Introduction
Submission of redacted clinical reports
Issuance of advance warning
Redaction procedure
Publication of final redacted reports
Redaction of commercially confidential information
Anonymisation of clinical reports


Introduction

On June 24 2015 the European Medicines Agency delivered an update(1) on the implementation of its policy concerning the publication of clinical data.

The policy(2) (adopted on October 2 2014) enables interested third parties access to clinical reports and individual patient data submitted as part of a marketing authorisation or post-marketing authorisation for an existing centrally authorised medicinal product. Clinical data submitted in accordance with the centralised marketing authorisation procedure for a medicinal product after January 1 2015 can be disseminated to interested third parties. On July 1 2015 the scope of the policy was expanded to include clinical data submitted as part of an application for an extension of a therapeutic indication or a line extension of a centrally authorised medicinal product.

The update provides stakeholders with information concerning procedural requirements and guidance on the redaction of commercially confidential information and the anonymisation of personal data.

Submission of redacted clinical reports

Under the policy, pharmaceutical companies are required to submit their proposals for redaction of clinical data between Day 181 and Day 220 of the procedure preceding marketing authorisation . Proposed redactions of clinical data provided in support of applications for an extension of an existing marketing authorisation to include a new indication must be submitted between 30 calendar days pre-opinion and 10 calendar days post-opinion. If a marketing authorisation application is withdrawn, the report must be submitted within 30 calendar days of the notification of withdrawal.

Companies are required to certify that the redacted clinical report reflects the version submitted for scientific review. This declaration may be presented in a cover letter to the European Medicines Agency. It must confirm that the only difference between the two reports is the proposed redactions.

Issuance of advance warning

Companies can receive up to three notifications as a warning to submit a redaction proposal alongside their marketing authorisation application or line extension application. Such a warning can come during the scientific review process following receipt of:

  • the validation letter from the agency;
  • the list of outstanding issues on Day 180 of the marketing authorisation application; and
  • the opinion letter from the Committee for Medicinal Products for Human Use.

For an extension of a therapeutic indication to an existing marketing authorisation, companies can receive a warning to submit a redaction proposal following receipt of:

  • the agency validation letter;
  • a request for supplementary information; and
  • the committee's opinion letter.

Finally, in the case of withdrawn applications, notification could be received following:

  • the agency validation letter; or
  • the withdrawal letter to the marketing authorisation application.

Redaction procedure

According to the European Medicines Agency's update, companies can determine their own methods for redacting proposed commercially confidential information. However, the final redacted version of the clinical report must demonstrate conformity with the agency's requirements. This includes the requirement to ensure that the text is searchable by providing documents in PDF format. Only text that is not redacted must be retrievable in a search. Redacted text must be clearly provided. Redaction codes in line with agency requirements must be identifiable and form part of the document. The final redacted document may be submitted as a separate sequence denoting 'supplemental information' as part of a separate document in the electronic common technical document format to the agency. This must be separate from the sequence under which the proposed documents were submitted. A cover letter must be attached with the final redacted version of the clinical report which verifies that it contains the requisite documents for publication.

Companies will have the opportunity to engage in only one round of redaction consultation exchanges with the European Medicines Agency. Based on the outcome of the assessment on the proposed redacted information, companies will be expected to update the redacted document to reflect the proposals agreed by the agency.

Publication of final redacted reports

Publication of the final redacted version of the clinical report should occur within 60 calendar days of the issuance of a European Commission decision granting or refusing marketing authorisation. The timeframe for the publication of a final redacted report submitted as part of an extension of authorisation of a medicinal product for a therapeutic indication or line extension will be 60 calendar days following the outcome of the European Commission Decision. Where an application is withdrawn, publication of the final redacted report could be issued within 150 calendar days of the notification by the company to the agency. These timeframes take into account an interim relief period of 20 calendar days in cases where a disagreement arises with the agency.

Redaction of commercially confidential information

As a general principle, the European Medicines Agency will not disclose trade secrets or commercially confidential information. However, information contained in clinical reports will be viewed as commercially confidential information only in limited circumstances. The update outlines the conditions which must be satisfied by companies in order to justify the redaction of claimed commercially confidential information contained in:

  • clinical overviews;
  • clinical summaries; and
  • clinical study reports.

A justification table detailing the proposed commercially confidential information to be redacted must accompany the submission of every clinical report. The table must list all proposed redactions concerning purported commercially confidential information. This tool is also intended to facilitate communication with companies. Subsequently, the table will not be subject to publication. The following three categories of information will be excluded from the scope of commercially confidential information:

  • existing information available in the public domain (eg, clinical trial registries or a patent application);
  • information that does not contain innovative features and falls within the public knowledge (eg, scientific and regulatory guidelines and guidance documents); and
  • certain general or administrative information, quality-related information, non-clinical and clinical-related information.

The agency highlights that the required level of detail must be "specific, pertinent, relevant, not overstated and appropriate" to the proposed justification for redacting the information. The agency also mentions certain conditions that must be satisfied by companies which wish to protect commercially confidential information. The following information must be demonstrated:

  • clear identification of the proposed information to be redacted;
  • innovative features within the context of public knowledge;
  • information which constitutes part of an ongoing development programme; and
  • how the disclosure of the concerned information could undermine the economic interest or competitive position of the information owner.

The agency may request additional information if the proposed justification is not considered to be sufficiently supported. If the justification is ultimately rejected by the agency a specific justification code will be provided in the justification table.

Anonymisation of clinical reports

Anonymisation methodologies (eg, masking, randomisation and generalisation) could be deployed by companies in the anonymisation of personal data. Although the agency does not require that a specific technique be used for the purposes of the anonymisation of clinical reports it does recommend "randomisation and generalisation techniques… in order to optimise the clinical usefulness of the information published". However, companies must demonstrate that anonymisation is achieved and that:

  • singling out, linkability or inference after anonymisation is no longer possible; and
  • an analysis on the re-identification of risk can be conducted.

The agency also recommends steps that companies could follow in order to develop an anonymisation process – including:

  • determination of direct identifiers and quasi-identifiers in the dataset (ie, clinical reports);
  • identification of possible adversaries and plausible attacks on data;
  • data utility considerations;
  • determination of the risk of re-identification threshold;
  • evaluation of the actual risk of re-identification;
  • anonymisation methodology;
  • documentation of the anonymisation methodology and process.

A report detailing the steps to achieve anonymisation must accompany the submission of the anonymised clinical reports. This report must outline the company's approach to the anonymisation of personal data.

Companies that fail to comply with the disclosure policy could be subject to remedial action, which is yet to be fully determined by the European Medicines Agency.

For further information on this topic please contact Elisabethann Wright or Ciara Farrell at Hogan Lovells by telephone (+32 2 505 0911) or email (ea.wright@hoganlovells.com or ciara.farrell@hoganlovells.com). The Hogan Lovells website can be accessed at www.hoganlovells.com.

Endnotes

(1) See www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2015/06/event_detail_001163.jsp&mid=WC0b01ac058004d5c3.

(2) See www.ema.europa.eu/docs/en_GB/document_library/Other/2014/10/WC500174796.pdf.

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