Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA Posts Draft Guidance on Using Pictograms on Packaging
The European Medicines Agency (EMA) has posted draft guidance on the use of approved pictograms on veterinary medicinal product packaging. EMA has drafted the document to create a harmonized set of pictograms marketing authorization holders (MAHs) can use to communicate effectively in the limited space available on product packaging.
MAHs already have the option to use pictograms — pictorial symbols for words — on the packaging of veterinary medicinal products. However, there has been a lack of guidance on what pictograms to use and how to deploy them effectively. The draft document is intended to address this gap. In doing so, EMA wants to make it easier for MAHs to predict whether it will approve pictogram-enhanced packaging and ensure users understand the meaning of the images.
EMA sees pictograms being used in two distinct contexts. On blister packs and other small pieces of packaging, EMA sees MAHs using pictograms instead of text. The other use is on labeling and product leaflets. In this context, EMA is encouraging sponsors to use pictograms to complement text.
Regardless of the context, EMA is proposing pictograms follow certain rules. The guidance, which was drafted by the Working Group on Quality Review of Documents, calls for pictograms to be a contrasting color to the background. Black on white is favored. EMA is discouraging MAHs from using highly glossy or metallic reflective colors. The regulator also wants MAHs to avoid using visual effects such as shading or incorporating promotional elements into their pictograms.
To help MAHs, EMA has released 13 pictograms depicting animals commonly treated by veterinary medicines, such as pigs, sheep and fish. The pictograms follow the plain, black-on-white style EMA advocates in the guideline. EMA plans to allow MAHs to use these pictograms to replace text on blister packs and other small forms of packaging. The regulator will prohibit the use of other pictograms in this context. EMA is encouraging MAHs currently using alternative pictograms to file to switch to the approved images.
EMA has left room in the guidance for a second set of pictograms, but this section is currently blank. MAHs will not be allowed to use these as-yet-unreleased pictograms to replace text.
The draft guidance is open for comment until 25 February.
Users Download 15,000 Documents in First Month of Clinical Data Sharing Program
Users downloaded approximately 15,000 documents from EMA's clinical data website in the month after it went live. The regulator posted an update on uptake after adding clinical data on Actavis' cancer drug Armisarte and a generic copy of Merck's antifungal product Cancidas to its database.
EMA introduced the website on 29 October to further its policy on the publication of clinical data. By 24 November, 1,251 people had signed up to use the site and downloaded documents 16,570 times. Almost 20% of the users are academics. EMA classes the remaining 80% of signups as general users. Only academics can download data. On an average day, the users are viewing documents 129 times and downloading more than three times as many.
The numbers are likely to have been boosted by the initial surge in interest in the new offering, but constrained by the limited amount of data available on day one. The site went live with data from two medicines, Zurampic, a gout product AstraZeneca licensed to Grünenthal earlier this year, and Amgen's multiple myeloma drug Kyprolis. Zurampic and Kyprolis are novel medicines, and the reports uploaded to the database reflect this status.
In contrast, Armisarte and Caspofungin Accord, the new drugs added to the site, were authorized in reference to existing medicines, although only the latter is a true generic. The presence of reference products and the route of administration of both drugs — infusion — led EMA to upload the clinical overviews found in module 2.5 of the common technical document on Armisarte and Caspofungin Accord. For other types of products, EMA will also publish clinical summaries and study reports.
The addition of the two medicines is the first step in a planned phased expansion of the repository. EMA intends to continue making monthly additions to the database until it starts meeting routine publishing timelines. For marketing authorizations, line extensions and indication expansions, EMA is aiming to publish within 60 days of the European Commission decision. EMA has given itself 150 days to post clinical reports on withdrawn applications and those submitted under Article 58.
EMA expects to start consistently meeting the timelines by the end of next year.
Four Years After Starting Revision, CHMP Finalizes Biosimilar Heparin Guideline
The Committee for Medicinal Products for Human Use (CHMP) has finalized the revised guideline on the development of biosimilars containing low molecular weight heparins. Adoption of the final text comes four years after the Biosimilar Medicinal Products Working Party (BMWP) agreed on draft changes to the original 2009 guideline.
When BMWP set out to revise the guideline, it wanted to facilitate the use of a risk-based approach to preclinical development and the waiving of the need to run dedicated efficacy trials in exceptional circumstances. The final guideline retains the risk-based goals — the text allows sponsors to skip in vivo studies if physicochemical and biological characterization show similarity — and is even more open to the waiving of efficacy trials than the original draft.
Whereas the draft only allowed for the waiving of clinical efficacy trials in exceptional circumstances, the final text states: "Pivotal evidence for similar efficacy will be derived from the similarity demonstrated in physicochemical, functional and pharmacodynamic comparisons. A dedicated comparative efficacy trial is therefore not considered necessary."
EMA has also added a new section on specific aspects of the quality comparison. The section calls on MAHs to provide information on the source of the heparin, its manufacturing process, mode of depolymerization and respective process conditions. EMA describes "comprehensive characterisation and comparison of the biosimilar" using state-of-the-art methods as essential.
The final guideline is due to come into force on 1 June.
Metal Contamination Triggers Recall of Teva Chewable Tablets
Teva is recalling 13 batches of chewable calcium-vitamin D3 supplements after identifying metal contamination in a "very small" number of tablets. The contamination is thought to result from a single batch of active pharmaceutical ingredient (API).
As any drug made from the batch of API could be contaminated, Teva is recalling all products that were produced from the raw material. The batches were distributed between March and August this year. People in possession of affected batches are to quarantine the products and return them to the original supplier for credit.
Officials at the UK Medicines and Healthcare Products Regulatory Agency (MHRA) have alerted healthcare professionals to the recall, which affects eight batches of 56-tablet packs and five batches of 112-tablet packs.
CHMP has adopted a final guideline on clinical investigation of medicinal products for prevention of venous thromboembolism in nonsurgical patients. The guideline updates a text that came into force in 2006. CHMP began the revision process in 2014 to update its definition of bleeding events, add secondary safety outcomes and clarify the use of imaging tests. Final Guideline
Marisa Delbò was elected as the new chair of EMA's herbal medicines committee. Press Release