Welcome to our European Regulatory Roundup, our weekly overview of the top regulatory news in Europe.
GCP Inspectors Retain Focus on Emerging Markets Despite Drop in Overall Visits
The European Medicines Agency (EMA) has revealed member states conducted 31% fewer good clinical practice (GCP) inspections in 2014 than they did in the previous year. The slump is partly attributable to an 8% dip in the number of inspections requested by the Committee for Medicinal Products for Human Use (CHMP).
CHMP asked officials to run 66 inspections in 2014, compared to 72 the year before. However, as some inspections that are requested in one year are not performed until the following reporting period, the inspectorates of member states only actually visited 57 sites in 2014. The breakdown of the figure shows emerging markets accounted for a larger cut of inspections than in previous years, with the proportion of visits to the Middle East, Asia Pacific and South America rising.
Last year, almost 20% of all inspections involved the Middle East and Asia Pacific, compared to 12% in 2013. Similarly, South and Central America were the focus of 10% last year, an increase of three percentage points over 2013. The actual number of inspections in both regions was flat year on year, but inspectorates paid far fewer visits to Europe and the United States. Inspections in Europe were down 39%, while visits to the US tumbled by 43%.
Despite a larger proportion of inspections taking place in countries that are often viewed as likely to harbor noncompliant trial sites, the rate at which deficiencies were identified fell year on year. In 2014, inspectors found an average of 11.8 deficiencies per visit, compared to 12.7 in the previous year. The proportions of critical, major and minor deficiencies was consistent year on year.
GCP Inspection Report
EMA Starts Publishing Safety Reports of Nationally-Authorized Medicines
EMA has begun publishing single assessments of periodic safety update reports (PSURs) for products that are only approved at a national level. Having adopted the policy, EMA is encouraging companies with nationally-authorized medicines to monitor the resource for reports of relevance to their products.
EMA began publishing single assessments of PSURs for centrally-authorized medicines in 2012. A year later, the regulator added both centrally and nationally-authorized products to the scope of its publication policy. The latest move rounds out the policy by adding single assessments of PSURs for active substances that are only found in nationally-authorized medicines. In doing so, EMA is aiming to further harmonize the implementation of safety measures across the region.
When a single assessment of a nationally-authorized medicine is needed, a lead member state is appointed to handle the task. The resulting report is reviewed by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) before a decision on further actions is taken. EMA is now publishing the outcomes of such assessments, as well as information in all official EU languages in cases where a variation of the marketing authorization is needed.
European Commission Clears Brazil and Israel to Ship APIs Without Certification
The European Commission has added Brazil and Israel to the list of countries that can ship active pharmaceutical ingredients (API) to Europe without first having each batch inspected and certified. The decision indicates the Commission considers APIs manufactured in Brazil and Israel as equivalent to Europe-made ingredients.
Europe began requiring manufacturers to obtain certification from their national regulators in 2013, at which time Australia, Japan, Switzerland and the United States were the only countries to be granted exemption from the law. Brazil and Israel joined the countries on the short list of nations to be cleared by the Commission exactly two years after the law came into force. The nods end a long wait for API manufacturers in Brazil and Israel.
Both countries applied for certification in 2012, in Israel’s case more than one year before the date on which the EU started requiring authorizations. The decision to exempt Israel from the law was based on the strength of an existing agreement between it and the EU on the conformity and acceptance of industrial products. Brazil gained its clearance after undergoing two on-site reviews and proposing an action plan earlier this year.
MHRA Moves to Speed Detection of Medical Device Safety Issues Using IT Tools
The United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has said it plans to buy or build IT tools this financial year to improve its ability to identify adverse events linked to medical devices at an early stage.
MHRA is specifically looking at improved signal detection and text analytics tools, assets it thinks will help it spot emerging safety issues before they affect lots of people. The tools are the latest phase of a push to bolster the regulator’s ability to detect and manage medical device-related safety issues. So far, this has entailed creating an IT thematic signal report facility. MHRA then reviews the signal reports to gauge both their priority and progress.
The IT drive is part of MHRA’s response to one of 12 recommendations made in an independent review of its medical device operations last year. Having spent the past year working on adopting the recommendations, MHRA published a report on its progress this week. The report details actions taken by to ensure the agency has enough clinically-trained staff, is collaborating with its peers in Europe and effectively collects and uses medical device incident data.
EMA Posts Draft Guidelines on Manufacturing Aspects of Marketing Submissions
EMA has released draft guidelines to clarify what information about manufacturing processes firms should include in marketing authorization applications (MAA). The document was drafted in light of increased outsourcing and the growing complexity of supply chains.
The draft is intended to replace the note for guidance on the manufacture of the finished dosage form, which was written in an era in which supply chains were simpler. With supply chains now featuring multiple companies from across the globe, EMA has updated its stance on what details companies should include in MAAs.
EMA has also worked the content and principles of ICH Q8 into the draft guidelines, which is now at the start of a lengthy consultation period. The regulator is accepting comments on the 13-page document until January 9, 2016.
EMA has opened an investigation into Quest Life Sciences, the Indian contract research organization (CRO) that received a warning from the World Health Organization (WHO) recently. British and Spanish inspectors have visited the CRO and found as yet undisclosed issues at its site, which WHO found to have made "critical" lapses in a trial of HIV drugs. Reuters
A French appeal court has ruled in favor of certification agency TUV Rheinland in a case involving faulty breast implants. TUV was initially found guilty of negligence for approving the implants but the appeals court has overruled the decision. The decision frees TUV from the need to compensate people affected by the faulty products. Reuters, AP
The Latvian State Agency of Medicines (SAM) has released its annual report. Clinical trial activity in the country trended upward in 2014, with 13% more studies taking place than in the previous year. Authorizations to conduct clinical trials were down slightly, though, as was the number adverse event reports sent to the regulator. SAM Notice