Inspections relating to Good Distribution Practice (GDP)

Distributors of human medicines and active substances are regularly inspected by HPRA GDP inspectors using a risk based approach to ensure compliance with GDP standards.

The HPRA is responsible for conducting inspections to determine whether wholesaling operations, including procurement, holding, supply and export of Human medicinal products and active substances, are in compliance with the EU Guidelines on Good Distribution Practice of medicinal products for human use and the EU Guidelines on Good Distribution Practice of active substances for medicinal products respectively.  It also reviews that requirements as detailed in the HPRA guide to registration requirements for active substance manufacturers, importers and distributors in Ireland are met.

Distributors located in Ireland are inspected on a routine basis to ensure compliance with GDP. 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 where the risk associated with the proposed new operation (e.g. distribution of cold-chain products) is deemed high. The frequency of inspections may increase depending on the activities of the site and the findings of previous inspections. 

The HPRA operate a system of risk based inspection planning. Scheduling of inspections is dependent on compliance risk (level of compliance in the last inspection) and intrinsic risk which is determined based on the complexity of the wholesale operations and criticality of the products.

Remote Inspections / Distant Assessments 

The HPRA has initiated a process to conduct inspections remotely via distant assessment. The requirement to conduct a distant assessment will be determined on a case-by-case basis.

Notifications will be sent in advance of the distant assessment in the same way as for an on-site inspection. The distant assessment process will, in general, follow a similar format to that for an on-site inspection and will commence with an opening meeting and conclude with a closing meeting via videoconference or alternative remote communication platform.

The communication platform used will be particularly important to facilitate the smooth running of the distant assessment. The sites hosting the distant assessment will be requested to propose a suitable communications platform and this will be agreed with the Inspector in advance of the distant assessment. The process will require electronic copies of documents and other information to be provided to the Inspector for review. Consideration should be given to the use of platforms that provide for live sharing of documents and videos, in addition to the use of cameras to allow for a virtual review of physical facilities, equipment and wholesaling operations, where applicable.

To avoid delays during distant assessment, companies will be requested to make certain documentation available prior to the commencement of the distant assessment. Documentation requirements will be specified in the pre-distant assessment notification. In certain circumstances, a distant assessment on its own may not be sufficient to enable a decision to be made regarding the level of compliance with GxP requirements and, as such, an on-site inspection may be performed at the earliest possible time. It is envisaged that this would generally focus on areas of the site that could not be inspected remotely and/or areas requiring further follow-up resulting from the distant assessment.

Inspections related to new applications for wholesale distribution authorisations (WDAs):

An inspection is conducted as part of the assessment for a new WDA application. Depending on the scope of the application additional supporting information may be requested to ensure proposed activities meet the definition of wholesaling as specified in the EU Guide to GDP and in the Medicinal Products (Control of Wholesale Distribution) Regulations 2007, as amended, i.e. procure, supply, holding and export. Further detail on information that may be requested as part of the application process is detailed in the HPRA Guide to New applications and variations to Wholesale Distribution Authorisations.

Following the first inspection to assess an application, the second inspection of a site will be performed within 12-18 months.

Routine inspections to assess compliance with GDP in Ireland follow the following procedure:

Notification of inspection:

The company will be notified by email typically 6 weeks prior to the proposed inspection date. The email notification will include the name and number of inspectors, duration of the inspection and a list of documents the company should prepare in advance of the inspection.

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 and the findings of previous inspections. The inspection will focus on the quality management system in place, review of storage areas and associated validation of equipment as applicable. A review of records is typically completed to ensure compliance of operations with the requirements of European Union GDP. Staff assigned to GDP operations will also be interviewed as part of the inspection.

Issuance of a report:

Following inspection, a report is issued to the inspected site where 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.

Critical Deficiency:

Any departure from Guidelines on Good Distribution Practice resulting in a medicinal product causing a significant risk to the patient and public health. This includes an activity increasing the risk of falsified medicines reaching the patients. A combination of a number of major deficiencies that indicates a serious systems failure. An example of a critical deficiency could be:

• purchase from or supply of medicinal products to a non-authorised person
• storage of products requiring refrigeration at ambient temperatures
• rejected or recalled products found in sellable stock. 

Major Deficiency:

A non-critical deficiency:

• which indicates a major deviation from Good Distribution Practice;
• or which has caused or may cause a medicinal product not to comply with its marketing authorisation in particular its storage and transport conditions;
• or which indicates a major deviation from the terms and provisions of the wholesale distribution authorisation;
• or a combination of several other deficiencies, none of which on their own may be major, but which may together represent a major deficiency. 

Other Deficiency:

A deficiency which cannot be classified as either critical or major, but which indicates a departure from Guidelines on Good Distribution Practice.

Inspected sites are requested to reply to the deficiencies stating proposed /completed 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 for clarification outlined in the inspection report. The responses are reviewed by the inspection team to determine whether or not they are acceptable. Further correspondence between the HPRA and the company may be required until satisfactory actions are agreed.  A GDP certificate will be issued on the EudraGMDP database if all actions proposed by the company in response to the deficiencies cited are deemed acceptable. Where the inspection has identified significant deficiencies a statement of non-compliance with GDP may be issued. Further information on GDP  certificates of compliance and of non-compliance can be found on the EMA website. Authenticity of GDP certification may be verified on the EudraGMDP database. The HPRA will not routinely issue hard copies of GDP certificates.  Hard copies of GDP certificates may be requested via the export certification process, details of which may be accessed via the Export Certification page.