Minor Variation for Registered pharmaceutical product in UAE

Transcription

1 Minor Variation for Registered pharmaceutical product in UAE Contents P. No. General Provision 3 General Instruction 4 Glossary 5 Variations EXCIPIENT: Replacement of an Excipient with a comparable Excipient of drug product: same or different functional characteristics of the Excipient EXCIPIENT: Change in coloring system used in the Drug Product: type or amount of one or more components EXCIPIENT: Change in Flavoring system used in the Drug Product: type or amount of one or more components EXCIPIENT: Change in the quantitative of excipient ±5%, Change in the quantitative composition of the coating of tablet or capsules amounting to 2% of total weight, Change to the volume of the granulating fluid to ±15% MANUFACTURING SITE: Change in site for the total process: bulk manufacturing + packaging + batch control/testing except releasing the finished product LABORATORY SITE: Change in site for batch control/testing of Drug Product MANUFACTURING SITE: Change in site for release of Drug Product 10 within the same country. MANUFACTURING SITE (SOURCE TRANSFER): Change in site for 10 release of Drug Product to a site in a different country. MARKETING AUTHORIZATION HOLDER IN COO: Change in the 10 name and/or address of a company of the finished products MANUFACTURING SITE: Deletion of any manufacturing site (including for an active substance, intermediate or finished product, 11 packaging site, manufacturer responsible for batch release, site where batch control take place) CONTAINER: Change in any part of the primary packaging material not in contact with the finished product formulation (Change in colour shape or dimensions of the container and/or closure system such as 11 colour of flip-off cap, colour code rings on ampoules, change of needle shield, logos, diagram, or picture ) CONTAINER: Change in the qualitative and/or quantitative 11 composition of the immediate packaging material CONTAINER: Addition or replacement or deletion of a measuring or

2 administration device not being an integrated part of the primary packaging (spacer devices for metered dose inhalers are excluded) PRODUCT NAME: New product name to replace existing name (no 12 change in formulation and in test specification) ACTIVE SUBSTANCE: Change in the name and/or address of a manufacturer of the active substance where No European 12 Pharmacopoeia certificate of suitability or any equivalent document is available ACTIVE SUBSTANCE: Change in the manufacturer of the active 12 substance formulation and in test specification) FINISHED PRODUCT SPECIFICATIONS/TEST METHODS 12 FINISHED PRODUCT: Change of dimensions of tablets, capsules, suppositories or pessaries without change in qualitative or quantitative 13 composition and mean mass.. FINISHED PRODUCT: Change in coating weight of tablets or change in weight of capsule shell ( in case of Immediate release oral 13 pharmaceutical forms, or Modified or prolonged release pharmaceutical forms) FINISHED PRODUCT: Change or addition of imprints, bossing or other markings (Except scoring/break lines) on tablets or printing on 13 capsules, including replacement, or addition of inks used for product marking STORAGE CONDITION: Change in Storage condition without change in shelf life and no other 13 changes or addition of a statement such as Protect from light, Change in storage conditions of reconstituted/diluted Drug Product SHELF LIFE: Extension of shelf life Drug Product and/or Change in shelf life after first opening of Drug Product and/or Change in shelf life 14 after dilution/reconstitution of Drug Product SHELF LIFE: Reduction of shelf life without change in the storage 14 condition. PACK SIZE: Change/ Addition of pack size without change in Container or closure system and/or without change in packaging material and doesn t affect on dose measurement or dose delivery: 1-14 Change in the number of units (e.g. tablets, ampoules) in a pack) 2- Change in the fill weight/fill volume of non-parental unit-dose products PACK SIZE:Adding of New pack size with new container or closure type and/or new packaging material type and/or new shelf life and/or 14 storage conditions and affects dose measurement or dose delivery PACK INSERT CHANGES : GRADE A, B, & C 15 Application Form 16 Receipt 19 2

3 I. General Provision 1. Certain changes to a pharmaceutical product have to be considered to fundamentally alter the basic nature of the drug product; therefore, can not be considered as minor variation. For such changes, an application for registration as a new product must be submitted. While evaluation such application, the Drug Control Department drug registration Unit shall also review whether the former registration should be withdrawn or not. Such changes include, Addition of one or more active substance(s) including antigenic components for vaccines. Deletion of one or more active substance(s) including antigenic components for vaccines. Quantitative change to the active substance(s) Replacement of the active substance(s) by a different salt/ester complex/derivative (with the same therapeutic moiety) Replacement of the active substance(s) by a different mixture of isomers (e.g. racemate by a single enantiomer) Replacement of a biological substance or product of biotechnology with one of a different molecular structure; modification of the rector used to produce the antigen/source material. Including a master cell bank from a different source. A new ligand or coupling mechanisms for a radiopharmaceutical. Change of bioavailability Change of Pharmacokinetics e.g. change in rate of release Change or addition of a new strength Change or addition of a new pharmaceutical dosage form Addition of a new route of administration (for parental administration, it is necessary to distinguish between the various routes like intra-arterial, IV IM SC etc). 3

4 2. The Following classes of products are considered variation according to given classes; A. Blood products 1. Source of blood 2. Processing steps 3. Quality Control testing method 4. Anticoagulants/ employed 5. Viral inactivation techniques 6. Excipient change 7. Stabilizer change B. Biotechnology & Immunological Products 1. Cell line related to the type of monoclonal antibodies produced 2. Culture type 3. Processing steps 4. The animal species employed for the production of polyclonal antibodies 5. Viral inactivation technique 6. Quality control testing method 7. Excipient C. Vaccines 1. Type of culture 2. Harvesting technique 3. Separation technique 4. Excipient The MAH should submit required information regarding change/variations included in relation to any of the above, to be reviewed on case by case basis. II. General Instruction The following Instructions are to be followed: 1. The application form for all types of minor variation dully filled, signed and stamped. 2. Application for Minor Variations shall not be accepted if the product registration has expired. 3. The required documents must be submitted in the letter head of the company, except that required from the relevant authority. All declarations 4

5 should also be on letterhead of the company but can be signed by Regulatory Manager locally or centrally. 4. All the documents must be submitted in proper file with Index. Incomplete applications and loose documents will not be accepted 5. All applications for approval of Minor variations must be accompanied by a covering letter from the manufacturer or the Marketing Authorization Holder (MAH) explaining the proposed variations in the product with justification for the same. 6. The covering letter shall be addressed to the Directorate of drug Control Department Photocopies of the certificates of registration/ re-registration and renewal thereof, and minor variation(s) approved earlier must be attached with application. Applicant (Manufacturer/ or MAH) shall fill the application form for minor variation in print, and submit along with necessary documents and samples. Samples, whenever submitted to the Drug Control Department must be identical to the sale pack to be registered in the department and accompanied by the certificate of analysis. Alternatively, submit samples with the same formula, alternative labels and with artwork copies, samples with actual labeling can be submitted with first commercial supply. The will number of samples at least two unless, samples required for analysis be decided by QC. 10. The documents and samples for Quality Control Laboratory (e.g. Stability data, dissolution profile, release & End Shelf life specifications test methods, validation of test methods) if required, must be submitted separated file, with a copy of covering letter and the application form. 11. The applicant shall be given a copy of the receipt after the documents have been verified and received in Drug Control Department. 12. Payment of fee for all variation at the time of submission 13. The term Authenticated means attested by the regulatory authorities/ministry of Foreign Affairs, and finally by the UAE Embassy or an y GCC state or any other country catering the interest of the GCC states, in the country of origin. III. Glossary Regulatory Authorities: Health authorities or other similar statutory bodies regulating the health affairs in the country of origin Marketing Authorization Holder (MAH) in COO 5

6 The MAH is the person, or Principle Company, or manufacturer responsible for making the finished product available in the market for use to the public. Manufacture Site it is the plant or premises where all or part of operations involved in the Manufacturing of pharmaceutical product are carried according to good Manufacturing Practice (GMP) Regulations. Certificate of pharmaceutical product (CPP) Must be as described in the criteria for registration of pharmaceutical product as per WHO format or equivalent organization. Certificate of GMP A documents issued by the regulatory authorities in the country of the manufacturing site, certifying that the manufacturing premises are confirming to the standards of the Good Manufacturing Practice stipulated by the WHO or the Regulatory Authorities in that country. Certificate of shelf life & Storage conditions A statement of the approved shelf life with storage conditions of the product. (Required if is not include in CPP) Certificate of Analysis A statement in original duly signed by the competent quality control personal and preferably stamped with the seal of the manufacturer, for the same batch of the sample submitted, specifying the following: Batch No., Manufacturing data, Expiry data, Result of analysis. Electronic certificates of analysis are also acceptable (no stamp, electronic signatures). Stability studies The capacity of a drug product to remain within established specifications to maintain its identity, strength, quality, and purity throughout the retest or expiration dating periods. The stability (long term & Accelerated) of the market formulations of the finished product (or formulations that may reasonably be expected to have the same stability) packaged as intended for marketing must have been tested in accordance with UAE guidelines. Bioequivalence Evidence of bioequivalence will usually be required for changes in products where bioavailability or clinical efficacy may be significantly altered as a result of the change. Evidence of bioequivalence with a reference product is the surrogate used, instead of clinical trial data, to demonstrate safety and efficacy. Oral dose forms are considered bioequivalent when 90% confidence intervals for the ratios of their geometric mean C max and AUC (from zero time to infinity for single doses or within a dosing interval at steady state) are within the range (wider limits may be appropriate for C max in certain circumstances where this can be justified on clinical grounds), and any difference between their T max s is within clinically acceptable limits. The above range is the maximum permitted for medicines that present a known or theoretical bioequivalence problem requiring an in vivo bioequivalence study. It may be tightened for medicines that have: 6

7 a narrow therapeutic index known serious dose-related toxicity a steep dose/effect curve Non-linear pharmacokinetics within the therapeutic dosage range. Dissolution Profile Dissolution studies should possess suitable discriminatory power and be carried out at 37 C and physiologically meaningful phs. More than one batch of each formulation should be tested. Comparative Dissolution profiles, rather than single point Dissolution test data, should be generated. The design should include: Individually testing at least six dosage units (e.g. tablets, capsules) of each batch. Mean and individual results should be reported along with their standard deviations or standard errors. Measuring the percentage of nominal content released at a number of suitably spaced time points to provide a profile for each batch, e.g. at 10, 20 and 30 minutes or as appropriate to achieve virtually complete Dissolution Conducting the tests on each batch using the same apparatus and, if possible, on the same or consecutive days. Final specifications for routine Dissolution testing of the test product should be based on the data generated in this comparative study used to support equivalence of the test and reference products. Price certificate Document showing the following: - name, pharmaceutical dosage form and pack size of the product - the Ex-factory, wholesale and retail prices of the product in the country of origin - The proposed CIF price of the product to the GCC states 7

8 Minor Variation The variations classified to Three main procedures as follows Changed medicine Type I/A: Approval of Drug Control Department is required (The evaluation through Minor Change Committee, and the certificate will be issued for the approval of variation) Changed medicine Type I/B: Approval Quality Control Laboratory only is required (The evaluation through Minor Change Committee is not required, and the certificate will be issued for the approval of variation). Changed medicine Type II: Notification to Drug Control Department with immediate implementation (The variation will be accepted /or rejected on the time of submission the file, and the certificate will issue within 30 days. Changed medicine Type III: Notification to Drug Control Department with immediate implementation (This type of variation doesn't required approval from Drug Control Department, but notification of variation should be submitted among with application form); certificate will not be issued. No Of variation 1 Description of Changes EXCIPIENT: Replacement of an Excipient with a comparable Excipient of drug product: same or different functional characteristics of the Excipient Procedure Type 1. Exact Composition of the Drug Product 2. Quality control laboratory File includes the new release and shelf life specifications and method of analysis of finished product and its validation. 3. Stability study (long term & accelerated) in accordance with the UAE Stability Guideline. 4. Shelf life statement. 5. Justification of the change (if applicable), and for not submitting Bioequivalence studies. 6. For solid dosage forms, Comparative dissolution profile data of at least 2 pilot scale batches of the finished product in the new and old composition. And justification for not submitting a new bioequivalence study. 7. If the excipient, e.g. magnesium or calcium stearate, stearic acid, gelatin, lactose etc.) that is, or potentially of animal origin, or comes into contact with material of animal origin during manufacture, the source of the material (or contact) must be declared, and evidence must be provided that the product is free from viruses, other micro-organisms and transmissible spongiform encephalopathy (TSE) agents, by submitting relevant EDQM certificates. 8. Samples with Certificate of Analysis. Note: Change in the source of an excipient, from a TSE risk to Vegetable or synthetic source: Declaration, that the specification remain unchanged and study or where possible declaration on equivalent of material. I/B 8

9 2 EXCIPIENT: Change in coloring system used in the Drug Product: type or amount of one or more components 1. Exact Composition of the drug product 2. Updated the finished product specification in respect of appearance/odour/taste and if relevant ) 3. Stability study (long term & accelerated) in accordance with the UAE Stability Guideline. Quality control laboratory File includes the new release and shelf life specifications and method of analysis of finished product in case of increase addition or replacement. 4. Sample of the new product 5. Documentary evidence that the specific source of the Transmitting Animal Spongiform Encephalopathies TSE risk material has been assessed by the competent authority and proofed that it s free from TSE contamination. 3 EXCIPIENT: Change in Flavoring system used in the Drug Product: type or amount of one or more components 1. Exact Composition of the drug product 2. Documentary evidence that the specific source of the Transmitting Animal Spongiform Encephalopathies TSE risk material has been assessed by the competent authority and proofed that it s free from TSE contamination. 3. Sample of the new product 4 EXCIPIENT: - Change in the quantitative of Excipient ±5% - Change in the quantitative composition of the coating of tablet or capsules amounting to 2% of total weight. - Change to the volume of the granulating fluid to ±15% 1. Exact Composition of the drug product 2. In case of coating, declaration from company states that coating have no modified release properties. I/B II III 5 MANUFACTURING SITE: Change in site for the total process: bulk manufacturing + packaging + batch control/testing except releasing the finished product II 1. Letter from the pharmaceutical company specifying the operation that will hold in the site 2. Copy of manufacturing site registration certificate. 3. Declaration from the company, state that no change in the quantitative & qualitative of the composition and manufacturing process. The declaration should be on the company original letterhead and be dated and signed by a qualified person that hold product license in the company. 6 LABORATORY SITE: Change in site for batch control/testing of Drug Product III 9

10 1. Covering letter to Drug Control Department 2. Formal accreditation as test laboratory or quality control standard certificate for the Laboratory issued by the relevant competent authority. 3. Updated release & end-shelf life specification for the product. MANUFACTURING SITE: Change in site for release of Drug Product 7 II within the same country. 1. Registration certificate for the manufacturing site issued by the UAE drug control department 2. Declaration from the company, state that no change in the quantitative & qualitative of the composition and manufacturing process. The declaration should be on the company original letterhead and be dated and signed by a qualified person that hold product license in the company. 3. Sample with new site name & address (If applicable). 8 MANUFACTURING SITE (SOURCE TRANSFER): Change in site for release of Drug Product to a site in a different country. 1. Registration certificate for the site issued by the UAE drug control department 2. Declaration from the company, state that no change in the quantitative & qualitative of the composition and manufacturing process. The declaration should be on the company original letterhead and be dated and signed by a qualified person that hold product license in the company. 3. Sample with new site name & address (If applicable). 4. Change of the country of origin for site that release the drug product, the following point is required addition to the above points: a) Authenticated CPP of each product from new source. b) price Certificate from the new source 9 Marketing Authorization Holder in COO: Change in the name and/or address of a company of the finished products 1. Company Application form Part 1 2. Declaration from the company state that the manufacturing site shall remain the same. The declaration should be on the company original letterhead and be dated and signed by a qualified person that hold manufacturer license in the company. 3. List of the related products. 4. Outer & Inner label of each Product (or art work), on company letter head signed & stamped. ( on CD preferably) 5. Sample with new company name & address (If applicable). I/A II 10

11 10 MANUFACTURING SITE: Deletion of any manufacturing site (including for an active substance, intermediate or finished product, packaging site, manufacturer responsible for batch release, site where batch control take place) 1. Letter from company outline the present and the proposed manufacturing site that take place in the manufacturing process. 2. Declaration from the company, state that no change in the quantitative & qualitative of the composition. The declaration should be on the company original letterhead and be dated and signed by a qualified person that hold product license in the company 11 CONTAINER: Change in any part of the primary packaging material not in contact with the finished product formulation (Change in colour shape or dimensions of the container and/or closure system such as colour of flip-off cap, colour code rings on ampoules, change of needle shield, logos, diagram, or picture ) 1. The Variation application form should clearly outline the present and proposed container 2. Outer & Inner label of each Product (or art work), on company letter head signed & stamped. ( on CD preferably) 3. Sample of new container/clouser (If applicable). III III 12 CONTAINER: Change in the qualitative and/or quantitative composition of the immediate packaging material I/B 1. The Variation application form should clearly outline the present and proposed container 2. Stability study (long term & accelerated) in accordance with the UAE Stability Guideline. 3. Approved end shelf life finished product specification. 4. Outer & Inner label of each Product (or art work), on company letter head signed & stamped. ( on CD preferably) 5. Sample of new container/clouser (If applicable). 13 CONTAINER: Addition or replacement or deletion of a measuring or administration device not being an integrated part of the primary packaging (spacer devices for metered dose inhalers are excluded) II 11

12 1. Letter from company describing, detailed drawing and composition of the device material. 2. Proof of CE marking 3. Data to demonstrate accuracy precision and compatibility of the device if NO CE marking available 4. Sample of the new device (If applicable) 14 PRODUCT NAME: New product name to replace existing name (no change in formulation and in test specification) IA 1. Approval of health authority in the country of origin of the new invented name. (Authenticated) 2. Declaration from the company, state that no change in the quantitative & qualitative of the composition and manufacturing site and process. The declaration should be on the company original letterhead and be dated and signed by a qualified person that hold product license in the company. 3. Outer & Inner label of the Product (or art work), on company letter head signed & stamped. ( on CD preferably) 4. Sample with new name (If applicable) 15 ACTIVE SUBSTANCE: Change in the name and/or address of a manufacturer of the active substance where No European Pharmacopoeia certificate of suitability or any equivalent document is available III 1. Copy of manufacturing license issued by the relevant drug regulatory agency in which the new name and/or new address is stated. 16 ACTIVE SUBSTANCE: Change in the manufacturer of the active substance 1. Certificate of Suitability or Equivalent documents been issued for the active substance. 2. Company statement confirming no change to Active Substance Specifications. II 17 FINISHED PRODUCT SPECIFICATIONS/TEST METHODS: revised specifications/test methods (no change in manufacturing process) product controlled according to a pharmacopoeia monograph (resulting from change to a different pharmacopoeia, not simply updating to the latest edition. or/ tightening of limits for active substance no other changes to specifications and no changes to test methods or/ adoption of additional or different specifications/test methods not specified in the pharmacopoeial monograph for a product otherwise controlled according to a pharmacopoeial monograph III 12

13 1. New Shelf Life Specification 2. New Release Specification 3. Test Procedure (Statement, that old & new methods are at least equivalent) 4. Validation of Test for Assay and Impurities 5. Copies of new and old certificates of analysis. 18 FINISHED PRODUCT: Change of dimensions of tablets, capsules, suppositories or pessaries without change in qualitative or quantitative composition and mean mass. 1. Comparative dissolution data on at least one pilot batch of the current and proposed dimensions. 2. Where applicable, data on breakability test of tablets at release must be given and commitment to submit data on breakability at the end of shelf life. 3. Samples of the finished product (If applicable) 19 FINISHED PRODUCT: Change in coating weight of tablets or change in weight of capsule shell ( in case of Immediate release oral pharmaceutical forms, or Modified or prolonged release pharmaceutical forms) 1. Exact Composition of the Drug Product 2. Comparative dissolution data on at least one pilot batch of the current and proposed dimensions. 3. Stability study (long term & accelerated) in accordance with the UAE Stability Guideline. 4. Approved end shelf life finished product specification. 5. Samples of the finished product (If applicable) 20 FINISHED PRODUCT: Change or addition of imprints, bossing or other markings (Except scoring/break lines) on tablets or printing on capsules, including replacement, or addition of inks used for product marking 1. Description of the drug product 2. Samples of the finished product (If applicable) Note: Finished product test method, release and shelf life specification have not been changed. STORAGE CONDITION: Change in Storage condition without change in shelf life and no other 21 IB changes or addition of a statement such as Protect from light, Change in storage conditions of reconstituted/diluted Drug Product III IB III 13

14 1. Stability study (long term & accelerated) in accordance with the UAE Stability Guideline. 2. Approved end shelf life finished product specification and where applicable specification after dilution/reconstitution or first opening 3. Description of packaging material (primary & Secondary) 4. Justification for the change. 5. Outer & Inner label of the Product (or art work), on company letter head signed & stamped. (CD preferably) 6. Samples of the finished product (If applicable) SHELF LIFE: Extension of shelf life Drug Product and/or Change in 22 shelf life after first opening of Drug Product and/or Change in shelf life after IB dilution/reconstitution of Drug Product 1. Stability study (long term & accelerated) in accordance with the UAE Stability Guideline. 2. Approved end shelf life finished product specification and where applicable specification after dilution/reconstitution or first opening 3. Description of packaging material (primary & Secondary) 4. Outer & Inner label of the Product (or art work), on company letter head signed & stamped. (CD preferably) 5. Samples of the finished product (If applicable) Note: The shelf life does not exceed five years 23 SHELF LIFE: Reduction of shelf life without change in the storage condition. 1. Justification for the reduction of shelf life. II 24 PACK SIZE: Change/ Addition of pack size without change in Container or closure system and/or without change in packaging material and doesn t affect on dose measurement or dose delivery: 1- Change in the number of units (e.g. tablets, ampoules) in a pack) 2- Change in the fill weight/fill volume of nonparental unit-dose products 1. Cover letter explaining the change 2. New Price certificate. 3. Outer & Inner label of the Product of new pack size (or art work), on company letterhead signed & stamped. (CD preferably). 4. Samples of the new pack size (If applicable) 25 PACK SIZE: Adding of New pack size with new container or closure type and/or new packaging material type and/or new shelf life and/or storage conditions and affects dose measurement or dose delivery IA IA 14

15 1. CPP or Approval letter from the Regulatory Authorities in the country of origin for the pack size change. (Authenticated) 2. New Price certificate. 3. Justification for the new pack size, showing that the new pack size is consistent with the dosage regimen and duration of use as approved in the SmPC. 4. Stability study (long term & accelerated) in accordance with the UAE Stability Guideline. 5. Approved end shelf life finished product specification where applicable. 6. Outer & Inner label of the Product of new pack size (or art work), on company letter head signed & stamped. (CD preferably) 7. Samples of the new pack size (If applicable) 26 PACK INSERT CHANGES Grade A Three Main Grades - Addition of new indication or Modified Indication and consequential changes included new dosage instructions. - New dosage regimen with no change to indication. - Deletion of (contraindications, warnings, side effects, precautions & drug interaction). 1. Declaration letter explaining the new changes. 2. Legalized approval of the Healthy Authorities of country of origin for the new changes. 3. Supportive clinical literature if the changes are related to new indications or new dosage regimen. 4. Comparison table between old & new pack insert. 5. Artwork or word document of old & new pack insert. Grade B Addition of (contraindications, warnings, side effects, precautions & drug interaction). 1. Declaration letter explaining the new changes. 2. Company core data sheet (CDDS) supporting the new changes. 3. Comparison table between old & new pack insert. 4. Artwork or word document of old & new pack insert. 5. Acceptance in other countries (if applicable). IA II Grade C - Revised wording of the pack insert with no actual changes to the approved information. - Re-design of label with no changes in the approved information. - Change in the size of label, printing color, font, etc Justification letter explaining the new changes. 2. Copy of the proposed pack insert. III 15

16 APPLICATION FOR REGISTRATION OF A MINOR VARIATION 1. DETAIL OF MARKETING AUTHORIZATION HOLDER IN COO Name of MAH Address/Street City Country Postal Code Website: 2. DETAIL OF LOCAL DISTRIBUTOR Authorized Distributor No. Of Store License Name of Manufacturing Site Date of Renewal 3. DETAIL OF THE MANUFACTURING SITE Date of Latest GMP certification issued: Certificate Registration No. issued by Drug Control Department Reg. Date 16

17 4. DETAIL OF PRODUCTS Trade Name Dosage Form Active Ingredients (INN or Scientific name) Strength Registration /or re- Registration certificate No: Date of Issue: 5. DESCRIPTION OF VARIATIONS (please specify descriptions according to UAE variation descriptions) Procedures Type 6. SCOPE (please specify scope of the changes(s) in concise way) 7. JUSTIFICATION FOR CONSEQUENTIAL CHANGES (if applicable) (Please give brief justification in case of consequential changes) 17

18 9. SPECIFY THE PRECISE PRESENT AND PROPOSED WORDING OR SPECIFICATION. Current product details Proposed details 10. DECLARATION I hereby submit an application for the above product to be varied in accordance with the proposals given above. I declare that: 1. There are no other changes than those identified in this application; 2. The change(s) will not adversely affect the quality, efficacy or safety of the product; 3. The required documents as specified for the variation(s) concerned have been attached to the application. 4. All conditions as set for the variation(s) concerned are fulfil Name & Designation of the signatory: Signature Address: Company stamp Date: 18

19 Product Name Receipt for Minor variation of registered product Form/Strength Manufacturer company Local Distributors/Address Description of Minor variation No. of Variation Procedure Type Receipt No: Checked & Received BY Signature Date : 19