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SOP Plug-and-play starting point Clinical & GCP

SOP: IMP Labelling and Expiry-Date Extension (Over-Labelling)

A plug-and-play SOP for investigational medicinal product labelling and the controlled extension of expiry dates by over-labelling: label content per CTR Annex VI, the second-check procedure, blind protection, reconciliation, roles, and a filled specimen.

Document type: SOP

Read and copy the template below into your own quality system. It is a generic starting point for your own internal use, provided as is, with no warranty; see the Terms and License. Adopting it does not by itself create compliance.

This is a ready-to-use SOP for IMP labelling and the controlled extension of expiry dates on labels already in the field (over-labelling). Labelling is the highest-frequency clinical-supply risk: a label error can dose a subject incorrectly, break a blind, or invalidate a trial, and an expiry-extension error means dosing expired product. 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

FieldEntry
Document titleIMP Labelling and Expiry-Date Extension (Over-Labelling)
Document number<<FILL: SOP-ID, e.g. SOP-CS-012>>
Version<<FILL>>
Effective date<<FILL>>
Supersedes<<FILL: prior version or "New">>
Document owner<<FILL: role, e.g. Head of Clinical Supply / QA>>
Applies to<<FILL: sites / trials in scope>>

1. Purpose

This procedure defines how <<FILL: COMPANY NAME>> designs, applies, and reconciles IMP labels, and how it extends the expiry date on labels already distributed, so that label content is correct, the blind is protected, expired product is never dosed, and every label is accounted for.

2. Scope

Applies to primary and secondary IMP labelling and to expiry-date extension by over-labelling for the trials in the header. Label content requirements are set by the Clinical Trials Regulation, not by GMP: confirm content against Articles 66 to 70 and Annex VI of Regulation (EU) 536/2014 for each trial, including the rules for auxiliary medicinal products.

3. Responsibilities

RoleResponsibility
Clinical supply / packagingDesigns the label, executes packaging and over-labelling, performs line clearance and in-process checks.
Regulatory affairsConfirms label content per country, including translations and local-language requirements.
Quality AssuranceApproves master label text and proofs; approves the packaging batch record; confirms reconciliation.
Qualified PersonConfirms at certification that labelling and any expiry extension were done correctly.
Second checkerIndependently verifies each over-labelled unit.

4. Definitions

  • Over-labelling: applying a new label (or label element) over an existing one, most often to extend the expiry date, without recalling the material.
  • Blind protection: ensuring the labelling operation does not reveal treatment assignment to anyone who must remain blinded.
  • Reconciliation: accounting for every printed label as applied, rejected, or destroyed.

5. Procedure: routine labelling

5.1 Master label text and proofs

  1. Draft label text against the CTR Annex VI particulars for the trial and each country.
  2. Regulatory affairs confirms content, translations, and local-language requirements.
  3. QA approves the master text and proofs before printing.

5.2 Packaging and in-process control

  1. Perform line clearance before the run: confirm no labels, product, or records from a prior run remain.
  2. Print and apply labels under the approved packaging batch record.
  3. Perform in-process checks (correct text, correct strength, correct trial code, legibility, correct placement).
  4. Reconcile printed labels against applied, rejected, and destroyed at end of run.

6. Procedure: expiry-date extension by over-labelling

Perform only when stability data supports the extended shelf life and the extension is authorised.

  1. Authorise. Confirm the extended expiry is supported by stability data and approved (sponsor and QA), and reflected in the PSF.
  2. Plan and protect the blind. Design the over-label so it does not reveal treatment assignment. Keep the original expiry date traceable (do not obscure the batch/code linkage needed for reconciliation).
  3. Prepare the batch record. Use a controlled over-labelling batch record listing the units, the old and new expiry, and the authorisation.
  4. Line clearance. Clear the area of other labels and materials.
  5. Apply and second-check. Apply the new expiry over-label. A second person independently confirms each unit: correct new date, original date still traceable, blind intact, correct unit.
  6. Reconcile. Account for every over-label as applied, rejected, or destroyed; the count must reconcile.
  7. Document. Complete the batch record; QA reviews; the QP confirms at certification that the extension was done under this procedure with second check.

7. Acceptance criteria

  • Label text matches the approved master and the protocol (strength, storage, trial code, expiry).
  • Local-language labels are present for every country in the trial.
  • Every printed and over-label is reconciled; none unaccounted for.
  • Expiry extension is stability-supported, authorised, second-checked, and blind-protected, with the original date traceable.
  • Date formats are unambiguous (month and year not confusable).

8. Records generated

Master label text and approved proofs; packaging batch record with reconciliation; over-labelling batch record with second-check evidence; stability/authorisation reference for the extension.

9. Common findings this SOP prevents

  • Label text not matching the approved master or protocol (wrong strength, storage, or trial code).
  • Missing local-language labels for a country in the trial.
  • Expiry extension without a controlled procedure, second check, or blind protection.
  • Poor reconciliation, so a wrong label reaching a subject cannot be ruled out.
  • Ambiguous date format confusing month and day.

10. References

Regulation (EU) No 536/2014 (Clinical Trials Regulation), Articles 66 to 70 and Annex VI (IMP and auxiliary medicinal product label particulars). EudraLex Volume 4 Annex 13 (Manufacture of Investigational Medicinal Products). Related reading: GMP for investigational medicinal products, good documentation practices.

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

11. Revision history

VersionDateAuthorSummary of change
<<FILL: 1.0>><<FILL>><<FILL>>Initial issue.

12. Approvals

RoleNameSignatureDate
Author<<FILL>>
Reviewer (QA)<<FILL>>
Approver (Quality Head / QP)<<FILL>>

Filled specimen

The following shows a completed over-labelling reconciliation for an example batch whose shelf life was extended by three months, so you can see how the second check and reconciliation read. The values are illustrative.

FieldEntry
Batch / unitsIMP-0042, 220 kits in the field recalled to depot for over-labelling
Old expiry / new expiry31 Aug 2026 / 30 Nov 2026
Stability / authorisationStability report STB-XYZ-07 supports 30 Nov 2026; approved CR-2026-088
Blind protectionOver-label covers expiry only; treatment code and kit number unchanged and unrevealed
Applied / rejected / destroyed218 applied / 2 rejected (misaligned) / 2 destroyed
Reconciliation220 = 218 + 2 destroyed; reconciled
Second checkEach of 218 units independently confirmed by second checker M. Ito; original date traceable
QP confirmation at certificationConfirmed extension procedure and second check complete

In this example the extension was stability-supported and authorised, the over-label covered only the expiry (so the blind held), every unit was second-checked, and the count reconciled with the two rejected units destroyed and accounted for. The original expiry stayed traceable so reconciliation still worked. A common failure is extending expiry without a second check, or in a way that obscures the code needed to reconcile, both of which this record makes impossible to skip.

How to adapt this SOP

  1. Set your document number, owner, and trials in scope in the header.
  2. Confirm the CTR Annex VI content and local-language requirements for each country before drafting master text.
  3. Build the over-labelling batch record with a mandatory second-check field per unit.
  4. Put this procedure in place before you need it; doing an extension under mid-trial pressure is how errors happen.
  5. Confirm every regulation in section 10 against the current published version before issue.
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