(Crescent "eshninlAgieement No. +6060 - You TECHNICAL AGREEMENT MARKET AUTHORISATION HOLDER (1) CRESCENT PHARMA LIMITED CONTRACT ACCEPTOR (2) MEDOPHARM PRIVATE LIMITED. IMPORTER & CONTRACT GIVER (3) CRESCENT PHARMA LIMITED Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31% October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1* August 2014 Page No.: 1 of 26(Crescent ‘Technical Agreement No. : 600160 - Vd TECHNICAL AGREEMENT FOR THE PRODUCTS LISTED IN APPENDIX 1 This document constitutes the Technical Agreement required under European Good Manufacturing Practice (GMP) Legislation 2003/04 EEC as amended to cover contract pharmaceutical processing by @ third party & CPMP Directives CPMP/BWP/1280/08 to demonstrate compliance with the ‘Note for guidance on minimising the risk of Transmitting Tranemissible Spongiform Encephelopathy (TSE). Ik defines the individual responsibilities of the Contract Giver and the Contact Acceptor and in partiouiar defines who is responsible for the GxP aspects of processing and specifies the way in which the Qualified Person releasing product batches for sale ensure that they comply with the Marketing Authorisation The Technical Agreement takes the form of a detailed chock list of all the activities associated with Sharrmaceutical production, analysis and release. Responsibility for each activity is assigned to one or more of the relevant parties in the appropriate tick box. If any element of the check list does not apply, it should be clearly Grossed through, not left blank. Its then appended to the legal contract which covers the commercial and other aspects of the Agreements amongst parties, including the Manufacturing Manual and Secrecy Agreement, if required, MARKETTING AUTHORISATION (MA) HOLDER | CONTRACT ACCEPTOR (2) a Modopharm Private limited Crescent Pharma Lie Addross Address ‘Medopharm Private Ltd, Senna eae 25 Pulliur 2 main road, Hampshire, R625 3ED ‘Trustpuram, Chennai ~ 600024. Tamil Nadu, England | India IMPORTER & CONTRACT GIVER,(3) Address of Manufacturing Plant rescent Pharma Lid (if different from the above) Unis 38 4, No.: 50, Kayarambedu Village, Quidhampton Business Units, Guduvanchery ~ 603202, Tamil Nadu, India Poihampton Lane, Hereinafter referred to as Manufacturer Overton Hampshire, RG25 SED England, UK ‘Technical Agreement between MA Holder (CRESCENT), Importor/Contract Giver (Crescent) and Contract Acceptor ((Medopharm Private Limited) Prepared: 31* October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1" August 2014 Page No:: 2 of 26x Crescent Fee Agrexment Ne 6016-04 21 Parties This agreement is made between: CRESCENT PHARMA LIMITED Units 3 & 4 Quidhampton Business Units, Polhampton Lane, Overton, Hampshire, G25 3ED, England, Hereinafter referred to as PL Holder AND Medopharm Private Ltd, 25 Pulliur 2" main roads, ‘Trustpuram, Chennai -- 600024, Tamil Nadu, India Address of Manufacturing Plant if (different from the above) No.: 50, Kayarambedu Village, Guduvanchery- 603203, Tamil Nadu, India Hereinafter referred to as Manufacturer Itis the responsibility of the respective companies to ensue that the relevant personnel are aware of the contents and implications of this agreement and its procedures. 2.2 Product ‘The products and their respective Marketing Authorisation numbers in the United Kingdom are listed in Appendix 1 ‘Technical Agreement between MA Holder (CRESCENT), Importer/Gontract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31 October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1" August 2014 Page No.: 3 of 26‘Crescent ‘Technical Agreement No: 600560 Vou 3 GENERAL REQUIREMENTS AND RESPONSIBILITIES 3.1 General requirements Each party will undertake not to vary anything explicit or implied in this Agreement other than by waritten consultation, and will give reasonable consideration to adopting any new standards, specifications and procedures at the written request of the other, 3.1 Regulatory/Statutory Requirements All parties, in good fath, will comply with the regulatory requirements (legislation and guidance) within the scape of this agreement, immediately highlighting to the other party deficiencies should they occur. All parties will be responsible for monitoring compliance against this agreement and its general review. In respect of its activities under this Technical Agreement;- 3.2.1 Contract Accepto: shall undertake to conform to the EU GMP Volume IV and as subsequently amer.ded, 32.2 MA Holder will furnish Contract Acceptor and the Contract Giver with up-to-date Marketing Authorizations for each PRODUCT. 3.2 EU Good Manufanturing Practice (GMP), and Good Distribution Practice (GDP) In respect of its activities under this Technical Agreement:- 3.3.1 Contract Acceptor shall comply with the requirements for GMP laid down in Commission Directive 2003/94/EC and chapter 7 of the Rules Governing Medicinal Products in the Européan Community Volume 1V ~ Good Manufacturing Practice for ‘Medicinal Products, ‘The Contract Acceptor and Contract Giver shall coraply with the Guidelines on Good Distribution Practice 94/C 63/03 from time to time, ‘Technical Agreement between MA Holder (CRESCENT), Importer/Gontract Giver (Crescent) and Contract Acceptor (Medophamm Private Limited) Prepared: 31° October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1° August 2014 Page No.: 4 of 26 \-(Crescent ‘Technical Agreement No. : 600160 - VO4 3.4 Marketing Authorization (MA) ‘The Marketing Authorisation Holder shall be responsible for maintaining and therefore applying for variation(s) to its MAs to accommodate the manufacture, packaging and testing of products at Contract Acoeptor ‘The MA holder shall be responsible for informing the Competent Authorities of any future variations to the MAs for the products, and for accordingly informing the Contract Acceptor and Contract Giver of the same. 3.5 Contact List ‘The MA Holder, Importer and Contract Acceptor shall ensure that the contact lists are kopt up to date (see section 6). 3.6 Subcontractors Contract Acceptor shall not subcontract to a third party any of the work entrusted under this Agreement without MA Holder’s prior evaluation, which may include auditing the subcontractor and written approval of the subcontractor along with the appropriate agreements and variations being put in place where appropriate. This shall also include other facilities that are owned by the Contract Acceptor. ‘The Contract Acceptor shall only use approved contract laboratories for testing that has been evaluated as per intemal procedures and shall have the relevant technical agreements in place 4.0 | PRODUCTION AND CONTROL 4.1 Contract Acceptor undertakes to ensure that its production and quality control, including analysis of the Intermediate product, Bulk product and Finished product, comply with'- 4.14 The requirements of MAs, 4.1.2. The requiements of this agreement, 4.1.3 The specifications set out in documentation, 4.1.4 The Contract Acceptor shall be responsible for carrying out stability studies to ICH requirements and maintaining records of the same for the products. Technical Agreement between WA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31% October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1° August 2014 Page No.: § of 26‘Crescent ‘Technical Agreement No, : 600160 - Vo4 42 43 43 44 45 46 Production Documentation Contract Acceptor’s production documentation shall be used. All master documents pertaining to the product under Appendix-1 shall be prepared by manufacturer and approved by Contract Giver Batch Numbering System Contract Acceptor’s Batch Numbering system shall be used. The system shall be a unique numbering system. Date of Manufacture and Expiry The shelf life and storage conditions of the product will be in accordance with the Tequitements of the MA and the expiry will be calculated from the date that manufacture (Date of Dispensing of the first raw material) of the batch commenced. Contract Acceptor’s system shall be used. Deviation, Out of specification, Incidents, non conformities from Manufacturing Process All deviations, Out of specification, and non-conformities shall be appropriately documented and approved by Managers designated by contract Acceptor from the Quality and Production departments, in accordance with approved procedure. Contract Acceptor shall be responsible for ensuring that such reports of investigations are attached to the relevant batch records, and are forwarded to Contract Giver, Any of the above that impact the quality of the product or/and has an impact on the Marketing Authorisation approval must be obtained in writing from Contract Giver prior to effecting the change for unplanned events these must be appropriately documented with the batch documentation, Time line for approvel of documents shall be given in the APPENDIX IT Use of Rework and Reprocessing materials No re-work is allowed in the manufacture of the products unless specifically authorised in writing by the Contract Giver. Reprocessing at different stages of packaging may be noceptable, however this must be in accordance to written procedures and the reprocessing process validated where relevant, ‘Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31" October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1% August 2014 Page No.: 6 of 28i] (Crescent ‘Technical Agreement No. : 600160 - V04 4.7 Supply of raw materials 4 Contract Acceptor will also be responsible to evaluating suppliers, agents! stockists, as potentially, agents could store, break bulk packs, re-lnbel and issue certificates of ; analysis, Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 34" October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1* August 2014 Page No.: 7 of 26 Y 7(Crescent 5.0 TECHNICAL AGREEMENT POINTS IN DETAIL GMP REQUIREMENTS FOR THE PRODUCTS LISTED IN APPENDIX 1 RESPONSIBILITIES GMP REQUIREMENTS MA | Contract Holder | Acceptor a) Q) Contract Giver 3) Importer & ‘Technical Agreement No. : 600160 - Vo4 11 ‘Manufacture and package bulk or finished products in accordance with European GMP’s as defined in Directive 2003/94/EC and any locally imposed xequirements, n/a n/a 12 | and packaging of the product Supply all information necessary for manufacture ala nia 13 Maintain a valid Manufacturing Licence or EU GMP Compliance certificate covering manufacture of the product issued by the relevant EU member state 14 Maintain “updated Marketing Authorisations covering the relevant products wa nia Ls "Maintain the Manufacturer/ Importer (MIA) licence covering the importation of the products’ from outside the EU and the EEA, Be wa, wa 1.6 Sourcing of Active materials in accordance with “note for guidance on minimizing the tisk of transmitting animal spongiform encephalopathy agents via human products as Directives CPMP/BWP/1230/98 Sourcing of excipionts in accordance with “note for guidance on minimizing the risk of transmitting animal spongiform encephalopathy agents via human products as Directives CPMP/BWP/1230/98 wa wa 17 ‘No change to formulation or process, potentially affecting the TSE status of the product shall be made without the prior written consent of the Contract Giver. wa n/a “Manufacture product in strict adherence to the approyed Marketing Authorisation ee a, ‘Technical Agreement between MA Holder (CRESCENT), Imporler/Contract Giver (Crescent) and Contract Acceptor (WMedopharm Private Limited) Prepared: 31" October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1" August 2014 Fage No.: 8 of 26(Crescent ‘Technical Agreement No, : 600160 - Vos ESPONSIBILIT Je GMP REQUIREMENTS a MA [ Contract | Holder} Acceptor (1). 2), Importer & 1.9* | Pormit audits of all relevant premises, procedures and documentation by the Contract Giver and it inspection by the Regulatory Authorities n/a v 1.10 | Not to subcontract any of the work fo a third pariy without prior agreement. This shall also include any other manufacturing site of the contract acceptor than the approved site, Any analytical work contracted out shall be to authorized and approved contract laboratories by the Contract. Acceptor ma na TAT | Approve all Manufactaring Instructions (Production Operation Instruction) —_ nla 1.12 | Make no changes to the product specification or manufacturing process without prior written agreement nia, Document any deviation, Out of Specification, 1.13 | non-conformities from defined procedures, including approval by Production and Quality Management. The deviations must form part of the batch documentation and be approved by the Head of QA and PL Holder QP : ‘Make no changes in the sourcing of any actives and | excipients waless otherwise authorised in writing and without changing registered specifications. wa wa 1-15 | Control the quality ofall actives and excipients according to specification by the application of approved analytical methods na Batch release by an authorised Qualified Person after review of the information specified in Sections 2, 3 and 4 to ensure compliance with the Marketing Authorisation. nia, ala 1.17 | Maintain all batch records for a minimum of one fear after expiry of the product an nla ‘Technical Agreement between MA Holder (CRESCENT), ImporterContract Giver (Crescent) and Contract Acceptor (Medophanm Private Limited) Prepared: 31 October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1% August 2014 Page No.: 9 of 26 y(Crescent ‘Technical Agroement No. : 600160 - VO4 RESPONSIBILITIES MA | Contract | Importer & Holder | Acceptor | Contract Giver 1 ___GMP REQUIREMENTS dl) (2) Q) 1.18] Maintznance of cGMP with updating of CEP for Active materials. Contract Acceptor shall advise the PL, Holderof any such changes. PL. Holderin tum will advise Contract Giver of such changes. i v v ‘The Contract Acceptor shall ensure that all additional tests(where relevant) mentioned in the , CEP are verified at the time of receipt of the Active ingredients Analytical Method Transfer for all products 1.19 | manufactured by the Contract Acceptor, and the na v a * | QC site(s) in the EU I { q 1.8* The MA Holder will notify immediately to the relevant Contract Acceptor and Importer any significant changes in Marketing Authorisation, including mandatory text changes, component changes, process changes that may affect the Quality, Safety and Efficacy of the Products 1.9* ‘The MA Holder and/or Contract Giver shall audit the Contract Acceptor to ensure compliance to GMP. The MA Holder may andit the Contract Giver fo ensure that compliance to GMP and the requirements of the MA, 1.19* The Contract Giver is responsible for providing the Analytical Method Transfer protocol to the Contract Acceptor and the QC site (s). The final report shall be signed off by the Contract Giver, the Contract Acceptor and the QC site(s). The responsibility for the management of the AMT is, with the Contract Giver. ‘Technical Agreement between WA Holder (CRESCENT), Importer/Coniract Giver (Crescent) and Contract Acceptor (Medophatm Private Limited) Prepared: 31" October 2017. Review Period: 3 Years ‘This Technical Agreement Supersedes: 1° August 2014 Page No.: 10-of 26 \y-‘Crescent ‘Technical Agreement Na. : 600160 - PROCUREMENT AND TESTING OF RAW MATERIALS FOR THE PRODUCTS LISTED IN APPENDIX 1 RISLONSNLTNIES WIA | Contract [Importer & Holder | Acceptor | Contraet Giver PROCUREMENT AND TESTING OF RAW oO | @ @ ‘MATERIALS EE 21 * "| Procurement of active substances (including a 7 7 Cettificates of Analysis, COA) 22° | Auditing and approval of API Sites as per EU ae i a ridelines / ICH Q7A, Storage of active substances we “a _| Sampling of active substances la . ai ‘Test Method for active substances jee ac we _| Analysis e substances (including a : 7 | documentation, COA) 4 [2.7 [Release of active substances _ me wa 2) Retain reference samples of active substances for S|, a years 2.9 Procurement of inactive subsiances (Including COA) |" nf ‘ wa 210 | Assessment and approval of [oe ~~ al 2.11 “| Storage of inactive substances la v we 2.12 | Sampling of inactive substances Eee aa ¥ na 2.13 | Test method for inactive substances_ [ae ¥ wa 2.14 Analysis of inactive substances (including a yw documentation, COA) 215 _[ Release of inactive substances [a ¥ a_i 2.16 | Retain reference sample of inactive substances as A Z a per policy : 7 2.17 (Routine confirmation of TSE siatoments of all TSE risk materials (API, excipients) , Finished product in accordance with “note for guidance on ss f te minimizing the risk of transmitting animal ] spongiform encephalopathy agents via human products as Directives CPMP/BWP/1230/98 eee Ee 2.1,25¢ ‘The Contract Acceptor shall only source the actives from sources approved on the Marketing Authorisation, or mamufteturers having (COS/EDMF) with Approval from MA Holder, ‘Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medophamm Private Limited) Prepared: 31" October 2017. Review Period: 3 Years ‘This Technical Agreement Supersedes: 1* August 2014 Page No.: 41 of 26 \(Crescent al ral Agreement No. : 600160 - Vo4 2.28 ‘The responsibility for the API auditing and therefore the API declaration by the QP responsible for batch relonse fies with the Contract Giver, however in some eases the Contract Giver may delogate the auditing to the Contract Acceptor if the Contract Giver ‘has established confidence that the personnel auditing on its behalf is independent and Competent. The API declaration is still ultimately be provided by the QP of the Contract Giver MANUFACTURE AND TESTING FOR THE PRODUCTS LISTED IN APPENDIX 1 RSLS MA | Contract] Importer & Holder Acceptor | Contract Giver 3 MANUFACTURE AND TESTING OF BULK a) a) 8) a see PRODUCT. [31 | Master Formula (or product structure) 32 | Batch size confirmation 3.3 | Batch Identification System for bulk manufacture 34° | Process Validation 35 ation 367 is (BOM) for bulk manufacture 37°} Manufacturing Instructions (Production Operating 38° | Production of bulk manufacturing (including batch documentation) sampling plan Sampling of bulk product Test method for bulk product ‘Analysis of bulk product Release of bulk product for packagin; _| Certificate of Analysis for bulk product 34,3.6,3.7 Process validation protocol, Bill of Materials and Manufacturing instruetions to be drafted by Contract Acceptor but approved by personnel nominated by the Importer ‘Technical Agreement between MA Holder (CRESCENT), importericontract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31" October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1“ August 2014 Page No.: 12 of 26 \-(Crescent STARA CTA ‘Technical Agreement No, : 600160 - VO4 PACKAGING DETAILS FOR PRODUCTS LISTED IN ANNEXURE 1 ‘RESPONSIBILITIES: ose MA | Contract [Importer & Holder] Acceptor | Contract Giver 4. PACKAGING. © @ @ al a up and labeling text (blister, carton, leaflet, label, [~ om we 42 | Artwork preparation ¥ ¥ wa 4.3% Artwork review and approval a ‘Specifications for packaging ma ae n/a, | Test methods for packaging materials __ wa, 4.6 | Procurement of packaping 1 cee nia 4.7 | Auditing and approval of suppliers of primary and nla _|_piinted packaging materials 4.8 [Inspection of packaging materials i wa 4.9 __ | Release of packaging materials nia 4.10 | Retain samples of printed packaging materials as pet aa | policy _ 4i1* | Validation of packaging process nia z wa 4.12 * | Bill of materials (BOM) for packaging na_| a 4.13 * | Packaging Instructions, wa ¥ wa 4.14 | Tn-process packaging controls (including i Z i documentation) al a 4:15 | Reconciliation of packaging materials na | wa 44, 4.11, 4.12, 4,1 The specifications shall be provided by the MA Holder in accordance with the Marketing Authorisation. Bills of material, validation process and packaging instructions to be drafted by the contract acceptor, but approved by personnel nominated by the importer/MA Holder 4.3. “All artwork must be approved by personnel authorized by the PL Holder. No changes must be made unless approved by the MA Holder, Al! changes must be communicated in writing, 4.4.* Contract Acceptor shalt not make any changes to the packaging specification unless agreed in waiting by the MA Holder, The MA Holders responsible for approval of artwork, but the Contract Acceptor will be responsible for ensuring all receipts comply with the approved artworks/ Proofs, ‘Technical Agreement between MA Holder (CRESCENT), ImporterContract Giver (Grescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31" October 2017. Review Period: 3 Years This Technical Agreement Supersedes; 1" August 2014 Page No.: 13 of 26 Nye‘Crescent ‘Technical Agreement No, : 600160 - Vos SPECIFICATIONS, TESTING AND RELEASE OF THE FINISHED PRODUCT trend results pertaining to the product listed in Appendix-L RRCONSLETIES NA] Contimet | importer 7 Holder | Acceptor | Contract s SPECIFICATIONS, TESTING AND REI Oo Q Giver FINISHED PRODUCT IEEE —|—_8 Finished Product Specification = wa Wa, ‘Test method for finished produet Te “ a wal ‘Analytioal Method validation [ae ¥ ale “Analysis of finished products Gnchuding ri documentation), ; Bae a nia Release of finished product by QP. wa la v Centificate of Analysis for finished product wa, ¥ ¥ Batch Identification system for finished product wie wa Finished product sampling plan, [va nla [5.9 | Sampling of finished produet wa nla 5:10 ~ | Retain reference samples of finished product for 1 a 7 c year after expiry date | Si _| Stability Study. __ | ae ¥ [5.12 | Stability Testing Protocol a ¥ a) Place the first 3 batches in market packs on stability | at 25°C/60% RE (long term), 30°C/65% RH (intermediate) & 40°C/75% RH (accelerated). Samples will be anelyzed at 30°C/65% RH (intermediate) only when there is a significant change at 40°C/75% RH (accelerated) nla ’ na Place 1 betch of product on stability per annum at 25°C/60%RUH (long term). 3 additional batches shall be placed on stability if \ any significant changes are made and approved through change control peer [b) [Test as per ICH puidelin wa__| a] c) Results concurrent with the finished product " 7 eet _| specification stated on the Marketing Authorization _ 4) | Report all valid out of specifications and out of ala . na Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopham Private Limited) Prepared: 31% October 2017. Review Period: 3 Years This Tech nical Agreement Supersedes: 1° August 2014 Page No.: 14 of 26 ‘ he ai ‘Crescent Tochninl Agreement No. 00160- Ved RESPONSTLITIES MA Contract] Importer? | wolder | Acceptor | Contract Giver BR SPECIFICATIONS, TESTING AND RELEASE. OF ony @ @) FINISHED PRODUCT 3.13 * | Complaints Z a)___| Collection and logging ¥ nla | b)___| Investigation and issue of reports ¥ ¥ ¥ ¢)___| Follow up on corrective action wa ¥ = d) | Adverse Event Reporting « wa we 5.14* | Annual product quality review a) | Review of raw materials used, particularly any [ changes (change in source) bia i i 6) | Review of critical in process controls and A A wa fee finished products results i ©) | Review of batches that fail to meet the a : established specification d) Review of ail changes carried out to process, i “| ry 7 | and analytical methods Peete ©) | Review of Marketing Authorization variations submitted/granted/refused including those for . nla n/a 3rd country dossiers 5 Roview of the results of stability monitoring E a " program EEE EEECEEEE EEE eee at 8) | Review of quality related retums, complaints and recalls, including export medicinal nla ’ ’ oducts: h) | Review of adequacy of previous corrective y e e actions za zt D A list of validated procedures and their He Z a revalidation dates : et 3) A list of qualified equipment and their cr iE wa requalification dates Ht Ee ee SAS [ProductRecall [_ Decision to initiate recall I v ala nla [ Approval of wording of notification to MHRA | __v wa wa ‘Management recall nia wa L Management of retumed product nla nia Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31% October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1 August 2014 Page No.: 15 of 26 W- rafe ‘Crescent Teena Agreement Ne: 60000-VO8 NSILATES [Ma ci Tmporter7 Holder | Acceptor | Contract Giver 5 SPECIFICATIONS, TESTING AND RELEASE OF a @ @) _FINISHED PRODUCT, _ | 5.16 | Responsibility to Authorities nh nla Liaison with Regulatory Authorities for approval,maintenance and updating of product, ’ Wa we Marketing Authorisation Check that sub-contractor has an appropriate fs ‘Manufacturing Licence “ ue ma Maintain safety/hazard and handling data on product and raw materials va ¥ wa Liaison with Health & Safety Authorities wa y ae (Local statutory) ct EEE Liaison with Environmental Protection 4 Authorities (Poilution Prevention) 5.1% Contract Acceptor will draft the finished product specification, but approval must be granted by personnet authorised by the Contract Giver, 5.4.* - Full testing to finished product specification will be carried out by the Contract Acceptor. ‘As per EU Guidelines on release of finished product by a QP within the EU (Directive 2003/94), fall testing to finished product testing will be undertaken at a laboratory nominated on the Marketing Authorisation and the Manufacturing Import Authorisation (MIA) within the EU prior to release of the finished goods, 5.5.* The imported goods shall be “quarantined” on receipt and stored at the site indicated on the Importer’s Licence. ‘The Importer shall organize for the batches to be tested. The QP on the Importer’s License shall be responsible for releasing the products for sale. 5.6.* The Certificate of Analysis and retained samples for the analysis within the EU shall be held with the batch records by the Importer 5.13.* Any complaints relating to Quality will be notified to the Contract Acceptor and the MA Holder(each party to inform the other on receiving quality related complaints). Contract Acceptor will carry out a full investigation and report its findings to the Contract Giver and the PL Holder, ‘The Contract Giver will be responsible for responding to the Complaint. Contract Acceptor will be responsible for implementing corrective actions as recommended by the investigation. Technical Agreement between MA Holder (CRESCENT), ImporteriContract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31° October 2017. Review Period: 3 Years H This Technical Agreement Supersedes: 1" August 2014 y Page No.: 16 of 26 7(Crescent inical Agroement No. : 600160 - Vd STORAGE AND TRANSPORTATION + MA — | Contract | Importer / 6. | STORAGE AND TRANSPORTATION OF BULK, Mokier | Acceptor | Contract MATERIAL FINISHED PRODUCT AND WASTE ® @ Giver ale. DISPOSAL. iz @) [6.1 "| Stomnge of bulk product upto packaging a v | a ['6.2* | Storage of finished product nia, ¥ wa, 63 | Storage under special conditions, og. refrigeration (specify conditions) | ¥ v ¥ Protect from heat, light and Moisture 6A_ | Transportation of bulk product to contract giver or designated third party under storage labeled | condition 6.5 | Transportation of finished product to Contract or designated distributor under storage labeled | wa nia ’ condition ‘Two data loggers required for cach consignment ransport under special condi | insurance for transportation ex-plant Customs Formalities 6.10 | Disposal of waste Bt = AT | Disposal of special waste, e.g, toxic waste, solvents, etc. (specify nature of waste and special disposal methods required) ala ¥ wa 65" Contract Giver will be responsible for the transportation of finished product from manufacturing site to U.K warehouse. Contract Giver will be responsible for ‘ensuring contracts are in place with On Time International Logistics Pvt. Ltd, and ensuring the produets is handled in accordanee with Iabel storage conditions, 66 Refer to the product list Appendix 1 for the stipulated transit conditions ‘Technical Agreement between MA Holder (CRESCENT), Importar/Gontract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31 October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1* August 2014 Page No.: 17 of 26 \Y7 (Crescent TocholentAgromment No 60160- V4 MANUFACTURING DOCUMENTS FOR THY PRODUCTS LISTED IN APPENDIX 1 ‘RESRONSIBILITIES A T MA | Contract Importer / 2 BATCH DOCUMENTATION Holder | Acceptor | Contract Giver a @ @ 71 | Manufacturing record Batch packaging record | Process Validation protocol cabs act We . wa Finished product Preparation documents : Batch specifications & Method of analysis { | Analytical method validation _ Approval of documents Batch Manufacturing record Batch packaging record Process Validation protocol Packaging Validation ala ’ Stability Protocol Finished product specifications & Method of analysis, | Analytical method vatidation_ Provide the following dooume 7.4. | / Contact Giver for all batches as specified below: | ‘Manuficturing Batch Record 7 Packaging Batch Reo a Certificate of Compliance os 4 ‘Tick the documents required below: oe Bill of Materials (BOM)for bulk product i (requested) ‘Analytical results for raw materials requested) | { [ Manufacturing Instructions (ifrequested) 4 nla In-process Control Record for manufacture Technical Agreement between MA Holder (CRESCENT), ImporteriGontract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31* October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 7" August 2014 ait Page No.: 18 of 26 y ji ;(Crescent BHARNA TAME ‘Technical Agreement No. : 600160 - V04 ‘RESPONSIBILITIES eae Po MAMolder | Contmnct | Importer / 1 BATCH DOCUMENTATION a) ‘Accepto | Contract Giver r @) ® Certificate of Analysis for active material (from API tn {2 v fa manufacturer and Finished product manufacturer) bss 7 Bill of Materials (BOM) for packaging LY. (frequested) Packaging Instructions v__| Gfrequested) Insprocess contral record for packaging [ala ~__| Gf requested), Reconciliation of packaging materials | afa |v nia Certificate of Analysis for Finished Product nla, al wa Data loggers ~ data / software ’ nla 7.4 * The data logger accompanying the shipment to the Contract Giver shall have a unique number. ‘The data logger, once received with the goods, shall be returned to the Contract Acceptor and a summary report (graphical presentation) depicting the minimum and maximum temperature and humidity shall be forwarded to the Contract Giver or alternatively the Contract Acceptor shall forwad the Software for downloading the data from data-logger and the Contract Giver would download the data from the logger, ‘Technical Agreement between MA Holder (CRESCENT), Importer/Gontract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31% October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1* August 2014 Page No.: 19 of 26 \(Crescent BHARRTA CANES "Technical Agreement No. : 600160 - VO4 6.0 CONTACT DETAILS The following points of contact are to be used for all discussions of specific issues pertaining to this agreement, MARKETING AUTHORISATION /. (1) AND IMPORTER AND CONTRACT GIVER. (3) CRESCENT PHARMA LTD. [For Commercial queriesi- ] Tek: ++ 44 (0)1256-772730 Name: Mr. Mohammed Al-Dooti Fax: + 44 (0)1256-772740 Department: Managing Director | E-mail: maidoori Jerescentpharma.com Tel: +44 (0) 1256-772730 ‘Yor Technical Queri ‘amet Mr. Stewart Manegold Fax: +44 (0) 1256-72740 Department: Quelity Manager E-mail: Smanegold@erescentpharma,com Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31" October 2017, Review Period: 3 Years ‘This Technical Agreement Supersedes: 1 August 2014 ¥ 7 Page No,: 20 of 26(Crescent BirAnna cna te ‘Technical Agreement No. : 600160 - VO4 CONTRACT ACCEPTOR (2) MEDOPHARM PRIVATE LIMI Tel: +91 44 30149987 For Commercial queries:- Pax: +91 44 30149991. Name: Mi. Udhan Kumar Chordia | Mobile: 0091-9994067890 Departments Chief Executive Officer | | zamait uko@medopharm.com For Technical queries:~ | Tet: 0091-44-30149999 ‘Name Mr. Sanjay Dasmohapatra (eee Departments President Mobile: 0091-9677759462 (Technical & Operations) Email:sanjaydas@medopharm.com 7.0 GLOSSARY OF TERMS * Starting material: Any substance used in the production of a medicinal product, but excluding, packaging materials. (e.g. Active Pharmaceutical Ingredients (APIs) or excipients). = Packaging material: Any material employed in the packaging of a medicinal product, excluding any outer packaging used for transportation or shipment, Packaging materials are referred to as primary or secondary according to whether or not they are intended to be in disect contact with the product, (Printed packaging materials means labels, leaflets or cartons). * Intermediate product: Partly processed material, which must undergo further manufacturing steps before it becomes a bulk product. (e.g. a granulate before 1 becomes bulk tablets). " Bulk produet: Any product which has completed all processi final packaging. (E.g. bulk tablets). stages up to, but not including * Finished product: A medicinal product, which has undergone all stages of production, including packaging in its final container, ‘Technical Agreement between MA Holder (CRESCENT), ImporterContiacl Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31% October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1* August 2014 Y Page No.: 21 of 26 7r (Crescent Tec Agent No. 640160- VK * Production: All operations involved in the preparation of a medicinal product, from receipt of materials, through processing and packaging, to its completion as a finished product, * Manufacture: All operations of purchase of materials and products, Production, Quality Control, release, storage, distribution of medicinal products and the related controls, * Packaging: All operations, including filling and labelling, which a bulk product has to undergo in order to become a finished product, Other definitions used in this agreement are those detailed or construed from the Commission Directive 2003/94/EC and chapter 7 of The Rules Governing Medicinal Produets in the European Community Volume IV ~ Good Manufacturing Practice for Medicinal Products. HISTORY OF CHANGES: # TANo. REASON FOR CHANGE | DATE OF APPROVAL 1 600160-NEW | Initial agreement | 27" November 2007 Basic time line for different activities a 2 sooise-vor | Baie 28" October 2010 Revision to point number 2.17; change : 3 600160—Vo2 | incontact details of Technical person @ | 01 May 2012 Medopharm; = He 4 Point Number 6.6 updated Change in contact details of Technical Saas 4 600160--Vo3 | Fon @ Medophann, 18th August 2014 Appendix 1 list of products updated 7 600160 vo4 | Updates to contacts and renewal of eae agreement i ‘Technical Agreement botween MA Hokler (CRESCENT), Importor/Goniract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31 October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1* August 2014 Page No.: 22 of 26ee iCrescent ‘Technical Agreement No. : 600160 - Vod APPENDIX I- LIST OF PRODUCTS aay = R | SHELRLIFE S.NO. | PRODUCT NAME MA NUMBER | (months) | 1 36 months before 1 | Amoxicillin 125mg/Sml | Oral Suspension 20416/0010 7 days after reconstitution 36 months before | ] ae reconstitution and 2 | Amoxicillin 250mg/Sml_| Oral Suspension 20416/0011 Faves reconstitution | 3 | Ampiciltin BP 250mg | Capsules 20416/0012 48 months in bulk pack 4 | AmpicillinBP 500mg —_| Capsules 20416/0013 36 months in bulk peck Co-Fluampicil | 5 (250mg+250mg) | Capsules 20416/0051 36 a in bulk oo aaa} x! icillin | 36 months in’ 6 Esme hylpenicillin |p stets an ae Amoxicillin Capsules iebrsssestveriant ; ~~ | 36 months in 7 1950 mg Capsules 20416/0573 | biter pack Amoxicillin C; v eH EERE z 6 inontl I ; 8 | 500 me, in Capsules | Capsules 204160574 | blister pack Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Crescent) and Contract Acceptor (Medopharn Private Limited) Prepared: 31 October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1" August 2014 Page No.: 23 of 26(Crescent ‘Technical Agreement No. : 600160 ~ VO4 BASIC TIME LINE FOR DIFFERENT ACTIVITIES APPENDIX IL RESPONSIBILITIES. MA Contract Importer / on BATCH DOCUMENTATION Holder Acegpter | Conte Giver cH DOCUMEN’ ae o o 1”) Master Documents Approval a wa Within One Batch Manufacturing Record/ Process Month Validation Protocol/ Product Hold Time Study Protocol/ Finished Product [_ Specification Stability Study Protoce 2 | Change Control Approval | 2.1 | Minor Change Control na nla ‘Within 15 3 3.1 | Minor deviation 32”) Major / Critical deviation = po |Jtours 4 [Tncident Report Within 2 days 3” | Market Complaints Investigation Pe nia Within 2 days Within One) nla fonth 3 nla ida CE ee ‘Within 2 days ia 6 | Out Of Specification Notification to client nla Within 2 days na (| 7 | Stability data updating ~T nia, ‘Onceiné | a Months 3” | Product Quality Review wa Onoe in 6a | Months 9 | Vendor Avdit wa | Asper the | As per the [Schedule __| Schedule Page No.: 24 of 26 Technical Agreement belwoen MA Holder (CRESCENT), Imporie/Contract Giver (Crescent) and Contract Acceptor (Medopharm Private Limited) Prepared: 31* October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1 August 2014 y .‘Crescent ‘eshnicl Agreement No: 600160- Vou BILITIES, MA Contract Importer / free BATCH DOCUMENTATION Hokder Accpter | Contac Ger | 7 ty Q) _ 10 | After receipt of data logger it shall be w/a, na returned fo contract acceptor | TT Data Togger data’s with graphical na | | Wa presentation shall be sent to contact giver | ‘The policies set forth herein shall be valid until amended or revoked by written agreement between CRESCENT PHARMA LIMITED and MEDOPHARM PRIVATE LIMITED, or until cessation of the reporting responsibility of CRESCENT PHARMA LIMITED or of the distribution responsibility of MEDOPHARM PRIVATE LIMITED. This agreement supersedes any previous technical agreements between the companies. wide Technical Agreement between MA Holder (CRESCENT), Importer/Contract Giver (Grascent) and Contract Acceptor (Medopharm Private Limited) Propared: 31° October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1% August 2014 Page No.: 25 of 26 yf 1 i ‘Crescent ecnln Agent No, 60060 Vo AUTHORISATION MARKETING AUTHORISATION HOLDER. (1) & IMPORTER AND CONTRACT GIVER. (3)- CRESCENT PHARMA LIMITED Full Name: Mr. MOHAMMED AL-DOORI Position _: Chief Executive E-mail maldoori@erescentpha Telephone: +44 (0)1256-772730 Fax 2+ 44 (0)1256-772740 Signature: Anil, CONTRACT ACCEPTOR- MEDOPHARM PRIVATE LID FullName —_ : Mr. SANJAY DASMOHAPATRA Position _: President (Technical and Operations) Mobile 0091.9677759462 E-mail sanjaydas@medopharm.com Telephone —_: 0091-044-30149999, Signature: War q FullName — : Mr. G VAIKUNDARAMAN Position: DEM Quality Control E-mail : ge@medopharm.com Telephone 1 0091-044-27438449 Bxtn: 115/125 Mobile + 0091-9677093364 Signatare: Pull Name — : Mr. RENJITH PURUSHAN Position AGM Quality Assurance E-mail renjith.p@medopharm.com ‘Telephone: 0091-044-27438449. Extn: 126/116 Mobile Signature: i Ab— ; ‘Technical Agreement beiween MA Holder (CRESCENT), ImportariContract Giver (Cre Contract Acceptor (Medopharm Private Limited) Prepared: 31" October 2017. Review Period: 3 Years This Technical Agreement Supersedes: 1 August 2014 Page.No.: 26 of 26