European Regulatory Roundup: EMA Launches Probe Into HPV Vaccine Safety (16 July 2015)

Posted 16 July 2015 | By Nick Paul Taylor

European Regulatory Roundup: EMA Launches Probe Into HPV Vaccine Safety (16 July 2015)

Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.

PRAC Starts Probe into Links Between HPV Vaccines and Two Syndromes

The European Medicines Agency (EMA) has started an investigation into possible links between human papillomavirus (HPV) vaccines such as Gardasil and two rare syndromes. EMA is confident the benefits far outweigh the risks but wants to investigate the link to cut the risk of uncertainty about the vaccines’ safety profiles undermining confidence in national immunization programs.

Officials in Denmark requested the investigation after noting an uptick in the number of reports linking HPV vaccines to complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS). As it stands, no causal relationship has been established. Both conditions affect unvaccinated people and their pathogenesis is uncertain. Even so, EMA wants to check if the number of cases of CRPS and POTS in the vaccinated population is higher than would be expected.

In part, the probe is an attempt to bring some scientific rigor to a topic that is often characterized by speculation and misinformation that can undermine confidence in the vaccines. “The persisting uncertainty with regard to causal association between CRPS/POTS and HPV vaccination may have a significant impact on future confidence in national vaccination programs,” the European Commission wrote in its referral to EMA’s Pharmacovigilance Risk Assessment Committee (PRAC).

PRAC has sent five questions to GlaxoSmithKline, Merck and Sanofi to assess what data they have on the association between their vaccines and the two syndromes from clinical trials, postmarketing surveillance and literature reviews. The pharmacovigilance body expects to have responses by next month, at which time it will start work on its assessment reports. PRAC plans to publish its recommendations in November.

Press Release, Commission Referral, PRAC Timetable, Manufacturer Questions

EMA Asks Companies to Give it More Time to Review Requests for Accelerated Assessment

EMA has changed its advice for companies that want to have their products reviewed under its accelerated assessment program. The regulator, which used to ask companies to send their requests 10 to 30 days before the start of the centralized procedure, is now recommending submissions be made two to three months ahead of the filing of the marketing authorization.

Officials at EMA made the change to ensure they have enough time to assess the suitability of the product for the program and make preparations for the start of the accelerated procedure. EMA is now also asking applicants to go to the procedure manager for guidance before filing their requests and strongly recommending they ask for a pre-submission meeting to talk over their proposals. The extra steps are intended to help applicants submit timely and complete requests.

EMA has added a new section of the advice document to provide further guidance on what details must be included in requests. The new section lists the information EMA needs to better integrate inspections to verify compliance with good clinical and manufacturing practices (GCPs/GMPs) into its accelerated assessment procedures. EMA wants to know the names and compliance history of each manufacturing site, as well as the details of who has done what in the clinical trial program.

Advice Document

UK Court Fines Fresenius Kabi After Manufacturing Mixup Leads to Patient Death

A court in the United Kingdom has fined Fresenius Kabi and its sister company £555,900 ($860,000) after their defective insulin syringes contributed to the death of a diabetic patient. The man died of multi-organ failure after being treated with insulin syringes that contained no active ingredient.

Fresenius Kabi and its sister company, Calea, which manufactured the product, were prosecuted by the Medicines and Healthcare Products Regulatory Agency (MHRA) for the death and sentenced by a court this week. With the coroner ruling that the lack of insulin in the syringes was a “major contributory factor” in the death of the patient, the court convicted Fresenius Kabi for its part in the medicinal failure.

The court made the ruling after hearing of the history of problems at the companies. In 2011, a cystic fibrosis patient was treated with pre-prepared tobramycin syringes manufactured by Calea that contained three times the prescribed dose. MHRA has also flagged failings at the site in Runcorn at which Fresenius Kabi and Calea operate. The shortcomings at the site include the lack of a regime to spot potential defects and stop them from happening again.

Press Release, FiercePharma

Greece Blocks Export of 25 Drugs to Stop Parallel Trade Profiteering

Greece has prohibited the export of 25 types of drugs to stem to outflow of products to countries in which they command higher prices. The action follows reports by pharmacists of a sharp rise in the re-export of medicines.

Officials at the Greek health ministry are still digging through data from the past 15 days to assess the state of the re-export market, but have already seen enough evidence to conclude they need to act. “Abuses have been discovered by some players,” a representative told Reuters. The continuing investigation could lead to the filing of complaints in Greece and overseas against people involved with the re-export of medicines.

The move to block the export of the 25 as-yet-unidentified medicines is in keeping with the calls of the European pharma industry, which is wary of seeing its products moved around the continent by others for profit. Such parallel trade is allowed under free trade rules in the European Union, but Greece is now a special case. “Human lives are in danger and they have to do something before the point of no return,” Theo Giannaros, director of a public hospital in Athens, told EurActiv.

Reuters, EurActiv

Other News:

EMA, the European Commission and the United States Food and Drug Administration (FDA) are to share best practices for involving patients across the lifecycle of medicines. The collaboration is part of how EMA and FDA intend to give patients a greater say in the regulatory process. EMA and FDA also committed to strengthening their collaborations on inspections and data integrity. Press Release

MHRA has created a smartphone app through which patients and healthcare professionals can submit reports of adverse events. The app is an expansion of MHRA’s long-running Yellow Card Scheme. Users can also sign up to receive alerts about medicines they are interested in and view the number of Yellow Cards associated with a product. Press Release

EMA has released a summary of a workshop it arranged to discuss how to improve the availability of veterinary vaccines in Europe. Suggestions considered at the workshop included increasing engagement with applicants to make regulatory outcomes more predictable, training assessors to make their decisions more consistent and lowering the data requirements. Press Release, Summary

The UK’s Accelerated Access Review team is seeking feedback from biopharma companies, hospitals and nonprofits. Officials are asking for the input as they work toward a December deadline for the publication of a final report into how to cut the time it takes for innovative drugs, medical devices and diagnostics to reach patients in the UK. Press Release 

EMA has called for representatives of patients’ organizations, healthcare professionals’ groups and veterinarians’ associations to apply to become members of its management board. Successful applicants will occupy the civil society seats on the board for a renewable three-year term, giving them a say in the appointment of the executive director and adoption of a budget. Press Release


Categories: Regulatory News

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