Phytopharmaceuticals and the Need for Legal Regulation

  Globally, herbal medicine has been recognized as an important alternative to modern allopathic medicine. Although herbal medicines are very popular in society, only a few medicinal plants have been scientifically evaluated for their potential in medical treatment. In most countries, herbal medicines fall short in drug regulation, are unregistered, and are generally not controlled by health authorities. For this reason, the safety of herbal medicines raises concerns. In the United States, the Food and Drug Administration (FDA) estimates that more than 50,000 adverse events are caused by herbal and other dietary supplements. [1] Furthermore, efficacy has not been established for most herbal medicines, and quality assurance has not been secured. The World Health Organization's (WHO) Traditional Medicine Strategy 2014-2023 (TM) has focused on increasing the safety, efficacy, and quality of TM by expanding the knowledge base and providing guidance on regulatory and quality assurance standards. Herbal medicine products include herbs, herbal materials, herbal preparations and plant parts, finished herbal products containing combinations of other herbal materials or active ingredients. [3] Herbs contain raw plant material; for example, leaves, flowers, fruits, seeds, and stems. Among herbal materials are, in addition to plants, fresh fruit juices, gums, fixed oils, volatile oils, resins, and dried herb powders. Herbal preparations form the basis for finished herbal products and may contain fragmented or powdered herbal materials or extracts, tinctures, and fatty oils of herbal materials. Finished herbal products consist of herbal preparations made from one or more plants. Regulations regarding herbal preparations vary from country to country. Globally, various different regulatory approaches are as follows: The same legal requirements for all products, the same legal requirements for all products and certain types of evidence not required for herbal medicines, exemption from all legal requirements for herbal medicines regarding registration or marketing authorization, exemption from all legal requirements for herbal medicines regarding registration or marketing authorization, herbal medicines subject to all regulatory requirements, herbal medicines subject to legal requirements regarding registration or marketing authorization.

In Europe, herbal preparations for marketing approval [5] are classified into three categories as follows:

- Traditional medicinal use provisions accepted on the basis of adequate safety data and reasonable efficacy. - Well-established medicinal use provisions proven by the provision of scientific literature establishing that the active substances of medicinal products have been in well-established medicinal use recognized in efficacy within the European Union for at least 10 years, and the safety level is considered acceptable as it could be classified below that of a product. - Safety and efficacy data in the company's own development alone or a combination of its own studies and bibliographic data. The FDA Botanical Drug Development Guidance [6] describes appropriate development plans for herbal medicines to be submitted in new drug applications and specific recommendations regarding the submission of investigational new drug applications. The term botanical means products containing plant materials, algae, macroscopic fungi, and combinations thereof. FDA guidance recommends that investigational new drug applications contain sufficient information to demonstrate that the drug is safe for testing in humans and that the clinical protocol is appropriately designed for its purposes. In addition to general legal regulatory requirements for nonclinical pharmacology/toxicology studies, clinical evidence for efficacy and safety—for botanical medicines, there are special requirements as follows to ensure the safety and quality of botanicals:

• Product definition and documentation of previous human experience:

- Description of the herbal raw materials used and known active components or chemical components. - Previous human experience. • Quality control: - Botanical raw material. - Botanical drug substance and drug product. • Characterization, chemical characterization, manufacturing processes, biologicalanalysis, specifications, stability, current good manufacturing practices, andenvironmental assessment. • Evidence of ensuring therapeutic consistency: - Botanical raw material control. - Quality control and manufacturing control by chemical testing. - Biological analysis. - Clinical data: Dose-response data and multiple batch clinical data. New regulations to be made in the regulation for phytopharmaceuticals should be in harmony with the United States, China, and other countries. This new regulation is expected to scientifically promote innovation and development of new drugs from botanicals and help gain acceptance of the use of herbal products by modern medicine. These regulations will encourage phytopharmaceutical drug development research for academia, researchers, and industry. [8] Gülşah Gedik Assist. Prof. PhD Trakya University Faculty of Pharmacy Department of Pharmaceutical Technology Department of Pharmaceutical Technology

References 1. FDA Should Take Further Actions to Improve Oversight and Consumer Understanding GAO-09-250: Published: 29 January, 2009. Publicly Released: 2 March, 2009. [Last accessed on 2016 Mar 07]. Available from: http://www.gao.gov/products/GAO-09-250 . 2. WHO Traditional Medicine Strategy 2014-2023. Geneva, Switzerland: World Health Organization; 2013. [Last accessed on 2016 Mar 07]. Available from: http://www.who.int/medicines/ publications/traditional/trm_strategy14_23/en/ [Google Scholar] 3. World Health Organization General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine. 2000. [Last accessed on 2016 Mar 04]. Available from: http://www. whqlibdoc.who.int/hq/2000/WHO_EDM_TRM_2000.1.pdf . 4. World Health Organization. Regulatory Situation of Herbal Medicines a Worldwide Review. 1998. [Last accessed on 2016 Mar 04]. Available from: http://www.who.int/medicinedocs/pdf/ whozip57e/whozip57e.pdf . 5. European Medicines Agency Herbal Medicinal Products. [Last accessed on 2016 Mar 07]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_ content_000208.jsp# . 6. Food and Drug Administration Botanical Drug Development Guidance for Industry. 2015. Aug, [Last accessed on 2016 Feb 24]. Available from: http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/UCM458484.pdf . 7. Narayana DA, Katiyar C. Draft amendment to drugs and cosmetics rules to license science based botanicals, phytopharmaceuticals as drugs in India. J Ayurveda Integr Med. 2013;4:245–6. 8. Arun Bhatt, Phytopharmaceuticals: A new drug class regulated in India, Perspect Clin Res. 2016 Apr-Jun; 7(2): 59–61.