EU Regulatory Roundup: EMA shares advice on validated computer systems used in clinical trials

Regulatory NewsRegulatory News
| 16 April 2020 | By Nick Paul Taylor 

Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA shares advice on validated computerized systems used in clinical trials
The European Medicines Agency (EMA) has published a notice about validating and qualifying all types of computerized systems used in clinical trials. EMA released the notice in response to “recent inspection findings” and their implications for the “integrity, reliability, robustness and acceptability of data.”
Computerized systems such as electronic case report forms and clinical trial management systems are now critical to the conduct of clinical trials and the collection of the data they generate, making the performance of the technology a key enabler of regulatory compliance.
EMA inspectors have found some sponsors are unable to provide the documentation needed to show their systems are qualified and validated. The advice published by EMA reminds sponsors that they are responsible for validating systems and providing associated documentation. Sponsors can use documents provided by the technology vendor to show the system has been qualified.
Another section of the EMA document emphasizes the need for “clear, written agreements” between sponsors and vendors. If the policies of a vendor make it impossible to establish a suitable contract, the sponsor must not use its technology in clinical trials. EMA is steadfast in its opposition to the use of technology provided by such vendors.
“[The ban] is irrespective of the number of sponsors making use of or having used the systems, the number of years such systems have been on the market etc., as serious GCP non-compliances and risks to data integrity, reliability and robustness could exist unnoticed if auditors and GCP inspectors are not allowed access as well as if potential serious breaches are not escalated appropriately by the vendor,” EMA wrote.
EMA published the new document in conjunction with an update to a question and answer page about good clinical practices. The updated questions cover the pitfalls of contractual arrangements with vendors of computerized systems and the level of validation and qualification EMA expects of sponsors that source technology from third parties.
EMA Notice, Q&A
MHRA posts guide to approving GxP documents while working from home
The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has published guidance on how people can approve paper good practice documents while working from home.
Organizations have told MHRA that processes that rely on wet ink signatures of paper documents are impossible to execute as staff are working from home due to the COVID-19 pandemic. The problem is affecting documents related to good practices in areas including manufacturing, distribution, clinical and laboratory.
In its public response, MHRA notes that many companies already have systems in place that support the remote electronic signing of documents. Such companies should continue to use those systems.
If a company lacks such a system, MHRA is open to them establishing alternative workflows that use the technologies they have available. Whether workers have access to printers, scanners, secure mail, smartphones or other technology will dictate the exact nature of the alternative workflows.
Recognizing that, MHRA has opted not to take a prescriptive approach, choosing instead to share principles that apply in all situations and risks to consider when remotely approving documents. The principles state controls should be proportionate to the risk, remotely issued signatures should be equivalent to handwritten signatures and the process should minimize the risk of misunderstanding.
MHRA Guidance
Major findings in MHRA pharmacovigilance inspections rise to new high
The number of major findings identified during MHRA pharmacovigilance inspections has hit a new high. On average, MHRA found almost 4.5 major pharmacovigilance problems in each inspection it conducted in the 2018 to 2019 financial year, more than twice as many as a decade earlier.
Data tracked by MHRA shows inspectors found up to 3.5 major failings per inspection in the decade starting in 2006. In 2009, the average number of major findings fell to two. After that, the figure rose steadily, with one downward blip in 2015, before plateauing at four major findings per inspection in 2016 and 2017. In 2018, the figure rose again.
The MHRA report featuring the data lacks an explanation for the trend but does include a breakdown of the types of issues that resulted in major findings. MHRA found at least one major failing at every inspection it conducted in 2018.
Risk management remained the most common cause of major findings, although its share of all the issues identified by MHRA fell year on year. MHRA also tracked a sharp decrease in noncompliance related to the quality management system. Those trends were offset by increases in problems linked to the collection and collation of adverse drug reactions and the management of adverse reactions.
The rise in major findings is an outlier in a dataset that is largely consistent with previous years. The number of critical and minor findings has remained in a narrow band over the past decade, as has the average number of inspection findings of all types. The total number of findings per inspection remains well down on the averages for 2006 to 2009.
MHRA Report
Dutch MEB tracks doubling in reports of potential drug supply problems
The Dutch Medicines Evaluation Board (MEB) has reported a sharp increase in reports of potential medicine supply shortages. MEB received reports of supply disruptions affecting 1,965 drug products last year, up from 1,029 in 2018.
Not all of the disruptions detailed in the reports will have led to shortages, and some of the increase in annual reports can be explained by better awareness of the system and greater willingness among companies to give MEB advanced warning of a potential problem. MEB said a solution was found for almost all shortages in 2019, although it acknowledges the workarounds can inconvenience patients.
MEB shared a breakdown of why problems are arising. More than half, 58%, of reports filed in 2019 related to production delays, quality control or drug release. Rising demand due to a shortage of a rival product was another frequently cited issue.
The sartan contamination problem also had an impact. MEB linked 8% of the reports to recalls such as the removal of sartan medicines from the market in response to evidence of contamination with a carcinogen.
MEB Notice (Dutch)
Finland restricts delivery of asthma drug to counter COVID-19-fueled stockpiling
The Finnish Ministry of Social Affairs and Health has restricted the sale of salbutamol asthma drugs to stop people building up “large at-home stocks.” 
In disclosing the restrictions, the Finnish Medicines Agency (Fimea) said medicine availability in the country is “at a fairly good level.” However, COVID-19 has caused an increase in use of certain drugs and, in Fimea’s words, “led to the inappropriate purchase of medicinal products among pharmaceutical users.”
Fimea wants to stop inappropriate purchases to avoid peaks in demand that may make it impossible for some people to access products they need. The restrictions are intended to achieve that goal by stopping people from buying more than one month’s worth of salbutamol products.
Finnish authorities are also seeking to stop bottlenecks emerging in other parts of the supply chain. For example, Fimea has stepped up its oversight of the orders pharmacies place with wholesalers to ensure they are not placing “unnecessarily large” requests for new stock. 
Fimea Notice
Other news:
Ireland has created an expedited regulatory and ethical review process for research related to COVID-19. HPRA Notice


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy