxicokinetics and pharmacokinetics in rodents and/or other species
  • Single-dose studies in rodents and occasionally dogs and primates
  • Subacute (14-28 day), subchronic (90 day), and/or chronic (90+ day) studies in rodents, dogs, and occasionally primates
  • Reproduction segment I––fertility studies in rodents
  • Reproduction segment II––prenatal developmental toxicity in rodents and rabbits
  • Reproduction segment III––postnatal development in rodents
  • Mutagenicity and genotoxicity studies of at least 2 varieties
  • Carcinogenicity studies in rats and transgenic mice
  • Immunotoxicity in rodents
  • Triggered specialized studies (e.g., phototoxicity and pyrogenicity)

Drug candidates that exhibit favorable toxicological profiles in pre-clinical testing may be candidates for human clinical trials. This step requires the submission of an Investigational New Drug application to FDA, detailing the results of animal pharmacology and toxicology studies, manufacturing information, and clinical protocols and investigator information. Contingent upon approval from FDA and an institutional human research ethics committee, as many as three phases of human trials may be required. For pharmaceutical products determined to be safe and efficacious in human trials, the final step prior to US commercialization is the submission of a New Drug Application, which must include sufficient information for the FDA to determine that (1) a new drug is safe and effective for its proposed use, (2) the benefits outweigh the risks, and (3) the proposed labeling requirements and the manufacturing methods and controls are adequate. Federal law also requires that all prescription and over-the-counter drugs marketed in the US satisfy the quality standards established by the US Pharmacopeial Convention. Once on the market, there are post-market surveillance controls with which a manufacturer must also comply.

Preclinical testing of new pharmaceutical candidates consumes many thousands of animals and is required for both the active medicinal ingredient(s) as well as any variants in a formulation or delivery system. Yet despite these costs, the FDA acknowledges that "a new [human] medicinal compound entering Phase 1 testing, often representing the culmination of upwards of a decade of preclinical screening and evaluation, is estimated to have only an 8 percent chance of reaching the market." Such high failure rates have called into question the accuracy of animal studies in predicting human clinical outcomes and prompted calls for greater acceptance and use of in vitro and "omic" techniques in preclinical safety testing, as well as new clinical approaches such as human microdosing (Phase 0).

Guidance Documents:

Vaccines, Blood, & Biologics

A biological product, as defined under the Public Health Service (PHS) Act, can include a "virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product … applicable to the prevention, treatment, or cure of a disease or condition of human beings." The PHS Act requires that all human biologics be licensed, appropriately labeled, and proven "safe, pure, and potent." Responsibility for ensuring the safety and efficacy of biologics intended for human use in the US rests with FDA’s Center for Biologics Evaluation and Research.

A company wishing to begin clinical trials of a biological product must submit an Investigational New Drug application to FDA describing the product, its method of manufacture, and quality control tests for release. In the case of a vaccine, manufacturers must demonstrate the following characteristics:

  • Purity, meaning that it is not contaminated with viable bacteria, viruses, or fungi
  • Safety, meaning that it is not dangerous or harmful – which is usually determined by means of "abnormal toxicity" or similar studies, in which groups of animals are injected with a vaccine and monitored for clinical signs of toxicity
  • Potency, meaning that it is effective in preventing infection – which is usually determined by means of a "challenge study," in which groups of animals are first inoculated with a vaccine and then exposed to a virulent strain(s) of the organism against which the vaccine is intended to protect; animals are then monitored for clinical signs of the infectious disease in question, which may involve considerable pain, suffering, and ultimately, death

A further pre-marketing requirement involves three phases of clinical trials in human volunteers to demonstrate safety and efficacy in the species of ultimate interest. If successful, a Biologics License Application is submitted for review by FDA regulators, as well as the agency’s independent Vaccines and Related Biological Products Advisory Committee.

Even after a vaccine is licensed, FDA may require manufacturers to submit the results of their own tests for potency, safety, and purity for each vaccine lot and/or samples of each vaccine lot to the agency for testing. It is estimated that approximately one-third of all animal use in toxicology occurs in the biologics sector.

Relevant alternative methods validated to date include ELISA batch potency tests for erysipelas and human tetanus vaccines, as well as a toxin binding inhibition (ToBI) test for human tetanus vaccine.

Biosimilars:

In 2010, the Patient Protection and Affordable Care Act amended the Public Health Service Act to "create an abbreviated licensure pathway for biological products that are demonstrated to be ‘biosimilar’ to or ‘interchangeable’ with an FDA-licensed biological product." This amendment is also referred to as the Biologics Price Competition and Innovation Act of 2009.

The Act stipulates that, "to have a product reviewed as a biosimilar or interchangeable, manufacturers must submit a 351(k) biologics license application (BLA) that includes, among other things, information demonstrating biosimilarity based upon:

  • Analytical studies demonstrating that the biological product is ‘highly similar’ to the reference product notwithstanding minor differences in clinically inactive components;
  • Animal studies (including the assessment of toxicity); and
  • A clinical study or studies (including the assessment of immunogenicity and pharmacokinetics (PK) or pharmacodynamics (PD)) sufficient to demonstrate safety, purity, and potency in 1 or more appropriate conditions of use for which the reference product is licensed and for which licensure is sought for the biosimilar product."

In some cases, the FDA might determine that one of these elements is unnecessary; manufacturers are therefore encouraged to "contact the appropriate review division to obtain input on a proposed development program."

Guidance Documents:

Medical Devices

The Federal Food, Drug, and Cosmetic Act broadly defines medical devices as including any "instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is … intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals…." Responsibility for ensuring the safety and effectiveness of medical devices lies with FDA’s Center for Devices and Radiological Health.

FDA classifies medical devices based on the level of control necessary to assure the safety and effectiveness of the device:

  • Class I devices present minimal risk to the user, such as tongue depressors, bedpans, elastic bandages, examination gloves, and hand-held surgical instruments and other similar types of common equipment. Devices in Class I are subject only to general controls, which cover issues such as manufacturer registration, good manufacturing techniques, proper labeling, pre-market notification, and general reporting requirements.
  • Class II devices require additional special controls to assure safety and effectiveness. Examples include surgical and acupuncture needles, suture material, dental implants, infusion pumps, and x-ray machines.
  • Class III devices require pre-market safety and efficacy review and approval by FDA because they are “purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health.” Examples include heart valves, implanted cardiac pace-makers and cerebral stimulators, and bone and breast implants.

FDA regulations for pre-market approval applications require the submission of summaries of all “nonclinical laboratory studies” as well as “clinical investigations involving human subjects” undertaken to demonstrate the safety and efficacy of a device for human use. However, specific testing requirements are not specified. Federal law also requires that all medical devices marketed in the US satisfy the quality standards established by the US Pharmacopeia. Once on the market, there are post-market surveillance and reporting requirements with which a manufacturer must also comply.

Guidance Documents:

Radiation-emitting Products

The FDA has regulatory authority over products that emit radiation, such as medical and therapeutic devices (e.g., diagnostic and treatment radiography, mammography, surgical lasers), security x-rays in airports and office buildings, laser pointers/players/printers, cell phones, and microwave ovens. For safety purposes, many of these devices must meet specific performance standards.

Oversight is conducted through the FDA’s Center for Devices and Radiological Health (CDRH), which established the "Radiological Health Program" to "protect the public from hazardous or unnecessary radiation exposure from radiation-emitting electronic products."

The program accomplishes this by:

  •  "Regulating radiation-emitting electronic products used for both medical and non-medical applications, under the authorities of the Electronic Product Radiation Control provisions and the Medical Device Amendments of 1976 to the Food, Drug, and Cosmetic Act;
  • Regulating facilities that perform mammography under the authority of the Mammography Quality Standards Act; and
  • Assisting in the protection of the public by supporting FDA’s radiation emergency response activities."

The program is a cooperative effort between numerous stakeholders "including States and other Federal agencies, professional organizations, academic institutions, users, manufacturers, and consumer groups."
CDRH has created an educational tool, "CDHR Learn," to provide industry with "comprehensive, interactive, and easily accessible" information about the steps required to bring new medical radiation-emitting devices to market.

Guidance Documents:

Animal and Veterinary

The marketing of veterinary pharmaceuticals and medicated livestock feeds in the US is regulated by the FDA’s Center for Veterinary Medicine (CMV) pursuant to the Federal Food, Drug, and Cosmetic Act (FFDCA). FFDCA requires that animal drugs and feeds be safe and effective and that edible animal products derived from treated animals be free of unsafe residues.

The FDA’s Office of New Animal Drug Evaluation (ONADE) is responsible for reviewing information submitted by sponsors of new animal pharmaceuticals, and for determining whether the new drug should be approved by the CVM for marketing. At the beginning of the approval process, the drug sponsor contacts ONADE to open an Investigational New Animal Drug file and discuss data requirements.

US requirements for veterinary pharmaceutical safety assessments have been harmonized with those of other major pharmaceuticals markets (i.e., Europe and Japan) under the auspices of the International Cooperation on Harmonization of Technical Requirements for Regulation of Veterinary Medicinal Products (VICH). Some VICH guidelines call for a wide array of animal studies, including the following:

  • Subchronic (90-day) and chronic (2-year) toxicity in rodents and/or dogs
  • Reproductive toxicity in 2 or more generations of rodents
  • Developmental toxicity in rodents and/or rabbits
  • Genotoxicity studies of at least 3 varieties
  • Testing for effects on human intestinal flora
  • Pharmacological effects
  • Immunotoxicity
  • Neurotoxicity
  • Carcinogenicity studies in rats and mice
  • Triggered “special” studies

Data must document:

  • Target Animal Safety;
  • Effectiveness;
  • Human Food Safety;
  • Chemistry, Manufacturing, and Controls; and
  • Environmental Impact (drug sponsors are also required to submit an Environmental Assessment to describe how a new drug might enter the environment and what effects it might have)

For veterinary pharmaceuticals determined to be safe and efficacious, the final step prior to US commercialization is the submission of a New Animal Drug Application (for generic copies of existing animal drugs, an Abbreviated New Animal Drug Application is available), which must include sufficient information for the FDA to determine that (1) a new drug is safe and effective for its proposed use, (2) the benefits outweigh the risks, and (3) the proposed labeling requirements and the manufacturing methods and controls are adequate. Once on the market, there are post-marketing surveillance controls with which a manufacturer must also comply.

Guidance Documents:

Cosmetics

The marketing of cosmetics in the US is regulated by the Office of Cosmetics and Colors within FDA’s Center for Food Safety and Applied Nutrition pursuant to the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Fair Packaging and Labeling Act. In contrast to most other products regulated by FDA, cosmetics––including shampoo, perfumes, makeup, moisturizers, lipsticks, nail polish, hair colors, toothpastes, and deodorants––are not subject to specific testing requirements or pre-market approval by the agency. However, the FFDCA broadly prohibits the marketing of adulterated or misbranded cosmetics, including any product (other than a hair dye ) that "bears or contains any poisonous or deleterious substance which may render it injurious to users under the conditions of use prescribed in the labeling thereof, or under conditions of use as are customary and usual." The FDA also invites participation by manufacturers, packers, and distributors in its Voluntary Cosmetic Registration Program (VCRP).  "The VCRP assists FDA in carrying out its responsibility to regulate cosmetics. FDA uses the information to evaluate cosmetic products on the market. …(V)oluntary submissions provide FDA with the best information available about cosmetic products and ingredients, their frequency of use, and businesses engaged in their manufacture and distribution (Federal Register, vol. 73, p. 76360, and vol. 69, p. 9339)." Information from the VCRP database is sometimes used by the Cosmetic Ingredient Review (CIR) panel in its safety assessments. When necessary to "address public safety concerns or provide information to support regulatory actions or guidance," the FDA will conduct its own research on cosmetic products and ingredients.

Guidance Documents:

Tobacco Products

The Family Smoking Prevention and Tobacco Control Act of 2009 gives the FDA regulatory authority over the manufacture and marketing of tobacco products (cigarettes, cigarette tobacco, roll-your-own tobacco and smokeless tobacco).  Among other details, the Act specifies that tobacco product manufacturers must provide the FDA with a list of ingredients for each product.  It also authorizes the FDA to establish product standards, regulate ingredient levels, based on scientific research on health effects.

New tobacco product applications must include health and safety information specified by sections 907 and 910 of the Federal Food, Drug & Cosmetic Act, as amended by the Tobacco Control Act.  These information requirements include, among other things, a detailed list of ingredients, components, and additives, and detailed description of the manufacturing process.

Guidance Documents:

 

Alternatives Policies & Actions

Though the FDA does not appear to have a specific policy on animal welfare or the 3Rs, it has stated (with regard to cosmetics, in particular) that it is "a strong advocate of methodologies for the refinement, reduction, and replacement of animal tests with alternative methodologies that do not employ the use of animals."  To that end, the FDA participates in inter-agency and international efforts to increase the use of non-animal alternatives, has also undertaken a number of research and development initiatives that are germane to the 3Rs, and invites public commentary on relevant guidance.

Inter-agency activities

The FDA is a member of the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).  In addition, informatics and computational safety analysis staff members in FDA’s Center for Drug Evaluation and Research have helped develop many of the in silico models now widely used within the agency. In 2010, the FDA joined a Memorandum of Understanding between the National Toxicology Program (NTP), NIH’s Chemical Genonomics Center (NCGC), and the Environmental Protection Agency (EPA), to collaborate on Tox21.  Under this MOU, the agencies agree to pool their unique resources and capacities to advance the use of high throughput screening technologies and computational modeling, to more rapidly and effectively assess chemicals for potential toxicity.  The FDA will share its extensive compilation of non-confidential, non-proprietary toxicological data acquired in product evaluations.  The collaboration is expected to yield a reduction or replacement of animals in regulatory testing…in parallel with an increased ability to evaluate the large numbers of chemicals that currently lack adequate toxicological evaluation."

In 2015, the FDA and EPA announced a Memorandum of Understanding to share data on pesticides and toxic substances.  The MOU "establishes a process of disclosure and sharing of their respective databases that will facilitate the decisions of each agency related to food safety, veterinary medications, and cosmetics."  The agreement has the potential to greatly reduce duplication or unnecessary additional in vivo testing.

The Tissue Chip for Drug Screening Initiative is a collaboration between the FDA, NIH’s National Center for Advancing Translational Sciences (NCATS), the Defense Advanced Research Projects Agency (DARPA), and a number of academic research partners to develop 3-dimensional microphysiological tissue- and organ-chip systems.  The chip systems are intended to be linked into a human-on-a-chip and used to safety-test pharmaceuticals, vaccines, or other biologic agents, and to test the effects of chemical and radiation exposures.

Modernization initiatives

  • In 2010, the FDA launched the Advancing Regulatory Science Initiative, an effort to move regulatory science "into the 21st century" by making better use of mechanistic data, cell-based models, and computational models.
  • The Critical Path  Initiative (CPI) is the "FDA’s strategy to drive innovation in the scientific processes through which medical products are developed, evaluated, and manufactured." Acknowledging that [m]any of the tools used today to predict and evaluate product safety and efficacy, and to manufacture products, are badly outdated from a scientific perspective," the FDA’s stated goal for CPI is to "bring new scientific discoveries — in fields such as genomics and proteomics, tissue engineering, imaging, and bioinformatics — to bear on product development, to improve the accuracy of the tests we use to predict the safety and efficacy of investigational medical products." In 2006, the FDA released a "Critical Path Opportunities List" that identified "specific areas where the sciences of product development had the greatest need for improvement." One byproduct of CPI is the Critical Path Institute (C-Path), a non-profit, public-private partnership between FDA and various industry and academic partners that seeks to improve and accelerate the drug development pathway "through the creation of new data standards, measurement standards, and methods standards that aid in the scientific evaluation of the efficacy and safety of new therapies."  Much of C-Path’s work continues to rely on animal models, however a C-Path collaboration with a Baylor University scientist – an in vitro system for testing tuberculosis drugs – was qualified by the European Medicines Agency (EMA, the European equivalent of the FDA), which means the EMA will "accept supportive data from research using this method." C-Path is also working on the creation of data standards that will ultimately facilitate data-sharing.
  • The FDA’s National Center for Toxicological Research (NCTR) "conducts scientific research to develop and support innovative tools and evaluation of approaches that FDA uses to protect and promote individual and public health." Research areas include: biomarker identification, bio-imaging, nanotechnology, personalized medicine, and regulatory science training.  Historically, a substantial proportion of NCTR research involves animal use. For example, NCTR maintains more than 80 animal breeding and holding rooms, a nonhuman primate research center, a phototoxicology research center, and an infectious disease biocontainment laboratory for use by its various research divisions. However, NCTR has also established a number of Centers of Excellence to further the development and application of new (-omic and in silico) technologies into FDA programs. The center also developed and released a number of publically available bioinformatics databases.
  • The FDA formed a Nanotechnology Task Force in 2006 to determine "regulatory approaches that encourage the continued development of innovative, safe, and effective FDA-regulated products that use nanotechnology materials." Many of the products regulated by the FDA contain nanomaterials, or use nanotechnologies in their manufacturing processes. The FDA describes its approach to regulating these materials and technologies as product-based, noting that it "will regulate nanotechnology products under existing statutory authorities, in accordance with the specific legal standards applicable to each type of product under its jurisdiction." The FDA’s Office of Regulatory Affairs "is charged with ensuring that FDA-regulated products that contain nanomaterials or otherwise utilize nanotechnology comply with current regulations and statutory requirements." The FDA has so far issued three final guidance documents on the use of nanotechnologies in food (for humans) and cosmetics, and one pertaining to the use of nanotechnology in food for animals. Many of the FDA’s own units conduct mission-specific regulatory science research in the area of nanotechnology. For example, CDER is studying the use of nanomaterials in drug products, CDRH is studying methods for characterizing the physical and bioactive properties of nanomaterials, and CFSAN is studying the dermal penetration of nanomaterials in cosmetics. These various efforts are coordinated by the FDA’s Office of the Commissioner of Nanotechnology Programs.
  • The Center for Drug Evaluation and Research (CDER) has launched a Drug Development Tools (DDT) Qualification Program to assist the manufacturers of new drug and biologic products " as they develop or refine a DDT for a specific context of use. CDER then will rigorously evaluate the submission for use in the regulatory process. Qualifying a DDT will allow sponsors to use the DDT in the qualified context of use during drug development without requesting that CDER reconsider and reconfirm the suitability of the DDT for the qualified context of use." The program has the potential to facilitate the development and use of alternative methods by streamlining the approval process, encouraging collaborations between submitters addressing "unmet needs" for methods, and making these methods publicly available for use in the qualified context. Qualification programs have so far been established for the qualification of biomarkers and clinical outcomes assessment, in addition to animal models.

Inviting public comment on alternatives

In 2014, the agency invited public input on its widely consulted "Redbook" (Toxicological Principles for the Safety Assessment of Food Ingredients), asking for "ideas and opinions on what should be included, changed, or even removed" from the current edition.  A transcript from the public meeting is available; among the proposals advanced, some constituents called for greater encouragement and acceptance of alternative methods.  An extension of the invitation further encouraged suggestions for "(n)ew assays, test methods, and endpoints that could be useful for safety assessment, with justifications for why and how these proposed new methods should be considered."

FDA Guidance Documents

The FDA introduced a database for searching all FDA Guidance Documents: http://www.fda.gov/RegulatoryInformation/Guidances/ucm2005656.htm

Electronic Records Submission

FDA created an electronic records submission application to facilitate voluntary reporting of product ingredients, certain new product applications, and after-market reporting (such as adverse events) for most products in its purview: http://www.fda.gov/ForIndustry/FDAeSubmitter/default.htm

Author(s)/Contributor(s):
Marilyn Matevia, PhD, AltTox Web Manager

AltTox Editorial Board reviewer(s):
George Daston, PhD
Pascaline Clerc, PhD