Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
Sanofi R&D Chief Calls for Urgent Harmonization of Regulations
The head of R&D at Sanofi has called for greater harmonization of global regulatory requirements after becoming frustrated with the perceived inconsistencies and inefficiencies of the current model.
Speaking at an event to mark the 20th anniversary of the European Medicines Agency (EMA) attended by Reuters, Elias Zerhouni said the fragmentation of regulatory attitudes is at odds with the increasingly global nature of drug development and supply. Designing development strategies that address regulatory divergence — which Zerhouni thinks is getting worse — is an expensive task for global biopharma companies.
Zerhouni said 20% of his R&D budget is allocated to bridging the gaps between different regulatory systems and yet inconsistent decisions are still the norm. “In my short experience of five years, I have not seen a single regulatory decision that was fully consistent across regulatory agencies,” Zerhouni said. The Sanofi R&D chief cited an analysis that found EMA and the US Food and Drug Administration (FDA) differed on whether to accept or reject 22% of drugs. Half of drugs are given different labels.
The history of EMA shows greater harmonization is possible, but finding common ground between regulators — which have small but significant differences in their outlooks — has proved challenging. Zerhouni said there is an urgent need to resolve such challenges. The G8 or G20 — the gatherings of powerful nations — could provide a platform from which to discuss regulatory harmonization. – Nick Paul Taylor Reuters
EMA Meets with Industry on Pharmacovigilance Requirements
The European Medicines Agency (EMA) recently held its third stakeholder meeting on pharmacovigilance requirements in the EU. Participants included representatives from the EMA as well as the Pharmacovigilance Risk Assessment Committee (PRAC) and the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh). Representatives from seven European industry associations also attended the meeting.
Presentations were given on a range of subjects, including post authorization safety studies (PASS), periodic safety update reports (PSUR), good pharmacovigilance practices (GVP) and pharmacovigilance information systems. Full details can be found in the documents tab on the EMA website. – Michael Mezher EMA Event Page
EMA Gives Support to Innovative Biomarker Research
The European Medicines Agency (EMA) has given its support to a group conducting innovative research on biomarkers of drug induced skeletal muscle injury. The Predictive Safety Testing Consortium (PSTC), represented by Critical Path Global Ltd, approached the agency for scientific advice on its studies. The agency’s Committee for Medicinal Products for Human Use (CHMP) adopted advice to be given to PSTC in February, and encourages the group to conduct nonclinical and early clinical studies to look into several of these biomarkers. – Michael Mezher EMA Letter
French Regulator Working with Allergan after Breast Implants Linked to Cancer
French drug agency ANSM is working with Allergan to ensure the safety of people who have received breast implants. The collaboration began after France’s national cancer institute INCa found a “clearly established link” between a rare type of tumor and implants, many of which were sold by Allergan.
INCa linked 18 cases of anaplastic large cell lymphoma that have arisen since 2011 to breast implants. More than 75% of the cases involve people who have breast implants manufactured by Allergan, the US company that was acquired by Actavis for $70 billion this week. Allergan told the AFP “the security of patients is our first priority” and it is working with ANSM to achieve this goal.
The risks are relatively low. With so few people suffering the side effect, INCa is recommending women with the implants keep them and try not to worry about the situation. However, with the latest scare coming so soon after the rupturing of the now-banned PIP implants, the cancer risk is another concern for ANSM and the 400,000 women in the country with breast augmentations. – Nick Paul Taylor AFP
Global Regulators’ Fight against Dementia
The Medicines and Healthcare Products Regulatory Agency (MHRA) released the conclusions from a recent summit on dementia held in Geneva, Switzerland on 10 November 2014. The summit marked the first time international regulators have met to address dementia and featured participation from 10 regulatory agencies, including the US Food and Drug Administration (FDA), Health Canada, Japan’s Pharmaceutical and Medicines Agency (PMDA) and the European Medicines Agency (EMA) along with several other European national authorities.
The regulators identified six work areas that could help address the development of dementia treatments in the future. These work areas include determining what caused companies to abandon dementia product development in the past, how to improve clinical trial efficiency and cross-border cooperation from regulators to promote the development of products to treat Alzheimer’s disease. – Michael Mezher MHRA Press Release
MHRA to Take Over Export Certificate Issuance from Dept. of Health
Beginning 1 April 2015, MHRA will begin accepting applications for certificate of free sale (CFS) for medical devices. These certificates are intended to show that a product is CE marked and eligible to be sold in the UK, and are required for devices being exported to some countries outside the EU.
As of 18 March 2015, companies can no longer apply for a CFS with the Department of Health (DH). There will be a two-week window of down time for CFS applications before MHRA begins accepting applications.
MHRA is also considering introducing a fee for companies applying for a CFS, after holding a public consultation on the subject last fall. – Michael Mezher MHRA Press Release
PRAC Calls for Restrictions on Pediatric use of Codeine
The Pharmacovigilance Risk Assessment Committee (PRAC) has recommended restricting the use of codeine as a pediatric cough and cold treatment further still. PRAC’s recommendations follow — and to a large extent mirror — an earlier review into the use of codeine as a pain treatment for children.
If PRAC’s recommendations are accepted by the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), healthcare professionals will be advised not to give kids under 12 years old codeine as a cold treatment. PRAC advised against administering codeine to children 12 to 18 years old who have problems with breathing, too. The review also recommended mandatory child-resistant packaging and a ban on codeine use during breastfeeding.
The age-based recommendations are underpinned by knowledge that the conversion of codeine into morphine in the body is particularly variable and unpredictable in young children. Kids with breathing problems are vulnerable to the side effects of the conversion because of how morphine can alter respiratory processes. PRAC found similar risks when considering the use of codeine as a treatment for pain, the outcome of which triggered the investigation into cough and cold therapies. – Nick Paul Taylor Meeting Highlights, Codeine Recommendations
Genzyme Rapped over ‘Misleading, Inconsistent and Disparaging’ Material
The Prescription Medicines Code of Practice Authority (PMCPA) has criticized Genzyme heavily over materials the company presented at a meeting. PMCPA said it was “astonished” Genzyme thought the material was non-promotional and imposed some of its strongest punishments against the biotech.
Genzyme presented material comparing its Fabry disease drug Fabrazyme to Shire’s rival product Replagal at a meeting of the Lysosomal Storage Disorders Expert Advisory Group in February 2014. Shire attended the meeting and was unimpressed, prompting it to file a complaint with PMCPA. Since then the rivals’ relationship has deteriorated — Genzyme accused Shire of spreading “incorrect rumors” — and a PMCPA panel has worked to figure out the facts of the case.
The outcome of the investigation looks bad for Genzyme. While PMCPA cleared it of seven of the 18 breaches it was accused of, the 11 guilty rulings include some strongly worded criticisms. The panel ruled that the material presented by Genzyme was “misleading, inconsistent...and disparaging,” in part because it concluded the slides implied FDA had rejected Shire’s Replagal application again. The breaches were serious enough for PMCPA to rule Genzyme had brought discredit on the industry.
As well as confirming the discredit ruling — which is among PMCPA’s harshest criticisms — a panel set up to hear Genzyme’s appeal told the company to send a corrective statement to all attendees of the meeting. The appeal panel felt the punishment was necessary given Genzyme’s “disregard for patient safety.” Further sanctions could follow if PMCPA is unimpressed by an audit of Genzyme’s processes. – Nick Paul Taylor PharmaPhorum, PMCPA Interim Report
UK Recommends use of Takeda Drug to Treat Bowel Condition
The UK’s price watchdog has given a positive opinion for Takeda Pharmaceuticals drug Entyvio, which is intended to treat ulcreative colitis, a painful bowel condition. The drug is approved in the UK for use when other therapies are not effective. The positive opinion from the National Institute for Health and Care Excellence (NICE) will clear the way for the drug to be covered by the National Health Service (NHS). – Michael Mezher NICE Press Release
UK Agency Seeks Real-World Examples of its Guidance Being Used
The UK’s National Institute for Health and Care Excellence (NICE) is asking health care practitioners for examples of when they have used the agency’s guidance during their practice. The request is part of a “shared learning” initiative NICE is undertaking to disseminate real-world examples of NICE guidance and standards being used. The agency is asking practitioners to share the results from these instances, as well as any lessons learned from their experience. – Michael Mezher NICE Shared Learning Submissions
Authorities have reinstated the CE Mark for St. Jude Medical’s Portico, a transcatheter aortic valve replacement. St. Jude paused sales of the device in September after detecting reduced valve leaflet mobility in a US clinical trial. Having conducted an investigation that reassured it the observation is asymptomatic, St. Jude is now ready to resume sales in Europe. FierceMedicalDevices
England’s Cancer Drugs Fund (CDF) has reversed an earlier decision to stop paying for patients with advanced breast cancer or metastatic renal cell carcinoma to receive Novartis’ Afinitor. CDF planned to drop Afinitor as part of its attempt to control spiraling costs, but the plan was criticized by patients and manufacturers. FiercePharma
The Human Fertilisation and Embryology Authority (HFEA) has admitted it lacks criteria for assessing whether the modification of embryo culture mediums by clinicians is classified as medical device production. HEFA has encountered such cases in the past and passed them on to MHRA, which ruled that medical devices that are not made available for sale fall outside its regulatory authority. Hansard
EMA has released a chart showing at which stages in the regulatory process committees should seek input from patients. The chart calls for such engagement at each step in the process, from decisions about orphan designations and provision of protocol assistance, through to the renewal of package leaflets and release of safety communications. EMA Chart
EMA has released a list of sources for identifying authorized medicinal products in the EU and European Economic Area (EEA). EMA Sources