Confirmation according to Annex 16 is the declaration by a Qualified Person for a defined manufacturing or testing step performed by their site on a batch. It confirms that this part was carried out in accordance with GMP and the written agreement. The Qualified Person certifying at the end of the supply and manufacturing chain can rely on such confirmations for their overall decision.
Partial response from a participating site
In complex supply chains, manufacturing, import, testing, and packaging are often not performed at a single location. Annex 16 requires at least one Qualified Person for each EU manufacturing site. If a site performs only partial operations on a batch, the Qualified Person there must at least confirm that these operations were carried out in compliance with GMP and according to the written agreement.
Confirmation does not limit responsibility to informal acknowledgement. It assigns the specifically described step to a Qualified Person and a site. If the agreement also requires the partial step to comply with the specifications of the marketing authorisation, the confirming person must have access to the necessary information. For Investigational Medicinal Products, the corresponding reference to the approved study and quality status must be established.
Confirmation is therefore primarily an instrument for the verifiable allocation of batch responsibility. It makes visible who was responsible for a specific manufacturing, packaging, or control step, for example, before the finished batch is certified by another Qualified Person. Without this assignment, the certifying person would have to evaluate the implementation of all preceding steps without a documented basis of responsibility.
Written agreement as a point of reference
The agreement between the participating parties defines which activities a site is responsible for and how deviations are assessed with regard to GMP and product requirements. Annex 16 requires that any division of responsibilities for batch compliance be defined in a document formally agreed upon by all parties. The confirmation thus refers not to an abstract site quality, but to the promised and executed scope of tasks.
The exemplary confirmation format in Annex 16 lists the product, manufacturing stage, batch number, address of the partial manufacturer, technical quality agreement, and the confirming Qualified Person. The content makes it clear why a mere audit certificate or an internal production report does not replace a confirmation: they lack the batch- and step-related declaration by the responsible QP.
Because multiple manufacturing authorisation holders may be involved, the agreement is also relevant across corporate boundaries. The certifying Qualified Person may either take full responsibility for all stages or share it with other Qualified Persons who have provided confirmations for defined manufacturing and control steps. The exact boundary must be documented.
Distinction from batch certification
Confirmation is not certification. The finished product batch is certified as a whole and exactly once by the responsible Qualified Person. In contrast, confirmations are issued for individual, defined activities carried out at different sites and, if applicable, under different manufacturing authorisations.
The certifying person retains responsibility for the final decision and ensures that all necessary steps have been completed under accepted pharmaceutical quality systems. They can rely on confirmations, but this does not replace their certification. Conversely, a partial confirmation does not certify that the finished packaged batch as a whole may be released.
Relevance for clinical trials
For Investigational Medicinal Products with shared manufacturing steps, confirmation prevents packaging, laboratory testing, or import from disappearing into an opaque chain of documents. The Qualified Person at the certifying site requires a clear statement for the final assessment as to which site performed which step and according to which agreed standards it was evaluated. Changes or deviations can thus be assigned to the correct professional responsibility.
Full-service CROs like Mediconomics support the coordination of quality agreements, the mapping of manufacturing and testing sites in study supply chains, and the consolidation of status information required by the sponsor, manufacturer, and depot for a traceable batch route. The QP confirmation itself is not delegated, but its interfaces with study supply are kept transparent.
Confirmations are particularly meaningful when the scope of the partial operation is described with such linguistic precision that it cannot be confused with a later final release. The batch number also binds this statement to the specific unit of the manufacturing chain.
Frequently Asked Questions (FAQ)
Can a confirmation be issued for the entire finished product batch?
The confirmation concerns a partial operation or a defined area of responsibility. The finished product batch is certified as a whole by the responsible Qualified Person.
Why must the division of responsibility be agreed upon in writing?
The agreement defines which activities a site is responsible for and how deviations are assessed. It is the benchmark to which the confirmation refers.
May different manufacturing authorisation holders be involved?
Yes. Annex 16 allows the certifying Qualified Person to share responsibility with QPs of other manufacturing authorisation holders, provided they provide confirmations for specific steps and the division is formally documented.
Regulatory References
- EU GMP Guidelines, Annex 16, Sections 1.4.1 to 1.4.3 – regulate partial manufacturing, division of responsibilities, and confirmations.
- EU GMP Guidelines, Annex 16, Appendix I – lists the contents of a confirmation for partial manufacturing.
- Detailed Commission Guidelines C(2017) 8179 final, Section 8 – describes the batch certification of Investigational Medicinal Products as a final decision.