MHRA Pharmacovigilance Inspection Metrics

The MHRA GPvP inspectorate recently published their latest inspection metrics for the period from April 2017 to March 2018. Since starting in 2009, the pharmacovigilance inspections metrics have been carried out annually.

During the period 1 April 2017 to 31 March 2018, the MHRA’s Good Pharmacovigilance Practice (GPvP) inspectorate conducted 22 inspections of marketing authorization holders (MAHs). The purpose of these inspections was to examine compliance with existing EU and national pharmacovigilance regulations and Good pharmacovigilance practice (GVP) guidelines. The number of inspections conducted during this period was fewer than in previous years with an overall increase in duration of each inspection. According to GVP Module III, the inspection schedule is developed using a risk-based approach. The increasing days spent per inspection can be attributed to the risk factors considered to compile the inspection. Key risk factors reviewed during the development of the inspection programme for 2017/18 were:

• Product risk,
• Complexity of the pharmacovigilance system (PS),
• Complexity and size of the organization(s) involved,
• Compliance and inspection history of an organization.

Categorization of findings

Four critical findings were identified during this reporting period. The critical findings were issued from three inspections. They were broadly associated with:

• Risk management (2),
• QMS, Quality management system (1),
• Ongoing safety evaluation (1).

In Addition, in these three inspections, there were also several major findings reported in other areas of the PS.

Furthermore, 89 major findings were identified in total and at least one major finding was reported in every inspection. The number of major findings reported ranged between one and eight. The topic with the highest proportion of major findings in the reporting period was

• risk management (25%) [e.g. maintenance of risk management plans (RMPs) and reference safety information (RSI)], followed by
• noncompliance in the QMS (21%) [e.g. procedures, record management, training, contracts; audit and deviation management, including CAPA management; PV system oversight and governance, including performance monitoring and role of the QPPV; information technology systems and applications], and
• ongoing safety evaluation (18%) [e.g. signal management, periodic safety update reports (PSURs)],
• Major findings for the provision of information for supervision by NCAs and inspection (16%) [e.g. inspection readiness, submission of information to NCAs, maintenance of information in XEVMPD],
• Management of adverse drug reactions (12%) [e.g. case processing: data entry, coding, assessment, follow-up and reporting; data management, including migration of safety data],
• Collection and collation of adverse drug reactions (7%) [e.g. spontaneous sources of safety data, like medical information, product quality complaints; literature searching; safety data exchange agreements].

There was a single major finding reported as ‘other’, which related to pharmacovigilance for biological medicines and resulted from failures to comply with the specific requirements in GVP chapter PII (Product- or population-specific considerations II: Biological medicinal products). This was not the only finding reported during the 2017/18 period against GVP chapter PII. Other findings in relation to breaches of GVP chapter PII have been reported under the specific area of failing, for example, in meeting the requirements for ongoing safety evaluation for biological medicines.

69 minor findings were reported during the reporting period. The quality management system was the largest proportion (26%) of minor findings, followed by management of adverse drug reactions (17%), risk management - ongoing safety evaluation - provision of information for supervision by NCAs and inspection (14% respectively), collection and collation of adverse drug reactions (9%) and clinical trials pharmacovigilance [e.g. maintenance of RSI for clinical trials, SUSAR reporting] (3%). There was a single finding reported for a minor failing related to management of social media programmes.

In summary, risk management is an area of specific concern.

Findings relating to both routine and additional risk management activities comprised the highest proportion of critical and major findings. According to the agency, the "MHRA GPvP risk-based inspection planning will continue to take product risk into account, with inspections in the programme that can be tailored to review product-specific aspects as well as pharmacovigilance systems".

The full metrics report is available on GOV.UK.