The guideline on sponsor management of investigational medicinal products ("IMPs") for use in clinical trials that was published by the European Medicines Agency ("EMA") on 14 September 2022 (the "Guideline") came into effect on January 1, 2023. The Guideline addresses the responsibilities of sponsors for the release and shipping of IMPs in line with Good Clinical Practice ("GCP") and Good Manufacturing Practice ("GMP"). The Guideline should be read in conjunction with the Delegated Regulation (EU) 2017/1569 on GMP and arrangements for inspections and the detailed Commission guidelines C(2017) 8179 on GMP for IMPs.
Article 63.1 of the Clinical Trials Regulation (EU) 536/2014 ("CTR") requires that IMPs be manufactured in accordance with GMP. The Regulation also authorises the European Commission to establish GMP principles through the adoption of delegated acts and related guidelines.
The Guideline divides the release procedure for IMPs to clinical trial sites into two phases: the preparation of a batch certification by the Qualified Person ("QP") and the regulatory release of IMPs by the clinical trial sponsor. Pursuant to Article 62.1 of the CTR, the QP verifies that each production batch of IMPs manufactured or imported in the EEA meets the quality standards that are established by the European Commission and certifies that these requirements are fulfilled. The sponsor must ensure that the required clinical trial authorisation has been granted before IMPs are released for delivery to clinical trial sites and pharmacies.
Although sponsors are responsible for the clinical trial up until the point IMPs have been delivered to the relevant trial sites, the Guideline provides that sponsors may delegate the regulatory release of IMPs to manufacturers. Where this task is delegated to manufacturers, the sponsor and the manufacturer must conclude a related written agreement. The sponsor must provide the manufacturer with all the information required to perform the regulatory release of IMPs to the clinical trial sites, including inspection reports and information on quality issues of IMPs.
Other issues related to GMP of IMPs, including sourcing, transport, storage, and re-labelling, may also be subject to a written agreement between the manufacturer and the sponsor. The purpose of the agreement is to ensure that the division of responsibilities among the parties is clearly defined.
In relation to the shipping of IMPs to trial sites, the Guideline states that measures should be taken that minimise "any risk of exposure to conditions that could impact quality and integrity of the product". These measures should include steps to ensure the security of the product against adulteration, tampering and theft. Compliance with Good Distribution Practice ("GDP"), should also be ensured, including measures concerning shipment documentation that ensure traceability, transportation specifications and storage conditions of IMPs as listed in the product specification file. The Guideline also provides that any derogation from the transportation instructions provided by the sponsor or on their behalf in relation to the shipment of IMPs should be documented and communicated to the sponsor or their representative. Derogations from the shipment conditions outlined in the product specification file must also be recorded and investigated by the sponsor in cooperation with the manufacturer. The impact of such derogation on the quality of the IMPs must be assessed and related corrective measures taken where necessary.
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