ICON plc has received a warning letter from the US Food and Drug Administration (FDA) over study management services provided to a client for two clinical trials conducted between 2004 and 2006 with an antibiotic for complicated skin and skin-structure infections.

The FDA letter “arises from its inspections of the company’s client and selected clinical sites and follows a similar letter issued to that client”, noted the global provider of outsourced clinical development services based in Dublin, Ireland.

ICON did not specify who the client was or the product involved. Enquiries prompted the statement: “Due to client confidentiality and as a policy, ICON does not comment on the specific details of studies we carry out on behalf of our sponsors”.
The most likely candidates, though, are Johnson & Johnson (J&J) and ceftobiprole, the anti-MRSA antibiotic developed by J&J in partnership with Switzerland’s Basilea Pharmaceutica.

The drug, which is aimed at complicated skin and skin structure infections, including diabetic foot infections, is sitting in regulatory limbo in the key US and European markets after the FDA identified deficiencies at trial sites used by J&J in its late-stage development of ceftobiprole.

The US company is reported to have farmed out Phase III development of ceftobiprole to ICON, while the timescale cited by the contract research organisation matches the dates in a warning letter sent by the FDA to Johnson & Johnson in August 2009. That letter did not mention ceftobiprole by name either, but Johnson and Johnson confirmed the US agency’s concerns related to the drug.

The FDA said an investigation of Johnson & Johnson Pharmaceutical Research & Development’s role as sponsor of the antibiotic studies had revealed “objectionable conditions” that were not adequately addressed in the company’s responses to a Form FDA 483 inspection report sent out in June 2008 and to later requests for information.

In November 2008, the FDA set back a decision on the New Drug Application for ceftobiprole until it had resolved “issues of data integrity” raised in a complete response letter for the drug. The letter cited J&J’s “failure to ensure proper monitoring of the studies” submitted with the NDA. It requested information on the company’s clinical quality assurance programmes and a new audit plan addressing “deficiencies in contract research organisation monitoring”.

Subsequently, the European Medicines Agency’s Committee for Medicinal Products for Human Use told J&J that full approval of ceftobiprole in the EU (for the treatment of complicated skin and soft tissue infections) would have to be stalled pending Good Clinical Practice inspections of trial sites run by Janssen-Cilag in the late development programme.

Recently, analysts were alarmed to find that the FDA would not be discussing ceftobiprole at an advisory committee meeting this month. Basilea has filed a damages claim against J&J over delays to the approval of ceftobiprole in the US and Europe.
ICON would not be drawn on what the FDA warning letter might mean for the company, when it expected to resolve the problems identified in the letter (which has not yet been made public) or what impact the FDA’s action might have on the ceftobiprole approval schedule.

“ICON is committed to working cooperatively and expeditiously with the FDA to address the matters raised in the letter,” the company stated.