197 P a g e International Standard Serial Number (ISSN): 2319-8141 International Journal of Universal Pharmacy and Bio Sciences 3(1): January-February 2014 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89*** ICV 5.13*** Pharmaceutical Sciences REVIEW ARTICLE!!! REGULATORY REQUIREMENTS FOR REGISTRATION OF DIETARY SUPPLEMENTS IN ASEAN AND AFRICAN COUNTRIES Sudheer Kumar Gumme 2 *, Pramod Kumar T M 1, Vidya Sabbella 2, Rohit Gujarati 2 1 Professor, M. Pharm, Ph.D, Department of Pharmaceutics, JSS University, Mysore 2 M. Pharm, Department of Regulatory Affairs, JSS University, Mysore. KEYWORDS: Food Supplements, ASEAN, African. For Correspondence: Sudheer Kumar Gumme * Address: M. Pharm, Department of Regulatory Affairs, JSS University, Mysore. E-mail : 19.sudheerkumar@gmail. com ABSTRACT Dietary supplements or food supplements are widely used across all ages and user groups and constitute a considerable business sector in most developed countries. Regulating supplements as a foodstuff and not a medicine is a challenging task as most of the Vitamins and Minerals pose high risk to the consumers when taken at higher levels than recommended especially fat soluble vitamins. Regulatory Authorities and Manufacturers are confronting with various challenges in setting the safe levels of these nutrients in Dietary Supplements. Most of the well regulated markets such as United States of America, Europe, Australia do not mandate the registration of dietary supplements before marketing them in their territory, however each of these nations have their own post marketing vigilance system to monitor the safety of the dietary supplements. Some semi-regulated markets such as ASEAN and African countries require manufacturer or marketing authorization holder to submit Quality, Safety, Efficacy and Administrative data for registration of the dietary supplements to grant license for marketing. The registration requirements varies among the countries not akin to that of registration of medicinal products because food supplements are generally considered as safe, hence some of the data are exempted for submission to save time and resources for applicants. A dietary supplement can also be considered under drug if any specific claims for treatment are made or the content of active ingredient is high such that additional safety parameters has to be justified subject to country regulations.
198 P a g e International Standard Serial Number (ISSN): 2319-8141 INTRODUCTION: After the air we breathe and the water we drink, for most people it is the food we eat that is the most important influence on our health and well-being, affecting our growth, development and maintenance of health throughout our lives. Social, demographic, economic and lifestyle changes determine our nutritional status and nutrition is now recognized to be a major contributor to morbidity and mortality rates and to the development of the chronic, non-communicable diseases including cardiovascular diseases and cancers. Many governments and international agencies around the world already recognize the need for supplementation in certain vulnerable groups. Healthcare costs are expected to rise dramatically in the next two decades, and much more attention needs to be focused on how they can be controlled. Two-thirds of US adults continue to take dietary supplements, with consumer confidence in the products remaining high, says the 2013 council for Responsible Nutrition (CRN) consume survey on Dietary supplements 1. The contributions of nutrition science and the application of the research to support the health and wellbeing of the growing world population continue to be exciting challenges for the foreseeable future. Even most stringent authorities like United States Food and Drug Administration (USFDA) do not regulate food supplements as compared with Medicinal Products reflecting the fact that they are safe enough with large therapeutic window. Almost every country makes registration of medicinal product compulsory by submitting entire data proving the Quality, Safety and Efficacy but dietary supplements do not fall under the category of medicines hence in most of the developed nations they are marketed freely without prior registration with the exception of few countries where necessary pre evaluation is conducted by respective authorities. DEFINITION OF A HEALTH / DIETARY / FOOD SUPPLEMENT 2 Health Supplements contain one or more, or combination of the following ingredients i. Vitamins, minerals, amino acids (natural or synthetic) ii. Substances derived from natural sources, including non-human animal and botanical materials in the form of extracts, isolates, concentrates; and iii. Are presented in any of the following dosage forms to be administered in small unit doses: e.g Tablets, Capsules, Soft gels, Liquids, Syrups and any other dosage form as may be approved by Licensing Authority.
199 P a g e International Standard Serial Number (ISSN): 2319-8141 CLAIMS FOR HEALTH SUPPLEMENTS 2 Nutritional (General) Health claims These claims for products having well documented ingredients, where the function of each ingredient is supported and documented in standard reference texts. These are intended for General health maintenance and wellbeing, Vitamin and/or mineral supplementation, such claims are permitted only when the relevant vitamin and mineral used in the product amounts to >30% the RDA value. Examples: Support good health and growth, Supplementing nutrition, nourish the body, Strengthen the body, Relieve general tiredness, weakness Functional Health Claims: These claims has to be substantiated through ingredient based evidence, and when necessary product based evidence and the claims made should not imply that the product is necessary or play a role in diseased states Example: General support maintenance of healthy functions, Assist in maintaining joint mobility, etc., RECOMMENDED DAILY ALLOWANCES (RDA): An RDA is the average daily dietary intake level; sufficient to meet the nutrient requirements of nearly all (97-98 percent) healthy individuals in a group. The dietary supplements should contain nutrients as per RDA limits specified by the authorities given in Table I and well below the Upper Levels (UL). The recommended overall intake of each nutrient in a day should not be greater than 200% of each nutrient s RDA or above upper tolerable limits. Maximum amounts of vitamins and minerals present in food supplements per daily portion of consumption as recommended by the manufacturer shall be set considering the upper safe levels of vitamins and minerals established by scientific risk assessment based on generally accepted scientific data and intake of vitamins and minerals from other dietary sources 3.
200 P a g e International Standard Serial Number (ISSN): 2319-8141 Vitamins/ Minerals Table I: Recommended Daily Allowances and Upper Levels of Vitamins and Minerals Unit Recommended Daily Allowances (RDA) Maximum daily intake / Upper levels(ul) EU 4 USA 5 WHO 6 Kenya 7 / Uganda 8 USA 5 WHO 6 ASEAN 9 Kenya 7 / Uganda 8 Vitamin A mg 0.8 0.9 0.4 1.5 3 0.6 1.5 3-7.5 Vitamin D IU 200 600 400 400 4000 2000 1000 800 Vitamin E mg 12 15 10 13.5 1000 1000 536 540 Vitamin K μg 75 120 -- 65-80 ND -- 0.12 160 Vitamin B1 mg 1.1 1.2 1.2 1.5 ND ND 100 25-100 Vitamin B2 mg 1.4 1.3 1.3 1.6 ND ND 40 25-100 Niacin mg 16 16 16 20 35 35 15 50-100 Pantothenic acid mg 6.0 5 5 10 ND ND 200 200-1000 Vitamin B6 mg 1.4 1.7 1.7 2.0 100 100 100 25-100 Folic acid μg 200 400 400 200 1000 1000 900 800 Vitamin B12 μg 2.5 2.4 2.4 6.0 ND 1000 600 500-2000 Biotin μg 50 30 30 3.0 ND -- 900 50-200 Vitamin C mg 80 90 45 60 2000 -- 1000 1000-6000 Calcium mg 6 1000 1000 1000 2500 -- 1200 1500 Magnesium mg 375 420 260 350 350# 350 350 800 Iron mg 14 8-18 9-27 10-18 45 -- 15 36 Copper mg 1.0 0.9 -- 2 10 -- 2.0 3 Iodine μg 150 150 150 150 1100 2100 150 300 Zinc mg 10 11 14 15 40 -- 15 30-50 Manganese mg 2 2.3 -- 2 11 -- 3.5 10 Selenium μg 55 55 34 70 400 400 0.2 400 Chromium μg 40 35 -- 200 ND 250 500 600 Note: RDA limits mentioned (USA) for adults below 70 years excluding special population (Infants, children, pregnancy & lactating) # The ULs for magnesium represent intake from a pharmacological agent only and do not include intake from food and water UL (Upper Level): A Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the general population. Unless otherwise specified, the UL represents total intake from food, water, and supplements. (USA) ND: Not Determined due to Lack of sufficient evidence on safety and Toxicity of the ingredient.
201 P a g e International Standard Serial Number (ISSN): 2319-8141 Table II: Major technical requirements for registration of Dietary Supplements in Kenya and Uganda 7, 8 S.No Key Requirement/Documents Kenya Uganda 1. Authorized representative in Kenya (Power of Attorney) 2. Valid Manufacturing License 3. Free Sale Certificate (FSC) 4. Justifications for inclusion of each ingredient 5. Unit dose composition with official references (BP, USP etc.,) 6. Executed Batch Manufacturing Record (BMR) 7. Specifications and Certificate of Analysis of each Raw material 8. Finish Product Specification and test procedures 9. Process Validation 10. Summary of Product Characteristics (SPC) 11. Specifications of packing material and proof of compatibility & suitability of container closure system 12. Stability Data 13. Literature reference for safety of the product 14. Samples in commercial packs along with Certificate of Analysis 15. Registration fee (US$) 1000 500 16. Timelines for approval (months) 6 -- 17. Validity of registration (Year) 01 -- 18. Good Manufacturing Practice (GMP) Inspection by authority Yes No
202 P a g e International Standard Serial Number (ISSN): 2319-8141 Table III: Requirements for Registration of Dietary Supplements in ASEAN Countries 10 Administrative and Technical Data for ASEAN Countries CFS / CPP Applicable to Cambodia, Indonesia, Malaysia, Philippines, Thailand, Vietnam Letter of Authorization Applicable to Indonesia, Malaysia, Philippines Quality data Applicable to Cambodia, Indonesia, Malaysia, Philippines, Thailand, Vietnam Safety data Applicable to Cambodia, Indonesia, Malaysia, Philippines, Thailand, Vietnam Efficacy data Applicable to Cambodia, Indonesia, Thailand S. No REQUIREMENT VT CM SP MM BD PL MY IN TL 1. GMP certificate -- 2. Formula 3. Raw material specification 4. Manufacturing process 5. Finished product specification -- 6. Stability study 7. Water content -- 8. Disintegration -- 9. Microbial contamination test Safety Data -- -- 10. Label/Pack insert Allowable levels of vitamins & minerals Heavy metal test (Lead, Arsenic, Mercury) 11. Monographs 12. Materia Medica 13. Published journals 14. Toxicological data Efficacy Data
203 P a g e International Standard Serial Number (ISSN): 2319-8141 15. References to support Efficacy/ Claims Monographs/Material Medica/Pharmacopoeia Published literatures 16 Clinical Trials 17 Post Marketing Control Monitoring of labeling, packaging & advertisement Monitoring of Adverse Effect Post Marketing Surveillance Sampling and Laboratory Test Inspection to the Manufacturer & Distributor 18 Dosage form Tablet Capsule Softgel Liquid form Pastilles Power Syrup Pil Required -Not Required Blank- Information not available BD - Brunei Darussalam: CM Cambodia: IN - Indonesia: MY Malaysia: MM Myanmar: PL - Philippines: SP Singapore: TH Thailand: VT Vietnam. Note: Only Seven countries among all ASEAN member states mention to register the Health Supplements before marketing in their territory (Brunei Darussalam, Cambodia, Indonesia, Malaysia, Philippines, Thailand, and Vietnam) 10. CONCLUSION: Many stringent regulatory bodies such as USFDA do not mandate registration of dietary supplements before marketing, because they are generally regarded as safe with broad therapeutic index. But this perception is different among few ASEAN and African nations where Pre-marketing registration of the Food Supplements is mandatory to market the products. The manufacturer or Marketing authorization
204 P a g e International Standard Serial Number (ISSN): 2319-8141 holder has to submit the required documents and samples to Regulatory Authority in which he intends to market the product. After thorough evaluation of the dossier marketing authorization may be granted or rejected. REFERENCES: 1. Stephen Daniells. CRN Survey: 85% of US adults confident in the safety, quality and effectiveness of dietary supplements [internet]. 2013, September 13. Available from: http://www.nutraingredients-usa.com/markets/crn-survey-85-of-us-adults-confident-in-thesafety-quality-and-effectiveness-of-dietary-supplements 2. Amy Peh. Health Supplement Guidelines. Singapore. Health Science Authority Regulatory Guidance; 2012 September. Pg. 19. Report No: GUIDE-CHP-300-005. 3. Article 5. Directive 2002/46/EC of the European Parliament and of the Council. Official Journal of the European Communities-2002, June, 10; L 183: 51-57. 4. Food Supplements. Summary information on the labelling of food supplements: Department of Health, govt. of UK; 2011 September; Pg.7. 5. Food and Nutrition Board, Institute of Medicine, National Academies. Dietary Reference Intakes (DRI). Institute of Medicine (IOM). USA; Pg.8. 6. World Health Organization (WHO), Food and Agricultural Organization (FAO) of United Nations. Vitamin and mineral requirement in Human Nutrition. Bangkok, Thailand. 1998 September. Second edition. Pg.361. 7. Pharmacy and Poison Board. Republic of Kenya. Registration of Food/Dietary Supplements and Borderline Products in Kenya. Guidelines to Submission of Applications. 2012. Pg.21. 8. Guidelines for Regulation of Food/Dietary Supplements in Uganda. Uganda. National drug Authority; 2009 March. Pg. 15; version: 5. 9. General Principles for Establishing Maximum Levels of Vitamins and Minerals in Health Supplements. Association of South East Asian Nations (ASEAN). Pg. 12. Version No: 4.0. 10. Profile of Definition, Terminology, and Technical Requirement of Traditional Medicines and Health Supplements among ASEAN Member Countries. Indonesia: The ASEAN Consultative Committee for Standards and Quality (ACCSQ) Product Working Group on Traditional Medicines and Health Supplements; 2006. Pg.37.