The European Medicines Agency (EMA) has released a new draft guideline intended to leverage pharmacogenomics in tracking and evaluating adverse events in products once they have received approval.

Background

Pharmacogenomics refers to the way in which different people are affected in different ways by the same drug, owing largely to their genetic composition. Some genes may cause a drug to be more potent than originally intended, while other genes may cause a drug to be less safe.

In other words, "there may be subsets or patients with a different benefit/risk profile," EMA wrote in its draft guidance, Key aspects for the use of pharmacogenomic methodologies in the pharmacovigilance evaluation of medicinal products.

The question for both regulators and industry, then, is this: How can pharmacovigilance-the monitoring of pharmaceutical products in post-marketing environments-take into account the pharmacogenomic differences between patients and translate them into more nuanced recommendations?

For example, assume a pharmaceutical company with an approved product received several reports of patients experiencing unexpected adverse events. In most instances, the company would need to report those events to EMA or the local competent authority, which in turn would evaluate the events and possibly issue a notice regarding an elevated risk of the event in the product.

A Matter of Safety

But does that really help patients to understand the risks of the product and how to properly use it? Not really, which is why EMA is calling on companies to work harder to identify genetic sub-populations who may have either increased or decreased sensitivity to medicines.

The process of identifying those patients should begin while the drug is in development, but continue long after approval, EMA said. Though regulators conceded that the process was easier said than done, and relied in large part on the state of the art of knowledge at the time of the drug's approval, efforts to understand differences in patients should remain a priority throughout a drug's lifecycle.

The draft guideline goes on to take note of various factors well known to most within industry: People of different ages, ethnicities and health statuses may experience pharmacological effects differently owing to their genes.

But perhaps most importantly, the guideline describes how industry can implement pharmacogenomics into risk-management plans (RMP), risk-minimization measures, signal detection and the benefit-risk evaluation of medicines.

"In the safety specification of RMP, important identified or potential risks or missing information related to the use of the medicinal products in the target population and potential off-label use, should be discussed with reference to pharmacogenomics," EMA wrote in the guideline.

Elsewhere in the guideline, EMA notes that "it is important that an effective pharmacovigilance system is in place in order to capture otherwise unidentified reactions related to specific genomic traits of individuals … unidentified genomic biomarkers' influence on serious adverse reactions may be discovered from the post-authorisation experience."

"Pharmacogenetic influence on the occurrence of therapy failure should be investigated in the post-authorisation period," regulators added.

Comments on the draft guideline are due by 30 July 2014.

 

Draft Guideline

EMA Statement