EU Court of First Instance holds that prominent Canadian researcher who discovered low efficacy and serious side effects of drug to treat thalassamia major during three clinical trials required by U. S. Food and Drug Administration and reported adverse data to EU agencies about to approve drug,

Dr. Nancy Fern Olivieri (applicant) is a Canadian physician and an internationally recognized specialist in the disease of thalassemia major (TM) (also known as Cooley's syndrome). [Editorial Note: Thalassemia is an inherited form of anemia caused by faulty synthesis of part of the hemoglobin molecule. It is difficult to treat.] The disease may affect as many as 20,000 EU citizens. Starting in 1989, the applicant undertook to run a pilot study to test the effectiveness of deferiprone. This is an oral medication used to counter the iron overload that results from the frequent blood transfusions needed to treat TM.

Based on the results of that trial, the applicant got in touch with the U.S. Food and Drug Administration (FDA) about the requirements for getting deferiprone approved in the United States. Under the FDA's guidance, the applicant helped to draw up protocols for each of the required three clinical trials. The applicant was the principal investigator for two of the trials and co-chairman of the steering committee for the third trial. Apotex Research Inc., a Canadian firm, financed all three clinical trials, which began in April 1993.

At some point during the tests, Dr. Olivieri reached the preliminary conclusion that deferiprone was ineffective in nearly half of the patients treated. She reported her concerns to the Review Ethics Board of her employer, the Toronto Hospital for Sick Children, and to the relevant authorities. In May 1996, Apotex decided to end the applicant's involvement in the three clinical trials and to abort two of the trials.

The applicant then did a later study without the financial support of Apotex. She found evidence that deferiprone was toxic to the heart and liver and that its use increased the risks of premature death from cardiac disease or hepatic fibrosis. The applicant, therefore, immediately stopped using deferiprone on humans. She and others presented those findings in an article at 339 New England Journal of Medicine 417 (Aug. 1998).

In February 1998, Apotex applied to the European Agency for the Evaluation of Medicinal Products (EMEA) for an EU marketing authorization under Article 4(1) of Regulation No. 2309/93 for Ferriprox, the active ingredient of which is deferiprone. Apotex also sent the reports from the three clinical trials of deferiprone, but the documents lacked Dr. Olivieri's signature.

The EU Committee for Proprietary Medicinal Products (CPMP) formulates the opinions of the EMEA. In January 1999, the CPMP put out an opinion that favored the grant of marketing authorization for deferiprone.

The EMEA sent this opinion to the Commission of the European Communities. Four months later, the Standing Committee on Medicinal Products for Human Use unanimously supported the Commission's draft decision.

On hearing about the CPMP's favorable opinion, Dr. Olivieri sent several letters and reports to both the EMEA and the CPMP. She told them about her observations on the low curativeness of deferiprone plus the substantial cardiac and hepatic risks linked to it. In June 1999, the Commission held up the pending authorization process to get further scientific clarification of the applicant's report. An ad hoc Expert Working Group (EWG) met to discuss the new information about the dangers of deferiprone.

The EWG determined, however, that the new data was inconclusive as to the relationship between deferiprone and hepatic fibrosis. Accordingly, it opined that there was no need to rethink the pending favorable recommendation for marketing authorization. The CPMP, therefore, decided to stick with its endorsement.

In November 1999, Dr. Olivieri filed the present suit at the Registry of the Court of First Instance (CFI) in Luxembourg. It sought to annul (1) the revised opinion and (2) the Commission decision Three months later, the CFI's Fifth Chamber granted Apotex leave to intervene. In March 2000, the Commission and the EMEA asserted a plea of inadmissibility under Article 230 EC.

The CFI decides to rule on this plea. The Court first finds Dr. Olivieri's application to annul the revised opinion inadmissible because the revised opinion qualifies as a mere preparatory or nonfinal measure not open to challenge under Article 230 EC.

Article 230 EC (ex Article 173) provides in pertinent part as follows: "The Court of Justice shall review the legality of acts ... of the Commission ... other than recommendations and opinions, ... intended to produce legal effects vis-a-vis third parties. ... Any natural or legal person may ... institute proceedings against a decision addressed to that person or against a decision which, although in the form of a regulation or a decision addressed to another person, is of direct and individual concern to the former."

The Commission and the EMEA, supported by Apotex, argued that the application is inadmissible by reason of lack of interest in bringing proceedings. The applicant countered that she has an interest in bringing the proceedings because she is seeking both to protect public health and the health of thalassemia patients and to defend her professional reputation.

The Court first examines the applicant's public health claim. The Court first points out "that none of the provisions of the applicable Community rules prohibits the Commission, prior to granting a marketing authorisation, from following a procedure during which persons other than the applicant for marketing authorisation are able to submit their observations so as to enable it to fulfil its duty to check, in the interest of public health, that all the information relating to the scientific evaluation of the product in question, whether it be favourable or unfavourable to the product, has indeed been made available to it." [73]

The Court notes that the applicant's function in the administrative procedure plays a role in determining whether she has an interest in bringing the action. The Court notes that "the Commission suspended the marketing authorisation procedure on its own initiative and requested the CPMP to obtain additional scientific clarification."

"Such a step is justified by the fundamental aim of safeguarding public health, which constitutes the framework for the Commission's work. ... [T]he Community rules require the Commission to confirm that the particulars and documents provided by the applicant for marketing authorisation are correct in order that it may assess the quality, safety and efficacy of that product and authorise its marketing."

"At that stage of the assessment procedure, the applicant could thus rely on the interest of protecting public health when she communicated to the CPMP additional information which might call in question the initial scientific assessment, given that the information provided by Apotex with its application for marketing authorisation or during the assessment procedure had been incomplete." [78-79]

Although the Court concludes that Dr. Olivieri indeed played a leading part in deferiprone research, it finds that the Commission decision was not "of concern" to the applicant here. ... "[A] Commission decision addressed to the applicant would have been of concern to her if it had refused to examine the information provided by her in the course of the procedure for the scientific assessment of deferiprone or there had been an implicit decision to reject that information, which would have been the case if the Commission had adopted the decision to grant marketing authorisation without having examined that information. She would have been entitled to contest the legality of either of those decisions before the Court of First Instance."

"However, following Dr Olivieri's involvement, the suspension of the marketing authorisation procedure and the Commission's decision to request a further examination, the initial scientific assessment of deferiprone was amended and supplemented by the CPMP. In the light of the contested decision and the opinions and reports on which it is based, none of the arguments submitted by the applicant in the course of the present proceedings supports the claim that the Commission failed to take into account the information directly communicated by the applicant in the course of the assessment procedure." [81-82]

In response to the applicant's claim that she has an interest in defending her professional reputation, the Court notes that her fine reputation played a major role in the reopening of the case. "Moreover, ... even if the applicant's professional reputation were to have been called into question in the contested decision, that would not have given her an interest in bringing proceedings to contest that decision, because Article 68 of Regulation No 2309/93 does not permit the Commission to take into account such matters in a decision to grant marketing authorization. [Cite]"

"It follows from the foregoing that the applicant has not established an interest in bringing proceedings in order to protect public health or in order to defend her professional reputation. Consequently, ... her application must be declared inadmissible." [98-100]

"Under Article 87(2) of the Rules of Procedure, the unsuccessful party is to be ordered to pay the costs if they have been applied for in the successful party's pleadings. Since the applicant has been unsuccessful, she must be ordered to bear her own costs and to pay those incurred by the Commission and the EMEA, including the costs relating to the interim proceedings." [101]

Citation: Nancy Fern Olivieri v EC Commission, EU: Case T-326/99; Celex No. 699A0326 (Court of First Instance, Fifth Chamber, 2003).