AUTH/3169/3/19 - Voluntary admission from Otsuka Europe

Revision of Jinarc SPC

  • Received
    12 March 2019
  • Case number
  • Applicable Code year
  • Completed
    05 July 2019
  • Additional sanctions
  • Appeal
    No appeal
  • Review
    Published in the May 2020 Review

Case Summary


Otsuka Pharmaceuticals Europe, voluntarily admitted that it might have breached the Code with regard to updates to the Jinarc (tolvaptan) summary of product characteristics (SPC).  Jinarc was used in certain patients with chronic kidney disease.

As Paragraph 5.6 of the Constitution and Procedure required the Director to treat a voluntary admission as a complaint, the matter was taken up with Otsuka Europe.

Otsuka Europe explained that there had been two parallel revisions to the Jinarc SPC since November and these had been communicated to the marketing authorization holder and all relevant European affiliates.  The preliminary investigation concluded that communication to the affiliates on 14 February could have been clearer on this point.

Otsuka Europe regretted that communications to EU affiliates about SPC revisions had caused confusion and that as a result there was a Jinarc SPC available on the eMC from 15 February to 1 March which contained the latest revision (addition of gout) but not the preceding revision (addition of blister wallet cards).  Otsuka Europe was concerned that there might have been a breach of the undertakings given in Cases AUTH/3041/6/18 and AUTH/3123/11/18.

Otsuka Europe stated that it also became aware in January 2019 that there was a mistake in the packaging and release of the Jinarc package leaflet in that the previous version of the package leaflet was packaged with the product.  The company notified the EMA and the Medicines and Healthcare products Regulatory Agency (MHRA) on 17 January 2019 about that situation.  During the following days the issue was discussed with the EMA.  The EMA confirmed on 6 February that no Direct Healthcare Professional Communication (DHPC) was required.

The detailed response from Otsuka Europe is given below.

The Panel noted that there had been two parallel revisions to the Jinarc SPC (addition of blister in wallets cards with new marketing authorization numbers and addition of gout as a common adverse drug reaction) and that the two revisions were each subject to separate applications to the EMA and therefore a combined consolidated version also had to be approved by the EMA.

The Panel noted, based on Otsuka Europe’s submission, that when two or more variation applications were submitted and/or assessed in parallel by the EMA, the procedures were kept separate, and further noted Otsuka Europe’s submission that, in this case, having an SPC with gout but without the preceding blister wallet cards revision was unavoidable.  However, the Panel noted Otsuka Europe’s submission that the communication to the affiliates dated 14 February regarding this matter could have been clearer so they could have planned how to deal with this situation, and that the communication regarding the consolidated SPC sent to the affiliates on 26 February had not followed the relevant SOP and caused confusion in the affiliates.

The Panel considered that the lack of clear communication by Otsuka Europe to its affiliates, which was compounded by the failure to follow, and lack of consistent application of, the relevant SOP, meant that Otsuka Europe had failed to maintain high standards and a breach was ruled.

The Panel noted that in Case AUTH/3041/6/18, Otsuka Europe was found in breach of the Code for promotional materials either missing prescribing information or not containing the latest version of the prescribing information, for Otsuka Europe’s governance of materials falling below acceptable standards, and Clause 2 for, inter alia, not providing prompt communication to Otsuka UK regarding SPC updates and poor governance which the Panel had considered had potential safety implications.  Although there was some overlap between Case AUTH/3041/6/18 and the current case, the Panel noted that there were important differences.  The subject matter of the former did not include the accuracy of communications about SPC updates in relation to Jinarc.  The voluntary admission in Case AUTH/3169/3/19 did not refer to use of materials with the incorrect prescribing information.  The Panel therefore considered, on balance, that the subject matter of the current case was sufficiently different to Case AUTH/3041/6/18 such that there was no breach of the undertaking given in that case. The Panel therefore ruled no breach of the Code including Clause 2 in this regard.

In relation to the admission of a breach of undertaking and Case AUTH/3123/11/18, Otsuka Europe referred to the email from Global Regulatory Affairs Region Europe dated 26 February 2019 and failure to follow process and causing confusion.  In Case AUTH/3123/11/18, Otsuka Europe was found in breach of, inter alia, Clause 9.1 for lack of clear and consistent instructions to employees and third parties in relation to SPC changes and Clause 2 for its failure to timely and robustly address inadequacies in this process.  The Panel considered that the breach of Clause 9.1 for the lack of clear communication to its affiliates and lack of consistent application of the relevant SOP in the current case (Case AUTH/3169/3/19) meant that Otsuka Europe had breached the undertaking given in Case AUTH/3123/11/18.  The Panel therefore ruled a breach of Clause 29.  The Panel considered that Otsuka Europe’s breach of undertaking meant that it had brought discredit upon, and reduced confidence in, the pharmaceutical industry and a breach of Clause 2 was ruled.

The Panel noted Otsuka Europe’s admission in relation to an out-of-date package leaflet being packaged with Jinarc at the manufacturing site.  The Panel noted Otsuka Europe’s submission that the manufacturing site was notified on 12 October 2018 of an upcoming revision to the leaflet with an implementation of 30 November 2018 but it mistakenly used the previous version.  The Panel considered that Otsuka Europe had been let down by its manufacturing site.  The Panel considered that the package leaflet was an important document for patients and such an error meant that Otsuka Europe had failed to maintain high standards and a breach of the Code was ruled.  The Panel considered that a breach of Clause 2 was a sign of particular censure.  The Panel noted that Otsuka Europe had liaised with the European Medicines Agency (EMA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) with regard to this error and noted the actions Otsuka Europe submitted that it had agreed with the EMA on the matter.  The Panel considered that, in these particular circumstances, and on balance, no breach of Clause 2 was warranted.