EMA Draft Guidance Seeks to Speed New Antibiotics Development

Regulatory NewsRegulatory News | 28 September 2015 |  By 

The European Medicines Agency (EMA) is seeking comment on a new draft guideline that could help industry use of pharmacokinetics (PK) and pharmacodynamics (PD) analyses to speed the development of novel antibiotics that target multidrug-resistant bacteria and address unmet medical needs.


Like in the US, the growth of bacteria resistant to a range of antibiotics, along with the need for new antibiotics to treat patients with limited or no treatment options, spurred the EMA to offer new ways to encourage antibiotics development.

The latest draft guidance focuses on PK analyses, which deal with how a drug is absorbed by the body, distributed through the organs, transformed and excreted, and PD analyses, which, in the context of antibiotics, relates to the drug's ability to kill or inhibit the growth of bacteria at a given dose.

Both analyses play an increasing role during antibiotic development by providing evidence around the appropriateness of the dose and frequency of administration to ensure the appropriate risk-benefit balance. They also provide data to inform the selection of dose regimens that may minimize the risk of developing resistant bacteria.

With reflections on recent scientific advances and the regulations, the guidance is meant to help industry conduct these analyses, which can potentially help to streamline a clinical development program.

"These analyses are particularly crucial in the development of new antibiotics that address unmet medical needs or target multi-drug resistant bacteria since they contribute to streamlining and accelerating the development using innovative data-gathering strategies, in line with the new regulatory approach described in the  EMA addendum to the guideline on the evaluation of medicines for the treatment of bacterial infections," EMA says.

Specifics of Draft Guidance

In some cases, EMA says, the use of PK-PD analyses to identify potentially efficacious dose regimens has reduced or replaced the need for clinical dose-finding studies, allowing companies to more quickly progress to pivotal efficacy studies.

But before embarking on such analyses, EMA points out that it's essential that companies collect adequate microbiological data to describe the range of minimum inhibitory concentrations of the test agent against individual species, genera or organism groups (e.g. enterobacteria) relevant to the proposed indications.

"PK-PD indices may be identified from in-vitro and/or in-vivo PD models, leading to establishment of nonclinical PD targets (PDTs) for the most important pathogens relevant to the intended clinical uses," EMA says.

In addition to the guidance, EMA is organizing an invitation-only  workshop on 12-13 November with experts from the field to discuss the draft guideline and its finalization. The workshop will be broadcast live on the EMA website.

Netherlands MEB

The draft guidance comes as Medicines Evaluation Board (MEB) of the Netherlands raised fresh alarms earlier this month about three antibiotics that will soon no longer be available there.

The MEB said it's "extremely concerning" that the antibiotics sodium penicillin G 1,000,000 IU, sodium penicillin G 10,000,000 IU and Penidural will no longer be available as these injections are part of various protocols followed by doctors to treat pneumonia, syphilis and various infections of the skin, muscles and tendons.

Drugmaker Astellas, which did not respond to a request for comment by press time, previously informed MEB that the discontinuation of the antibiotics is due to the fact that the excipient sodium citrate is no longer available.

"As these penicillins are no longer available, doctors will start using broad-spectrum antibiotics. This contradicts the aim of counter-acting resistance against antibiotics," MEB says

The MEB says it's consulting with the Dutch Health Care Inspectorate (IGZ) to find solutions and, temporarily, alternative products can be imported with a physician’s declaration via the Dutch Health Care Inspectorate. In addition, the MEB has asked Astellas to explore other ways to keep these antibiotics on the market in the Netherlands.

EMA draft guideline

MEB warning


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