EU Regulatory Roundup: Regulatory Action Against Fresenius Kabi's Calea Affects UK Product Supply
Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has found fault with the manufacturing process at a Calea facility. MHRA warned that Calea has cut its output while it works to resolve the problems, creating the risk of disruption to the supply of total parenteral nutrition (TPN) bags in the UK.
The problem centers on a sample taken by Calea during the inspection as part of routine monitoring to detect microbial contaminants in the production area and on the staff that work there. Analysis of the sample revealed the presence of bacteria. The equipment lacked the sensitivity to conclusively state the exact type of bacteria found in the sample. As such, MHRA is proceeding as if the bacteria is the worst-case organism, namely the known human pathogen Bacillus cereus.
There is no evidence that products manufactured and sent to patients were contaminated. However, the potential for harm, coupled to evidence that Calea was noncompliant with MHRA guidance from 2015, led the agency to ask the company to implement important changes to mitigate the risk to patients.
The 2015 guidance covers MHRA’s interpretation of good manufacturing practice requirements for sites that make specials, a category of unlicensed medicines. MHRA’s 2015 update to the guidance addressed topics including cleaning validation, identification of microorganisms and other areas with implications for sterility assurance.
Output from the Runcorn site will be down while the remediation work is going on. Calea is working to get the site back up to speed but UK authorities are taking contingency measures to ensure the ongoing availability of TPN bags, including by convening a group of experts to review alternatives to products made at the facility in Runcorn.
The supply disruption could affect patients with intestinal failure. Calea makes TPN bags tailored to the needs of individual patients to enable physicians to provide nutritional support intravenously.
MHRA Notice
Switzerland Asks Companies to Delete Old Accounts Within Weeks
The Swiss Agency for Therapeutic Products (Swissmedic) has asked companies to delete unneeded user accounts by 23 August. Swissmedic made the request to stop legacy data being migrated unnecessarily to the new E-Government Identity and Access Management (eIAM) environment.
Swiss officials are currently working to harmonize user registration, identification and management in Swissmedic eGov Services Users in the belief it will simplify operations and improve security. With the changes due to take effect by the middle of September, Swissmedic is working to ensure the transition goes smoothly.
Those efforts include encouraging users to delete unneeded accounts. Swissmedic wants companies to delete the accounts by 23 August as after that the user management function in the eGov portal will be unavailable for around two weeks. During that period, companies will not be able modify user accounts.
Swissmedic plans to migrate user accounts to the new eIAM environment on the weekend of 7 and 8 September and make the full functionality of the new system available on 9 September. To access the new environment, users will need to go through an onboarding process involving a code that they will receive via email during the migration process.
Under the new system, all users will need to use two-factor authentication to access their accounts. This process will entail the delivery of a mobile transaction authentication number when a user tries to access their account.
Swissmedic Notice
EMA Advises Against Use of Novartis MS Drug During Pregnancy
The European Medicines Agency (EMA) has recommended against the use of Novartis’ multiple sclerosis drug Gilenya in certain women. The restriction affects women who are pregnant or could become pregnant and are not using effective contraception.
Under the new advice, women who become pregnant while taking Gilenya must stop taking the drug immediately and be closely monitored throughout the pregnancy, including through the use of ultrasonography examinations. EMA wants women who are able to have children to take a pregnancy test before starting treatment. If the the test is negative, the women may take Gilenya, provided they use effective contraception until two months after stopping taking the drug.
EMA made the recommendations after reviewing evidence linking fingolimod, the active substance in Gilenya, to birth defects. The risk of birth defects in babies exposed to fingolimod is twice as high as in the general population. Heart, kidney, bone and muscle defects have been the most commonly-reported problems in babies exposed to Gilenya.
EMA Notice
Swissmedic Rolls Out New Test For Contaminants of Sartan Products
Swissmedic has upgraded the laboratory test it uses to detect nitrosamines in sartans. Swissmedic said the revised test for the contaminants is more robust and sensitive than its predecessor.
Using the new test, Swissmedic can detect N-nitrosodimethylamine and N-nitrosodiethylamine at levels ranging from two to six parts per billion, depending on the contaminant and sartan medicine being evaluated. The limits of quantification for the new test range from five to 20 parts per billion. The new test uses gas chromatography–mass spectrometry to detect contaminants at those levels.
Swissmedic said the new test is more robust and sensitive than the one it introduced late last year.
Swissmedic Notice
Spain Highlights Drop in Human, Veterinary Antibiotic Use in Annual Report
The Spanish Agency of Medicines and Medical Devices (AEMPS) has reported a drop in human and veterinary use of antibiotics. Consumption of the drugs in humans and animals was down 7.2% and 32.4%, respectively, over the analyzed three-year period.
AEMPS made the reduction of antibiotic use a priority in 2018 to help Spain execute its national plan for antibiotic resistance. Spain designed the plan to comply with the European Commission’s 2011 call for member states to establish programs to counter antibiotic resistance. The Commission request addressed topics including the development of policies on rational antibiotic use in humans.
The Spanish regulator shared details of its contribution to the antibiotic plan in its annual report. The report also detailed AEMPS interventions to restore drug supply during disruptions, its work to apply a ministerial order on homeopathic medicines and the number of clinical trials authorized in 2018.
AEMPS Notice (Spanish)
Other News:
AEMPS has issued an alert about the need to protect neonate parenteral nutrition solutions from light. The alert reflects the potential for light to drive the generation of degradation products such as peroxides that can lead to serious adverse reactions in premature infants. One study found reduced mortality in neonates when the solutions are protected from sources of light. AEMPS Alert (Spanish)
Accord-UK is recalling two batches of aripiprazole oral solution over the potential for small particles of the active material to be present in the product. The small particles could affect the efficacy of the atypical antipsychotic, although the company is yet to receive relevant product complaints or adverse reaction reports. MHRA Notice