Template: Product Specification File (PSF) Structure for an IMP

This is a ready-to-use structure for an investigational medicinal product’s product specification file (PSF), the controlling reference the QP certifies each batch against because an IMP has no marketing authorisation. Use it as the index and content map for one controlled PSF per IMP, updated in step with the IMPD/IND. Replace every <<FILL: ...>> placeholder. A filled specimen index follows. Verify each cited regulation against the current source before you rely on it.

Control header

How to use

The PSF is a living, controlled compilation. It may reference documents held elsewhere (a spec, a method, a batch record) rather than duplicate them, provided each reference is version-controlled. Keep one PSF as the single source of truth, update it through change control in step with the IMPD/IND, and confirm at every certification that the PSF, the released-against specification, the IMPD/IND, and the certificate of analysis all agree.

PSF section map

1. Administrative and control

• 1.1 PSF identity, version, and change history (what changed, when, under which approval).
• 1.2 Linked trial(s), IMPD/IND references and versions.
• 1.3 Manufacturing and importing sites and their MIA(IMP)/authorisation references.
• 1.4 Named QP(s).

Content: <<FILL>>

2. Drug substance

• 2.1 Specification (tests, methods, acceptance criteria) with method qualification/validation status.
• 2.2 Manufacturing and control summary.
• 2.3 Reference standards.

Content: <<FILL>>

3. Drug product

• 3.1 Composition and description.
• 3.2 Specification (release and shelf life), methods, and their status.
• 3.3 Master batch record reference.
• 3.4 In-process controls.

Content: <<FILL>>

4. Comparator and placebo (if applicable)

• 4.1 Comparator sourcing and authenticity documentation.
• 4.2 Placebo composition and specification.
• 4.3 Re-packaging comparability data and the resulting expiry basis.

Content: <<FILL>>

5. Packaging and labelling

• 5.1 Packaging instructions and master packaging record reference.
• 5.2 Label text referencing CTR Annex VI particulars; approved proofs.
• 5.3 Expiry-extension (over-labelling) basis and procedure reference.

Content: <<FILL>>

6. Blinding and randomisation

• 6.1 Blinding design and the blinded assessment reference.
• 6.2 Randomisation arrangements at the level the QP needs to confirm integrity without being unblinded.
• 6.3 Code-break arrangements.

Content: <<FILL>>

7. Testing and release

• 7.1 Testing methods and their qualification/validation status.
• 7.2 Release requirements and the specification released against.
• 7.3 Certificate of analysis format.

Content: <<FILL>>

8. Stability

• 8.1 Stability protocol and current data summary.
• 8.2 Shelf-life justification, including any extension basis.

Content: <<FILL>>

9. Traceability and imported product

• 9.1 Traceability from the active substance forward.
• 9.2 For imported IMP: the third-country GMP standard and the GMP-equivalence assessment; importation-testing arrangements.

Content: <<FILL>>

10. Quality events

• 10.1 References to deviations, OOS, and change controls affecting the product.

Content: <<FILL>>

The agreement check (a load-bearing control)

At each certification confirm these all agree:

If any two disagree, certification waits until they are reconciled.

Acceptance criteria

• One controlled PSF exists per IMP, under document control.
• Every referenced document is version-controlled and traceable.
• The PSF is updated through change control in step with the IMPD/IND.
• The agreement check passes at every certification.
• The change history lets a reviewer see what changed, when, and under which approval.

References

EudraLex Volume 4 Annex 13 (Manufacture of Investigational Medicinal Products); Annex 16 applied to IMPs. Regulation (EU) No 536/2014 and Commission Delegated Regulation (EU) 2017/1569; ICH Q6A/Q6B for specification content. Related reading: GMP for investigational medicinal products, certificate of analysis.

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

Revision history

Filled specimen

The following shows a completed PSF index header and an agreement-check row for an example IMP, so you can see how the control reads. The values are illustrative.

In this example the PSF and the released-against spec agree at 0.3%, but the IMPD still shows 0.5% because the amendment is pending. The agreement check catches the mismatch, so certification against the tightened limit waits until the IMPD amendment is handled. That is the whole reason the PSF and IMPD are checked against each other at certification, not assumed to match: a spec tightened ahead of its dossier amendment is a common, quiet source of certification findings.

Common inspection findings this template prevents

• No single controlling PSF, so the QP certifies against scattered, inconsistent documents.
• PSF drifting out of sync with the IMPD/IND.
• Spec, PSF, and CoA disagreeing at the moment of certification.
• Re-packaged comparator expiry with no comparability basis captured.
• Change history absent, so the QP cannot see what changed or under which approval.

How to adapt this template

1. Set your PSF number and linked trial/IMPD references in the header.
2. Populate each section by reference to your version-controlled source documents rather than duplicating them.
3. Run the agreement check at every certification and hold on any mismatch.
4. Update the PSF through change control whenever the IMPD/IND changes.
5. Confirm every regulation against the current published version before issue.