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 QualityCMC

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 reportReceiving 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 qualityProcess robustnessRegulatory compliance

Requirements

• Transfer Process Phases1 - Pre-evaluation

oOriginates in company Operational Unit transfer request form describing the product is issued

oRegulatory at sending site performs compliance assessment of product in all markets

2 - Feasibility StudyoTransfer request form Sending and

Receiving sites determine means and timelines

Requirements

• Feasibility Study outcomes are :o Definition of objectives and organizationo Appointment of transfer team leader, coordinators

at S & R sites, cross-functional transfer teamo 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 releaseo Accelerated conditions or extended post-approval study in case

of stability sensitive producto Zones III/IV markets : stability study to be consideredo 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 :

o Review of process validation performed in SS by the RSo Quality assessment based on APR or separate risk analysiso Production of pilot or industrial batches at RSo 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 TransferProduct Leader

ocompiles all results in reportoAssesses 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 marketoApproval from Regulatory Authorities

obtainedoValidation successfully executed and

reportedoAll products specifications are met including

stability dataRelease decision : RS Quality Head

Thank You

Any Questions