PRODUCT TRANSFER

1. PRODUCT TRANSFER

2. Scope • This scope applies to all Product transfers of marketed : • Active Pharmaceutical Ingredient • Intermediate • Pharmaceutical product • Medical Device • From : • one site to another site within the same company • one site to an external sub-contractor or visa versa • Between two sub-contractors • This scope does not apply to transfers of new products from Development to commercial manufacturing

3. Responsibilities • Operational Sourcing Committee : propose, review, approve transfers • Project leader : solution of transfer-related issues, preparation of transfer protocol, communication with sites and operational management • Site project coordinator : at sending and receiving sites, focal point for communication, ensure coordination and oversight within their site, can be project leader

4. Responsibilities • Cross-functional transfer team (representatives from involved functions at sending and receiving sites) : performing activities associated with transfer : manufacturing and control processes • Quality at originating site assess compliance status of receiving site / feasibility study • Regulatory at both sites: define regulatory strategy with Quality • CMC

5. Responsibilities • Regulatory at sending site: assess receiving site is authorised by Regulatory Authorities for Manufacture and testing of concerned API or pharmaceutical form • Site quality management : • sending and receiving site review and approve transfer protocol and report • Receiving site review and approve validation protocol • Quality function has final responsibility to accept or reject transfers

6. Responsibilities • Sending site : supply product to market until final approval from receiving site : avoid stock-out!

7. Requirements • Transfer must ensure maintenance of: • Product quality • Process robustness • Regulatory compliance

8. Requirements • Transfer Process Phases • 1 - Pre-evaluation • Originates in company Operational Unit transfer request form describing the product is issued • Regulatory at sending site performs compliance assessment of product in all markets • 2 - Feasibility Study • Transfer request form Sending and Receiving sites determine means and timelines

9. Requirements • Feasibility Study outcomes are : • Definition of objectives and organization • Appointment of transfer team leader, coordinators at S & R sites, cross-functional transfer team • Quality and compliance assessment of receiving unit : company own site or subcontractor with audit result. For subcontractor: in case no audit available perform GMP audit. If critical findings : raise CAPA prior to starting operational transfer phase • Regulatory evaluation : regulatory strategy defined (cf. slide 4 for responsibilities)

10. Requirements • Feasibility Study outcomes are (cont.) : • Product stability evaluation assessed by sending site based on post-approval study results • Technical feasibility evaluation : » sending site creates transfer dossier with technical details » existing documents available to receiving site » receiving site assess technical feasibility : process and product » if changes needed : pilot or industrial trials to be performed and evaluation of impact » major change required (development/new process) outside of this scope » complete study documented

11. Requirements • 3 - Transfer Protocol • Defined and based on feasibility study results • All activities, associated responsibilities and timelines described • Stability protocol and Regulatory strategy/actions included • APIs : protocol must include strategy how to include new manufacturing site in all dossiers and necessary stability studies of medicinal products or medical device • Stability protocol : validation batches with 3 months stability results assessment before receiving site batches release • Accelerated conditions or extended post-approval study in case of stability sensitive product • Zones III/IV markets : stability study to be considered • Transportation stability study to be considered • Protocol reviewed and approved (cf. slide 4)

12. Requirements • 4 – Operational Phase • Responsibility : Receiving Site • Analytical transfer : before process transfer • Preparation of Process validation : • Review of process validation performed in SS by the RS • Quality assessment based on APR or separate risk analysis • Production of pilot or industrial batches at RS • Orders of required materials, components, equipments • Installation of required qualification of equipments, utilities and facilities. Any change change control ; equipment transferred to be requalified prior to use • RS Staff trained and documented on all aspects of transfer process

13. Requirements • Preparation of Process validation (cont.) • New product introduced in cleaning validation plan at RS • Process validation • Performed by RS according to validation protocol • Manufacture 3 consecutive batches at least • Representative of SS can be requested • Validation performed when all validation protocol requirements are met and RS quality management approves report • Regulatory Activities • prepares documents for variations • Review and submission : same process as usual • In case Pre-AI, submission after review and approval by Quality • Other submissions after review and approval by Site Quality Head

14. Requirements • 5 – Finalisation of Product Transfer • Product Leader • compiles all results in report • Assesses the overall success of transfer • In-case of development report : included in transfer report • SS and RS Quality Heads review and approve product transfer report • Regulatory approvals must be obtained before project is considered completed

15. Requirements • 6 – Batch Release • Batches released to market • Approval from Regulatory Authorities obtained • Validation successfully executed and reported • All products specifications are met including stability data • Release decision : RS Quality Head

16. Thank You Any Questions