1. MALAYSIA OTC Abridged Evaluation

ABRIDGED EVALUATION OFOTC PRODUCTS– MALAYSIA EXPERIENCEMinistry Of Health MalaysiaMS ISO 9001:2008 CertifiedSELF-CARE CONFERENCE AND 2nd SELF-CARERROUND TABLEBangkok, Thailand17th September 2015Anis TalibNational Pharmaceutical Control BureauMinistry of Health MalaysiaJalan Universiti 46730 Petaling JayaMALAYSIATel : 603603-78835400 Fax : 603603-79562924Website : www.bpfk.gov.myMember of PharmaceuticalInspection CooperationSchemeWHO CollaboratingCentreFor Regulatory Control ofPharmaceuticals

PRESENTATION OUTLINEIntroduction OTC - Abridged vs OTC Full Evaluation Fees, Timeline, Registration Process &Requirements Issues & Challenges 2

INTRODUCTION3

GENERIC PRODUCT A product that is essentially similar to a currentlyregistered product in Malaysia. The term generic is notapplicable to biologic products.1) Scheduled Poison: Known as Controlled Medicine/ Controlled Poison Pharmaceuticalproducts which contain scheduledpoison(s) as listed in the First Schedule under thePoisons Act 1952.4

2) Non-Scheduled Poison: Known as Non-Poison or “Over-the-Counter”, OTC Products containing active ingredients which arenot listed in the First Schedule under Poisons Act1952; and is excluding active ingredient which iscategorised under health supplements or naturalproducts or cosmetics5

REGISTRATION PHASESNEW PRODUCTSPhase 1Phase 2Phase 3Phase 4Phase 5Phase 6RegistrationAug 2007(Veterinary)Regulatorycontrol ofActivePharmaceutical Ingredient(API)**BIOTECHNOLOGYRegistrationAug NARYMEDICINELicensingMay 1987ACTIVEPHARMACEUTICAL ationJan 1992(TraditionalMedicine)RegistrationFeb mportersJan 1999LicensingJan 2004Licensing1 July 2012*No licensingRequirementsas registrationof API islinked gWholesalersJuly ce(to beannounced)1st January 2008 – Registration of Cosmetics replaced by*NOTIFICATION1st July 2012:All manufacturers shall be certified for GMP as directed via Directive Arahan di BawahPeraturan 29, Peraturan-peraturan Kawalan Dadah dan Kosmetik 1984 Bil. 1 Tahun 2012** Voluntary registration of API commenced in April 2011, started with New Drug Products (NDP), followedby mandatory registration of API for NDP which were implemented in January 2012. As for Generics, themandatory registration of API will be announced at a later date.6

OTC - ABRIDGED VS OTC FULLEVALUATION7

GENERIC duledPoisonAbridgedEvaluationFullEvaluation8

OTC ProductsFull EvaluationAbridged EvaluationAll products other than thelisted categories underAbridged Evaluation1.2.3.4.5.Antiseptics/ skin disinfectantsLocally-acting lozenges/ pastillesTopical analgesic/ counter-irritantsTopical nasal decongestantsEmollient/ demulcent/ skinprotectants6. Keratolytics7. Anti-dandruff8. Oral care9. Anti-acne10. Medicated plasters/ patch/ pad11. Topical antibacterial* Generally dosage forms otherthan external (skin) and locallyacting dosage forms eg. oral ,parenteral, rectal, vaginal, ocular,otic etc.* Generally external (skin) and locally-actingdosage forms eg. creams, ointments,9lozenges, pastilles (relatively lower riskcompared to OTC Full Evaluation)

ABRIDGED EVALUATION FOR OTCPRODUCTS1. Antiseptics/ skin disinfectants;2. Locally-acting lozenges/ pastilles;3. Topical analgesic/ counter-irritants;4. Topical nasal decongestants;5. Emollient/ demulcent/ skin protectants;6. Keratolytics;7. Anti-dandruff;8. Oral care;9. Anti-acne;10. Medicated plasters/ patch/ pad; and11. Topical antibacterial.OTC Abridged Characteristic : External (skin)preparation and locally- acting10(lozenges/pastilles) dosage forms.

OTC ABRIDGE EVALUATION - EXAMPLES11

No CategoryExamplesActive ingredient(s)1.Antiseptics/ skindisinfectants* For use on thehuman bodyDettol AntisepticLiquid, EusolSolutionisopropyl alcohol, ethylalcohol, chlorhexidine,povidone-iodine, acriflavine,chloroxylenol, cetrimide2.Locally-actinglozenges/pastillesSore throat/ coughlozenge egStrepsils,Fisherman Frienddequalinum, menthol,amylmetacresol,dichlorobenzyl hol, camphor, methylanalgesic//gel for muscle and salicylate, capsaicincounter-irritants joint pain (musclerub)4.Topical nasaldecongestantsVicks Vaporubmenthol, camphor,eucalyptus oil5.Emollient/demulcent/ skinprotectantsAqueous cream,Calamine lotioncalamine /- zinc oxide126.KeratolyticsWart and anti-corn salicylic acid, sulfur, ureasolution

No CategoryExamplesActive ingredient(s)7Anti-dandrufftar, selenium sulfide8Oral care9Anti-acnesalicylic acid, triclosan,benzoyl peroxide,resorcinol10Medicatedplasters/ patch/padmenthol, camphor, methylsalicylate, glycolsalicylate, ntisepticmouthwash/garglespovidone-iodine, thymol,chlorhexidine, hexetidine,cetylpiridiniumantiseptics, anti-acne13

OTC FULL EVALUATION EXAMPLES14

No dinBenzyl benzoate/perubalsam/zinc oxide1.Anti-haemorrhoids2.Anti-scabies/licebenzyl s/overdosagetreatmentacetylcysteine,calcium folinate,protamine, isodium edetate4.Antacids & antiflatulent5.AntihelminticsGaviscon Liquidsimethicone,polydimethylsiloxane(PDMS), activatedcharcoalalbendazole,mebendazole15

No CategoryExamplesActive ingredient(s)Gadovistgadolinium based (gadobutrol,gadobenate, gadodiamide,Iodinated6.Contrast media forMagnetic ResonanceImaging (MRI)7.Diluents/solvent/vehicle/carrier solution forcompatible electrolyteconcentrates andmedicationswater for injection, glucose,sodium chloride infusion solution8.Enzymes & bile saltslysozyme, papain, fungaldiastase, pancreatin9.Expectorantguaiphenesin, ipecahuanha,ammonium chloride10. HaematinicsCosmoferinjectioniron salts (eg. ferrous fumarate ,ferric sodium citrate, irondextran/iron sucrose/ironpolymaltose complexes), vitaminB substances11. LaxativesFleet,PicoprepBisacodyl, lactulose, psyllium ,16liquid paraffin,

No CategoryExamples13. Non-radioactive diagnosticpreparations14. Non-opiod analgesicsActive ingredient(s)fluorescein sodiumPanadolparacetamol /- caffeine, aspirin15. Oral Rehydration Salts(ORS) & antidiarrhoealsdiosmectite, kaolin/pectin/kaolinpectin16. Osteoarthritis adjuvanttherapyglucosamine, /- chondroitin,methylsulfonylmethane (MSM)17. Phosphate binderscalcium carbonate/acetate,aluminium hydroxide18. Potassium bindersodium/calcium polystyrenesulphonate19. Total Parenteral Nutrition(TPN)Amino acids17* excluding tryptophan

No CategoryExamplesActive ingredient(s)20. Topical antipsoriasis/eczematar, polytar, zinc oxide21. Topical antifungalsclotrimazole, terbinafine,tolnaftate, amorolfine, ciclopirox,benzoic acid/salicylic acid/sulfur,zinc undecenoate, naftifinehydrochloride22. Vitamin B substances forneurological/nervedisorders & anaemia23. Vitamin D (cholecalciferol)and its analoguesNeurobionMecobalamin, thiamine,cyanocobalamine, pyridoxine, BcomplexVitamin D analogues alfacalcidol, calcitriol18

FEES, TIMELINE, REGISTRATIONPROCESS & REQUIREMENTS19

PROCESSING FEESNo123ProductCategoriesPharmaceutical(New DrugProducts &Biologics)Pharmaceutical(Generics andHealthSupplements)NaturalProductsProcessingFees (RM)Analysis Fees (RM)Total Fees (RM)Single active ingredient :3,000.004,000.00Two or more activeingredients : 4,000.005,000.00Single active ingredient :1,200.002,200.00Two or more activeingredients: 0.00

TIMELINENo.Product Category(A)Full Evaluation* Duration(Inclusive screeningprocess)1. New Drug Products245 working days2. Biologics245 working days3. Generics (Scheduled Poison)210 working days4. Generics (Non-Scheduled Poison)210 working days* Upon receipt of complete application.21

No.Product Category(B)Abridged EvaluationGenerics (Non-Scheduled Poison/OTC)5. a) Single active ingredientb) Two (2) or more active ingredientsNatural Products6. a) Single active ingredientb) Two (2) or more active ingredients7. Health Supplementsa) ** Single active ingredientb) ** Two (2) or more active ingredients** Applicable for:i) General or Nutritional Claims; andii) Functional Claims (Medium Claims)c) Disease Risk Reduction Claims(High Claims)* Upon receipt of complete application.*Duration(Inclusive screeningprocess)a) 116 working daysb) 136 working daysa)b)a)b)c)116 working days136 working days116 working days136 working days245 working days22

Overview of Product RegistrationProcessPre-Submission of RegistrationApplication* GMP InspectionSubmission of RegistrationApplication and Screening ProcessData Evaluation** Sample testingMeeting of the Drug Evaluation Committee (twice monthly)Meeting of the Authority (monthly)ApprovalAssigning a registration number(MAL no.) & Issuance of certificateRejectionAppealRegulation 18, CDCR 1984*** LicensingPost-Registration ProcessSurveillance & PharmacovigilanceorAmendments/Variations* Good Manufacturing Practice (GMP)Certification** For natural products only23*** Application for Import and/or WholesaleLicense

ORGANIZATION OF APPLICATION DOSSIERCountry-specificadministrative data.Not part of ACTDPart ITable ofContents,CommonAdministrative Data& Product InformationPart IIQualityOverall Summary& ReportsPart IIINon-clinicalOverview,Summary& Study Reports*ACTDPart IVClinicalOverview,Summary,AssessmentReports,& Study Reports*24* Upon Request

ABRIDGED EVALUATION VS FULL EVALUATIONTimeline for OTC Abridge Evaluation (116-136 workingdays) is faster compared to Full Evaluation (210working days)2. OTC Abridged Evaluation does not required completePart I & II documentation like Full Evaluation.3. These following major documents are exempted forOTC abridged evaluation :(i)Part I, Product Information pharmacodynamics, pharmacokinetics andpregnancy & lactation information(ii) Part II - BA/BE Study Report, ProcessValidation Report & Analytical ValidationReport* bypass Centre for Quality Control pre-registration25documentation evaluation1.

HOW WE EVALUATE?1.2.3.4.5.6.Relevant Acts & Regulations (Poison Act, CDCR etc)DCA Policies/Circulars/Directives, Meeting Minutes (JKPP,DCA, policy, JKPPP), GMP Status List (updated monthly)Guidelines (DRGD, ACTD/ASEAN / WHO / EMA /USFDA/Health Canada)Standard References ((Martindale, Micromedex,Pharmacopeia [BP,EP USP], Innovator’s PI & CoA, Approved PI& SmPC from Reference countries eg UK EMC)Pharmasearch Database (Search by product name, APIsubstance, dosage form, manufacturer)Evaluator’s Checklist/Manual, NPCB PI templateFor OTC Products, we also use USFDA Federal Register& Health Canada Monograph as references27

ISSUES & CHALLENGES28

OTC ABRIDGED EVALUATION –ISSUES & CHALLENGES OTC Classification is heavily tied up to Poison Act 1952 reclassification from poison to non-poison (OTC) drugauthorised by Poison BoardThe registration process is not really ‘simplified’, only somemajor requirements are not required and the timeline isfaster‘Grey area’/interphase products eg.: Pharmaceutical/TMHS Interphase Medical Device/ Drug Interphase Cosmetic/Drug InterphaseNew Drug Products (NDP) containing Non-ScheduledPoisons eg. New form/salt, new dosage form, new route of administration,new combination of active ingredients, new indications/ dosageetc.29

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Benzyl benzoate/peru balsam/zinc oxide 2. Anti-scabies/lice benzyl benzoate, crotamiton, permethrin, malathion 3. Antidotes/overdosage treatment acetylcysteine, calcium folinate, protamine, charcoal, phytomenadione, deferoxamine, pralidoxime, disodium edetate 4. Antacids & antiflatulent G