Inspections relating to manufacturer’s authorisations

Manufacturers of medicines are regularly inspected by the HPRA’s GMP inspectors using a risk based approach to ensure compliance with GMP standards.

The HPRA is responsible for conducting inspections to determine whether manufacturing operations are in compliance with the EU Guide to Good Manufacturing Practice (GMP). In addition to routine inspections to determine ongoing compliance, non-routine (for cause) inspections may be performed, for example, in relation to a variation application or a serious quality defect.

Manufacturers located in Ireland are inspected on a routine basis, every 2 – 3 years. The frequency of inspections may increase depending on the activities of the site and the findings of previous inspections. A copy of the risk-based planning form can be requested upon close out of the inspection by contacting inspect@hpra.ie. The HPRA also conducts inspections of manufacturing sites located in third countries where it is a supervisory authority for the site concerned. The HPRA is deemed to be the supervisory authority when the site of batch certification for the imported product is located in Ireland.  The HPRA may also carry out inspections of third country manufacturers where the inspections have been delegated by a supervisory authority in another Member State. Third country inspections of manufacturing sites may also be requested by the European Medicines Agency (EMA).

Routine inspections of manufacturers located in Ireland follow the following procedure:

Notification of inspection:

The company will be notified usually 6 weeks prior to the proposed inspection date.

Inspection:

HPRA inspectors will perform the inspection. The duration of the inspection and the number of inspectors present on an inspection will vary depending on the complexity of the activities conducted at the site.

Issuance of a report

Following inspection, a report is issued to the inspected site with a conclusion regarding compliance with GMP. Deficiencies are classified into three categories; critical, major and other. A summary for the criteria for judging deficiencies as critical, major or other are detailed below. For the full definition please refer to the EMA compilation of community procedures on inspections and exchange of information.

  • Critical Deficiency:

    A deficiency which has produced, or leads to a significant risk of producing either a product which is harmful to the human or veterinary patient or a product which could result in a harmful residue in a food producing animal.

  • Major Deficiency:

    A non-critical deficiency: which has produced or may produce a product, which does not comply with its marketing authorisation

    or

    which indicates a major deviation from EU Good Manufacturing Practice

    or

    (within EU) which indicates a major deviation from the terms of the manufacturing authorisation

    or

    which indicates a failure to carry out satisfactory procedures for release of batches

    or

    (within EU) a failure of the Qualified Person to fulfill his legal duties

    or

    a combination of several “other” deficiencies, none of which on their own may be major, but which may together represent a major deficiency and should be explained and reported as such.

  • Other Deficiency:

A deficiency, which cannot be classified as either critical or major, but which indicates a departure from good manufacturing practice.

(A deficiency may be “other” either because it is judged as minor, or because there is insufficient information to classify it as a major or critical).

Inspected sites are requested to reply to the deficiencies stating proposed /actual corrective action(s) relating to the individual deficiency and date(s) for completion of the corrective action(s). It is expected that any critical or major findings are addressed immediately.

Company response to report and close out

The company must provide a response to the deficiencies and points to note outlined in the inspection report. The responses are reviewed by the inspection team to determine whether or not they are acceptable. A GMP certificate may be issued with the inspection report where no critical or major deficiencies were observed. In other cases a GMP cert will be issued upon receipt of responses which have been deemed acceptable. Where responses are deemed unacceptable a statement of non-compliance may be issued.