MHRA Clarifies Licensing Status of Avastin for Intravitreal Administration
Following a request for judicial review by drugmakers Bayer and Novartis, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a statement clarifying that Roche's Avastin (bevacizumab) can be compounded for intravitreal administration.The judicial review was brought in response to a policy adopted by the UK's National Health Service's 12 Clinical Commissioning Groups to use Avastin to treat wet age-related macular degeneration (AMD) as the preferred treatment for that indication despite the fact that Avastin is not licensed for that indication and two other drugs, Novartis' Lucentis (ranibizumab) and Bayer's Eylea (aflibercept), are authorized for such use.
Background
Regulators and competition authorities in Europe have sparred with Roche and Novartis over the off-label use of Avastin to treat wet AMD. While Avastin is not approved to treat AMD, it has been seen as a cheaper alternative to Lucentis, which was developed by Roche's Genentech and subsequently licensed to Novartis.
Both Roche and Novartis were fined about €90 million by the Italian Competition Authority in 2014 over their efforts to encourage the use of Lucentis over Avastin. Those fines were upheld by the Court of Justice of the European Union in 2018.
MHRA Policy
As part of the judicial review, the UK High Court requested that MHRA determine whether the compounding of Avastin for intravitreal administration goes beyond what is permissible under off-label use and would thus be considered an unlicensed medicine.
In an accompanying document, MHRA points out that under UK law, off-label use involves the use of a licensed medicine for indications or populations outside its label or "in any other way in which its use is not specified," which has been interpreted to include different dosages, dosing frequencies, durations of use and different routes of administration.
"In reaching this conclusion, MHRA considers that a distinction needs to be drawn between the functions regulated in the European scheme of medicines regulation, and the clinical use of products within that marketplace," MHRA writes, noting that the regulatory scheme for medicines in the EU dictates how medicinal products are placed on the market, but does not control how they are prescribed or used by professionals once on the market.
MHRA acknowledges that were single dose syringes of Avastin for intravitreal use to be placed directly on the market, those would be considered unlicensed medicines and would require marketing authorization or an exemption for special clinical need.
MHRA