The European Medicines Agency (EMA) published a draft guideline on the responsibilities of the sponsor with regard to handling and shipping of investigational medicinal products (IMPs) for human use for comment. Comment Deadline is August 31, 2018.
The proposed guideline lays down the principles for the two-step release and shipping of IMPs by the Qualified Person (QP) and the Sponsor in accordance with good clinical practice (GCP) and good manufacturing practice (GMP) referred to in the Template for IMP batch release in Part III of the EU GMP Guidelines (Eudralex Volume 4). The guideline also describes the areas of interface between the manufacturer and the sponsor and the required contractual agreements.
The guideline complements the Delegated Regulation GMP for IMPs and arrangements for inspections and the Detailed Commission Guidelines on GMP for IMPs for human use (currently in Annex 13 of EudraLex Volume 4).
All related documents, including the Template for IMP batch release, are applicable as from the date of entry into application of the EU Clinical Trials Regulation (CTR). It is currently expected that the CTR (and all related regulations and guidelines) will not apply before March 2020.
The published draft guideline on the responsibilities of the sponsor states that IMPs should remain under the control of the sponsor until after completion of the two-step procedure, consisting of
- the batch certification by the QP, and
- the regulatory release by the sponsor for use in a clinical trial.
Both steps should be recorded and retained in the clinical trial master file (TMF) held by, or on behalf of, the sponsor. The certification of each batch by the QP of the manufacturer ensures that the provisions of GCP (according to the CTR) and GMP (according to the Delegated Regulation) have been complied with and documented.
The sponsor should have standard operating procedures (SOPs) in place that describe the regulatory release process within the organization.
This step should be documented and approved prior to the shipment of IMPs to the clinical investigator sites or pharmacy where applicable, to ensure that a trial does not start without the necessary arrangements and approvals in place.
It should be ensured that the shipping of the IMPs minimizes any risk while ensuring that the quality of the product is maintained and the applicable elements of guidelines on Good Distribution Practice (GDP) of medicinal products for human use are taken into consideration. Furthermore, transfers of IMPs from one trial site to another should remain the exception.
According to the Commission Delegated Regulation, the responsibilities of the manufacturer and sponsor should be appropriately defined, agreed and controlled in a written contract. This contract should clearly establish the duties of each party, taking into account the EU GMP Guidelines, Part I, Chapter 7 (Outsourced Activities). Examples of such responsibilities include (but are not limited to):
- Re-labelling responsibilities,
- Comparators (sourced from an authorized vendor and arrangements for recalls),
- QP: The most up to date information should be provided for consideration during the batch certification process in accordance with the documents set out in the clinical trial applications,
- Manufacturing and control methods (any proposed revision should be appropriately communicated between the manufacturer and the sponsor as this may require submission of a substantial modification to the clinical trial application),
- Decoding arrangements and the respective responsibilities of each party,
- Subcontraction of any agreed responsibilities (not without prior evaluation and approval from the contract giver),
- Responsibilities for recall, return and destruction of IMPs,
- Availability of documentation required in the clinical TMF (e.g. batch documentation, documentation related to assembly and packaging of IMPs) to the sponsor until after the retention period according to the Delegated Regulation,
- Storage retention of samples,
- Arrangements for destruction of IMPs,
- Manufacturer responsibility for the regulatory release,
- Specification of the exact role of manufacturer (e.g. specific tasks and GMP related responsibilities) in the chain of manufacturers (in case a sponsor is not a manufacturer and relies on a chain of contracted manufacturers),
- Responsibilities on the handling of deviations during shipment to investigators,
- Process of transfer.