Transparency andAccess to Informationin the US and Canada

Linda BowenHead of US Regulatory Policy & IntelligenceSanofi

26th AnnualEuroMeeting

25-27 March 2014ACV, Vienna

Austria

DisclaimerThe views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated.

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Disclaimer

The views expressed in this

presentation are the personal views

of the author and do not

necessarily represent the views of

Sanofi U.S., a Sanofi Company

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Agenda

• United States (FDA)– Transparency Initiative

– Freedom of Information

• Canada (Health Canada - HPFB)– Transparency Initiative

– Access to Information

• Comparison of US-Canada-EU

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FDA’s Transparency Initiative

• Background– In response to President’s Obama Open

Government Initiative (January 21, 2009).

– Government should be transparent, participatory and collaborative (see FOIA.gov).

• Objective– To render FDA much more transparent and open to

the American public by providing the public with useful, user-friendly information about agency activities and decision-making.

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Important to rememberwhat is already “publicly available”

• Approval Information– Advisory Committee Briefing Information (FDA)

– Approval Packages/SBoAs (Drugs@FDA) - redacted

– Device Clearances and Approvals (510ks and PMAs)

• Patent and Exclusivity Information for drugs (Orange Book)

• Company post marketing requirements and commitments

• Pediatric Information and PREA Non-Compliance letters

• Comments and citizen petitions (www.regulations.gov)

• Compliance Information– EIRs, 483s, untitled letters, warning letters, NOOH, NIDPOE,

debarments, CIIL (clinical investigator inspection list)

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What is NOT “publicly available”

• FDA generally does not disclose any information about the existence, status, or contents of an application submitted to the Agency, until the product has been approved, licensed, or cleared. Statutes and FDA regulations generally prohibit the release of information from or about an unapproved application. This includes:– INDs or IDEs

– INDs or IDEs on clinical hold

– Marketing applications and supplements (NDA, ANDA, BLA…)

– Refusal to file information

– Issuance of a complete response letter

– Unapproved drug or uncleared 510k that has been withdrawn

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FDA’s Transparency Initiative - 3 Phases

• Three Phases– Phase I - Improving the understanding of FDA

basics (completed but ongoing updates).

– Phase II - Improving FDA’s disclosure of information to the public (ongoing).

– Phase III - Improving FDA’s transparency to regulated industry (ongoing).

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Transparency Initiative - Phase I

• Phase I: FDA Basics - In January 2010, FDA launched a web-based resource called FDA Basics, which provides the public with basic information about FDA.

• Includes videos, Ask Us webinar series, how drugs are approved, Device Basics, and more.

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Transparency Initiative - Phase II

• Relates to FDA’s proactive disclosure of information the agency has in its possession, and how to make information about agency activities and decision-making more transparent, useful, and understandable to the public, while appropriately protecting confidential information.

• The task force released a report on May 19, 2010, which contained 21 draft proposals expanding the disclosure of information by FDA while maintaining confidentiality for trade secrets and individually identifiable patient information.

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Transparency Initiative - Phase II

• Topic areas for consultation:– Adverse Events (1)

– Docket Management Process (1)

– Enforcement Priorities and Actions (2)

– Import Procedures (1)

– Inspections (2)

– Product Applications (10)

– Recalls (3)

– Warning and Untitled Letters (1)

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Transparency Initiative Phase IICompleted Proposals

Progress Report 6 of the 21 completed

• Draft Proposal 4: FDA should post on its Web site all Agency Workplans that are older than five years, starting with FY 2001.

• Draft Proposal 5: Import Filer Evaluation Outcomes

• Draft Proposal 6: Inspections Database

• Draft Proposal 7: FDA should generate, and share with the public, information about the most common inspectional observations of objectionable conditions or practices that are made during inspections of FDA-regulated establishments and post that information online on a regular basis. Inspection Observations

• Draft Proposal 19: Addressing marketplace confusion (food)

• Draft Proposal 21: Expanded posting of warning and untitled letters

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Transparency Initiative - Phase III

• January 6, 2011, FDA released a report containing 19 action items and five draft proposals to improve transparency to regulated industry. The report groups the action items and draft proposals into five categories:

– Communicating Information About Agency Procedures

– Product Application Review Process

– Guidance Development

– Regulations Development

– Import Process

• FDA solicited public comment until March 6, 2011.

• There have been 10 completed action items.

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• Action Item 1: FDA Basic for Industry

• Action Item 3: Regulatory Process

• Action Item 5: Strategic Priorities

• Action Item 6: Meetings, Conferences, & Workshops

• Action Item 7: Product Application and Petition Review Process

• Action Item 8: FDA Basics for Industry

• Action Item 11: 12/2011 report

• Action Item 12: FDA Basics for Industry – Guidances

• Action Item 15: Import Program Managers

• Action Item 16: Import Alert

Completed Proposals 2/2014

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FDA Transparency Initiative: Compliance

• October 2011: FDA report on Proposals for Public Comment to Increase Transparency by Promoting Greater Access to the Agency’s Compliance and Enforcement Data

• 8 draft proposals to make FDA’s publicly available compliance and enforcement data more accessible and user-friendly

• January 2012 - FDA report . All 8 proposals adopted by the Agency

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Transparency Initiative - United States

What we’ve seen so far• FDA-TRACK (Transparency Results Accountability

Credibility Knowledge Sharing) is a new agency-wide program performance management system that monitors over 100 FDA program offices through key performance measures.

• FDA Transparency Blog

• FDASIA Track

• Unified Agenda Track

• FDA Basics for Industry

• Web portal compliance and enforcement actions.

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Open FDA

• FDA announced in February 2014 a new webpage and initiative called openFDA. FDA explained that openFDA will soon provide "API (application programming interfaces) and raw download access to a number of high-value structured datasets," including adverse events, recalls, and documentation like structured product labeling (SPL) data.

• Run by FDA's Office of Informatics and Technology Innovation (OITI), openFDA will offer easy access to FDA public data and highlight projects using these data in both the public and private sector to further regulatory or scientific missions, educate the public, and save lives.

• Beta access to the openFDA API will open in summer 2014 at earliest, with full public release expected by the end of 2014.

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Freedom of Information Act

• The Freedom of Information Act was enacted in 1966, with major amendments in 1996 – the “Electronic Freedom of Information Act Amendments” and then again in 2007 - Public Law 110-175 – “The Openness Promotes Effectiveness in our National Government Act of 2007”.

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FOIA Exemptions

• Of the nine exemptions, three (in red) most often form the basis for the withholding of information by FDA:

– (1) classified national defense and foreign relations information– (2) internal agency rules and practices– (3) information that’s prohibited from disclosure by another law– (4) trade secrets and other confidential business

information– (5) inter-agency or intra-agency communications that are

protected by legal privileges– (6) information involving matters of personal privacy– (7) certain information compiled for law enforcement

purposes– (8) information relating to the supervision of financial institutions– (9) geological information on wells.

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The Logbook

FDA monitors progressOf FOI Requests on theFDA-Track Freedom ofInformation Act Dashboard

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Report of the Auditor General ofCanada to the House of Commons

– On November 22, 2011, a report was published which represents the results of a performance audit conducted by the Office of the Auditor General of Canada under the authority of the Auditor General Act.

– Recommendations agreed to by Health Canada; development and implementation of these recommendations has already begun

• Regulating clinical trials (3)

• Reviewing drug submissions (4)

• Monitoring post-market studies (2)

• Enforcing compliance with the regulations (1)

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Report of the Auditor General ofCanada to the House of Commons

– An update presented in a March 2013 reportshowed that most recommendations were completed or would be complete by June 2014.

• Safety (CT inspection, ADRs for CT, Safety assessments)

• Timeliness (CT inspection, Review deadlines, prioritize complaints)

• Transparency (CT registration, review information, COI)

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Proactive Transparency• Drug Products Database

• Notice of Compliance (

Notice of Compliance with Conditions NOC/c

• Summary Basis of Decision for drugs and devices

• Licensed Natural Health Products Database

• Medical Device Active License Search

• Device Establishment Licenses Listing

Product Monographs

) list

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Proactive Transparency

Canada Vigilance Adverse Reaction Online Database

Recalls and Safety Alerts

Drug Establishment Licenses Listing

Cosmetic Ingredient Hotlist

Register of Innovative Drugs (exclusivity)

Patent Register

Clinical Trials Database

Consultations (Consulting with Canadians - HC)

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What is NOT “publicly available”

• Detailed organizational charts• Health Canada (TPD, BGTD, NHPD) does not disclose

information about the existence, status, or contents of an application submitted to the Agency, until the product has been approved.– Clinical Trial Applications (CTA)– New and Abbreviated Drug Submissions (NDS/ANDS), supplements– Notifiable Changes– Screening Deficiency Notice– Notice of Deficiency– Notice of Noncompliance– Clarification Requests (Clarifax)

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Access to Information RequestsCompletedATI Requests Completed - HC

Beginning 1/1/2012,

summaries posted within 30 calendar days after the end of

each month during which the

responses to requests were

issued

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ATI Requests Completed as of Jan. 2014

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Approvals - Nelarabine

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Approval in US, EU and Canada

Orphan Product DesignationNDA (NME)

Authorized under Accelerated ApprovalPriority Review

Submitted 29-April-2005Approved 28-Oct-2005

Orphan Product Designation 16-June-2005Centralized Procedure

Authorized under Exceptional CircumstancesProtocol Assistance 27-Jan-2006

Submitted 26-May-2006Approved 22-August-2007

Submitted 28-Sep-2005NON issued 22-Dec-2006

Response filed 08-Mar-2007NOC/C issued 22-Sep-2007

ND issued 23-Oct-2007SBD issued 12-May-2008

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Indication

ATRIANCE is indicated for the treatment of patients with T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.

ATRIANCE is indicated for the treatment of patients with T-cell acute lymphoblastic leukemia andT-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.

ARRANON is indicated for treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens

From the SPC

From the SBD From the Labeling

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Approval in US, EU and Canada:Post-approval commitments

The following post-approval marketing commitments are described in the Approval Letter and required under accelerated approval regulations, 21 CFR 314.510, •Submit the results of the proposed phase III trial (AALL0434) to be conducted by the Children’s Oncology Group to demonstrate Nelarabine’s clinical benefit. First patient enrolled: April 2006 End of safety phase: 4Q 2009 Complete accural: 4Q 2012 Complete 3-year follow-up: 4Q 2015. Availability of study report: 4Q 2016 A request for a Special Protocol Assessment should be submitted prior to initiation of the study.

•Data from the completed study AALL0434 (Phase III, Pediatric and Adult populations): Intensified Methotrexate, Nelarabine, and Augmented BFM Therapy for Children and Young Adults with Newly Diagnosed T-cell Acute Lymphoblastic Leukemia.• Data from the completed study PGAA107062 (Phase II, Pediatric and Adult populations): Phase II Study with Nelarabine for Patients with refractory or recurrent T-ALL or T-lymphoblastic lymphoma.• Data from a Post-Marketing Surveillance Study for Atriance™ in the indicated patient population under 21 years of age receiving the 650 mg/m2 dose of Nelarabine.

•The Applicant has committed to provide data from an on-going COG study AALL0434. Initialsafety data will be submitted when available (anticipated 2010), final data will be submittedwhen available (anticipated 2016).•The Applicant has committed to provide data from a Post-Marketing Surveillance Study forAtriance in the indicated patient population under 21 years of age receiving the 650mg/m2 doseof Nelarabine. The protocol will be submitted within 1 month after the Marketing Authorisationhas been granted. Annual reports will be submitted as part of annual reassessment of theMarketing Authorisation issued under exceptional circumstances. A study synopsis will besubmitted within 6 months of study completion (anticipated 2012).

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US: 534 page Arranon SBoA

• Approval Letter(s) – 5 pages• Printed Labeling – 20 pages • Medical Review(s) – 76 pages • Chemistry Review(s) – 13 pages • Pharmacology Review(s) – 105 pages • Statistical Review(s) – 37 pages • Microbiology Review(s) – 6 pages • Clinical Pharmacology Biopharmaceutics Review 84 pages • Administrative Document(s) & Correspondence 188 pages

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EU: 84 page Atriance EPAR

• In all 22 languages (at that time)

– Summary for the public – 3 pages

– All Authorised Presentations – 1 page

– SPC – 33 pages

• In English Only

– Scientific Discussion (6) – 44 pages

– Procedural steps before authorisation – 2 pages

– Steps taken after authorisation (8) - 1page

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Canada: 23 page Atriance Notice ofDecision/SBD

• Notice of Decision - 2 pages

• Notice of Compliance with conditions – 3 pgs

• Summary Basis of Decision - 21 pages

• Product Monograph (consumer information part 3) – 4 pages

• Is on the register of innovative drugs; NOC date 2007-09-22; 6 year no-file date 2013-09-22; data protection ends 2016-03-22

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SUMMARY

• Important to keep a balance between transparency of facts that may concern the public and the respect of patient privacy and commercially sensitive information.

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Questions?

Special thanks to Susanna Del-Signore for her feedback on the presentation

Linda.Bowen@Sanofi.com

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