Europe

The European Union has developed the “Directive on Food Supplements,” which has been adopted by the European Parliament and took effect in August of 2005. The 25 countries that make up the European Union implemented the directive, which contains a “positive list” of vitamin and mineral ingredients that are allowed in food supplements.

The Codex Alimentarius Commission, a joint project of the Food and Agricultural Organization of the United Nations and the WHO, also adopted international guidelines on vitamin and mineral food supplements in the Summer of 2005. The Draft Guidelines for Vitamin and Mineral Food Supplements include “other ingredients,” which may include herbs when included in a supplement. Food supplements that include herbal ingredients “should also be in conformity with the specific rules on vitamins and minerals.” In addition, the World Trade Organization has developed an international Agreement on the Application of Sanitary and Phytosanitary Measures, which defines standards for food safety, veterinary drug and pesticide residues, contaminants, methods of analysis and sampling, and codes and guidelines for hygienic practice (American Herbal Products Association, 2005).

The European Agency for the Evaluation of Medicinal Products has developed guidance documents for Human and Veterinary Medicinal Product Quality (European Agency for the Evaluation of Medicinal Products, 2001). Guidance includes qualitative and quantitative measures of active substances; description of preparation methods, material controls, intermediate and finished testing procedures, and final stability tests.

The same agency has also developed guidelines on specifications, test procedures, and acceptance criteria for herbal medicinal products, herbal drugs, and herbal drug preparations (European Agency for the Evaluation of Medicinal Products, 2001). The document provides a uniform set of specifications for herbal products.

To further the standardization effort and to increase European scientific support, the phytotherapy societies of Austria, Denmark, Belgium, France, Germany, Ireland, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, Turkey, and the United Kingdom founded the European Societies’ Cooperative on Phytotherapy (ESCOP). ESCOP objectives include: developing a coordinated framework to scientifically assess herbal medicines for humans, promoting their acceptance within general medical practices, and supporting phytotherapy research and the production of reference monographs.

China

Traditional Chinese Medicine production has been undergoing modernization, standardization, and internationalization efforts for the past 10 years. The “Five P’s” that have formed the basis for these changes are: Good Agricultural Practice (GAP), Good Manufacturing Practice (GMP), Good Laboratory Practice, Good Clinical Practice, and Good Selling Practice. The focus on certification and registration of herbal/TCM manufacturers has been strong. Good Manufacturing Practices are fundamental requirements for registration. China has more than 1500 herbal material manufacturers that have completed GMP certification. The GAP outlines environmental conditions; seeds and propagation materials; cultivation practices; harvesting and primary processing; packaging, transportation, and storage; quality control; personnel and equipment; and documentation requirements. Good Agricultural Practices are being implemented, with farmers and raw ingredient suppliers reaching full compliance by 2007 (Starling, 2003).

Japan

Japan has also developed Good Agricultural and Collection Practices for Medicinal Plants (GACP) 2003. The GACP provides technical guidance for the production of medicinal plant materials for crude drugs, finished crude drugs, and Kampo medicines. Areas covered include cultivation and collection of medicinal plants, postharvest processing, and quality control of plant materials. Reference standards for the GACP include the Japanese Pharmacopoeia and Japanese Standards for Herbal Medicines. The regulation of herbal products in Japan is similar to that for chemical drugs.

Africa

African nations have a wealth of natural resources and have developed a renewal program for their plant genetic resources (International Environmental Law Research Centre, 2002-2003). The focus of the program will be on agriculture, health and nutrition, environment, poverty alleviation, and scientific/technical research. Herbal medicine for human and animal health is strong in local cultures and traditions, where the ratio of traditional herbalists to villagers is 1:200. Up to 80% of rural populations depend on traditional medicine to meet their primary healthcare needs. Realizing the potential of scientific, health, and economic impact, the Plant Genetic Resources program simultaneously focuses on strengthening environmental conservation through the development of national and regional programs.

Australia

The Australian Register of Therapeutic Goods (ARTG) was established under the Therapeutic Goods Act (TGA) of 1989. The ARTG database contains two basic lists—medicines and medical devices. A search of the ARTG database reveals more than 1000 “herbal” products that have been registered. Australia has adopted the guidelines produced by the European Agency for the Evaluation of Medicinal Products. The guidance documents for Human and Veterinary Medicinal Product Quality (European Agency for the Evaluation of Medicinal Products, 2001) include qualitative and quantitative measures of active substances, description of preparation methods, material controls, intermediate and finished testing procedures, and final stability tests.

Australia has also adopted the same agency’s guidelines on specifications, test procedures and acceptance criteria for herbal medicinal products, herbal drugs, and herbal drug preparations (European Agency for the Evaluation of Medicinal Products, 2001). The document provides a uniform set of specifications for herbal products.

New Zealand

The regulation of herbal substances in New Zealand is the same as in Australia. This came about through the formation of a joint agency in December of 2003—the Trans-Tasman Therapeutic Products Agency—with full implementation in July of 2005. Core issues of the joint effort are identified in a consultation paper; these include definition of “herbal substance,” naming of herbally derived substances that do not meet the definition, regulation of complex and nontraditional herbal extracts, expression of dry/fresh weight equivalence, extracts, and the standardization of herbal ingredients. Key objectives of the Trans-Tasman Therapeutic Products Agency were to develop a regulatory scheme for products to safeguard public health and safety in both Australia and New Zealand and to facilitate trade and closer economic relations between these countries. Therefore, New Zealand uses the same guidance documents for Human and Veterinary Medicinal Product Quality as those produced by the European Agency for the Evaluation of Medicinal Products.

Canada

In January of 2004, the Natural Health Products (NHP) regulations came into effect. These regulations establish NHPs as a subset of drugs, and allow a 6-year transition period. Canadian regulatory oversight will include the following: (1) premarketing review and approval; (2) GMP; (3) a manufacturing site license; (4) clinical trial processes; and (5) a postmarketing surveillance program for adverse reactions.

United States of America

The regulatory status and quality control processes applied to herbal supplements for use in animals are topics that are confusing and involve issues that most people do not clearly understand. Further complicating these issues is the fact the regulatory situation is changing rapidly as discussions between industry participants and regulatory agencies continue; therefore, what is true today may not be true tomorrow.

Definitions

Background

Although supplements are commonly available for animals, similar to products available for human use, most people do not understand that there is no specific regulatory category for dietary supplements (herbal products) for animals. The timeline examines events that specifically created categorical recognition for human products now referred to as “dietary supplements,” and it explains why the human category does not apply to supplements for companion animals (Box 8-1).

Before President Clinton signed the Dietary Supplement Health Education Act, dietary supplements for humans were considered food or drugs. DSHEA created a specific category for dietary supplements and made allowances for these products to be legally marketed under certain provisions defined in the language of the bill. One of the primary items addressed the use of labeling claims. Overt drug claims that referred to a product involving the diagnosis, prevention, treatment, or ability to cure a disease were prohibited; however, claims involving a product’s ability to effect the “structure or function” of the body were allowed.

Although it was widely assumed, most people do not realize that DSHEA did not mention the use of these products for animals. Examination of the Congressional record suggests that the issue of products being useful for companion animals was simply not considered when language for the Bill was discussed. Nonetheless, because the benefit of these products for humans has been recognized, the animal supplement industry continues to grow, and the availability of various products for animals increases.

In today’s regulatory environment, in the absence of a specific category, supplements labeled for animals are considered animal feeds that contain unapproved ingredients or unapproved drugs, depending on intended use. In point of fact, neither category provides an appropriate or realistic pathway; however, the FDA/CVM further elaborated:

Many herbal ingredients have been given GRAS status by the FDA and the AAFCO and are categorized as feed additives, with their intended use defined as “spices and other natural seasonings and flavorings,” or “essential oils, oleoresins, and natural extractives” (AAFCO, 2004). The quantity of the ingredient added to animal food should not exceed the amount reasonably required to accomplish its intended physical, nutritional, or other technical effect in the food (FDA 21 CFR Sec 582.1). When GRAS ingredients with the intended uses listed previously are incorporated into an animal supplement with the purpose being to “effect the structure or any function of the body,” they are then considered by regulatory agencies to be unapproved ingredients, thereby causing the product to be “adulterated.” Intended use is designated by claims made by the manufacturer in labeling and advertising statements (US Dept of Health and Human Services, 2004). Although current regulations do not contain a category for these GRAS ingredients intended for use as “animal supplements affecting the animal’s body structure or function,” an appendix list has been included.

Many industry members have tried to label these products as animal feed, in following the recommendations of the AAFCO. This regulatory pathway is inappropriate; however, in the absence of a specific alternative, the animal feed category was viewed as the only viable choice and came with its own set of challenges. There is no consistency among State Feed Control Officials in regulating these products or ingredients. Companies that attempt to provide supplement products and comply with feed guidelines are faced with inconsistency among the states. In other words, one state may allow the products to be sold or may require specific labeling on a formula that may not be acceptable to another state. It is quite clear that providers cannot develop and sell different labeled product for each different state. Some states have taken a hard line stand in issuing “stop sale” orders to companies when products are found in distribution. In an extreme example, the State of Iowa issued the following directive on September 18, 2003:

Therefore, all products that contain unapproved feed ingredients labeled as animal feed would be removed from the marketplace. This crisis was averted because of a significant Grass Roots effort by the National Animal Supplement Council (www.nasc.cc) that focused on the State of Iowa.

What Exists Today?

More than 62% of American households own a nonhuman food chain (NHFC) animal (dog, cat, or horse) (American Pet Product Manufacturers, 2001), and 90% of veterinarians use supplements in their practice. Numerous studies indicate that about a third of these NHFC animals receive a daily dietary supplement (AVMA, 2002; Yankelovich Consultants, 2000; Healthy Pets 21 Consortium, 2001). Thus the rights of more than 20% of American households to give their horses, dogs, or cats supplements are affected by this issue.

Supplements used in NHFC animals closely resemble human dietary supplements, with ingredients such as glucosamine, methylsulfonyl methane (MSM), herbs, vitamins, and minerals. They are used by animal owners and veterinarians to assist with normal physiologic functions, enhance wellness, affect the structure/function of body tissues/systems, and—in the case of some products—avoid or forestall the need to euthanize their dog, cat, or horse.

In 1994, recognizing that an unpredictable, inconsistent, inappropriate regulatory pathway for dietary supplements was restricting access to products that had the potential to enhance wellness, Congress passed the Dietary Supplement Health Education Act (DSHEA). In 1996, while acknowledging that “the definition of dietary supplement in DSHEA does not explicitly state whether it includes or excludes animals other than man (Federal Register, 1996),” the FDA took the position that DSHEA should not apply to animals, citing arguments that relied largely on protection of the human food chain.

Because of the FDA’s interpretation, which made no distinction between “production” and NHFC animals, no viable regulatory framework or approval pathway exists for NHFC animal supplements. Depending on their intended use, NHFC animal supplements are sometimes regulated as animal feeds with unapproved ingredients (subject to enforcement under potentially 50 different feed laws) and in some cases are regulated by the FDA Center for Veterinary Medicine as unapproved animal drugs.

With regard to human supplements, the FDA has stated the following:

However, with regard to NHFC animal supplements, the CVM claims to be prevented from taking a similar approach because “DSHEA does not apply to animal products.” This inconsistency is a legislative oversight that finds no basis in logic.

A rational federal framework must be established to supersede the current ad hoc, patchwork regulatory policy applied to dietary supplements for NHFC animals, primarily dogs, cats, and horses. The present environment of high regulatory uncertainty—including “stop sale” orders from numerous state feed control officials—restricts consumer and possibly professional access to products and interferes with interstate commerce. Potentially imminent restrictions on animal owner access to products that are readily available for humans threaten to become an emotional issue affecting more than 20% of American households, but this can be avoided by a reasonable solution that accomplishes the objectives of all stakeholders.

Industry Efforts

Through the NASC, industry members have attempted to work within the existing framework to obtain “feed ingredient definitions” for both glucosamine and MSM—two substances with a significant history of safe use in both NHFC animals and humans. The FDA rejected both applications, indicating, “We do not believe it is in the public interest to regulate glucosamine as food or a food additive under the FFDCA (FDA, 2002),” and responded with similar language for MSM.

The new animal drug approval (NADA) process is currently industry’s only alternative and can cost many millions of dollars. Given the smaller market size, the rules against patenting natural ingredients, and the potential for substitution with similar human products that do not face such requirements, the business-limiting factors for animal supplement providers render the NADA process unrealistic.

In an attempt to address these issues, the National Animal Supplement Council, a nonprofit industry association representing approximately 70% of the industry, put forward a comprehensive program of industry self-regulation titled Compliance Plus, which was submitted in April of 2002 to both the FDA Center for Veterinary Medicine and AAFCO. Compliance Plus consists of four major initiatives:

NASC has promptly delivered on each of the commitments made in the Compliance Plus program. The FDA/CVM has attempted to respond to the cooperation from the NHFC supplement industry by regulating NHFC animal supplements with an intended use other than feed as “unapproved drugs of low regulatory priority.” However, this is not a viable long-term solution for several reasons: