GMP and quality defects

Good Manufacturing Practice (GMP) is a quality assurance system for the pharmaceutical industry. The quality of a medicinal product can only be assured by a carefully defined and controlled production process.

Medicinal products must therefore always be produced and checked in accordance with:

  • the established quality norms for the intended use and
  • the terms and conditions of the marketing authorisation.
News update December 2020

IGJ experiences delays in GMP inspections

GMP inspection by the Dutch Healthcare and Youth Inspectorate (IGJ) is required for various national applications for marketing authorizations or applications for decentral procedures (DCP’s). However, the IGJ is currently facing a backlog in the processing of these inspections. Partly because of the corona crisis, the IGJ has not been able to perform inspections on location. When inspections became possible again, the IGJ gave the priority to locations that might play a role in production of corona vaccines.

Partly because of that situation, the processing of permit applications has been delayed. Many of the inspections for applications submitted in 2020 will not take place this year. The IGJ does not expect to be able to carry out the inspections until 2021, but cannot give an exact date under the current circumstances. The delay applies to both human and veterinary medicines.
 

When is the IGJ the designated inspection authority?
The IGJ is designated as inspection authority when the end manufacturer is located in the Netherlands. If the release manufacturer is established in our country and the manufacturer of the final product is located outside the European Union, the IGJ still is the authority to carry out the inspection of the manufacturer of finished product outside the EU. Are multiple release countries listed in the file? Then the European Medicines Agency (EMA) will appoint a so-called Supervisory Authority, which is responsible for supervision outside the EU.

More information can be found on the websites of the IGJ and Farmatec (both in Dutch).

GMP certificate

In the Netherlands, the Health and Youth Care Inspectorate (IGJ) is the supervisory body that carries out inspections to investigate whether the manufacturer complies with the rules for GMP. A GMP certificate is issued if GMP compliance has been confirmed.

The IGJ also inspects GMP compliance of manufacturers in countries outside of the European Union. This is done at the request of the European Medicines Agency (EMA) and the MEB. At the request of the MEB, the IGJ also gives advice about the manufacturers as proposed in  the marketing authorisation dossier (site clearance).

When a manufacturer deviates from the GMP quality requirements, the MEB can decide to request the marketing authorisation holder to remove the specific manufacturer from the marketing authorisation dossier via variation. This is done in consultation with the IGJ, other European Inspectorates and the CMDh/EMA.

If this may result in a shortage of a medicinal product in the Netherlands, the marketing authorisation holder must report this at the Medicine shortages and defects notification centre.

Suspension of withdrawal of a CEP

The European Directorate for the Quality of Medicines and Healthcare (EDQM) issues certificates (CEPs) to the manufacturers of active pharmaceutical ingredients. A CEP is a confirmation that the pharmaceutical substance or active ingredient has been produced in accordance with the quality regulations for the preparation of medicinal products. CEP stands for 'Certificate of Suitability to the monographs of the European Pharmacopoeia'.

The EDQM inspectors investigate whether manufacturers comply with GMP and whether their production processes are in line with the approved CEP dossier. Inspectors from EU/EEA Member States also contribute to these inspections.

The Certification Database on the EDQM website shows whether a CEP is valid. The EDQM can suspend or withdraw a CEP on the following grounds:

  • Inspection of the active pharmaceutical ingredient's manufacturer shows that the manufacturer is not complying with GMP or CEP requirements.
  • The active pharmaceutical ingredient's manufacturer refuses to allow the inspection.
  • On request by the manufacturer of an active pharmaceutical ingredient:
    • If they are temporarily unable to produce in accordance with the approved CEP dossier
    • If production has ceased, the factory has closed or the CEP is no longer applicable.

The MEB aims to request removal of manufacturers with a suspended or withdrawn CEP from the marketing authorisation dossiers. Depending on the type of marketing authorisation, the MEB aims to coordinate this on a European level.

If the suspension or withdrawal of a CEP may result in a shortage of a medicinal product in the Netherlands, the marketing authorisation holder must report this at the Medicine shortages and defects notification centre.

Always inform the MEB about a quality defect

A marketing authorisation holder must always report a quality defect to the MEB. The marketing authorisation holder is obliged to do so under Article 49, paragraphs 3 and 4 of the Medicines Act.

It is important to inform the MEB of a quality defect of any medicinal product for which a marketing authorisation has been issued in the Netherlands. The MEB can subsequently initiate the necessary regulatory actions.

The marketing authorisation holder must report the quality defect to the Medicine shortages and defects notification centre.

GMP guidelines

The principles of GMP are set out in Commission Directive 2003/94/EC.