Appendix A
Other Approaches to Considering the Safety of Dietary Supplements

The following text provides an overview of the different approaches taken by other groups to consider the safety of dietary supplements. Please note that the summaries reflect information published or provided by the organizations involved, and do not reflect judgments or endorsements of the committee.

AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

The Agency for Healthcare Research and Quality (AHRQ) of the U.S. Department of Health and Human Services aims to sponsor, conduct, and disseminate research to improve the quality and effectiveness of health care. Other federal agencies, private sector agencies, and Congress have asked AHRQ to review and evaluate the scientific information on specified topics to be used as the basis for clinical guidelines, performance measures, and other quality improvement tools. This AHRQ program is referred to as the Evidence-based Practice Centers, and it has produced “evidence reports” requested by other federal agencies on the effectiveness and safety of a limited number of dietary supplements. The San Antonio Evidence-based Practice Center (EPC) at the University of Texas Health Sciences Center, working under contract to AHRQ, has completed reports on garlic and milk thistle. In addition, the Southern California Evidence-based Practice Center/RAND is developing an evidence report on the clinical efficacy and side effects of ephedra.

The EPC evidence reports are based on a systematic analysis of the relevant scientific data. Other groups, such as the well-known Cochrane Collaboration, prepare and maintain similar evidence-based reviews. These reviews are based on a weighting/ranking methodology and are dependent on judgments that are based on well-defined criteria.

The first step of an AHRQ review is to identify relevant citations through what is intended to be an exhaustive search of the literature in a variety of electronic databases. Additional citations are identified from bibliographies, manufacturers, and technical experts. Both English and non-English references are included in the search. In general, only published full articles are used, but additional unpublished information provided by authors of published studies are also included.

Independent reviewers on the EPC staff read the titles and abstracts of all the identified citations and exclude those citations that do not meet certain selection criteria on types of participants, interventions, control groups, outcomes, and study designs. To assess adverse



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements Appendix A Other Approaches to Considering the Safety of Dietary Supplements The following text provides an overview of the different approaches taken by other groups to consider the safety of dietary supplements. Please note that the summaries reflect information published or provided by the organizations involved, and do not reflect judgments or endorsements of the committee. AGENCY FOR HEALTHCARE RESEARCH AND QUALITY The Agency for Healthcare Research and Quality (AHRQ) of the U.S. Department of Health and Human Services aims to sponsor, conduct, and disseminate research to improve the quality and effectiveness of health care. Other federal agencies, private sector agencies, and Congress have asked AHRQ to review and evaluate the scientific information on specified topics to be used as the basis for clinical guidelines, performance measures, and other quality improvement tools. This AHRQ program is referred to as the Evidence-based Practice Centers, and it has produced “evidence reports” requested by other federal agencies on the effectiveness and safety of a limited number of dietary supplements. The San Antonio Evidence-based Practice Center (EPC) at the University of Texas Health Sciences Center, working under contract to AHRQ, has completed reports on garlic and milk thistle. In addition, the Southern California Evidence-based Practice Center/RAND is developing an evidence report on the clinical efficacy and side effects of ephedra. The EPC evidence reports are based on a systematic analysis of the relevant scientific data. Other groups, such as the well-known Cochrane Collaboration, prepare and maintain similar evidence-based reviews. These reviews are based on a weighting/ranking methodology and are dependent on judgments that are based on well-defined criteria. The first step of an AHRQ review is to identify relevant citations through what is intended to be an exhaustive search of the literature in a variety of electronic databases. Additional citations are identified from bibliographies, manufacturers, and technical experts. Both English and non-English references are included in the search. In general, only published full articles are used, but additional unpublished information provided by authors of published studies are also included. Independent reviewers on the EPC staff read the titles and abstracts of all the identified citations and exclude those citations that do not meet certain selection criteria on types of participants, interventions, control groups, outcomes, and study designs. To assess adverse

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements clinical events, all types of human studies are used (e.g., randomized controlled trials, prospective trials, case-control, and cohort studies). Data are abstracted from the literature and analyzed by independent reviewers with clinical and methodological expertise. The analysis includes an assessment of the internal validity and quality of the studies. The data analysis includes generation of evidence tables, graphical summaries, statistical tests, and meta-analyses. The results and conclusions of the analyses are summarized in an evidence report that contains conclusions on the current knowledge on the efficacy and adverse effects of the substance and provides recommendations for future research. Reports are available on the AHRQ website (http://ahrq.gov). Nominations for clinical topics to be reviewed by an Evidence-based Practice Center are solicited through notices in the Federal Register. Topics must meet specific selection criteria including high incidence; significance for the needs of Medicare, Medicaid, or other federal health programs; high cost; controversy about effectiveness; and availability of scientific data. Based on this process, the dietary supplements milk thistle and garlic, in addition to over 70 other nondietary supplement topics, have been reviewed (AHRQ, 2002). U.S. PHARMACOPEIA-NATIONAL FORMULARY The U.S. Pharmacopeia-National Formulary (USP-NF) develops and provides standards of identity, strength, quality, purity, packaging, and labeling of drugs sold in the United States in the form of standards monographs; these standards monographs do not consider the inherent safety of the substance. The USP standards are recognized by Congress in the Federal Food, Drug, and Cosmetic Act of 1938 (21 U.S.C. § 321 et seq.) as the official compendium of the United States, making its established standards for drugs essentially similar to federal regulations (USP, 2002a). From its first publication in 1820, the USP contained monographs for hundreds of botanicals; however, most of them were removed by the end of the 1930s due to the changes in medical practices and the arrival of synthetic organic medicinal compounds in the U.S. marketplace. In 1990, in response to a USP Convention Resolution, the USP Committee of Revision, an independent body of elected scientific experts representing industry, academia, and government agencies, established public standards for vitamins, minerals, and their combination products. These standards monographs, along with general chapters that include manufacturing practices for nutritional supplements, were grouped together and published within a separate section of the USP called Nutritional Supplements. In 1995, after passage of the Dietary Supplement Health and Education Act (DSHEA), the USP Convention, in recognition of the resurgence in the use of botanicals by the American public, adopted a resolution that encouraged the USP Committee of Revision to establish public standards for botanical dietary supplements. In response to the Convention resolution, the USP Committee of Revision generated a list of approximately 20 widely used botanicals for public standards monographs. Criteria for identification of these botanicals included lack of safety risk, extent of use by consumers, interest from regulatory agencies, positive assessment by recognized pharmacognosists, and the ability of the botanical to meet typical requirements for USP monographs. History of traditional use and pharmacological action were also considered. Standards monographs are not developed for botanicals that the USP believes may be associated with a significant safety risk (USP, 2000a, 2002b).

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements Once a botanical has been approved for inclusion in the USP or NF13, analytical methods are requested from several manufacturers and reviewed by the USP Expert Committee relating to dietary supplements. Before official adoption into USP-NF, public comment on proposed standards is generated by publicizing them in Pharmacopoeia Forum (Personal communication, V.S.Srinivasan, U.S. Pharmacopeia, February 11, 2001). U.S. PHARMACOPEIA DIETARY SUPPLEMENT VERIFICATION PROGRAM Distinct from its monograph development program, the USP launched its Dietary Supplement Verification Program (DSVP) in October 2001. This program’s goal is to ensure that dietary supplement products contain the ingredients stated on the product label (Personal communication, V.S.Srinivasan, U.S. Pharmacopeia, February 11, 2001). Dietary supplement manufacturers who pay to participate in the program will have their products reviewed by USP, and if the product meets the DSVP program requirements, the product will be granted a USP certification mark. This mark is intended to signify that the product contains the ingredients stated on the label in the declared amount and strength, meets stringent standards for product purity, meets specified limits on known contaminants, and has been manufactured under good manufacturing practices according to the USP-NF General Chapter on Manufacturing Practices for Nutritional Supplements and the FDA’s Advance Notice of Proposed Rulemaking for good manufacturing practices (USP, 2001). Importantly, the DSVP certification mark is not intended to imply safety or efficacy of dietary supplement ingredients. AMERICAN HERBAL PHARMACOPOEIA The American Herbal Pharmacopoeia (AHP), a nonprofit organization, develops monographs on the quality, effectiveness, and safety of botanical medicines commonly used in the United States (Blumenthal, 1997). The monographs include botanicals with origins in Ayurvedic, Chinese, and Western traditions and includes information from both traditional and scientific sources (CRN, 1998; Upton, 1999). The monographs are intended to provide consumers, health professionals, and botanical manufacturers with the knowledge required for using and manufacturing botanical products safely and effectively, and to provide regulatory bodies and researchers with guidance for integrating botanical products into the health care system (AHP, 2001). Selection of a botanical for monograph development can be made by three methods. A Prioritization Committee consisting of professional herbalists, botanical industry representatives, and herbal educators produces a list of priority botanicals based on the extent of their use or the unique value of the botanical. A second method is through monograph sponsorship. Because AHP seeks funding and technical support for development of monographs from interested organizations or companies, a sponsored botanical may be given higher priority than was assigned by the Prioritization Committee (AHP, 2001). Thirdly, AHP considers what other groups have done. If there is an existing monograph of a botanical on the prioritization list, AHP may use, with permission, relevant sections of that monograph as a starting point for its own monograph development (AHP, 2001). 13   Whether a botanical monograph is admitted into the USP or its companion guide, the NF, currently depends on its approval status, as determined by the USP. If the botanical has an FDA- or USP-approved use, then standards are developed for it and it is published in the USP; otherwise, the standards for the botanical are published in the NF.

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements According to AHP, the first step in the development of an AHP monograph is a search of the primary literature. Primary literature is preferred, but secondary literature such as review articles may be used if considered acceptable or necessary. The search is not limited to English-language references. To address the safety of the botanical, a review of the toxicological literature is done and includes data on acute and chronic toxicity; use during pregnancy, lactation, fetal development, and driving; mutagenicity; teratogenicity; and carcinogenicity. All reported side effects, contraindications, and negative interactions are reviewed (AHP, 2001). Next, each section of the monograph is assigned to a writer with expertise in that section area, and the writer is provided with the results of the literature search. Once the sections are drafted, the AHP editor and at least one other expert in the specific field reviews them. All the sections are then incorporated into an initial monograph draft. This draft is then circulated to a peer-review committee of botanists, chemists, herbalists, pharmacists, pharmacologists, pharmacognosists, and physicians (AHP, 2001). Reviewer comments are incorporated into the draft and the initial authors review and approve their sections. Before it is finalized for publication, the monograph is reviewed by an expert of either the botanical under review or the physiological system that the botanical affects (AHP, 2001). AMERICAN HERBAL PRODUCTS ASSOCIATION The American Herbal Products Association (AHPA) is a national trade association for the botanical products industry. In response to passage of DSHEA, AHPA convened a special subcommittee of their Standards Committee to address the need for a comprehensive review of safety data for botanical ingredients sold in North America. According to AHP A, the goal of this committee, which consisted of three natural product scientists and practicing herbalists, was to critically evaluate safety and categorize botanicals based on safety. These evaluations are published as The Botanical Safety Handbook (McGuffin et al., 1997). The committee reviewed botanicals that were on the market in the United States, identified primarily by reviewing Herbs of Commerce, another AHPA publication (Foster et al., 1992). After identifying which botanicals to include, AHPA reported that its committee reviewed the available scientific literature for data on human and animal toxicity, traditional use, regulatory status in numerous countries, and current usage of herbs in the United States, China, India, Europe, and Australia. Notably, the committee also relied on its own and others’ expertise and clinical experience for the evaluations. There was no formal weighting of the data used for the evaluations; however, there were some exclusionary criteria. The monographs did not include the following data, conditions, or related products: excessive consumption, safety or toxicity concerns based on isolated constituents, toxicity data based solely on intravenous or intraperitoneal administration, traditional Chinese and Ayurvedic contraindications, gastrointestinal disturbances, potential drug interactions, idiosyncratic reactions in sensitive individuals, allergic reactions, contact dermatitis, well-known toxic plants that are not found in products on the market, homeopathic herbal preparations, essential oils, botanical products to which chemically-defined active substances had been added, or environmental factors, additives or contaminants. The AHPA review committee followed guidance from the World Health Organization’s (WHO) Programme on Traditional Medicines (WHO, 1991), which states that regulatory action is not necessary for traditionally used products that have not been shown to be harmful unless new evidence necessitates a risk-benefit assessment. The AHPA safety classification was based on an assumption of rational, informed use of botanicals and the committee stated that it

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements carefully considered the intended use of the substance within the historical context of that use (McGuffin et al., 1997). As listed in the exclusionary criteria above, the committee reported that it did not extrapolate toxicity data of isolated constituents and did not use data from studies that had excessive or irresponsible consumption patterns (McGuffin et al., 1997). Once the committee reviewed all available information, the botanicals were assigned to one of four safety classes. Class 1 are botanicals that the AHPA committee believes can be used safely when used appropriately. Class 2 are botanicals for which certain restrictions apply (see subclasses) unless otherwise directed by an expert qualified in the use of the substance. Class 2a are botanicals only to be used externally. Class 2b are botanicals not to be used during pregnancy. Class 2c are botanicals not to be used while lactating. Class 2d are botanicals for which other use restrictions have been specified in the monograph. Class 3 are botanicals for which significant data exist to recommend special labeling: “to be used only under the supervision of an expert qualified in the appropriate use of this substance.” Class 4 are botanicals for which the AHPC committee found insufficient data for classification. NATURAL MEDICINES COMPREHENSIVE DATABASE The publishers of Pharmacist’s Letter and Prescriber‘s Letter created the Natural Medicines Comprehensive Database (NMCD) that is available online and in printed version (NMCD, 2002). The stated goal is to bring together in one place the consensus of the available data on natural medicines so that practitioners do not need to search multiple sources to find scientifically reliable and clinically practical information on botanical medicines and supplements for their patients. NMCD reports that it provides an assessment of the available data regarding safety and effectiveness of each natural medicine reviewed and that it covers nearly every natural medicine on the market in North America (NMCD, 2002). New product reviews are prioritized based on market saturation and requests by health professionals (Personal communication, P.Gregory, NMCD, February 21, 2002). For each product that is reviewed, a research team of pharmacists, physicians, and pharmacologists begins the process with a literature search. Initially, when the database was first being developed, the research team consulted reference textbooks such as the Commission E Report, the Physician’s Desk Reference, and AHPA’s Botanical Safety Handbook for their evaluation of the literature. However, the research team soon turned to the primary literature using electronic databases such as Medline and Toxline to find the pertinent literature. For the most part, the research team limited their search to English-language references. However, non-English articles of special significance are also included. For the safety evaluation, the team relied mainly on human data; animal data were rarely used (Personal communication, P.Gregory, NMCD, February 21, 2002). After completion of the literature review, the information is evaluated and a consensus on any relevant issues is reached by the research team (NMCD, 2002), and then a single author drafts the reviews. The draft is then sent out for review to two or three pharmacists and physicians who were not on the research team. After this review, final drafts are added to the database (Personal communication, P.Gregory, NMCD, February 21, 2002). Each product is rated according to specific criteria as: likely safe., possibly safe, possibly unsafe, likely unsafe, or unsafe. Natural products that are rated likely safe are those for which there is general agreement among reliable references that the product is safe when used appropriately or those for which a governmental body has approved their use. A product is rated possibly safe if the reputable references suggest that the product might be safe when used

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements appropriately or there are human studies that report no serious adverse effects. A rating of possibly unsafe requires that there is some data suggesting product use might be unsafe. Likely unsafe indicates agreement among reputable references that the product can be harmful or there are reliable reports of harm to product users. A rating of unsafe is based on finding general agreement among reliable references that the product should not be used, reliable reports of clinically significant harm to product users, or safety warnings issued by a reliable agency for the product. Special mention is made if use during pregnancy, lactation, or in children presents special concerns. Natural products that have different uses (e.g., oral versus topical use) may receive more than one rating (NMCD, 2002). WORLD HEALTH ORGANIZATION WHO has developed international specifications for medicinal plants that are the most widely used in an effort fill the need for current, authoritative information on their safety and efficacy. WHO has published the first volume of 28 monographs on selected medicinal plants (WHO, 1999). A second volume is in press, and a third volume has been approved and is in preparation. The medicinal plants and products in each volume of monographs were selected by a WHO advisory group based on the extent of each plant’s use and importance throughout the world and on the sufficiency of the data available to evaluate safety and efficacy. The goal is to include information on safety, effectiveness, and quality control of botanical medicines. The monographs present descriptive information, purity tests, chemical constituents, medicinal uses, clinical studies, pharmacology, contraindications, warnings, precautions, adverse reactions, and posology.14 Each monograph was drafted under the direction of a team of experts in botanical medicines and medicinal plants. Information for the monographs was collected from a review of the literature, bibliographies, review articles, pharmacopoeias from several countries, reference books, and the NAPRALERT database. Once drafted, the monographs were reviewed by a large number of additional experts throughout the world with expertise in traditional medicine, drug regulation, drug evaluation, and pharmaceutical science. Finally, WHO convened a Consultation on Selected Medicinal Plants that consisted of 16 experts in medicinal plants and drug regulation to approve, modify, or reject the proposed monographs. WHO plans to periodically supplement and update the monographs as new data are made available (WHO, 1999). COMMISSION E In 1978 the Second Medicines Act in the Republic of Germany went into effect, requiring a scientific review of all medicines in the pharmaceutical market including conventional drugs and medicinal plants and phytomedicines. This resulted in the formation of a series of scientific commissions. Commission E was established by the German Minister of Health to review botanical drugs and preparations from medicinal plants. This 24-member committee was made up of physicians, pharmacists, nonmedical practitioners, pharmacologists, toxicologists, and biostatisticians (Blumenthal, 1998). According to the Commission E member consulted, at least 60 percent of the commission members had practical experience with phytomedicines (Personal communication, H.Schilcher, Commission E, March 19, 2002). The Commission completed its monograph work in 1994; however, it has met since 1994 to review drug registrations 14   From the Greek, posos, (how much), representing the science or doctrine of dosing.

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements (Blumenthal, 1997). The monographs produced by Commission E have been compiled and published in English by the American Botanical Council (Blumenthal, 1998). This publication and input from Commission E also describes the process used by Commission E, in addition to input from a member of the Commission E as the basis for this summary (Personal communication, H.Schilcher, Commission E, March 19, 2002). The stated objective of Commission E was to ensure that approved botanicals were reasonably safe when used according to the product label instructions and to remove unapproved botanicals from the market even if they only posed minor safety risks (Blumenthal, 1998). Commission E reviewed 378 botanicals used in German folk medicine for both safety and effectiveness (Blumenthal, 1997; Personal communication, H.Schilcher, Commission E, March 19, 2002). It was the manufacturer’s responsibility to provide proof of quality (Blumenthal, 1998). Safety and effectiveness were assessed using the published scientific literature. Approximately 100 to 200 worldwide references were consulted for each botanical (Personal communication, H.Schilcher, Commission E, March 19, 2002). The Commission considered data on traditional use, chemical composition, pharmacology, and toxicology and used data from clinical studies, in vitro and in vivo studies, field studies, epidemiological studies, case reports, and unpublished proprietary data submitted by manufacturers that included chemical, lexicological, pharmacological, and clinical testing data. The Commission also reviewed summaries produced by Kooperation Phytopharmaka (an umbrella organization of about 120 pharmaceutical manufacturers). These Kooperation Phytopharmaka summaries were based on literature reviews and clinical experience, but did not contain any recommendations about the product under review (Blumenthal, 1998). According to the American Botanical Council’s description, controlled clinical studies appear to have been considered the most useful type of data (Blumenthal, 1998). If no controlled studies were available, safety was evaluated based on other types of data such as well-documented review articles, older clinical trials, and well-documented knowledge of traditional usage. Blumenthal (1998) indicates that Commission E did not accept long-term therapeutic or traditional use as sufficient evidence of safety without additional data, and that field and case studies were only used when they had been evaluated according to scientific standards. Once the Commission finished drafting a monograph for a botanical medicine, it was published and comments were solicited from scientists and other experts. The Commission then prepared a final draft of the monograph. Notably, the monographs do not include references. An unpublished justification with relevant references for the monographs are kept; however, these justifications cannot be accessed except in cases of legal disputes (Blumenthal, 1998). Each substance was assigned one of three approval ratings: (1) positive (approved), (2) negative (unapproved), or (3) negative-null (unapproved). Positive/approved substances were considered reasonably safe when used according to the dosage, contraindications, and other warnings specified in the monograph. If safety concerns outweighed the potential benefits of a substance, the monograph was assigned a negative (unapproved rating). No dosage recommendations were provided for substances assigned a negative rating, and the intent of the Commission was the immediate withdrawal of these substances from the market. If no risk was found, but also no substantiated efficacy, the substance was designated as negative-null (unapproved). If manufacturers could later document the efficacy of such substances, the products could be approved; however, no new monographs would be produced (Blumenthal, 1998).

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements HEALTH CANADA NATURAL HEALTH PRODUCTS DIRECTORATE In Canada vitamin and mineral supplements, herbal products, homeopathic preparations, and traditional Chinese, Ayurvedic, and native North American medicines are considered to be natural health products (NHPs). At present, there are no specific regulations for NHPs—they are regulated as either foods or drugs depending upon the active ingredient, the form of the product labeling, and the presence or absence of claims. In 1997, in response to growing concerns about access to NHPs, the Minister of Health asked the Canadian House of Commons Standing Committee on Health to conduct a full review of how NHPs were regulated in Canada and how the government could better provide Canadians with the safety, quality, and freedom of choice that they were seeking. Following extensive consultation, the Standing Committee issued its report in November 1998. The report contained 53 recommendations, including the establishment of a new regulatory authority specifically for the regulation of NHPs. In March 1999 the government accepted all of the recommendations of the Standing Committee and announced the creation of the Office of Natural Health Products (now the Natural Health Products Directorate) within Health Canada (the federal department of health) as the authority charged with developing and maintaining a regulatory framework for NHPs. An Expert Advisory Committee with expertise in medicine, biostatistics, nutrition, traditional medicines, herbs, aromatherapy, toxicology, biochemistry, botany, pharmacognosy, pharmacology, pharmacy, and homeopathy was appointed to support the work of the Directorate. The Natural Health Products Directorate has proposed a regulatory framework for NHPs, which would be considered a subset of drugs under the Canadian Food and Drugs Act. The Natural Health Product Regulations were published in the Canada Gazette, Part I, for comment on December 22, 2001. One of the most complex issues in developing the regulatory framework has been defining what is and is not a natural health product (Personal communication, M. Cheney, Health Canada, June 11, 2002). The proposed definition of an NHP contains two parts: a function part and a substance part. The function part captures those substances that are manufactured, sold, or represented for use in the diagnosis, treatment, mitigation, or prevention of a disease, disorder, or abnormal physical state or its symptoms in humans; restoring or correcting organic functions in humans; or maintaining or promoting health or otherwise modifying organic function in humans. This part of the definition allows for the full range of claims normally associated with drugs. The substance component of the definition is driven by the medicinal ingredient. There is an inclusion list of the substances that may be contained within NHPs and an exclusion list of substances that are not NHPs. The former list includes vitamins, minerals, amino acids and essential fatty acids, probiotics and plant or plant material alga, fungus or nonhuman animal material or an extract or isolate provided the primary molecular structure is not altered. Exclusions include antibiotics, biologies, and products administered by injection. The main components of the proposed NHP Regulations are requirements for product licensing, site licensing, good manufacturing practices, clinical trials, packaging and labeling, and reporting of adverse reactions. Under product licensing, each NHP sold in Canada will undergo an assessment before it is authorized for sale. The application for a product license would be required to provide specific information about the NHP, including the quantity of medicinal ingredients it contains, the specifications, the intended use or purpose, and supporting safety and efficacy data. The Natural Health Products Directorate is developing standards of evidence that will indicate the type of information required to support various claims for NHPs.

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements In addition, the applicant for a product license would be required to show that the product will be manufactured, packaged, labeled, distributed, and imported in accordance with good manufacturing practices. The regulatory framework proposed will provide for the conduct of clinical trials to allow the industry to test new products, including products that have not received market authorization, where no other data are available. The regulations would not place any requirements on the clinical trial investigator, who must be a health professional regulated by the laws of the province where the clinical trial site is located and whose scope of practice under those laws must be directly related to the subject matter of the clinical trial. The regulations do require, however, that one member of the Research Ethics Board of the study be knowledgeable in complementary or alternative health care. The regulations would require that the trial be conducted in accordance with good clinical practices and that adverse reactions be reported. Final regulations are expected by the end of 2002 (Personal communication, M.Cheney, Health Canada, June 11, 2002). EUROPEAN SCIENTIFIC COOPERATIVE ON PHYTOTHERAPY The European Scientific Cooperative on Phytotherapy (ESCOP) was created in 1989 to promote the scientific status of phytomedicines and the harmonization of their regulatory status in Europe. ESCOP is an umbrella organization of national associations for phytotherapy from countries both within and beyond the European Union. Monographs are produced by a Scientific Committee of ESCOP, a subgroup of delegates from participating member countries, with expertise in medicine, phytotherapy, pharmacognosy, pharmacology, and regulatory affairs (ESCOP, 2001). The goal is to compile monographs to provide information on the therapeutic uses and safety of botanicals that are widely used in European medicine and pharmacy (Blumenthal, 1997; ESCOP, 2001). Information on quality is not included in these monographs (Blumenthal, 1997). The Scientific Committee, with assistance from researchers on specific plants, drafts the monographs by evaluating information from the published scientific literature (ESCOP, 2001). Once a monograph is drafted, it is reviewed by an independent board of supervising editors, consisting of academic experts in phytotherapy and medicinal plants. The monographs are then published as fascicules, each containing 10 monographs; 60 monographs have been published to date (ESCOP, 2001). REFERENCES AHP (The American Herbal Pharmacopoeia). 2001. Monographs Defined. Developing Quality Control and Therapeutic Monographs: Monograph Prioritization, Development, Review, Finalization and the Value of Monographs to Health Professionals, Industry and Consumers. Online. Available at http://www.herbal-ahp.org/mgdefine.html. Accessed November 12, 2001. AHRQ (Agency for Healthcare Research and Quality). 2002. Evidenced-based Practice Centers. Online. Available at http://www.ahrq.gov/clinic/epc/. Accessed June 17, 2002. Blumenthal M. 1997. Herbal monographs. HerbalGram 40:30–38. Blumenthal M, ed. 1998. Therapeutic Guide to Herbal Medicines. The Complete German Commission E Monographs . Austin, TX: American Botanical Council. CRN (Council for Responsible Nutrition). 1998. Reference on Evaluating Botanicals. Washington, DC: CRN.

OCR for page 106
For Comment: Proposed Framework for Evaluating the Safety of Dietary Supplements ESCOP (The European Scientific Cooperative on Phytotherapy). Publications. ESCOP Monographs. Online. Available at http://www.escop.com/publications.htm. Accessed November 12, 2001. Foster S, Moley T, Awang D. 1992. Herbs of Commerce. Austin, TX: American Herbal Products Association. McGuffin M, Hobbs C, Upton R, Goldberg A. 1997. American Herbal Product Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press. NMCD (Natural Medicines Comprehensive Database). 2002. About the Database. Online. Available at http://www.naturaldatabase.com/aboutdb.asp. Accessed January 7, 2002. Upton R, ed. 1999. American Herbal Pharmacopoeia and Therapeutic Compendium. Valerian Root, Valerian officinalis. Analytical, Quality Control, and Therapeutic Monograph. Santa Cruz, CA: American Herbal Pharmacopoeia. USP (The United States Pharmacopeia). 2001. USP Board of Trustees Agrees to Continue Proceeding with Pilot Program for Dietary Supplement Verification. Online. Available at http://www.usp.org. Accessed October 31, 2001. USP. 2002a. USP 25-NF 20. Rockville, MD: United States Pharmacopeial Convention, Inc. USP. 2002b. USP Fact Sheet. Online. Available at http://www.usp.org. Accessed June 18, 2002. WHO (World Health Organization). 1991. Report of the Consultation to Review the Draft Guidelines for the Assessment of Herbal Remedies. Munich, Germany, June 19–21, 1991. Geneva: WHO. WHO. 1999. WHO Monographs on Selected Medicinal Plants, Volume I. Geneva: WHO.