Quality Controls and Product Standards: A Research Priority-Setting Conference (March 8-9, Vancouver)

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Table of Contents

• Executive Summary
• Introduction
• Research Priorities, Strategies and Next Steps
• 1. Develop Methods for Assessing Botanical Identity
• 2. Perform Research to Inform the Development of Purity Specifications
• 3. Perform Research to Identify and Develop Reference Materials
• 4. Develop Analytical Methods to Determine Markers
• 5. Evaluate and Identify Biologically Active Components
• 6. Develop Methods to Monitor Outcomes
• Concluding Remarks
• Appendix A - Participant List
• Appendix B - Agenda
• Appendix C - Research Priorities from each Working Group

Executive Summary

On March 8-9, 2002, the Natural Health Products Directorate (NHPD) convened a conference to establish research priorities pertaining to quality controls and product standards for natural health products (NHPs) in Canada, especially with regard to botanical products. The Canadian participants included representatives from academia, industry, complementary and alternative health care practice, research and various government agencies. Two participants from the USA, including a representative from the Office of Dietary Supplements at the National Institutes of Health, also contributed their expertise.

Through group and plenary discussions, the participants identified six research priorities as well as strategies and next steps that would advance these goals. The implementation of these recommendations would assist the NHPD in its mission to ensure that Canadians have access to safe, effective and high-quality NHPs and to accurate and detailed information required to make properly informed choices.

Research Priorities, Strategies and Next Steps

1. Develop methods for assessing botanical identity. The inclusion of unintended or undeclared botanicals in a product represents a serious problem, as it is one of the most common causes of adverse effects.

a) Develop a database. Information concerning botanical identity, reference standards and various methods that may be used to assess identity should be collected in a database and critically evaluated to help identify research priorities.

b) Establish a hierarchy of methods. Since there are a variety of methods that can be used to identify botanicals, it is necessary to establish a hierarchy of methods that are scientifically rigorous, cost effective and practical.

c) Develop a system to track identification. A system must be developed to permit the identification of botanical products without ambiguity through all stages, from harvesting through manufacturing. A Certificate of Identity blended with Good Agricultural Practices (GAPs) is envisioned.

d) Construct a virtual network. The construction of a virtual and comprehensive network of experts in botanical identification would aid these efforts.

e) Survey the industry. A survey of the industry would also aid in the determination of the following specific identification needs: which botanicals are a priority; the range and most common types of preparation forms that require identification; and the capacity needs pertaining to education, training and knowledge transfer.

2. Perform research to inform the development of purity specifications. Canadians want NHPs that are free from contaminants. While tolerance levels for many impurities have been established for food items, this is not the case for NHPs.

a) Review existing data and develop a database. It is necessary to review the existing data on botanical purity and to identify individuals and agencies with research expertise in this field. When other agencies or countries have studied tolerance levels and developed GAPs and good manufacturing processes (GMPs), this data will be critically evaluated.

b) Identify gaps in knowledge and practice. Presently, there are gaps in our knowledge and practices that permit contaminants to enter into NHPs. These gaps should be identified and prioritized so that effective efforts can be directed at limiting contamination.

c) Develop Canadian GAP guidelines. A project team should be formed to aid the development of Canadian GAPs that would enhance product safety by reducing product contamination.

d) Form a network. A network of researchers with expertise in the field of purity specifications should be created to facilitate the efficient development of research initiatives and the effective transfer of information, thereby enhancing training and education.

3. Perform research to identify and develop reference materials. Reference materials are essential to the scientific evaluation of botanical quality because they are a critical component of identity, purity and strength testing. Presently, reference materials are not readily available within Canada as there is no official source for authenticated reference materials.

a) Identify a lead agency. There is a need to identify or designate a lead agency in Canada that can initiate and foster this initiative.

b) Identify interested partners. Research partners should be identified and research collaborations should be established both domestically and internationally.

c) Establish protocols and programs. Protocols for the identification and development of reference materials will need to be established by the research network. A program for the development and validation of methodologies for establishing and analyzing reference materials should also be initiated.

4. Develop analytical methods to determine markers. Marker compounds are constituents that naturally occur within an NHP and are often used to quantify the potency of a particular product or to standardize batches during manufacturing. However, many markers are not related to the biological activity of the product and, therefore, are not necessarily the best determinant of either quality or potency.

a) Establish a national committee of experts. A national committee with technical expertise would coordinate inter-laboratory studies for the creation of official analytical methods.

b) Tasks of the national committee. The national committee would prioritize the botanicals that will be the object of such research; compile and critically review the methods currently used to determine and analyze markers; and coordinate the development of officially validated methods to determine and analyze markers. The national committee should work in collaboration with the group that is overseeing the development of reference materials.

5. Evaluate and identify biologically active components. The potency of a product is usually determined by the quantity of the active ingredient present that will produce the desired therapeutic effect. For most botanical medicines, these biologically active ingredients have not been conclusively identified or understood.

a) Need for basic science research. The mechanisms of action for NHPs and botanical remedies in particular need to be more thoroughly understood. Relevant biological assays are required to obtain meaningful measurements of potency and efficacy. Researchers should take advantage of the existing infrastructures that link producers, academia, government and industry. To avoid duplication, the latter should network with researchers developing methods for botanical identification.

b) Establish a database. A peer-reviewed database of existing bioassays and mechanisms of action should be established. This would also promote technology and knowledge transfer, help to avoid unnecessary duplication of research and increase the efficiency and progress of related research.

c) Establish a virtual network. Researchers in areas related to NHPs should be linked through a virtual network.

d) Determine which NHPs should be researched. The research priorities regarding biological assays and mechanisms of action would be influenced by the major health problems facing Canadians.

6. Develop methods to monitor outcomes. Is there 'value added' when regulations formally stipulate the quality controls and product standards that must be applied to the growing, production, distribution, marketing, and sale of NHPs?

a) Measure outcomes. Measuring the effects of initiatives to improve quality controls and product standards for NHPs would determine the impact of these new regulations and practices on the safety, efficacy, accessibility and quality of NHPs. Such monitoring and measures would also review the ability of Canadian citizens and health care providers to make more informed choices.

b) Establish baseline values. Baseline values need to be established prior to the enactment of new regulations to determine current traits and patterns and the subsequent impact of new initiatives.

c) Survey social attitudes. A research project should be developed to measure the social attitudes of the Canadian population (or sub-populations such as the HIV/AIDS community, and/or paediatrics and youth) with respect to the safety, efficacy, and accessibility of NHPs, as well as the degree of informed choice and wellness.

During the working and plenary sessions, the participants shared their expertise and opinions with considerable enthusiasm and goodwill. Several of them noted a certain urgency for these research initiatives to be undertaken expeditiously, even as they acknowledged the various challenges that need to be overcome. They felt that the realization of these research priorities would help to address several concerns related to quality controls and products standards for NHPs in Canada. Consequently, advancing these research priorities would assist the NHPD with its goal of ensuring that Canadians have access to safe, effective, and high-quality NHPs and to accurate and detailed information required to make properly informed choices.

On March 8-9, 2002, the Natural Health Products Directorate (NHPD) convened a conference to establish research priorities pertaining to quality controls and product standards for natural health products (NHPs) in Canada, especially with regard to botanical products. The Canadian participants included representatives from academia, industry, complementary and alternative health care practice, research, and various government agencies. Two participants from the USA, including a representative from the Office of Dietary Supplements at the National Institutes of Health, also contributed their expertise.

Through group and plenary discussions, the participants identified six research priorities as well as strategies and next steps that would advance these goals. The implementation of these recommendations would assist the NHPD in its mission to ensure that Canadians have access to safe, effective and high quality NHPs and to accurate and detailed information required to make properly informed choices.

Research Priorities, Strategies and Next Steps

1. Develop methods for assessing botanical identity. The inclusion of unintended or undeclared botanicals in a product represents a serious problem, as it is one of the most common causes of adverse effects.

1. Develop a database. Information concerning botanical identity, reference standards and various methods that may be used to assess identity should be collected in a database and critically evaluated to help identify research priorities.
   
   
2. Establish a hierarchy of methods. Since there are a variety of methods that can be used to identify botanicals, it is necessary to establish a hierarchy of methods that are scientifically rigorous, cost effective and practical.
   
   
3. Develop a system to track identification. A system must be developed to permit the identification of botanical products without ambiguity through all stages, from harvesting through manufacturing. A Certificate of Identity blended with Good Agricultural Practices (GAPs) is envisioned.
   
   
4. Construct a virtual network. The construction of a virtual and comprehensive network of experts in botanical identification would aid these efforts.
   
   
5. Survey the industry. A survey of the industry would also aid in the determination of the following specific identification needs: which botanicals are a priority; the range and most common types of preparation forms that require identification; and the capacity needs pertaining to education, training and knowledge transfer.

2. Perform research to inform the development of purity specifications. Canadians want NHPs that are free from contaminants. While tolerance levels for many impurities have been established for food items, this is not the case for NHPs.

1. Review existing data and develop a database. It is necessary to review the existing data on botanical purity and to identify individuals and agencies with research expertise in this field. When other agencies or countries have studied tolerance levels and developed GAPs and good manufacturing processes (GMPs), this data will be critically evaluated.
   
   
2. Identify gaps in knowledge and practice. Presently, there are gaps in our knowledge and practices that permit contaminants to enter into NHPs. These gaps should be identified and prioritized so that effective efforts can be directed at limiting contamination.
   
   
3. Develop Canadian GAP guidelines. A project team should be formed to aid the development of Canadian good agricultural practices (GAPs) that would enhance product safety by reducing product contamination.
   
   
4. Form a network. A network of researchers with expertise in the field of purity specifications should be created to facilitate the efficient development of research initiatives and the effective transfer of information, thereby enhancing training and education.

3. Perform research to identify and develop reference materials. Reference materials are essential to the scientific evaluation of botanical quality because they are a critical component of identity, purity and strength testing. Presently, reference materials are not readily available within Canada as there is no official source for authenticated reference materials.

1. Identify a lead agency. There is a need to identify or designate a lead agency in Canada that can initiate and foster this initiative.
   
   
2. Identify interested partners. Research partners should be identified and research collaborations should be established both domestically and internationally.
   
   
3. Establish protocols and programs. Protocols for the identification and development of reference materials will need to be established by the research network. A program for the development and validation of methodologies for establishing and analyzing reference materials should also be initiated.

4. Develop analytical methods to determine markers. Marker compounds are constituents that naturally occur within an NHP and are often used to quantify the potency of a particular product or to standardize batches during manufacturing. However, many markers are not related to the biological activity of the product and, therefore, are not necessarily the best determinant of either quality or potency.

1. Establish a national committee of experts. A national committee with technical expertise would coordinate inter-laboratory studies for the creation of official analytical methods.
   
   
2. Tasks of the national committee. The national committee would prioritize the botanicals that will be the object of such research; compile and critically review the methods currently used to determine and analyze markers; and coordinate the development of officially validated methods to determine and analyze markers. The National Committee should work in collaboration with the group that is overseeing the development of reference materials.

5. Evaluate and identify biologically active components. The potency of a product is usually determined by the quantity of the active ingredient present that will produce the desired therapeutic effect. For most botanical medicines, these biologically active ingredients have not been conclusively identified or understood.

1. Need for basic science research. The mechanisms of action for NHPs and botanical remedies in particular need to be more thoroughly understood. Relevant biological assays are required to obtain meaningful measurements of potency and efficacy. Researchers should take advantage of the existing infrastructures that link producers, academia, government and industry. To avoid duplication, the latter should network with researchers developing methods for botanical identification.
   
   
2. Establish a database. A peer-reviewed database of existing bioassays and mechanisms of action should be established. This would also promote technology and knowledge transfer, help to avoid unnecessary duplication of research and increase the efficiency and progress of related research.
   
   
3. Establish a virtual network. Researchers in areas related to NHPs should be linked through a virtual network.
   
   
4. Determine which NHPs should be researched. The research priorities regarding biological assays and mechanisms of action would be influenced by the major health problems facing Canadians.

6. Develop methods to monitor outcomes. Is there 'value added' when regulations formally stipulate the quality controls and product standards that must be applied to the growing, production, distribution, marketing, and sale of NHPs?

1. Measure outcomes. Measuring the effects of initiatives to improve quality controls and product standards for NHPs would determine the impact of these new regulations and practices on the safety, efficacy, accessibility and quality of NHPs. Such monitoring and measures would also review the ability of Canadian citizens and health care providers to make more informed choices.
   
   
2. Establish baseline values. Baseline values need to be established prior to the enactment of new regulations to determine current traits and patterns and the subsequent impact of new initiatives.
   
   
3. Survey social attitudes. A research project should be developed to measure the social attitudes of the Canadian population (or sub-populations such as the HIV/AIDS community, and/or paediatrics and youth) with respect to the safety, efficacy, and accessibility of NHPs, as well as the degree of informed choice and wellness.

During the working and plenary sessions, the participants shared their expertise and opinions with considerable enthusiasm and goodwill. Several of them noted a certain urgency for these research initiatives to be undertaken expeditiously, even as they acknowledged the various challenges that need to be overcome. They felt that the realization of these research priorities would help to address several concerns related to quality controls and products standards for NHPs in Canada. Consequently, advancing these research priorities would assist the NHPD with its goal of ensuring that Canadians have access to safe, effective, and high quality NHPs and to accurate and detailed information required to make properly informed choices.

Introduction

On March 8 - 9, 2002, the Natural Health Products Directorate (NHPD) convened a conference to consider research priorities pertaining to quality controls and product standards for natural health products (NHPs) in Canada, especially with regard to botanical products. The conference was held at the Coast Plaza Stanley Park Hotel in Vancouver, British Columbia. The participants included representatives from academia, industry, complementary and alternative health care practice, and various government agencies including the National Research Council (NRC), the Natural Sciences and Engineering Research Council (NSERC), Agriculture and Agri-Food Canada (AAFC), Health Canada and the NHPD.¹ The conference was co-chaired by Michael J. Smith, Senior Advisor at the NHPD, and Allison McCutcheon from the Department of Botany at the University of British Columbia.

The objectives for the conference were threefold:

1. to establish priorities and strategies related to fostering, conducting and supporting research in the quality and analysis of NHPs
   
2. to act as a forum for constructive dialogue between all relevant stakeholder groups
   
3. to develop and identify initiatives that support the proposed regulatory framework of NHPs in Canada and the development of relevant policy

Following welcoming remarks by the co-chairs and general introductions by each of the participants,² the conference began with a keynote address by Allison McCutcheon entitled "Issues in Botanical Quality." Joseph M. Betz of the Office of Dietary Supplements (National Institutes of Health, USA) offered an American perspective on quality controls and product standards for NHPs. Don Beatty from Boehringer-Ingelheim (Canada) Ltd. provided a perspective from industry, Robin Marles of the University of Manitoba presented a researcher's viewpoint and Peter Chan of the NHPD gave the perspective of a regulator.

After a morning of presentations followed by lunch, the facilitator reviewed the conference objectives and the steps by which the discussions would proceed. He noted that while the NHPD might not be able to act on every recommendation proposed, it was nevertheless important for the participants to provide clear and detailed advice for each of their proposals. The participants (including the presenters) then assembled into five pre-selected working groups. Each working group considered a variety of research possibilities that might improve quality controls and contribute to the development of Canadian NHP standards. Each group eventually narrowed their proposals to a list of five research priorities. (The research priorities suggested by each working group are recorded in Appendix C.) During the plenary session that followed, a representative from each group provided an overview of that group's research priorities to the other participants. After consultation with the participants, these research priorities were subsequently consolidated into the following list of priorities.

Preliminary List of Research Priorities

1. develop a database on existing literature
   
2. develop methods for assessing botanical identity
   
3. perform research to inform the development of purity specifications
   
4. perform research to identify and develop reference materials
   
5. develop analytical methods
   
6. evaluate and identify biologically active components
   
7. develop methods to monitor outcomes
   
8. develop standards for specific botanicals based on their intended use (safety specifications and compositional specifications)

A number of areas that required capacity building to facilitate this research were also identified. The most prominent area was the need for education and training. Other needs that were identified included:

• a national collection of authenticated reference materials
  
• analytical methods validation
  
• a database of chemical and physical information

On the second day of the conference, the participants voted to further narrow their focus to six research priorities (items 2 through 7, above). Working groups for each of these six research priorities were formed by participant self-selection. During the working session that followed, each working group devised strategies that would advance their particular research priority. The opportunities and challenges (pros and cons) that would be encountered in the implementation of each strategy were considered and discussed. A reporter from each group once again presented their work to the other participants during the succeeding plenary session.

In the third and final working session, the working groups discussed the 'next steps' that could be taken to implement each strategy that they had identified during the previous session. The working groups provided concrete and practical steps to guide the implementation of the various strategies that were chosen for the research priority that had been the focus of their attention. The 'next steps' were to provide a map that would describe who would be doing what, and when they would be doing it. Possible sources of funding (if applicable) were also to be identified.

The results of these deliberations are described in the remainder of this report. In the discussion that follows, each research priority is introduced by a description of the issue that indicates the importance of that priority. The recommendation pertaining to this issue is then proposed. Strategies and possible next steps for advancing the proposal are then presented - sometimes in separate sections and sometimes blended into one discussion.

Research Priorities, Strategies and Next Steps

1. Develop Methods for Assessing Botanical Identity

Issue

Probably for as long as humans have recognized the value of medicinal plants, people have also been interested in ensuring that they are either taking or administering the correct plant. Accordingly, the importance of proper plant identification becomes apparent. Although quality and purity of product is also important, an important first step for product safety is the correct identification of the botanicals used in any preparation. The inclusion of unintended or undeclared botanicals in a product represents a serious problem, as it is one of the most common causes of adverse effects.

Recommendation

Research to develop methods for assessing botanical identity

1. Develop a database. There is a substantial body of information in the scientific literature pertaining to botanical identity, including data on problems encountered, reference standards and various methods that may be used to assess identity. This information should be collected into a database and critically evaluated to help identify research priorities, both in terms of the specific plants that most urgently require study and the most appropriate methods for each botanical. It is important to establish a priority list of botanicals that are most relevant to Canadians and this list should be reviewed and updated on an ongoing basis. While the data in the literature represent a valuable resource, it should also be recognized that this information must be read critically. The sizable amount of information published in foreign languages will constitute a significant challenge in the creation of the database. Once a database has been constructed, the dissemination of this information could be challenging.

2. Establish a hierarchy of methods. Since a variety of methods can be used to identify botanicals, a hierarchy of methods should be established. The methods must be scientifically rigorous, cost effective and practical. Again, the literature can provide a wealth of information in this regard, since much information and expertise already exists, particularly in the areas of pharmacognosy and ethnobotany. The current techniques and technologies can be reviewed and the prospect of new, innovative technologies can be explored. The preferred methods in the hierarchy should provide unambiguous and definitive results while being both rigorous and practical. That is, the method should permit a high level of confidence in its results.

The range of methods that may be considered in the development of this hierarchy could include organoleptic techniques; macroscopic and microscopic assessment of plant morphology; the possible use of transmission electron microscopes (TEMs) and scanning electron microscopes (SEMs); the use of analytical methods employing thin-layer chromatography (TLC); gas chromatography (GC); high performance liquid chromatography (HPLC); gas chromatography-mass spectrometry (GC-MS); and liquid chromatography-mass spectrometry (LC-MS) and/or DNA analysis. The identification of a characteristic fingerprint for each botanical would be the desired outcome. The methods must also be economically and logistically practical. The specific type of methodology to be used would depend on whether it is for qualitative or quantitative purposes. A shortage of trained technicians and researchers could present a challenge, as might the variety of botanical formulations and matrices that must be assessed.

3. Develop a system to track identification. There is a need to develop a system for tracking the identification that has been assigned to any botanical product, whether it has been identified at the time of harvest, early stages of collecting and shipping raw materials, or during the various processes of manufacturing a product. A paper trail of plant identity helps to make seed certification possible. It also facilitates the identification of raw materials including whole plants, processed plants and extracts. It is recommended that the NHPD determine the requirements for seed certification for botanicals, perhaps in consultation with industry, seed producers, Agriculture Canada and the provinces. While it may be possible to use existing models as a template, it may also be necessary to develop new programs for certification that address the unique needs of certifying the seeds of medicinal plants. Such certification must lead to the unambiguous identification of seeds or plants. It may also be necessary to include provisions that permit testing for genetically modified organisms (GMO) or GMO contamination.

These efforts would result in a Certificate of Identity (C of I) program that would be characterized by rigorous methodology and high-quality reference materials. The C of I could be blended into GAP procedures. The grower, the broker and/or the manufacturer would pay for the C of I. Since it is presently possible to obtain a C of I from universities (e.g., the University of Saskatchewan) and various contract laboratories, such testing is both possible and practical. The C of I testing would be correlated with official reference materials and would include the collection of voucher specimens. There would be a need to develop of system for certification of authorities who can provide a C of I. The Standards Council of Canada could certify these authorities.

The need for such reliable identification is clear, and the interest in such an initiative seems to be broad. It is believed that the ability to properly track the identification of botanical products at all stages of growing, processing, manufacturing and distribution adds value to the final product, and is consequently an added-value benefit to each link in that chain. It should be possible to 'piggy-back' this initiative on existing organic certification procedures, and it may be possible to link this strategy to other efforts at the World Health Organization as well as Canadian federal and provincial governments. At the same time, it is recognized that it will be difficult to develop a credible system that is also practical, and it may be challenging to establish such excellence within international markets.

4. Construct a virtual network. The construction of a virtual and comprehensive network of experts in botanical identification would aid these efforts. The network might include recognized researchers as well as several people who have attended this research priority-setting conference. The expert members could also be found in academia, industry and government laboratories. The network would collaborate with similar networks and develop a relational database of plant species, methods of identification and researchers doing work in this field. It could seek funding from the NHPD, Canadian Institutes of Health Research (CIHR), the NRC and NSERC. Because the network is virtual, it would be possible to draw on expertise from across Canada and around the world. The consultative processes that the NHPD has initiated over the past two years have already had the added benefit of bringing many and various experts into contact with each other.

The network would need to develop a clear focus with effective coordination and leadership. It would have to be sensitive to the proprietary rights of industry and the competing priorities of its members who would undoubtedly come from a variety of backgrounds. During the meeting, members of the working group expressed strong interest in continuing to work together to facilitate creation of the proposed virtual network of experts that would assess botanical identity.

5. Survey industry. A survey of the industry would also aid in the determination of specific identification needs, particularly:

• which botanicals are a priority
  
• the range and most common types of preparation forms that need identification
  
• the capacity needs pertaining to education, training and knowledge transfer pertaining to methods.

The survey could be distributed to national industry associations such as the Nonprescription Drug Manufacturers Association of Canada (NDMAC) and the Canadian Health Food Association (CHFA), as well as to various provincial associations, academia, Agriculture Canada and contract laboratories. Funding for such a survey might be obtained through a collaborative and strategic research grant from industry and trade associations such as the CHFA, organic food associations, the Saskatchewan Nutraceutical Network (SNN) and the British Columbia Functional Food and Nutraceutical Network (BCFN); from academia and contract laboratories; and from such government agencies as NSERC, Health Canada, and/or the Canadian Adaptation and Rural Development (CARD) program of Agriculture Canada.

2. Perform Research to Inform the Development of Purity Specifications

Issue

Canadians want products, whether they are food or NHPs, which are free from contaminants. These concerns relate directly to product purity and safety. Contamination of NHPs could include the accidental inclusion of heavy metals, microbials, foreign matter, pesticides and herbicides, and radioactive elements. An NHP could also be contaminated by the accidental inclusion of extraneous materials (i.e., by-products introduced during the manufacturing processes) and unwanted parts from the plant that is mentioned on the product label, or by the accidental inclusion of parts from another plant species. Impurities may also include intentionally included adulterants such as the wrong plant part, other botanicals, previously extracted botanical material, marker compounds and pharmaceutical drugs. While tolerance levels for many impurities have been established for food items, this is not the case for NHPs. There is a need to develop specifications for product purity that are specific to NHPs.

Recommendation

Research to inform the development of specifications for product purity.

1. Review existing data. It is necessary to review the existing data on botanical purity and to identify individuals and agencies with research expertise in this field. Creating linkages among these experts would facilitate information exchange and the coordination of research. Tolerance levels for contaminants have already been established by many countries for various commodities, particularly with respect to food items. Some of this information might have relevance to a study of contaminants in NHPs, and botanical remedies in particular. GAPs and good manufacturing practices (GMPs) have also been developed in many countries. These activities as well as existing regulatory initiatives should be part of a comprehensive and critical review. The information should be consolidated to provide a knowledge base to inform research initiatives and to identify priorities.

This initiative will be challenged by the great diversity of products that already exist in the marketplace. It will also need to contend with the continuing introduction of new plants and products. Furthermore, the data already gathered and the research already undertaken must be critically reviewed, since it is imperative that the reliability and validity of the data are scrutinized and evaluated.

2. Identify gaps in knowledge and practice. Presently, there are gaps in our knowledge and practices that permit contaminants to enter into NHPs. These gaps should be identified and prioritized so that effective efforts can be directed at limiting contamination. More specifically, there is a need to develop and improve methods for the detection and prevention of contamination. GAPs and GMPs can substantially reduce the contamination of NHPs. Although applicable to both domestically produced and imported products, different strategies may be required for products originating in countries that do not have GAP and/or GMP standards. There is also a need to improve our knowledge of plant part toxicity - i.e., to determine if certain parts of a botanical remedy might be toxic for human consumption.

As is often the case, funding can be a challenge for such an initiative. The prioritization of which botanicals, what type of contaminants and which processes need to be addressed should be guided by the results of the literature search, the costs involved, the time that is required and the practicality of achieving the goal with current techniques. Other challenges include the education of the various stakeholders as well as technology and knowledge transfer.

Next Steps

To implement this recommendation, the following next steps are suggested:

1. Develop Canadian Good Agriculture Practice guidelines. The development of Canadian GAPs is essential. To advance this strategy, a project team would be formed in collaboration with the farm food safety branch of Agriculture Canada. Team members would include:

• an expert in hazard assessment critical control practices (HACCP)
  
• a representative from the Natural Health Products Directorate (NHPD) so that GAPs could flow seamlessly with GMPs
  
• producers, including wild crafters and growers of spices, medicinal herbs and culinary herbs
  
• a coalition of the herb and spice industry

The team would consult with:

• practitioners
  
• processors
  
• various researchers including agronomists, agricultural engineers, and/or analytical chemists
  
• representatives from the NRC, especially the Plant Biotechnology Institute (PBI) of the NRC, and the Canadian Food Inspection Agency (CFIA) of Agriculture Canada. (While Agriculture Canada will only fund research on safety - and not quality or the construction of a database - the latter factors must also be addressed if the former is to be adequately dealt with.)
  
• a representative from the American Herbal Products Association (AHPA) (could serve in an advisory capacity)
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2. Consult with the AHPA. Consult with the AHPA to determine the state of their efforts to ensure the purity of herbal products and to discern if it would be possible to work collaboratively with them.

3. Develop Good Agricultural Practices. During the next two years, the team should work on the development of GAPs with the aid of funding from Agriculture Canada. GAPs would enhance product safety by reducing product contamination by microbials, heavy metals, pesticides, herbicides, extraneous plant parts, unintended plants and other foreign matter.

4. Develop a database. During the next two years, an initiative to form and fund a database of purity information would be realized. This database would undergo a critical appraisal by the network members (see next item). It might be possible to formulate this database in collaboration with other strategic planning groups who recognize the need for a botanical database. Funding might be obtained from NSERC or regional partners such as provincial governments. It might be possible to form a partnership with the University of Guelph and/or the University of Saskatchewan, or similar academic centres.

5. Form a network. A network of researchers with expertise in this field should be created. The network could include members from industry (production and manufacturing), academia, provincial and federal agricultural ministries, and possibly from complementary and alternative healthcare professions. The network could also establish linkages with private and public researchers as well as coalitions such as the Saskatchewan Herb and Spice Association, the SNN and the BCFN. This network would facilitate the efficient development of research initiatives and the effective transfer of information and would further enhance training and education.

3. Perform Research to Identify and Develop Reference Materials

Issue

Central to the issue of quality control and product standards for NHPs is the need for accurate, authenticated and widely accepted reference materials for botanical medicines. Reference materials are essential to the scientific evaluation of botanical quality since they are a critical component of identity, purity and strength testing. Without reference materials, product quality cannot be determined since it is not possible to perform standardized and scientific analyses of products. At the present time, the identification of reference materials occurs on an ad hoc basis within the industry and there is no official source for reference materials. Nevertheless, there are well-established mechanisms for the production and distribution of official reference standards. In other fields, official reference materials are typically used in conjunction with validated pharmacopoeial methods or analytical testing protocols to establish the identity, strength and/or purity of a product. The reference materials needed for the assessment of botanicals include not only well-characterized, isolated chemical compounds, but also botanical reference standards in the form of herbarium vouchers, raw material and standardized extract vouchers. Presently, reference materials are not readily available within Canada since there is no official source for authenticated reference materials. In some cases, chemical reference standards may be purchased from chemical supply houses, but their identity and purity are not assured and the cost of purchasing these chemical standards is often prohibitive.

Recommendation

Research to identify and develop reference materials

1. Identify a lead agency. Firstly, there is a need to identify or designate a lead agency in Canada that can initiate and foster this initiative. There are existing government agencies that have demonstrated an ability to deal with the technical and administrative aspects of such an endeavour. Given the current interest within Canada to develop regulations pertaining to NHPs, there seems to be a climate that would be positive to this initiative. It may also be possible to forge a collaboration involving experts at Agriculture Canada, the United States Pharmacopeia (USP), and the Association of Official Analytical Chemists (AOAC).

This lead agency would need to gain credible international recognition. To do so, it would need to involve the various Canadian stakeholders in a unified effort, and to develop a network both national and international in scope. The long-term sustainability of the lead agency would need to be guaranteed.

2. Identify interested partners. Secondly, research partners would be identified and research collaboration would be established. Given the expanding interest in NHPs in Canada and abroad, it should be possible to develop a pool of highly qualified people that includes both Canadian and international partners. To avoid duplication of efforts, it would be especially important to forge a collaborative arrangement with the current American initiative lead by the AOAC. Since stakeholders recognize the need for reference materials, it might be possible to obtain funding for this initiative from both industry and various research funding agencies. Existing Canadian industries might also be a potential source for pure chemicals.

Despite these opportunities, no committed funding currently exists and the scientific expertise related to reference materials for NHPs (and especially botanicals) is not well established in Canada.

3. Establish protocols and programs. Thirdly, protocols for the identification and development of reference materials would need to be established by the research network. A number of Canadian laboratories and institutes have the necessary equipment and experience with the required technologies to accomplish this work. Some existing networks of expertise also could be tapped into to facilitate this work.

A program for the development and validation of methodologies for establishing and analyzing reference materials should be initiated. The priority botanicals and their target analytes would need to be determined and the necessary calibration standards would have to be set. The ability to trace reference materials and to establish a chain of custody are challenges that would need to be addressed if credible reference standards are to be developed.³ Even once these steps are completed, the process could be both time consuming and costly (even if very necessary). For example, the National Institutes of Standards and Technology (NIST) in the United States publishes about two new reference standards per year. Therefore, although little work has been done in this area to date, it is necessary to avoid any duplication of efforts. To do so, international networking must be established.

The research that would be applied to the development of reference standards for NHPs could be linked to research exploring stability and storage issues, the identification of appropriate markers, the chemical properties of various NHPs and the isolation of chemical constituents. This linkage could also help to avoid the duplication of efforts.

Next Steps

To advance the strategies associated with this research proposal, the following three steps are suggested.

1. Identify individuals, agencies and associations with expertise in this field and convene an expert advisory committee (EAC). It may also prove valuable to get input from the group addressing analytical methods,⁴ since these methods will largely determine the required reference materials.
   
2. The EAC should identify funding sources as well as supportive national and international partners.
   
3. The EAC should establish timelines and priorities for the program.

The following model is suggested as one way that these partnerships might be linked. ( See Figure 1.)

Figure 1. Partnerships to Research Reference Materials Image
(This will open in a new window with a file size of 5 K )
(You may have to use the scroll bar to see the entire image)

The various partners could be representatives from the different organizations listed in the text balloons in Figure 1. The EAC would be drawn from these partners and implement the action plan. Reference materials would be determined as expeditiously as possible, paralleling the benchmarks already established by the National Institute of Standards and Technology (NIST) in the United States. A priority list of reference standards needs to be established at the outset of this project.

4. Develop Analytical Methods to Determine Markers

Issue

At present, there are numerous methods that may be used to analyze a given botanical, and the robustness of these methods is varied. Consequently, the results of botanical analyses often vary significantly between laboratories. There is a strong need for the development and industry-wide adoption of one rigorous method for each botanical. Similarly, the markers used in these analyses also vary widely throughout the industry. Marker compounds are one or more constituents that naturally occur within an NHP, particularly within botanical remedies. It has sometimes been suggested that the quantity of these marker compounds can be used to quantify the potency of a particular product. They can also be used to ensure standardization of the product consistency from batch to batch during manufacturing, and are subsequently often associated with the assurance of quality. However, many markers are not related to the biological activity of the product, and are, therefore, not necessarily the best determinant of either quality or potency. Furthermore, marker analysis alone does not ensure the correct identity or purity of the botanical.

Recommendation

Develop analytical methods to determine markers.

1. Establish a national committee of experts. A national committee with technical expertise needs to be established. It would coordinate inter-laboratory studies for the creation of official analytical methods. Members of the committee would be drawn from experts in academia, government and industry. Since there is an internationally recognized need to harmonize both the methods and the markers used in the manufacture, standardization and quality control of products, the committee should be able to tap into this widespread interest. The national committee would also take advantage of research already completed, so that efforts would not be duplicated. Such prudence is particularly warranted since funding for such projects is not usually readily available.

2. Tasks of the national committee. More specifically, the national committee would:

• prioritize the botanicals that will be the object of such research
  
• compile and critically review the methods and markers that are presently being used
  
• coordinate the develop of officially validated methods to determine and analyze markers

The national committee should be established by a blue ribbon panel of judges drawn from recognized and scientifically qualified persons at arms-length from the interested agencies. The members should be selected from representatives of the relevant scientific disciplines drawn from academia, government and industry. Participation should also be encouraged from extra-national agencies such as the Office of Dietary Supplements (part of the National Institutes of Health in the United States), the AOAC and the AHPA.

3. Linkage with other efforts. The national committee should work in collaboration with the group that is overseeing the development of reference materials.⁵

4. Funding. Some funding for this initiative might be obtained from industry associations since they will directly benefit from the national committee's work. Additional funding might be gleaned from national and provincial funding agencies.

5. Timelines. A search for prospective members of the national committee could be completed within the next six months. The committee should be established prior to the passage of the NHP regulations.

5. Evaluate and Identify Biologically Active Components

Issue

The potency of a product is usually determined by the quantity of the active ingredient required to produce the desired therapeutic effect. For most botanical medicines, the biologically active ingredients that produce the desired therapeutic effect have not been conclusively identified. Furthermore, it is possible that more than one biologically active compound or class of constituents produces the therapeutic effect. Other constituents might have a necessary and vital influence (i.e., additive, synergistic or antagonistic effects) on the biologically active component(s). The ratio of these components might be more important than their total quantities.

Recommendation

Perform research to evaluate and identify biologically active components.

1. Need for basic science research. The mechanisms of action for NHPs, and botanical remedies in particular, need to be more thoroughly understood. Furthermore, relevant biological assays are required to obtain meaningful measurements of potency and efficacy. Therefore, basic science research should be undertaken to develop these bioassays and mechanisms of action.

The researchers should take advantage of the existing infrastructures that link producers, academia, government and industry. Appealing to these partnerships, they should seek funding at all levels. As a result of this research, quality controls could be enhanced across the industry and technology transfer could be encouraged. To avoid the duplication of research, it would be wise for these researchers to network with researchers engaged in the development of methods for botanical identification.⁶

It will be necessary to determine which botanicals and/or products should be the focus of the initial research. Priority should be given to those bioassays that would contribute to enhanced clinical outcomes for human health. Since concerns over intellectual property rights may be raised, this matter would need to be addressed at the outset.

2. Establish a database. A peer-reviewed database of existing bioassays and mechanisms of action should be established. Such an endeavour would promote technology and knowledge transfer. It would help to avoid unnecessary duplication of research and increase the efficiency and progress of related research. A database would also encourage the development of cross-disciplinary collaboration among interested parties.

Establishing the reliability of data and updating the database would be an ongoing challenge just as it could be difficult to retrieve all of the relevant literature. However, the benefits greatly outweigh these challenges.

Next Steps

1. Establish a virtual network. Researchers in areas related to NHPs should be linked through a virtual network. Such a network would be similar to two earlier attempts at network building - the Natural Sourced Medicine Research Network originating from Dalhousie University, and the Herbal Research Network initiated in Western Canada. A leader/coordinator for this national network would need to be identified. The existing expertise in bioassay and mechanisms of action research in Canada would also need to be identified. This latter task could be realized through a survey (similar to the cardiovascular survey directed by Dr. Grant Pierce of the University of Manitoba). The following disciplines would be included among those surveyed: botany, phytochemistry, herbalist and traditional healers, pharmacognosy, pharmacology, toxicology, biochemistry, biology, nutrition and clinical sciences. Through the survey, the network would not only discover who else might be undertaking research in this area, but it would also inform others of this initiative. Consequently, a significant increase in awareness would result.

The first goal of the network, once the survey is completed, would be to establish a database on bioassays and mechanisms of action, as described above.

2. Determine which NHPs should be researched. The research priorities in biological assays and mechanisms of action would be influenced by the major health problems facing Canadians. In other words, the NHPs that might best serve these health needs, or the NHPs that are most commonly used to treat these diseases, would be the focus of research. These health priorities would undoubtedly include the treatment of cardiovascular disease, cancer (particularly breast, prostate and lung cancer), diabetes and other metabolic diseases, infectious diseases, neurodegenerative diseases and diseases of the immune system. By aligning with existing efforts to treat these diseases, it may be possible to partner with existing funding agencies and integrate into their mandates and strategic initiatives. NHPs that are used for the prevention of diseases and the promotion of health should also be considered.

3. Call for proposals. The network would also call for proposals for investigator-initiated bioassay and mechanisms of action projects. These proposals could seek funding from CIHR and NSERC, as well as from industry and government.

6. Develop Methods to Monitor Outcomes

Issue

While it is generally agreed that establishing quality controls and ensuring good product standards for NHPs would benefit consumers, is this necessarily the case? Is value added when regulations formally stipulate the quality controls and product standards that must be applied to the growing, production, distribution, marketing and sale of NHPs? If it could be demonstrated that improving quality controls and product standards would provide added benefit to consumers, would this not validate the work of the NHPD and the enactment of regulations for NHPs?

Recommendation

Measure and monitor quality control initiatives.

1. Monitor progress and measure outcomes. Monitoring the progress and measuring the outcomes of the quality controls and product standards regulations and initiatives is imperative to assessing their impact on the safety, efficacy and quality of NHPs. Such monitoring and measures will also review the ability of Canadian citizens and health care providers to make more informed choices in their selection and use of high-quality, safe and effective NHPs.

2. Establish baseline values. Prior to the enactment of new regulations, baseline values need to be established for two of the populations in particular that would be targeted in such a study - namely the general Canadian population and Canadian health care providers. It would be necessary to determine current traits and patterns for these populations if the effects of the new regulations and initiatives are to be monitored and measured. Through the use of surveys, researchers would assess the attitudes, awareness, perceptions and practices relative to NHPs for each of the target populations. The researchers would explore how their attitudes, awareness, perceptions and practices relate to the safety, efficacy, access and informed use of NHPs. The researchers would also measure the general wellness of each member of that population group.

Quality Controls and Product Standards: A Research Priority-Setting Conference (March 8-9, Vancouver)

Specific Traits and Dynamics of Each Target Population

	Population - Canadian Population	Population - Health Care Prov & Researchers	Population - NHPD	Population - Industry and Retail
Focus - Safety	X	X	X	X
Focus - Efficacy	X	X	X	X
Focus - Access	X	X	X	X
Focus - Informed Use	X	X	X	X
Focus - Wellness	X	X	X	X

The research questions and methods would be tailored to address the specific traits and dynamics of each target population. For example, to assess the impact of quality control regulations and initiatives on each population's attitudes, awareness, perceptions and practices pertaining to the quality, safety and efficacy of NHPs, the researchers might make the following queries:

• Canadian population
  • Are Canadians aware of the possibility to file an Adverse Event Report?
    
  • What are their perceptions of the safety, efficacy and accessibility of NHPs?
    
  • How do they access information concerning NHPs; do they feel well informed when making a decision?
    
  • Are they aware of the new regulations coming forth from the NHPD? If yes, what are their views?
• Health care providers
  • Are health care providers aware of the possibility to file an Adverse Event Report? Have they ever filed such a report? Are they aware of the reporting process?
    
  • What are their perceptions concerning the safety, efficacy and quality of NHPs?
    
  • To what extent do they use NHPs in their practice?
    
  • To what extent to they monitor or note NHP use among their patients?
• NHPD
  • Has the NHPD dealt with any health hazards alerts?
    
  • Has it been part of any initiatives to recall products?
    
  • What is its role in the pre-market review process? How does this help to ensure that Canadians have safe, high-quality NHPs that they can choose?
    
  • How is it adding to Canadians' knowledge of NHPs so that they can make informed choices?
• Industry
  • What is its role in the product review process?
    
  • How is it making use of caution and warning labeling?
    
  • What is its current market penetration?
    
  • How have consumer choices and current regulations enhanced or limited the availability of cost-effective, science-based, high-quality, safe and effective products?

Next Steps

1. Identify funding. Potential sources of funding for such a research project must be identified and could include:

• the Institute of Population and Public Health, part of CIHR
  
• Canadian Institute for Health Information (CIHI)
  
• the Social Sciences and Humanities Research Council (SSHRC)
  
• health insurance providers

2. Survey social attitudes. A research project to measure the social attitudes of the Canadian population (or sub-populations such as the HIV/AIDS community or paediatrics and youth) should be developed and refined through consultation with:

• the sources of research funding and various stakeholders (e.g., industry, CIHR, and professional associations such as the Canadian Pharmacists Association, Canadian Medical Association, Canadian Naturopathic Association, etc.)
  
• relevant partners (e.g., sub-population coalitions)
  

Operational definitions for the focus categories (i.e., safety, efficacy, access, informed choice and wellness) should also be developed at this stage.

3. Timelines. It would be best if the surveys to establish baseline information on two of the target populations - the general Canadian population and Canadian health care providers - could be completed prior to the regulations being enacted, or prior to the regulations being printed in Canada Gazette II.

Concluding Remarks

During the working and plenary sessions, the participants shared their expertise and opinions with considerable enthusiasm and goodwill. Several of them noted a certain urgency for these research initiatives to be undertaken as expeditiously as possible, even as they acknowledged the various challenges to be overcome. They felt that the realization of these research priorities would help to address several concerns related to quality controls and products standards for NHPs in Canada. Consequently, advancing these research priorities would assist the NHPD with its goal of ensuring that Canadians have access to safe, effective and high-quality NHPs and to the accurate and detailed information required to make properly informed choices.

At the end of the second day, Philip Waddington, Director General of the NHPD, expressed his gratitude for the very fine work and recommendations of the participants. He observed that while all of the points raised were important, only some of them fell within the mandate of NHPD. Accordingly, the NHPD will be working diligently to ensure that the information and ideas generated during this conference will be effectively utilized and dispersed. The conference co-chairs echoed his thanks.

Appendix A - Participant List

Valerie Assinewe
Ottawa, Ontario

Dennis V.C. Awang
MediPlant Consulting Inc
White Rock, British Columbia

Branka Barl
University of Saskatchewan
Saskatoon, Saskatchewan

Don Beatty
Boehringer Ingelheim (Canada) Ltd
Vancovuer, British Columbia

Joseph M. Betz
Office of Dietary Supplements / NIH
Bethesda, Maryland
USA

Joe-Anne Blanchette
Natural Health Products Directorate
Ottawa, Ontario

Doris Braslins
Natural Sciences & Eng. Res. Council
Ottawa, Ontario

Colin Briggs
University of Manitoba
Winnipeg, Manitoba

Paula N. Brown
BC Institute of Technology
Burnaby, British Columbia

Roxy Campbell
Natural Factors
Burnaby, British Columbia

Peter Chan
Natural Health Products Directorate

Thomas K. H. Chang
University of British Columbia
Vancouver, British Columbia

Ed Croom
Indena USA East Inc.
Pasippany, New Jersey
USA

Alison Duncan
University of Guelph
Guelph, Ontario

Ann Eastman
BC Research Inc.
Vancouver, British Columbia

Albert Fok
Kiu Shun Trading Company Ltd.
Vancouver, British Columbia

Emma Guns
The Prostate Centre at Vancouver General Hospital
Vancouver, British Columbia

Pierre S. Haddad
University of Montreal
Montreal, Quebec

Maureen Hatanaka
NRC - Industrial Research Assistance Program
Kelowna, British Columbia

Tracey Innes
Agriculture & Agri - Food Canada
New Westminster, British Columbia

Gary Leong
Jamieson Laboratories Ltd.
Windsor, Ontario

Gillian Leverkus
Canadian Coalition Herbal Associations
Mill Bay, British Columbia

Yuan-chun Ma
Canadian Phytopharmaceuticals Corp.
Richmond, British Columbia

Robin Marles
Brandon University
Brandon, Manitoba

Allison McCutcheon
University of British Columbia
Vancouver, British Columbia

Brian Mori
Health Canada
Burnaby, British Columbia

Helen Nicolidakis
Health Canada
Burnaby, British Columbia

Michael O'Connell
Ashbury Biologicals
Toronto, Ontario

Jason Quigley
Naturally Nova Scotia Health Products Ltd.
Dartmouth, Nova Scoia

Kerry Reinhard
Health Canada
Ottawa, Ontario

Paul Saunders
Canadian College of Naturopathic Medicine
North York, Ontario

Scott Sawler
NDMAC
Ottawa, Ontario

Jackie Shan
CV Technologies
Edmonton, Alberta

Gaye Sims
JR Laboratories Inc.
Upper Tantallon, Nova Scotia

Michael J. Smith
Health Canada
Ottawa, Ontario

Roumiana Stefanova
Naturally Nova Scotia Health Products Ltd.
Dartmouth, Nova Scotia

Ralph Sturgeon
National Research Council of Canada
Ottawa, Ontario

Philip Waddington
Natural Health Products Directorate
Ottawa, Ontario

Facilitator: Dennis Patrick O'Hara

Invited, but unable to attend:

Jim Hudson
University of British Columbia
Vancovuer, British Columbia

Karen Cooke
Centre for Integrated Healing
Vancouver British Columbia

Appendix B - Agenda

Friday, March 8th

9:00 a.m.
Welcome
Michael J. Smith & Allison McCutcheon

9:10 a.m.
Introductions (all participants)

From where do we begin...

9:45 a.m.
Overview of Current State of Quality Control & Product Standards Allison McCutcheon
University of British Columbia

10:05 a.m.
U.S. Perspective
Joe Betz
Office of Dietary Supplements, NIH

Table talk

10:30 a.m.
Break

Views from the field...

11:00 a.m.
Industry Perspective
Don Beatty Boehringer-Ingelheim

Research Perspective
Robin Marles
Brandon University

Regulator's Perspective
Peter Chan
Natural Health Product Directorate

Table talk

12:30 p.m.
Lunch

1:30 p.m.
First Working Group Session - Establishing the Priorities (see mini-agenda)

3:30 p.m.
Break

3:45 p.m.
First Plenary Session
Each group will have 10 minutes in the plenary session to report the priorities it has identified. The goal is to construct a single list of priorities derived from the reports of the various groups.

5:30 p.m.
Adjourn
Participants complete questionnaire on first day's proceedings.

Saturday, March 9, 2002

9:00 a.m.
Re-cap of polling results & questionnaire from first day

9:15 a.m.
Second Working Group Session - Establishing the Strategies (see mini-agenda)
Participants self-select into the priority of their interest.

10:30 a.m.
Break

10:45 a.m.
Second Plenary Session
Each group will have 10 minutes in the second plenary to report back on the strategies that it has identified. The goal will be to construct a single list of preferred strategies derived from the reports of the various groups.

12:30 p.m.
Lunch

1:30 p.m.
Report on the voting in the morning session & re-cap of where we're at

1:40 p.m.
Third Working Group Session - Identifying the Next Steps (see mini-agenda)
Participants self-select into the strategy of their interest. Each group will determine the next steps that might be taken to implement that strategy and the relative timeline for each step.

2:45 p.m.
Break

3:00 p.m.
Third Plenary Session
Each group will have 7 minutes in plenary to report back on the next steps it identified. The rest of the plenary will have an opportunity to comment on and validate the identified next steps.

4:15 p.m.
Concluding Remarks

4:30 p.m.
Adjourn
Participants complete questionnaire on second day's proceedings.

Appendix C - Research Priorities From Each Working Group

Group 1

1. Literature review and compilation of a database on existing quality data, including international information. This would include information on methods, markers, reference standards, preparation forms, standards in other countries and expertise available in Canada.
2. Establish criteria for evaluating data compiled in item number one.

After the priorities have emerged from steps one and two:

1. Determine research methods for assessing botanical identity.
2. Evaluate and identify biologically active components relevant to intended pharmacological application.
3. Research techniques and processes to reduce contaminants to acceptable levels in finished products.

Group 2

1. Build a 21^st century information system that explores 'what's out there' with respect to definitions and specifications. This system would be both a database and a network.
2. Develop test methods relating to plant identification and characterization, potency, purity and reference materials. Follow the National Institutes of Standards and Technology (NIST) model.
3. Develop a database pertaining to research on herbs. Maintain the database with updates.
4. Derive specifications for what should and should not be included in specific products. Adulterants would be identified to enhance product safety.
5. Education in the specialty of pharmacognosy would be made a priority.

Group 3

1. Increase identification capacity (capabilities) for botanicals.
2. Establish reliable and accurate reference standards.
3. Develop and validate laboratory methods through inter-collaborative studies (lab proficiency).
   
4. Develop GAPs. Support quality controls and safety at the production level to enhance purity. Support agronomy research.
5. Support education and training.

Group 4

1. Develop a scheme that would result in the Certification of Botanical Identity.
2. Establish purity specifications for raw materials.
3. Establish validated analytical methods for characterization of NHPs. Include an international scope.
4. Generation of artifactual reference materials.
5. Prioritize top botanicals for research to meet the needs of Canadians.

Group 5

1. Research to develop validated authentication methods and tools. Reference collection is critical.
2. Development and validation of analytical methods (methodology) for quality testing.
3. Development of methods to monitor outcomes of quality controls, standards and regulations, focused on the impact to consumers and industry.
4. Research to define and enhance safety of botanical products: purity, toxicity and efficacy.
5. Develop standards (i.e., safety and compositional specifications) for specific botanicals based on intended usage.

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