Low API and excipient volumes vital to win authorisation under EU PIP says EMA

Pharmas should use lower API and excipient volumes if seeking authorisation under the EU Paediatric Investigation Plan (PIP) says the EMA.

The advice came from Catherine Tuleu, chair of the European Medicine Agency’s Paediatric Formulation Innovation Committee, who told attendees at AAPS in Chicago, US last week to be mindful of the potential risks high dose drugs pose for children.

“Don’t use big volumes then you can’t overdose easily” she said, adding that drugmakers also need to “consider who will administer the treatment often the parents, rather than a trained physician.”

As for excipients Tuleu said: “Consider that a patient in intensive care will be receiving a lot more drugs will be exposed to a lot of excipients compared to a child on a one week course.”

During the same symposium, FDA director of the Division of Product Quality Research Mansoor Khan, said another way to ensure safe excipient usage in drugs for children is to look at those already on the market.

“There are formulations which are already approved in the US, for instance drops, syrups, suspensions, sprinkles, capsules, inhaled therapies and rectal administration,” he said. “If it has been used before and is safe, then use it.”

Tuleu agreed and added that consulting databases such as ESNEE (European Study of Neonatal Exposure to Excipients), which looks into the safe use of excipients for neonatal indications, could also help.

New formulations

Also in attendance was Anne Zajicek, chief of the US National Institute of Health’s (NIH) Child Health and Human Development programme, who put forward the opposing view, suggesting that – where there is a need for drug delivery designed specifically for children – new formulations can increase the chances of approval.

Zajicek explained that some drugs are administered in inappropriate forms for children, citing a document from the Children’s Hospital of Minnesota which explains how parents can crush tablets at home before mixing them with food to make them more acceptable.

“But in treatments such as chemotherapy you’re exposing the whole house to harmful substances,” she said.

Tuleu also agreed that new dosage forms could help address this, suggesting mini tablets that can be taken by children as young as six months old as an example.

“Placebo tablets have been shown to be accepted by two to three year olds, who even preferred it to syrup,” she said. 

“The parents preferred it too because often the work involved preparing medications – such as mixing it with food products – is tricky and easy to get wrong."