new drug submission form - Trinidad & Tobago

GOVERNMENT OF REPUBLIC OF TRINIDAD AND TOBAGOMINISTRY OF HEALTHCHEMIST- FOOD AND DRUGS DIVISIONNEW DRUG SUBMISSION FORMInstructions:In order to expedite the processing of your New Drug Submissions, please ensure/provide that: -1. (a) The New Drug Submission Forms (Form A, B and C) are filled out properly.As much information as possible must be filled out on the forms provided.DO NOT PUT - “SEE DOSSIER”You may use a blank sheet of paper if more space is required and attach to the form.(b)All relevant technical data such as - clinical studies, product description,product formulation/specification, methods of analysis, certificateof analysis must be provided to support each new Drug Submission.(See detailed of requirements attached).2. Each drug is properly certified - original “Free Sale Certificate”/“Certificateof Pharmaceutical Product” (CPP) is required from the relevant Health Authorities.3. Five (5) samples of each drug be provided in its finished pharmaceuticalform in which it is to be sold.4. Sample(s) of the active ingredient(s) be provided.5. Submission must be presented in four separate sections (dossiers) clearly labeled using thefollowing format:1. Administrative- See Section 1 of detailed of requirements of New Drug Submission (NDS).- Completed Application Form.2. Chemical Documentation- See Section 2 of Detailed of Requirements for New Drug Submission.3. Clinical - include non-clinical data and clinical data including Bioequivalence Studies)- See Section 3 of Detailed of Requirements for New Drug Submission.4. Other- See Section 4 - 7 of Detailed of Requirements for New Drug Submission.-Dossiers must be submitted in Duplicate.6. REGISTRATION FEE: $750.00 (T.T.) payable in advance.1

ChecklistTo be completed by Applicant(1) Certificate in respect of Imported Drugs Completed Application FormTRINIDAD AND TOBAGOMINISTRY OF HEALTHCHEMISTRY/FOOD AND DRUGS DIVISIONDETAILED OF REQUIREMENTS FOR NEW DRUG SUBMISSIONFree Sale Certificate - Original, Apostille and Attested1.1. Certificate of Free Sale Issued by the Drug Regulatory Authority of the Manufacturing Country or Exporting Country.a) Brand name of the product (if any)b) Generic name (INN) of the active ingredient(s)c) Dosage strength and dosage formd) Complete name and address of the manufacturere) A statement that the product is freely sold in the country of origin.or Certificate of Pharmaceutical Product - Original, Apostille and Attested1.2 Issued in accordance with the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving inInternational Commerce (CPP). It applies to the case of imported medicines, as it is the certificate issued by the NationalRegulatory Authority (NRA) that issues the registration. This certificate also attests to the Good Manufacturing Practices(GMP) of the manufacturing laboratory(ies).(2) Chemical Documentation(A) Finished Product2.A.1 Specifications(a) Provide a complete description of the quality indexes or specifications(physical, chemical, and microbiological) and acceptable limits in tableformat, independently of the methods of analysis and quality reference(reference pharmacopeia or manufacturer);(b) Justify any omission of the quality indexes established in the referencePharmacopoeias for the product whose registration is being requested;(c) All solid forms of controlled or modified release (tablets, capsules, ovules)require time-release testing.2.A.2 Method of Analysis(a) Provide information on the methods of analysis used for quality control: A specific monograph, when from a reference pharmacopeia; A complete description of the method of analysis, when fromthe manufacturer.2

2.A3 Certificate of Analysis - Original(a) Include a certificate with evidence of the quality specifications issuedby the manufacturer of the finished product. In the case of initialproduction of products in development, it is acceptable that the testswere conducted in pilot batches.2.A4 Stability DataSubmit the stability study, including the following:a) Study protocol:b) Quality specifications and methods of analysis;c) Detailed description of the container closing system usedwith the product being evaluated;d) Storage conditions (temperature, light sensitivity and relativehumidity in the environment);e) Results from at least three lots of the finished product (usingpreferably different lots of the Active Pharmaceutical Ingredient);f) Conclusions and proposed expiration date and storage conditions;g) The professional responsible for the study should sign off on thestability studies;h) When the dosage form of the medicine is accompanied by a solventor diluents, include stability studies on the diluted, dissolved or dispersedproduct, as applicable, in the conditions under which it s to be utilized;i) If more than one vehicle is used for its preparation, submit data from thestability studies conducted for each of them;j) If a product is packaged in two or more container closing systems, presentthe stability studies for each of them.k) If a product is packaged in two or more volumes, stability studies have to bepresented according to international regulations in force.l) It is required the submission of accelerated studies and long term (shelf-lifeor shelf-life only.2.A.5 Disintegrationa) Equipment and apparatus required;b) Test parameters;c) Test medium;d) Specification.2.A.6 Dissolution Profilea) Equipment and apparatus required;b) List of chemical/reagents required;c) Test parameters i.e. type and volume of dissolution medium, rotationrate, temperature of solution and timed) Preparation of dissolution medium, preparation of sample andstandard solution (if any), etc.e) Type and method of analysis (HPLC, UV, etc) and test procedures.For example, if HPLC method is used, test method has to includethe preparation of mobile phase, brand and type of column used, runtime, detector used (UV, RI, etc), injection volume, system suitabilitytest and other parameters.f) Typical chromatograms/UV spectrum for sample & standardsolution, system suitability etcg) Complete formula for calculation. For example, „slow release‟products calculation must include quantity of active substance in themedium volume which has been taken out for analysis.3

2.A.7 Five (5) SamplesB. Active Ingredient(s)2.B.1 Specificationsa) Provide a complete description of quality indexes or specifications(physical, chemical and microbiological) and acceptable limits, withthe quality reference (reference pharmacopeia or from the manufacturer);b) If the reference is from the manufacturer, include any impurities resultingfrom the synthesis, their identification and the rationale justifying acceptablelimits.2.B.2 Method of Analysisa) A specific monograph, when from a reference pharmacopeia;b) A complete description of the method of analysis, when from the manufacturer.2.B.3 Certificate of Analysis (each ingredient) - Originala) Include a certificate of analysis from the original manufacturer, withverification of its respective quality specifications, with correspondenceto the lots used in the product to be registered.One (1) gram of each(3) Pharmaceutical Documentation(A)(B)(C)(D)Pharmacodynamic dataGeneral PharmacologyTests supporting efficacyPharmacokinetic dataAbsorptionDistributionBiotransformation/MetabolismExcretionBiological equivalencePharmacotherapeutic dataTherapeutic usesClinical trialsTherapeutic equivalenceToxicity dataAll typesN.B.Data: - Published and In-house.4

(4) Manufacturing Details4.1 Manufacturing/Unit Composition Formulaa) Include a description of its qualitative and quantitative composition,by dosage unit and percent (weight or volume), detailing eachcomponent, Active Pharmaceutical Ingredient(s), preservatives,stabilizers and excipients.4.2 Brief Manufacturing Direction/Procedurea) A description of the manufacturing process that includes all stepsor stages up to completion of the finished product, along with itspackaging and labeling;b) A flow chart of this process that includes the stages of formulation,fill, lyophilisation (if applicable), labeling and packaging, indicatingthe points at which material input occurs and indicating intermediatesteps, critical points, and controls in this process;c) In cases where more than one manufacturer is involved in the process,the flow chart should include the step(s) in which each of them participates;d) Information on process validation;e) Reprocesses, with justification and duly validated, whenever applicable.4.3 Brief Manufacturing Controlsa) Description of controls at critical steps or stages and key intermediateproducts;4.4 Sampling and Testing Procedures4.5 GMP CertificateGMP Certificate Issued by the Drug Regulatory Authority of the Manufacturing CountryThe certificate shall be issued by the regulatory agency on pharmaceuticals from thecountry of origin of the drug product.A statement that the manufacturer is duly registered with the regulatory authorityshall be included.A statement that the facilities are regularly inspected and found to conform withcurrent Good manufacturing Practices (GMP) shall also be included.5. Packaging Materials (Containers and Closures)DescriptionCompositionSize and dimension requirements (guage, thickness, etc.)with target value and acceptable tolerancesColourProcesses necessary to make the article acceptableto pharmaceutical production (e.g. coating, washing,sterility of surfaces, etc.)Samples5

6. Ink and PrintingColour of InkChemical Composition of InkDescription of Ink (colour fast, light resistant, rubresistant, reflectance, etc.)Other characteristics of Ink (odour, distribution, etc.)Printing - capacity to smear, smudge, scoff or beremoved during normal handling of the package7. Package InsertText for the package insert, should contain at least information indicated below.a) International Non-proprietary Name (INN) and Anatomical TherapeuticChemical Classification (ATC);b) Brand name;c) Dosage Form;d) Concentration;e) Contents/volume;f) Number of doses per container (for multi-doses packaging),when applicable;g) Composition;h) Declaration of excipients;i) Route of administration;j) Indications (resulting from clinical trials that assess themedicine‟s efficacy);k) Instructions for use;l) Posology/dosage;m) Maximum dose in 24 hours, for over-the-counter (OTC) products;n) Precautions;o) Warnings;p) Adverse reactions;q) Contraindications;r) Interactions;s) Overdose (risk and information on how to manage risk);t) Use during pregnancy and breast-feeding;u) The importance of monitoring patient use and where to reportpossible problems with the medicine;6

ALTERNATIVE/HERBAL MEDICINES IN TRINIDAD AND TOBAGOThe history of man has shown that multiple choices exist for protecting human health. Today‟s worldwide revival in theinterest of natural products as preventative and therapeutic agents and the accompanying high demand for naturalremedies have drawn the attention of the Ministry of Health in Trinidad and Tobago.The Ministry has a responsibility to protect the health of the citizens. This requires the establishment of rules to governthe registration, importation, manufacture, storage, distribution, sale and use of herbal medicinal products. This is aspecial responsibility of the Chemistry/Food and Drugs Division in Port of Spain.A Herbal Sub-Committee has been established by the Drug Advisory Committee to advise and assist the latterCommittee on standards, schedules and conditions of sale for herbal medicinal preparations, and any other mattersconnected therewith.The Drug Advisory Committee recommends to the Honourable Minister of Health, products for Approval.The Herbal Sub-Committee consists of persons with interests and expertise in taxonomy, pharmacy, pharmacognosy,pharmacology, chemistry, conventional medicine and herbal medicine.Assessment for product registrationAny drug, if unknown by name, form, properties and actions would cause complications. So too, wouldA known drug if badly administered. To ensure that safe and efficacious herbal drugs reach the consumer,the following are considered by the Sub-Committee in the assessment of each herb and herbal medicinalproduct:1. Nomenclature 8. Properties2. Part of plant used 9. Pharmacology3. Historical Aspects 10. Clinical Aspects4. Habitat 11. Safety5. Botanical Description 12. Indication6. Pharmcognosy 13. Formulation7. Phytochemistry 14. DosageDuring the last five (5) years approximately 13% of the approved medicines were of herbal origin.7

Requirements for the label of a Herbal Medicine:The label of a package of a Herbal Medicine shall carry -(a) on the main panel of both the inner and the outer labels -(i)(ii)the name (Proper or Common), dosageform and the standard, if any, under which the herbalmedicine was manufactured;a correct statement of the net contents in termsof weight, measure or number;(b) on both the inner and outer labels -(i)(ii)(iii)the name of the manufacturer or distributor ofthe herbal medicine;the address of the manufacturer or distributor,except that where the immediate containercontains five milliliters or less, this statementneed not be made on the inner label;in the case of a herbal medicine which consistsof more than one ingredient, a quantitative listof the active ingredients;The Botanical Name of the plant(s)used and part(s) thereof, shall be declared.the common or vernacular name of plant(s) usedmay be declared.(iv)(v)(vi)(vii)(viii)dosage regimen and adequate directions for use in theEnglish Language;the expiry date;directions as to the type of storage necessaryto maintain the potency, efficacy, safety orproperties of the herbal medicine;a declaration of any warnings or contraindications,if applicable;the declaration;CAUTION: “Keep out of the reach of children”.“If pregnant or breast feeding ask ahealth care professional before use”.(c) on any panel, including the panel at the bottom of the package –(i)(ii)the batch or lot number; andany registration number, if applicable.8

FORM CFor Official UseReceiving No:Control No:DAN No:WorksheetTo be filled out by Applicant upon presentation ofNew Drug Submission/Supplemental Submission(1) Name of Drug/Form/Strength :………………………………………………………………(2) Name and Address of Manufacturer or :……………………………………………………..Distributor:…………………………………………………………………………………….(3) Phone Number (if local manufacturer):……………………………………………………….(4) Country of Origin:…………………………………………………………………………….(5) Name & Address of Importer:……………………………………………………………………………………………………………………………………………………………………(6) Phone Number:…………………………………………………………………………………(7) List of ingredients (Active Only)NAME QUANTITY NAME QUANTITY(8) Claims/Indications:……………………………………………………………………………………………….…………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………FORM CNew drugs/supplementary submissions worksheet9

FORM BTRINIDAD AND TOBAGONEW DRUG SUBMISSION FORMSecond Schedule, Division 3, Food and Drugs Act Chap 30:01To:The Chief Chemist/Director of Food and Drugs,#115 Frederick Street, Port of Spain, Trinidad.We hereby make the New Drug Submission for ...................................................................and attach the following information IN DUPLICATE:(a) a description of the New Drug, its proper name and trade name; [ ](b) a statement of all ingredients, route of administration, dosage, claims to be made,contra-indication and side-effects (if known), and description of pharmaceutical formin which it is to be sold; [ ](c) details of tests applied to control potency, purity and safety of new drugs; [ ](d) labels and samples of the new drug in the finished pharmaceutical form; (Note 1) [ ](e) samples of the components - active ingredient(s); [ ](f) certificates as specified in (g) to (j) in para. 3 (f) (i)-(v) Div.3, of the SecondSchedule of the Food and Drugs Regulations; [ ]Canada [ ] United Kingdom [ ]F.D.A., U.S.A. [ ] Australia [ ](g) certificates from State or City authorities in the United States respecting the saleand conditions of sale in the United States; [ ](h) certificates in English Language recognised as having adequate experience andfacilities for assessing the safety of new drugs by the Ministries of Health inBelgium [ ] Netherlands [ ] Denmark [ ]France [ ] Sweden [ ](i) certificates (with English translation) from other authorities in.......................................................................................... (2);(j) detailed reports of animal test [ ] and/or clinical trials [ ] to establish the safety of thenew drug (Note 2).We undertake to inform you of any change made in the conditions of use, labelling, pharmaceutical form,dosage, or strength, purity, quality of the drug which makes them significantly different to those given inthis submission, (para. 5 of this Division of the Regulations).We also undertake to inform you of any report of unexpected side-effects, injury, toxicity, or sensitivityreaction associated with the use of this New Drug in any way (para. 9 of this Division of the Regulations)................................................. ...........................................................................DateImporters/Manufacturers Agentin Trinidad and Tobago10

NEW DRUG SUBMISSION FORM -B(TYPE OR FILL IN BLOCK LETTERS)TRADE NAME ............................................................................................................FORM .....................................................................................................................….INGREDIENTS:(SEE NOTES)QUANTITY OR % QUANTITY OR %1 72 83 94 105 116 12CLAIMS, INDICATIONSKNOWN CONTRA INDICATIONS SIDE-EFFECTSDOSAGEMANUFACTURER(Complete Name &Address)NAME:ADDRESS:IMPORTER/AGENT(Complete Name &Address)NAME:ADDRESS:PHONE:Notes: The pharmaceutical form (tablet, capsule, cream, elixir, injection etc.,) must be indicated. Differentstrengths in the same form (e.g. 1.5 and 10 mg tablets) must be treated separately.Active ingredients must be listed before inactive ingredients. Quantities should be given in appropriateunits, or in percentages (for creams, liquids), or in amounts per ml or per ampoule.11

FOR OFFICIAL USE ONLYCONDITION OF SALE:1. FREE SALE2. THIRD SCHEDULE3. CONTROLLED4. DEFERREDCOMMENTS:12