This is a ready-to-use matrix for products whose manufacture spans multiple sites and multiple Qualified Persons. Annex 16 permits a chain of stage-level confirmations that feed a single final certification, but only if the chain is unbroken and traceable: every stage has a named confirming or certifying party, and every confirmation actually reaches the QP who signs the final certification. This matrix makes that chain visible and shows where it would break. Replace every <<FILL: ...>> placeholder and keep it under version control, reconciled to the underlying quality and technical agreements. A filled specimen follows. This is general guidance to adapt and verify, not legal or regulatory advice.
Document control header
| Field | Entry |
|---|---|
| Matrix title | Multi-Site Certification Confirmation Chain, <<FILL: product name>> |
| Document number | <<FILL>> |
| Version | <<FILL>> |
| Product(s) covered | <<FILL>> |
| Final certifying QP | <<FILL: name, site>> |
| Linked agreements | <<FILL: list quality/technical agreement numbers>> |
1. Purpose
Confirm, stage by stage, who confirms or certifies what, and that the resulting chain of evidence reaches the final certifying QP intact. Annex 16, Section 5 permits different QPs to take responsibility for different stages (for example, a QP certifies the bulk product and a different QP certifies the finished pack); Section 7 addresses the written arrangements needed when stages sit in different member states. Only the QP performing final certification takes responsibility for the whole batch, and does so by relying on the documented confirmations below, not by re-verifying each stage personally.
2. Terminology used in this matrix
- Confirmation: a documented statement from a QP or an equivalent authorized function at an intermediate stage that the stage met GMP and the agreed conditions. Confirmation is not the final Article 51 act.
- Certification: the final Article 51 act performed once, by the QP who takes responsibility for the whole batch, relying on the confirmations below it.
- Chain break: any stage where a confirmation is missing, undated, not attributable to a named person, or not demonstrably transmitted to the next stage or the final certifying QP.
3. The confirmation chain
| Stage | Site (name, country) | Activity performed | Confirming / certifying party (name, role) | What is confirmed | Confirmation reference / date | How it reaches the next stage or the final QP |
|---|---|---|---|---|---|---|
<<FILL: e.g. Active substance>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL: e.g. CoA + confirmation letter transmitted with the shipment; agreement ref>> |
<<FILL: e.g. Bulk / intermediate>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
<<FILL: e.g. Drug product / fill-finish>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
<<FILL: e.g. Secondary packaging / labelling>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
| Final certification | <<FILL: release site>> | Final Article 51 certification | <<FILL: final certifying QP>> | Whole batch, relying on all confirmations above | <<FILL: certification register entry ref>> | Enters certification register; batch eligible for release for sale/supply |
4. Chain-integrity check
For each row above, confirm:
| Check | Result |
|---|---|
| Every stage in the actual manufacturing route appears as a row (no stage silently skipped) | <<FILL: Yes/No>> |
| Every confirming party is named, not just a site or a function | <<FILL>> |
| Every confirmation carries a date and is contemporaneous with the stage it covers | <<FILL>> |
| Every transmission mechanism (how the confirmation physically or electronically reaches the next party) is stated, not assumed | <<FILL>> |
| A written agreement exists covering every cross-site or cross-QP handoff in the chain | <<FILL>> |
| The final certifying QP can produce every upstream confirmation on request, not just summarize it from memory | <<FILL>> |
Any “No” is a chain break. Resolve it before relying on the chain for certification, either by obtaining the missing confirmation, correcting the agreement, or, if the gap cannot be closed, having the final QP perform the missing verification personally.
5. Acceptance criteria
This matrix is acceptable when every manufacturing stage the product actually passes through is represented, every confirming or certifying party is a named individual with documented authority to confirm at that stage, every handoff has a stated transmission mechanism and a covering written agreement, and the final certifying QP has, on file, every confirmation the chain depends on.
Filled specimen
Illustrative, for a sterile injectable with a three-site chain: third-country API, EU bulk/fill site, and a separate EU packaging site.
| Stage | Site | Activity | Confirming / certifying party | What is confirmed | Confirmation ref/date | Transmission |
|---|---|---|---|---|---|---|
| Active substance | <<FILL: third-country site>> | Synthesis, API isolation | Not QP-confirmed at this stage (non-EU, no local QP); covered by QP declaration and reliance assessment instead | GMP compliance of the API per QP declaration | QPD-2025-011, audit 2025-04-09 | CoA and audit-based declaration held by the certifying QP; not a stage confirmation in the Section 5 sense |
| Drug product / fill-finish | <<FILL: EU site>> | Aseptic fill, lyophilization | Dr. A. Lindqvist, Site QP | Batch met GMP, in-process controls in limits, media-fill status current | STG-CONF-A4471, 2026-07-18 | Confirmation letter and batch summary transmitted electronically to the release site per QAG-2024-018 |
| Secondary packaging / labelling | <<FILL: EU packaging site>> | Cartoning, serialization, labelling | M. Ruiz, Site QA (delegated confirming authority per site agreement) | Label reconciliation balanced; serialization data uploaded; anti-tampering device applied and verified | STG-CONF-A4471-PKG, 2026-07-19 | Packaging confirmation and label reconciliation transmitted with the batch documentation package |
| Final certification | EU release site | Final Article 51 certification | Dr. R. Gomez, certifying QP | Whole batch, relying on the fill-finish and packaging confirmations plus the QP declaration | Register entry, batch A-4471, 2026-07-20 16:42 | Enters certification register; batch eligible for release |
Chain-integrity check: all rows present, all confirming parties named, all dates contemporaneous, transmission mechanism stated for each handoff, agreements QAG-2024-018 (fill-finish) and <<FILL: packaging site agreement>> cover both handoffs, and the certifying QP holds copies of STG-CONF-A4471 and STG-CONF-A4471-PKG on file. No chain break.
Common inspection findings this matrix prevents
- A final certifying QP who can describe the supply chain verbally but cannot produce the actual upstream confirmations on request.
- A packaging or intermediate stage silently omitted from the chain because no one owns documenting it, discovered only when an inspector traces a specific batch end to end.
- Confirmations that exist but were never actually transmitted to the final certifying QP, sitting instead in the intermediate site’s own files.
- Cross-site handoffs with no covering written agreement, so responsibility at the boundary between two sites is genuinely ambiguous.
- A confirming party’s authority to confirm at their stage never documented, so the confirmation itself has no demonstrable standing.
How to adapt this matrix
- Add or remove stage rows to match your actual manufacturing route; a simple two-site chain needs only two intermediate rows plus final certification, a complex biologic may need five or six.
- Where a stage sits outside the EU with no local QP, state explicitly how that stage’s compliance reaches the certifying QP (a QP declaration, an audit-based reliance assessment, or a direct confirmation from a recognized authority), rather than leaving the row blank.
- Reconcile every transmission mechanism against the actual quality or technical agreement clause that requires it; if the agreement is silent on a handoff this matrix requires, fix the agreement.
- Re-issue this matrix whenever the manufacturing route, a site, or a confirming party changes; it describes the chain for a specific product’s current route, not a permanent template.