GUIDELINES FOR SUBMISION OF POST- APPROVAL …

1 GUIDELINES FOR SUBMISION OF post - APPROVAL VARIATION medicine applications FOOD, medicine AND HEALTHCARE ADMINSTRATION ANDCONTROLAUTHORITY OF ETHIOPIA(EFMHACA)First EditionDecember, 2015 Guideline forSubmission of post - APPROVAL variations medicines application1 Table of OF THIS OF I: DOSSIER REQUIREMENTS FOR MAJOR variations TO REGISTERED or addition of a manufacturing site of primary packing process of finishedpharmaceutical or addition of a manufacturing site of manufacturing process of finishedpharmaceutical to quality control testing of the finished pharmaceutical product.

2 Replacement oraddition of the site where batch control/testing takes and/or addition of alternative manufacturer/site of the of (qualitative or quantitative) excipients or inactive in the qualitative and/or quantitative composition of the immediate packaging in the batch size of the finished pharmaceutical product (change in batch size more than10 fold both up-scaling & down scaling for non-sterile and for all batch size change for sterile product) in the manufacture process of finished pharmaceutical in the colouring system or the flavouring system currently used in the finishedpharmaceutical in coating weight of tablets or change in weight of capsule in the specification of the finished pharmaceutical product ( Addition of new of testparameter & limit).

3 27 Guideline forSubmission of post - APPROVAL variations medicines in test procedure of the finished pharmaceutical or addition of imprints, bossing or other markings on tablets or printing on capsules,including replacement, or addition of inks used for product of dimensions of tablets, capsules, suppositories or pessaries without change inqualitative or quantitative composition and mean in the fill weight/fill volume and/or change of shape or dimension of container orclosure for non-sterile or addition of pack size/fill volume and/or change of shape or dimension of containeror closure for sterile solid and liquid of drug of the shelf-life of the finished pharmaceutical product (As packaged for sale, afterfirst opening, after dilution or reconstitution)

4 And change in the storage and/or additional indications/dosing regimen/patient population/inclusion of clinicalinformation extending the usage of the product)..32 SECTION II: DOSSIER REQUIREMENTS FOR MINOR variations TO REGISTERED MINOR variations WHICH REQUIRE PRIOR of local agent (s).. in the name of the finished pharmaceutical product (FPP).. or replacement of the company or party responsible for batch release of finishedpharmaceutical or addition of a manufacturing site of secondary packing process of finishedpharmaceutical change in the manufacturing process of in the batch size of the inthe specification of an in test procedure for of a new or updated TSE European Pharmacopoeia certificate of suitability for anAPI39 Guideline forSubmission of post - APPROVAL variations medicines in the shelf life or re-test period and storage condition of in specification of an excipient (specification limits are tightened or

5 Addition of newtest parameter and limit).. in test procedure for an in source of an excipient or reagent from a TSE risk to a vegetable or in the specifications of the immediate packaging of the finished to a test procedure on the immediate packaging of the finished in any part of the (primary) packaging material not in contact with the finishedpharmaceutical product formulation (such as colour of flip-off caps, colour code rings on ampoules,change of needle shield ( different plastic used)).. (replacement, addition or deletion) in supplier of packaging components or devices(when mentioned in the dossier); spacer devices for metered dose inhalers are to in-process tests or limits applied during the manufacture of the finished product(including tightening and addition of new in-process).

6 In the batch size of the finishedpharmaceutical product (Up to 10-fold compared tothe registered batch size and down scaling).. change in the manufacture of the finished pharmaceutical in pack size of the FPP Change in the number of units ( tablets, ampoules, etc.)in a pack including outer carton pack sizes for , replacement or deletion of a measuring or administration device that is not anintegrated part of the primary packaging (spacer devices for metered-dose inhalers are excluded) of the shelf-life of the finished pharmaceutical product (As packaged for sale, afterfirst opening, after dilution or reconstitution)

7 And change in the storage forSubmission of post - APPROVAL variations medicines minor variations such as (Change logo of applicant/manufacturer, Change in the designor layout of packaging, Change in the colour of design of the package, Correction and/or statementsof the label or Periodic update prescribing information)..48B. MINOR variations REQUIRES in the name and/or address naming of the marketing authorization holder of theregistered in the name and/or address naming of amanufacturer of the active in the name and/or address naming of a manufacturer of the finished pharmaceuticalproduct (FPP).

8 Of any manufacturing site (including for an API, intermediate or finishedpharmaceutical product, packaging site, manufacturer responsible for batch release, site wherebatch control takes place).. of a new or updated European Pharmacopoeia certificate of suitability for an to comply with an officially recognized pharmacopoeia (BP, Ph Int, JP, Ph Eur, USP)-Change in the specification of API & Excipients to comply with of a new or updated European Pharmacopoeia certificate of suitability for of a new or updated TSE European Pharmacopoeia certificate of suitability for and/or statements of the label or Periodic update prescribing III: variations THAT MAKE A NEW APPLICATION/ EXTENSION APPLICATION IV.

9 STABILITY REQUIREMENTS FOR variations AND CHANGES TO REGISTERED FINISHEDPHARMACEUTICAL PRODUCTS (FPPS)..56 Major V: CONSIDERATION OF SRA PROCEDURE FOR VARIATION forSubmission of post - APPROVAL variations medicines application5 ANNEX I-APPLICATION II-TYPES OF post APPROVAL variations REQUIRING SAMPLES FOR LABORATORY III-PAYMENTS FOR post APPROVAL forSubmission of post - APPROVAL variations medicines application6 Guideline forSubmission of post - APPROVAL variations medicines application7 ABBREVIATIONSAPIA ctive Pharmaceutical IngredientBPBritish PharmacopoeiaBSEB ovine Spongiform EncephalopathyCEEuropeanConformityCEPE uropean Pharmacopoeia Certificate of suitabilityNDRAN ationalDrug Regulatory AuthorityEFMHACAFood.

10 medicine and Healthcare Administration and Control Authorityof EthiopiaGMPGood Manufacturing PracticeFPPF inished Pharmaceutical ProductICHI nternational Conference on HarmonizationINNI nternational Non-Proprietary Name'N'NotificationNDANew Drug ApplicationPhIntInternational PharmacopoeiaJPJapanese PharmacopoeiaOOSOut OfSpecificationPhEurEuropean PharmacopoeiaSmPCSummary of Product CharacteristicsSRAS tringent Regulatory AuthorityTSET ransmissible Spongiform EncephalopathyUSPU nited States PharmacopoeiaWHOW orld Health OrganizationGuideline forSubmission of post - APPROVAL variations medicines application8 ACKNOWLEDGEMENTThe Food, medicine and Health Care Administration and Control Authority (EFMHACA) ofEthiopia would like to acknowledge and express its appreciation to the United States Agency forInternational Development (USAID) and the U.