Qualified Person Certification and EU Batch Release: Annex 16 in Practice

In the European Union, no medicinal product reaches a patient until a named individual takes personal, legal responsibility that the batch was made and tested in accordance with the law and the marketing authorisation. That individual is the Qualified Person, the QP. Certification by the QP is the legal act that converts a finished batch into a product that may be sold or supplied. It is not a signature of convenience and it is not the same thing as QA approval of a batch record. It is a defined legal duty under EU pharmaceutical law, and the person carrying it can be held personally accountable.

This article covers what QP certification means, the legal basis, the content of the QP declaration, how reliance works across a supply chain, the difference between certification and release, the actual decision procedure a QP follows, and the inspection findings that recur in this area. The reference text throughout is the EudraLex Volume 4 GMP guide, Annex 16, “Certification by a Qualified Person and Batch Release,” current version effective 15 April 2016.

The legal basis: where QP certification comes from

The QP role is written into EU primary legislation, not just guidance. Two directives create it.

• Directive 2001/83/EC (the Community code relating to medicinal products for human use), Articles 48 to 52, requires every manufacturing and importation authorisation holder to have at its disposal at least one Qualified Person. Article 51 sets out the QP’s core duty: recording in a register, or an equivalent document, confirmation that every batch was produced and tested as the applicable law and the terms of the marketing authorisation require.
• Directive 2001/82/EC historically did the equivalent for veterinary products. For veterinary medicines the framework has since moved to Regulation (EU) 2019/6, applicable from 28 January 2022, which carries the QP concept forward.

For investigational medicinal products, the QP duty is set by Directive 2001/20/EC and, since 31 January 2022, by the Clinical Trials Regulation Regulation (EU) 536/2014, with the relevant GMP detail in Annex 13 of the EU GMP guide. Certification of IMPs has its own nuances, covered briefly later and in the linked article on Annex 13.

The qualifications a person must hold to act as a QP are set in Article 49 of Directive 2001/83/EC: a defined educational base (pharmacy, medicine, chemistry, pharmaceutical chemistry and technology, or biology and similar), plus at least two years of practical experience in qualitative analysis, quantitative analysis, and other testing and checking of medicinal products, in one or more authorised manufacturers. National competent authorities recognise and, in several member states, formally register or assess QPs. The detailed operating expectations sit in Annex 16, which tells the QP how to discharge the Article 51 duty in real supply chains.

Annex 16, Section 1.1 establishes the principle that a QP certifying a finished batch can base that decision partly on the advice and decisions of other people, that this dependence has to be written down, and that anyone the QP leans on must be suitably qualified and trained for the part they play.

The risk rationale is straightforward. Patients cannot inspect a sterile injectable or verify a tablet’s content uniformity. The QP is the single accountable human checkpoint who confirms, before product reaches the market, that the whole chain of manufacture, testing, and authorisation actually held together. Putting that duty on a named, qualified, legally exposed person is the control that makes the rest of the GMP system enforceable.

Certification versus release: two different acts

A frequent confusion, and a frequent interview trap, is treating “certification” and “release” as synonyms. Annex 16 separates them deliberately.

• Certification is the QP’s legal act under Article 51. The QP confirms each batch complies with GMP, the marketing authorisation (MA), and any other relevant legal requirement, and records that confirmation in a register or equivalent. Certification is performed once per batch and cannot be delegated. The QP’s name is attached to it.
• Release for sale or supply (often called “release” or “physical release”) is the act of making the certified batch available to the market. This can be an administrative or logistics step, and in many companies it is performed by a separate function (supply chain, a release coordinator) once certification is complete and any remaining controls (such as confirmation that all sites in the supply chain are appropriately authorised) are satisfied.

Annex 16 makes the point that a batch may be certified but held back from release, for example pending a commercial decision, a final transport confirmation, or release testing in a destination market. Certification is the regulatory gate; release is the commercial and logistics gate that follows it.

The practical sequence: QP certifies, then the batch is released for sale. You can certify without immediately releasing. You can never release a non-certified batch.

What the QP is certifying: the full scope of the duty

When a QP certifies, the confirmation is broad. Section 1.7 of Annex 16 sets out the conditions a QP has to satisfy before certifying. A working QP treats them as a list of what must hold true, regardless of who actually did each part. Paraphrased, the main confirmations cover:

1. That the batch, and the way it was made, fits the marketing authorisation (and, for IMPs, the clinical trial authorisation and product specification file).
2. That production met GMP, or, for product made outside the EU, GMP at a standard no lower than EU GMP.
3. That the manufacturing and testing processes carry a valid validation status and that this particular batch ran on the validated process.
4. Any deviations or planned changes to production or quality control were authorised under the company’s pharmaceutical quality system and were either closed or assessed as not affecting the batch’s compliance.
5. All required in-process and finished-product testing and checks were performed, including any additional sampling, inspection, tests, or checks required by deviations or changes.
6. All required GMP audits of active substance manufacturing sites and other relevant sites were performed.
7. The importation and testing of products from third countries (if applicable) met the legal requirements, including any reliance on a Mutual Recognition Agreement (MRA).
8. The supply chain of the active substance and the finished product is documented and known, including written confirmation that the active substance was manufactured in accordance with GMP (the “QP declaration” for the active substance is separate, covered below).
9. The transmission of safety-relevant information (for example, to pharmacovigilance) is in place.
10. Ongoing stability and other relevant data continue to support the product.

The QP does not personally repeat every test or re-audit every site. The duty is to ensure these things are true and to take personal responsibility that the system delivering them is reliable. That is why reliance, documented and justified, is central to the role.

Reliance: how a QP certifies without doing everything

No QP physically observes every step at every site, particularly in modern global supply chains where the active substance, drug product, primary packaging, and finished packaging may all happen at different companies on different continents. Annex 16 explicitly permits the QP to certify based, in part, on the advice and decisions of others, provided certain conditions hold.

The reliance principle in Section 1.5 of Annex 16 sets clear conditions. Paraphrased, a QP who depends on others has to:

• Know first-hand, through experience and the pharmaceutical quality system, that those people and systems can be trusted (personal knowledge of their reliability).
• Make sure the parties being depended on actually fall under GMP and are audited, whether directly or through the company’s supplier qualification and audit program.
• Pin down responsibilities in writing, through technical or quality agreements.

What this looks like in practice: a QP at the EU importing/release site does not personally test the active substance, but relies on the supplier qualification program, the audit reports of the API site, the analytical results provided, and the quality agreement that defines who is responsible for what. The QP must be able to demonstrate, if asked by an inspector, the basis for that reliance, including the audit history and the agreement.

Section 1.6 of Annex 16 stresses that the QP retains overall responsibility even when relying on others. Reliance distributes the work, not the accountability. A QP cannot say “the contract lab signed off the testing” as a defence if the testing was inadequate. The QP is expected to have assured themselves that the contract lab was competent and that the arrangement was governed properly.

The role of the technical/quality agreement

Where multiple sites and multiple QPs are involved, a written agreement is mandatory. Annex 16, Section 7, addresses sites in different member states and multi-stage supply chains. The agreement should define which QP at which site is responsible for which stage, how information flows, who certifies the final batch, and how deviations and changes at any site are communicated to the certifying QP. See the linked article on CDMO oversight and quality agreements for how these are structured and what clauses inspectors look for.

The QP declaration for the active substance

A specific deliverable that confuses many newcomers is the written confirmation of GMP compliance of the active substance manufacturer, commonly called the “QP declaration.” This is required for marketing authorisation applications and is distinct from batch certification, although the same person often produces both.

Under Directive 2001/83/EC as amended by Directive 2011/62/EU (the Falsified Medicines Directive), the QP of the medicinal product manufacturer must confirm that the active substance used has been manufactured in accordance with GMP for active substances. The European Commission publishes a template for this declaration. The QP declaration states, for each active substance and each API manufacturing site listed in the MA dossier, that the QP has verified GMP compliance, typically through an on-site audit (performed by the QP, by the company, or by a competent third party on the company’s behalf and whose report the QP has reviewed).

What goes into a QP declaration:

• Name and address of the finished-product manufacturing site and the responsible QP.
• The active substance(s) and the manufacturing site(s) covered.
• A statement that the API is manufactured in compliance with the detailed GMP guidelines for active substances (Part II of the EU GMP guide, which corresponds to ICH Q7).
• The basis of the confirmation, usually the date and outcome of the most recent audit, and who conducted it.
• The QP’s signature and date.

Acceptance criteria for a good QP declaration: it is current (the audit interval is justified and not expired against the company’s risk-based audit schedule), it covers every API site in the MA, it names the auditor and audit date, and it is supported by an audit report on file that the QP has actually read. A common gap is a declaration that references an audit whose report the QP never reviewed, or where the audit predates a significant change at the API site.

The QP decision procedure, step by step

Here is the sequence a QP actually follows before putting their name to a batch. The order matters because each gate depends on the one before.

Step 1: Confirm the batch is within the scope of the manufacturing/importation authorisation and the MA. The product, dosage form, strength, and the site performing each operation must all be covered by valid authorisations. For imports, confirm the import testing obligation status (full testing, or reliance on an MRA/Annex 16 Section 1.7.21 arrangement).

Step 2: Review the executed batch record and the batch certificate/summary. Confirm the batch followed the registered process, all critical steps were performed and signed, in-process controls met limits, and yields are within expected ranges. See the linked batch record review article for what a thorough review covers.

Step 3: Review the certificate of analysis and confirm finished-product testing. All registered tests performed, all results within specification, the testing lab appropriately authorised, methods validated or compendial as registered. Confirm any out-of-specification results were properly investigated and concluded, and that an invalidated OOS has a sound scientific basis.

Step 4: Review deviations and changes affecting the batch. Every open or closed deviation touching this batch must be assessed for product impact. Planned changes must have been approved before implementation. A deviation that is still open and unresolved generally blocks certification unless its impact on the batch has been formally assessed and concluded as acceptable.

Step 5: Confirm validation status. Process validation, cleaning validation, analytical method validation, and equipment/computerised system qualification covering this batch are all current. A batch made on equipment whose qualification has lapsed is a certification problem.

Step 6: Confirm the supply chain and API GMP status. The active substance came from an audited, GMP-compliant site covered by the QP declaration. The full chain (API, intermediates, drug product, packaging) is documented and authorised.

Step 7: Confirm any reliance is properly governed. For any element you did not directly verify, confirm the quality agreement, supplier qualification, and audit history support reliance, and that the relevant confirmation (for example, certification of a bulk stage by another QP) is on file.

Step 8: Confirm ongoing/post-approval commitments. Stability program on track, any post-approval commitments and variations reflected, pharmacovigilance information transfer functioning.

Step 9: Make the decision and certify. If all gates pass, certify the batch in the register, recording the date, the batch, and your identity. If any gate fails, the batch is rejected or held, with the reason documented, and the deviation/investigation process is invoked.

Acceptance criteria for the certification act itself

A certification is correct when:

• It is recorded in a register or equivalent document, retrievable and attributable to the named QP, with date.
• The record makes clear which batch and which MA it relates to.
• The supporting decision (the batch review) is documented and available, even if the certification entry itself is brief.
• It was made before the batch was released for sale, not retrospectively to paper over a release that already happened.

A worked example: certifying an imported sterile injectable

Consider a sterile injectable whose active substance is made in a third country, drug product manufactured at an EU site, and final certification performed at an EU release site. Here is how a QP at the release site would work through the gates.

Certification entry in the register:

Product:        Generic Injectable 10 mg/mL, MA No. <ref>
Batch:          A-4471 (12,400 units)
Manufactured:   <site>, fill/finish
Tested:         <QC lab>, all results within MA specification
Deviation:      DEV-2026-0188, assessed, no batch impact
QP declaration: API site GMP confirmed, audit 2025-04-09 (ICH Q7)
Certified by:   <QP name>, <date/time>
Decision:       CERTIFIED for sale/supply in EU/EEA

Now change one fact: the autoclave excursion impact assessment is inconclusive because the validated cycle has no defined margin for the extended hold time. The QP cannot certify. The correct action is to hold the batch, escalate the deviation to a full investigation, and require either supportive data (for example, re-validation data or a scientific bracketing argument) or rejection. Certifying “to keep the schedule” while the sterility assurance question is open is exactly the kind of decision that ends careers and triggers recalls.

Roles and responsibilities

Certification is a single-person act, but the system feeding it involves many functions. Clear separation matters because inspectors probe whether the QP had independent visibility or was simply rubber-stamping.

A point that recurs in inspections: the QP must have the authority and independence to refuse certification, including against commercial pressure. If the reporting line or culture means a QP cannot realistically say no, the control is compromised. Annex 16 Section 1.4 expects the responsibilities of all QPs involved to be defined in writing.

Multi-QP and multi-site supply chains

Modern products often involve several QPs across several stages. Annex 16 Section 5 and Section 7 address how this is handled.

• One QP per certification, final certification once. Different QPs may take responsibility for different stages (for example, a QP certifies the bulk product, another certifies the finished pack). Only the QP performing the final certification before release takes responsibility for the whole batch, relying on the earlier-stage confirmations.
• Confirmation versus certification. Intermediate stages may be subject to “confirmation” by a QP at that stage rather than full certification. The final certifying QP relies on those confirmations. The terminology distinction matters in interviews: confirmation is a documented statement that a stage met GMP and the agreed conditions; certification is the final Article 51 act.
• Cross-border arrangements. When stages occur in different member states, written agreements must define how each QP’s responsibilities connect and how the final certifying QP gets the information needed. The chain of confirmations must be unbroken and traceable.
• Sampling for importation. Annex 16 addresses where samples are taken for import testing and the conditions under which samples taken at the manufacturing site (rather than re-sampling on EU arrival) are acceptable, subject to validated transport and a justified arrangement.

The key mental model: build the certification like a chain of evidence. Every stage that someone else performed must arrive at the final QP as a documented confirmation, governed by an agreement, supported by audit. The final QP signs for the whole chain.

Handling deviations, OOS, and unexpected results at certification

The QP decision is rarely “everything is perfect.” Real batches carry deviations and the occasional OOS. The QP’s skill is judging product impact.

For each open or recent event, the QP asks:

1. Does it affect this batch? If a deviation occurred on a different batch or a different campaign, it may not be in scope, but the QP should confirm that.
2. Is the investigation concluded with a sound root cause and a defensible impact assessment? An OOS that was invalidated needs a scientifically valid assignable cause, not a convenient one. See the linked OOS investigation article.
3. Is any additional testing or checking warranted? Annex 16 Section 1.7.5 explicitly notes that deviations or changes may require additional sampling, inspection, tests, or checks. The QP can require these before certifying.
4. Is the change properly approved? A change implemented without prior approval is itself a deviation and may block certification.

The defensible position is documented in the batch review: the deviation, its assessment, the conclusion, and the rationale that the batch still meets GMP and the MA. An undocumented “professional judgement that it was fine” is not defensible.

Unexpected results found after certification

If a problem surfaces after a batch has been certified and released (a stability failure, a complaint trend, a late OOS on a retained sample), the QP is part of the response: assessing whether other batches are affected, deciding on quarantine, and supporting any recall decision. Certification is not the end of the QP’s interest in a batch.

QP certification of investigational medicinal products

For IMPs, certification follows Annex 13 and, under the Clinical Trials Regulation 536/2014, the equivalent provisions, with Annex 16 principles applied. Differences worth knowing:

• The QP certifies against the product specification file and the clinical trial authorisation rather than a marketing authorisation, because an IMP has no MA.
• For IMPs imported from third countries where there is no MRA covering the activity, the certifying QP confirms each batch was manufactured and checked to standards at least equivalent to EU GMP, but full re-testing on import may be reduced where justified, because the comparator and blinding constraints differ.
• Blinding and comparator sourcing add specific checks (for example, confirming the comparator’s provenance and that blinding operations did not compromise quality).

The linked article on GMP for investigational products (Annex 13) covers this in depth.

Common mistakes and recurring inspection findings

These are the patterns that show up in EU GMP inspection findings and deficiency letters around QP certification. None reference any specific company; they are the generic, repeating themes.

• Certification without genuine review. The register shows certifications, but there is no evidence the QP actually reviewed the deviations, OOS investigations, or change controls affecting those batches. Inspectors test this by picking a batch with a known deviation and asking the QP to walk through how it was assessed.
• Open deviations at certification. Batches certified while a relevant deviation or investigation was still open, with no documented impact assessment justifying that the batch could proceed.
• QP declaration gaps. A QP declaration that covers some but not all API sites in the MA, references an audit report the QP never read, or relies on an audit that is overdue against the company’s own risk-based schedule.
• Reliance without basis. The QP relies on a contract testing lab or another site but cannot produce the quality agreement, the supplier qualification, or the audit history. Reliance is asserted, not demonstrated.
• Confusing certification with QA batch approval. The QA batch-record sign-off is treated as if it were the QP certification, with no clear, attributable Article 51 act recorded.
• Lack of QP independence. Evidence (emails, reporting lines, timing) that the QP was pressured to certify to meet supply targets, or that batches were effectively released before certification was complete.
• Inadequate handling of post-certification problems. A stability failure or complaint surfaces, but there is no documented QP-led assessment of impact on other certified batches.
• Register deficiencies. The certification register is incomplete, not contemporaneous, not attributable, or cannot be reconstructed for a specific batch.
• Changes implemented before approval. Process or specification changes made before the corresponding variation or change control was approved, then quietly certified.
• MRA misuse. Relying on a Mutual Recognition Agreement to waive import testing for a product, dosage form, or operation not actually covered by that MRA’s scope.

The thread running through these: certification is only as good as the documented evidence behind it. “I am an experienced QP and I judged it acceptable” is not a record. The decision and its basis must be reconstructable years later.

Interview-ready: questions and strong answers

These are the questions a hiring manager or an inspector asks on this topic, with the shape of a strong answer.

Q: What is the difference between certification and release? Certification is the QP’s legal act under Article 51 of Directive 2001/83/EC confirming the batch complies with GMP and the MA, recorded in a register, done once per batch, and not delegable. Release for sale is the subsequent act of making the certified batch available to the market, which can be an administrative step performed by another function. You can certify and hold; you can never release without certification.

Q: Can a QP certify based on the work of others? Yes. Annex 16 Section 1.5 permits reliance on the advice and decisions of others, provided the QP has personal knowledge of their reliability, those parties are subject to GMP and audit, and responsibilities are defined in writing. The QP retains overall responsibility regardless. Reliance distributes work, not accountability.

Q: A batch has an open deviation when it reaches you. What do you do? I do not certify a batch with an unresolved deviation unless the deviation’s impact on that specific batch has been formally assessed and concluded as acceptable, with documented rationale. If the investigation is incomplete or the impact is uncertain, the batch is held. I may also require additional testing or checking, which Annex 16 explicitly allows, before deciding.

Q: What is the QP declaration and how does it differ from certification? The QP declaration is a written confirmation, required for the MA, that the active substance is manufactured to GMP (Part II of the EU GMP guide, equivalent to ICH Q7), normally based on an audit of the API site. It is a dossier deliverable about API GMP compliance. Certification is the per-batch Article 51 act. The same QP often does both, but they are different documents serving different purposes.

Q: An OOS result was invalidated. What do you check before certifying? That the OOS investigation followed a defined procedure, that the invalidation rests on a scientifically valid, documented assignable cause (a real laboratory or sampling error, not a convenient explanation), that any retesting or resampling was justified and pre-defined, and that the conclusion is consistent with the rest of the batch data. If the assignable cause is weak, the original result stands and I treat the batch accordingly.

Q: How does certification work when manufacturing spans several sites and countries? Each stage may be confirmed or certified by a QP at that stage, but only the QP performing the final certification before release takes responsibility for the whole batch, relying on the documented confirmations of the earlier stages. Written agreements must define who is responsible for what and how information reaches the final certifying QP. The chain of confirmations has to be unbroken and traceable.

Q: What gives the QP the right to refuse certification? The legal duty under Article 51 is personal. The QP must have the authority and independence to refuse, including against commercial pressure. A QP cannot be directed to certify. If a batch does not meet GMP or the MA, the QP rejects or holds it, and that decision stands on its own legal footing.

Q: What happens if a defect is found after you certified and released a batch? Certification does not end my responsibility. I assess whether other batches are affected, decide on quarantine, and support the recall decision and field action as needed. The post-certification response is part of the role, alongside reporting through the quality system and to authorities where required.

Practical tips

• Keep your certification register clean, contemporaneous, and reconstructable. If you cannot show, batch by batch, what you certified and when, everything else is harder to defend.
• Treat the quality agreement as a working document, not a filing-cabinet formality. When reliance is questioned, the agreement plus the audit history is your evidence.
• Maintain a personal log of the basis for reliance on each major supplier and site, including audit dates and any open issues. It makes the inspection conversation far smoother.
• Diary your QP declarations against the API audit schedule so none lapse. An overdue API audit quietly invalidates the declaration’s basis.
• When you hold a batch, document the reason and the path to resolution at the moment of the decision, not later. The contemporaneous record is what protects you.
• Build a habit of asking “if an inspector picked this exact batch, could I walk them through every deviation and reliance decision from memory plus the file?” If not, the review is not finished.
• Know your MRA scope precisely. Misapplying an MRA to waive import testing is a recurring and avoidable finding.

Related articles

• Batch disposition decisions
• Batch record review in GMP
• OOS investigation process
• GMP for investigational products (Annex 13)
• CDMO oversight and quality agreements
• ICH Q7 API GMP
• Supplier and vendor qualification
• Certificate of analysis
• Deviation management
• The pharmaceutical quality system
• Recall management and field actions
• FDA versus EMA inspection dynamics