PRODUCT TRANSFER

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

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

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

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

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

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

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

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)

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

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)

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

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

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

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

Thank You Any Questions