Regulatory Information Resources For Nutraceuticals and Functional Foods: Resource Guide

Regulatory Information
Resources for Nutraceuticals

and Functional Foods:
Resource Guide
Prepared for
NRC-IRAP, Atlantic & Nunavut region
Prepared by
Mary Veling, Information Specialist, NRC-CISTI
In consultation with
Valerie Baker, Technical Business Analyst, NRC-IRAP
Number
11-5399
Date
February 2012 (replaces August 2011 version)
NRC-CISTI employees make every effort to obtain information from reliable sources.
However, we assume no responsibility or liability for any decisions based upon the information presented.
2012 National Research Council of Canada
Regulatory Information Resources for Nutraceuticals &

Feb. 2012
Functional Foods: Resource Guide
Contents
1
Introduction ................................................................................................................................... 4
Nutraceuticals and Functional Foods ......................................................................................... 5

2.1
Canada ..................................................................................................................................... 5
2.1.1
Natural Health Products ...................................................................................................... 5
2.1.2
Novel Foods ....................................................................................................................... 7
2.2
United States ............................................................................................................................ 7
2.2.1
2.3
Dietary supplements ........................................................................................................... 7
European Community ............................................................................................................... 9
2.3.1
Food Supplements ............................................................................................................. 9
2.3.2
Novel Foods ..................................................................................................................... 10
Drugs / Pharmaceuticals ............................................................................................................ 10

3.1
Canada ................................................................................................................................... 10
3.2
United States .......................................................................................................................... 11
3.3
European Community ............................................................................................................. 12
3.3.1
Medicinal Products ........................................................................................................... 12
3.3.2
Herbal Medicinal Products ................................................................................................ 12
3.3.3
Orphan Medicinal Product ................................................................................................ 13
3.3.4
Paediatric Medicine .......................................................................................................... 14
Biologics and Subsequent Entry Biologics (Biosimilars) ........................................................ 14

4.1
Canada ................................................................................................................................... 14
4.2
United States .......................................................................................................................... 15
4.3
Clinical Trials .............................................................................................................................. 16

5.1
Canada ................................................................................................................................... 16
5.2
United States .......................................................................................................................... 16
5.3
5.4
International Clinical Trial Registries ....................................................................................... 17
Veterinary Drugs, Biologics and Feeds..................................................................................... 17

6.1
Canada ................................................................................................................................... 17
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6.1.1
Veterinary Biologics .......................................................................................................... 18
6.1.2
Novel Animal Feeds.......................................................................................................... 18
6.2
United States .......................................................................................................................... 18
6.2.1
Veterinary Biologics .......................................................................................................... 19
6.2.2
Animal Feeds.................................................................................................................... 19
6.3
Note:
- Unless otherwise noted all resources in sections for Canada are from Health Canada.
- Canadian consolidated Acts and regulations are sourced from the Justice Laws Website at the Department of
-
Justice.
The U.S. Code of Federal Regulations (CFR) and other US regulations are sourced from FDsys, GPOs
Federal Digital System which replaces GPO Access. Access is also available through e-CFR but it is not an
official legal edition of CFR.
CFR is an annual publication that codifies the general and permanent rules published in the Federal Register
by the departments and agencies of the Federal Government. It is divided into 50 titles that represent broad
areas subject to Federal regulation. C.F.R. 9 revised January 1 and C.F.R 21 revised as of April 1 are the two
primary regulations referred to in this document. To find the CFR titles on FDsys it is best to use the Retrieve
by Citation, if you know the title and part or section numbers. Option is listed under Advanced Search on
FDsys home page search box.
European Community (EC) regulations are covered, not the individual Member State regulations. Community
legislation referred to in this document includes both regulations and directives. Regulations are laws that
take effect in all Member States, while directives are binding on the Member States to achieve the result
through their own legal framework.
EC regulations and directives are sourced from EUR-Lex, the European Union law site. For this guide the
permanent link to the Directive or Regulation was used. This will retrieve the main record with the record
history and text of the legislation. The record includes links to any amendments should include a link to the
latest consolidated version in PDF, if available.
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1 Introduction
This resource guide was developed as a tool to facilitate easy access to regulatory information for
nutraceutical and functional food product development and marketing. It provides links to selected
Canadian, U.S. and European information resources for the laws and regulations that pertain to
nutraceuticals and related products. These information resources also include links to guidance
documents and databases or listings for approved products and clinical trials. Other subject areas such
as pharmaceuticals, biologics and veterinary drugs are covered where they relate to nutraceuticals and
functional foods.
There is no global uniformity for regulating
nutraceuticals. Approaches vary by country
and Canada, the U.S. and Europe do not
have regulations that specifically refer to
nutraceuticals or functional foods. Instead
regulations refer to such categories as
natural health products, dietary/food
supplements or novel foods. Definitions vary
and deciding where a product fits is often difficult
and dependent on national perceptions.
Nutraceuticals sits between food and
drugs, or pharmaceuticals, and depending
on the claims made and the countrys
legislation the nutraceutical may fall within
either drug or food regulations.
Regulation of nutraceuticals and functional foods is becoming more stringent. This means that
companies working in these areas will need to pay special attention to the regulations that affect their
products and watch for any new or revised regulations. Complying with regulations is often a complex
effort that may require advice from regulatory specialists.
Two sources for monitoring the regulatory environment are the Regulatory and Legislation section of
New Hope 360 1, and Nutraceuticals World. For the second source you need to search the site for
regulation related items. The site's search only allows for a single term or a phrase. If you need more
precise information than it's best to use Google's site search capability, for example: china regulations
OR regulatory site:www.nutraceuticalsworld.com.
New Hope 360 is a digital marketplace providing information from various sources including Functional Ingredients
magazine.
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2 Nutraceuticals and Functional Foods

2.1 Canada
Although there are no standard definitions for nutraceuticals and functional foods, Health
Canada proposes the following definitions:
A nutraceutical is a product isolated or purified from foods that is generally sold in
medicinal forms not usually associated with food. A nutraceutical is demonstrated to
have a physiological benefit or provide protection against chronic disease.
A functional food is similar in appearance to, or may be, a conventional food, is
consumed as part of a usual diet, and is demonstrated to have physiological benefits
and/or reduce the risk of chronic disease beyond basic nutritional functions.
-
According to Health Canada (Section 3.1) there are no regulations dealing specifically with
nutraceuticals or functional foods. All foods and drugs fall under the provisions of the Food
and Drugs Act (R.S., 1985, c. F-27) and the Food and Drug Regulations (C.R.C., c.870).
They may be considered a drug if the claims made by the manufacturer meet the definition
of a drug. If a drug, then they are generally regulated as a subset of drugs under the Natural
Health Products Regulations (SOR/2003-196).
Additional information on Functional Foods and Nutraceuticals is available from Agriculture

and Agri-Food Canada.
2.1.1 Natural Health Products

Health Canada defines natural health products (NHPs) as
Vitamins and minerals
Herbal remedies
Homeopathic medicines
Traditional medicines such as traditional Chinese medicines
Probiotics, and
Other products like amino acids and essential fatty acids
Natural health product as defined in the Natural Health Products Regulations (SOR/2003196):
natural health product means a substance set out in Schedule 1 or a combination of
substances in which all the medicinal ingredients are substances set out in Schedule
1, a homeopathic medicine or a traditional medicine, that is manufactured, sold or
represented for use in
(a) the diagnosis, treatment, mitigation or prevention of a disease, disorder or
abnormal physical state or its symptoms in humans;
(b) restoring or correcting organic functions in humans; or
(c) modifying organic functions in humans, such as modifying those functions
in a manner that maintains or promotes health.
Substance components set out in Schedule 1 include plants, algae, bacteria, fungi, animal
products (human or otherwise), and homeopathic medicines, including probiotics, amino or
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Feb. 2012
fatty acids, vitamins, and minerals. NHPs may also comprise extracts, isolates, or synthetic
versions of the same substances.
Natural health products are considered to be a subset of "drugs" under the current Food and
Drugs Act.
-
Regulating authority for NHPs is the Natural Health Products Directorate (HHPD), Health
Products and Food Branch, Health Canada.
Natural Health Products main page.
The Natural Health Products Regulations (SOR/2003-196) (Canada Dept. of Justice)

contains requirements for manufacturing, packaging, labelling, storing, importing,
distributing and selling natural health products.
Overview of the Natural Health Products Regulations Guidance Document can be used to
determine whether a product is governed by the Natural Health Products Regulations.
Classification of Products at the Food-Natural Health Product Interface: Products in Food

Formats, Natural Health Products Directorate and Food Directorate, Health Canada, June
10, 2010. Food or natural health product? This guidance document can be used to help
determine if a product in a food format is a natural health product.
About Natural Health Product Regulation in Canada provides a more concise overview of
the topic, with links to key resources.
Health claims for natural health products, updated November 2010.
Natural Health Products guidance documents.
Good Manufacturing Practices Guidance Document, Natural Health Products Directorate,

Health Canada, August 2006, version 2.0.
NHPs Labelling Guidance Document is intended to help product license applicants

interpret the labelling and packaging requirements specified in Section 5 of the Natural
Health Products Regulations when selling a natural health product within Canada.
Clinical Trials for Natural Health Products guidance document.
Consumer Advertising Guidelines for Marketed Health Products (for Nonperscription

Drugs including Natural Health Products guidance document.
Licensed Natural Health Products Database searchable database of natural health

products that have been licensed for sale in Canada. Each product profile includes a list of
medicinal and non-medicinal ingredients.
Natural Health Products Ingredients Database (NHPID) searchable database of

acceptable medicinal and non-medicinal ingredients used in Natural Health Products.
Traditional Herbal Medicines guidance documents.
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2.1.2 Novel Foods
Novel foods are described by Health Canada as:
- Foods resulting from a process not previously used for food;
- Products that do not have a history of safe use as a food (that is, products that
have never been used as food); or
- Foods that have been modified by genetic manipulation, also known as genetically
modified foods, GM foods, genetically engineered foods or biotechnology-derived
foods.
Nutraceuticals or functional foods may, every now and then, fit within this definition.
-
Genetically modified (GM) food and novel foods are regulated by Health Canada under
Division 28 of the Food and Drug Regulations (C.R.C., c. 870).
Novel foods guidance documents.
Guidelines for the Safety Assessment of Novel Foods, Food Directorate, Health Products
and Food Branch, Health Canada, June 2006.
Frequently Asked Questions - Biotechnology and Genetically Modified Foods (and other
novel foods, including labelling).
Novel Food Decisions Approved Products a list of approved GM foods and novel
foods.
2.2 United States

In the US herbs and botanicals are regulated under dietary supplements.
2.2.1 Dietary supplements

The Dietary Supplement Health and Education Act of 1994 defines a dietary supplement as a
product taken by mouth that contains a dietary ingredient that supplements the diet. The dietary
ingredients may include vitamins, minerals, herbs or other botanicals, amino acids, and
substances such as enzymes, organ tissues, glandulars, and metabolites. Whether the dietary
supplement is in powder or liquid or other form, the DSHEA places dietary supplements in a
special category under the general umbrella of "foods," not drugs, and requires that every
supplement be labelled a dietary supplement.
-
Dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) under
the under the Dietary Supplement Health and Education Act of 1994 (DSHEA).
Regulations for dietary supplements are codified in the Code of Federal Regulations (Title
21) Food and Drugs. These are in various sections and can be found by searching for
dietary supplements. The regulations pertain mainly to labelling.
Dietary supplements Industry Information and Regulations, principal regulations that

govern the labelling and claims for dietary supplements.
Dietary Supplements Regulations & Laws, including Current Good Manufacturing

Practices (CGMPs).
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Feb. 2012
Dietary Supplement Labeling provides requirements and guidance for labelling and
making claims for supplements (e.g. qualified and structure/function claims).
Dietary Supplements Labels Database of the National Library of Medicine provides

information about label ingredients in more than 6,000 selected brands of dietary
supplements.
Guidance for Industry: Dietary Supplement Labeling Guide, Center for Food Safety and
Applied Nutrition (CFSAN), FDA, April 2005.
Guidance for Industry: Questions and Answers Regarding the Labeling of Dietary
Supplements as Required by the Dietary Supplement and Nonprescription Drug Consumer
Protection Act, FDA, December 2007; Revised December 2008 and September 2009
Guide to Nutrition Labeling and Education Act (NLEA) Requirements, FDA, August 1994.
Summary of qualified health claims for food and dietary supplements.
Health Claims Meeting Significant Scientific Agreement (SSA) provides guidance

documents and listing for approved food and dietary supplement health claims.
If a botanical dietary supplement is intended for use in the diagnosis, cure, mitigation,
treatment or prevention of disease in humans then it is investigated as a new drug and
subject to drug regulations, see Frequently Asked Questions on Botanical Drug Product
Development.
Safety of dietary supplements is the responsibility of the manufacturer. Once a product is

marketed the FDA can only restrict or remove a product from the marketplace by showing
that a dietary supplement is unsafe. See Guidance for Industry: Questions and Answers
Regarding Adverse Event Reporting and Recordkeeping for Dietary Supplements as
Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act.
FDA, October 2007; Revised June 2009.
Some food ingredients are classified as "generally recognized as safe" or "GRAS.

Information on GRAS at FDA.
GRAS Notice Inventory inventory of GRAS notices filed since 1998. Can search by
substance or browse listing. Data includes the basic GRAS records and FDAs letter
describing there response, if no longer pending.
GRAS Substances (SCOGS) Database (see link to Launch Database at the bottom of
the page) - provides opinions and conclusions from 115 SCOGS 2 reports published
between 1972-1980 on the safety of over 370 Generally Recognized As Safe (GRAS) food
substances.
Guidance for Industry: Frequently Asked Questions about GRAS.
Select Committee on GRAS Substances (SCOGS)
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2.3 European Community
In the European Community, nutraceuticals are at the boundary between drugs and food.
-
Nutraceutical products with specific therapeutic claims are considered drugs see Section
3.3 in this document.
Nutraceutical products with non-therapeutic claims are regulated independently by member

states, most often falling under food regulations and standards.
The EU legislation does not specifically reference nutraceuticals or functional foods. Instead
there is EU legislation on food supplements and novel foods.
Herbal medicinal products are covered in Section 3.3.2 in this document.
Non-medicinal herbal products can be regulated as foods or food supplements.
2.3.1 Food Supplements

A food supplement is defined in Directive 2002/46/EC 3 as:
(a) food supplements means foodstuffs the purpose of which is to supplement the
normal diet and which are concentrated sources of nutrients or other substances with a
nutritional or physiological effect, alone or in combination, marketed in dose form,
namely forms such as capsules, pastilles, tablets, pills and other similar forms, sachets
of powder, ampoules of liquids, drop dispensing bottles, and other similar forms of
liquids and powders designed to be taken in measured small unit quantities;
(b) nutrients means the following substances:
(i) vitamins,
(ii) minerals.
-
According to the definition, food supplements are subject to Regulations that cover
foodstuffs except where specifically provided for in the food supplements legislation.
To fall under the food supplements legislation, Directive 2002/46/EC, the product must be in
concentrated form and in measured small unit quantities. Otherwise, the food law regulation,
Regulation (EC) No 178/2002 4 would apply.
Nutrition and health claims are regulated under Regulation (EC) No 1924/2006. 5 The
regulation allows for three functional claims: general function claims are covered in Article
13.1; new function claims are covered in Article 13.5; and claims on disease risk reduction
and claims referring to children's development and health are covered in Article 14.
Health claims must be submitted to the European Food Safety Authority (EFSA) for
evaluation Guidance for applicants on health claims.
Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the
Member States relating to food supplements
Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general
principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in
matters of food safety
Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health
claims made on foods
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-
Health claims assessed by the European Food Safety Authority (EFSA) for which the
authorisation procedure is finished may be found in the EU Register on nutrition and health
claims made on food. Includes authorised and rejected health claims.
2.3.2 Novel Foods

Novel foods are defined in Regulation (EC) No 258/97 6 as:
Novel foods are foods and food ingredients that have not been used for human
consumption to a significant degree within the Community before 15 May 1997 and
which fall under various categories.
-
Rules for safety assessment of novel foods and novel food ingredients are covered by
Regulation (EC) No 258/97.
Novel Foods and novel food ingredients main page
Novel Foods and novel food ingredients Review of Regulation (EC) 258/97.
List of Commission Decisions authorising the placing on the market of novel food.
The Novel Food Catalogue is a listing of foods and food ingredients that has been
collected since the Novel Food Regulation (Regulation 258/97/EC) entered into force is in
three parts. The document also may contain information on the history of use by Member
States of food supplements and ingredients used exclusively in food supplements. See link
to Novel food catalogue at the bottom of the page.
3 Drugs / Pharmaceuticals
3.1 Canada
Drugs as defined in the Food and Drugs Act (R.S., 1985, c. F-27), Canada Dept. of Justice:
drug includes any substance or mixture of substances manufactured, sold or
represented for use in
(a) the diagnosis, treatment, mitigation or prevention of a disease, disorder or
abnormal physical state, or its symptoms, in human beings or animals,
(b) restoring, correcting or modifying organic functions in human beings or
animals, or
(c) disinfection in premises in which food is manufactured, prepared or kept;
-
Food and Drug Regulations (C.R.C., c.870), Canada Dept. of Justice.
Guidance Documents for drug products provide interpretation of policies and governing
statues and regulations.
Good Manufacturing Practices (GMP) Guidelines - 2009 Edition (GUI-0001). The

guidelines apply to pharmaceutical, radiopharmaceutical, biological, and veterinary drugs.
Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997 concerning novel foods and
novel food ingredients
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-
Drug Product Database product specific information on drugs approved for use in
Canada; includes human pharmaceutical and biological drugs, veterinary drugs and
disinfectant products.
3.2 United States

Drug is defined in section 201(g)(1) of the Federal Food, Drug, and Cosmetic Act as:
The term "drug" means (A) articles recognized in the official United States
Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official
National Formulary, or any supplement to any of them; and (B) articles intended for
use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or
other animals; and (C) articles (other than food) intended to affect the structure or any
function of the body of man or other animals; and (D) articles intended for use as a
component of any article specified in clause (A), (B), or (C).
-
The U.S. Food and Drug Administration (FDA) regulates all drugs through the Federal Food,
Drug, and Cosmetic Act and its amendments.
Drug regulations are codified in the Code of Federal Regulations (Title 21) Food and Drugs.
Regulations specific to new drug applications can be found in Part 310 of the C.F.R. 21.
Within the FDA, the Center for Drug Evaluation and Research (CDER) is responsible for
drug products.
Form and submission requirements for new drugs Investigational New Drugs (IND) and
New Drug Applications (NDA) stages, as well as forms for orphan drugs and generic drug
products.
Good manufacturing practice (GMP) documents for drugs.
CDER and other FDA drug guidance documents.
Guidance for Industry: Botanical Drug Products, CDER, June 2004. (PDF 347KB / 52
pages)
Frequently Asked Questions on Botanical Drug Product Development.
FDA Basics for Industry a new website launched Jan 2011 by the FDA to help companies
and others with basic information on the regulatory process. This site pulls together
information from the regular FDA site, making it easier for industry to locate what they need.
Drugs @ FDA database of approved brand name and generic prescription and over-thecounter human drugs and biological therapeutic products. Records provide brief product
information such as active ingredients, company name, approval date and approval
documents.
Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations

prescription, over-the-counter and discontinued drug products database. Records provide
brief product information.
Stay informed on drug topics through FDA e-mail alerts, news feeds and podcasts.
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3.3.1 Medicinal Products
Medicinal product is defined in Directive 2001/83/EC 7 as:
(a) Any substance or combination of substances presented as having properties for
treating or preventing disease in human beings; or
(b) any substance or combination of substances which may be used in or
administered to human beings either with a view to restoring, correcting or modifying
physiological functions by exerting a pharmacological, immunological or metabolic
action, or to making a medical diagnosis.
The substance may be human, animal, vegetable or chemical.
-
The European Medicines Agency (EMA) is responsible for the evaluation of human and
veterinary medicines developed by pharmaceutical companies for use in the European
Union. The scientific evaluations of human medicines are carried out by the Committee for
Medicinal Products for Human Use (CHMP).
EU legislation and procedures for the regulation of medicinal products for human use see
Volumes 1 and 2-4 and 9-10 of The Rules Governing Medicinal Products in the European
Union.
The primary EU legislation is Regulation (EC) No 726/2004 of the European Parliament and
of the Council of 31 March 2004 laying down Community procedures for the authorisation
and supervision of medicinal products for human and veterinary use and establishing a
European Medicines Agency.
Human medicines: Regulatory and procedural guidance index.
European Public Assessment Reports (EPARs) for human medicines that have been
granted a Community marketing authorisation by the European Commission. Search options
for this database include browse by therapeutic area. Records provide extensive
information.
3.3.2 Herbal Medicinal Products

Directive 2004/24/EC 8 provides definitions for herbal medicinal products, herbal preparations
and herbal substances.
-
Herbal medicinal product: Any medicinal product, exclusively containing as active

ingredients one or more herbal substances or one or more herbal preparations, or one or
more such herbal substances in combination with one or more such herbal preparations.
Herbal substances: All mainly whole, fragmented or cut plants, plant parts, algae, fungi,
lichen in an unprocessed, usually dried, form, but sometimes fresh. Certain exudates that
have not been subjected to a specific treatment are also considered to be herbal
substances. Herbal substances are precisely defined by the plant part used and the
Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to
medicinal products for human use
8
Directive 2004/24/EC of the European Parliament and of the Council of 31 March 2004 amending, as regards traditional
herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use
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Feb. 2012
botanical name according to the binomial system (genus, species, variety and author).
-
Herbal preparations: Preparations obtained by subjecting herbal substances to treatments

such as extraction, distillation, expression, fractionation, purification, concentration or
fermentation. These include comminuted or powdered herbal substances, tinctures,
extracts, essential oils, expressed juices and processed exudates.
EMAs Committee on Herbal Medicinal Products (HMPC) prepares the Community list of
herbal substances, preparations and combinations thereof for use in traditional herbal
medicinal products, and establishes Community herbal monographs.
Herbal medicinal products: Regulatory and procedural guidance documents see

specifically: Directive 2004/24/EC of the European Parliament and of the Council of 31
March 2004 amending, as regards traditional herbal medicinal products, Directive
2001/83/EC on the Community code relating to medicinal products for human use.
Additional information can be found on the EMAs main page for Herbal Medicinal Products.
Database of herbal substances designated for assessment by the European Medicines

Agency's Committee on Herbal Medicinal Products (HMPC). Records with final status can
include key documents such as herbal monographs and assessment reports.
Non-medicinal herbal products are regulated as foods or food supplements see Section
2.3.1 in this document.
3.3.3 Orphan Medicinal Product

Orphan medicinal product is defined in Regulation (EC) No 141/2000 9 as:
A medicinal product shall be designated as an orphan medicinal product if its sponsor can
establish:
that it is intended for the diagnosis, prevention or treatment of a life-threatening or
chronically debilitating condition affecting not more than five in 10 thousand persons
in the Community when the application is made, or
that it is intended for the diagnosis, prevention or treatment of a lifethreatening, seriously debilitating or serious and chronic condition in the
Community and that without incentives it is unlikely that the marketing of the
medicinal product in the Community would generate sufficient return to justify
the necessary investment; and
that there exists no satisfactory method of diagnosis, prevention or treatment of the
condition in question that has been authorised in the Community or, if such method
exists, that the medicinal product will be of significant benefit to those affected by that
condition.
-
Orphans: Regulatory and procedural guidance documents see specifically Regulation

(EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on
orphan medicinal products.
Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal
products
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Feb. 2012
-
EMAs Committee for Orphan Medicinal Products (COMP) is responsible for reviewing
applications from persons or companies seeking 'orphan medicinal product designation' for
products they intend to develop for the diagnosis, prevention or treatment of life-threatening
or very serious conditions.
3.3.4 Paediatric Medicine

Paediatric medicine is defined in Regulation (EC) No 1901/2006 10 as:
'medicinal product authorised for a paediatric indication means a medicinal product
which is authorised for use in part or all of the paediatric population and in respect of
which the details of the authorised indication are specified in the summary of the
product characteristics drawn up in accordance with Article 11 of Directive
2001/83/EC.
-
Paediatric medicines: EU Paediatric Regulation.
The main responsibility of the EMAs Paediatric Committee (PDCO) is to assess the content
of paediatric investigation plans and adopt opinions on them in accordance with Regulation
(EC) 1901/2006 as amended.
4 Biologics and Subsequent Entry Biologics (Biosimilars)

4.1 Canada
Biologics are derived from natural sources humans, animals or microorganisms. They
include a wide range of products such as vaccines, blood or blood components, cytokines,
monoclonal antibodies, proteins, and gene therapy products. They are considered a subset of
drugs, but have a slightly different regulatory approach. This is due, in large part, to their
molecular complexity and their sensitivity to changes in storage or the manufacturing process
--- as a result, much more emphasis is placed on the manufacturing process and on quality
control. Health Canada
A Subsequent Entry Biologic is a biologic drug that enters the market subsequent to a
version previously authorized in Canada, and with demonstrated similarity to a reference
biologic drug. A subsequent entry biologic relies in part on prior information regarding safety
and efficacy that is deemed relevant due to the demonstration of similarity to the reference
biologic drug and which influences the amount and type of original data required. Health
Canada
-
Regulatory responsibility for biologics is with Health Canadas Biologics and Genetic
Therapies Directorate.
Regulatory initiatives for Biologics, Radiopharmaceuticals and Genetic Therapies.
Vaccine regulation regulatory initiatives.
10
Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products
for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation
(EC) No 726/2004
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Feb. 2012
-
Blood and Blood Components regulatory initiatives.
Cells, Tissues, and Organs for Transplantation and Assisted Human Reproduction
regulatory initiatives.
Fact Sheet for Subsequent Entry Biologics in Canada.
Guidance documents for Subsequent Entry Biologics (SEBs).
Annex 2 to the Current Edition of the Good Manufacturing Practices Guidelines Schedule
D Drugs (Biological Drugs) (GUI-0027) provides GMP for biological drugs.
4.2 United States

Biological products include a wide range of products such as allergenics, blood and blood
components, gene therapy, human tissues and cellular products, vaccines, and
xenotransplantation products. FDA
Follow-on protein products refers to proteins and peptides that are intended to be
sufficiently similar to a product already approved under the Federal Food, Drug, and
Cosmetic Act or licensed under the Public Health Service Act to permit the applicant to rely
on certain existing scientific knowledge about the safety and effectiveness of the approved
protein product. FDA. This is equivalent to Canadas subsequent entry biologics or the EUs
biosimilars.
-
The Center for Biologics Evaluation and Research (CBER) is the Center within FDA that
regulates biological products for human use, under various laws, including the Public Health
Service Act and the Federal Food, Drug, and Cosmetic Act and its amendments.
Regulations specific to biological products can be found starting in Part 600 of the Code of
Federal Regulations (Title 21) Food and Drugs. C.F.R.21 defines biological products as any
virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention,
treatment or cure of diseases or injuries of man.
Biologics Guidance, Compliance & Regulatory Information.
Follow-on protein products, compilation of presentations, and public comments on scientific

and regulatory issues related to the development of follow-on protein products.
Human Cell and Tissue Establishment Registration (HCTERS) Public Query Application
database of registered, inactive and pre-registered human cells, tissue, and cellular and
tissue-based product establishments.
Stay informed on biologics by subscribing to biologics mailing lists. This listing for FDA
news feeds includes one specific to Vaccines, Blood and Biologics.
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Advanced therapy medicinal product is defined in Regulation (EC) No 1394/2007 11 as any
tissue engineered products, gene therapy medicinal products, or somatic cell medicinal
products for human use.
-
The European Medicines Agencys (EMA) Committee for Advanced Therapies (CAT) is
responsible for the scientific evaluation of ATMP marketing authorisation applications
submitted by pharmaceutical companies. CAT prepares a draft opinion which is submitted to
EMAs Committee for Medicinal Products for Human Use (CHMP), the committee
responsible for human medicines at the Agency.
Advanced therapies: Regulatory and procedural guidance documents.
Scientific guidelines on gene therapy and on cell therapy and tissue engineering are
available to help applicants prepare marketing-authorisation for advanced therapy medicinal
products.
5 Clinical Trials
5.1 Canada
-
Clinical trials guidance documents Health Canada.
Clinical Trials Manual.
Clinical Trials for Natural Health Products guidance document.
5.2 United States

-
Running clinical trials: Regulations.
Running clinical trials: Guidance documents.
Running clinical trials: Draft regulations and guidances.

-
EudraCT is a database of information on the content, commencement and termination of all

clinical trials in the European Union (from 1 May 2004 onwards). It was established in
accordance with Directive 2001/20/EC, and is managed by the European Medicines
Agency. This is not a searchable database. It functions as a system to obtain a EudraCT
number and submit clinical trial application forms.
Clinical trials guidelines volume 10 of The Rules Governing Medicinal Products in the
European Union.
11
Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy
medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
Page 16 of 20

Feb. 2012
5.4 International Clinical Trial Registries
-
NIH ClinicalTrials.gov Register of federally and privately supported clinical trials conducted
in the United States and around the world.
Current Controlled Trials search and register clinical trials, can also search across multiple
clinical trial registers (ISRCTN registers and ClinicalTrials.gov.
International Clinical Trials Registry Platform (ICTRP) World Health Organization; includes
data sets from ClinicalTrials.gov, ISRCTN and other national registries like the Australia
New Zealand Clinical Trials Registry.
6 Veterinary Drugs, Biologics and Feeds

6.1 Canada
Veterinary drugs are defined in the Food and Drugs Act and fall under the general definition
of a drug see Section 5.1 in this document.
Canadian Food Inspection Agency (CFIA) describes a veterinary biologic as:
- a helminth, protozoa or micro-organism,
- a substance or mixture of substances derived from animals, helminths, protozoa
or micro-organisms, or
- a substance of synthetic origin
that is manufactured, sold or represented for use in restoring, correcting or modifying
organic functions in animals or for use in the diagnosis, treatment, mitigation or
prevention of a disease, disorder, abnormal physical state, or the symptoms thereof,
in animals. Veterinary biologics include vaccines, bacterins, bacterin-toxoids,
immunoglobulin products, diagnostics kits, and any veterinary biologic derived
through biotechnology. (definition based on the Health of Animals Act (1990, c. 21))
CFIA describes novel feeds as feeds composed of or derived from microorganisms, plants
or animal sources that:
(a) are not approved as livestock feed in Canada (not listed in Schedule IV or V of the
Feeds Regulations)
(b)and/or contain a novel trait
Novel feeds include microbial products (e.g. forage inoculants, fermentation products)
plants with novel traits, and plants with no history of use as feed, and products/byproducts of biotechnology-derived animals. (definition based on the Feeds
Regulations, 1983 (SOR/83-593))
-
The Veterinary Drugs Directorate of Health Canada evaluates and monitors the safety and
efficacy of veterinary drugs in Canada under the Food and Drugs Act (R.S., 1985, c. F-27)
and the Food and Drug Regulations (C.R.C., c.870).
Veterinary drugs: Guidance documents and veterinary drug approval process.
All Veterinary Natural Health Products are considered drugs under the Food and Drug
Regulations and are subject to Division 8 requirements of the Regulations.
Search the Drug Product Database to find veterinary drugs approved for use in Canada.
Page 17 of 20

Feb. 2012
6.1.1 Veterinary Biologics
-
The Canadian Food Inspection Agency (CFIA) is responsible for regulating and licensing
veterinary biologics and veterinary biologics manufacturing facilities in Canada, under the
Health of Animals (1990, c. 21) Act and the Health of Animals Regulations (C.R.C., c. 296).
Veterinary biologics: Guidance document and forms.
Veterinary biologics licensed in Canada list by species and by manufacturer.
6.1.2 Novel Animal Feeds

-
CFIA also regulates novel livestock feeds under the Feeds Act (R.S., 1985, c. F-9) and the
Feeds Regulations, 1983 (SOR/83-593).
Novel Feeds information at CFIA Novel feeds including frequently asked questions.
6.2 United States

As defined by section 201(v) of the Federal Food, Drug, and Cosmetic Act.
The term "new animal drug" means any drug intended for use for animals other than
man, including any drug intended for use in animal feed but not including such animal
feed.
As defined by section 201(w) of the Federal Food, Drug, and Cosmetic Act),
The term "animal feed" means an article which is intended for use for food for animals
other than man and which is intended for use as a substantial source of nutrients in
the diet of the animal, and is not limited to a mixture intended to be the sole ration of
the animal.
Veterinary biologics are vaccines, bacterins, diagnostics, etc, which are used to prevent,
treat, or diagnose animal diseases.
The Center for Veterinary Medicine (CVM), within the FDA, regulates new drugs intended for
animal use under the Federal Food, Drug, and Cosmetic Act and its amendments. The
responsible office within CVM is the Office of New Animal Drug Evaluation (ONADE).
Animal drug regulations are codified in the Code of Federal Regulations (Title 21) Food and
Drugs. Regulations specific to new animal drug applications can be found in Part 514 (PDF /
36 pages) of the C.F.R. 21. Parts 500 to 599 in Subchapter E Animal drugs, feeds and
related products (PDF: 2 MB / 582 pages) may also apply.
New Animal Drug Application: Guidance documents.
Animal Drugs @ FDA database of all animal drugs approved for safety and effectiveness.
Page includes links to the eight sections of the Green Book. Records provide product
details including dosage.
Page 18 of 20

Feb. 2012
6.2.1 Veterinary Biologics
-
The Animal and Plant Health Inspection Service (APHIS) regulates veterinary biologics
(vaccines, bacterins, antisera, diagnostic kits, and other products of biological origin) under
the Virus-Serum-Toxin Act (PDF: 17KB) and the Code of Federal Regulations (Title 9)
Animals and Animal Products, Chapter 1, Parts 101 t0 123. Also available as Subchapter E
Viruses, serums, toxins, and analogous products; organisms and vectors (Parts 101-124).
(PDF: 810KB / 195 pages, January 1, 2011).
Veterinary biologics: Regulations and guidance documents.
6.2.2 Animal Feeds

-
Animal feeds are regulated by the Division of Animal Feeds of the CVM, as covered by the
Federal Food Drug and Cosmetic Act (which defines food as "articles used for food or drink
for man or other animals"). Therefore, supplements or additives to animal feeds are
considered foods, food additives, or new animal drugs depending on the intended use.
Mills that manufacture medicated feed must be licensed per the Animal Drug Availability
Act of 1996 and its regulations as codified in the Code of Federal Regulations (Title 21)
Food and Drugs, Part 515 Medicated feed mill license. (PDF: / 5 pages, April 1, 2011).
Guidance for Industry #120: Veterinary Feed Directive Regulation Questions and Answers
(PDF / 11 pages), March 26, 2009.

Veterinary medicinal product is defined in Directive 2001/82/EC 12 as:
a) Any substance or combination of substances presented as having properties for
treating or preventing disease in animals; or
b) any substance or combination of substances which may be used in or administered
to animals with a view either to restoring, correcting or modifying physiological
functions by exerting a pharmacological, immunological or metabolic action, or to
making a medical diagnosis.
The substance may be human, animal, vegetable or chemical.
-
The European Medicines Agency (EMA) is responsible for the evaluation of human and
veterinary medicines developed by pharmaceutical companies for use in the European
Union. The scientific evaluations of veterinary medicines are carried out by the Committee
for Medicinal Products for Veterinary Use (CVMP).
EU legislation and procedures for the regulation of medicinal products for veterinary use
see Volumes 4 and 5-9 of The Rules Governing Medicinal Products in the European Union.
European Medicines Agencys collection of information relating to veterinary medicines and

their regulation.
12
Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating
to veterinary medicinal products
Page 19 of 20

Feb. 2012
-
European Public Assessment Reports (EPARs) for veterinary medicines that have been
granted a Community marketing authorisation by the European Commission. Search options
for this database include browse by species. Records provide extensive information.
Page 20 of 20

Regulatory Information Resources For Nutraceuticals and Functional Foods: Resource Guide

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Regulatory Information

Resources for Nutraceuticals

NRC-IRAP, Atlantic & Nunavut region

Mary Veling, Information Specialist, NRC-CISTI

Valerie Baker, Technical Business Analyst, NRC-IRAP

February 2012 (replaces August 2011 version)

2012 National Research Council of Canada

Regulatory Information Resources for Nutraceuticals &

Nutraceuticals and Functional Foods ......................................................................................... 5

Natural Health Products ...................................................................................................... 5

Novel Foods ....................................................................................................................... 7

United States ............................................................................................................................ 7

Dietary supplements ........................................................................................................... 7

European Community ............................................................................................................... 9

Food Supplements ............................................................................................................. 9

Novel Foods ..................................................................................................................... 10

Drugs / Pharmaceuticals ............................................................................................................ 10

United States .......................................................................................................................... 11

European Community ............................................................................................................. 12

Medicinal Products ........................................................................................................... 12

Herbal Medicinal Products ................................................................................................ 12

Orphan Medicinal Product ................................................................................................ 13

Paediatric Medicine .......................................................................................................... 14

Biologics and Subsequent Entry Biologics (Biosimilars) ........................................................ 14

United States .......................................................................................................................... 15

European Community ............................................................................................................. 16

Clinical Trials .............................................................................................................................. 16

United States .......................................................................................................................... 16

European Community ............................................................................................................. 16

International Clinical Trial Registries ....................................................................................... 17

Veterinary Drugs, Biologics and Feeds..................................................................................... 17

Regulatory Information Resources for Nutraceuticals &

Veterinary Biologics .......................................................................................................... 18

Novel Animal Feeds.......................................................................................................... 18

United States .......................................................................................................................... 18

Veterinary Biologics .......................................................................................................... 19

European Community ............................................................................................................. 19

Regulatory Information Resources for Nutraceuticals &

Regulatory Information Resources for Nutraceuticals &

2 Nutraceuticals and Functional Foods

Additional information on Functional Foods and Nutraceuticals is available from Agriculture

2.1.1 Natural Health Products

Regulatory Information Resources for Nutraceuticals &

Natural Health Products main page.

The Natural Health Products Regulations (SOR/2003-196) (Canada Dept. of Justice)

Classification of Products at the Food-Natural Health Product Interface: Products in Food

Health claims for natural health products, updated November 2010.

Natural Health Products guidance documents.

Good Manufacturing Practices Guidance Document, Natural Health Products Directorate,

NHPs Labelling Guidance Document is intended to help product license applicants

Clinical Trials for Natural Health Products guidance document.

Consumer Advertising Guidelines for Marketed Health Products (for Nonperscription

Licensed Natural Health Products Database searchable database of natural health

Natural Health Products Ingredients Database (NHPID) searchable database of

Traditional Herbal Medicines guidance documents.

Regulatory Information Resources for Nutraceuticals &

Novel foods guidance documents.

2.2 United States

2.2.1 Dietary supplements

Dietary supplements Industry Information and Regulations, principal regulations that

Dietary Supplements Regulations & Laws, including Current Good Manufacturing

Regulatory Information Resources for Nutraceuticals &

Dietary Supplements Labels Database of the National Library of Medicine provides