transparency policies of the european medicines agency

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Medical Law Review, Vol. 25, No. 3, pp. 456–483 doi:10.1093/medlaw/fwx002 Advance Access Publication: February 23, 2017

TRANSPARENCY POLICIES OF THE EUROPEAN MEDICINES AGENCY: HAS THE PARADIGM SHIFTED? DARIA KIM* Max-Plank Institute for Innovation and Competition, Munich, Germany

ABSTRACT This article reflects on the state of play as regards access to non-summary clinical trial data in the European Union (EU). In particular, it examines the scope of access under the recent transparency policies of the European Medicines Agency (EMA) that attempt to break away from the presumptively confidential treatment of clinical trial data. In light of the emerging case law of the Court of Justice of the European Union on clinical trial data disclosure, it remains highly uncertain what data, and under what conditions, can be lawfully released by the EMA. Under the applicable regulations, the scope of the accessible data depends on the interpretation of commercially confidential information—the notion derived from the exception to the fundamental right of access to documents. Accordingly, the analysis focuses on the application of this exception, taking into account the specifics of clinical data, the context in which disclosure occurs, and the interests that are at stake. The main complexity is found in defining the scope of the relevant and legitimate interests to be balanced when applying the exception. Overall, it is argued that the current regulatory framework does not provide a sufficient legal basis to support the objectives pursued by the EMA’s policies. KEYWORDS: Clinical trial data, Access, The European Medicines Agency, Commercially confidential information

*

Max-Planck-Institut fu¨r Innovation und Wettbewerb, Marstallplatz 1, Mu¨nchen, 80539, Germany, daria. [email protected] The author thanks the anonymous reviewers of the Medical Law Review, Dr. jur. Owais Hassan Shaikh and William Wortley for the comments on the drafts. No Conflict of Interest to declare.

C The Author 2017. Published by Oxford University Press; all rights reserved. V

For Permissions, please email: [email protected]



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I. INTRODUCTION Access to clinical trial data—especially access beyond the summary-level results—has been subject to a long-standing debate.1 In the European Union (EU), a new spin on the controversy was triggered by the transparency policies of the European Medicines Agency (EMA)—the 2010 policy of request-based access2 and the 2015 policy for publication of clinical data.3 On 20 October 2016, the EMA published the first clinical reports related to two medicines: the released documents comprise ‘approximately 260,000 pages of information for over 100 clinical reports’.4 Earlier, the European Ombudsman hailed the data publication initiative as ‘a paradigm shift’.5 According to the EMA Executive Director, Guido Rasi, the policy ‘sets a new standard for transparency in public health and pharmaceutical research and development’, and such ‘unprecedented level of access to clinical reports will benefit patients, healthcare professionals, academia and industry’.6 The promise is significant, in light of the fact that the EMA is the holder of the largest stock of clinical trial data in the EU, that the commercial sponsors account for the major share of clinical trials in the EU,7 and that non-summary trial data, for the most part, usually remains unavailable to the scientific community and the public in general.8 Alongside the implementation of the EMA’s publication policy, the EU regulatory framework for clinical trials has undergone a notable change—the adoption of 1

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For an overview of international initiatives, see eg PC Gøtzsche, ‘Why We Need Easy Access to All Data from All Clinical Trials and How to Accomplish It’ (2011) 12 Trials 249; The Multi-Regional Clinical Trials Center at Harvard University, ‘Overview of Data Disclosure Initiatives: Current and Ongoing Data Transparency Activities in the Pharmaceutical Industry’ (2014) Brief accessed 30 October 2016. The EMA, ‘European Medicines Agency Policy on Access to Documents (Related to Medicinal Products for Human and Veterinary Use)’ (2010) Policy/0043, EMA/110196/2006 accessed 30 October 2016 (thereinafter, 2010 access policy). The EMA, ‘The European Medicines Agency Policy on Publication of Clinical Data for Medicinal Products for Human Use’ (2014) Policy/0070, EMA/240810/2013 accessed 30 October 2016 (thereinafter, 2015 publication policy). The 2015 publication policy supplements the EMA 2010 policy. The EMA, ‘Opening up Clinical Data on New Medicines. EMA Provides Public Access to Clinical Reports’ (20 October 2016) Press Release, EMA/650519/2016 accessed 30 October 2016. European Ombudsman, ‘Decision on Own-initiative Inquiry OI/3/2014/FOR Concerning the Partial Refusal of the European Medicines Agency to Give Public Access to Studies Related to the Approval of a Medicinal Product’ (8 June 2016) Case OI/3/2014/FOR, Report, para 71. The EMA, ‘Publication of Clinical Reports. EMA Adopts Landmark Policy to Take Effect on 1 January 2015’ (2 October 2014) EMA/601455/2014 accessed 30 October 2016. See European Commission, ‘Impact Assessment Report on the Revision of the “Clinical Trials Directive” 2001/20/EC Accompanying the Document Proposal for a Regulation of the European Parliament and of the Council on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001/20/ EC’ SWD (2012) 200 final, 8 accessed 30 October 2016. See eg P Doshi and T Jefferson, ‘Clinical Study Reports of Randomised Controlled Trials: An Exploratory Review of Previously Confidential Industry Reports’ (2013) 3(2) British Medical Journal Open 1, 1 (examining the sample of seventy-eight clinical study reports and concluding that such reports represent a ‘mostly hidden and untapped source of detailed and exhaustive data on each trial’).

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Regulation (EU) 536/2014 harmonising the rules for conducting clinical trials in the EU.9 The Regulation also provides for the set-up of a new EU database in order ‘to ensure a sufficient level of transparency in the clinical trials’ by making publicly accessible ‘all relevant information as regards the clinical trial submitted through the EU portal’.10 The EMA’s publication policy and the EU database initiative are distinct measures:11 While the former provides for the publication of data submitted to the EMA for marketing authorisation (MA) through the centralised procedure after 1 January 2015, the latter applies to the data generated in the clinical trials approved under the new regulation (that is foreseen to become publicly available not earlier than in 2019–2020).12 Within the EU institutional framework, broad access to clinical trial data has been strongly advocated by the European Ombudsman, whose recommendations triggered the change to the EMA’s approach in 2010.13 In the most recent inquiry concerning the public access to clinical data held by the EMA, the Ombudsman was not convinced that all redactions of the clinical reports at issue were justified14 and took the position that ‘the entirety of a clinical study report should ultimately be disclosed’.15 Academic discourse provides an extensive normative account as to why broad access to clinical trial data is socially desirable, if not imperative. The main healthcare benefits of access are broadly associated with the improved reproducibility of research results, enhanced transparency of regulatory decision-making, elimination of duplicative research, and advancement of scientific knowledge.16 In this regard, the EMA 9 10 11

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reg (EU) 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC [2014] OJ L158/1, rec 82. ibid, rec 67. See the EMA, ‘Questions and Answers on the European Medicines Agency Policy on Publication of Clinical Data for Medicinal Products for Human Use’ (2014) EMA/357536/2014 (thereinafter, Questions and answers) 6–7 (clarifying that the EMA’s publication policy ‘will serve as a useful complementary tool ahead of the implementation of the new Clinical Trials Regulation’). ibid 6. European Ombudsman, ‘Decision of the European Ombudsman Closing his Inquiry into Complaint 2560/ 2007/BEH against the European Medicines Agency’ (24 November 2010) para 80. Ombudsman (n 5) para 64. The Ombudsman’s inquiry was initiated after the EMA and the pharmaceutical company AbbVie had concluded an agreement, according to which the EMA could grant public access to the redacted versions of AbbVie’s clinical reports. ibid, paras 73–74. The literature on this topic is extensive. See, generally, JPA Ioannidis, ‘Why Most Clinical Research Is Not Useful’ (2016) 13(6) PLoS Medicine 1; VS Moorthy and others, ‘Rationale for WHO’s New Position Calling for Prompt Reporting and Public Disclosure of Interventional Clinical Trial Results’ (2015) 12(4) PLOS Medicine 1; The Institute of Medicine of the National Academies, Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk (National Academy of Sciences 2015); Gøtzsche (n 1); C Laine and others, ‘Reproducible Research: Moving Toward Research the Public Can Really Trust’ (2007) 146(6) Annals of Internal Medicine 450; Ben Goldacre, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients (Farrar, Straus and Giroux 2014); CW Jones and others, ‘Non-Publication of Large Randomized Clinical Trials: Cross Sectional Analysis’ (2011) British Medical Journal 347; M Angell, The Truth About the Drug Companies: How They Deceive Us and What to Do About It (Random House 2005). In view of the numerous problems associated with private provisioning of clinical trials, scholars have argued for the public good approach to clinical research. See eg JH Reichman, ‘Rethinking the Role of Clinical Trial Data in International Intellectual Property Law: The Case for a Public Goods Approach’ (2009) 13(1) Marquette Intellectual Property Law Review 1; A Taubman, ‘Unfair Competition and the Financing of Public Knowledge Goods: The Problem of Test Data Protection’ (2008) 3(9) Journal of Intellectual

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policy and the new EU database present a remarkable attempt to break away from the presumptively confidential treatment of non-summary clinical trial data.17 A more pertinent question is how effectively these measures operate that, in turn, depends on how access measures fit within the present legal and regulatory framework. The EMA’s publication policy provides for the proactive disclosure of clinical reports in downloadable and searchable formats,18 as well as anonymised individual patient-level data (IPD),19 without the need for remuneration to be paid to the trial sponsors. Not surprisingly, the publication policy was opposed by the research-based sector of the biopharmaceutical industry. During the public consultations conducted by the EMA, industry representatives claimed that disclosure of clinical data, even for non-commercial research purposes impedes innovation incentives.20 Moreover, they claimed that it invoked trade secrets protection21 and the obligation for protection of undisclosed information under the Agreement on Trade-Related Aspects of Intellectual Property Rights.22 (Paradoxically, while opposing the EMA’s policy for access to data, pharmaceutical companies have been the most active users of the system.23)

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Property Law & Practice 591; TR Lewis, JH Reichman and AD So, ‘The Case for Public Funding and Public Oversight of Clinical Trials’ (2007) 4(1) Economists’ Voice 1; WA Ray and CM Stein, ‘Reform of Drug Regulation – Beyond an Independent Drug-Safety Board’ (2006) 354(2) New England Journal of Medicine 194; T Lemmens, ‘Leopards in the Temple: Restoring Scientific Integrity to the Commercialized Research Scene’ (2004) 32(4) Journal of Law, Medicine & Ethics 641. See P Doshi and T Jefferson, ‘Open Data 5 Years on: a Case Series of 12 Freedom of Information Requests for Regulatory Data to the European Medicines Agency (2016) 17(78) Trials 1, 1 (finding that the ‘EMA is the only regulator in the world that is routinely releasing original clinical trial data, but release can take considerable time to occur and often only after a lengthy correspondence’). See also the EMA (n 4) 1 (stating that ‘EMA is the first regulatory authority worldwide to provide such broad access to clinical data’). This is possible for identified users under the terms of use for academic and other non-commercial research purposes. See 2015 publication policy (n 3) 14. ibid 2. See also the EMA, ‘External Guidance on the Implementation of the European Medicines Agency Policy on the Publication of Clinical Data for Medicinal Products for Human Use’ (2 March 2016) EMA/ 90915/2016 (thereinafter, External guidance) 6; Questions and answers (n 11) 3 (clarifying that ‘to avoid confusion, as noticed during the public consultation, the term “raw data” will no longer be maintained, but instead the term “individual patient data” (IPD) will be used’). See eg the submissions by the German Association of Research-based Pharmaceutical Companies and the Danish Association of the Pharmaceutical Industry, the European Medicines Agency, ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/240810/2013)’ (2 October 2014) EMA/ 349245/2014, 23, 26, 70, 74; BioIndustry Association, European Medicines Agency, ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/240810/2013)’ (2 October 2014) EMA/ 342115/2014, 12; The EuropaBio, ‘Overview of comments received on “Publication and access to clinicaltrial data” (EMA/240810/2013)’ (2 October 2014) EMA/344107/2014, 28. For an overview of submissions, see the EMA, ‘Outcome of Public Consultation on “Policy 0070 on Publication and Access to Clinicaltrial data”’ (2 October 2014) EMA/34238/2014 accessed 30 October 2016. See eg the German Pharmaceutical Industry Association, ibid 10–13; The EuropaBio, ibid 27–28. Agreement on Trade-related Aspects of Intellectual Property Rights, 15 April 1994, Marrakesh Agreement Establishing the World Trade Organization, Annex 1C, Legal Instruments—Results of the Uruguay Round, 33 ILM 1197 (1994) (thereinafter, the TRIPS Agreement). Such claim was raised, in particular, by Pfizer— see ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/240810/ 2013)’ (2 October 2014) EMA/344107/2014, 86. See P Doshi and T Jefferson, ‘The First 2 Years of the European Medicines Agency’s Policy on Access to Documents: Secret No Longer’ (2013) 173(5) JAMA Internal Medicine 380. See also Case T-718/15R PTC Therapeutics International v EMA (Order of the President of General Court of 20 July 2016, ECLI:EU:T:2016:425) para 38.

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Under the EMA policy terms, access to clinical data can be granted with the exception of commercially confidential information (CCI).24 Likewise, data in the new EU database shall be publicly accessible unless confidentiality is justified, inter alia, on the grounds of protection of CCI.25 Earlier this year, the EMA also released new guidance on the identification and redaction of CCI from the dossiers submitted for drug MA, as well as the anonymisation of clinical reports for the purpose of their prospective publication in accordance with the EMA’s 2015 publication policy.26 The guidance requires the applicants to submit a detailed specification of how disclosure would affect their commercial interests, while the last word as to whether the justification is sufficient and adequate remains with the EMA.27 In general, the EMA assumes that ‘clinical data cannot be considered CCI’28 except in the limited circumstances.29 Notably, the Advisory Group on Legal Aspects did not ‘manage to reach an agreement [as to] whether or not clinical trial data contain CCI’.30 Meanwhile, the issue of whether clinical reports can qualify as CCI came to the fore in a series of disputes at the Court of Justice of the European Union (CJEU). Since the adoption of the 2010 access policy, several pharmaceutical companies have successfully objected to the EMA’s decision to disclose their clinical reports. In all cases, the General Court ordered interim measures suspending the EMA’s decisions in order ‘to prevent serious and irreparable harm to the applicant’s interests’.31 While there has been no decision on the merits yet as to whether clinical reports—in part or in entirety—shall be subject to confidential treatment, these disputes demonstrate the complexity of policy and legal issues involved and the conflict between public and commercial interests at stake. Whereas in the European Ombudsman’s opinion ‘public health should always trump commercial interests’,32 in the case of access to clinical trial reports, it was ‘not obvious’ to the General Court whether, as a result of weighing up of interests, ‘the balance will clearly be in favour of the public interest defended by the EMA’.33 While the Ombudsman asserted that ‘the public interest in disclosure will

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The 2015 publication policy (n 3) 4. reg (EU) 536/2014 (n 9) Art 81(4)(b). External guidance (n 19). ibid 47–54. The 2015 publication policy (n 3) 4; reg (EU) 536/2014 (n 9) rec 68. The 2015 publication policy (n 3) 6. The Clinical Trial Advisory Group on Legal aspects (CTAG5), ‘Final Advice to the European Medicines Agency’ (30 April 2013) lines 8–10, 21 accessed 30 October 2016 (putting forward the arguments for and against). It should be noted that the consideration of the potential harm to commercial interests prevailed over the EMA’s arguments in the assessment of urgency for the application of interim measures. See Case T-235/15 R Pari Pharma v EMA [2015] OJ C381, para 58 (emphasising ‘that weighing up of interests, to be carried out by the Court adjudicating on the substance of the case, should not be confused with that carried out for the purpose of the present interim proceedings’); PTC Therapeutics International v EMA (n 23) para 122; Case T-44/13R AbbVie v EMA [2013] ECLI:EU:T:2013:221, para 48; Case T-73/13R InterMune v EMA [2013] ECLI:EU:T:2013:222, para 37. Ombudsman (n 5) paras 73–74 (emphasis added). AbbVie v EMA (n 31) para 69; InterMune v EMA (n 31) para 54 (emphasis added).

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generally defeat any claim of commercial sensitivity’,34 the General Court held that disclosure requires a ‘delicate assessment’35 of the interests involved. This article underscores the significance of this emerging case law. Unlike in the USA, where case law on disclosure of efficacy and safety data held by the US Food and Drug Administration (FDA) is more extensive and has a longer history,36 the issue of disclosure of clinical data submitted for regulatory review has come under the purview of the CJEU only recently. In view of uncertainty as to whether clinical reports and data might qualify as CCI, the CJEU’s interpretation can bear directly on the effectiveness of the EMA’s transparency policies and the new EU database—not only in terms of legal certainty, but, most importantly, the scope of data that can be lawfully released.37 This case law demonstrates the conflict of interests and the uneasy position of the EMA being trapped between the impetus for disclosure of clinical study reports in their entirety38 and the claims of the research-oriented pharmaceutical companies for protection of their commercial interests and innovation incentives by data confidentiality. It also shows that, absent the clear legal test of applying the exception for commercial interest protection to clinical trial data, the current rules of access do not present a systematic solution that could provide legal certainty. As argued by the EMA, ‘the systematic suspension of any decision authorising the disclosure of documents to third parties [due to] interim relief . . . raises a question of principle as regards the effective application of Regulation No 1049/2001’, and that ‘several other requests for access to the reports at issue were pending the EMA’s decision’.39 While recognising these concerns as ‘legitimate and well founded’, the CJEU did not find them to be ‘connected to the form of order sought in [the] appeal’.40 Against this background, the article examines the scope of access to clinical trial data held by the EMA under the applicable regulatory framework. In focus is the notion of CCI, its interpretation and the application of the related exception. Section II of the analysis outlines the background and the legal basis of the EMA’s access and publication policies. Section III reviews recent cases, in which pharmaceutical

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Ombudsman (n 5), summary (emphasis added). AbbVie v EMA (n 31) para 69; InterMune v EMA (n 31) para 54; Pari Pharma v EMA (n 31) para 58. At this point, it might be too early to make a comparative analysis of the EU and US case law, at least not until the CJEU adjudicates on the substance in the disputes discussed in this article. The general trend in the USA is, nevertheless, worth being noted. After the Supreme Court recognised proprietary nature of efficacy and safety data and qualified their disclosure by the US FDA as a regulatory taking (Ruckelshaus v Monsanto, 467 US 986 (1984)), in more recent cases, courts have been upholding the FDA’s refusal to grant a third party access on the basis of Exemption 4 under the Freedom of Information Act for ‘commercial or financial information . . . [that is] privileged or confidential’, if the party objecting to disclosure ‘meets the [] burden of showing a likelihood of substantial competitive injury’. See Government Accountability Project v US Dept of Health and Human Services, 691 F Supp 2d 175-6 (DDC 2010). See the EMA, ‘New Judicial Decisions at Odds with EMA’s Efforts to Allow Access to Documents on Medicines’ (29 September 2016) Press Release, EMA/526600/2016 accessed 30 October 2016 (citing the statement of Stefano Marino, EMA’s Head of Legal Department, that the EMA ‘will welcome a clear indication on this point from the Court of Justice’). Ombudsman (n 5) para 73. Case T-235/15R Pari Pharma v EMA (Order of the General Court of 23 May 2016) ECLI:EU:T:2016:309, para 19 (emphasis added). ibid, para 44.

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companies contested the EMA’s decision to grant a third party access to their clinical reports. Section IV analyses how the exception to the right of access to documents based on the protection of commercial interests can be applied to clinical trial data. Section V summarises the conclusions drawn from the current state of play and highlights the main regulatory controversies identified by the analysis. I I . T HE EM A ’S T RA N SP A R EN C Y P OL IC I ES

A. The Background Until 1 December 2010, the EMA treated documents submitted by drug sponsors for MA as presumptively confidential.41 The new policy on access to documents originated, received, or possessed by the EMA was adopted in order ‘to ensure the widest possible access . . . concerning any matter related to the policies, activities and decisions falling within the EMA’s remit and responsibilities’.42 The policy change was triggered by the recommendations of the European Ombudsman that were issued upon the investigations concerning the complaint brought by the Nordic Cochrane Centre against the EMA. The dispute arose after the EMA had denied Cochrane Centre access to clinical study reports and trial protocols related to two anti-obesity drugs, on the grounds of protecting the commercial interests of the original document holders. Upon investigation, the Ombudsman concluded that documents at issue ‘did not fall within the commercial interests exception’.43 A more progressive step came in 2015, when the EMA adopted a new policy on proactive publication of clinical data (including IPD) submitted to the EMA under the centralised MA procedure.44 The policy is being implemented in two steps: first, only clinical reports shall be subject to publication; secondly, individual anonymised patient-level data is expected to be released, once the Agency ‘find[s] the most appropriate way’ of making data available ‘in compliance with privacy and data protection laws’.45 Access can be granted under the condition that the released data are used for scientific, noncommercial research purposes and, explicitly, not for the purpose of generic drug approval.46 The objective is 2-fold: first, to enable public scrutiny by allowing external investigators to verify the original analysis and conclusions and, secondly, to develop new knowledge and facilitate new drug R&D through the secondary analysis of data.47 In 41 42

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Case C-389/13P(R) EMA v AbbVie [2013] ECLI:EU:C:2013:794, para 6. The 2010 access policy (n 2) 3. Prior to the policy adoption, access to documents was regulated under the EMA’s Rules for the implementation of reg 1049/2001 on access to its documents, EMEA/MB/203359/ 2006 [2006]. European Ombudsman (n 13). The 2015 publication policy (n 3) para 4.2 (specifying the effective dates of policy implementation). The 2015 publication policy does not supersede the 2010 access policy: ‘any natural or legal person may continue to submit a request for access to documents to the Agency independently of the proactive publication mechanisms established by this policy’; ibid 1. ibid 7. See also Questions and answers (n 11) 3 (clarifying that ‘various aspects relating to IPD [individual patient data] will be clarified with stakeholders, including the issues such as . . . how . . . to provide access to IPD and under which conditions’). The 2015 publication policy (n 3) Annex 1, para 3; Annex 2, para 3 (providing for model terms of use of the released data that preclude the use the clinical reports ‘to support an application to obtain a marketing authorisation and any extensions or variations thereof for a product anywhere in the world’). ibid 3–4.

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particular, by making clinical data available proactively, the EMA is pursuing the goal of making ‘medicine development more efficient by establishing a level playing field that allows all medicine developers to learn from past successes and failures’.48

B. The Legal Basis The EMA’s 2010 access policy explicitly references Article 15 of the Treaty on the Functioning of the European Union (TFEU) and Regulation (EC) 1049/200149 and reinforces that openness and transparency are the ‘paramount values enshrined in the TEU and in the TFEU [that] strengthen the principles of democracy and good administration’.50 The specific obligation to ‘adopt rules to ensure the availability to the public of regulatory, scientific or technical information concerning the authorisation or supervision of medicinal products which is not of a confidential nature’ is laid down in the EMA’s founding regulation.51 The 2015 publication policy was adopted to ‘extend [the EMA’s] approach to transparency’ and ‘without prejudice’ to Regulation (EU) 536/201452 and Regulation (EC) 1049/2001.53 Therefore, both access and publication policies can be viewed as the regulatory measures giving effect to the right of access to documents as guaranteed under Article 15(3) TFEU and Article 42 of EU Charter of Fundamental Rights (CFR),54 and are subject to the conditions set out in Regulation (EC) 1049/2001.55 Table 1 outlines the legal framework applicable to clinical trial data held by the EMA. The EMA’s transparency policies can be seen as being within the scope of the right of access to documents enshrined in Article 42 CFR, insofar as they apply to documents—ie ‘any content whatever its medium . . . concerning a matter relating to the policies, activities and decisions falling within the institution’s sphere of responsibility’ 56 —that are received and in the possession57 of the EMA. The policy terms do not delimit the citizenship of applicants, expanding the scope of beneficiaries beyond EU citizens.58 The possibility to download and save clinical reports under the terms of use for academic and other non-commercial research purposes59 corresponds to Article 10 of Regulation (EC) 1049/2001 that provides for access to documents ‘either by consulting them on the spot or by receiving a copy, including, where available, an electronic copy, according to the applicant’s preference’.

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ibid 4. Council reg (EC) 1049/2001 regarding public access to European Parliament, Council and Commission documents [2001] OJ L145/43. Furthermore, the policy references reg (EC) 45/2001 in relation to protection of privacy integrity of trial participants; ibid 4 The 2015 publication policy (n 3) 1. reg (EC) 726/2004, Art 80. The 2015 publication policy (n 3) 2. ibid 1. Explanations relating to the CFR (2007/C 303/02) [2007] OJ C 303/17, C 303/28. reg (EC) 726/2004, Art 73. reg (EC) 1049/2001, Art 3(a). ibid, Art 2(3). According to Art 2(2) of Regulation (EC) 1049/2001, the ‘institutions may, subject to the same principles, conditions and limits, grant access to documents to any natural or legal person not residing or not having its registered office in a Member State’. The 2015 publication policy (n 3) 5–6.

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TABLE 1. The legal framework applicable to access to clinical trial data held by the EMA Legal sources

Selected provisions (emphasis added)

The TFEU

Article 15(3) Any citizen of the Union, and any natural or legal person residing or having its registered office in a Member State, shall have a right of access to documents of the Union institutions, bodies, offices and agencies, whatever their medium, subject to the principles and the conditions to be defined in accordance with this paragraph.a Article 42 Any citizen of the Union, and any natural or legal person residing or having its registered office in a Member State, has a right of access to documents of the institutions, bodies, offices and agencies of the Union, whatever their medium. Recital 4 The purpose of this Regulation is to give the fullest possible effect to the right of public access to documents and to lay down the general principles and limits on such access in accordance with Article 255(2) of the EC Treaty. Article 4 2. The institutions shall refuse access to a document where disclosure would undermine the protection of:— commercial interests of a natural or legal person, including intellectual property. ... 3. As regards third-party documents, the institution shall consult the third party with a view to assessing whether an exception in paragraph 1 or 2 is applicable, unless it is clear that the document shall or shall not be disclosed. Article 13 3. The Agency shall immediately publish the assessment report on the medicinal product for human use drawn up by the Committee for Medicinal Products for Human Use and the reasons for its opinion in favour of granting authorisation, after deletion of any information of a commercially confidential nature. The European Public Assessment Report (EPAR) shall include a summary written in a manner that is understandable to the public. The summary shall contain in particular a section relating to the conditions of use of the medicinal product. Article 73 Regulation (EC) No 1049/2001 of the European Parliament and of the Council of 30 May 2001 regarding public access to European Parliament, Council and Commission documents (2) shall apply to documents held by the Agency.Article 80

The CFR

Regulation (EC) No 1049/2001

Regulation (EC) 726/ 2004

Continued

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TABLE 1. Continued Legal sources

Regulation (EU) 536/ 2014

a

Selected provisions (emphasis added) To ensure an appropriate level of transparency, the Management Board, on the basis of a proposal by the Executive Director and in agreement with the Commission, shall adopt rules to ensure the availability to the public of regulatory, scientific or technical information concerning the authorisation or supervision of medicinal products which is not of a confidential nature. Recital 68 For the purposes of this Regulation, in general the data included in a clinical study report should not be considered commercially confidential once a marketing authorisation has been granted, the procedure for granting the marketing authorisation has been completed, the application for marketing authorisation has been withdrawn. Article 81 1. The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a EU data-base at Union level. [. . .] The EU database shall contain the data and information submitted in accordance with this Regulation. ... 4. The EU database shall be publicly accessible unless, for all or part of the data and information contained therein, confidentiality is justified on any of the following grounds: ... (b) protecting commercially confidential information, in particular through taking into account the status of the marketing authorisation for the medicinal product, unless there is an overriding public interest in disclosure.

The provision corresponds to Art 255 of the EC Treaty.

As for the scope of documents, Regulation (EC) 726/2004 does not specify the contents of MA dossiers that shall be publicly available ‘to ensure an appropriate level of transparency’,60 while Regulation (EU) 536/2014 obliges trial sponsors to submit to the EU database a summary of the results within 1 year from the end of a clinical trial and the clinical study report if the trial results are intended to be used for the purpose of obtaining MA for the investigational drug.61 Notably, Regulation (EU) 536/

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reg (EC) 726/2004, Art 80. reg (EU) 536/2014 (n 9) Art 37(4).

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2014 does not mandate to transfer IPD,62 as it is envisaged in the second phase of the EMA’s 2015 policy.63

C. The Notion of CCI Both Regulation (EC) 726/2004 and Regulation (EU) 536/2014 contain an exception from disclosure for information of a commercially confidential nature. Highlighting ‘the lack of a legal definition’, the EMA considers CCI as ‘any information which is not in the public domain or publicly available and where disclosure may undermine the economic interest or competitive position of the owner of the information’.64 The Agency, though, presumes that in general ‘clinical data [comprising clinical reports and IPD] cannot be considered CCI [except for] in limited circumstances’.65 To clarify such circumstances, the policy annex lists the elements of clinical reports that may potentially be considered as CCI including: product development rationale, overviews of biopharmaceutics and clinical pharmacology, benefits and risks, conclusions, summaries of biopharmaceutical studies and clinical pharmacology studies, and reports of biopharmaceutical studies.66 These sections, however, shall not be redacted ‘unconditionally’ but only upon the EMA’s review of the submitted justification.67 The EMA 2016 Guidance on the identification and redaction of CCI specifies four categories of information that shall not be considered as CCI, namely, information that is already in the public domain, information that does not bear any innovative features (common knowledge), additional information the disclosure of which would be in the public interest, and information lacking sufficient or relevant justification.68 In particular, the following statements shall be deemed as irrelevant, if unsupported. Information is commercially confidential, competitively sensitive information and includes intellectual property including trade secret information. The analytical methods are [the company]’s intellectual property, which [the company] developed by expending a significant amount of time, and human, financial and commercial resources.69 Applicants need to clarify how the disclosure of certain content would undermine their economic interests and indicate ‘the innovative features of the information in the

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ibid (stipulating that ‘[f]or cases where the sponsor decides to share raw data on a voluntary basis, the Commission shall produce guidelines for the formatting and sharing of those data’). As mentioned earlier, the EU database initiative under reg (EU) 536/2014 and the EMA’s publication policy are distinct measures; the latter applies only to clinical data submitted to the EMA for MA on or after 1 July 2015. See n 12. The 2010 access policy (n 2) 4 (emphasis added). The 2015 publication policy (n 3) 4. ibid, Annex 3. External guidance (n 19) 47. ibid 52. ibid 53–54 (emphasis added). See also 2015 publication policy (n 3) Annex III (exemplifying sections of clinical study reports that can be subject to redaction as CCI, and the plausible justifications).

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context of the common knowledge within the specific scientific area’.70 Thus, the qualification of the contents of MA dossiers as CCI is fact-dependent rather than category-specific, and the applicant’s arguments are subject to a case-by-case assessment by the EMA. In this regard, the 2016 Guidance does not provide much assistance as to what particular justifications shall be deemed as relevant and satisfactory. Meanwhile, absent the clear criteria under the Agency’s bylaws, the issue of the qualification of clinical study reports as CCI was raised in a few recent cases I I I . R E C E N T C AS E S A T TH E CJ E U O N T H E E M A ’ S D I S CL O S U R E O F C L I N IC A L R E P O R T S

A. Facts and Proceedings The CJEU was first confronted with the issue of disclosure of clinical reports by the EMA when two pharmaceutical companies—AbbVie and InterMune—brought actions in early 2013.71 In AbbVie v EMA, a university science student petitioned for access in connection with the preparation of the master’s thesis, which was related to the clinical study reports that had supported the MA of AbbVie’s drug Humira.72 In InterMune v EMA, access was requested by the pharmaceutical company Boehringer Ingelheim GmbH and concerned the clinical reports submitted for the MA of InterMune’s drug Esbriet.73 In both cases, the applicants succeeded in obtaining interim measures suspending the EMA’s decisions to grant a third party access. On appeal, the CJEU overturned the injunctions74 and referred both cases back to the General Court to examine the possibility of the partial disclosure of the reports at issue, decreeing that the companies needed to establish ‘with a sufficient degree of probability’ the likelihood of ‘serious and irreparable damage’ caused by disclosure.75 Thereafter, the proceedings in both cases were discontinued pursuant to the applicants’ requests.76 Two subsequent cases arose over the clinical reports for orphan drugs.77 In PTC Therapeutics International v EMA, a request for access was filed by an unknown pharmaceutical company78 concerning the main clinical study conducted for the drug

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71 72 73 74 75 76 77

78

External guidance (n 19) 52. The criterion for information to be considered as CCI and thus protected against disclosure ‘which has already been revealed to some extent, can be inferred from, or has as its scientific backbone the content of textbooks or scientific guidelines, should not be included in the proposed redactions’; ibid 47–48. Case T-44/13 AbbVie v EMA, Action brought on 29 January 2013, OJ C79; Case T-73/13 InterMune UK v EMA, Action brought on 11 February 2013, OJ C114. AbbVie v EMA (n 31) para 20. InterMune v EMA (n 31) para 13. Case C-390/13P(R) EMA v InterMune [2013] ECLI:EU:C:2013:795, para 57; EMA v AbbVie (n 41) para 55. EMA v AbbVie (n 41) para 52; EMA v InterMune (n 74) para 54. Case T-73/13 InterMune v EMA (Order of the General Court of 29 June 2015) OJ C311; Case T-44/13 AbbVie v EMA (Order of the General Court of 17 July 2014) OJ C361. For the criteria of designation as an orphan drug, see Art 3(1)(a) of Council Regulation (EC) 141/2000 on orphan medicinal products OJ 2000 L18/1. For instance, one of such criteria is that a drug is ‘intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in 10 thousand persons in the Community’. PTC Therapeutics International v EMA (n 23) para 38.

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Translarna—an ‘ultra-orphan’ medicinal product developed by PTC Therapeutics. In Pari Pharma v EMA, access to Pari Pharma’s similarity and superiority reports was sought by Novartis Europharm. Novartis’ product TOBI Podhaler was approved as an orphan medicinal product and protected under market exclusivity.79 Subsequently, Pari Pharma developed a drug Vantobra that was approved by the EMA by way of derogation of market exclusivity of TOBI Podhaler due to Vantobra’s therapeutic advantage in terms of significantly reduced treatment time.80 In both cases, the General Court ordered interim measures, having found that the ‘likelihood of the applicant suffering serious and irreparable damage [caused by disclosure had] been established to the requisite legal standard’ to satisfy the conditions of a prima facie case.81 Later on, the interim measures ordered in favour of Pari Pharma were appealed by the EMA and cancelled82 due to the change of circumstances. Namely, Pari Pharma and Novartis concluded an agreement allowing the latter to use the reports at issue for the purpose of the court proceedings;83 hence, the granted interim measures ‘no longer serve[d] their purpose’.84 As emphasised by the Vice-President of the CJEU, ‘no erga omnes effect can be attached to the decision at issue’,85 and any subsequent request for the same documents would be subject to the EMA’s assessment under Regulation (EC) 1049/2001.86

B. The Claims and the Legal Basis 1. Protection in the meaning of private life of business undertakings In all four cases, protection against disclosure was claimed on the basis of the right to respect for private life under Article 7 of the CFR and Article 8 of the European Convention of Human Rights (ECHR).87 In the most recent case, the applicant also invoked the exception under Articles 4(2), (3) of Regulation (EC) 2049/2001 claiming that clinical reports ‘in their entirety constitute commercially confidential information [and that] the EMA failed to carry out a balancing exercise as required by law’.88 The CJEU did not adjudicate on the question of whether disclosure of clinical reports by the EMA infringes these provisions in any of the cases. 79

80

81 82 83 84 85 86 87 88

Market exclusivity for orphan drugs is a special type of regulatory protection, under which the first company that obtains a MA for an orphan drug can enjoy exclusivity in the market as similar medicinal products for the same therapeutic indication will not be approved by a drug authority for a limited time period. See Art 8 of Regulation (EC) 141/2000. Pari Pharma v EMA (n 31) para 8. Pursuant to Art 8 of Regulation (EC) 141/2000, orphan medicinal products can benefit from 10-year market exclusivity during which no other can obtain MA for the same therapeutic indication. Exclusivity protection can be circumvented if another applicant can establish that its medicinal product, although similar, is safer, more effective or otherwise clinically superior. PTC Therapeutics International v EMA (n 23) paras 109, 122; Pari Pharma v EMA (n 31) paras 90, 91, 110. Case C-406/16P(R) EMA v Pari Pharma (Order of the Vice-President of the Court of 18 October 2016) ECLI:EU:C:2016:775. Case T-269/15 Novartis Europharm v European Commission, ECLI:EU:T:2016:279. EMA v Pari Pharma (n 82) para 61. ibid, para 60. ibid. Pari Pharma v EMA (n 31) para 40; AbbVie v EMA (n 31) para 24; InterMune v EMA (n 31) para 16; PTC Therapeutics v EMA (n 23) para 27. Case T-718/15 PTC Therapeutics International v EMA, Action brought on 9 December 2015, OJ C59 (emphasis added).

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The lack of the relevant case law was highlighted by the General Court finding that ‘the specific confidentiality issues . . . as well as the EMA’s new access policy, have not yet been adjudicated on by the Courts of the European Union’,89 and that ‘the judge hearing the application for interim measures is thus confronted with complex scientific issues which . . . call for a detailed examination in the main proceedings’.90 Having referenced the cases dealing with the analogous issue of confidential treatment of documents submitted by commercial entities for regulatory review, the court concluded that they ‘do not provide any useful indictors as to whether highly technical scientific documents, such as [clinical and non-clinical study] reports, should receive, by virtue of their very nature, confidential treatment’.91 Therefore, one can only speculate how Article 7 of the CFR and Article 8 of the ECHR, which guarantee the right to respect for private and family life, may apply to disclosure of clinical reports in the context of drug MA. As such, their applicability to the activities and documents of business undertakings cannot be excluded. In Varec v Belgian State, the CJEU relied on the interpretation of the European Court of Human Rights, holding that ‘the professional or commercial activities of either natural or legal persons’ can fall within the protection of ‘private life’ in the meaning of Article 8 ECHR and Article 7 of the CFR.92 However, one could argue that the nature of the particular information and the type of the activity would matter for the purposes of qualification as the undertaking’s ‘private life’. In Varec v Belgian State, the activities concerned the company’s participation in a tender for track lines for tanks, and the files at issue contained the technical information including manufacturing plans and the industrial process.93 In a recent case Borealis Polyolefine v Bundesminister, the reports in question comprised information regarding environmental emissions required by the state authority to determine the allocation of emission allowances.94 The Advocate General doubted whether the data submitted for that purpose had to be treated confidentially, notwithstanding the claim that it contained business secrets, for which reason the European Commission (hereafter, ‘the Commission’) had refused to grant a third party access to the documents.95 Likewise, one can question whether the activities related to the assessment and authorisation of medicinal products can be defined as the ‘private life of a business undertaking’. Furthermore, even if such protection can be affirmed, disclosure might be justified on the public interest grounds such as protection of public health.96

2. Clinical reports as property and intellectual property One may wonder why the pharmaceutical companies invoked Article 7 CFR and Article 8 ECHR when claiming confidentiality protection for the allegedly proprietary 89 90 91 92 93 94

95 96

Pari Pharma v EMA (n 31) para 60 (emphasis added). ibid, para 51; PTC Therapeutics International v EMA (n 23) para 63. Pari Pharma v EMA (n 31) para 61 (emphasis added). Case C-450/06 Varec v Belgian State [2008] ECR I-581, para 48. ibid, para 18. Joined Cases C-191/14 and C-192/14 Borealis Polyolefine GmbH and OMV Refining & Marketing GmbH v Bundesminister fu¨r Land- und Forstwirtschaft, Umwelt und Wasserwirtschaft (Opinion of AG Kokott of 12 November 2015) ECLI:EU:C:2015:754. ibid, paras 142–45. The exceptions provided under Art 8(2) ECHR apply to the rights under Art 7 CFR. See Explanations relating to the CFR (n 54) C 303/20.

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information, technical know-how, and business secrets.97 For instance, AbbVie asserted that disclosure would ‘constitute serious and irreparable damage of its fundamental rights such as the right to property’.98 Similarly, Pari Pharma claimed that: [t]he compilation of confidential raw data and publicly available information and the conclusions drawn by the applicant . . . constitute the applicant’s valuable commercial information and are its property.99 These claims could, arguably, fall within Article 17 CFR which guarantees protection of property including intellectual property.100 Under international law, undisclosed information is recognised as a subset of intellectual property, even though protection is not stipulated in the form of exclusive rights.101 In the earlier cases, the CJEU also recognised protection of business secrets as a general principle of EU law.102 It has been debated whether confidential information can be protected within the meaning of a ‘possession’ under Article 1 of the First Protocol of the ECHR and Article 17(1) CFR, as well as being protected as intellectual property under Article 17(2) CFR.103 This article does not intend to analyse this issue; however, it can be noted that if a dispute over clinical reports arises at the national level, disclosure can be objected to on the basis of the national law on trade secrets, that is to be harmonised under the recently adopted Directive on the protection of undisclosed know-how

97 98 99 100

101

102 103

Pari Pharma v EMA (n 31) paras 41–42. See also InterMune v EMA (n 31) paras 16, 45; AbbVie v EMA (n 31) para 59; PTC Therapeutics International v EMA (n 23) para 31. EMA v AbbVie (n 41) para 31. Pari Pharma v EMA (n 31) para 44 (emphasis added). See also P Oliver, ‘Privacy and Data Protection: The Rights of Economic Actors’ in Sybe de Vries, Ulf Bernitz, and Stephen Weatherill (eds), The EU Charter of Fundamental Rights as a Binding Instrument: Five Years Old and Growing (Bloomsbury Publishing 2015) 313 (arguing that ‘economic actors do not enjoy the full benefit of the protection afforded by Art 7 [CFR] in contrast, there can be no doubt that companies enjoy the full benefit of both Arts 16 and 17 [CFR] Accordingly, it seems preferable to treat business secrets as falling under one or other of the latter provision, or perhaps both.’). Art 39 of the TRIPS Agreement. See European Commission, ‘Impact Assessment accompanying the document proposal for a Directive of the European Parliament and of the Council on the protection of undisclosed know-how and business information (trade secrets) against their unlawful acquisition, use and disclosure’ SWD (2013) 471 final, 66, 105 (emphasising the difference between trade secrets and intellectual property rights in that ‘[c]ontrary to intellectual property rights, the protection of trade secrets against misappropriation does not institute any exclusive right’ and highlighting the inconsistency of terminology and diversity of legal regimes applicable to confidential information among the EU Member States). See also Committee on Legal Affairs, ‘Report on the proposal for a directive of the European Parliament and of the Council on the protection of undisclosed know-how and business information (trade secrets) against their unlawful acquisition, use and disclosure’ (2015) (COM (2013) 0813 – C7-0431/2013 – 2013/ 0402(COD)) A8-9999/2015, 14. Case C-1/11 Interseroh Scrap and Metal Trading GmbH v Sonderabfall-Management-Gesellschaft RheinlandPfalz [2012] ECLI:EU:C:2012:194, para 43. In general, trade secret protection is recognised as a form of intellectual property but not as exclusive rights. For an overview of positions, see European Commission (n 101) 249–51. For the analysis whether confidential information can be protected as property and intellectual property in the context of Art 1 of the First Protocol of the ECHR and Art 17 CFR, see TF Aplin, ‘Confidential Information as Property’ (2013) 24(2) King’s Law Journal 172.

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and business information.104 Theoretically, some reports’ contents may meet the criteria set out in Article 2 of the Directive. For instance, during the EMA’s public consultations, Novo Nordisk submitted that clinical trial reports contain ‘detailed strategic and operational information revealing general company know-how about the efficient and competitive set-up of clinical studies, such as trial site performance’ and ‘disclosure of such information could provide competitors with a roadmap to facilitate their own product development programs’.105 Similarly, AbbVie claimed that clinical reports ‘represent the proprietary information and specialist technical know-how of the originator company. . . [and] contain a substantial amount of commercially confidential information and know-how. . .’.106 The assessment of these claims would require element-by-element analysis of a report’s contents. Even if certain parts might qualify as ‘possessions’, protection can be subject to the reservation under Article 17(1) CFR, which allows for control over and use of reports to be ‘regulated by law in so far as is necessary for the general interest’.107 Disclosure by a drug authority pursues public policy objectives and occurs in a scenario other than the unauthorised acquisition, use and disclosure by dishonest practices108 that form the core of trade secret protection. In this regard, the Directive on trade secrets envisages that ‘tailoring of measures’ of trade secret protection ‘should not jeopardise or undermine fundamental rights and freedoms or the public interest, such as public safety, consumer protection, public health and environmental protection. . .’.109

C. The Unresolved Issues In the cases reviewed above, the substantive question of whether the EMA’s disclosure of clinical reports infringe Article 8 ECHR, Article 7 CFR, Article 339 TFEU, and Article 4(2) of Regulation (EC) 1049/2001 was left for the court adjudicating in the main proceedings to decide.110 The General Court noted that: [a] distinction must be drawn between, on the one hand, information which is inherently secret, such as business secrets of a commercial, competition-related, financial or accounting nature, or confidential, such as purely internal

104 The European Parliament legislative resolution of 14 April 2016 on the proposal for a directive of the European Parliament and of the Council on the protection of undisclosed know-how and business information (trade secrets) against their unlawful acquisition, use and disclosure (COM (2013) 0813 – C7-0431/ 2013 – 2013/0402(COD)). 105 The EMA, ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/ 240810/2013)’ (2 October 2014) EMA/354914/2014, 70–71 (emphasis added). See also the submission by the German Pharmaceutical Industry Association (BPI), ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/240810/2013)’ (2 October 2014) EMA/349245/2014, 14 (emphasis added). 106 AbbVie v EMA (n 31) para 59 (emphasis added). 107 Explanations (n 54) C 303/23. 108 Directive on the protection of trade secrets, Art 4. 109 ibid, rec 21. 110 AbbVie v EMA (n 31) para 66; InterMune v EMA (n 31) para 52; Pari Pharma v EMA (n 31) para 67; PTC Therapeutics International v EMA (n 23) para 75.

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information, and, on the other hand, documents or information which may be secret or confidential for a reason that the applicant must provide.111 Furthermore, the General Court referred to ‘the degree of novelty and the scale of the investment made by the applicant in terms of time and cost’ for the purpose of compiling clinical trial data as a potential justification for confidential treatment.112 Notably, in contrast to this view, the EMA’s 2016 Guidance states that the expenditures in terms of the amount of time, human, financial, and commercial resources in clinical trials are irrelevant to justify the redaction.113 In this regard, a final ruling from the CJEU clarifying the factors to be considered when assessing confidentiality protection would have more weight than the EMA’s guidance, which renders a non-binding interpretation of the exception. Thus, absent the decision on merits, the relevant test for the legality assessment of disclosure of clinical reports by a regulatory authority under current EU law remains unclear. At the same time, the similarity of the wording of the exceptions under Articles 13 and 80 of Regulation (EC) 726/2004, Article 81(4)(b) of Regulation (EU) 536/2014, and Article 4(2) Regulation (EC) 1049/2001, as well as the systematic relationship between these regulations, suggests that access to clinical reports shall be exercised within the scope of the right of access to documents. The next section analyses how the particular exception for protection of commercial interests under Article 4(2) of Regulation (EC) 1049/2001 can apply, taking into account the specifics of clinical study reports and the context in which disclosure occurs. IV . A P P L YI NG TH E E X C EP T IO N FO R PR OT EC TI ON OF COM M E R C I A L I N T E R E S T S T O C LI NI C AL D ATA

A. The General Principle As a rule, restrictions on the exercise of fundamental rights can be justified only if they ‘correspond to objectives of general interest pursued by the Community and do not constitute, with regard to the aim pursued, disproportionate and unreasonable interference undermining the very substance of those rights’.114 Although Article 42 CFR does not contain specific safeguards, the scope of the right of access is to be determined according to the principles of proportionality and necessity.115 The narrow interpretation of the exceptions to the right of access to documents has been affirmed by the CJEU, which held that the exceptions must be ‘interpreted and applied strictly’,116 ‘in the light of the principle of the right to information and the principle of proportionality’,117 and 111 InterMune v EMA (n 31) para 17 (emphasis added). 112 Pari Pharma v EMA (n 31) para 54; PTC Therapeutics International v EMA (n 23) para 66 (emphasis added). 113 See n 69. 114 Explanations (n 54) C 303/32-33 (emphasis added). 115 Art 52(1) CFR stipulates that limitations of the fundamental rights shall be ‘subject to the principle of proportionality [and] may be made only if they are necessary and genuinely meet objectives of general interest recognised by the Union or the need to protect the rights and freedoms of others’). 116 Joined Cases C-39/05P and C-52/05P Sweden and Turco v Council [2008] ECR I-4723, para 36, with further references. 117 Case C-353/99P Council v Hautala [2001] ECR I-9565.

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in a manner which is ‘compatible with the other [regulations]’ in the absence of the explicit primacy of one regulation over the other.118 In principle, with regard to thirdparty documents, the institution requested to grant access shall consult the document submitter and assess whether the exceptions are applicable.119 Such assessment must be ‘specific in nature’120 and account for the particular circumstances.121 The intersection of different fundamental rights creates duality. On the one hand, protection of confidentiality can be viewed as a limitation on the right of access. On the other hand, disclosure can constitute a limitation on protection under Articles 7 and 17 CFR (if such protection is confirmed for clinical reports). As observed by the General Court, ‘although the concept of “commercial interests” has not been defined in the case law, the Court has made clear that it is not possible to regard all information concerning a company and its business relations as covered by the exception under Article 4(2) of Regulation (EC) No 1049/2001’.122 At the same time it also acknowledged that, even though Regulation (EC) 1049/2001 intends to ‘confer on the public as wide a right of access as possible to documents of the EU institutions’, the right is subject to certain limits based on reasons of public or private interest.123 Therefore, disclosure would necessitate a ‘delicate assessment’124 of the interests involved. Such individual evaluation can be burdensome for a public authority; as argued by the EMA, the case-by-case ‘justifi[cation] of the redaction in detail would run counter to the efficient use of resources and would slow down the release of documents’.125 To avoid undue holdups, in some situations, as discussed below, access to documents can be regulated by the legal presumptions of confidentiality (or nonconfidentiality).

B. The Existence of a General Presumption for Clinical Data Under Regulation (EC) 1049/2001, third-party documents can be disclosed upon the consultation with the submitter of the original document, ‘unless it is clear that the document shall or shall not be disclosed’.126 Such legal presumptions can also be provided under sector-specific legislation. For instance, in the area of the environmental regulation, when the request for access concerns information regarding emissions, an overriding public interest in disclosure is presumed to outweigh the protection of

118 Case C-365/12P Commission v EnBW Energie Baden-Wu¨rttemberg AG [2014] ECLI:EU:C:2014:112, para 84, with further references. 119 reg (EC) 1049/2001, Art 4(3). 120 Cases T-355/04 and T-446/04 Co-Frutta v Commission [2010] ECLI:EU:T:2010:15, para 123. 121 See Commission v EnBW Energie Baden-Wu¨rttemberg (n 118) para 63, with further references. 122 Case T-344/08 EnBW Energie Baden-Wu¨rttemberg AG v Commission [2012] ECLI:EU:T:2012:242, para 134, with further references (emphasis added). See also Case T-403/05 MyTravel Group v Commission [2008] ECR II-02027 [33] (reinforcing that ‘the mere fact that a document concerns an interest protected by an exception cannot of itself justify application of that exception’). 123 See Case T-110/15 International Management Group v European Commission [2015] ECLI:EU:T:2012:242, para 25, with further references. 124 AbbVie v EMA (n 31) para 69; InterMune v EMA (n 31) para 54; Pari Pharma v EMA (n 31) para 58. 125 Ombudsman (n 5) para 18. 126 reg (EC) 1049/2001, Art 4(3) (emphasis added).

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commercial interests.127 The provision under Regulation (EC) 1367/2006 constitutes lex specialis that modifies the exceptions under Regulation (EC) 1049/2001. The existence of such a presumption has been recently confirmed in the case Stichting Greenpeace Nederland and PAN Europe v Commission,128 while the Commission refused to grant access on the grounds of protection of business secret,129 the General Court upheld the presumption of the overriding public interest.130 Another example can be seen in the area of merger control, where the Commission Notice provides for special rules on ‘access to the file’—ie any documents obtained, produced, or assembled by the Commission during the investigations.131 Access can be granted to the parties involved in the merger investigations with the exception of internal documents, business secrets, and other confidential information.132 Even though these procedural rules do not constitute lex specialis deviating from the general rules under Regulation (EC) 1049/2001,133 the CJEU has recently upheld the existence of a general presumption that disclosure of documents exchanged between the Commission and undertakings during merger control proceedings undermines, in principle, both protection of the objectives of investigation activities and that of the commercial interests of the undertakings involved in such a procedure.134 As already stated, the EMA generally assumes that ‘clinical data cannot be considered CCI’.135 Recital 68 of Regulation (EU) 536/2014 also declares that ‘in general the data included in a clinical study report should not be considered commercially confidential’ upon the grant of a MA or the withdrawal of an MA application.136 However, absent a specific provision in the actual body of the Regulation, this statement cannot be 127 Council Regulation (EC) 1367/2006 on the application of the provisions of the Aarhus Convention on Access to Information, Public Participation in Decision-making and Access to Justice in Environmental Matters to Community institutions and bodies [2006] OJ L264/13, Art 6(1). 128 Case T-545/11 Stichting Greenpeace Nederland and PAN Europe v Commission [2013] EU:T:2013:523. 129 In particular, ‘the Commission considered that . . . on balance, the need to protect the intellectual property rights of [documents submitters] outweighed the public interest in disclosure of the information. In the Commission’s view, disclosure of the information contained in the document at issue would allow competing undertakings to copy the production method followed by the operators which had sought the inclusion of glyphosate, which would lead to considerable loss for those operators and leave their commercial interests and intellectual property rights unprotected . . . .’ ibid, para 9 (emphasis added). 130 ibid, para 76. 131 Commission Notice on the rules for access to the Commission file in cases pursuant to Arts [101 and 102 TFEU], Arts 53, 54, and 57 of the EEA Agreement and Council reg (EC) 139/2004, OJ 2005/C 325/07. 132 ibid, para 2.10. 133 ibid, paras 1, 2 (emphasising the difference between access to file, as a guarantee of the right of the defence, and access to documents under Regulation (EC) 1049/2001). See also G Goddin, ‘Recent Judgments Regarding Transparency and Access to Documents in the Field of Competition Law: Where Does the Court of Justice of the EU Strike the Balance?’ (2011) 2(1) Journal of European Competition Law & Practice 10. ditions Odile Jacob SAS [2012] ECLI:EU:C:2012:393, para 123; Case C134 Case C-404/10P Commission v E 477/10P Commission v Agrofert Holding [2012] ECLI:EU:C:2012:394, para 84. 135 See n 28. 136 See also 2015 publication policy (n 3) 4, 6, (emphasis added).

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regarded as having the effect of a legal presumption comparable to one concerning information on the environmental emissions. Quite the opposite, Article 81(4)(b) of Regulation (EU) 536/2014 contains a reservation, meaning that data in the database: shall be publicly accessible unless, for all or part of the data and information contained therein, confidentiality is justified on . . . the . . . grounds [of] protecting commercially confidential information, in particular through taking into account the status of the marketing authorisation for the medicinal product, unless there is an overriding public interest in disclosure . . . (emphasis added). Furthermore, the obligation on the institution to carry out a specific, individual examination of the content covered by the request for access has been waived for certain categories of documents by the CJEU. So far, the general presumptions of confidentiality have been acknowledged with regard to the documents related to the procedures for reviewing state aid, the assessment of concentrations, the pleading lodged by one of the institutions in court proceedings, and infringement proceedings during the prelitigation stage.137 As for clinical data, the General Court has not excluded that the Court adjudicating on the substance may recognise that clinical reports shall enjoy a general presumption of confidentiality ‘by their very nature’, ‘taken as a whole’ and thus deny the specific examination ‘of the individual pieces of information’.138 However, the fact that the Court of Justice sent the first two cases back to the General Court to examine whether it was possible to authorise partial access to the reports at issue in light of the applicants’ proposals for redaction,139 suggests that no general presumption was recognised.140 Thus, the EMA is, in principle, required to assess the requests for CCI redaction and consider the interests at stake on the case-by-case basis.141

C. Defining Commercial Interests in Confidentiality To qualify for the exception, the risk of impediment of commercial interests must be ‘reasonably foreseeable and not purely hypothetical’.142 However, at the point when access to clinical data is petitioned for, the prospective effects of disclosure may not be adequately evaluated. As the General Court pointed out:

See Commission v EnBW Energie Baden-Wu¨rttemberg (n 118) para 66, with further references. Pari Pharma v EMA (n 31) para 105; PTC Therapeutics International v EMA (n 23) para 124. EMA v AbbVie (n 41) para 55; EMA v InterMune (n 74) para 57. Nevertheless, in the subsequent disputes, the General Court did not consider that it would be ‘appropriate, in view of the specific features of proceedings seeking the protection of allegedly confidential documents . . . to consider a partial solution consisting in protecting only certain pieces of information, while allowing access to other pieces of information to be granted’. See PTC Therapeutics International v EMA (n 23) para 127; Pari Pharma v EMA (n 31) para 109. 141 As held by the CJEU in EMA v Pari Pharma, ‘the fact that the reports at issue have already been disclosed in the present case cannot prevent the EMA from examining any other request for access concerning the same reports by subjecting that request to the procedure laid down in Regulation No 1049/2001 and thereby enabling Pari Pharma to oppose any disclosure under one of the grounds provided for in Art 4 of that regulation’. EMA v Pari Pharma (n 82) para 57 (emphasis added). 142 Sweden and Turco v Council (n 116) para 43.

137 138 139 140

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the applicant would have to expect that an undetermined and potentially unlimited number of current and potential competitors all over the world will obtain those reports in order to exploit them in numerous ways, which, depending on the status of their research and development programmes, could entail harmful effects in the short, medium or long term, liable to thwart any expansion strategy on the applicant’s part.143 The effects of disclosure on the commercial interests of the original drug sponsors can be defined in relation to their competitive position in the relevant market, in particular, in terms of facilitating the entry of a competing drug. As argued by Pari Pharma: each month of delayed market entry of a competitor that has to find a way to overcome the existing hurdles to market entry by itself without having access to the applicant’s proprietary information contained in the reports at issue constitutes a considerable commercial advantage, even if it is not precisely quantifiable.144 Although potential effects on competition might not be quantifiable, they can be qualified by distinguishing among the types of competition—ie competition by imitation (generic), improvement, and substitution. As for generic–originator competition, third-party access—albeit under the terms for non-commercial use—can pose a risk that the released reports can serve the purpose of the approval of an identical drug. Such use is explicitly prohibited under the EMA’s policy terms.145 Yet, some innovator companies have raised concerns that the accessed reports can be used for generic drug approval ‘in regions where the originator company does not have a marketing authorisation, or where no stewardship or adequate protection for CCI exists’.146 It should be noted that, in such a case, data would fulfil the regulatory function (ie obtaining a marketing approval), while the qualitative and quantitative formulation of the originator drug can be ‘reverse engineered’ without accessing the originator’s MA dossier.147 The impact of the generic entry on the competitive position of the original drug sponsor can be substantial, but can be determined only in the context of the particular market conditions.148 Pari Pharma v EMA (n 31) para 100 (emphasis added). ibid, para 77 (emphasis added). The 2015 publication policy (n 3) Annex 1, para 3; Annex 2, para 3.2. Pfizer, ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/240810/ 2013)’ (2 October 2014) EMA/344107/2014, at 85; German Pharmaceutical Industry Association, ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/240810/2013)’ (2 October 2014) EMA/349245/2014, 11; The EuropaBio, ‘Overview of comments received on “Publication and access to clinical-trial data” (EMA/240810/2013)’ (2 October 2014) EMA/344107/2014, 27. See also EMA v AbbVie (n 41) para 32. 147 AK Bansal and V Koradia, ‘The Role of Reverse Engineering in the Development of Generic Formulations’ (2 August 2005) PharmaTech.com accessed 30 October 2016. 148 See European Commission, Competition DG, Pharmaceutical Sector Inquiry, final report (2009) 78 (finding for the analysed sample that in the markets with generic entry ‘average prices dropped by almost 20%

143 144 145 146

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As for competition by improvement, insights gained from clinical reports can speed up the development of a superior follow-on product.149 For instance, AbbVie argued that disclosure: would undermine the protection of [AbbVie’] commercial interests [as] the . . . competitors could use the disputed reports to improve their competitive position with (actually or potentially) competing products in the highly competitive class of TFN antagonists. [Clinical trial] reports . . . provide a very specific road map for a company wishing to develop a TNF antagonist for the therapeutic use in question, by enabling it to develop a similar ‘biologics/biosimilar’ strategy in order to produce a follow-on medicinal product or to add new therapeutic indications to an existing medicinal product. The reports also provide information . . . which could reduce the development process for a medicinal product by two to three years.150 Similarly, InterMune alleged that damage by disclosure would arise due to: the future use of the information [in] requested documents by the InterMune companies’ competitors – and specifically by Boehringer Ingelheim GmbH . . .– in order to develop a medicinal product which would compete with the medicinal product Esbriet. . .151 Although the General Court found these lines of arguments as ‘purely hypothetical’,152 it is highly possible that access to non-summary data can facilitate the development of a product that would improve therapeutic efficacy or safety of the existing drug.153 The actual impact on competition would depend on the degree of the substitutability between the original and subsequently developed drugs. Furthermore, knowledge gained from patient-level trial data might ‘uncover new areas of research’154 and prompt the development of a new drug that might form a new market and compete by substitution. As envisaged by the NAS Health and Medicine Division, sharing ‘raw’ clinical data can enable:

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150 151 152 153 154

after the first year following [loss of exclusivity] and about 25% after two years. In rare cases, for some medicines in some Member States, the decrease in the average price index was as high as 80-90%.’). PTC Therapeutics International v EMA (n 23) para 92. See also JA DiMasi and C Paquette, ‘The Economics of Follow-on Drug Research and Development. Trends in Entry Rates and the Timing of Development’ (2004) 22(2) Pharmacoeconomics 1, 2 (defining a follow-on new drug as ‘a new drug entity with a similar chemical structure or the same mechanism of action as that of a drug already on the market . . .[ie] a new entrant to a therapeutic class that had already been defined by a separate drug entity that was the first in the class (sometimes referred to as the breakthrough drug)’). AbbVie v EMA (n 31) para 60 (emphasis added). EMA v InterMune (n 74) para 34 (emphasis added). InterMune v EMA (n 31) para 40. Moreover, disclosed findings on secondary effects of tested drug candidates that had not been the primary endpoints of a trial could reveal new therapeutic uses of the underlying compound. The US Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry, ‘Policy on releasing and sharing data’ [2005] 4 accessed 30 October 2016.

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additional scientific discoveries by allowing other investigators to carry out alternative or additional analyses to test the robustness of published findings . . . to plan meta-analyses; and to carry out exploratory studies to generate new hypotheses.155 Given the unpredictable nature of drug R&D, such probability is hard to ascertain. Theoretically, non-summary research data can reveal certain correlations between the chemical structure and the pharmacological characteristics of the tested compounds that may guide other drug developers and researchers to alternative chemical structures and development of new drugs.156 If so, companies would have a strong incentive to restrict access to primary data in order to retain the advantage in competition by R&D efforts.157 In sum, it is difficult to conceive a situation when disclosure of MA dossiers might not entail dynamic competitive effects.

D. Defining Public Interests in Disclosure The commercial interests of pharmaceutical companies ‘in not having their reports disclosed’are to be weighed up against ‘the general interest guaranteeing the broadest public access possible to documents held by the European Union’.158 While the institution should undertake a balancing of interests,159 the party petitioning for access needs to ‘refer to specific circumstances to establish an overriding public interest which justifies the disclosure of the documents concerned’.160 In ClientEarch v Commission, access to documents on the compliance of the national legislation with EU environmental law was claimed on the grounds that: the principles of transparency and democracy entail that citizens have the right to be informed of the extent to which national law is compatible with European Union environmental law and to participate in the decision-making process.161 The CJEU, however, found the argument too ‘general’ and, thus: 155 The Institute of Medicine of the National Academies (n 16) 84 (emphasis added). See also Krumholz and others, ‘Sea Change in Open Science and Data Sharing Leadership by Industry’ (2014) 7(14) Circulation: Cardiovascular Quality Outcomes 499. 156 See eg MS Lauer, ‘Data Primarily Collected for New Insights’ in Grossmann and others (eds), Clinical Data as the Basic Staple of Health Learning: Creating and Protecting a Public Good (National Academy of Sciences 2010) 90, 91 (viewing clinical trials as ‘rich sources of observational data, useful for exploring questions that go beyond their original hypotheses’ (emphasis added)). 157 Innovation has been viewed as the main form of competition in the pharmaceutical industry. See L Orsenigo, G Dosi, and M Mazzucato, ‘The Dynamics of Knowledge Accumulation, Regulation, and Appropriability in the Pharma-biotech Sector: Policy Issues’, in M Mazzucato and G Dosi (eds), Knowledge Accumulation and Industry Evolution. The Case of Pharma-Biotech (CUP 2006) 402, 407 (stipulating that ‘[o]n the supply side, the pharmaceutical industry is inherently characterized by non-price competition. . . . producers are attributed (temporary) monopoly power through patent protection’). 158 InterMune v EMA (n 31) para 54; AbbVie v EMA (n 31) para 69; Pari Pharma v EMA (n 31) para 58. 159 Sweden and Turco v Council (n 116) paras 44, 45. 160 See Case C-612/13P ClientEarth v Commission [2015] ECLI:EU:C:2015:486, para 90, with further references. 161 ibid, para 91.

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‘not capable of demonstrating that the principles of transparency and democracy raised in [that] case issues of particularly pressing concern which could have prevailed over the reasons justifying the refusal to disclose in their entirety the contested studies placed in a file relating to the pre-litigation phase of infringement proceedings. . .’.162 What public interests would be relevant for the balancing test in disputes concerning clinical trial data? In view of the relationship between Regulation (EC) 1049/2001 and the EMA’s transparency policies, the public interests at stake should be defined in relation to and within the scope of the right of access to documents.163 The latter is considered to be the ‘core aspect’ of the principles of transparency, democracy, and good administration of the EU political system.164 For instance, as emphasised in Sweden and Turco v Council, the interest to be protected by non-disclosure of the document concerned needs to be balanced against: the public interest in the document being made accessible in the light of the advantages stemming . . . from increased openness, in that this enables citizens to participate more closely in the decision-making process and guarantees that the administration enjoys greater legitimacy and is more effective and more accountable to the citizen in a democratic system.165 In other words, the public interest should relate to the decision-making and administrative procedures of an EU authority or institution. This idea also corresponds to the definition of a ‘document’ under Regulation (EC) 1049/2001—ie ‘any content whatever its medium . . . concerning a matter relating to the policies, activities and decisions falling within the institution’s sphere of responsibility’.166 Likewise, the EMA confines the scope of publicly accessible documents to the documents ‘concerning any matter related to the policies, activities and decisions falling within the EMA’s remit and responsibilities’.167 In other words, for the purpose of applying the exception, the relevant public interest should pertain to the Agency’s own decision-making exercised within the scope of its regulatory mandate. The EMA’s functions are primarily associated with the scientific assessment of safety, efficacy, and quality of medicinal products for human or veterinary use intended to be commercialised in the Member States.168 Consequently, the relevant public interest shall be seen in being informed 162 ibid, para 93, with further references. 163 ibid, para 92 (holding that ‘it is true that the overriding public interest which may justify the disclosure of a document need not necessarily be distinct from the principles which underlie Regulation No 1049/2001’), with further references. 164 reg (EC) 1049/2001, rec 2. See also D Curtin and J Mendes, ‘Article 42 – Right of Access to Documents’ in S Peers and others (eds), The EU Charter of Fundamental Rights. A Commentary (Hart Publishing 2014) 1104. 165 Sweden and Turco v Council (n 116) para 45. 166 Regulation (EC) 1049/2001, Art 3(a) (emphasis added). 167 The 2010 access policy (n 2) 3 (emphasis added). rec 10 of reg (EC) 1049/2001 states that access to documents received by the EU institutions should be granted in order ‘to bring about greater openness in the work of the institutions’. 168 reg (EC) 726/2004, rec 19, Art 57.

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about and able to participate in the decision-making regarding drug authorisation and supervision.169 The right of access can be exercised, for example, by the ability to verify the validity of the EMA’s risk–benefit analysis concerning a particular drug and understand its therapeutic characteristics and value.170 In Pari Pharma v EMA, the EMA generally claimed that there was an overriding public interest justifying disclosure of Pari Pharma’s similarity and superiority reports as they contained ‘scientific information, including the opinions and the assessment reports’ related to the MA of Vantobra.171 However, in that case, access was petitioned by Pari Pharma’s competitor Novartis, in order to support its action for the annulment of the EMA’s decision to authorise Vantobra, which had been approved by way of derogation of market exclusivity of Novartis’ product. In that situation, access would serve the purpose of protecting market exclusivity of Novartis’ drug by annulling the EMA’s decision.172 In a recent case, Commission v EnBW, access was also requested for litigation purposes: As asserted by the claimant, ‘there was no other way of obtaining the evidence’ in order to claim compensation before the national court for the damage allegedly caused by the cartel that had been censured by the Commission.173 The Court, however, did not find an overriding public interest that would justify disclosure of the documents at issue.174 Likewise, the General Court in InterMune failed to see any specific public interest behind the request for access in view that access was requested by a competing undertaking.175 One could speculate that in Pari Pharma v EMA there was a particular public interest of accessing the similarity and superiority reports. Had the EMA erred in approving Vantobra as clinically superior over TOBI Podhaler, it would have impaired innovation incentives provided by market exclusivity protection. Hypothetically, social costs of such ‘error’ would correspond to new medicines that could have been developed by Novartis due to market exclusivity protection. The argument is, however, purely theoretical, and it remains to be seen whether any of the currently pending disputes will reach the stage when public and commercial interests are weighed up.

E. Public Interests beyond Transparency Besides transparency, the EMA publication policy pursues several objectives, namely, ‘to avoid duplication of clinical trials, foster innovation and encourage development of new medicines’.176 Similarly, the implementation of the new EU database for clinical 169 Art 80 of reg (EC) 726/2004 stipulates that information related to the authorisation or supervision of medicinal products shall be made available to the public in order ‘to ensure an appropriate level of transparency’. 170 Ombudsman (n 5) paras 44, 72 (putting forward an argument that clinical reports can reveal important information concerning a possible off-label use). 171 Pari Pharma v EMA (n 31) para 25. 172 ibid, para 58. 173 Commission v EnBW Energie Baden-Wu¨rttemberg (n 118) paras 131–32. 174 ibid. See also Co-Frutta v Commission (n 120) para 133 (holding that ‘it is not possible to categorise the applicant’s commercial interests as being an ‘overriding public interest’). In that case, access to the documents was requested in order to prove whether the competitors were involved in fraudulent practices. 175 InterMune v EMA (n 31) para 47. 176 The EMA, Clinical data publication accessed 30 October 2016.

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data intends to ‘contribute to . . .fostering the innovation capacity of European medical research’.177 These goals are distinct from those related to transparency of drug approval and supervision and can be defined as economic efficiency-oriented—ie to optimise drug R&D by eliminating duplicative research and to promote dynamic efficiency at the sector level by enabling secondary analysis of the research data. Recent studies emphasise the important role of non-summary data from previous clinical research in facilitating new drug development. The proposition is that the greater availability of data from previous clinical trials can make the subsequent drug R&D more informed, targeted, and efficient.178 For instance, the report of the National Academies of Science submits that: data sharing could open up opportunities for exploratory research that might lead to new hypotheses about the mechanisms of disease, more effective therapies, or alternative uses of existing or abandoned therapies that could then be tested in additional research.179 According to the British Pharmacological Society, evidence from prior clinical trials allows: to extrapolate likely effect of new drugs, doses and combinations, . . . more quickly eliminate potentially troublesome compounds earlier in the drug development process [and] focus [R&D] efforts on more relevant targets . . . .180 Drug R&D is characterised by high uncertainty and oftentimes compared to a ‘lottery game’.181 Pharmaceutical companies have economic incentives to restrict access to research data if it can reduce the ‘natural lead time’ afforded by competitors’ trial and errors. As claimed by the Therapeutics International: competitors will also be able to mine the data in the report at issue in order to restructure their own clinical trials and avoid some of the trial-and-error development which it had to undertake.182

177 reg (EU) 536/2014 (n 9) rec 67. 178 See P Smith, ‘Registries and Care with Evidence Development’ in Grossmann and others (eds), Clinical Data as the Basic Staple of Health Learning: Creating and Protecting a Public Good (National Academy of Sciences 2010) 125, 129; F. Koenig and others, ‘Sharing Clinical Trial Data on Patient Level: Opportunities and Challenges’ (2015) 57(1) Biometrical Journal 8; H-G Eichler and others, ‘Access to Patient-Level Trial Data—A Boon to Drug Developers’ (2013) 369 The New England Journal of Medicine 1577. 179 The Institute of Medicine of the National Academies (n 16) para 28, with further references. 180 The British Pharmacological Society, ‘Pharmacology Skills for Drug Discovery’ 2, 5, accessed 30 September 2016. 181 J Sutton, Technology and Market Structure. Theory and History (The MIT Press 2001) 197, 228. On random screening, see eg RM Henderson, L Orsenigo and G Pisano, ‘The Pharmaceutical Industry and the Revolution in Molecular Biology: Exploring the Interactions Between Scientific, Institutional, and Organizational Change’ in DC Mowery and RR Nelson (eds), Sources of Industrial Leadership: Studies of Seven Industries (CUP 1999) 267–311. 182 PTC Therapeutics International v EMA (n 23) para 92 (emphasis added).

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At the outset, one can hardly predict which particular drugs can eventually be developed as a result of the secondary analysis of data.183 At the same time, it cannot be denied that the launch of a new drug would affect commercial interests of the initial trial sponsor. In this regard, the EMA’s intention to establish ‘a level playing field’184 by disclosing data appears controversial and inherently contradicts the Agency’s own definition of CCI in that disclosure can speed up the development of a new drug that might compete with that of the submitter of the original reports where disclosure may undermine the economic interest or competitive position of the owner of the information. It might be so that the original drug sponsor (and the initial holder of the reports) also conducts R&D directed at the development of a new drug that can be ‘prompted’ if other drug developers access the data. This might be the case of improving the approved drug or developing a new use of the underlying compound. In the opinion of the European Ombudsman, the interference with the ongoing new drug development is ‘the main, if not only, legitimate justification for redacting information from a clinical study report’.185 As a solution, the Ombudsman proposed that MA applicants—in addition to the requirement to provide a redacted version of the clinical report— should also provide ‘a public disclosure schedule, specifying the categories of information that can be disclosed at a later date and the event that will trigger such disclosure’.186 However, if disclosure can lead to the development of an improved product—eg a new dosage—in the Ombudsman’s view, it shall be justified under the overriding public interest.187 While the legitimacy of the EMA’s objectives of fostering innovation through disclosure of clinical trial reports and (anonymised) IPD cannot be doubted, the question is whether they are relevant for the purpose of public interest assessment when applying the exception under Article 4(2) of Regulation (EC) 1049/2001. In a strict sense, these policy goals go beyond public interests associated with the right of access—ie the ability to scrutinise the Agency’s decisions within its own regulatory mandate. Certainly, these additional objectives relate to the EMA’s role as an institution within the healthcare system. Yet they differ in nature from those underlying the right of access to documents. This suggests that economic efficiency-oriented policy objectives might require further economic analysis and merit a special regulatory treatment. In other words, the right allowing access to documents might be too narrow to support the economically oriented objectives pursued through access initiative. In view of the foregoing, the main complexity in applying the exception can be seen in defining the scope of the relevant and legitimate interests to be balanced in this specific context. The rules of access cannot be consistently applied, unless this policy 183 See D Kim, ‘Knowledge Sharing as a Social Dilemma in the Pharmaceutical Industry’ (2016) 71(4) Food and Drug Law Journal 673 (discussing different scenarios of drug development in view of clinical trial data as a source of biomedical knowledge). 184 The 2015 publication policy (n 3) 4. 185 Ombudsman (n 5) para 73. 186 ibid. 187 Ombudsman (n 5) para 44 (stating that ‘it might well be the case that the development relates also to a known “possible” use of the product and it could even be the case that doctors are already using the product, off-label, for that use. In such circumstances, there would also be strong reasons to consider, if the product is being used off-label, that there is an overriding public interest in the disclosure of the information at issue’).

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question is clarified. In a science-driven sector such as the pharmaceutical industry,188 the reservation for the use of ‘non-commercial research’ purposes may not help protect the commercial interests of the trial sponsors, as virtually any ‘piece of the contents’ of the MA dossiers if ‘spills over’ and is re-used by other drug developers can facilitate the development and launch of a new, potentially competing drug. V . CO NC L U D I N G R EM A R K S In view of the foregoing, paradigm of access to clinical trial data in the EU perhaps has not ‘shifted’ yet, as it has been aspired, but certainly ‘tilted’ towards greater transparency and availability of data. The actual scope of data that can be lawfully released by the EMA, however, remains unclear and, to a large extent, depends on the interpretation of the notion of CCI. Other major points of ambiguity concern the legal nature and sources of protection of data against regulatory disclosure, the scope of legitimate economic interests of commercial drug sponsors, and the particular interests that are relevant for the balancing exercise when applying the exception for their protection. As discussed above, different public interests can potentially justify both confidentiality protection of data as well as measures promoting access. Overall, it follows from the analysis that the existing regulatory framework can provide limited support for the EMA’s proactive practice of granting third-party access to data, especially, with regard to patient-level data. The scope of access under the EMA’s transparency policies is confined within the limits of the fundamental right of access to documents. Under such approach, disclosure of clinical trial data can be justified insofar it is necessary to ensure transparency of the Agency’s own decisionmaking regarding marketing approval and supervision of drugs. This implies that the objectives such as facilitating research and new drug development—albeit legitimate and highly important—exceed the legal basis of the EMA’s policies.

188 See eg B Achilladelis and N Antonakis, ‘The Dynamics of Technological Innovation: The Case of the Pharmaceutical Industry’ (2001) 30 Research Policy 535, 550.