Medicines Control Council : General Information
Registration of MedicinesGeneral InformationMEDICINES CONTROL COUNCILGENERAL INFORMATIONThis guideline is intended to provide recommendations to applicants wishing to submit applications for the registration ofmedicines. It represents the Medicines Control Council’s current thinking on the safety, quality and efficacy of medicines. It isnot intended as an exclusive approach. Council reserves the right to request any additional information to establish the safety,quality and efficacy of a medicine in keeping with the knowledge current at the time of evaluation. Alternative approaches maybe used but these should be scientifically and technically justified. The MCC is committed to ensure that all registered medicineswill be of the required quality, safety and efficacy. It is important that applicants adhere to the administrative requirements toavoid delays in the processing and evaluation of applications.Guidelines and application forms are available from the office of the Registrar of Medicines and the website.First publication released for implementation and commentMay 2003Release for additional commentNovember 2003Deadline for commentNovember 2003Date for finalisation/implementationDecember 2003Version 2: General editing – page numbers in index, 2.5, 3.1.2, 3.1.3 a) b), 4.1,4.4, 4.17, 8, 10, and amendment of sections 2.2.2, 2.9, 3.1.4, 4.2, 4.5, 4.6, 4.7,4.14, 5, 5.2, 13.1, 13.2, 13,3, 13.4, 13.5, 13.6, 13.7, Attachment AVersion 2 Date for implementationMay 200612 July 2006Version 3: Additions to 2.7.5, 2.10.5, 13.4; amendments to 4, 5.2, Attachment AVersion 3 Date for implementationMay 200725 June 2007Version 4: Amendment of sections 2.9, 2.10.5, 3.1.3 a), 4, 4.7, 4.10, 5.1, 5.2,13.3, 13.4, Attachment AVersion 4 Date for implementation – except 3.1.3 a), b)Version 4 Date for implementation of 3.1.3 a), b)March 20081 May 20081 August 2008REGISTRAR OF MEDICINESMS M HELA2.01 General information Feb08 v4.docApril 2008Page 1 of 48
Registration of MedicinesGeneral InformationTABLE OF pplicant / Proposed Holder of Certificate of Registration (PHCR)Confidentiality / Secrecy3442.42.52.62.72.8LanguageWhere to submit applicationsWhen a product should be registeredTypes of applicationsEvaluation procedures445562.92.102.112.12FeesSame or separate applicationsTransitional conversion tableCancellation and withdrawal of applications67893Requirements of an application93.13.1.13.1.2PART 1PART 1APART 1BAdministrative informationAdministrative particularsTable of Contents99113.1.33.1.43.23.33.4PART 1CPART 1DPART 2PART 3PART 4LabellingForeign RegistrationBasis for registration and overview of applicationPharmaceutical and analyticalPre-clinical studies11141415153.54PART 5Clinical studiesPreparation and submission of an application15155Presentation of screening and post-screening copies166Expedited review process6.16.218Medicines on EDLNew Chemical Entities19197Abbreviated medicine review process (AMRP)198Expert reports209Proprietary name policy2010Manufacturing requirements2411Samples2412Standardised package insert warnings2413Coding of submissions36Attachment A – Pre-screening checklist43Attachment B – 3.1.3 a), b) - to be superseded by the Package Inserts forHuman Medicines guideline442.01 General information Feb08 v4.docApril 2008Page 2 of 48
Registration of MedicinesGeneral InformationGUIDELINES FOR THE REGISTRATION OF MEDICINESGENERAL INFORMATIONNOTE: These guidelines outline the format and data requirements for preparation and submission of anapplication for registration of medicines, and should be read in conjunction with the Medicines and RelatedSubstances Act, 1965 (Act 101 of 1965), and the Regulations to this Act.1INTRODUCTIONThe registration of medicine in South Africa is governed by the provisions and requirements of theMedicines and Related Substances Control Act No. 101 of 1965, (hereafter 'the Act') and theRegulations and Guidelines published in terms thereof.These Guidelines describe the information required for the registration of “medicines” and for anapplication to amend a registered medicine. The information submitted will be evaluated in terms of theprovisions of the Act.The aim of these Guidelines is to assist applicants in the preparation of documentation for theregistration of medicines for human use. The types of medicine include a new medicine for a newchemical entity (NCE), a multisource (generic) product, a product line extension, and a biologicalmedicine.It is a legal requirement that data submitted for evaluation should substantiate all claims and shouldmeet technical requirements of quality, safety and efficacy of the product for the purposes for which itis intended. The Guidelines are meant to guide the applicant in meeting the requirements of the Act. Itis acknowledged, however, that in some instances scientific developments may dictate alternativeapproaches. When a deviation from a guideline is decided on, a detailed motivation giving thereason(s) for the deviation and justification for the alternative approach should be included in the expertreport submitted with the application.Whenever there is doubt, applicants are advised to consult the Medicines Control Council (MCC) forconfirmation and/or clarification before completing and submitting the application form; refer to thewebsite for contact details. Applicants should always refer to the current version of the relevantGuidelines for the Registration of Medicines and the Addenda thereto before completing theapplication form.Guidelines are constantly evolving as a result of scientific developments and harmonisation of therequirements of regional and international regulatory authorities. The MCC (Council) endeavours toregularly update the guidelines to reflect current thinking and keep its technical requirements andevaluation policies in line with “best international medicines regulatory practice”.2GENERAL2.1SCOPELegislation requires that the Council shall register every medicine before it may be sold/marketed.An application for the registration of a medicine should therefore be submitted for evaluation andapproval.These guidelines are relevant only to human medicines including biological and complementarymedicines. Separate guidelines apply to the registration of veterinary medicines and medical devices.2.01 General information Feb08 v4.docApril 2008Page 3 of 48
Registration of MedicinesGeneral Information2.2APPLICANT/PROPOSED HOLDER OF THE CERTIFICATE OF REGISTRATION (PHCR)2.2.1Eligibility to apply for registration of a medicine is governed by Regulation 22 of the Act. An applicationmay be made by any of the following:a)b)c)a person, body corporate/juristic person, company, residing and doing business in South Africa;a close corporation incorporated in South Africa; ora company in South Africa with at least-a responsible delegated person residing in South Africa andan authorised person residing in South Africa who must be a person with appropriateknowledge of all aspects of the medicine and who shall be responsible for communicationwith Council.2.2.2If the applicant is not a registered pharmacist or pharmacy the application should be co-signed by aregistered pharmacist, as defined in the Pharmacy Act (Pharmacy Act 53 of 1974 as amended). Thismay be the Responsible Pharmacist or another registered pharmacist responsible for regulatory affairsand with appropriate knowledge of all aspects of the medicine. This person should be in the full-timeemploy of the company. Proof of registration (copy of certificate) of the pharmacist who signed thedossier, and the Responsible Pharmacist, in terms of Act 53 must be included.2.2.3An Applicant/PHCR should submit a Site Master File (SMF) in accordance with the SMF guideline. Forsubsequent applications reference to the allocated SMF number will suffice.2.3CONFIDENTIALITY/SECRECYThe confidentiality of information submitted to the MCC is governed by Section 34 of the Act. TheMCC, committee members or staff of the Medicines Regulatory Affairs (MRA), may NOT disclose to any person, any information acquired in the exercise of powers or performance offunctions under the Act and relating to the business affairs of any person, exceptx for the purpose of exercising his/her powers, or for the performance of his/her functions underthe Act, orx when required to do so by any competent court or under any law, orx with the written authority of the Director-General, oruse such information for self-gain or for the benefit of his employer.The MCC may insist on written confirmation of the identity and affiliation of an individual inquiringtelephonically, or in person, about a medicine. No information shall be disclosed telephonically unlessthe Medicines Control Officer knows the enquirer is entitled to receive the information.2.4LANGUAGEIn terms of Regulation 22(4) of the Act, all applications and supporting data submitted to the MCCshould be presented in English (British). Original documents not in English should be accompanied byan English translation.2.5WHERE TO SUBMIT APPLICATIONSApplications should be posted to Private Bag X 828, Pretoria, 0001 or preferably be delivered by theapplicant, rather than a courier, to Room 214, Hallmark Building, 237 Proes Street, Pretoria, where theywill be logged and acknowledged. All correspondence should be addressed to the Registrar ofMedicines and should be clearly coded as indicated in section 13 of this guideline.The MCC will not take responsibility for documents posted or delivered to any other place or in anyother manner.2.01 General information Feb08 v4.docApril 2008Page 4 of 48
Registration of Medicines2.6General InformationWHEN A PRODUCT SHOULD BE REGISTEREDA product is liable for registration with the Medicines Control Council if any of the following apply.i)Any of the ingredients of a product is listed in one of the Schedules to the Act;ii)The product is a medicine by virtue of the definition of a medicine in the Act.iii)iv)The Act defines a medicine as:"any substance or mixture of substances used, or purported to be suitable for use, ormanufactured or sold for use in;(a)the diagnosis, treatment, mitigation or prevention of disease, abnormal physical ormental state, or the symptoms thereof in man; or(b)restoring, correcting or modifying any somatic or psychic function in man;and includes any veterinary medicine.”If the product falls under any of the pharmacological classifications as specified in Regulation 25of the Act.The intended use of a product and the text/words used in promoting the product, even if noclaims are reflected on the label, render the product registerable. A substance not ordinarilyeaten or drunk by man cannot be considered a foodstuff just because no apparent medicinalclaims are made for it.The relevant provisions and guidelines shall apply to a medicine called up as a complementarymedicine.2.7TYPES OF APPLICATIONSMedicine applications for registration for humans are divided into the following types for thedetermination of fees and allocation to reviewers for evaluation:2.7.1New chemical entity applications that include pre-clinical and clinical information in support of theefficacy and safety of the formulation/dosage form, indication/s and dosage regimen.2.7.2Multisource/generic applications and innovator product line extension applications that include clinicalinformation in support of efficacy and safety of the formulation/dosage form, or indication/s or dosageregimen.2.7.3Multisource/generic applications and innovator line extension applications that include comparative bioavailability/bioequivalence studies as proof of efficacy.2.7.4Multisource/generic applications and innovator line extension applications that include comparative dissolution studies as proof of efficacy that include any other comparative studies as proof of efficacy others, not mentioned above e.g. liquids/solutions.2.7.5Biological medicines: Biopharmaceuticals and BiosimilarsBiological medicine: A medicine where the active ingredient and/or key excipients have been derivedfrom living organisms or tissues, or manufactured using a biological process. Biological medicines canbe defined largely by reference to their method of manufacture (the biological process). These includeinter alia medicines prepared from the following substrates:(i) Microbial cultures (fermentation);(ii) Plant or Animal Cell cultures (including those resulting from recombinant DNA or hybridomatechniques);(iii) Extraction from biological tissues; and(iv) Propagation of live agents in embryos or animals.2.01 General information Feb08 v4.docApril 2008Page 5 of 48
Registration of Medicines2.7.5General InformationTypes of applications - Biological medicines continuedThe living substrate may be genetically modified in a number of ways to provide the required activeingredient, including recombinant DNA technology or hybridoma techniques.Biological Medicines include, but may not be limited to the following:(i) Plasma-derived products, e.g. Clotting factors, Immunosera, etc;(ii) Vaccines;(iii) Biotechnology-derived medicinal products (rDNA products) e.g. rHu-antihemophilic factors,Hormones, Cytokines, Enzymes, Monoclonal antibodies, erythropoietins;(iv) Human Gene therapy.It has been the practice, in South Africa, that Council will decide that certain well-characterised lowmolecular weight medicinal biological compounds, such as antibiotics, insulin etc be excluded frombiological medicine status, and they are therefore not reviewed by the Biological Medicines Committee.Biopharmaceutical: Patented biological medicine.Biosimilar: A biological medicinal product referring to an existing biological medicinal product for whichregistration has been applied for.2.8EVALUATION PROCEDURESRoutineExpeditedAMRP2.9refer point 6refer point 7FEESThe following non-refundable fees are relevant:2.9.1A non-refundable screening fee payable with the screening submission.2.9.2An application fee payable with the full submission of the application for registration.2.9.3A registration fee, payable when the application complies with all the requirements for registration, andwhich is payable before a registration certificate is issued.2.9.4An annual retention fee to maintain registration.2.9.5A fee to cover any amendments to the dossier or certificate.2.9.6A fee to cover any inspection of any manufacturing site.2.9.7A fee to cover authorization of the use of an unregistered medicine.2.9.8The fees are published in the Government Gazette and are also available on the website.2.9.9Methods of payment: By cheque or electronic payment / direct transfer.Also refer to the Bank Detail guideline for electronic payment / direct transfer.Cheques should be made out to ''Medicines Control Council''. Only bank guaranteed cheques will beaccepted and are to be submitted in a separate envelope attached to a copy of the covering letter ofthe relevant submission(s).Direct electronic payment should include a clear reference, e.g. the product application number orpurpose of the payment. Proof of electronic payment / direct transfer must be submitted in a separateenvelope attached to a copy of the covering letter of the relevant submission(s).Refer to 4.7 below for payment submitted with new applications.2.9.10 To ensure evaluation of the relevant submission(s) (2.9.3 to 2.9.7 above) a copy of proof of payment /cheque must also be attached to the original covering letter of the relevant submission.2.01 General information Feb08 v4.docApril 2008Page 6 of 48
Registration of Medicines2.10General InformationSAME OR SEPARATE APPLICATIONSFor the purpose of registration the following products will be regarded as either being the same productor separate product applications:TYPE OF APPLICATIONSApplicationSameSeparate2.10.1 Each individual dosage form of a particular medicineX2.10.2 Variations of the active pharmaceutical ingredient (API) of a productX2.10.3 Tablets/Capsules/Suppositories/Lozengesa) Different pack-sizes of exactly the same strength and formulation.Xb) Different strengths and formulations.Xc) Uncoated and coated tablets of the same strength and formulation.X2.10.4 Syrups/Liquids/Solutions(excluding parenterals) /Creams/Ointmentsa) Different container sizes of the same strength and formulation.Xb) The same container size of different strengths and formulations.X2.10.5 Ampoules and Vials and Large Volume Parenteralsa) Ampoules or single dose vials containing identical solutions of the samestrength but of different volumes (i.e. resulting in different total doses).Xb) Ampoules containing solutions of different strengths.Xc) Ampoules and single dose vials containing e.g. dry powder, crystals ofdifferent mass.Xd) Ampoules and single dose vials containing the same respective masses ofe.g. dry powder, crystals.Xe) Ampoules, single dose vials, as well as pre-filled disposable syringes andcartridges containing identical solutions of the same strength and samevolume of liquid.Xf)XDental cartridges containing different volumes of fluids of the same strength(provided the dose remains constant).g) Ampoules containing “water for injection”, but of different volumes.Xh) Special ampoules of dry powder and “water for injections” contained in thesame unit, but intended for mixing at the time of injection if water forinjections is fully described in dossier.Xi)Ampoules containing identical solutions of different volumes used only asdiluent in the reconstitution of a preparation for parenteral use.Xj)Multidose vials containing different volumes of the same strength andformulation with the same dosage schedule.Xk) Multidose vials and a single dose ampoule of the same formulation if thesingle-dose ampoule corresponds to the dose indicated for the multidosevial.Xl)Multidose vials containing dry powder of different mass of the sameformulation, and the same concentration when reconstituted.Xm) An ampoule of diluent packed together with any preparation includingbiological medicines if diluent is fully described in dossier.X2.01 General information Feb08 v4.docApril 2008Page 7 of 48
Registration of MedicinesGeneral Information2.10.5 Ampoules and Vials and Large Volume Parenterals - continuedSamen) Infusion solutions of the different volumes and of the same formulation whichare packed in containers of exactly the same type of material depending onthe relevant information submitted.Xo) Infusion solutions of the same formulation and of the same or differentvolume which are packed in containers made of different types of materials.Xp) A preparation, packed in plastic containers, intended to be marketed in glasscontainers containing the same volume and the same formulation.XSeparateq) Products with the same strength and formulation but with different coloursand/or flavours.Xr)Applications containing the same API(s) applying for additional indicationswhich render the product in a different scheduling status, or differentpharmacological classification, or have any other restrictions imposed otherthan the original application.Xs) Removal of antimicrobial preservative from single dose presentation ofregistered vaccine that included a preservative in the original approvedformulationX2.10.6 Same formulation with different proprietary names whether of the same ordifferent applicants2.11XTRANSITIONAL CONVERSION TABLEThe Medicines Registration Form (MRF1) replaces the MBR1 form for the application for registration ofa medicine prescribed by the Act. Biological medicines no longer have a separate form.Circulars issued before and during the transformation process made reference to the Annexures of theprevious MBR1 application forms. For ease of reference the following conversion table is included.MBR1 Biol*MRF1AnnexuresPARTFront pageSUBJECT* biological1AAdministrative Data1151CPI / PIL / Label263BFormulation / final filling lot formulation*2103BFormulation diluent if applicable/ final filling lot reconstituting liquid/diluent*3-3AA
Registration of Medicines General Information 2.01 General information Feb08 v4.doc April 2008 Page3 of 48 GUIDELINES FOR THE REGISTRATION OF MEDICINES GENERAL INFORMATION NOTE: These guidelines outline the format and data requirements for preparation and submission of an application
Drug Interactions with Enteral Nutrition (general use) Guidance regarding enteral administration of medicines and interactions between medicines and enteral feeds, including feeding breaks General points: This list is not exhaustive - contact ward pharmacist, practice pharmacist or Medicines Information (01355 584879 or medicines.information .
NEW MEDICINES, BETTER MEDICINES, BETTER USE OF MEDICINES 3 FOREWORD FOREWORD The Society leads and supports the development of the pharmacy profession including the advancement of science, practice, education and knowledge in pharmacy, as well as promoting public understanding of pharmacy
Before we get into the detail there are some commonalities of all stop smoking medicines that you need to know. Stop smoking medicines increase quit rates All stop smoking medicines increase the chances of stopping smoking for good. Smokers should be encouraged to use one of the licensed stop smoking medicines to aid them in stopping smoking.
Chapter 1. Biological medicines have revolutionized the treatment . 6 Since their first use in the 1980s, biological medicines have grown to become an indispensable tool . Chemically synthesized medicine Growth hormone Antibody. Producing biological medicines tends to be more
Yes. Some medicines used by older people can make it easy to get hypothermia. These include medicines you get from your doctor and those you buy over-the-counter, such as some cold medicines. Ask your doctor if the medicines you take may affect body heat. Always
certain medicines you put yourself at even greater risk. Combining alcohol with some medicines can lead to falls and serious injuries, especially among older people. MEDICINES MAY HAVE MANY INGREDIENTS Some medications—including many popular painkillers and cough, cold, and allergy remedies—contain
medicine. Name the two sources of all drugs. Identify four different types of medicines and their effects on the body. Identify five different ways that drugs can enter the body. Describe why some drugs are considered drugs of abuse. Differentiate between prescription medicines and over-the-counter medicines.
(half serious, half playful) Yes – except for last summer, when you never came near me –Sheila (Act 1) Suggesting that she doesn [t fully trust him, despite the fact that theyre going to be married soon, but again shows how she is childish, and relatively light-hearted, as she is still half playful [ even in something which could be seen as quite serious. men with important work to do .
