Euro Roundup: EMA seeks feedback on quality, therapeutic equivalence of inhaled drugs

The European Medicines Agency (EMA) has released two draft guidelines for consultation on inhaled medicines. One covers the pharmaceutical quality of inhalation and nasal medicinal drugs, while the other addresses therapeutic equivalence between orally inhaled products.

The quality document was drafted to replace a 2006 guideline. EMA said its aim is to consolidate the 2006 guideline with related published questions and answers while “taking into consideration recent advancements in the field, common practice and new regulations, including the medical device regulation.”

Some of the existing text remains, but the titles and content of most subsections have changed. EMA proposes to add some new subsections and completely delete others.

One addition is a subsection on novel excipients, where EMA explains that companies should provide “full details of manufacture, characterization, and controls with cross-reference to supporting safety data” for excipients that have not previously been used in inhaled products. EMA also requested the name and address of the supplier and a general outline of the manufacturing and purification processes.

The quality draft references the other guideline now open for consultation, noting that the two guidelines are complementary and should be read in conjunction.

The therapeutic equivalence draft is the second revision of a guideline. Like earlier versions, the text explains the requirements for demonstrating therapeutic equivalence between orally inhaled products for asthma and chronic obstructive pulmonary disease.

In the updated text, EMA clarifies the use of a stepwise approach. Equivalence could be shown “if all in vitro requirements are fulfilled or else preferably by means of pharmacokinetics if equivalent systemic exposure (as a surrogate marker for safety) and equivalent lung absorption/deposition (as a surrogate marker for efficacy) is demonstrated in spite of some in vitro differences.”

It is “generally not recommended” to aim to show equivalence using pharmacodynamic or clinical endpoints “as these are deemed insensitive,” according to the document. That thinking led the agency to shorten or delete text on pharmacodynamic and clinical endpoints that were in the previous version of the guideline.

The agency has also shortened a section on children and adolescents. In many cases, EMA now accepts the same age limits as for the reference product. Officials also explained the conditions for extrapolating pharmacokinetic data from healthy volunteers to the full patient population and deleted some general information on pharmaceutical forms.

EMA is accepting feedback on the therapeutic equivalence draft until 30 October and on the quality draft until 31 October.

Quality Draft, Equivalence Draft

EMA consults on private information in marketing authorization filings

EMA and the Heads of Medicines Agencies are seeking feedback on a proposed approach to identifying personal data and commercially confidential information in marketing authorization application dossiers.

The agencies defined a common approach to what should be considered personal data and commercially confidential information in 2012 and agreed to update it last year. The resulting draft applies to documents on medicinal products for human use under the national, mutual recognition, decentralized and centralized procedures.

EMA will apply the rules to initial and variation applications once those applications are “finalized,” a term defined as meaning the authorization has been granted, refused or withdrawn. The principles also apply to orphan designations, pediatric investigation plans and scientific advice.

The agencies have proposed principles on the protection of personal data, explaining that the term mainly applies to experts with legally defined responsibilities, staff without legally defined responsibilities, clinical trial subjects and patients in the context of medicine safety. The draft features paragraphs about each type of personal data.

EMA and its collaborators have also provided principles for the redaction of commercially confidential information, a term the draft defines as “information that is not in the public domain or publicly available, and where its disclosure may undermine the economic interest or competitive position of the owner of the information.”

Regulators will assess redactions proposed by the owner of the information, taking into account their justification, to decide whether the commercially confidential definition applies. EMA will not consider information that is in the public domain to be commercially confidential unless it was made public “through a breach of the law.”

The consultation closes on 28 June.

Draft Guidance

MDCG publishes guidance on in vitro diagnostic medical device safety reporting

The Medical Device Coordination Group (MDCG) has shared guidance on safety reporting in performance studies of in vitro diagnostic (IVD) medical devices under the new regulation.

The In Vitro Diagnostic Medical Devices Regulation (IVDR) requires sponsors to report to all member states “without delay” serious adverse events that have a causal relationship with the device as well as certain other safety findings generated in performance studies. The regulation says the “period for reporting shall take account of the severity of the event” and allows sponsors to submit an initial incomplete report to ensure timely reporting.

MDCG has interpreted those requirements in a 23-page document that covers topics such as the reporting method and timelines and how to assess causality. Sponsors must tell national authorities about the most serious events within two calendar days. The deadline for other types of safety events is seven calendar days.

Sponsors must assess and categorize the relationship between the IVD and each serious adverse event. MDCG said “clinical judgment must be used” and relevant documents such as the investigator’s brochure must be consulted. Sponsors should also consider confounding factors such as the natural history of the disease.

The assessments inform the categorization of adverse events into one of four levels of causality: not related, possible, probable and causal relationship. MDCG has provided details of each group, explaining that an IVD could be found to have a causal relationship to an adverse event when an error in use caused harm to the subject.

MDCG Guidance

PRAC rules out link between GLP-1 drugs and suicidal ideation

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has found there is insufficient evidence to support a causal link between GLP-1 receptor agonists and suicidal and self-injurious thoughts and actions.

PRAC began investigating the class of medicines, which includes Novo Nordisk’s blockbuster diabetes and weight-loss molecule semaglutide, in June 2023 after seeing case reports of suicidal thoughts and thoughts of self-injury. The reports covered patients on semaglutide and liraglutide, another Novo drug. PRAC expanded the investigation to cover other GLP-1 molecules in November 2023.

“After reviewing the available evidence from non-clinical studies, clinical trials, postmarketing surveillance data, and the available studies, the PRAC considers that no update to the product information is warranted,” EMA wrote. “The marketing authorization holders for these medicines will continue to monitor these events closely, including any new publications.”

The conclusion was informed by an analysis of electronic health records that found no causal association as well as another EMA study that reached a similar conclusion.

EMA Notice

Euro Roundup: EMA seeks feedback on quality, therapeutic equivalence of inhaled drugs

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