AUTH/2422/7/11 - Pharmacosmos v Vifor

Ferinject leavepiece

  • Received
    27 July 2011
  • Case number
  • Applicable Code year
  • Completed
    15 November 2012
  • Breach Clause(s)
    7.2 (x2)
  • Sanctions applied
    Undertaking received
  • Additional sanctions
    Audit of company’s procedures
  • Appeal
    No appeal. Report from PMCPA Panel to Appeal Board
  • Review
    February 2013

Case Summary

Pharmacosmos complained about a Ferinject (ferric carboxymaltose) solution for injection/infusion leavepiece issued by Vifor Pharma. Ferinject was indicated for the treatment of iron deficiency when oral preparations were ineffective or could not be used. The claims at issue were both referenced to Geisser (2009).
The detailed responses from Vifor are given below.
Pharmacosmos alleged that the claim 'Ferinject avoids dextran-induced hypersensitive reactions' was not balanced or fair because there was no mention that Ferinject itself might cause hypersensitivity reactions as stated in the Ferinject summary of product characteristics (SPC). The material was not sufficiently complete to enable the recipient to form their own opinion of the therapeutic value of the medicine.
The Panel noted that the Ferinject SPC, stated that 'Parenterally administered iron preparations can cause hypersensitivity reactions including anaphylactoid reactions, which may be potentially fatal ... Therefore, facilities for cardio-pulmonary resuscitation must be available'. Hypersensitivity including anaphylactoid reactions was listed as an uncommon side effect. The only reference to this possible side effect to Ferinject in the leavepiece was in the prescribing information. The Panel did not accept Vifor's submission that the prescribing information provided all the relevant safety information about hypersensitivity reactions. Claims had to be capable of standing alone without reference to, inter alia, prescribing information to correct an otherwise misleading impression.
In the Panel's view, the claim highlighted the hypersensitivity issue and sought to minimise the prescriber's concerns about such reactions with Ferinject and in that regard might compromise patient safety. The Panel considered that the claim was misleading and a breach was ruled.
Pharmacosmos alleged that the claim 'Ferinject has a low molecular weight thus limiting adverse events' which appeared as a bullet point immediately beneath the claim at issue above was misleading. There was no proven link between the molecular weight of Ferinject and the adverse event rate.
The Panel noted that Geisser stated that the tolerability of iron compounds depended not only on the reactivity of the iron and how easily it was released from the carbohydrate but also on the size of the iron-carbohydrate complex and the nature of the carbohydrate moiety. A relationship between release rate and acute toxicity was noted. The Panel considered that the claim implied a simplecorrelation between molecular weight and side effects. In the Panel's view the situation was more complex than that. The Panel considered that the claim sought to minimise a prescriber's concerns about all side effects with Ferinject and in that regard might compromise patient safety. The Panel ruled that the claim was misleading and in breach of the Code.
During its consideration of the case, the Panel noted that both of the claims at issue had been ruled to be misleading with regard to the safety profile of Ferinject; it considered that each would minimise a prescriber's concerns in that regard. Activities prejudicial to patient safety were regarded as serious matters and so the Panel reported Vifor to the Appeal Board in accordance with Paragraph 8.2 of the Constitution and Procedure.
The Appeal Board was extremely concerned about the material at issue; that it had the potential to compromise patient safety was a serious worry. It had been certified as required by the Code. The Appeal Board was concerned that, as in Case AUTH/2411/6/11, this case raised very serious concerns regarding the expertise of Vifor signatories and the role of senior management in compliance matters.
The Appeal Board noted that Vifor had accepted that it had made serious errors and in that regard it had already started to review its policies and procedures. Nonetheless, the Appeal Board decided that Vifor's procedures in relation to the Code should be audited as soon as possible by the Authority. The audit would take place at the same time as that required in Case AUTH/2411/6/11. On receipt of the audit report the Appeal Board would consider whether further sanctions were necessary.
Vifor was first audited in November 2011 and upon receipt of that audit report the Appeal Board was concerned that Vifor had much work to do. It noted from Vifor's response that a preliminary corrective and preventative actions programme had been drawn up. It requested that Vifor be asked to provide timescales. It also decided that Vifor should be asked to provide copies of the correspondence between the company and its head office about the audit report and details about the role of an external consultant.
The Appeal Board was concerned to note that since deciding that Vifor should be audited, another case, which involved a breach of undertaking (Case AUTH/2442/10/11), had been considered by the Panel. On the day of the audit that case was still on going and so was not discussed. The Appeal Board noted, however, that the case had now completed.
The Appeal Board decided that Vifor should be reaudited in March 2012. On receipt of the report for that audit, the Appeal Board would consider if further sanctions were necessary.
Upon receipt of the March 2012 audit report the Appeal Board was disappointed at the lack of progress since the November 2011 audit particularly with regard to the revision of standard operating procedures (SOPs). The Appeal Board noted that new staff were due to be appointed. The Appeal Board considered that Vifor should be re-audited in six months time at which point it expected there to be significant improvement. In the meantime Vifor should provide by the end of June a detailed interim response to the recommendations of the March 2012 audit to include an update on recruitment and SOPs. If the Appeal Board was not satisfied then the reaudit would be brought forward.
Upon receipt of the next audit report, the Appeal Board would decide whether further sanctions were necessary.
On consideration of the interim response from Vifor the Appeal Board decided there was no need to reaudit sooner than the currently arranged date, in October 2012.
Upon receipt of the October 2012 audit report, the Appeal Board noted that good progress had been made since the last audit. New staff had been appointed who would have key roles in compliance. New standard operating procedures had been written and resources had been committed to Code compliance. The Appeal Board considered that on the basis that Vifor's current commitment to compliance was maintained, no further action was required.