The European Medicines Agency (EMA) has released for consultation a new guideline on assessing the preclinical safety of products intended to be used by patients with decreased renal function.
The kidney is responsible for filtering waste products from the body, among other essential functions. In patients with decreased renal function, the kidney is sometimes unable to process all metabolized chemicals (such as those from pharmaceutical products) out of the body, leading to adverse health effects.
For regulators and product manufacturers, this represents a common problem. Ageing patients often experience a decrease in renal function, and patients with renal disease are not uncommon. How, then, can regulators ensure that drugs intended for these patients are safe?
A newly revised guideline, on the evaluation of the pharmacokinetics of medicinal products in patients with decreased renal function, aims to provide more-and safer-options for patients with renal impairment.
As EMA notes in the guideline, "patients with renal impairment are often excluded from the pivotal studies establishing efficacy and safety of a new medicinal product"-something EU regulators don't seem eager to change.
Instead, they're recommending an approach based on pharmacokinetic data intended to determine how drugs will function in patients with decreased renal function. That data will be used to establish dosing recommendations in those patients, the guideline states.
"The need to perform a pharmacokinetic study in subjects with decreased renal function and the design and conduct of such a study depend on the characteristics and intended use of the drug under investigation." Regulators add in the guideline. "The development of dosing recommendations should be based on the change in drug exposure or plasma concentrations at decreased renal function as well as on the pharmacokinetic/pharmacodynamic relationship for the drug."
EMA said it would highly recommend studying drugs that are eliminated mainly by the liver, and also revised the prior guideline to place additional emphasis on the use of an "accurate method" for determining the glomerular filtration rate (GFR), or the rate at which the liver is able to process blood.
The guideline includes proposed study designs, measures of renal function, how to collect and analyze samples, and how to develop dosing recommendations based on data.
Comments on the draft are due by 31 August 2014.
On the evaluation of the pharmacokinetics of medicinal products in patients with decreased renal function