What Do The 2017 MHRA Pharmacovigilance Metrics Say About Data Integrity?
Written by Arkivum VP Health & Life Sciences Daniel Hickmore
This year’s MHRA Pharmacovigilance Inspection Metrics Report provides more food for thought among those of us working in the area of data integrity within the pharmaceutical industry.
The headline summary of this year’s report on the MHRA’s investigations into UK marketing authorisation holders (MAHs) is that six critical, 150 major and 84 minor findings were identified between April 2016 and 2017. Of those six critical findings ‒ the ones that can halt the stride of even a towering pharma giant ‒ two were in signal management, then one each in reference safety information, supervision and oversight, non-interventional programmes and system failure.
As the MHRA itself notes, this represents a further decrease in critical findings, with 11 reported in the previous year. However, the report makes no conclusive statement on why that might be, suggesting only that there may be a “positive trend towards compliance”.
So what does this mean for those of us in the industry who are embedding best practices in data integrity and information management?
Let’s look more closely at the areas where critical and major findings were most prevalent this year:
Data Integrity in Signal Management
Two of this year’s six critical findings were in this area, compared to only one last year. The report points to a “repeated failure to include all available safety data in signal detection activities” in one case, and in the other, “inadequate document control for safety reviews”. Signal management also represented 11% of major findings.
Underlying these failings are inaccuracies and data management processes that fall short of the ALCOA (Attributable; Legible; Contemporaneous; Original; Accurate) framework that MHRA recommends for safeguarding data integrity.
Data Integrity in Reference Safety Information
One of this year’s six critical findings was in reference safety information. Here, the lack of data integrity and systematic document control led to a situation where clinical safety was severely compromised, with out-of-date product characteristics and superseded patient information remaining publicly available on a corporate website.
Patients were put at risk with the absence of special warnings, precautions and contraindications for many products. 17 of this year’s major findings (11%) were in the area of reference safety information. This is a significant increase from last year, when only seven major findings were in this area.
Data Integrity in Supervision and Oversight
This year’s one critical finding in supervision and oversight indicates a failure to make appropriate safety data, records and documentation available. In last year’s report, supervision and oversight represented the largest proportion of critical findings, and “provision of complete and accurate information to national competent authorities” came in for a special mention from the MHRA.
Data integrity is essential in this area. There needs to be a failsafe mechanism in place that brings together all the data and documents related to the audit trails ‒ a real problem when up to 70 systems with 40 years’ of data are involved ‒ and make them available to the inspectors. Extending best practice to outsourced agencies is another difficulty, one that the MHRA report references.
Data Integrity and Pharmacological System Failures
In line with last year’s report, there was one critical system failure finding this year. The global pharmacovigilance system in question had failed to comply with EU and national legislation ‒ the report described this as a “serious breach”.
Data integrity at a system level involves collecting and collating safety information into an archive repository. Without that, the MAH in question had failed to:
- Report serious suspected adverse reactions to the Agency
- Carry out product safety evaluations
- Provide for system maintenance and oversight
Data Integrity in Quality Management
One particular striking finding in this year’s MHRA metrics was that major findings in the area of quality management are up by 82% compared with 2015-2016. This equates to 40 major findings, compared to 22 last year. The report noted poor implementation of risk-based audits of the pharmacovigilance system and management of non-compliance.
Capturing audit information and maintaining its credibility across multiple systems is a known problem in the pharmaceutical industry, and the MHRA found several instances of this deficiency.
What Is the Direction of Travel in MHRA Inspection Metrics?
Improvement over time seems slight, although there was a significant decrease in critical findings this year of almost 50%, as we’ve mentioned.
So what are the data integrity lessons we should take away? Data integrity is certainly a talking point in today’s pharmaceutical industry. It really is striking how many MHRA findings come down to data integrity. And more than that, it’s clear that it’s top of mind for inspectors at the MHRA and elsewhere. We know anecdotally that if data integrity issues arise during an inspection, then regulators will dig deeper.
Today’s regulatory inspectors are a new breed. No longer satisfied with paper-based record management, they are digital first and hands on in their approach. They have business intelligence expertise, and the younger ones are particularly keen to access electronic records themselves and analyse them.
This is a tricky cultural change for many in the pharmaceutical industry, where risk-based thinking can easily give rise to change aversion. But most, if not all, of the professionals in the sector that we speak to recognise that digital is here to stay. Mindful of the devastating effects of regulatory action such as an MHRA critical finding, are keen to find a way forward.
Meeting the Pharmacological Data Integrity Challenge
We speak with pharmaceutical decision-makers about archiving and preservation strategies and how best to manage metadata. We also explain that data integrity is about so much more than compliance management ‒ important though that is when it consumes up to 25% of pharma businesses’ operating costs.
When data integrity is in place, it safeguards patient safety and clinical excellence, and gives real-time clarity to clinical decision-making.
In its draft GxP Data Integrity Definitions and Guidance for Industry, the MHRA can be surprisingly pragmatic ‒ saying, for example, that companies should balance data risk with other quality and compliance issues. However it is insistent on the implementation of a “fully documented system that provides an acceptable state of control based on the data integrity risk with supporting rationale”.