UK Pharmacovigilance Inspectors Report Drop In Critical Findings For Third Year In Row
Executive Summary
For the first time in nearly a decade, UK pharmacovigilance inspectors have not issued any critical findings in relation to reference safety information, but RSI continues to draw major findings.
The UK Medicines and Healthcare products Regulatory Agency has reported a drop in the number of critical findings from good pharmacovigilance (GPvP) inspections for the third consecutive year.
Approximately, one in every seven inspections that the MHRA conducted between April 2017 and March 2018 resulted in a critical finding, compared to one in six in 2016-2017 and one in three in 2016-2015, said Mandeep Rai, operations manager at the MHRA's GPvP Inspectorate.
The decline in the number of critical inspections is good news, according to Rai, who was speaking at the MHRA's 2018 Pharmacovigilance Symposium in London on May 3. "Hopefully, this means that compliance is generally improving and there is a positive trend," she said of the reports of critical findings, which represent a serious violation of applicable legislation and guidelines.
The figures from the inspections undertaken in 2017-2018 are not final as several inspections are still open, Rai clarified. But they indicate "a steady progression to positive compliance" by companies. The final metrics will be published on the MHRA's website later this year.
Regarding the number of critical findings reported, four were reported from the 22 inspections in 2017-2018, six were reported from the 36 inspections in 2016-2017, 11 from the 34 inspections in 2015-2016, 27 from the 47 inspections in 2014-2015, and 18 from the 56 inspections in 2013-2014.
Inspection figures indicate a steady progression to positive compliance by companies – Mandeep Rai, operations manager, MHRA's GPvP Inspectorate
Of the four critical findings reported in 2017-2018, two related to risk management, one related to signal management and the other concerned the supervision and oversight of the pharmacovigilance system. By contrast, signal management was an area of high concern in 2016-2017, resulting in two critical findings.
Looking at the inspection metrics for the last six years, Rai said the most common critical findings have related to shortfalls in signal management and reference safety information (RSI). Non-compliance in these areas often lead to problems such as delays in the identification of new risk information or no action being taken on new information. "These kinds of issues pose significant risk to patients and, therefore, are more likely to meet the criteria for a critical finding. So it is no surprise that these two topics have been the leaders on the board for a while," she said.
The figures from 2017-2018 mark the first time in nearly 10 years that the MHRA has not come across any critical findings in relation to RSI. "That's really positive," said Rai. RSI had also become a hot topic during Good Clinical Practice inspections in 2016, when EU clinical trial sponsors became inundated with objections from regulators across Europe on this front, resulting in their trials being delayed. (Also see "UK MHRA Takes Companies To Task Over Trial Safety Information Reporting" - Pink Sheet, 4 Nov, 2016.)
Table 1. Overview of GPvP inspection findings from MHRA's annual inspections
|
Reporting Period |
Inspections Undertaken |
Critical Findings |
Major Findings |
Minor Findings |
|
April 2017-March 2018* |
22 |
4 |
Data Unavailable |
Data Unavailable |
|
April 2016-March 2017 |
36 |
6 |
150 |
84 |
|
April 2015-March 2016 |
34 |
11 |
94 |
111 |
|
April 2014-March 2015 |
47 |
27 |
169 |
155 |
|
April 2013-March 2014 |
56 |
19 |
192 |
172 |
* Figures are not final as several inspections are still open
Source: MHRA
Major Findings On The Rise
While the number of critical findings have continued to decline over the past few years, there has been an increase in the number of major findings reported. The MHRA regards major findings as those that could potentially pose a risk to public health, or potentially adversely affect the rights, safety or well-being of patients or represent a violation of legislation and guidelines.
Rai explained that most of the inspections now identify four to five major findings. "Although RSI is not such a critical issue anymore, we are reporting a higher number of major findings in this area," she said.
While the figures on major findings reported in 2017-2018 are not available yet, the MHRA reported 150 major findings from the 36 inspections in 2016-2017 – an increase of approximately 60% compared with 2015-2016 when the MHRA reported 94 major findings from 34 inspections.
The three areas that contributed to an increase in major findings in 2016-2017 were:
1) Quality assurance and quality systems, which together accounted for nearly 27% of all major findings: Regarding quality assurance, MHRA inspectors detected issues such as inadequate procedural support for critical pharmacovigilance activities, inadequate training of personnel conducting critical pharmacovigilance activities, and problems with the management of pharmacovigilance records.
With respect to quality assurance, inspectors detected audit-related issues, such as critical aspects of the pharmacovigilance system not being subjected to an audit, incomplete risk assessments for scheduling audits, and auditors not having sufficient pharmacovigilance expertise. Major findings issued also related to how marketing authorization holders (MAHs) managed non-compliance and their failure to implement effective and timely corrective and preventive action plans.
To ensure compliance, Rai said when non-compliances, deviations or near misses are identified, companies should document these properly (including in the pharmacovigilance system master file (PSMF), conduct a full root cause analysis, undertake further assessments and an impact assessment, escalate the issue if required, and plan resources accordingly.
2) RSI and signal management, which comprised 11% of all major findings: With respect to RSI, Rai said inspectors were still seeing issues associated with failure or delays in submitting safety variations, and delays in making changes to the safety sections of the summary of product characteristics.
When examining compliance on this front, Rai explained that inspectors look at timelines and check whether safety changes are being detected through the signal management process and implemented through necessary variations. Inspectors also examine the interface between various departments at a company – such as pharmacovigilance, medical and regulatory affairs – to check whether there is good coordination to implement any necessary changes in the manufacturing process, public facing websites and with regard to the dissemination of information to sales forces. "Consideration should also be given to assessing the impact of these changes on other safety-related communication, such as risk management plans, abbreviated prescribing information and other documents such as investigator brochures and informed consent forms," she added.
3) Oversight and supervision of the pharmacovigilance system: Rai said the MHRA had seen instances of the MAH failing to support the qualified person for pharmacovigilance (QPPV), particularly with respect to oversight of some pharmacovigilance processes conducted by third-party service providers. The MHRA has also come across instances of deficiencies in the maintenance of the PSMF and the Article 57 database, which can impact the MAH and national competent authority’s ability to oversee and supervise the pharmacovigilance system.
From the editors of Scrip Regulatory Affairs.