Guidance for Industry: Reconsideration of Final Decisions Issued for Human Drug Submissions

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

Contact: Therapeutic Products Directorate
Biologics and Genetic Therapies Directorate

Published by authority of the Minister of Health

Date Adopted: 2005/11/30
Effective Date: 2006/03/01
Administrative Changes Date: 2006/12/11

Health Products and Food Branch

Our mission is to help the people of Canada maintain and improve their health.
Health Canada

HPFB's Mandate is to take an integrated approach to the management of the risks and benefits to health related to health products and food by:

• Minimizing health risk factors to Canadians while maximizing the safety provided by the regulatory system for health products and food; and,
• Promoting conditions that enable Canadians to make healthy choices and providing information so that they can make informed decisions about their health.

Health Products and Food Branch

© Minister of Public Works and Government Services Canada 2005

Available in Canada through
Health Canada - Publications
Brooke Claxton Building, A.L. #0913A
Tunney's Pasture
Ottawa, Ontario
K1A 0K9

Tel: (613) 954-5995
Fax: (613) 941-5366

Également disponible en français sous le titre : Révision des décisions finales sur les présentations de drogues pour usage humain

Foreword

Guidance documents are meant to provide assistance to industry and health care professionals on how to comply with the policies and governing statutes and regulations. They also serve to provide review and compliance guidance to staff, thereby ensuring that mandates are implemented in a fair, consistent and effective manner.

Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in approach. Alternate approaches to the principles and practices described in this document may be acceptable provided they are supported by adequate scientific justification. Alternate approaches should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As a corollary to the above, it is equally important to note that Health Canada reserves the right to request information or material, or define conditions not specifically described in this guidance, in order to allow the Department to adequately assess the safety, efficacy or quality of a therapeutic product. Health Canada is committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read in conjunction with the accompanying notice and the relevant sections of other applicable guidances.

Table of Contents

• 1. Policy Objectives
• 2. Scope and Application
• 3. Policy Statements
• 4. Roles and Responsibilities
• 5. Guidance for Implementation
  • 5.1 Filing of the Request for Reconsideration
    • 5.1.1 Letter of Intent
    • 5.1.2 Request for Reconsideration
  • 5.2 Format and Content of the Request for Reconsideration
    • 5.2.1 Relevance of Information Filed
  • 5.3 Review of the Request for Reconsideration
    • 5.3.1 Provision of External Advice
    • 5.3.2 Review by the Office
    • 5.3.3 Consultation by the Office
    • 5.3.4 Recommendation by the Office
  • 5.4 Decision by the Director General
  • 5.5 Follow-up Action by the Manager of RPMD/RAD
  • 5.6 Dissemination of the Reconsideration Decision: Internally
  • 5.7 Dissemination of the Reconsideration Decision: Externally
• 6. Effective Date
• Appendix 1: Reconsideration Process Map
• Appendix 2: Performance Targets: Reconsideration Process
• Appendix 3: Summary Basis of Reconsideration Decision Template

1. Policy Objectives

To ensure that drug submission-related disputes that arise are resolved effectively, efficiently, and in accordance with the Health Products and Food Branch (HPFB) Guiding Principles on Dispute Resolution (available on the Health Canada website).

2. Scope and Application

This document applies to disputes arising between Health Canada and sponsors over final decisions (excluding those related to cost recovery) issued for one of the following drug submission types:

• New Drug Submission (NDS);
• Supplemental New Drug Submission (S/NDS);
• Abbreviated New Drug Submission (ANDS);
• Supplemental Abbreviated New Drug Submission (S/ANDS);
• Notifiable Change (NC);
• Clinical Trial Applications (CTA) and Amendments (CTA-A);
• Applications for Drug Identification Number (DINA) (includes DINBs);
• Blood Establishment Licence Application Submissions (Lic. Applic.); or
• Blood Establishment Licence Amendment Submissions (Lic. Amend.).

This guidance document applies to all sponsors of human drug submissions, and to all Therapeutic Products Directorate (TPD) and Biologics and Genetic Therapies Directorate (BGTD) staff involved in the drug submission process.

This document supercedes the Health Canada policy: Appeals Procedures for Drug Submissions, which came into effect April 4, 2003.

3. Policy Statements

The Reconsideration process is a formal dispute resolution process and is intended to be initiated when informal mechanisms have failed to resolve the issue(s). Refer to Appendix 1 for a map of the Reconsideration process.

Appendix 2 outlines performance targets for each step of the process, for various submission and decision types. The Directorates will make every effort to expedite those processes and steps that are within their control; in addition, the sponsor may request that an expedited process be followed as outlined in Section 5.3.1(c).

If, at any time during the Reconsideration process, the sponsor files a Notice of Application to the Federal Court to resolve the matter, the Directorate will terminate the Reconsideration process.

Following the issuance of a final decision (Section 5.1), sponsors may file a Request for Reconsideration. A Letter of Intent must be filed within 30 calendar days of the date of the final decision under dispute, clearly stating the sponsor's intention to commence the Reconsideration process (Section 5.1.1).

Within 45 calendar days of the date of the acknowledgement of the Letter of Intent, the sponsor must submit a Request for Reconsideration to the Director General of the appropriate Directorate (Section 5.1.2). The Request for Reconsideration should be a brief, high-level summary of the issue(s) in dispute, and should not introduce new issues (Section 5.2).

The information filed will be assessed for relevance to the issue(s) under dispute. The Reconsideration process is not an opportunity to add to the content of the original submission, or to circumvent established processes for refiling submissions. As such, new studies will not be accepted as part of the Request for Reconsideration (Section 5.2.1).

The sponsor and the review bureau/centre will have the opportunity to present their positions on the issues under dispute to the Director General, who will make the Reconsideration decision. To assist with the resolution of a Request for Reconsideration, the Directorate may refer one or more issues under dispute to an external panel for advice (either an existing Scientific Advisory Committee or a Reconsideration Panel). Other issues may not be appropriate for referral to an external panel and may be reviewed internally (Section 5.3).

The Reconsideration decision will be issued by the Director General. For each issue under dispute, the Director General may uphold or amend his/her original position, or refer the issue back to the review bureau/centre for re-evaluation and preparation of a new decision letter reflecting the re-evaluation of the issue under dispute (Section 5.4).

Reconsideration decisions will be disseminated externally via a Summary Basis of Reconsideration decision to be posted on the Health Canada web site. The document will be a factual document summarizing the Directorate's position on a particular issue, and will not contain proprietary or identifying information about the drug or the sponsor (Section 5.7).

4. Roles and Responsibilities

The following bullets outline the major responsibilities of each partner in the formal Reconsideration process.

Director General

The Director General of TPD or BGTD or his/her designate is responsible for:

• refusing Reconsiderations filed for decisions that are not eligible;
• deciding whether to consider information filed in the Request for Reconsideration;
• deciding on the process for the disposition of the Request for Reconsideration;
• deciding on the use and membership of the Scientific Advisory Committee or Reconsideration Panel (if applicable); and
• making the Reconsideration decision.

Drug Submission Sponsor

The drug submission sponsor is responsible for:

• filing a Letter of Intent (two copies) and a Request for Reconsideration (two copies) for eligible (final) decisions;
• ensuring the Request for Reconsideration package is complete;
• providing nomination(s) for one member of a Reconsideration Panel if formed;
• working with the Office of Science (Policy Bureau, TPD) or the Office of Quality and Risk Management (BGTD) to draft questions to be posed to the external panel (Scientific Advisory Committee or Reconsideration Panel) (if applicable); and
• making a presentation to the Director General, the Office of Science or the Office of Quality and Risk Management, and the Scientific Advisory Committee or Reconsideration Panel (if applicable).

Office of Science / Office of Quality and Risk Management

The Office of Science (Policy Bureau, TPD) and the Office of Quality and Risk Management (BGTD) are responsible for:

• responding to inquiries regarding the Reconsideration process;
• responding to extension requests related to the Reconsideration process;
• assessing the relevance of information filed in the Request for Reconsideration, with the input of the Regulatory Project Management Division (TPD) or the Regulatory Affairs Divisions (Biotherapeutics and Quality, or Blood, Tissue, Organ and Vaccines, BGTD) and the review bureau/centre as needed;
• reviewing information provided by the sponsor and the review bureau/centre related to the Reconsideration process;
• recommending to the Director General a process for the disposition of the Request for Reconsideration;
• making recommendations to the Director General regarding the membership of the Scientific Advisory Committee or Reconsideration Panel (if applicable);
• coordinating the Scientific Advisory Committee or Reconsideration Panel and managing its operations (if applicable);
• consulting with other areas of expertise as needed, and communicating any new considerations to all involved parties;
• preparing an Issue Analysis Summary with recommendations on the disposition of the Request for Reconsideration;
• identifying potential policy/guidance issues and referring them to the Director of the Policy Bureau (TPD) or the Centre for Policy and Regulatory Affairs (BGTD);
• identifying potential missed opportunities for dispute prevention and early resolution;
• disseminating Reconsideration decisions internally in TPD/BGTD;
• preparing a Summary Basis of Reconsideration Decision for each Reconsideration decision and arranging for its translation and posting on the Health Canada web site; and
• forwarding all documents generated during the Reconsideration process to the Regulatory Project Management Division (TPD) or the Regulatory Affairs Divisions (Biotherapeutics and Quality or Blood, Tissue, Organ and Vaccines, BGTD) for filing.

Regulatory Project Management Division / Regulatory Affairs Divisions

The Regulatory Project Management Division (TPD) and the Regulatory Affairs Divisions (Biotherapeutics and Quality or Blood, Tissue, Organ and Vaccines, BGTD) are responsible for:

• responding to inquiries regarding the Reconsideration process;
• determining whether decisions are eligible for Reconsideration when a Letter of Intent is filed;
• acknowledging receipt of the Letter of Intent if the decision is eligible for Reconsideration;
• assisting the Office of Science (Policy Bureau, TPD) or the Office of Quality and Risk Management (BGTD) with the assessment of the relevance of information filed in the Request for Reconsideration;
• ensuring follow-up actions are taken on each submission after the Reconsideration decision has been made;
• ensuring documents generated during the Reconsideration process are appropriately filed, and tracking is complete; and
• ensuring Reconsideration decisions, and recommendations for dispute prevention and early resolution are incorporated into the process for future submissions.

Review Bureau/Centre Directors

The Directors of the review bureaux (TPD) or centres (BGTD) are responsible for:

• ensuring that review reports and decision letters accurately and completely reflect the bureau/centre's position on the submission;
• assisting the Office of Science (Policy Bureau, TPD) or the Office of Quality and Risk Management (BGTD) with the assessment of the relevance of information filed in the Request for Reconsideration;
• providing nomination(s) for one member of a Reconsideration Panel if formed;
• working with the Office of Science or the Office of Quality and Risk Management to draft questions to be posed to the external panel (Scientific Advisory Committee or Reconsideration Panel) (if applicable);
• ensuring a presentation is made to the Director General, the Office of Science or the Office of Quality and Risk Management, and the Scientific Advisory Committee or Reconsideration Panel (if applicable);
• ensuring follow-up actions are taken on each submission after the Reconsideration decision has been made; and
• ensuring Reconsideration decisions, and recommendations for dispute prevention and early resolution are incorporated into the process for future submissions.

Scientific Advisory Committee / Reconsideration Panel

The Scientific Advisory Committee or Reconsideration Panel is responsible for:

• making recommendations in answer to specific questions concerning the issue(s) under dispute;
• identifying potential policy/guidance issues to be referred to the Policy Bureau (TPD) or the Centre for Policy and Regulatory Affairs (BGTD); and
• identifying potential missed opportunities for dispute prevention and early resolution.

Submission and Information Policy Division

The Submission and Information Policy Division, TPD is responsible for the following (for both TPD and BGTD):

• receiving Letters of Intent and Requests for Reconsideration;
• forwarding the Letter of Intent and the Request for Reconsideration to the appropriate areas; and
• acknowledging receipt of Requests for Reconsideration filed.

5. Guidance for Implementation

The Reconsideration process is a formal dispute resolution process and is intended to be initiated when informal mechanisms have failed to resolve the issue(s).

If, at any time during the Reconsideration process, the sponsor files a Notice of Application to the Federal Court to resolve the matter, the Directorate will terminate the Reconsideration.

Refer to Appendix 1 for a map of the Reconsideration process.

Appendix 2 outlines performance targets for each step of the process, for various submission and decision types. The Directorates will make every effort to expedite those processes and steps that are within their control; in addition, the sponsor may request that an expedited process be followed as outlined in Section 5.3.1(c).

5.1 Filing of the Request for Reconsideration

Sponsors may file a Request for Reconsideration following the issuance of one of the following final decisions:

• Rejection of Priority Review Request under the Priority Review Policy;
• Rejection of Request for Advance Consideration under the Notice of Compliance with Conditions Policy;
• Screening Rejection Letter (SRL) (including New Drug Letter);
• Notice of Deficiency - Withdrawal Letter (NOD/W);
• Notice of Non-compliance - Withdrawal Letter (NON/W);
• Not Satisfactory Notice (NSN);
• Unacceptable Licence Application Letter;
• Unacceptable Licence Amendment Letter; and
• Rejection of Accelerated Licence Amendment Submission.

As per the Health Canada Policy Priority Review of Drug Submissions, sponsors may file a second Request for Priority Review status in the event the first is rejected (refer to the Priority Review of Drug Submissions Policy and Guidance Document for more information). The rejection of either the first or second Rejection of Priority Review Request is eligible for a Request for Reconsideration. However, sponsors may only file a Request for Reconsideration of the first rejection or file a second Request for Priority Review status - they may not file both.

As per the Health Canada Policy Notice of Compliance with Conditions, sponsors may file a second Request for Advance Consideration in the event the first is rejected (refer to the Notice of Compliance with Conditions Policy and Guidance Document for more information). The rejection of either the first or second Rejection of Advance Consideration is eligible for a Request for Reconsideration. However, sponsors may only file a Request for Reconsideration of the first rejection or file a second Request for Advance Consideration - they may not file both.

5.1.1 Letter of Intent

Within 30 calendar days of the date of the final decision under dispute, the sponsor must submit a Letter of Intent to the Director General of the appropriate Directorate. The Letter of Intent should clearly state the sponsor's intention to commence the formal Reconsideration process. Two copies of the Letter of Intent should be filed.

For both TPD and BGTD submissions, the Letter of Intent should be sent to the attention of the Submission and Information Policy Division (SIPD) at the address below. Note that sending the document to a location other than SIPD may result in delays.

Submission and Information Policy Division
Therapeutic Products Directorate
Finance Building, A.L. # 0201A1
101 Tunney's Pasture Driveway
OTTAWA, Ontario
K1A 0K9
Fax: (613) 941-0825

SIPD will forward the Letter of Intent to the Manager of the Regulatory Project Management Division (RPMD, TPD) or the Regulatory Affairs Division (Biotherapeutics and Quality, or Blood, Tissue, Organ and Vaccines, RAD, BGTD) as appropriate.

The Manager of RPMD/RAD or his/her designate (hereafter referred to as "the Manager of RPMD/RAD") will review the Letter of Intent to determine whether the decision under dispute is one for which a Request for Reconsideration can be filed (i.e. whether the decision is one listed in Section 5.1).

If the decision for which the Letter of Intent was filed is eligible for Reconsideration, the Manager of RPMD/RAD will acknowledge receipt of the Letter of Intent and indicate that the decision is eligible for Reconsideration. The Manager of RPMD/RAD will forward the Letter of Intent to the Office of Science (Policy Bureau, TPD) or the Office of Quality and Risk Management (BGTD) (hereafter referred to as "the Office").

If the decision for which the Letter of Intent was filed is not eligible for Reconsideration, the Manager of RPMD/RAD will ensure the sponsor is contacted and the Reconsideration process and the mechanisms available for dispute resolution are explained. The Reconsideration will be refused by the Director General or his/her designate (hereafter referred to as "the Director General").

5.1.2 Request for Reconsideration

The sponsor must submit a formal Request for Reconsideration addressed to the Director General of the appropriate Directorate within 45 calendar days of the date of the acknowledgement letter sent by the Manager of RPMD/RAD. Two copies of the Reconsideration package should be filed.

For both TPD and BGTD submissions, the Request should be sent to the attention of SIPD at the address given in Section 5.1.1. Note that sending the document to a location other than SIPD may result in delays.

SIPD will acknowledge receipt of the Request and will forward it to the Office and the Manager of RPMD/RAD.

The Office may grant requests for extension of the time allowed to file the Request for Reconsideration. Extension requests should be filed in writing to SIPD at the address given in Section 5.1.1, and should include a rationale for the request. The rationale will be evaluated and a decision will be made by the Office on a case-by-case basis.

5.2 Format and Content of the Request for Reconsideration

The Request for Reconsideration is expected to be filed in the prescribed format (see template posted on the Health Canada website) and contain the following information:

• a copy of the decision for which Reconsideration is requested;
• statements, in numbered paragraphs, with the sponsor's definition of the issue(s) of contention, linking closely with the points of the original decision;
• for each issue identified, the grounds of the dispute in numbered paragraphs;
• the sponsor's preferred process for resolution of the Request for Reconsideration (i.e. referral of one or more issues to an existing Scientific Advisory Committee or to a newly created Reconsideration Panel, review of one or more issues by the Office, or a combination of the two);
• the name of one or more nominees for a Reconsideration Panel (see below for more information); and
• whether the sponsor wishes to follow an expedited process for obtaining external advice, as outlined in Section 5.3.1(c).

Two copies of the Reconsideration package should be filed. If the Reconsideration package is not complete, the Office will contact the sponsor to request additional information.

The grounds should be cross-referenced to the information filed in the original submission (and/or the response to a Screening Deficiency Notice, NOD, or NON if applicable). The Request for Reconsideration should be a brief, high-level summary of the issue(s) in dispute, and should not introduce new issues. The issues and the grounds should not exceed a total of 20 pages (not including supporting references).

The sponsor is requested to provide nomination(s) for one member of the Reconsideration Panel with expertise relevant to the resolution of the matter. To ensure that nominees can comply with conflict of interest requirements the sponsor should not contact the nominee(s), and should not provide them with any material for review prior to the official appointment of the member by the Director General. The nominees should not have been involved with the sponsor for the product in question and should not have expressed their views regarding the product in question. Refer to section 5.3.1 for more information.

The decision letter and supporting review documents will provide the review bureau/centre's definition of the issue(s) and grounds. Together, the documents from the sponsor and the review bureau/centre will form the basis for deliberations by the Office, an external panel if consulted, and the Director General.

5.2.1 Relevance of Information Filed

The Office, with the input of the Manager of RPMD/RAD and the review bureau/centre as needed, will assess all information filed in support of the Request for Reconsideration to determine whether it is relevant to the issue(s) under dispute. The Director General may refuse information filed on the recommendation of the Office.

The Reconsideration process is not an opportunity to add to the content of the original submission, or to circumvent the process for refiling submissions as outlined in the Management of Drug Submissions Guidance (MDSG) or the Management of Blood Establishment Submissions Guidance (MBESG). As such, new studies will not be accepted as part of the Request for Reconsideration.

The decision to refuse information will be communicated in writing by the Director General in the letter issued to the sponsor in Section 5.3.

If information was filed and refused by the Director General, the sponsor may submit this information as part of a refiled submission in accordance with Section 5.6 of the MDSG or Section 6 of the MBESG. The Manager of RPMD/RAD will ensure the sponsor is contacted to determine whether it wishes the information to be considered in accordance with the MDSG or MBESG. If so, the sponsor will be asked to submit the information as part of a refiled submission, with a new control number and new fees (not applicable to blood establishment submissions). The sponsor will be asked to inform RPMD/RAD in writing whether it wishes the Request for Reconsideration to continue without the new information, or to withdraw the Request and await a final decision on the new submission.

Sponsors are discouraged from pursuing both a Reconsideration and a refiled submission on the same issue, due to the limited resources of TPD/BGTD. The two will not proceed simultaneously; the sponsor will be contacted by RPMD/RAD to choose which one should proceed first. The other will continue once the first has been completed.

5.3 Review of the Request for Reconsideration

The Office will review the material presented and will recommend a process to be followed for the disposition of the Request. Options include the referral of issues under dispute to an external panel (an existing Scientific Advisory Committee as described in 5.3.1 or a Reconsideration Panel as described in 5.3.1(b)), the review of issues by the Office, or a combination of the two. Some issues identified in the Request for Reconsideration may be referred to an external panel, while others within the same Request may be addressed by the Office.

Issues that may be appropriate for referral to an external panel include:

• interpretation of available data;
• disagreement in applied methodology; and
• relative weights given to data impacting on the risk/benefit assessment of the submission information.

Issues that generally are not appropriate for referral to an external panel may include those that involve:

• submission of false information;
• allegations of bias;
• matters in which regulatory policy/guidance or procedures are the dominant concern; and
• an issue on which the Directorate has available recent external independent expert opinion.

The Office will make a recommendation to the Director General on the appropriateness of seeking external advice on one or more issues; the Director General will make a decision and will inform the sponsor. The letter to the sponsor will contain the proposed process for disposition of the Request, including details about the process and rationale for seeking external advice if applicable. If any information filed within the Request is refused as described in Section 5.2.1, this will also be outlined in the letter.

5.3.1 Provision of External Advice

If the Director General decides it is appropriate to seek external advice, the issues will normally be referred to an existing Scientific Advisory Committee (SAC) with expertise relevant to the issue. The Office may choose to convene a sub-set of SAC members with relevant expertise to deal with the issues, or the SAC may be supplemented by ad hoc members if additional expertise is required. In both situations, the sponsor will have the opportunity to participate in choosing the panel members. If a relevant SAC does not exist, a Reconsideration Panel will be formed (see Section 5.3.1(b)). The Office is responsible for coordinating the SAC or Reconsideration Panel and managing its operations.

(a) Scientific Advisory Committee Meeting

Consistent with its advisory role, the SAC will not be asked to make a decision on the submission; rather, advice will be solicited through one or more direct questions related to the specific outstanding issue(s) identified. The Office will work with the sponsor and the review bureau/centre to draft specific questions to be posed to the SAC.

The Office will ensure background material is provided to the SAC with enough time for review and consideration.

Formal presentations should be made to the SAC by both the sponsor and the review bureau/centre representative. The Office will set the agenda and allot an appropriate time for each speaker. Each presentation should consist of a brief overview of the salient points of the issue(s) under dispute, and will be followed by a question and answer period. The Director General will be present for both parties' presentations so that both have an opportunity to be heard by the person who will make the Reconsideration decision. In addition, both parties will be present during both presentations and the question and answer periods that follow. The Director General will then leave the SAC to its independent deliberations and discussions of the specific questions to be considered by the SAC on the issues identified.

The Chair of the SAC, will submit a report capturing each question, the discussion, and the agreed-upon response. This final version will become the official record of the meeting.

Costs associated with the SAC meeting will be paid by the Directorate in accordance with Treasury Board guidelines.

(b) Reconsideration Panel

As outlined above, if there is no SAC with expertise relevant to the issue, a Reconsideration Panel will be formed. The membership of the Reconsideration Panel will be determined by the sponsor and by the Directorate as follows:

• one member selected by the Director General from nominations by the sponsor;
• one member selected by the Director General from nominations by the relevant Bureau/Centre Director; and
• one member appointed by the Director General, who, when possible, is a member of an existing SAC and who will chair the Reconsideration Panel.

As stated in Section 5.2, the sponsor is requested to provide nomination(s) for one member of the Reconsideration Panel with expertise relevant to the resolution of the matter, as an attachment to the Request for Reconsideration. To ensure that nominees can comply with conflict of interest requirements the sponsor should not contact nominees, and should not provide them with any material for review prior to the official appointment of the member by the Director General. The nominees should not have been involved with the sponsor for the product in question and should not have expressed their views regarding the product in question.

Generally, the sponsor's nominee will be accepted by the Director General, unless he/she has an identified conflict. In this situation, the sponsor will be notified by the Office and asked to provide another nominee.

The Office will solicit nominations for one member of the Reconsideration Panel from the review bureau/centre Director. The Office will review the membership of existing Scientific Advisory Committees and will make a recommendation to the Director General for the chair of the Reconsideration Panel.

The Office will contact nominees for their curriculum vitae. Members will be chosen based on their experience, expertise, and/or analytical skills relevant to the review of a particular disputed issue. All Panel members must meet conflict of interest and security clearance requirements. Any person who was involved with decisions related to the submission, or reviewed information related to the submission on behalf of the Directorate or sponsor will not be eligible as a member of the Reconsideration Panel. Detailed information on security and conflict of interest requirements is available from the Office.

The Office will contact nominees provided by the sponsor and the review bureau/centre and determine whether they are interested and available to participate in the Panel. The Office will then make a recommendation to the Director General on the membership of the Panel.

Costs associated with the Panel meeting will be paid by the Directorate in accordance with Treasury Board guidelines.

The roles and responsibilities of the Panel, and the process for obtaining its advice will be the same as for the SAC outlined in Section 5.3.1(a). Consistent with its advisory role, the Panel will not be asked to make a decision on the submission; rather, advice will be solicited through one or more direct questions related to the specific outstanding issue(s) identified.

(c) Expedited Process for External Advice

If the sponsor wishes to expedite the process for external advice, it may be possible to conduct the SAC or Reconsideration Panel meeting by telephone or video conferencing. The sponsor should indicate in the Request for Reconsideration package whether it wishes to pursue an expedited process if possible. Although this option is available for all decisions, particular efforts will be made to expedite the process when the Request for Reconsideration relates to one of the following decisions:

• Rejection of a Priority Review Request under the Priority Review Policy;
• Rejection of a Request for Advance Consideration under the Notice of Compliance with Conditions Policy;
• Screening Rejection Letter, Notice of Deficiency - Withdrawal Letter, or Notice of Non-compliance - Withdrawal Letter for a priority submission;
• Not Satisfactory Notice for a CTA or CTA-A;
• Not Satisfactory Notice for a Notifiable Change; or
• Unacceptable Licence Application or Amendment Letter for an accelerated submission.

A meeting held by telephone or video conferencing will follow the same format as described in Section 5.3.1(a), with presentations by the sponsor and review bureau/centre.

Options to expedite the process will be presented to the sponsor in the letter from the Director General described in Section 5.3.

5.3.2 Review by the Office

As described above, some issues within a Request for Reconsideration may not be appropriate for referral to an external panel, and instead will be reviewed by the Office. In the letter issued in Section 5.3, the Director General will extend an invitation to the sponsor to meet to discuss these issues. At this meeting, both the sponsor and the review bureau/centre representatives will present their positions on the remaining issue(s) to the Director General and the Office. The formal presentations will be followed by a question and answer period. The purpose of the meeting will be to provide both parties with an opportunity to be heard by the person who will make the Reconsideration decision. It is intended to be non-confrontational, but will allow for a full discussion of the issue(s).

Where one or more issues will be referred to an external panel while others in the same Request will be reviewed by the Office, the meeting with the Director General will be held on the same day as the meeting of the external panel (SAC or Reconsideration Panel) if possible.

5.3.3 Consultation by the Office

The Office may consult with areas of expertise within Health Canada as needed throughout its review. For example, the Office may discuss regulatory or guidance issues with the Director of the Policy Bureau (TPD) or Centre for Policy and Regulatory Affairs (BGTD), the Manager of RPMD/RAD, or Health Canada Legal Services.

If new considerations (for example, new safety information) are raised during this consultation, or at any point during the Reconsideration process, they will be communicated to all involved parties (i.e. sponsor, review bureau/centre, SAC or Reconsideration Panel, etc.).

5.3.4 Recommendation by the Office

The Office will prepare an Issue Analysis Summary (IAS) containing the issues, analysis, and recommendations on the disposition of the Request. The IAS will include a summary of the process, information considered in the analysis, and detailed recommendations for follow-up actions to be taken.

The Office has several options for the disposition of Requests for Reconsideration. For each issue under dispute, the Office can recommend that, upon Reconsideration, the Director General choose one of three options:

• to uphold his/her original position on the issue;
• to amend his/her original position on the issue and ask that an amended version of the original decision letter be issued; or
• in exceptional circumstances, to refer the submission back to the review bureau/centre for re-evaluation of the issue under dispute and request that a new decision letter be prepared reflecting the re-evaluation of the issue under dispute. The new decision letter would then be eligible for Reconsideration, for that issue only. This would normally be recommended only in exceptional cases where the process was not appropriately applied and/or pertinent information was not appropriately considered.

In addition to its recommendation on the disposition of the Request, the SAC or Reconsideration Panel, and/or the Office can refer issues to the Director of the Policy Bureau (TPD) or CPRA (BGTD) for consideration for future guidance development, or recommend that an existing guidance document be revised.

During the course of its review, the SAC or Reconsideration Panel, and/or the Office may determine that the dispute could have been prevented at an earlier stage; that is, that there were missed opportunities for dispute prevention and/or earlier resolution. The SAC or Reconsideration Panel, and/or the Office can make suggestions as to how a similar dispute should be prevented or resolved at an earlier stage in the future. These recommendations will be referred to the Manager of RPMD/RAD and the review bureau/centre Director(s) for incorporation into the process for future submissions.

5.4 Decision by the Director General

The Office will forward its recommendation(s) to the Director General for decision. The Director General will make a final Reconsideration decision and will inform the sponsor; copies of the Reconsideration decision will be sent to the Office, the review bureau/centre Director and the Manager of RPMD/RAD for follow-up. Issues may also be forwarded to the Director of the Policy Bureau (TPD) or CPRA (BGTD) for consideration for future guidance development or with a recommendation to revise an existing guidance document.

5.5 Follow-up action by the Manager of RPMD/RAD

Once the decision is issued and communicated to the Manager of RPMD/RAD and the review bureau/centre Director(s), it is their responsibility to ensure appropriate follow-up actions are taken.

Specific follow-up actions related to the submission will depend on the nature of the Reconsideration decision. If the Directorate's position on one or more issues under dispute is amended, then an amended decision letter will be prepared for the Director General's signature.

If the Reconsideration decision was to refer the submission back to the review bureau/centre for re-evaluation, the Manager and review bureau/centre Director(s) are responsible for ensuring that the appropriate process is followed, and/or the appropriate information is considered in the re-evaluation. In this situation, the submission will be placed in the queue based on its original target date (this will place the submission near or at the front of the queue). As the original target will likely have passed, the Manager will ensure a new target date is set and communicated to the sponsor. The new target will be set on a case-by-case basis, depending on such factors as the number of issues involved, the quantity of data to be reviewed, the complexity of the issues and the data, etc.

After each Reconsideration Decision is made, the Office will forward all documents generated during the Reconsideration process to RPMD/RAD. The Manager of RPMD/RAD will ensure that the documents generated during the review of the Request for Reconsideration are appropriately filed and tracking is complete. The Manager and review bureau/centre Director(s) should ensure that the decision is integrated into the drug submission process and decision making framework, and therefore sets a precedent for future decisions as appropriate.

The Manager and review bureau/centre Director(s) are also responsible for ensuring that any recommendations made by the SAC or Reconsideration Panel, and/or the Office, concerning dispute prevention or early resolution are appropriately communicated within RPMD/RAD and the review bureaux/centres, and are integrated into the submission process.

5.6 Dissemination of the Reconsideration Decision: Internally

The Office will inform all staff of the relevant review bureaux/centres and RPMD/RAD of the Reconsideration Decision, directing them to the decision letter and accompanying IAS.

5.7 Dissemination of the Reconsideration Decision: Externally

The Office will prepare a summary of the IAS, which will include a description of the issue, the information considered, and the decision, for each issue under dispute. The document will not contain proprietary or identifying information about the drug or the sponsor; rather, it will be a factual document summarizing the Directorate's position on a particular issue. This Summary Basis of Reconsideration Decision will be sent to the sponsor for review prior to publication. The sponsor will be asked to identify issues that are considered to be commercially confidential and to provide supporting rationale, within 21 calendar days. The SBRD will be posted on the Health Canada web site.

A template for the SBRD is attached as Appendix 3.

6. Effective Date

This guidance document is effective as of March 1, 2006.

Appendix 1: Reconsideration Process Map

Legend

Abbreviations

BGTD: Biologics and Genetic Therapies Directorate
CPRA: Centre for Policy and Regulatory Affairs (BGTD)
DG: Director General
DSTS: Drug Submission Tracking System
IAS: Issue Analysis Summary
NOD/W: Notice of Deficiency - Withdrawal
NON/W: Notice of Non-compliance - Withdrawal
Office: Office of Science (TPD) or Office of Quality and Risk Management (BGTD)
PB: Policy Bureau (TPD)
RPMD: Regulatory Project Management Division (TPD)
RR: Request for Reconsideration
SIPD: Submission and Information Policy Division
RAD: Regulatory Affairs Division (Biotherapeutics and Quality, or Blood, Tissue, Organ and Vaccines, BGTD)
SRL: Screening Rejection Letter
TPD: Therapeutic Products Directorate
Unacc. Lic. App./Am. Letter: Unacceptable Licence Application or Amendment Letter

Appendix 2: Performance Targets: Reconsideration Process

Section	Step in Reconsideration Process	Output of Step	Performance targets (calendar days)
			SRL, NOD/W, NON/W, Unacc. Lic. App./ Am. Letter (non-priority/accelerated submission)	All other submission and decision types 1
5.1.1	Sponsor files Letter of Intent.	Letter of Intent filed to SIPD. Letter of Intent forwarded to RPMD/RAD.	30 (from date of original decision)
	RPMD/RAD determines eligibility of decision for reconsideration.	If decision is eligible: acknowledgement letter issued. Letter of Intent forwarded to Office. If decision is not eligible: sponsor contacted, Request for Reconsideration refused.	5 (from date of receipt in RPMD/RAD)
5.1.2	Sponsor files Request for Reconsideration.	Request for Reconsideration filed to SIPD.	45 (from date of acknowledgement letter)
	SIPD acknowledges and processes Request for Reconsideration.	Acknowledgement letter issued; Request for Reconsideration forwarded to Office, RPMD/RAD.	5 (from date of receipt in SIPD)
5.2.1	Office, RPMD/RAD (with review bureau/centre as needed) assess information filed for relevance.	If information is not relevant: information refused; Request for Reconsideration may continue; Refile submission may be submitted. If information is relevant: Request for Reconsideration continues.	15 (from date of receipt in Office)	10 (from date of receipt in Office)
5.3	Office reviews information and sends memo to DG with recommendation re: appropriateness of seeking external advice.	Issues clearly defined; initial analysis of positions conducted; memo written to DG with proposed process for disposition of the Request for Reconsideration.
	DG makes decision re: relevance of information filed, appropriateness of seeking external advice.	Letter to sponsor issued.	5 (from date of receipt in Director General's office)
5.3.1	Review by external panel: Office creates Reconsideration Panel (if applicable), holds SAC/ Reconsideration Panel meeting.	If Reconsideration Panel is formed: chair and members chosen; contracts drafted and signed; and conflict of interest & security clearance requirements met. Questions for SAC/Reconsideration Panel drafted; meeting held; presentations made; questions answered.	If Reconsideration Panel is formed: 60 2 (from date of letter to sponsor (5.3)) If issues are referred to existing SAC: 30 2 (from date of letter to sponsor (5.3))	If Reconsideration Panel is formed: 602 (from date of letter to sponsor (5.3)) If issues are referred to existing SAC, or sponsor chooses to hold meeting by teleconference: 302 (from date of letter to sponsor (5.3))
	Chair of SAC/Reconsideration Panel submits report.	Report submitted to Office.	7 (from date of panel meeting)
5.3.2	Review by the Office: Office holds meeting with DG, sponsor, review bureau/centre.	Meeting held; presentations made.	30 (from date of letter to sponsor (5.3))	If sponsor chooses to meet by teleconference: 15 (from date of letter to sponsor (5.3))
5.3.3 5.3.4	Office analyses issues, consults as necessary, drafts IAS.	IAS drafted, including Recommendation(s).	21 (from the later of date of finalization of report (5.3.1) or of meeting (5.3.2))	10 (from the later of date of finalization of report (5.3.1) or of meeting (5.3.2))
5.4	DG makes Reconsideration decision	Decision letter issued to sponsor.	5 (from date of receipt in Director General's office)

¹ SRL, NOD/W, NON/W (priority submission); NSN for NC, CTA or CTA-A; Rejection of Request for Priority Review Status; Rejection of Request for Advance Consideration under the Notice of Compliance with Conditions Policy; Unacceptable Licence Application or Amendment Letter (accelerated submission).

² Every effort will be made to meet this target; however, unforseen delays can occur as a result of conflict of interest and security clearance requirements, and the need to accommodate schedules of external experts.

Appendix 3: Summary Basis of Reconsideration Decision Template

Summary Basis of Reconsideration Decision (SBRD): <Brief description of issue under dispute, e.g. "Applicability of Health Canada Policy Bioequivalence of Proportional Formulations - Solid Oral Dosage Forms">

Date Issued: yyyy/mm/dd

Health Products and Food Branch

Our mission is to help the people of Canada maintain and improve their health.
Health Canada

HPFB's Mandate is to take an integrated approach to the management of the risks and benefits to health related to health products and food by:

• Minimizing health risk factors to Canadians while maximizing the safety provided by the regulatory system for health products and food; and,
• Promoting conditions that enable Canadians to make healthy choices and providing information so that they can make informed decisions about their health.

Health Products and Food Branch

Également disponible en français sous le titre : Sommaire des motifs de décision de révision (SMDR) <Brève description de la question en litige, p. ex., « Conditions d'application de la politique de Santé Canada Bioéquivalence des formulations proportionnelles - Formes pharmaceutiques orales solides » >

Foreword

Health Canada's Summary Basis of Reconsideration Decision (SBRD) documents outline the scientific and regulatory considerations that factored into Health Canada's decision to grant or deny a Request for Reconsideration filed as per the Health Canada Guidance Document: Reconsideration of Final Decisions Issued for Human Drug Submissions. The SBRD has been prepared in such a way that allows stakeholders to be aware of decisions made, without disclosing potentially confidential information about a submission that may not have received authorization.

Summary Basis of Reconsideration Decision

The sponsor filed a <type of submission> for <brief description of submission, e.g. 'proposing a change in tablet formulation', or 'for a combination product for the treatment of hypertension in patients for whom combination therapy is appropriate.'> to the <Directorate>. <Brief explanation for the reasons for the negative decision, e.g. 'The sponsor provided comparative dissolution profiles but did not submit a supporting comparative bioavailability study; a Not Satisfactory Notice was issued on this basis.' Or, 'A Notice of Noncompliance - Withdrawal was issued on the basis that there was insufficient data to support the safety and efficacy of the combination, the combination was not selected using an appropriate clinical trial, and there were insufficient numbers of patients studied, especially long term.'>

The sponsor filed a Request for Reconsideration of the <decision>, stating that <brief summary of the sponsor's description of the issues>.

<Brief description of the process for Reconsideration and the Reconsideration decision, e.g. 'The TPD upheld the original decision on the grounds that the above-referenced TPD policy clearly applies to this submission, and therefore ....' or 'The issue was referred to the Scientific Advisory Committee on Cardiovascular and Renal Therapies, who agreed with the sponsor's position and recommended that the original decision be amended. The Office of Science concurred with the SAC's recommendation. The Director General of TPD amended the original decision and referred the submission back to the review bureau; all issues were subsequently resolved and a Notice of Compliance was issued.'>