This is a ready-to-use protocol for the comparability work needed before a marketed comparator is re-packaged or re-labelled for use in a blinded trial. Replace every <<FILL: ...>> placeholder, set your own document numbers, and route it through your normal protocol approval process. A filled specimen follows. Verify every cited reference against the current source before you rely on it. This content is educational reference, not regulatory advice.
Approval page
| Field | Entry |
|---|---|
| Protocol title | Comparator Re-Packaging and Re-Labelling Comparability Assessment |
| Protocol number | <<FILL: PROTOCOL-ID, e.g. CMP-PROT-009>> |
| Version | <<FILL: version>> |
| Effective date | <<FILL: effective date>> |
| Comparator product | <<FILL: name, strength, marketing authorisation holder>> |
| Trial(s) this supports | <<FILL: trial identifier(s)>> |
| Role | Name | Signature | Date |
|---|---|---|---|
| Author (clinical supply / CMC) | <<FILL>> | ||
| Reviewer (QA) | <<FILL>> | ||
| Approver (Qualified Person) | <<FILL>> |
1. Objective
Generate and document the data needed to show that re-packaging or re-labelling a marketed comparator, for example by over-encapsulation, blister replacement, or removal from original packaging, does not adversely affect its stability, release characteristics, or appearance match to the test product, and to assign a justified expiry for the re-packaged form.
2. Scope
Applies to any comparator re-packaged or re-labelled for blinding or kit assembly in <<FILL: trial identifier>>. It does not cover the comparator’s own authorised shelf life or specification; that stays the marketing authorisation holder’s responsibility, not yours.
3. System / product description
| Field | Entry |
|---|---|
| Comparator as marketed | <<FILL: description, original packaging, authorised shelf life>> |
| Re-packaging / re-labelling operation | <<FILL: e.g. over-encapsulation into opaque capsule, removal of blister and re-blistering>> |
| Test product it must match | <<FILL>> |
| Blinding requirement driving the operation | <<FILL>> |
4. Prerequisites
- The re-packaging process is defined and the equipment qualified.
- The comparator’s authorised product information and any available stability data from the marketing authorisation holder have been obtained.
- A sourcing and authenticity check on the comparator batch(es) used in this assessment is complete and documented (see the sourcing control in the parent article).
5. Roles
| Role | Responsibility |
|---|---|
| CMC / clinical supply | Designs the re-packaging process, executes the protocol, compiles the report. |
| QA | Reviews the protocol and report, confirms acceptance criteria were met. |
| Qualified Person | Confirms, at IMP certification, that the re-packaged comparator’s comparability data supports its use and assigned expiry. |
6. Acceptance criteria (set before testing begins)
| Attribute | Acceptance criterion |
|---|---|
| Appearance match to test product | <<FILL: indistinguishable to a blinded observer, including weight within +/- X%>> |
| Dissolution or release rate | <<FILL: e.g. f2 similarity factor >= 50, or equivalent per the relevant method>> |
| Assay / content after re-packaging | <<FILL: within +/- X% of the pre-re-packaging value>> |
| Stability under the re-packaged form | <<FILL: no significant change at the proposed re-packaged expiry, per the defined stability protocol>> |
| Impurity profile after re-packaging | <<FILL: no new or increased degradation product above the qualified threshold>> |
7. Test cases
| Test ID | Step | Expected result | Actual result | Pass/Fail | Tester | Date |
|---|---|---|---|---|---|---|
| CMP-01 | Blinded appearance comparison of re-packaged comparator against test product by an independent, blinded assessor | Indistinguishable per acceptance criterion | ||||
| CMP-02 | Weight check, re-packaged comparator vs test product, n = <<FILL>> units each | Within the acceptance range | ||||
| CMP-03 | Dissolution / release-rate comparison, re-packaged vs original marketed comparator | Meets the defined similarity criterion | ||||
| CMP-04 | Assay and impurity profile, immediately post-re-packaging, vs the original marketed comparator | Within acceptance criteria, no new degradation products | ||||
| CMP-05 | Stability of the re-packaged form at the proposed storage condition, through the proposed re-packaged expiry | No significant change against the defined stability acceptance criteria |
8. Deviation handling
Any test case result outside its acceptance criterion is a protocol deviation. Document it, investigate it, and state plainly whether it affects the proposed re-packaged expiry or the blinding claim before the report is finalized, because a reader six months later should not have to guess what an open deviation meant for the conclusion. A failed appearance or weight match (CMP-01/02) is not only a comparability failure; treat it as a blinding-integrity risk and escalate it the same way you would escalate a code-break, since the two failure modes threaten the trial in the same place.
9. Summary and conclusion
| Field | Entry |
|---|---|
| All acceptance criteria met | <<FILL: Y/N>> |
| Proposed expiry for the re-packaged comparator | <<FILL: date or duration, and basis>> |
| Blinding integrity confirmed | <<FILL: Y/N, basis>> |
| Conclusion | <<FILL>> |
| Approved by (QP, name, date) | <<FILL>> |
10. Attachments
- Raw data for each test case.
- The independent blinded appearance assessment record.
- The stability protocol and interim/final data.
- The sourcing and authenticity record for the comparator batch(es) used.
11. References
Commission Delegated Regulation (EU) 2017/1569 and the Detailed Commission guidelines on GMP for IMPs (the current Annex 13 of EudraLex Volume 4). ICH Q1A(R2), Stability Testing of New Drug Substances and Products (general principles, applied here to the re-packaged form). ICH Q6A, Specifications (dissolution/release-rate comparison methodology).
Confirm the current version of each reference before issue.
Filled specimen
A Phase 3 trial compares a marketed 10 mg oral tablet (test) against a marketed 10 mg comparator from a different manufacturer. Both are over-encapsulated into identical opaque capsules with matching placebo bead-fill to achieve blinding.
Acceptance criteria: appearance indistinguishable to a blinded assessor, weight within +/-3%, dissolution f2 similarity factor >= 50 against the un-encapsulated comparator, assay within +/-2% of the pre-encapsulation value, no new degradation product above 0.10% at 6 months accelerated storage.
Results: CMP-01 passed, a blinded panel of three could not distinguish test from comparator capsules; CMP-02 passed, mean weight difference 1.1%; CMP-03 passed, f2 = 61; CMP-04 passed, assay 99.3% of pre-encapsulation value, no new degradation products detected; CMP-05 passed at the 6-month interim pull, stability continuing to the planned 12-month readout.
Conclusion: the re-packaged comparator is comparable to the original marketed product and indistinguishable from the test product; a 9-month expiry is assigned pending the 12-month stability readout, which will support an extension if the trend continues. Approved by the Qualified Person on this basis; QP certification of comparator batches references this protocol’s report number.
Common inspection findings this protocol prevents
- A comparator re-packaged into trial kits with an assigned expiry that outruns the stability data actually generated on the re-packaged form.
- No blinded appearance assessment on record, so a claim of “indistinguishable” rests on an unblinded, informal judgment.
- A dissolution or release-rate change introduced by the re-packaging process that was never tested before the comparator went into trial supply.
How to adapt this protocol
- Set acceptance criteria appropriate to the dosage form; a parenteral comparator’s comparability questions (reconstitution behavior, extractables from a new container) differ from an oral solid’s.
- If the comparator is sourced from more than one batch or market over the trial’s duration, repeat the sourcing and authenticity check, and assess whether the comparability data still applies to the new batch.
- Keep the proposed expiry conservative relative to the stability data actually in hand; extend it through a documented amendment once longer-term data supports it, not in advance of the data.