Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
MHRA Updates Guidance on Determining Whether an app is a Medical Device
The United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) has updated its guidance on determining whether an app is classified as a medical device. The new guidance features revised flowcharts to help software developers understand whether an app needs a CE mark.
MHRA released initial guidance on the topic in 2014. The flowchart in that guidance directed users to different regulatory outcomes based on the functions of their apps. MHRA has taken a similar approach to the revised guidance, but changed the details and the packaging. The current version is an interactive PDF that software developers can click through to receive advice on whether their apps are likely to be classed as medical devices. The guidance also features advice for users.
When a software developer opens the PDF, they are asked a series of questions, such as whether their program is incorporated into a device, has a medical purpose or works directly with data obtained in vitro. The idea is to guide users to the regulatory status that applies to their app. Possible outcomes include “not a medical device,” “a medical device accessory” and “an IVD medical device.” MHRA provides details of what each of these designations means for the software developer.
“Where apps or stand-alone software make a diagnosis or recommend a treatment, people should check for CE-marking before using their apps and developers should make sure they are complying with the appropriate medical device regulations,” John Wilkinson, MHRA’s director of medical devices, said.
MHRA Guidance, More
EMA Tells MAHs to Include History of Pharmacovigilance Inspections in Clinical Addendums
The European Medicines Agency (EMA) has added a full history of pharmacovigilance inspections to the list of information marketing authorization holders (MAHs) must include in addendums to clinical overviews. Manufacturers submit these addendums as part of the process of renewing MAs through the centralized procedure.
EMA uses the addendums to assess the data on the risks and benefits of a product that exist at the time of the renewal. As such, it has historically asked MAHs to include details of any actions taken for safety reasons since the last renewal or initial MA. EMA still wants MAHs to provide descriptions of any safety-motivated actions, such as the suspension of a product or halting of a clinical trial, but it now also wants manufacturers to provide details of the global regulatory status of their systems and products.
The regulator wants MAHs to submit a history of regulatory inspections of their pharmacovigilance systems. This submission must include details of which regulator conducted the inspection, on which date and at which of the MAH’s sites. EMA is also demanding details of the type of inspection and the product or products covered by the visit, as well as an analysis of how the findings affect the risks and benefits of the drug that is up for renewal. The second new piece of information requested by EMA is an overview of the countries in which the product is approved and marketed.
EMA informed MAHs of the revised requirements in an update to its question and answer document on renewals. The question on how to present addendums to clinical overviews and other aspects of renewal applications was one of four changed by EMA this month. Many of the changes are minor. For example, EMA has added a clarification that it will not accept renewal applications earlier than 11 months before the MA is due to expire. EMA also now wants to know the reasons for not renewing a MA. In the past, it only wanted an explanation if the decision was not commercial in nature.
The amendments were part of one of two changes to question and answer documents released by EMA this week. EMA’s other updates affected its advice on periodic safety update reports. Again, the changes are relatively minor. Among the more significant changes are revised details about who to contact with questions about fees. In the past, EMA simply referred MAHs to another document. The revised advice document goes further, notably by detailing the information MAHs should include in the queries and the amount of time they can expect to wait for an answer.
EMA Q&A, More
Boehringer, MHRA Share Alert Following Complaints About Heart Attack Drug
MHRA has shared a drug alert from Boehringer Ingelheim, which released the alert in response to complaints about the rubber stopper on a product used in heart attack, pulmonary embolism and stroke patients.
Users alerted Boehringer to a potential problem with the product, Actilyse, after finding the rubber stopper was being pushed into the vial during reconstitution, making the drug unusable. Boehringer provides a transfer cannula for this process and suspects improper use of this equipment is partly to blame for the problems.
In an attempt to stop the issue from recurring, Boehringer and MHRA have released a guide to using the cannula. Using an eight-point list of instructions and a four-frame diagram, Boehringer has tried to walk users through the process of effectively reconstituting Actilyse, from the opening of the blister pack through to the dissolution of the mixture.
Actilyse has a long history of use in the UK and beyond. The drug was introduced in the late 1980s and established itself as part of the pathway for treating heart attacks in the years that followed. In 2012, the UK National Institute for Health and Care Excellence (NICE) expanded use of the drug to the treatment of acute ischemic stroke following a review of the data.
MHRA Adds AbbVie Leukemia Drug to Early Access to Medicines Scheme
MHRA has awarded a positive scientific opinion to Venetoclax, an experimental treatment for chronic lymphocytic leukemia (CLL) in development at AbbVie. The decision grants AbbVie access to MHRA’s early access to medicines scheme (EAMS), enabling patients in the UK to take the unapproved drug.
AbbVie is currently testing Venetoclax in a clutch of clinical trials, either alone or in combination with rituximab. European regulators will need to view data from the pivotal trials before deciding whether to approve it, but MHRA has seen enough in the limited results generated to date to conclude Venetoclax is a suitable candidate for EAMS.
MHRA made the decision after looking over data from three studies, in which 400 mg daily doses of Venetoclax triggered a response in 73% of patients. Most responders continued to feel the benefits for more than one year, and cancer cells became undetectable in some patients. The studies also linked the drug to some severe side effects, but MHRA thinks the benefits outweigh the risks.
The positive opinion adds Venetoclax to a small, elite club. Since starting EAMS in 2014, MHRA has issued fewer than 10 positive scientific opinions and one rejection. Venetoclax joins Bristol-Myers Squibb’s Opdivo, Merck’s Keytruda and Novartis’ Entresto on the list of drugs known to have been accepted onto the scheme.
MHRA Opinion, More
A man in the UK was sentenced to 10 months in prison for illegally importing and selling erectile dysfunction drugs. The legal proceedings followed a raid by MHRA investigators, in which 267,000 doses of unlicensed erectile dysfunction medicines were found in a garden shed. A subsequent analysis found the man had made £27,000 ($36,000) selling 451,000 doses. MHRA Statement
The European Commission has approved Gilead Sciences’ once-daily HIV drug Truvada. Press Release