Pharmacovigilance Inspections Report

Recommendation

6/7 June 2023

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The MHRA GVP inspectorate recently published the latest pharmacovigilance (PV) inspection report for the period from April 2020 to March 2021. The inspection metrics have been published since 2009 and are based on PV inspections carried out annually. They include information on

• the number and type of marketing authorization holders (MAHs) inspected,
• the areas associated with common inspection findings,
• the number of critical, major and minor findings.

Following the Brexit, the UK entered a transition period where Union law continued to apply and therefore inspections continued to be conducted in accordance with EU regulations (until 31 December 2020). Since the end of the transition period, inspections have been conducted in accordance with the Human Medicines Regulations 2012 (HMR) and GVP Module III, as modified by the "Exceptions and modifications to the EU guidance on good pharmacovigilance practices that apply to UK MAHs and the licensing authority".

Remote Inspections

All inspections in 2020/21 were conducted remotely due to the ongoing COVID-19 pandemic. Routine inspections were prioritized based on areas of highest risk to patients and public health. In addition, the majority of the routine inspections were focused on core PV activities (i.e. collection of safety information, management and reporting of adverse drug reactions (ADRs), aggregate reporting and signal management).

According to the MHRA, remote inspections were made possible by using online platforms that facilitated document sharing and video conferences, for which both inspectors and inspected organizations could securely access. A number of different remote inspection approaches were piloted to determine the most suitable approach. These approaches included inspections comprised entirely of document review, with no interviews with company staff, and inspections spread over several weeks. However, in the end, the preferred inspection mode was a hybrid approach which consisted of targeted interviews conducted remotely and review of data and documents. "The experience and learnings from the remote inspections completed during the pandemic will likely shape alternative inspection approaches in the future", says the agency.

Types of Inspections & Summary of Findings

In total, 37 inspections of 36 MAHs were conducted during this reporting period. Five inspections were conducted due to a previous critical finding, 16 were "for cause" inspections and 16 inspections were planned as part of routine inspection scheduling. The majority of inspections were focused on routine PV activities.

The largest number of all findings (regardless of grading) related to the quality management system (QMS), followed by risk management, and ongoing safety evaluation. These three topics also had the highest proportion of findings in the previous reporting period (2019/20). In detail, the following findings have been observed:

• Critical findings
  5 critical findings were identified:
  - Two were in relation to risk management (maintenance of reference safety information, implementation of additional risk minimization measures), 
  - Two for ongoing safety evaluation (signal management, periodic safety update reports),
  - One was reported for the management of ADRs (case processing activities).
  
  
• Major findings
  In total, 59 major findings were identified. The largest proportion of findings was reported in relation to
  - risk management & management of ADRs, followed by
  - ongoing safety evaluation & the QMS.
  
  
• Minor findings
  76 minor findings were identified during this reporting period. The largest proportion of minor findings was in relation to the QMS followed by risk management, ongoing safety evaluation and management of ADRs.

There were four inspections where no findings were reported. These inspections had a targeted scope, focusing on one specific technical area.

Routine Inspections & Routine Pharmacovigilance Activities

The majority of findings identified from routine inspections within routine PV activities were relating to the QMS. Within this topic, most findings were reported under the subtopic of audit and deviation management (including CAPA management). Such findings included:

• Significant delays to issue PV related audit reports, leading to delays in investigating associated non-compliance.
• No documented audit strategy or risk-based assessment for audit planning.
• Critical PV processes or internal PV processes were not taken into account for the audit strategy.

The greatest number of major findings was reported for ongoing safety evaluation, e.g. deficiencies with signal management processes and periodic safety update reports (PSURs). One major finding was reported in relation to clinical trial pharmacovigilance. For management of ADRs, most of the findings were related to the subtopic of case processing (data entry, coding, assessment, follow-up and reporting).

For more detailed information please see the Pharmacovigilance inspection metrics report for April 2020 to March 2021 in the MHRA Inspectorate Blog.