EMA's Updated Guidance On Monitoring Off-Label Use Of Medicines Expected By Year End
This article was originally published in SRA
The European Medicines Agency is expected to finalize by the end of this year revisions to its policy on how drug companies should record and report off-label use of medicines not associated with an adverse reaction.
The revised policy will likely provide much needed clarity to the pharmaceutical industry on this important topic, and help companies achieve regulatory compliance.
While instances of off-label use associated with an adverse event have to be routinely collected by drug companies and reported to regulatory authorities if the case fulfils certain criteria, companies are also required to take into consideration any information related to a drug's off-label use, whether or not it is associated with an adverse event, for inclusion in the drug's periodic safety update report (PSUR).
"We all know these requirements, but it's the reality of how these things are played out that is [posing] a challenge," said Emma Du Four, senior director (regulatory policy and intelligence) at AbbVie, who was speaking at a conference organized by the Drug Information Association in London for qualified persons for pharmacovigilance (QPPVs).
Du Four explained that there is variability among regulators on how these requirements should be met, which has created uncertainty among inspectors and has also resulted in some companies currently putting "every instance of confirmed off-label use, of which they become aware, into their global safety database, even if there is no associated adverse event."
The EMA's revised policy on the management of individual reports of off-label use that do not lead to suspected adverse reactions will be published in an updated question and answer document intended to support the implementation of the EU pharmacovigilance legislation1.
In July, members of the EMA's pharmacovigilance committee, PRAC, were asked to comment on the draft revised policy2. "We are currently reviewing the remarks raised by PRAC members in July with the aim to present a new version to PRAC and finalise the document by the end of 2015. Until a new update is adopted, the current guidance provided in question 8.2 of the Q&A document" should be followed, an EMA spokesperson told Scrip Regulatory Affairs.
Earlier this year, the draft revised policy3 was also presented to industry stakeholders at the second EMA-industry platform meeting on the operation of EU pharmacovigilance legislation on Jan. 12. At that meeting, the EMA had clarified that if a marketing authorization holder receives a report on the off-label use of a drug with no adverse reaction, there is no legal requirement to record such reports in the company's database for the collection of individual case safety reports (ICSRs). Also, there is no requirement to submit ICSRs on off-label use if not linked to a suspected adverse reaction.
However, the EMA clarified that such information has to be collected by companies in order to fulfil other pharmacovigilance tasks, such as: conducting signal detection; continuously monitoring the benefit-risk balance of medicinal products; producing PSURs; and informing regulators of any changes to the drug's benefit-risk balance.
Hence, appropriate recording mechanisms should be in place to ensure that these reports of off-label use are considered in signal management activities and included in Risk Management Plans and PSURs, as necessary, the EMA said at the January meeting.
References
1. Questions and Answers to support the implementation of the Pharmacovigilance legislation - Update, November 2012 (EMA/228816/2012 – v.3), Nov. 30, 2015, www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2012/05/WC500127658.pdf
2. PRAC: Minutes of the meeting on 6-9 July 2015 (EMA/PRAC/269153/2015), posted online Sept. 23, 2015, www.ema.europa.eu/docs/en_GB/document_library/Minutes/2015/09/WC500194105.pdf
3. Q&A on Off-Label Use: EMA Industry Stakeholder Platform - Operation of EU Pharmacovigilance Legislation, Jan. 12, 2015, www.ema.europa.eu/docs/en_GB/document_library/Presentation/2015/03/WC500184248.pdf