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

UK Panel Calls for Rethink of Antibiotic Regulation

A globally focused, United Kingdom-led review of antimicrobial resistance has called for regulators to rethink their approach to the field. The panel sees regulators playing a role in ensuring the sensible use of existing antibiotics and encouraging the development of new products.

Detailed recommendations for regulators will follow in future reports, but this week’s publication — the second to be released by the committee — outlines the areas in which it thinks regulators can help. One of the five key themes of the review is the need for coherent international action by regulators and other players to control the use of antibiotics in people, animals and the environment.

The European Medicines Agency (EMA), European Centre for Disease Prevention and Control (ECDC) and the European Food Safety Authority (EFSA) are already taking steps in this direction, notably through the collaborative research program that published its first report this week. The collaborators found significant variations in the use of antimicrobials in food-producing animals.

This week’s U.K.-led review calls for the globalization of such projects to ensure authorities have the clearest possible picture of antimicrobial resistance. Current surveillance is fragmented, leading to public health officials having an incomplete picture of the global situation. Equally, many systems rely on old data, an issue the panel thinks can be resolved as healthcare digitizes.

The major, unresolved question is how to encourage the development of products to counter the superbugs once they have been identified. The report sees a role for regulators in incentivizing development and also questions whether unclear or burdensome approval pathways have hindered progress to date.

AMR Report I Regulatory Focus

MHRA Posts Guidance for Production of Unlicensed ‘Specials’

The United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) has released guidance for “Manufacturing Specials” (MS), the term it uses for production of certain unlicensed medicines. MHRA allows the production of MS-licensed drugs when a patient needs a specific formulation of a product that differs from commercially available treatments.

Such situations typically involve small batches of a defined range of products that lack marketing authorization and are treated somewhat differently in terms of good manufacturing practices (GMPs). Companies operating under these conditions are not required to prepare a Product Quality Review (PQR), a difference that MHRA explains in its guidance Q&A document.

The Q&A supplements the existing requirements laid out in Guidance Note 14 by attempting to answer many of the common uncertainties faced by companies that manufacture MS-licensed, aseptically prepared products using closed systems. Open system production is covered by European guidance.

In the 41-page Q&A, MHRA explains its expectations with regard to the labeling of MS products, how to handle recalls and the legality of marketing such drugs. Several sections — such as computerized systems — are currently blank, but MHRA expects the document to grow and evolve over time. The decision to use a Q&A format was motivated by the desire to create an easily updatable document. 

MHRA Guidance

MHRA’s Online Medical Device Platform Nears go Live Date

MHRA’s online medical device registration platform is due to go live. MHRA is introducing the Devices Online Registration System (DORS) as part of its move away from paper documents.

DORS is scheduled to come online on 11 February, after which it will run in parallel to the existing paper system for three months. MHRA will close the paper-based device registration system on 11 May. DORS will cover class I medical devices, in vitro diagnostics and other low-risk products.

Relatively little is changing in the handover. Companies already registered only need to set up a DORS account when they want to change details or add a new device, at which time MHRA will ask for some information and then activate the user. The fee for new registrations is still £70 ($106).

MHRA Notice

Indian Generics Firms Downplay Impact of EMA ban

Indian generic manufacturers affected by EMA’s action against GVK Bio have downplayed its impact. The proposed suspension of 700 products tested by GVK includes drugs sold by seven Indian companies, most of which expect the ban to have little impact on their business.

Sarabjit Kour Nangra, an analyst at Angel Broking, backed up the manufacturers’ confident outlooks. “As Europe is a small market for many of these Indian companies such as Dr Reddy's and Lupin, the suspension of drugs from the markets of individual European countries will not have any significant impact on the revenues,” Nangra told Business Standard.

Drugs sold by Dr Reddy’s — including the anti-epileptic levetiracetam and diabetes drug pioglitazone — are on the EMA list, but the company does not expect the suspension to affect its finances.

Business Standard

MHRA Seizes 10,000 Vials of GcMAF in Raid of Unlicensed Plant

MHRA has seized more than 10,000 vials of an unlicensed medicine during an inspection of a facility in Cambridgeshire. The vials were marketed as Globulin component Macrophage Activating Factor (GcMAF), a blood drug that was touted as a miracle cancer cure on the back of some questionable trials in the 2000s.

Much of the research on GcMAF has since been discredited — leading to the retraction of a paper last year — but an unlicensed market for the product has developed. MHRA discovered a plant in Cambridgeshire was supplying some of this demand and warned consumers about a dozen websites that sell GcMAF.

The production plant does not comply with good manufacturing practices, but — as Derek Lowe at In the Pipeline notes — its managers had gone to the trouble of sourcing blood plasma starting material. The plasma was not approved for use in humans or drugs, however.

MHRA Notice I In the Pipeline

Vendor: 75% of Large Pharma Firms are Behind Schedule on Serialization

The European Falsified Medicines Directive is still three years away from coming into force, but a vendor thinks 75% of top pharma companies are already behind schedule on their preparations.

Brian Daleiden, vice president of marketing at TraceLink, told Outsourcing-Pharma the estimate is underpinned by experience of preparing for track-and-trace requirements in other markets. Adopting serialization software and hardware across a large production network with multiple packaging lines while maintaining output can be challenging.

Companies that work extensively with contract packagers face a different set of issues. With multiple clients all pushing to have their products serialized within a set period of time, contract packagers may be forced to prioritize some customers over others.

Outsourcing-Pharma

Other News:

European authorities have awarded CE Marks to Advanced Bionics and OrthAlign. Advanced Bionics received the status for two versions of its HiRes 90K cochlear implants, both of which can now undergo 1.5T MRI scans without removing the internal magnet. The OrthAlign CE Mark covers its positioning devices for knee and hip surgeries. Press Release I More

EMA has released the clutch of documents that were discussed at its recent veterinary meeting. The documents include the updated reflection paper on the risk of antimicrobial resistance transfer from companion animals and guidelines on what to do when a vaccine is suspected to be contaminated with bovine viral diarrhea virus. Reflection Paper I EMA Guidelines

MHRA has warned healthcare professionals about faulty endobronchial tubes. The Cobb connectors of the affected lots can detach, potentially resulting in the system failing to ventilate the patient. MHRA Report I Field Safety Notice