European Regulatory Roundup: EMA Offers New Pharmacovigilance Updates (17 December 2015)

Regulatory NewsRegulatory News | 17 December 2015 |  By 

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

EMA Releases More Pharmacovigilance Documents

The European Medicines Agency (EMA) has released a batch of draft pharmacovigilance documents. EMA covers multiple aspects of good pharmacovigilance practice (GVP) in the texts, from changes to a template for direct healthcare professional (HCP) communication, to tweaks to a biologics-focused document.

In total, EMA published four draft documents this week. Two of the documents address aspects of communicating with HCPs. EMA is proposing multiple changes to the template letter used by marketing authorization holders (MAHs) to inform HCPs of safety concerns. Many of the changes amount to a reordering of existing elements, but EMA has also added new lines, such as the need to frame the alert in the context of the therapeutic indication.

EMA has also provided a communication plan and checklist to guide MAHs through the process of informing HCPs of safety issues. The plan recommends that when multiple companies are authorized to market the same active pharmaceutical ingredient, the businesses collaborate to craft one letter each of them can send to HCPs. EMA also offers advice on the value of using the title of the letter to outline the safety concern.

Further guidance on safety communication is provided in an updated version of module XV, a text that goes into greater detail about the structures and processes used in communications about the safety of products. EMA has made multiple changes to the text, which now places greater emphasis on the need to deliver “relevant, clear, accurate and consistent messages” while also softening language about the use of graphical presentations of the risk posed by a product.

The final draft document proposed by EMA covers specific considerations for biologics. EMA wants to update the text to reflect the release of other documents of relevance, such as the Guideline on Similar Biological Medicinal Products. All of the documents are open for comment until the end of February. EMA then plans to make any necessary changes quickly and have final texts in place by the end of the second quarter. 

Draft Letter, Communication Plan, Biologics, Module XV

MHRA Cuts Thalidomide Starting Dose in Flurry of Advice to HCPs

The United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) has reduced the recommended starting dose for thalidomide in people aged 75 years and older. MHRA made the change as part of a clutch of revisions to its advice to HCPs on the use of certain drugs.

HCPs are now advised to start elderly patients on 100mg of thalidomide a day, a dose MHRA thinks will cut the risk of adverse reactions. Based on Phase III data, MHRA sees patients aged 75 years and older having a greater risk of experiencing such reactions than younger people. Thalidomide sold by Celgene is used in combination with melphalan in patients with multiple myeloma aged 65 years and older who are ineligible for treatment with high-dose chemotherapy.

MHRA released the updated thalidomide recommendation alongside three other alerts for HCPs. The alerts provide advice on the use of antiretrovirals, mycophenolate mofetil and bisphosphonates. With the exception of products containing zidovudine, stavudine or didanosine, the labels of antiretrovirals will no longer warn of the risk of fat redistribution or lactic acidosis. The change comes two months after EMA dropped its warning on the HIV drugs.

The UK regulator is now also advising against giving mycophenolate mofetil during pregnancy because of the risk of birth defects and miscarriage. Finally, MHRA is recommending that HCPs look for signs of reduced blood flow in the external auditory canals of people taking bisphosphonates.

Thalidomide, Antiretrovirals, Mycophenolate Mofetil, Bisphosphonates

Guidelines on Asthma Clinical Trials Set to Come Into Force in May

EMA has adopted a final guideline on the clinical development of treatments for asthma. The text gives clinical trial sponsors more specific advice on control-based management, testing asthma treatments in children and developing immunotherapies.

Sponsors last received asthma trial-specific guidance from EMA in 2003, since when authorities have updated international clinical recommendations for the common chronic inflammatory disease. EMA set out to revise its guidance to reflect these changes in 2013, but having wrapped up a public consultation at the end of that year, the advance of the document stalled until the Respiratory Drafting Group agreed on a final text this May.

The final text, which is due to come into force in May, covers the same topics as the draft document but EMA has tweaked and expanded multiple sections. EMA removed a line about using a lack of airway hyper-responsiveness to exclude an asthma diagnosis when a controller medication is absent. The regulator also revised the text covering how to evaluate whether a drug is working in children, dropping the line “the primary endpoint should be asthma control” in favor of broader advice.

In the final text, EMA wrote: “The goal of treatment is to achieve good control of symptoms and to reduce the risk of exacerbations. A number of composite scores for the assessment of asthma control have been developed and specifically validated for use in children above six years of age.”

EMA Guideline

HMPC Calls for Data on Multiple Herbal Medicines

The Committee on Herbal Medicinal Products (HMPC) has called for scientific data on five groups of products. HMPC wants the data to inform assessments of herbal tea combinations to treat urinary tract disorders and possible revisions to the monographs covering five plant-derived therapies.

EMA’s HMPC wants to harmonize standards for herbal tea combinations across the European Union. To support this work, the committee is seeking data on herbal tea combinations, particularly those that are known to have been used to treat urinary tract disorders for more than 30 years. HMPC wants information on the posology, preparation instructions and other factors about combinations with such a long, documented history of use.

The other five calls for data published by HMPC cover products derived from valerian, olives, yarrow, echinacea and artichoke. Monographs for all of the plants are nearing their five-year reviews, an event HMPC is preparing for by soliciting data from pharma industry associations, HCPs, patients, governmental institutions and other organizations. HMPC is accepting submissions until 15 March.

Tea, Valerian, Olives, Yarrow, Echinacea, Artichoke

Other News:

EMA’s Committee for Medicinal Products for Veterinary Use (CVMP) has recommended extending the marketing authorization for Mérial’s Zactran to cover the treatment of swine respiratory disease in pigs. The committee rejected a request by Intervet to market a spot-on solution form of Bravecto for dogs and cats. CVMP made multiple other rulings at the meeting. Press Release

A subsidiary of Sanofi is recalling batches of omeprazole 20mg gastro-resistant capsules from the United Kingdom. MHRA alerted HCPs to the recall after the subsidiary, Zentiva, learned that the capsule shells of some products were more brittle than intended. Pharmacists are advised to quarantine affected batches and send them back to the wholesaler. MHRA Alert

EMA is to hold a workshop for micro-, small- and medium-sized companies on the statistics of clinical trials early next year. The one-day workshop, which is scheduled for February, is designed to help smaller sponsors handle the statistical side of exploratory and confirmatory clinical trials. Registration is open until 22 January. EMA Notice

Guido Rasi, the recently reinstated head of EMA, has laid out his vision for his five-year term. Focus


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy