The regulatory release of the investigational medicinal product is the pre-shipment verification of whether the approvals required for the clinical trial are actually in place. It complements the batch certification by the Qualified Person and concerns the trial and approval status, not the quality assessment of the batch. Only when both release steps are fulfilled may an investigational medicinal product be dispatched for use in the clinical trial.
Second Step Before Trial Shipment
For investigational medicinal products, the release chain can consist of two separate decisions. First, the Qualified Person assesses the batch based on GMP documentation and certifies its conformity. Independently of this, it must be clarified before shipment whether the clinical trial is approved in the relevant context and whether relevant substantial amendments have been taken into account. Regulatory release thus answers a different question than the batch testing.
The Commission Guideline requires that relevant clinical trial approvals and amendments be available in the Product Specification File. It also requires the manufacturer to ensure that the necessary approvals exist prior to shipment. If the manufacturer is additionally commissioned by the sponsor with this step, the division of tasks between the two should be defined in an agreement.
Regulatory release is therefore not merely a logistical status in the depot. It requires that information from the regulatory management reliably reaches the organization initiating the shipment. A validly certified batch must be withheld if the relevant trial site, the trial country, or a relevant amendment has not yet reached the required approval status.
Information Basis and Allocation of Responsibility
The Product Specification File creates the link between batch-related data and the clinical approval status. This is where relevant approvals, amendments, the protocol, and, if applicable, randomization codes are brought together as a reference. For regulatory release, it is not sufficient to know only a general trial approval; the specific constellation applicable to the intended delivery is decisive.
The sponsor bears responsibility for the clinical trial and must provide the manufacturer with the information required for any assumed release step. Technical or quality agreements should therefore determine who identifies changes, who assesses their impact on supply, and who documents a hold or shipping release. These tasks may be distributed, but they must not remain unresolved between the sponsor, manufacturer, and depot.
Following release, storage and transport conditions remain relevant. The guideline requires that investigational medicinal products be stored and transported after QP certification under conditions that maintain the quality and safety of the supply chain. The regulatory shipping status does not replace this product obligation.
Distinction from batch certification
Batch certification by the Qualified Person evaluates the finished product batch against GMP requirements, the clinical trial specifications, and the associated quality documentation. It is a formal quality act per batch. Regulatory release, on the other hand, checks whether the use of this certified batch in the specific clinical trial is approved.
Both steps are prerequisites for shipment, but they are identical neither in timing nor in technical scope. Approval of the study does not confirm that a specific batch has been properly manufactured and tested. Conversely, a QP certification does not release a shipment if the trial approval status does not yet support its use. This difference is central to the management of international or amended trials.
Relevance for clinical trials
In operational trial management, regulatory release prevents material from reaching a center before its inclusion and the relevant version of the clinical trial are regulatorily secured. In the event of subsequent changes to the protocol, labeling, or delivery countries, the shipping decision must therefore reflect the current release status. Otherwise, a correctly produced investigational medicinal product could be used in the wrong place or under a trial status that is no longer covered.
Full-service CROs like Mediconomics provide support by maintaining regulatory country and amendment overviews, by reconciling CTA information with depot and shipping lists, and through escalation pathways for blocked or newly released delivery destinations. In this way, the separation between quality certification and trial-related shipping release can also be maintained in practice.
Shipping release should therefore rely on a documented status that clearly distinguishes between site, country, protocol version, and relevant amendment. A general statement that the trial is “approved” does not sufficiently describe this application-specific checkpoint.
Frequently Asked Questions (FAQ)
Can a QP-certified batch be shipped immediately?
Not based on certification alone. Before shipment, it must additionally be established that the required clinical trial approvals for the intended use are in place.
Who is permitted to perform the regulatory release?
The actual execution can be delegated to the manufacturer. The responsibilities and information flows required for this should be contractually defined between the sponsor and the manufacturer.
Does regulatory release refer to the quality of the product?
No. It refers to the approval status of the clinical trial. The quality compliance of the batch is the subject of certification by the Qualified Person.
Regulatory References
- Detailed Commission Guidelines C(2017) 8179 final, Section 8 – describes certification, regulatory release, and shipment prior to trial use.
- Regulation (EU) No. 536/2014, Articles 62 and 63 – regulates certification and GMP requirements for investigational medicinal products.
- Delegated Regulation (EU) 2017/1569, Article 12 – specifies the duties of the Qualified Person for investigational medicinal products.