EU Regulatory Roundup: EU Drafts Guidance on Assessing the Benefits and Risks of Phthalates
Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.EU Drafts Guidance on Assessing the Benefits and Risks of Phthalates
The European Commission has published draft guidelines on assessing the risk and benefits of using phthalates in medical devices. Officials published the guidelines to help manufacturers comply with restrictions on the use of phthalates in the incoming Medical Device Regulation.
Phthalates are widely used as plasticizers, but their merits are being re-evaluated in light of evidence that they can be carcinogenic, mutagenic, toxic to reproduction and endocrine disrupting. Other tests have shown phthalates can be released from plastics and come into contact with humans, meaning they could have negative effects on health in the real world.
European officials responded to the risk by establishing restrictions on the use of phthalates in device regulations that are due to come into next year. The regulations state medical device manufacturers can use phthalates with negative effects on reproduction and the endocrine system below a certain concentration if they provide proper justification. In justifying their decision, manufacturers should analyze the risks posed by alternatives to phthalates and their effects on device performance,
The draft guidance is intended to help manufacturers of medical devices make these assessments. Working with the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER), the Commission has set out a framework for phthalate risk-benefit assessments and delved into the steps manufacturers will need to take.
Specific points addressed in the 55-page document include the need to take the intended use of a device into account when assessing its benefits and risks. SCHEER thinks this is important, as some subpopulations, such as breastfeeding women, will be far less tolerant to risk than others.
The Commission is accepting feedback on the draft until 29 April. Beyond that, European officials will finalize the text but plan to return to the topic at a later date. SCHEER identified multiple possible approaches to benefit-risk assessments when drafting the guidelines but lacked the data to evaluate many of the options. To remedy that situation, SCHEER is encouraging manufacturers to generate data on the alternatives. SCHEER plans to reassess the guidelines after three years of use.
Commission Notice, Draft Guidance
MHRA Adds Guide to Registering Artwork to Growing Body of No-Deal Advice
The Medicines and Healthcare products Regulatory Agency (MHRA) has added to its growing body of advice on preparing for a no-deal Brexit. The latest document covers the steps companies will need to take to register new drug packaging artwork if the United Kingdom leaves without a deal.
In a no-deal scenario, MHRA will convert European Union marketing authorizations into clearances to sell products in the UK. MHRA has previously described details of the conversion process but omitted details of how the change will impact on drug packaging artwork. The guide released this week fills that gap in MHRA’s library of Brexit advice.
The latest guide states companies must register amended artwork after receiving a UK marketing authorization. This will entail submitting the name and address of the marketing authorization holder or its representative, the UK authorization number and the name and address of the product manufacturer for batch release. MHRA is giving companies 21 months from the UK’s departure to complete this process.
MHRA also used the update to confirm it will continue to accept multi-language packs, provided all their information complies with UK requirements, and outline its approach to products that came to market via the mutual recognition or decentralized submission pathways.
The impact of Brexit on pharmaceutical packaging operations came up in a recent debate that led up to Parliament voting to empower itself to evaluate alternative ways out of the current logjam. Anna Soubry, a politician who left the ruling Conservative Party over its handling of Brexit, described how an 850-person pharmaceutical production facility in her constituency “does not know what to print on its boxes, because it does not know what the outcome is going to be.”
Seeing the response of a Conservative politician to her comment, Soubry said the person seemed to find her talk of the “crisis” facing the pharmaceutical company “amusing,” before going on to state that “British business will never forgive the Conservative party” for its handling of Brexit.
MHRA issued its artwork advice days before adding another section to its guide for exporters of active substances. The new section covers exports of biological products. Holders of UK marketing authorizations covering biological active substances will not need to register separately as producers of active substances. No written confirmation will be issued to these companies.
MHRA Guidance, Debate Transcript, API Advice
GMDN Agency Welcomes Alignment of Medical Device Database to Global Nomenclature
The GMDN Agency has welcomed the Commission’s position on the nomenclature of its Eudamed database of medical devices. European officials opted to use Italy’s national classification of medical devices (CND) on the proviso it maps to the global nomenclature managed by the GMDN Agency.
Eudamed is set to go live next year in support of the safety and performance requirements mandated by the incoming medical device regulations. Ahead of the launch, the Commission considered which medical device nomenclature to use in the naming and categorizing of medical devices the database. The Commission published its findings earlier this month.
The Commission has supported development of the global medical device nomenclature (GMDN) since the 1990s, but chose to use Italy’s CND in Eudamed. The CND nomenclature will “be mapped to the GMDN nomenclature.”
The GMDN Agency, a nonprofit tasked with maintaining the global nomenclature, interpreted the decision as a positive for GMDN, stating the Commission had identified the “need to strongly align to” its international standard. The nonprofit thinks GMDN will play a role in the database.
“It is our understanding that in the future manufacturers will continue to be able to use the GMDN Code in the Eudamed system,” the GMDN Agency wrote in a statement.
GMDN Notice, Commission Statement
Norway Clears Drugmakers to Send Safety Notices to Pharmacies by Email
The Norwegian Medicines Agency (NOMA) has started allowing drugmakers to send safety alerts out via email. NOMA thinks promoting the shift to electronic communication will make it easier to spread information among healthcare professionals.
Drugmakers in Norway used to have to post physical copies of safety updates and training materials to pharmacies and healthcare centers. These documents are intended to ensure products are used safely when they first come to market and keep healthcare professionals abreast of changes to their risk-benefit profiles.
NOMA’s decision to permit the transmission of this information via email is underpinned by a belief that electronic communication has some notable advantages. In addition to the aforementioned potential for materials to spread faster, NOMA also highlighted reduced resource use and impact on the environment as benefits of the change.
Manufacturers will continue to work with NOMA to prepare materials, but will distribute them via a different route.
NOMA Notice (Norwegian)
Other News:
MHRA is recalling three batches of losartan products as part of its ongoing effort to counter the risk of contamination with substances including nitrosamine N-nitroso-N-methylamino butyric acid. The latest recall, which follows four similar actions over the past eight months, affects products sold in the UK by Accord Healthcare. Statement
Novartis is distributing an English-language version of Lucentis in Switzerland due to a shortage of the local version. The Swiss regulator granted Novartis a time-limited clearance to provide the English product. Notice (French)