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European Qualified Person Association - Publications/Question
and Answer Documents
How to become a Qualified Person
Q: I am a Chemist. How can I become a QP?
A: In Article 49 of Directive 2001/83 (for veterinary medicinal products, please read Article 53 of Directive 2001/82) – please see the
QP Regulations, the qualification level as well as the necessary professional experience of a QP is defined. The EU requirements as defined in these Directives have to be transferred to national law in each EU Member State. However, there are a number of differences in the EU Member States due to the fact that each Member State can implement the directives into national law with slight modifications.
Our recommendation is to discuss this matter with the respective authority in the Member State you plan to work as QP.
Q: Can companies outside the EU but with an MRA have a QP according the EU Directive. Can such a person be certified by the EU?
A:
Things that need to be considered are:
- The QP is linked to a European Manufacturing authorisation.
- If the "QP" is an employee of a company outside the EU, he/she is not employed by a company with an European manufacturing authorisation and therefore can not act as a QP.
- There is no such thing as a certification to be a QP. A QP is registered by the authority of the respective EU member state.
It is normal practice for a product manufacturer in a third country to have an EU-based importer who can provide the services of a QP? This EU-based QP would assess and certify a product/batch imported into the EU.
Q: Does a QP from an EU Member State who is appointed by the Member State’s Main Pharmaceutical Inspectorate as a QP and is chemist and not a pharmacist can move to Germany and still carry out duties of QP?
A: Although the educational background would not be considered sufficient by the various local authorities in Germany to be initially accepted as a QP, a Chemist would be accepted once he/she is registered as a QP in another Member State. So once a QP is eligible and registered by another Member State authority he/she could apply as a QP in Germany. However it needs to be decided by the local German authority (e.g. Regierungspräsidium or local government). Many Member States require that a QP speaks the local language to be able to understand batch records, certificates and other GMP-related documents.
Q: If a company is based in Switzerland and produces pharmaceutical products, what are the possibilities to become a QP?
A: As Switzerland is not an EU Member State, the applicable Directives apply via the MRA.
The QP in Switzerland is called the "Fachtechnisch verantwortliche Person".
To become a Fachtechnisch verantwortliche Person, an academic qualification is needed (for finished products and intermediates usually a pharmacist). Other academic qualification is acceptable in case of proven experience and for APIs and blood products.
The Notification is handled by Swiss Medic and the "Fachtechnisch verantwortliche Person" will be named on the manufacturing license. We would recommend contacting Swiss Medic for further information.
Q: There are certain professional bodies in UK who can grant QP status and can advise people that they are eligible for QP status as per EU Directives. However, it appears that some Member States do not recognise the defined education and experience requirements for becoming a QP as per EU Directives. In France for example the 'Pharmacien Responsable' has to be a pharmacist qualified and registered in France. Is it possible to operate as a QP recognised by markets where our products are commercialised (all EU), while not being considered a QP by the country of manufacture?
A: Directives are only binding as to the result to be achieved– and leave national authorities the choice of form and methods. The EU requirements as defined in the Directives have to be transferred to national law in each EU Member State. However, there are a number of differences in the EU Member States due to the fact that each Member State can implement the directives into national law with slight modifications. This national law is the binding one.
To operate as a QP one has to be named by the holder of the marketing authorisation in the EU and must be registered/ accepted by the EU member state where the company resides.
Duties and responsibilities of the Qualified Person
Q: A company has recently been inspected by the respective national Inspectorate, and some of the observations in this inspection related to the role of the QP with respect to the quality system. For example, the authority asked for a description of the QP's responsibility with respect to the approval of controlled documents (documents in the quality system). Is this required in the QP relevant legislation?
A: It is a common misconception in these days that the QP is considered being responsible for all aspects of a Quality Management System, especially for approval of all kinds of documents, forms and reports.
Although the QP’s tasks and responsibilities are manifold it must be clearly stated that a QP is not automatically the Head of a Quality Management System, Head of Quality Assurance, or Head of a Quality Control Unit. This may be the case in smaller companies but very often, this is not the case. The QP then has to rely not only on other QPs but also on other staff and the Quality System, especially the Head of Production and the Head of Quality Control.
So it is the QP’s duty to ensure that certain pre-requisites are fulfilled as described in Annex 16 to the EU GMP Guide.
There is no requirement in the European regulations and Guidelines that the QP has to approve any other documents than the release documentation. However, a QP should be involved in the implementation and maintenance of the Quality (Management) System. But the QP is not obliged to implement and run the Quality System.
So if a company has a Quality Control Unit and/or a Quality Assurance Unit with experienced and authorised staff - why should the QP approve controlled documents?
Contract Qualified Persons
Q: Is there any guidance available defining “sufficient” time on a site to familiarise a Contract QP with the Quality System?
A: There is no guidance available. The time on site will depend on the complexity of the quality system. An important consideration is the maturity and stability of the system. If the system is mature and stable a shorter time on site may be indicated, provided that the contract specifies that the QP must be made aware of any changes that affect the quality system.
Q: Outsourcing the QP batch release:
- what are the pre-requisites (GMP and legal)?
- what experience is needed?
- are there any existing models as a reference?
A: The QP must be endorsed by the competent local authority according to the national law. There must be a written agreement between the QP and the manufacturer, clearly describing the role and responsibility. The permanent availability of the QP must be assured, the frequency of on-site availability and the way the QP gets all relevant information must be defined.
The QP must be appropriately experienced in the manufacture and quality control of the product type manufactured by the contract giver. In case the products need additional formal education or experience – like with regard to blood products, the QP must comply with these requirements.
Q: When IMPs are imported from outside the EU; how could I set up a working relationship as a contract QP when it comes to liability and insurance?
A: As a contract QP you are a “normal” contracting party (i.e. just like any other service provider for the company but with the specific legal responsibilities and risks of a QP) and therefore no employee of the company. That means that you are not covered by any of the insurance programmes which companies usually provide for their employees (e.g. D&O insurance). As a result, you should mention that fact – and the related legal risks – during your contract negotiations with the company.
Ideally, there should be an indemnification clause in the service contract providing for that ‘the company indemnifies the contract QP from any and all third party claims related to the services which the contract QP may perform under the service contract’. If your current contract does not contain such provision, you should ask the company to sign an amendment with aforesaid clause.
You can also ask the company to get yourself explicitly included in its D&O insurance contract (some insurers may actually be ready to do so because of the specific situation of the contract QP).This inclusion could be the first part of the contractual provision, followed by the indemnification clause mentioned above.
Release Decisions
Q: An API is contaminated with very small amounts of glass (<0.02%). The API is micronized and then pressed to tablets (oral). Giving the fact that glass has a very low toxicology; would you release the batch of the final product?
A: No. There is an excellent quote in the European Pharmacopoeia, Chapter 1. “General Notices, Tests and Assays”: “... It is not presumed, for example, that an impurity that is not detectable by means of the prescribed tests is tolerated if common sense and good pharmaceutical practice require that it be absent.” Good Manufacturing Practice and Good Pharmaceutical Practice require glass particles to be absent in APIs that will be used to manufacture oral solid preparations without any filtration step that would remove the particles!
If during its production the API has undergone a last purification step by re-crystallisation after filtration using charcoal or a filter aid, this step should be repeated with the contaminated API (reprocessing) to remove the contaminant.
Q: A sterility test failed most likely because of a contamination during testing: is a re-test justified?
A: A retest of a positive sterility test must be very carefully justified based on a root cause investigation giving evidence that there has been a contamination in the laboratory during preparation or testing. It is not appropriate and acceptable to re-test based on mere suspicion.
Reasons to invalidate a positive result would be e.g.
- Microbiological monitoring of the sterility testing facility shows evidence for a failure like detection of the contaminant(s) in the testing environment. This has to be proven by genetic identity of both isolates!
- Microbial growth is found in the negative controls
- After identifying the microorganisms isolated from the test, the growth of this species can be clearly linked to failures with respect to the material and/or the technique used when conducting the sterility test procedure - e.g. contaminated media or non sterile sterility testing units
Q: A product (sterile eye drops) meets all specifications. However during production some microbiological monitoring results were not OK. Can I certify the batch?
A: Microbiological monitoring data are not describing the microbiological status of the batch itself. Monitoring data are considered to give information about the controlled environment. A level excursion in micro monitoring may be an indicator that there are deviations from the usual process, but they do not automatically indicate a microbiological problem of the batch. Following a positive outcome of a risk assessment of the non conforming monitoring results (type of contamination, level of contamination, place of the monitoring, other monitoring data, trending) it might well be possible to certify the batch.
Q: What should happen if OOS investigations are inconclusive?
A: The certifying Qualified Person should fully consider all of the information prior to making any decisions as to the final disposition of the batch. Any decision to release a batch where OOS results have not been invalidated should come only after a full investigation has shown that the OOS result does not reflect the quality of the batch. In making such a decision quality assurance and the Qualified Person should always err on the side of caution.
(source: MHRA Q&A)
Role of the Qualified Person in the Company
Q: Is it possible to name more than one QP for the release of one certain product and if yes, can each QP be named as responsible for different sub-types of the product?
A: It is perfectly possible to name more that one QP and they can be named for different sub-types of product.
Q: Does the QP have to confirm acceptance of the company’s QA-System in writing or is signing of job descriptions and/or signing key-SOPs sufficient?
A: There is absolutely no regulatory or GMP requirement or expectation that a QP has to sign off job descriptions or key SOPs. In addition there is no formal requirement that a QP has to “confirm acceptance” of the company’s QA-System.
Pharmaceutical manufactures usually run regular Quality Management Reviews that include a documented management assessment of the suitability of the Quality System. Therefore we would consider it appropriate and adequate that the QP is a regular member of this board.
Q: From a GMP and legal point of view, is there any problem that QP/QA and QC are the same person?
A: The only requirement under GMP is that the person responsible for production and the person responsible for quality control are independent. The QP can be the person who is also responsible for QC or the person who is responsible for QA (or both). In practice the QP certifying batches of product should not be the person who is responsible for their production.
Q: Who should sign the Quality Agreement? The QP only? QA? Legal? Head of production/QC? Business?
A: Quality Agreements should be considered GMP documents. Therefore involvement of the Legal Departments can be limited. According to the latest revision of chapter 7 of the EU GMP Guide (“Outsourced activities”) ...
7.12 “A contract should be drawn up between the Contract Giver and the Contract Acceptor which specifies their respective responsibilities and communication processes relating to the outsourced activities. Technical aspects of the contract should be drawn up by competent persons suitably knowledgeable in related outsourced activities and Good Manufacturing Practice.”
Chapter 2.7 of the revised chapter 2 of the EU GMP Guide (“Personnel”) states:
“The heads of Production and Quality Control generally have some shared, or jointly exercised, responsibilities...— the approval and monitoring of contract manufacturers;”
Keeping these two chapters in mind, I would advocate for the Head of Production and Quality Control to sign a Quality Agreement. The QP must be informed, but there is no obligation for him/her to sign the Quality Agreement.
Q: If an audit required by Annex 16 is performed by corporate QA or a global QA function of the same company but part of different legal entity (e.g. from US), will I need a contract or is an SOP sufficient?
A: European understanding on different legal entities even within the same global company has to be considered as independent to each other in terms of GMP. According to Chapter 7 EU GMP all services contracted out should be covered by a contract. If such a service is provided to the QP by a global function it should be covered by a contract. Topics to be considered are provisions of influence on sequence, audit agenda, audit reports availability, auditor rating and possibilities to accompany the audit as an auditor.
Q: Annex 11 states that “There should be close cooperation between all relevant personnel such as Process Owner, System Owner, Qualified Persons and IT. All personnel should have appropriate qualifications, level of access and defined responsibilities to carry out their assigned duties.“ What should be understood by “close cooperation between all relevant personnel …”? What formal requirements should be observed?
A: No defined formal requirements exist for close co-operation between all relevant personnel during validation. But efforts must be made to ensure that a corresponding division of roles and tasks between the relevant personnel is clearly defined and implemented, including IT.
(source: ECA Q&A)
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