On the 26th February, the Medicines & Healthcare products Regulatory Agency (MHRA) released their latest update in series of guidance documents for industry organisations and professionals in the United Kingdom (UK) relating to Pharmacovigilance Inspection Metrics.
In summary of their MHRA Report, the MHRA have added the latest Pharmacovigilance Inspection Metrics Report: April 2019 – March 2020, with insight into both the number and type of Marketing Authorisation Holders (MAHs) inspected by the Good Pharmacovigilance Practice (GPvP) inspectorate; information relating to common areas and trends for inspection findings, as well as the range of minor, major and critical findings during this period.
The MHRA outlined that the 22 MAHs selected for inspection during this period were selected via the use of risk-based methodology, consisting of factors ranging from the complexity of the pharmacovigilance system; nature, complexity, size and compliance history of companies within the system, as well as product specific factors – all in agreement with GVP Module III.
The report refers to data collected during the period of 1st April 2019 – 31st March 2020; recognising significant macro-environmental impacts, such as the UK’s departure from the European Union (EU) in January 2020.
Types of Inspections
With regards to the types of inspections carried out during this period, the MHRA outlined that 5 (22.7%) were conducted due to critical findings in previous inspections, 1 due to intelligence received and 16 (73%) as part of routine inspection scheduling – 4 of which having never been inspected previously, 12 being re-inspections and all being a balanced blend of innovative or generic pharmaceutical organisations.
Overview of Findings
From these inspections, the MHRA have provided overviews for minor, major and critical findings during this period.
Within the report, a total of 46 minor findings raised during this period – a 120% increase on the previous reporting period, with the most common areas for minor findings outlined as the following:
- Quality Management System (26%)
- Risk Management (26%)
- Ongoing Safety Evaluation (15%)
- Management of Adverse Drug Reactions (13%)
- Collection and collation of Adverse Drug Reactions (13%)
- Other (7%)
With regards to major findings, whilst it is worth noting that 1 inspection raised 0 findings, it can be seen that a total of 76 major findings were raised during this period – an average of 1-7 findings per inspection. The most common areas for major findings were:
- Risk Management (30%)
- Quality Management System (26%)
- Ongoing Safety Evaluation (18%)
- Management of Adverse Drug Reactions (17%)
- Other (8%)
A total of 5 critical findings were found during this period – all of which were in the area of risk management and can be broken down into the following areas:
- Maintenance of reference safety information (3)
- Implementation of addition risk minimisation measures (1)
- Management of additional pharmacovigilance activities in Part III of RMP (1)
Risk management was a notable area in this report, and was cited as the leading cause of critical findings, with a distinct increase during this period (5 critical findings) compared to the periods 2015-2019 (1-2 critical findings per metric period). However, it is worth noting that this remains less than what has been previously recorded in the periods 2012-2015 (approx. 8-10 critical findings per metric period).
The leading cause of major findings during this period was also Risk management (30%, up 9% from the previous metrics period) and the joint leading cause of minor findings (26%, up 10% from the previous metrics period).
In correlation with the critical findings during this period, it can be seen that failing to update RSI and failing to comply with PASS obligations were highlighted by the MHRA as the overall leading causes for risk management findings, with the next biggest cause being failures in the implementation of risk management measures.
The MHRA noted that whilst they use additional risk management measures as a means for prioritising inspections, the critical findings in the current metrics period were largely about routine risk management measures.
Quality Management Systems
Quality Management Systems was also a topic highlighted within this report.
Whilst there were no critical findings for quality management systems during this period, the area was found to be the second largest cause of critical findings overall as, when reviewing critical findings between 2012-2020, this area yielded no more than half the number of critical findings of risk management.
As for major findings, quality management systems were again the second largest during this period (26%, up 11% from the previous metrics period), behind risk management, and the joint leading cause of minor findings (26%, up 8% from the previous metrics period) alongside risk management.
CAPA management was highlighted by the MHRA as the leading cause of quality management system findings and, more specifically, failure or delays in developing CAPAs; failure to close CAPAs on time, and CAPAs not properly addressing root causes of deviations.
Incomplete or incorrect PSMF annexes were cited as the second leading cause of quality management system findings; particularly Annex B (lists of contracts and agreements) and H (list of products covered by the pharmacovigilance system).
Ongoing Safety Evaluation
Despite ongoing safety evaluations not being specifically highlighted by the MHRA, it is worth noting that this was the third most significant source of findings during this period.
Whilst there were no critical findings during this period for ongoing safety evaluation, this area remained the third biggest cause of critical findings overall. However, this topic still has less than half the number of critical findings of risk management, and there have been no critical findings for quality management systems since 2018.
Ongoing safety evaluation findings were the third biggest cause of major findings during this period (18%, down 1% from the previous metrics period) and the second leading cause of minor findings (15%, with no figure provided for the previous metrics period).
Management of ADRs
Whilst the management of ADRs was also not specifically highlighted by the MHRA, this was the fourth most significant source of findings during this period.
Management of ADRs provided no critical findings in the current metric period, but remained the fourth biggest cause of critical findings. However, this topic has considerably less critical findings than the 3 areas above, with no critical findings having been cited since 2016.
Management of ADRs was the fourth biggest cause of major findings in the current metrics period (17%, up 3% from in the previous metrics period) and the fourth leading cause of minor findings (13%, with no change from the previous metrics period).
PharSafer always carefully monitor the results published by varied regulatory authorities, regarding both pharmacovigilance as well as good clinical practise inspections, in order to ensure that not only is PharSafer interpreting the regulations correctly but also that any findings can be communicated with our clients; so that it is clearly understood what needs to be performed in these disciplines, in order to operate a compliant system.
It is clear from these findings that there are various areas that are being exposed in terms of the lack of adherence to the regulations, with the quality management system featuring heavily in all grades of findings.
In addition, errors at the start of the process with case handling are also prevalent and this is not surprising in view of the very manual approaches required at present by companies in terms of their case processing systems.
The opportunities to remove some of these findings through automation and monitoring have never been greater and, with that, PharSafer have invented a whole new system for case processing; with not only high degrees of automation but also intelligence in recognising potential case errors.
The speed with which case processing can be done under the PharSafer RAPTAR system will also allow staff greater freedom in ensuring quality management is improved and other areas such as risk management and minimization can be properly resourced.
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PharSafer will continue to monitor updates made to guidance released by the MHRA and other Regulatory Agencies and communicate any new information as it becomes available.