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Regulatory News | 03 August 2017 | By Nick Paul Taylor
Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
The European Medicines Agency (EMA) is encouraging drug developers and regulators to consider the needs of older people when designing and assessing medicines and their packaging. EMA took the step to drive the development of products that cater to the difficulties some older people face when trying to break tablets or open containers.
Members of EMA’s Quality Working Party set out their thinking in a draft reflection paper. The text outlines how various approaches to the design and packaging of medicines affect older people. Examples cited by EMA include the consequences of decisions about the route of administration, dosing frequency and container closure systems. This gives the document a broad scope in keeping with EMA’s desire for it to condense the current state of discussions on the topic.
EMA wants to focus the next stage of the discussion on three sections of the reflection paper and three broader points. In the paper, EMA picks out the accuracy of tablet breaking as a topic about which it wants feedback. The agency thinks all tablets that have a break-mark must split into equal pieces when broken at that point. This applies to all populations, but is especially relevant to older people, who may find it hard to break tablets. EMA wants to avoid this to improve adherence.
The agency also wants feedback on the minimum data in regulatory submissions on the delivery of drugs via feeding tubes. Given some people rely on this route of administration, EMA wants drug developers to ensure at least one preparation of their active ingredients is suitable for delivery via feeding tubes. The product information for this preparation should include instructions.
EMA’s final point for discussion relates to the use of multi-dose dispensing systems and multi-compartment compliance aids. Use of these systems entails taking medicines from their original packaging and putting them into compartmentalized boxes designed to aid compliance. EMA is concerned this may affect stability and is encouraging companies to study the topic.
The agency also wants feedback on three broader topics relating to the paper. Officials want to know if a reflection paper is more appropriate than formal guidance, which would provide technical and regulatory requirements. EMA is also seeking feedback on the target audience for the paper and the use of the term “older people” rather than “the elderly.”
EMA is accepting feedback on the draft until the end of January. Depending on the feedback it receives, EMA may use the reflection paper and comments as the basis for draft guidelines. Either way, the agency expects sponsors to take the points raised in the paper into consideration when filing applications to market or modify products.
EMA Statement, Reflection Paper
EMA has indicated its willingness to accept reduced nonclinical development packages for certain radiopharmaceuticals. The agency made the case for streamlining development of candidates with well-known molecular structures and those that are given at microdoses in a draft concept paper.
Today, there is no specific guidance about the nonclinical development of radiopharmaceuticals for therapeutic and diagnostic purposes apart from Euratom documents on calculating the absorbed dose of radiation. This means the unlabeled components — also known as “cold” parts — of conjugated radiopharmaceuticals are subject to general nonclinical guidance, despite sometimes having distinct risk-benefit profiles.
EMA wants to address this gap with guidance tailored to radiopharmaceuticals. In a concept paper drafted to move it toward this goal, EMA outlines how the guidance may affect development. If the cold parts of a radiopharmaceutical are well known or administered in doses low enough to have negligible pharmacological activity, EMA is proposing to allow reduced nonclinical development. This is expected to reduce the use of animals and accelerate development.
The guidance will also address biodistribution studies of the cold parts of radiopharmaceuticals, good laboratory practices and types of clinical settings in which candidates are used. Given the breadth of products that fall under the banner “radiopharmaceutical” — some of which are made in small quantities without the goal of winning market authorization — EMA plans to release “generally-applicable development principles” rather than specific instructions.
EMA is accepting feedback on the draft until the end of October. The agency plans to release draft guidance on guiding principles for the nonclinical development of radiopharmaceuticals six months after completing the concept paper consultation.
Officials in Europe have given manufacturers of methylprednisolone injections containing lactose until the middle of 2019 to provide data on reformulations of their products. The demand follows a review that found the drugs may trigger allergic reactions because they contain traces of proteins from cow’s milk.
Doctors use methylprednisolone injections to treat allergic reactions. However, reports of patients suffering from bronchospasm, anaphylaxis and other serious allergic reactions after receiving the drug led to an investigation by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC). The committee ruled there is no safe level of cow’s milk protein. Given the injections are administered to patients with allergies in emergency settings where not all details of their medical histories are always known, this makes it difficult to safely administer the shots.
Now, the Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh) has endorsed PRAC’s recommendation. CMDh handles questions about drugs approved in multiple member states under the mutual recognition or decentralised procedure. As such, the group’s endorsement advances the case against methylprednisolone injections.
CMDh’s goal now is to eliminate cow’s milk proteins from the products. To do this, the group has asked manufacturers of affected drugs to “provide data allowing the replacement of formulations containing lactose from cow’s milk.” Manufacturers have until the middle of 2019 to provide the data.
In the meantime, CMDh is working to update product information to state products containing lactose must not be given to patients with cow’s milk protein allergies. Clear warnings against the use of the drugs in these patients will also be added to vials and packaging.
Kite Pharma Is set to become the first company to have a marketing authorization filing assessed under EMA’s Priority Medicine (PRIME) pathway. The status grants Kite accelerated assessment of its CAR-T cell therapy, axicabtagene.
Axicabtagene, also known as KTE-C19, was one of the first four experimental drugs admitted to the PRIME program last year. Since then, the candidate has come through a clinical trial in patients with aggressive forms of non-Hodgkin lymphoma, giving Kite the data it needs to file for approval of the CAR-T in Europe.
The novel aspects of PRIME, such as the appointment of a rapporteur, mainly apply to drugs during clinical trials. Now that Kite has filed for approval, axicabtagene will follow an accelerated assessment timeline that predates the creation of PRIME. Accelerated assessment cuts the review time from 210 days to 150 days.
Kite’s filing means it should become the first company to win approval for a CAR-T therapy in Europe. Novartis filed first in the United States but, while it also has PRIME status, it is yet to do so in Europe.
Tags: European regulatory roundup, drugs for older people, radiopharmaceuticals