SOP: QP Certification of Investigational Medicinal Products

This is a ready-to-use SOP for Qualified Person (QP) certification of investigational medicinal product (IMP) batches used in EU/EEA clinical trials. An IMP has no marketing authorisation, so the QP certifies against the product specification file, the approved trial authorisation, GMP appropriate to the stage of development, and the sponsor’s order, rather than against an MA. Replace every <<FILL: ...>> placeholder and route it through your document control. A filled specimen follows. Verify each cited regulation against the current source before you rely on it.

Document control header

1. Purpose

This procedure defines how <<FILL: COMPANY NAME>> certifies IMP batches for use in EU/EEA clinical trials, so that no batch is used before certification and every certified batch has a defensible package showing why certification was justified.

2. Scope

Applies to all IMP, comparator, and placebo batches certified for EU/EEA trials by the QP(s) named under the site’s Manufacturer’s/Importer’s Authorisation for IMPs (MIA(IMP)). It covers batches manufactured in the EU/EEA and imported from third countries. It does not cover commercial batch certification, governed by <<FILL: SOP-ID for commercial QP release>>.

3. Responsibilities

4. Definitions

• Product specification file (PSF): the IMP’s controlling reference document, holding the specifications, manufacturing and packaging instructions, methods, and release requirements. The QP certifies against it.
• Certification: the QP’s act confirming the batch was manufactured and checked in accordance with GMP appropriate to the stage of development, the PSF, the clinical trial authorisation/approved IMPD, and the sponsor’s order.
• Imported IMP: IMP manufactured outside the EU/EEA, requiring the QP to assess GMP equivalence of the third-country site.

5. Procedure

5.1 Confirm prerequisites before certification

1. The manufacturing/importing site holds a current MIA(IMP) and operates under GMP.
2. A named, eligible QP is recorded for the site.
3. The trial is authorised (CTA under the CTR) in each country of intended use, confirmed with regulatory affairs.

5.2 Assemble the certification package

QA assembles and the QP reviews:

1. Batch manufacturing and packaging records, complete and reviewed.
2. Certificate of analysis showing the batch meets the IMP specification in the PSF.
3. The PSF reference and version.
4. The IMPD/CTA reference confirming authorisation for the intended use.
5. For imported IMP: confirmation of the third-country GMP standard and any importation-testing arrangement, with the QP’s GMP-equivalence assessment.
6. Confirmation that labelling, including any expiry extension, was performed under a controlled procedure with second check.
7. Resolution of any deviations or OOS results affecting the batch.

5.3 QP review and decision

1. QP confirms records are complete and the batch meets the PSF specification.
2. QP confirms the trial authorisation covers the country and arm of intended use.
3. QP confirms labelling and blinding integrity (without needing the treatment assignments).
4. QP assesses imported-product GMP equivalence where relevant, and the basis for any reduced importation testing.
5. QP confirms deviations and OOS are closed or justified.

5.4 Certify and record

1. The QP certifies the batch and records certification in the certification register (section 8) with date and signature, contemporaneously.
2. Only certified IMP is released to depots/sites.
3. If any element fails, the batch is held and the reason recorded; it is not certified until resolved.

5.5 Do not certify if

• The trial is not authorised in the intended country or arm.
• Imported IMP has no documented GMP-equivalence assessment.
• Labelling or expiry extension lacks evidence of the controlled procedure and second check.
• The PSF is out of date relative to the current IMPD.
• Any deviation or OOS affecting the batch is unresolved.

6. Acceptance criteria

• No batch is used in a trial before QP certification.
• The certification register is complete and contemporaneous.
• For any certified batch, the QP can produce the package showing why certification was justified.
• The QP’s declaration aligns with the trial authorisation in each country of use.
• Imported IMP is certified only with a documented GMP-equivalence assessment.

7. Records generated

Certification package per batch; certification register entries; GMP-equivalence assessments for imported IMP; hold records for batches not certified.

8. Certification register (record structure)

9. References

Regulation (EU) No 536/2014 (Clinical Trials Regulation); Commission Delegated Regulation (EU) 2017/1569 (GMP for IMPs). EudraLex Volume 4 Annex 13 (Manufacture of Investigational Medicinal Products; the Detailed Commission guidelines of 8 December 2017). EudraLex Volume 4 Annex 16 (Certification by a Qualified Person and Batch Release), applied to IMPs. Related reading: GMP for investigational medicinal products, Qualified Person batch release under Annex 16.

Confirm the current version and clause numbers of each reference before issue.

10. Revision history

11. Approvals

Filled specimen

The following shows a completed certification register entry for an example imported IMP batch, so you can see the evidence a QP relies on. The values are illustrative.

In this example the batch was imported, so the QP recorded the GMP-equivalence assessment and the importation identity test before certifying, and confirmed the CTA covered both countries of intended use (Germany and Spain). A common finding is certifying imported IMP without a documented equivalence assessment, or against a CTA that does not cover one of the arms or countries. The register entry makes both checks visible.

Common inspection findings this SOP prevents

• IMP used before QP certification, or certification recorded after the fact.
• QP certifying against a trial authorisation that does not cover that country or arm.
• Imported IMP certified without a documented GMP-equivalence assessment of the third-country site.
• Expiry-extension over-labelling accepted at certification without evidence of the controlled procedure and second check.
• Product specification file out of date relative to the current IMPD.

How to adapt this SOP

1. Set your document number, MIA(IMP) site, and named QP(s) in the header.
2. Point the cross-references in sections 2 and 5 to your real batch-review, labelling, and deviation procedures.
3. Adapt the certification register fields to your quality system and trial portfolio.
4. Confirm the imported-product equivalence approach against your MIA(IMP) and current guidance.
5. Confirm every regulation in section 9 against the current published version before issue.