ANNEXURE 17 ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING Document No, (Main TA) Not applicable Addendum Ne. | _AD-02 THIS ADDENDUM TO AGREEMENT is made on the 0! Apsil 2019 to the Main Agreement made on 26" February 2018 BETWEEN Name | Bristol Laboratories Limited | Unit3 ,CanalSide,NorthBridgeRoad, Berkhamsted, Hertfordshire, HP4TEG red Office Company. Name | Medopharm Pvt Registered Office Henceforth known as the “Contract Acceptor (CAY” Individually referred to as ‘Party’ and collectively referred to as Parties’. \ BLLICQA/0A7/17/08 CONFIDENTIAL Bage 1 of 10oe ANNEXURE 17 “a Be ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING Document No. (Main TA) Not applicable ‘Addendum No. I ‘AD-02 PURPOSE: This addendum is prepared to amend the clause of Serialization, Elemental Impurity ssessment, Excipient Risk Assessment , Supply Chain Mapping , Quality Assurance, Reject and Recall of Batches , Warehouse And Shipping, Handling Of Market laint , Product Quali ew . Quality Defects , Stability Study , Notification related Quality Systems, Planned and ss idors, Documentation to be Supplied with 1, SERIALIZATION: The CA shall ensure that the pharmaceutical product supplied should have pharmaceutical Serialization system in place for tracking and tracing of product. This shall be accordance with the commission delegated regulation (BU) 2016/161 on Falsified medicines directives “laying down detailed rules for the safety features appearing on the packaging of medicinal products for human Use”. Details on commercial part shall be described in commercial agreement. 2. ELEMENTAL IMPURITY ASSESSMENT OF DRUG PRODUCTS: CA is responsible to provide elemental impurity assessment for each product in scope of TA in accordance with the EMEA “Guideline on the specification limits for residues of metal catalysts oF metal reagents” (EMA/CHMP/QWP/109127/2015), ICH Q3D and other applicable regulations before commercialization of the product. An updated statement must be issued after changes to the manufacturing process, materials, equipment and utility of the Product, if applicable, 3. EXCIPIENT RISK ASSESSMENT: 3.1 CA is responsible to perform risk assessment of all the excipients to ensure that these are suitable for use in medicinal products in accordance with the Official Journal of The Buropean Union 2015/C 95/02 which are being used in the products covered in scope of this technical agreement. CA is responsible to provide these excipient risk assessments on request from CG. 32 CA shall identify the Critical excipients beiig used for CG products. While determining the criticality of excipients, following shall be considered: 3.2.1 Role of excipient in the formutation 3.2.2 Proportionate of excipients in the formulation, 3.3 Identified excipients shall be documented, an index will be maintained for the same.and shall be shared with CG. The vendors of critical excipients must be audited by CA and the ‘outcome of audit should be shared with CG. Where justified an alternate assessment for audit of excipient vendors may be provided to CG BLLICQA/04711 7/08 CONFIDENTIAL, Page 2 of 10ANNEXURE 17 iB [ APPENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING” Document No, (Main TA) Not applicable | “Addendum No. AD-02 4. SUPPLY CHAIN MAPPING AND ASSESSMENT OF DRUG PRODUCTS: CA Is responsible to provide information on supply chain mapping and assessment for each Product in scope of this TA including information on registered Key starting material / intermediate, APIs, excipients and packaging materials (primary and printed/sccondary) as per femplates provided by CG before commercialization of the product, 5. QUALITY ASSURANCE: CA will collect QP samples (from initial, middle and end of packing run) and send to CG for BU testing in a separate box identified as QP samples. Upon arrival in the UK, CG will organize the impling (wherever applicable) and testing of the samples at an approved batch contro} laboratory as por CG's MIA, 6 REJECTS AND RECALLS OF BATCHES $1 CA watrants to CG that, upon delivery to CG, all. Product supplied to Agreement shall 6.1.1 Meet the specification of the applicable Marketing Authorisation: 6.1.2 have been Manufactured in accordance with all applicable national the place of Manufacture, including, but not limited to, those. rules and regulation: CG under this nd local laws, Promulgated by any relevant regulatory authority and relevant professional stendards, and codes of conduct; 613 Have been Manufactured, labelled, packaged and stored in accordance with the provisions in this Agreement and shall comply with the established processing and packaging instructions; 6:14 Have been Manufactured in accordance with any process or specifications set forth or otherwise referenced in the applicable marketing authorisation for finished packed resentation of the Products in the Territory; 6.15 Have been manufactured in accordance with all applicable GMP; and; 61.6 Shall meet the quantities ordered by CG and shall be in and free of any damage (whether to the Product or packaging) loading. 62 CG shall be entitled to reject. in whole or part good condition at the point of 4 delivery of the Produets where such Products are defective or fail to comply with the Warranties contained in Article 6.1 of this Agreement unless the defect {ailure to store such Products in accordance with the storage requirements applicable marketing authorisation after delivery to CG 6.3 CG shall give written notice to CA of any defeet or failure in the Products: 63:1 where the defect or failure is apparent on reasonable inspection); or arises ont of a contained in the \.. BLLICQA/047/17/08 CONFIDENTIAL, Page 3 0f 103 ANNEXURE 17 its ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING Document No. (Main TA) Not applicable ‘Addendum No. ‘AD-02 $3.2 affer CG has become aware of a latent defect or failure, such as during stability studies 64 CG shall be deemed to have accepted the delivery of Product in its entirety if it fails to provide such notice within the prescribed lime periods above. 6.5 The decision to recall a batch rests with CG. The nature and urgency of # recall will be Eeided following discussions, where necessary, between the relevant Regulatory Authority, CA and CG. 6 Once the decision to recall a batch has been taken, the recall will be initiated by CG and will inform CA of any action tht is required, CA shall indemnify CG against any and all elsiens, demands, losses, proceedings, costs and expenses (including without limitation reasonat iy legal fees) which may be brought or asserted against CG, its employees, Tepresentatives or suffered or incurred by CG, its employees, agents or representatives on Secunt of any of them being held to be liable without proof of fault in respect of any damage oF oss suffered by any third party or incurred by CG including without limitation any recall costs arising from; 6.6.1 any fault or defect in the Manufacturing, packaging or labelling of the Products 6.6.2 any fault or defect arising out of the improper storage of the Product priot to shipment and 6.6.3 CA breach of this agreement and/or negligence and/or wilful defeult 6.7 In the event that any regulatory authority issues a recall or takes similar action in connection With the Products supplied hereunder or any batch thereof, or a court of competent Jurisdiction orders such a recall by reason of a possible safety tisk ot for any other seein Stee Crt CG recalls the Products supplied by reason of a possible safety risk or for any other safety reason, then CG shall notify CA who shall comply with all reasonable, instructions of CG. Ail expenses incurred by CG, including but not limited o any payments rade by CG for the finished goods supplied by CA, of such recall shall be bone by CA if the Products that are the subject of the recall due to any of the reasons above and/or quality defect of supplied products. 7.0 WAREHOUSE AND SHIPPING: 7.1 CA shall ensure that the transporters shall be qualified and there shall be valid agreement between CA & Transporters, 7.2 CA shall not dispatch the split quantity of the batches unless authorized by CG. All the times full batch quantity should be dispatched BLLICQAI047/17/08 CONFIDENTIAL Page 4 of 10T ANNEXURE 17 M3] ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING ; Document No, (Main TA) Not applicable ‘Addendum No. [Apo 13 8.0 81 8.2 83 9.0 10.0 11.0 a shall ensure that suitable transport conditions relevant tothe product shall be adhered to, Where required CA shall use temperature-controlled shipping containers. All the shipments ‘Bust be accompanied by two Data-loggers per container and or per batch. CA shall eneure {o carry out temperature mapping of the containers used for transportation to justify Placement positioning of data loggers. These data-loggers should be purchased against pre- agreed, pre-approved Specification along with calibration certificate. ‘The temperature throughout the shipment should be recorded and ean be reproduced if required by MURA or any other relevant Regulatory Authority. Data- loggers to be downloaded by CG and data Will be provided to QP, The decision on any excursions remain with CG's QP Any Considerable trend in excursions shall be communicated to CA, HANDLING OF MARKET COMPLAINT: The investigation for the complaints should be completed within 21 ealendar days unless otherwise justified by CA. Interim report to be prepared and submitted within the 2 ealendar day timeline by CA in case the investigation is expected to get completed post 21 calendar days, Along with the interim report, the CA needs (o mention the timelines by when the investigation can be completed to CG. {nthe case of a ertieal complaint CG make an intial response within one working day, an interim investigation based on document and retention sample review (wherever applicable) needs to be submitted by the CA within 4 calendar days and the final investigation within 2 calendar days, In case of major complaint initial investigation needs to be submitted by the CA within 10 ‘calendar days and the final investigation within 21 calendar days PRODUCT QUALITY REVIEW: CA shall responsible to supply Product Quality Review ‘reports for each of the produets to CG on an annual basis. All PQRs must be competed and Submitted to CG within 15 calendar days from scheduled period. Any delay of completing the PQRs must be justified in deviation by CA QUALITY DEFECTS: CA should inform all OOS, OOT and LI reported for the products Within 48 hours from the reporting time along with preliminary investigation to CG. A detailed investigation shall be provided within 30 days from the date of OOS, OOT and Ll reported at, cA. STABILITY STUDY: CA shall be responsible for carrying out stability studies to ICH requirements and maintaining records of the same for the products. CA shall submit the annual stability study schedule or stability protocol for the products in scope of this TA to CG advance. The stability report shall be provided after completion of stability study for each point to CG as per schedule. me BLLICQA/047/1 7/08 CONFIDENTIAL, Page 5 of 103) ANNEXURE 17 ie ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING Document No. (Main TA) Not applicable ‘Addendum No. AD-02 12.0 NOTIFICATION RELATED QUALITY SYSTEM: CA shall send all notification em: related to quality systems (Change Control, deviations, out of specification etc.) which are raised at CA to following email id. Bristol PM@bristol-tabs.co.nke 13.0 Planned and Unplanned Changes - CG must prior approve all prospective changes proposed by CA in writing prior to undergoing the formal in-house Change Control Procedure. Similarly, all major unplanned deviations need to be reviewed and approved by CG and shall be closed by CA prior to release and dispatch of batch to CG 14.0 Annual assessment of API vendors: CA shall perform annual assessment of each API vendors 15.0 15.1 15.2 153 15.4 for the following: ~ Validity of Technical agreement, - API written confirmation, - CEP/DMF status, - TSE/BSE certificate, ~ GMP compliance status, - Route of transportation, = Consignments received / Approved / Rejected ~ Any significant changes ‘The outcome of these assessments should be shared with CG and should be considered in POR Documentation to be Supplied with Batches: For each batch of Finished Produet supplied, CA shall supply CG with uniquely identified (ic, numbered) Certificate of Analysis in the agreed format (i. including specifications, results and any cross reference to OOS, OOT, Laboratory Incidents) and CoC signed by CA Responsible Person, that the batch (¢s) has / have been manufactured, packed and controlled, in accordance with GMP, and in accordance with the requirements of the MA, along with Copies of the completed batch documents. The CA shall also provide loading list along with batch documentation as per Annexure-I, ‘The CA shall also ensure CG that, the scanning of batch documentation have been verified that the scan documents provided are similar with the paper copies of batch documentation available at site and evidence shall be provided to CG along with batch documentation, ‘The batch documentation and quality control documentation relating to a batch record should be retained in a secure location for iRer the certification by Qualified Person for batch release. ere relevant the respective batch documents must be stamped e.g, Process Validation batch must be stamped as “Process validation batch” on first page; the batch where stability samples are taken must be stamped as “Stability study batch” on first page. \y. BLL/CQA/047/17/08 CONFIDENTIAL Page 6 of 10ANNEXURE 17 3 ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING | Document No. (Main TA) ‘Not applicable. | Addendum No. ‘AD-02 APPENDIX II] Responsibility Chart General Responsibility ca_|ce Vendor audit for the APY manufacturer including verification of vendor Y |v ication/audit of Registered KSM/Intermediate and auditor credentials Ee Identification of critical excipients and their assessments v Ine ‘Vendor audit for critical excipients vendors and report to be submitted v nla wc Shipment and Distribution cA v ‘la Responsibility Data loggers: Placement of 2 Data loggers per container to be into the QP shipper, data-loggers positioning should cover far end of the container. The shipper & pallet nos. of Data loggers, to be mentioned in the Invoice & Pkg, list. Reference Samples and Records Responsibility ce Provide Copies of all Batch documents listed below to the contract givers Manufacturing Batch Record | Packaging Batch Record Certificate of Compliance Bill of Materials (BOM) for bulk manufacture Analytical Results for raw materials Manufacturing Instructions Tn-process control record for manufacture. Certificate of analysis for active material Bill of Materials (BOM) for packaging Packaging Instructions In-process control record for packaging Reconciliation of packaging materials Certificate of Analysis of Finished Product Details of investigations related to OOS / OOT / LE Loading list of batch Evidence for verification of batch documents scanning, f \. BLL/CQA/047/1 7/08 CONFIDENTIAL Page 7 of 10ANNEXURE 17 33 ADDENDUM TO TRCHNICAL AGREEMENT FOR CONTRACT MANUFACTURING Addendum No. ‘AD-02 Document No. (Main TA) Not applicable ANNEXURET Loading List of Containers Date: Product Name (s) Batch Number (3) Packing List Enclosure Data loggers numbers Container number Data logger Switch on time Hrs Container & reefer vehicle temperature before loading Ke Daio & Thine of start of Uoading of i container Daie & time of completion Loading ___Hirs Hrs j activity Total staffing tine ‘Time and temperature at the time of door losing of containers Time: ‘Container gate out time & temperature [ fom the fatory Time: Prepared By: Checked By: Sign/date Sign/daie All other terms and condition mentioned in ginal agreement remains unchangs o BLLUCQA/047/17/08 CONFIDENTIAL, Page 8 of 10ANNEXURE 17 a ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING Document No. (Main TA) Not applicable ‘adda. | Bristol Laboratories Limited (CG) ‘Medopharm Private Limited (CA) Contact No. : +44 1442 200 922 Email —_: pritigabristol-tabs,co.uk Date Signature: ‘Name : M.P. Chandra Shekhar Name 7 Sanjay Dasmohapatra Designation : Head~Corporate Quality | Designation : President (Technical & Assurance Operations Contact No. ; +44 1442 200 922 Contact No. : 00914430149999 00914430149953 Email : chandra@bristol-labs.co.uk Email sanjaydas@medopharm.com Date : 9 Date fet Mpoif 079 Signature a Signature wy ‘Name + Priti Ramachandran ‘Name +P R Abdul Hameed Designation : Director Quality & | Designation : Executive Director- Technical Regulatory Affairs & Operations Contact No, : 009144301490001/2 009130149958 Email: hameed@medophar Date 01-04. 2019 Signature BLL/CQA/047/1 7/08 CONFIDENTIAL, Page 9 of 10‘| ANNEXURE 17 ae ADDENDUM TO TECHNICAL AGREEMENT FOR CONTRACT MANUFACTURING Document No. (Main TA) Not applicable Addendum No. | AD-02 HISTORY CARD OF TECHNICAL AGREEMENT Sr. | Document Reason Page No. No. no. 01 |Not applicable New Document 7 ‘To amend clause for Confidentiality of Vendor audit reports and documentation 02 | Addendum ~1 04 ‘To amend the clause of Serialization, Elemental Impurity Assessment, Exeipient Risk Assessment , Supply Chain Mapping , ‘Quality Assurance, Reject and Recall of Batches , Warchouse And Shipping, Handling| Of Market Complaint , Product Quality mi Review , Quality Defects , Stability Study, Notification related Quality Systems, Planned and Unplanned Changes, Annual assessment of API vendors, Documentation to be ‘Supplied with Batches, Appendix-IMl and Annexure I included, 03 AD-02 \. 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