Euro Roundup: EMA floats ‘change in paradigm’ for pregnant and breastfeeding patients in clinical trials

The European Medicines Agency (EMA) has published draft recommendations on how to include and retain pregnant and breastfeeding patients in clinical trials.

EMA and other regulatory agencies developed the guideline through the International Council for Harmonisation (ICH) to address the lack of evidence of how people who are pregnant or breastfeeding respond to medicines. Pregnant and breastfeeding patients are respectively included in 0.4% and 0.1% of all clinical trials submitted to EMA.

Yet, “The vast majority of pregnant people take medications, for example because of chronic diseases, infections or pregnancy complications,” EMA said. The same applies to breastfeeding individuals. The lack of data can lead to suboptimal treatment decisions and potential harm.

ICH E21 is designed to address the knowledge gap. EMA said the guideline “marks a change in paradigm in the development of medicines in pregnancy and breastfeeding.” The guideline features advice on the appropriate inclusion of pregnant and breastfeeding individuals in trials to facilitate the generation of data that allow for evidence-based decision-making on the safe and effective use of medicinal products.

The guideline makes separate recommendations for pregnant and breastfeeding patients. When a drug is likely to be used by individuals of child-bearing potential, sponsors should collect data in the patient population as early as possible. Sponsors addressing an “especially high medical need” should aim for “early acquisition of data from pregnant individuals unless there exists justification for postponement.”

ICH E21 covers the evidence sponsors need to support the inclusion of pregnant patients in clinical trials, what to do when there are gaps in the evidence and how to proceed when data suggest there is a safety concern. The benefits of use in pregnancy may still outweigh the potential risks when a safety concern is identified, ICH said.

Another section of the guideline addresses how to recruit and retain pregnant individuals. ICH suggests engaging patient advocacy groups, organizations managing disease specific registries and clinicians experienced in conducting research in pregnant individuals before starting a trial to reduce barriers to recruitment. The outreach can show how to make trials less burdensome for pregnant participants.

EMA is accepting feedback on the draft until 15 September.

Press Release

MHRA shares guidance on developing bacteriophages for therapeutic use in the UK

The Medicines and Healthcare products Regulatory Agency (MHRA) has published the UK’s first official guidance to support the safe development and use of phage therapies.

Interest in the therapeutic use of bacteriophages, viruses that can infect and destroy bacteria, has grown as microbes have developed resistance to antibiotics. Lawrence Tallon, chief executive at MHRA, outlined the need for the guidance.

“Some infections are becoming harder to treat when antibiotics are ineffective against them, and patients urgently need new options,” Tallon said. “Phage therapy is one of several promising approaches. This guidance brings together relevant standards to provide clarity for researchers and companies, so they can develop these treatments safely and bring them to the people who need them.”

The viruses currently used therapeutically break through the cell wall and destroy the bacterial host. Other bacteriophages incorporate their DNA into the host genome. Such lysogenic viruses are yet to be used therapeutically. MHRA wants to see sufficient evidence the mechanism does not pose an unacceptable risk before supporting their use. Synthetic phages are outside of the scope of the guidance.

MHRA’s guidance covers two types of phage therapy. Viruses can be given as a defined cocktail that shows effective killing of the patient clinical isolate or as a personalized therapy designed to address a resistant bacterial infection or help a patient who is intolerant to standard antibiotics.

The UK is yet to authorize a bacteriophage medicinal product. Phage therapies are classed as medicinal products — and could be treated as gene therapy medicinal products when genetically modified — and need to meet the same efficacy, safety and quality approval requirements as other medicines. The MHRA guidance covers the law on special circumstances when exemptions to the rules may apply.

Other sections of the guidance collate the range of UK and international documents that apply to phage therapies. The documents do not specifically relate to bacteriophages but apply to the products because phage therapies meet the medicinal product definition.

MHRA Guidance, Press Release

EMA updates nitrosamine advice for marketing authorization holders and applicants

EMA has shared new advice on marketing authorization holders and applicants’ ongoing responsibilities related to nitrosamines.

In an update to existing guidance, EMA said holders that are yet to report on their nitrosamine impurities risk assessment or evaluation “should do so as a matter of priority.” The request applies to companies that need to provide updates to previous notifications. EMA said holders have an obligation to monitor and mitigate nitrosamine risks throughout the drug lifecycle and should take precautionary measures.

Companies that need to implement corrective and preventative actions should adopt the changes within three years of the establishment of acceptable intake limits. EMA wants companies that are unable to hit the deadline to provide a detailed justification to the relevant authorities.

“At all steps, [holders] should promptly inform authorities if findings indicate an immediate risk to public health,” EMA said. “EU competent authorities may check compliance with the expectations on nitrosamines through routine inspections and marker surveillance activities.”

EMA Advice

Swissmedic revises conjugated pneumococcal vaccine rules to support immunobridging

The Swiss Agency for Therapeutic Products (Swissmedic) has begun considering extrapolations of efficacy based on immunobridging as evidence in support of conjugated pneumococcal vaccine applications.

Swissmedic updated its requirements for authorization of the vaccines in light of evidence such as data on their real-world use. Growing experience with the vaccines, both in Switzerland and overseas, led the regulator to support the use of immunobridging. The approach allows researchers to infer the efficacy of a vaccine through a surrogate measure.

Companies have shown conjugated pneumococcal vaccines are effective in adults aged 65 years and older and children younger than five years of age. Younger adults typically mount a stronger immune response than seniors, suggesting the vaccines will also be effective in both populations.

Swissmedic said new pneumococcal vaccine efficacy studies would require very large sample sizes that limit the feasibility of the trials. Rather than run such large studies, developers can give Swissmedic “comparative immunogenicity data for different age groups together with a sound justification for the proposed immunobridging strategy” to extrapolate efficacy.

Swissmedic Notice

ABPI warns UK could lose £11B in pharma R&D investment over drug pricing policy

Pharma trade group ABPI has warned “very high and unpredictable medicines sales clawbacks” could deprive the UK of £11 billion ($15 billion) in R&D investment by 2033.

Drugmakers pay the UK government a portion of revenue from sales of branded medicines to the health service. A report commissioned by ABPI predicted that the UK will lose the R&D investment if the payment rate stays above 20%. The UK can prevent the lost R&D investment by returning new medicine payment rates to the pre-2023 levels of below 10%, according to the report.

One-fifth of companies expect to reduce R&D investment as a direct result of the current payment rate. The proportion of companies that said the UK is one of the top three countries to launch medicines has fallen from 30% in 2022 to 13% in 2025.

Press Release

Euro Roundup: EMA floats ‘change in paradigm’ for pregnant and breastfeeding patients in clinical trials

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