APPENDIX 4: GUIDELINE ON REGISTRATION OF HEALTH

2y ago
80 Views
3 Downloads
413.12 KB
61 Pages
Last View : 1m ago
Last Download : 2m ago
Upload by : Albert Barnett
Transcription

Drug Registration Guidance Document (DRGD)APPENDIX 4: GUIDELINE ON REGISTRATION OF HEALTHSUPPLEMENTSIMPORTANT NOTES:This guideline will serve as an additional reference guide for the registration ofhealth supplement products which consist of pharmaceutical active ingredients forhuman use as well as ingredients derived from natural sources.Applicants are advised to refer to Drug Registration Guidance Document for thecommon requirements for the preparation of a well-structured dossier applicationto be submitted for product registration.Outline:4.1Definition4.1.1 Health Supplement (HS)4.1.2 Indication4.1.3 Route of Administration4.1.4 Exclusion as Health Supplement4.1.5 Exemption4.2Active Ingredients4.3Maximum Daily Levels of Vitamins and Minerals for Adults Allowed inHealth Supplements4.4Health Supplement Claim4.4.1 Conditions4.4.2 Types and Evidence of Claims4.4.3 Claims Substantiation4.4.4 Illustrative Substantiation EvidenceSpecific Dossier Requirement for Registration of Health Supplements4.5Attachment 1:Checklist of Dossier Requirement for Health SupplementsAttachment 2:Table 20: Allowable Claims for Specific Active Ingredients inHealth SupplementsAcknowledgementsNational Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 230

Drug Registration Guidance Document (DRGD)4.1DEFINITION4.1.1 HEALTH SUPPLEMENT (HS)A Health Supplement (HS) means any product that is used to supplement a diet and tomaintain, enhance and improve the health function of human body. It is presented in smallunit dosage forms (to be administered) such as capsules, tablets, powder, liquids and shallnot include any sterile preparations (i.e. injectable, eyedrops). It may contain one or more,or the following combination:i) Vitamins, minerals, amino acids, fatty acids, enzymes, probiotics, and otherbioactive substances;ii) Substances derived from *natural sources, including animal, mineral and botanicalmaterials in the forms of extracts, isolates, concentrates, metabolite;iii) Synthetic sources of ingredients mentioned in (i) and (ii) may only be used where thesafety of these has been proven.4.1.2 INDICATIONi) Used as a Health Supplement;ii) Vitamin and mineral supplements for pregnant and lactating women.4.1.3 ROUTE OF ADMINISTRATIONOral4.1.4 EXCLUSION AS HEALTH SUPPLEMENTS:Health Supplements shall NOT include:i) Any product as a sole item of a meal;ii) Any injectable and sterile preparation;iii) Any cells, tissues, organs or any substance derived from the human body;iv) Any substance listed in the Schedule of the Poison Act;v) Any other route of administration other than the oral route.4.1.5 EXEMPTIONExtemporaneous preparations that have been prepared and given directly to the patient bya healthcare practitioner during the course of treatment.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 231

Drug Registration Guidance Document (DRGD)4.2ACTIVE INGREDIENTSListed active ingredients can be checked trough http://npra.moh.gov.my/ of product search.4.3MAXIMUM DAILY LEVELS OF VITAMINS AND MINERALS FORADULTS ALLOWED IN HEALTH SUPPLEMENTSNO.VITAMINS & MINERALSUPPER DAILY LIMIT1.Vitamin A5000 IU2.Vitamin D1000 IU3.Vitamin E800 IU4.Vitamin K (K1 and K2) 10.12mg5.Vitamin B1 (Thiamine)100 mg6.Vitamin B2 (Riboflavine)40 mg7.Vitamin B5 (Panthothenic Acid)200 mg8.Vitamin B6 (Pyridoxine)100 mg9.Vitamin B12 (Cyanocobalamin)0.6 mg10.Vitamin C (Ascorbic Acid)11.Folic Acid0.9 mg12.Nicotinic Acid15 mg13.Niacinamide (Nicotinamide)450 mg14.Biotin0.9 mg15.Boron6.4 mg16.Calcium17.Chromium18.Copper2 mg19.Iodine0.3 mg20.Iron 220 mg21.Magnesium350 mg1000 mg1200 mg0.5 mgNational Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 232

Drug Registration Guidance Document (DRGD)NO.VITAMINS & MINERALSUPPER DAILY LIMIT22.Manganese3.5 mg23.Molybdenum0.36 mg24.Phosphorus800 mg25.Selenium0.2 mg26.Zinc15 mgNote:1. Vitamin K (K1 and K2) is restricted only for combination with other vitamins andminerals in oral preparations. Vitamin K (K1 and K2) as a single ingredient in anoral preparation is not allowed.2. For pre and antenatal use, as part of a multivitamin and mineral preparation,levels higher than the 20mg limit established for adults may be permitted at thediscretion of the Authority.3. Any form of fluoride as an ingredient is not permitted in formulation of healthsupplement products.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 233

Drug Registration Guidance Document (DRGD)4.4HEALTH SUPPLEMENT CLAIM4.4.1 CONDITIONSAll claims made for HS shall:i)ii)iii)iv)v)vi)vii)be consistent with the definition of HS;enable consumers to make an informed choice regarding products;not be misleading or false;support the safe, beneficial and appropriate use of the product;maintain the level of scientific evidence which is proportional to the type ofclaims;be for health maintenance and promotion purpose only;not be medicinal or therapeutic in nature, such as implied for treatment, cure orprevention of disease.4.4.2 TYPES AND EVIDENCE OF CLAIMSi)A health supplement claim refers to the beneficial effects of consuming HS topromote good health and well-being (physical and mental) by providing nutrition,enhancing body structure/ function, relieving physiological discomfort and/orreducing the risk of health related conditions or diseases.ii) Types of HS claims are:o General or Nutritional Claims;o Functional Claims (medium);o Disease Risk Reduction Claims (high).iii) For a HS product making a General or Functional Claim on vitamin(s) and/ormineral(s), it must contain minimum of 15% of the Codex Nutrient Reference Value(NRV) per daily dose of the vitamin(s) and/or mineral(s). Other ingredients must besubstantiated by the evidences to which it has been supported.For example, if vitamin is less than 15% NRV, then the specific claim for this vitaminis not allowed unless there is evidence to support effect below this value.iv) For a HS product making Disease Risk Reduction Claim, it must be substantiated bythe evidences to which it has been supported.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 234

Drug Registration Guidance Document (DRGD)(i) Table 1: General or Nutritional ClaimsLevel ofclaimDefinitionExamples/Wording ofclaimGeneral General Health SupportsorMaintenancehealthyNutritionalgrowth andClaims Benefits derived developmentfromsupplementation Nourishesbeyond normalthe bodydietary intake Relievesgeneraltiredness,weakness Helps tomaintaingood health For energyand vitalityCriteriaEvidence tosubstantiate HSclaims Is in line with1 or more of theestablished nutrition followingknowledge inevidences:reference textsi) Standard reference Is related to generale.g. referencewell-being in linetextbooks,with scientificpharmacopoeia,knowledgemonographs Claim does not refer ii) Recommendationsto the structureon usage fromand/or function ofreferencethe human bodyregulatoryauthorities or In accordance to HS referenceprinciples andorganisationspractice in Malaysia Forstrengtheningthe bodyPlease refer to Illustrative Substantiation Evidence List for the list of acceptable references,organisations and authorities.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 235

Drug Registration Guidance Document (DRGD)(ii) Table 2: Functional Claims (medium)Claims must be adequately substantiated through ingredient-based evidence and whennecessary through product-based evidence.Types ofHS claimDefinitionFunctional Maintains orClaimsenhances the(medium)structure orfunction ofthe humanbody,excludingdiseaserelated claimsExamples/Wording ofclaimsAcceptableclaims basedon the singleingredientCriteriaFor claims onestablishednutrients andingredients suchas vitamins &minerals withdailyrecommendedvaluesEvidence to substantiateHS Claims1 or more of the followingevidence:i) Standard reference e.g.reference textbooks,pharmacopoeia,monographse.g. Vitamin Ahelps toii) Recommendations onmaintainusage from referencegrowth, visionregulatory authorities orand tissuereference organisationsdevelopment Meet theconditions foriii) Good quality scientificnutrientfunctionevidence from human Vitamin Dclaimsassetobservational studieshelps inbytheAuthority(refer to ASEANnormalGuidelines on efficacydevelopment Claimshavedata requirement) (only inandconsistentthe event that humanmaintenancescientificexperimental study isof bones andsupportnot ethical, animalteeth.according tostudies will be acceptedscientificreviewtogether with Chondroitinandevaluationepidemiological studieshelps toor other scientificpromoteliterature andhealthy joints In accordanceto HS principlesdocumented traditionaland practice inuse)Malaysiaiv) Peer-reviewed scientificdata or meta-analysisPlease refer to Illustrative Substantiation Evidence List for the list of acceptable references,organisations and authorities.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 236

Drug Registration Guidance Document (DRGD)(iii) Table 3: Disease risk reduction (high)Types ofHS claimDefinitionExamples/Wording ofclaimsDisease Significantly Helps toriskaltering orreduce risk ofreductionreducing aosteoporosisrisk factor ofbya disease orstrengtheninghealth related bonecondition. Helps toreduce the riskofdyslipidaemiaCriteriaEvidence tosubstantiate HS Claims The relationshipCompulsory evidence:between the HSi) Scientific evidenceingredient or productfrom humanand disease riskintervention study onreduction isingredient and/orsupported byproductconsistent scientific ii) Toxicological studyevidence(chronic)iii) Pharmacological Documented instudyauthoritativeAt least 1 additionalreference textsevidence: Recognised by theAuthority referenceor internationalorganisations orregulatoryauthorities Adheres to the keyprinciples of HSclaimsi)Standard referencee.g. referencetextbooks,pharmacopoeia,monographs etc.ii) Recommendationson usage fromreference regulatoryauthorities orreferenceorganisationsiii) Evidence frompublished scientificreviews or metaanalysisiv) Report prepared byexpert committees/expert opinion(subject to theAuthority approval)Please refer to Illustrative Substantiation Evidence List for the list of acceptable references,organisations and authorities.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 237

Drug Registration Guidance Document (DRGD)4.4.3 CLAIMS SUBSTANTIATIONClaims must be in line with the respective HS principles and supported by adequateevidence. To reflect the total available usage evidence (including relevant scientificevidence), the evidence shall be summarized as part of the substantiation document for theclaim as in the Table 4 ageandadministration routeDuration designStudypopulationSummary offindingsLimitations ofthestudySource ofevidencei) Authorii) Titleiii) Publicationdetailsiv) Yearv) Type(text, )Note: Evidence not summarised as in the above format will not be further evaluated.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 238

Drug Registration Guidance Document (DRGD)4.4.4 ILLUSTRATIVE SUSBSTANTIATION EVIDENCEi) Reference textsa.b.c.d.e.f.g.h.i.Martindale, latest edition. The Complete Drug. Pharmaceutical Press, 2009.The ABC Clinical Guide to Herbs. American Botanical CouncilWHO Monographs on Selected Medicinal PlantsBritish PharmacopoeiaUnited States PharmacopoeiaIndian PharmacopoeiaChinese PharmacopoeiaNatural Standards (www.naturalstandard.com)Office of Dietary Supplements, National Institutes of Health - Dietary SupplementFact Sheets(http://ods.od.nih.gov/Health Information/Information About Individual Dietary Supplements.aspx)ii) Organisationsa.b.c.d.e.f.American Botanical Council (www.herbalgram.org).American Nutraceutical Association (www.ana-jana.org)CODEX AlimentariusGlobal Information Hub for Integrated Medicine (http://www.globinmed.com)National Centre for Complementary and Alternative Medicine (http://nccam.nih.gov/)Office of Dietary Supplements, National Institutes of Health (USA)(http://ods.od.nih.gov)iii) Reference regulatory authoritiesa.b.c.d.e.Australia TGAChinese Health Authority on Chinese medicinal herbsEuropean CommissionHealth CanadaUnited States FDANotes:1. This list is not meant to be exhaustive and will be reviewed from time to time.2. The Authority will nonetheless conduct a detailed evaluation of the evidence included in thereport to ensure that the health claim is substantiated.3. The Authority will be willing to consider review other than the listed above, if the standards ofevidence are consistent with those of the Authority.4. All references must be current.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 239

Drug Registration Guidance Document (DRGD)4.5 SPECIFIC DOSSIER REQUIREMENT FOR REGISTRATION OFHEALTH SUPPLEMENTSPRODUCT VALIDATION1.PRODUCT NAME May include product name, dosage form and strength (e.g. XYZ Capsule 500mg) Dosage form and strength of product would need to be entered as part of productname to allow for multiple dosage forms (e.g. tablet, capsule) and strengths (e.g.200mg and 400mg) for any particular named (proprietary or generic) product. In any event if found that registered product name is similar to another registeredproduct, NPRA reserve the rights to request for the change in the product name. Product with more than 1 active ingredient could not include strength of activeingredients in the product name. Product name may be included together with the brand name or trademark name, ifapplicable. Any product name which is the same or similar either in writing/ pronunciation, withthe product name of an adulterated product is prohibited.Table 5: List of Non-Permissible Product Name for Health Supplement ProductsNo.IssueExample1.Prohibited use of disease names as stated Diabetes, Asthma, Cancerin the Medicines (Advertisement and Sale)Act 1956 (revised 1983)2.Prohibited use of a single active ingredientas a product name in products containingmore than one active ingredient unlessproduct name contains words such as‘Plus, Compound, Complex, HerbanikaIf the product contain Vitamin C,Vitamin E and Fish OilProduct name: “Vitamin C” is notallowed but product name:“Vitamin C Plus” is allowed.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 240

Drug Registration Guidance Document (DRGD)No.IssueExample3.Prohibited use of superlativeNames which indicates superiority inefficacyPower, Superior, Pure, Mustajab,Safe, Healthy, Penawar, VIP,Good, World Number 14.Prohibited use of spelling of words which Go Out GOUT (label)may cause confusionUtixi)Words which involve names of/partthereof:20 disease names prohibited in the Medicines(Advertisement and Sale) Act 1956 (Revised1983)ii) Other diseases without scientific proofiii) Prohibited indication5.Prohibited use of names which may cause B For Energy?ambiguityAmbiguous product name6.Prohibited use of names which may beoffensive or indecent7.Product name which is not congruent with The active ingredient is Eveningthe active ingredient.Primrose oil (EPO) and theproduct name: “Marine tablet” isnot allowed.8.Prohibited use of product names which has Words such as miracle, magic,elements of ludicrous beliefmagical, miraculous, saintly,Statementsreferringtoancient heavenlybelieve/negative spirits/supernatural powerSENXBIG SEnXBIG(label)Sexy, Enjoy, Paradise, Heavenly,Blue boy, Casanova, DesireNational Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 241

Drug Registration Guidance Document (DRGD)No.IssueExample9.Prohibited use of product names similar to Elegen vs L-gen vs L-jen Fortethe existing approved product namesvs FortProduct name similar to the spelling andpronunciation of words of an existing productnames10.Prohibited use of product names which Juice, Health drink, Beverage,may cause ambiguity in the nature of Kookyproduct (drug/ food/ beverage)Product name similar to a food/ beveragename11.Prohibited use of product names which Dr Sunny, Professorrepresents professional advice or opinion12.Product name that symbolize a claim13.Product name that uses strength but Iftheproductcontainsformulation contains more than one active multivitamins and minerals.ingredient.Product name:“XXX multivitamins and minerals500mg” is not allowed.14.Other prohibited product namesMinda, IQ, Smart, Unique, UltraMega, Detox, Defence, Immunity15.Names of organs and brainHeart, kidney, skin, liverVigour, Youthful, High, HiNote:1. This list is not meant to be exhaustive and will be reviewed from time to time.2. The Authority reserves the right to disallow any other words, phrases or graphics for productlabel which in its opinion is misleading, improper or not factual.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 242

Drug Registration Guidance Document (DRGD)2.DOSAGE FORM Dosage forms allowed:a)b)c)d)Tablets- fervescence tablet, uncoated tablet, enteric coated tablet, Sugarcoated tablet, Film coated tablet, extended release tablet;Capsules- Soft capsule, Hard capsule, Enteric coated capsule, Chewable softcapsule, Extended released capsule;Powder/ Granules;Liquid- Emulsion, syrup, spray, suspension. Products in the shape of animal dosage forms are not allowed. Supporting data from established reference (e.g. Standard Pharmacopeia) shall berequired for new dosage form. The form that correctly describes it in terms of its product quality controlspecifications and performance shall be selected. A separate application for registration is required for each dosage form. The following documents will have to be provided during submission of productdossier for Sustained-release/ Extended-release/ Timed-release dosage formi)ii)iii)iv)3.Protocol of analysis;In-Process Quality Control (IPQC);Finished Product Specification (FPQC);Certificate of Analysis (COA).ACTIVE INGREDIENTName of Active Ingredient: Please select active ingredient from the search database. If substance is not listed,please select the ‘Not Listed Ingredient’ button. Automatic e-mail will be send toNPRA for notification. Approved names, pharmacopoeia names of ingredients shall be used wheneverpossible.National Pharmaceutical Regulatory Division, Ministry of Health Malaysia.Second Edition, Sept 2016. Revised July 2018Page 243

Drug Registration Guidance Document (DRGD)Strength of active ingredient : To enter the content of active ingredients (numerical) and then select the weightsand measures from the given list. Content of ingredients shall be expressed as appropriate in the following manner:a. quantity per dose unit (e.g. for unit dose formulations - tablet, capsule, lozenge,etc.)b. percentage composition - %w/w, %w/v, %v/v, etc.c. weight per ml. (e.g. for solutions,suspension etc.)d. quantity (percentage or amount) per measured dose (e.g. oral liquids, drops,etc.)Metric weights and measures shall be used. Source of Active ingredient: To specify the source such as animal, plant, synthetic or others (to specify)USE OF PROTECTED/ ENDANGERED INGREDIENTSa) PROTECTED/ ENDANGERED WILDLIFE SPECIESIt is the responsibility of the applicant to ensure that the ingredient(s) derivedfrom wildlife species its

c. WHO Monographs on Selected Medicinal Plants d. British Pharmacopoeia e. United States Pharmacopoeia f. Indian Pharmacopoeia g. Chinese Pharmacopoeia h. Natural Standards (www.naturalstandard.com) i. Office of Dietary Supplements, National

Related Documents:

Issue of orders 69 : Publication of misleading information 69 : Attending Committees, etc. 69 : Responsibility 69-71 : APPENDICES : Appendix I : 72-74 Appendix II : 75 Appendix III : 76 Appendix IV-A : 77-78 Appendix IV-B : 79 Appendix VI : 79-80 Appendix VII : 80 Appendix VIII-A : 80-81 Appendix VIII-B : 81-82 Appendix IX : 82-83 Appendix X .

Appendix G Children's Response Log 45 Appendix H Teacher's Journal 46 Appendix I Thought Tree 47 Appendix J Venn Diagram 48 Appendix K Mind Map 49. Appendix L WEB. 50. Appendix M Time Line. 51. Appendix N KWL. 52. Appendix 0 Life Cycle. 53. Appendix P Parent Social Studies Survey (Form B) 54

Appendix H Forklift Operator Daily Checklist Appendix I Office Safety Inspection Appendix J Refusal of Workers Compensation Appendix K Warehouse/Yard Inspection Checklist Appendix L Incident Investigation Report Appendix M Incident Investigation Tips Appendix N Employee Disciplinary Warning Notice Appendix O Hazardous Substance List

Step-by-Step Guide to Registration Step 1: Prepare for Registration Make sure you meet the eligibility requirements for enrolling. Check the Registration Timeline to ensure registration is open. Note the following: Registration and Payments All registration and payments must be done online using the steps below. Plan Ahead:

The Need for Adult High School Programs 1 G.E.D.: The High School Equivalency Alternative 9 An Emerging Alternative: The Adult High School Ciploma 12 Conclusion 23 Appendix A -- Virginia 25 Appendix B -- North Carolina 35 Appendix C -- Texas 42 Appendix 0 -- Kansas 45 Appendix E -- Wyoming 48 Appendix F -- Idaho 56 Appendix G -- New Hampshire .

Appendix 4 . Clarification of MRSA-Specific Antibiotic Therapy . 43 Appendix 5 . MRSA SSI . 44 Appendix 6 . VRE SSI . 62 Appendix 7 . SABSI related to SSI . 74 Appendix 8 . CLABSI – Definition of a Bloodstream Infection . 86 Appendix 9 . CLABSI – Definition of a MBI -related BSI . 89 Appendix 10 . Examples relating to definition of .

Appendix E: DD Form 577 for Appointing a Certifying Officer 57 Appendix F: Sample GPC Appointment Letters 58 Appendix G: Formal Reporting Requirements 66 Appendix H: Semi-Annual Surveillance Report Template 70 Appendix I: GPC Thresholds 73 Appendix J: Glossary – Sections I and II 75 Chapter 1: The Government Purchase Card Program 1-1. Purpose a.

Appendix D: Active Voice vs Passive Voice . Appendix E: Examples, Use of D0000 . Appendix F: Additional Examples for Principles 2-6 . Appendix G: Examples, Use of D8100 . Appendix H: Examples, Lack of Documentation . Appendix I: Examples, DPS Does Not Match Findings . Appendix J: Examples, Repeating Regulations in the DPS