What is a Qualified Person (QP), and what does EU GMP Annex 16 require for batch certification?

1What a Qualified Person is.

Article 48 of Directive 2001/83/EC requires every holder of a manufacturing authorisation to have “permanently and continuously at his disposal the services of at least one qualified person”, responsible in particular for the duties in Article 51. The holder may take the role personally if they meet the qualification conditions.¹ Importers hold the same kind of authorisation, under Article 40(3).²

Article 49 sets the minimum qualifications: a university course of at least four years in pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry and technology, or biology, covering subjects the Directive lists (three and a half years can suffice when followed by a year’s training that includes six months in a public pharmacy), and at least two years’ practical experience of analysing and testing medicinal products in authorised manufacturers. A five-year course cuts the experience by one year, a six-year course by eighteen months. Under Article 52, Member States enforce the duties through administrative measures or a professional code of conduct, and may suspend a QP temporarily once administrative or disciplinary proceedings against them begin.¹

Inside the company, EU GMP Chapter 2 has senior management appoint the heads of Production and Quality Control and, where they don’t carry the Article 51 duties themselves, at least one QP designated for the purpose. The organisation chart must show the QP’s position. The QP’s responsibilities “may be delegated, but only to other Qualified Person(s)”.³

2What the law asks a QP to certify.

Article 51 makes the QP responsible for securing three things.¹

• Each batch made in the EU was “manufactured and checked in compliance with the laws in force in that Member State and in accordance with the requirements of the marketing authorization”.
• Each batch from a third country has undergone, in a Member State, “a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary” to meet the marketing authorisation.
• For products placed on the EU market, the safety features are affixed to the packaging.

Where the EU has an arrangement with the exporting country, such as a mutual recognition agreement, the QP may be relieved of the import testing.¹² The QP certifies each production batch “in a register or equivalent document”, kept up to date as operations are carried out and available to inspectors for at least five years. A batch controlled this way in one Member State is exempt from the controls in another when it travels with the control reports the QP signed.¹

The Directive is law, transposed by each Member State. Annex 16 is guidance: the Commission publishes it in EudraLex Volume 4 under Article 47 to interpret the GMP principles. The current text is dated 12 October 2015 and came into operation on 15 April 2016.² US drug CGMP has no equivalent named role: 21 CFR 211.22 gives the quality control unit the authority to approve or reject drug products, and 211.192 has it review and approve production records before a batch is released or distributed.⁴

3How Annex 16 separates certification from release.

Annex 16 places “ultimate responsibility” for a product’s safety, quality and efficacy over its lifetime on the marketing authorisation holder, and responsibility for each individual batch on the QP. Batch release has three parts: checking manufacture and testing against defined release procedures; certification by a QP, which “represents the quality release of the batch”; and transfer to saleable stock or export, which takes that certification into account.²

Each batch of finished product must be certified by a QP within the EU before release for sale, supply or export, and only a QP of a manufacturer or importer named in the marketing authorisation can certify it. Until then the batch stays at the manufacturing site or moves under quarantine to an approved site. Safeguards against uncertified batches reaching saleable stock may be physical, such as segregation and labelling, or “validated computerised systems”. The QP’s notice of certification to the site that transfers stock must be “formal and unambiguous”.²

4What the QP checks before certifying.

Section 1.6 lists what the QP must personally ensure: certification is permitted under the manufacturing authorisation, national requirements are met, and the certification is recorded. Section 1.7 lists 21 points the QP must secure. Those tasks may be delegated to trained staff or third parties, and the QP relies on the pharmaceutical quality system, with “on-going assurance that this reliance is well founded”.²

EMA adds that supply chain records should identify every entity involved in a specific batch, including suppliers and outsourced activities.⁵

5When several sites or an import are involved.

Every EU site performing manufacturing steps must have at least one QP. A QP at a site doing only part of the work confirms that its operations followed GMP and the written agreement. The certifying QP may take full responsibility or share it with confirming QPs, and that sharing must be set out in a document all parties agree.² EMA confirms that the QP performing final certification “holds overall responsibility” for the batch.⁵

For products made outside the EU, physical importation and certification are the last stages of manufacture. Unless an MRA or similar agreement applies, the certifying QP ensures the batch was tested in a Member State. Sampling at the third-country site needs a documented technical justification, including formal quality risk management, an audit and a comparative study.²

6Unexpected deviations and remote certification.

A QP may certify a batch affected by an unexpected deviation from the marketing authorisation or GMP only if every registered specification is met, the deviation is investigated and its root cause corrected, and a quality risk management assessment concludes its impact is negligible.² EMA adds that a deviation is “unexpected” only until it is discovered. Repeats after that are changes that need a variation. In exceptional cases, where the authorities have confirmed the need to avoid disrupting supply, certification may continue while corrective and preventive action is under way.⁵

EMA’s July 2023 questions and answers allow remote certification where the national competent authority accepts it. It must still take place within the EU/EEA or Northern Ireland, the IT systems used should comply with Annex 11, only the QP may have editing access to the certification function, and the electronic signature must reflect Annex 11.⁵

7How it runs in Seal.

In Seal, batch release runs as one release case. The executed batch record, material genealogy, laboratory evidence and quality reviews come together, and each requirement has an owner, a source and a recorded outcome. QA records its disposition for a defined batch population, and in the EU the QP then certifies under Annex 16. Manufacturer disposition stays separate from market-specific gates, so a released batch isn’t assumed to be distributable everywhere.

Neil can prepare a batch for review: it checks execution, laboratory and quality evidence against your review requirements and drafts a source-linked brief, with missing evidence requested. The brief does not release a batch or replace a signature. QA decides the disposition and the QP certifies.