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

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• Therapeutic Products Directorate
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Therapeutic Products and Biologics and Genetic Therapies Directorates

Summarised Comments and Recommendations from External Consultations

The draft guidance document entitled Reconsideration of Final Decisions Issued for Human Drug Submissions, along with accompanying documents, were generated by the TPD/BGTD Dispute Resolution Committee (DRC). The DRC was mandated to conduct a review of both Directorates' appeal processes for drug submissions, and to make recommendations for appropriate mechanisms to prevent and address drug submission-related disputes.

On February 22, 2005, the draft guidance document entitled Draft Guidance for Industry: Reconsideration of Final Decisions Issued for Human Drug Submissions (dated February 15, 2005) was posted on the Health Canada website for comment by April 29, 2005. Also posted for comment were two Issue Analysis Summaries, entitled Alternative Models for Dispute Resolution in TPD and BGTD and Dissemination of Reconsideration Decisions in TPD and BGTD, and proposals for related changes to six Health Canada guidances and policies. The following is a summary of the comments received, together with discussions and recommendations for revisions.

The comments are excerpts from the original responses. Issues in the "Comment Received" column are discussed when the comment first appears, or, in some cases, where the issues are most applicable. The comment is not repeated when it or a similar comment appears later in the document.

Each suggestion has been attributed as follows:

Industry associations: 2, 10, 12
Pharmaceutical companies

Innovator pharmaceutical companies: 1, 3, 4, 5, 6, 7, 8, 11, 12, 13
Generic pharmaceutical companies: 9

General comments

Comment Received: Several respondents suggested that an external (impartial) panel of experts should always be used in the reconsideration of final decisions. (9, 11, 12)

One respondent suggested that due to the nature of NON-prescription drug submissions, where there is no contact with TPD until a final decision has been made, a process should be implemented whereby a NON-prescription drug sponsor has the opportunity to resolve the dispute with either the Director or Division Chief of the responsible area before having to file an intent to commence the formal dispute resolution process. (2)

DRC Discussion and Recommendation: External panels cannot always be used in the reconsideration as not all matters are appropriate for referral externally. For example, for regulatory issues the experts would be lawyers, not scientists. The formation of a panel will be the favoured option if feasible, however it cannot be automatic. No change made.

The Senior Medical Advisor Bureau is working to improve communication with sponsors of NON-prescription drug submissions. Even in situations where they are not contacted about their submissions, sponsors always have the option of contacting the Directorate. Dispute prevention and early resolution measures such as teleconferences or post-Notice meetings are available for all submissions, including NON-prescription submissions. A Regulatory Project Manager has been assigned to the NON-prescription Drug Evaluation Division, and consideration is being given to assigning a similar resource to DIN submissions.

1. Policy Objectives

No comments received.

2. Scope and Application

Line Number(s) 8-16

Comment Received: Several respondents suggested that NODs and NONs be included in the scope of the reconsideration process. (4, 7, 11) One respondent suggested that NOC/c-QN be included in the scope of the reconsideration process. (4)

Several respondents recommended allowing time to finalize and assess the success of the new initiatives before relying on them as a mechanism for reducing the number of disputes. There was also concern that NON and NODs may be issued due to time constraints in the review process. (4, 7, 11)

DRC Discussion and Recommendation: Including NODs, NONs, and NOC/c-QNs in the scope of the reconsideration process does not allow the review process to operate fully on its own. To do so would significantly increase the submission burden, when there are still ways to salvage the submission. A response to these notices is in itself a mechanism to resolve disputes, as are discussions held after a Notice has been issued.

With many of the 'new' initiatives, the Directorates are simply more broadly applying the best practices already established in some areas. Therefore, many of the initiatives have had success in localized areas. There is no intention to issue a decision prematurely to meet targets.

3. Policy Statements

No comments received.

4. Roles and Responsibilities

General Comments

Comment Received: One respondent indicated that further clarification is needed regarding the roles and responsibilities with respect to responding to inquiries about the reconsideration process. It was suggested that examples be given on when the sponsor would contact the Office rather than the RPMD/RAD and vise versa. (5)

One respondent suggested that the current Level 2 appeals are very well managed by the Office of Science and therefore, the effectiveness of the new Reconsideration process would be enhanced by an increase in both the resources and authority of this group. (8)

DRC Discussion and Recommendation: Both areas will be responsible for responding to queries about the Reconsideration process; sponsors may contact either group. The DRC decided it was not necessary to provide further clarification.

The Office of Science will have authority over the Reconsideration process for TPD decisions; at this time it is not known whether additional resources will be needed as a result of this new guidance.

Director General

Line Number(s)60-66

Comment Received: One respondent suggested that the giving the DG authority over the complete acceptance of the Reconsideration request, process, selection of the reviewers and the decision creates a lack of objectivity in the process from the start. The respondent suggested the limiting the DG's responsibilities to the following:

DRC Discussion and Recommendation: The process is intended to be a Reconsideration of the original decision, therefore the DG must retain authority over the process. The Reconsideration request will be accepted or rejected based on the criteria outlined in the guidance; the process will be based on recommendations from the Office, as will the selection of reviewers.

Drug Submission Sponsor

Line Number(s)67-75

Comment Received: One respondent suggested that it should be the Sponsor's responsibility to select the desired Reconsideration process and not the Office. (9)

DRC Discussion and Recommendation: The sponsor may recommend the desired process for reconsideration in their package, but the decision must remain with the Directorate (see comment re: referral of issues to external panel on page 1). Section 5.1 and the Reconsideration template will be revised to indicate the sponsor should indicate its desired process for Reconsideration in the package.

Line Number(s)72

Comment Received: Two respondents suggested that the Sponsor should have the responsibility to select rather than nominate one member of the Reconsideration Panel (if formed). (7, 9)

DRC Discussion and Recommendation: The Directorates have a responsibility to assess whether the nominee meets the Department's Conflict of Interest criteria, therefore the selection should remain with the Directorate. However, generally the sponsor's nominee will be chosen unless he/she has an identified conflict. In this situation the sponsor will be notified and asked to provide another nominee. The guidance will be clarified (Section 5.3.1).

OoS/OMC

Line Number(s)76-102

Comment Received: One respondent suggested that, in order to ensure an arm's length approach, the Office should be responsible for the process but that the "hearing" would be presided by an outsider whose name is drawn from a list of persons possessing both the qualities and experience to form an opinion. That person would make recommendations to the Director General who will motivate the decision rendered. (10)

One respondent suggested that the Office should send a copy of the IAS with recommendations on the disposition of the Request for Reconsideration to the Sponsor. (4)

DRC Discussion and Recommendation: The review by the Office is necessary to put the recommendation in context, and to provide regulatory expertise that may be lacking in the Reconsideration panel. This is a critical part of the process and cannot be eliminated.

The IAS outlines the recommendation and the supporting rationale; giving the sponsor an opportunity to review the IAS prior to the decision being rendered is essentially equivalent to adding another level of appeal. The guidance makes the commitment that if new issues are raised, they will be forwarded to the sponsor; therefore, the sponsor will have already had the opportunity to respond to all issues identified in the IAS.

RPMD/ RAD

Comment Received: One respondent suggested that the Office (and not the RPMD/RAD) should be responsible for assessing the relevance of the information filed in support of the Request for Reconsideration. (13)

DRC Discussion and Recommendation:The Office will make the decision on relevance, in consultation with RPMD/RAD. The guidance will be clarified.

One respondent suggested that the current Level 2 appeals are very well managed by the Office of Science and therefore, the effectiveness of the new Reconsideration process would be enhanced by an increase in both the resources and authority of this group. (8)

5. Guidance for Implementation

5.1

Comment Received: One respondent suggested that the following final decisions for NON-prescription drugs should be added under the Screening Rejection Letter or added as new categories for which a Reconsideration intent can be filed:

• New Drug Letter
• Screening Deficiency Notice
• Labelling Standard Letter (2)

DRC Discussion and Recommendation: A New Drug Letter is a form of Screening Rejection Letter. The guidance will be revised to add this example. A Screening Deficiency Notice and a Labelling Standard Letter are not final notices and are not eligible for reconsideration (see comment on page 2)

5.1.1

Line Number(s)162-163

Comment Received: One respondent suggested that the guidance be revised to indicate that a Letter of Intent must be filed within (no less than) 15 calendar days of the Sponsor's receipt date of the reviewer reports. (1)

Two respondents suggested that the timeline for the sponsor to submit a Letter of Intent be increased to 30 calendar days. There was concern that due to the fact that it takes several days to receive the review reports, the allotted time would be insufficient to allow sponsors the time to obtain the necessary approvals to proceed with the formal process. (2, 5)

DRC Discussion and Recommendation: The process for issuance of review reports will be examined, to ensure targets can be met. The Directorates will commit to a more realistic target of 7 calendar days to issue review reports, instead of accompanying the decision. (The Management of Drug Submissions Guidance will be revised accordingly.) In addition, the time to file a Letter of Intent will be extended to 30 days (see next comment).

Agreed. The guidance will be revised to extend the Letter of Intent target to 30 days.

Line Number(s)178-181

Comment Received: One respondent suggested that the time required for completing each step of the reconsideration process be consistently included throughout the guidance document [e.g. SIPD will acknowledge receipt of the Letter of Intent (within 5 calendar days) and ....]. (5)

DRC Discussion and Recommendation: The DRC determined that this would make the document too complicated and lengthen it unnecessarily. The targets for the sponsor are clearly outlined in the text of the guidance document; all timelines are described in Appendix 2.

Line Number(s)182-185

Comment Received: Two respondents suggested that eligibility criteria used by the Manager of RPMD/RAD in determining whether the decision under dispute is one for which a Request for Reconsideration can be filed, be outlined in this guidance document in order for the Sponsor to correctly identify opportunities for reconsideration and submit a comprehensive Letter of Intent. (4, 8)

One respondent suggested that a review of the Letter of Intent by the Manager of RPMD/RAD would seem to be an unnecessary and time-consuming step. (8)

DRC Discussion and Recommendation: The eligibility criteria are already outlined in the guidance, in Section 5.1. The guidance will be revised to clarify that these are the criteria to be used by RPMD/RAD.

The review of the Letter of Intent is necessary so that, if the decision is not eligible for reconsideration, the sponsor is informed as soon as possible.

Line Number(s)191-194

Comment Received: Two respondents suggested that in the event that the Request filed by the Sponsor is eligible for Reconsideration, it should be added that the Manager of RPMD/RAD will ensure that the Sponsor is contacted and the Reconsideration process and the mechanisms available for dispute resolution are explained. (5, 7)

DRC Discussion and Recommendation: The mechanism available for dispute resolution is outlined in the guidance document, for decisions eligible for Reconsideration; therefore it is not necessary for RPMD/RAD to contact the sponsor. The guidance will be revised to include an acknowledgement letter issued by RPMD/RAD that will indicate that the Reconsideration will proceed in accordance with the guidance document.

5.1.2

Line Number(s): 196-198

Comment Received:One respondent suggested that the sponsor should be given an opportunity to meet with Health Canada on a case-by-case basis when filing a Request for Reconsideration. (13)

One respondent suggested that the timeline for the sponsor to submit a Request for Reconsideration be increased to 60 calendar days. There was concern that the sponsor's work on the Request for Reconsideration would be delayed by the timing of the receipt of the reviewer's reports. (5)

One respondent suggested that when Health Canada deems a decision to be eligible for Reconsideration, in addition to forwarding the Letter of Intent to the "Office", a letter should also be sent to the Sponsor and from the date of this letter (rather than the date of the final decision), a Sponsor must submit a formal Request for Reconsideration within 45 days. (1)

DRC Discussion and Recommendation:It is suggested that the sponsor file the Request for Reconsideration prior to meeting with Health Canada, so that everyone is informed of the issues. However, as at any stage in the submission process, a sponsor may request a meeting and Health Canada will consider the request.

Agreed. The guidance will be revised to extend the target for the Reconsideration package to 45 days from the date of the acknowledgement letter issued by RPMD/RAD.

Agreed. As discussed above, an acknowledgement letter will be issued indicating that the Reconsideration will proceed according to the guidance. The deadline has been extended to 45 days from the date of the acknowledgement letter issued by RPMD/RAD.

Line Number(s): 205-208

Comment Received: One respondent suggested that the timelines for reviewing an extension request process be captured in the "Performance Targets" in Appendix 2. (7)

DRC Discussion and Recommendation: The extension request process is to be an exceptional occurrence; the Office will process these as quickly as possible.

5.2

Line Number(s): 213

Comment Received: One respondent requested clarification on the numbering system - does Health Canada require the paragraphs or lines to be numbered? (4)

DRC Discussion and Recommendation: The guidance states that paragraphs should be numbered.

Line Number(s): 224-225

Comment Received: One respondent suggested that the page restriction on the Request for Reconsideration document permit some flexibility to allow Sponsors to provide comprehensive, adequate information in support of their request. (1)

DRC Discussion and Recommendation: Twenty pages is considered sufficient by the DRC and only one sponsor indicated it was insufficient. In addition, it does not include supporting references. As with all guidances, sponsors should discuss alternate approaches with the Directorate prior to filing.

5.2.1

Line Number(s): 233-235

Comment Received: One respondent suggested that it should be clearly stated that a refusal of information applies only to:

• the submission of new information not previously submitted by the sponsor
• information not directly or indirectly pertaining to the submission under dispute (9)

DRC Discussion and Recommendation: This is incorrect, a refusal of information applies to information that does not pertain to the issues under dispute. This is stated in the guidance.

Line Number(s): 236-240

Comment Received: One respondent suggested that it is not satisfactory for there to be no provision for submission of additional data during the Reconsideration process. The restrictions of the Management of Drug Submission Policy rarely allow sufficient time for the generation of additional data to respond to issues raised in NONs and NODs. (8)

DRC Discussion and Recommendation: The guidance states that no new clinical trials can be submitted during the Reconsideration process as these should be reviewed by the review bureau/centre as a refiled submission; it is not appropriate that these be reviewed only by the Office or by an external panel. It is not the intent of the Management of Drug Submissions Guidance to allow time to generate additional data in response to a Notice. Provisions of new data during the submission process are outside the scope of this project, and would form part of a comprehensive review of the Management of Drug Submissions Guidance.

Line Number(s): 243-252

Comment Received: One respondent indicated that clarification was needed around the re-filing of rejected information (i.e. will any information be forwarded directly to the bureau as opposed to the sponsor preparing a new submission that included the new information?). (7)

One respondent requested clarification around the permissibility to have one issue under reconsideration and a new submission on the same issue simultaneously. (7)

DRC Discussion and Recommendation: The new information would be filed as a refiled submission by the sponsor; this would be explained by RPMD/RAD. The guidance will be clarified.

The guidance will be clarified to indicate that sponsors are discouraged from pursuing both a Reconsideration and a refiled submission on the same issue, due to limited resources. The sponsor will be asked to choose which one will proceed first; they will not proceed simultaneously. The guidance will be clarified.

5.3

Line Number(s): 273-278

Comment Received: One respondent suggested that, in addition to the details of administrative nature, the letter to the sponsor should also contain the reasons for referring the issue to a SAC/Reconsideration panel. (13)

DRC Discussion and Recommendation: Agreed. The guidance will be revised.

5.3.1

General comments

Comment Received: One respondent indicated "under section 5.3.1, the DG can limit the scope of the appeal to one or more direct questions" (12)

One respondent suggested that a clearly defined process for meetings between Health Canada, the Sponsor, and external advisors should be included to ensure that the meetings are well-organized, efficient, productive and properly documented. (7)

One respondent suggested that the specific reasons for the Directorate's decision to conduct an external or internal review should be made clear to the Sponsor. Should an external review be identified as appropriate for a certain issue, the sponsor should be made aware of the SAC assigned and the reasons for choosing the specific individuals on that panel. TPD should then provide the sponsor with the CVs of the members nominated. (7)

DRC Discussion and Recommendation: This quote could not be located in the section/document under review.

This is an implementation issue. An SOP will be drafted and will include, for example, provisions to share presentations a week before the meeting.

The rationale for the proposed process for disposition of the request will be outlined to the sponsor in the letter from the DG. If there is an issue of expertise, CVs are shared with the parties involved.

Line Number(s): 280-282

Comment Received: One respondent suggested that for generic abbreviated submissions, rather than using the SACBB, a specially-appointed three person reconsideration panel should be used. There was concern that the SACBB would not have the expertise and has other on-going business. (12)

Given the size of the SAC-BB, it is likely that a subset of the committee would be chosen with appropriate expertise. If expertise is lacking, the panel could be supplemented with ad hoc members as described in the guidance.

Line Number(s): 282-286

Comment Received: Two respondents suggested that in the event the Office chooses to convene a sub-set of SAC members or supplement ad hoc members to the SAC, the Sponsor should be involved in the selection process (i.e. given the option to approve sub-set SAC, or should select the supplementary SAC members from a list of nominees put forward by the review Bureau). (1, 7)

DRC Discussion and Recommendation: The Office would propose the committee to be used, and which members would form part of the panel; the sponsor would be contacted to propose additional members. The guidance will be revised to indicate that the sponsor will participate in the selection of the members.

Line Number(s): 290-293

Comment Received: One respondent suggested that the sponsor's role in the preparation and review of the background document be clarified. (13)

One respondent suggested that the background document and questions be prepared jointly between Health Canada and the sponsor. (13)

One respondent suggested that "enough time" be replaced with a specific timeframe. (13)

DRC Discussion and Recommendation: This is an operational issue and will be addressed in SOPs to be drafted prior to implementation of the guidance.

This is an operational issue and will be addressed in SOPs to be drafted prior to implementation of the guidance.

This is an operational issue and will be addressed in SOPs to be drafted prior to implementation of the guidance.

Line Number(s): 294-302.

Comment Received: Two respondents suggested that all parties be present during each other's presentations/discussions and question and answer sessions. (4, 13)

DRC Discussion and Recommendation: Agreed - this is how the meetings were intended to proceed. The guidance will be clarified.

Line Number(s): 303-306.

Comment Received: Several respondents suggested that the Sponsor should be given the opportunity to review the draft record of the SAC proceedings. (1, 5, 7, 13)

One respondent suggested that if a SAC is tasked with providing advice about a reconsideration decision, the minutes of this meeting be held as confidential, shared only with the relevant members of Health Canada and the Sponsor. (7)

DRC Discussion and Recommendation: As with the IAS, discussed on page 4 (comment re: sharing IAS prior to decision being made), there will be no new issues contained within the record of proceedings for the SAC.

The proceedings of SAC meetings are not shared beyond Health Canada and the sponsor if the issues are submission-specific.

Line Number(s): 309-317.

Comment Received: One respondent suggested that in selecting the membership of the Reconsideration Panel, the Sponsor should select a panel member based on nominees put forward by the Review Bureau and in turn, the Review Bureau would select a panel member based on nominees put forward by the Sponsor. (1)

DRC Discussion and Recommendation: As discussed above (comment on page 4), the selection of nominees should rest with the Directorates.

Line Number(s): 313-317.

Comment Received: Several respondents suggested that it would be more than difficult to nominate potential members of the Reconsideration Panel under the stipulated conditions. It was suggested that the conflict of interest should be evaluated on a case-by-case basis and after full disclosure of all past interactions with the company. It is not realistic to suggest that nominees should not have past experience with the Sponsor. (1, 4, 7, 8, 13)

One respondent suggested that the membership of the Reconsideration Panel be determined by the following:

• One member selected by the sponsor
• One member selected by the DG from nominations by the relevant bureau; and
• One member appointed by the DG who, when possible, is a member of an existing SAC and who will chair the Reconsideration Panel but will not provide opinion either to the other two members or the DG on the issue under dispute. (9)

One respondent suggested that the selection process for the reconsideration panel should be modelled after the New Drug Committee procedure of the Food and Drug Regulations, Division 8, C.08.009(3). TPD and the sponsor would each select one member of the reconsideration panel and together, choose a third member who will serve as chair. (12)

DRC Discussion and Recommendation: The process as proposed is current practice for the selection of members for an external panel. CoI is currently evaluated on a case-by-case basis.

The expertise of the chair is important in developing the recommendations of an external panel; relying on only two experts may not provide enough expertise to answer the questions posed. It is not clear in this situation who would write the report or what the role of the Chair would be if no opinions were to be provided. No changes to the guidance have been made.

The Directorates have a responsibility to assess whether the nominee meets the Department's Conflict of Interest criteria, therefore the selection should remain with the Directorate. The Directorate Management Committees decided that the chair will be chosen from nominations by the Office, to allow the DG to seek out particular expertise missing in the two panel members, and to allow selection of the chair from an existing SAC where possible. No change made.

Line Number(s): 318-324.

Comment Received: Several respondents suggested that it would be difficult for the sponsor to obtain a copy of the nominee's CV without any contact with the nominee. It was suggested that to do so might be in violation of PIPEDA, as prior consent must always be obtained prior to the release of any personal information. (1, 4, 5, 6)

DRC Discussion and Recommendation: The guidance will be revised to indicate that the sponsor should provide names, and the Office will ask the nominees for their CVs. A package will be prepared and shared with the sponsor and the review bureau with a summary of the panel members' expertise relevant to the issues under dispute. The guidance will be revised, and reference to the package will be included in the SOP to be drafted.

Line Number(s): 327-328.

Comment Received: One respondent suggested that the process by which the Bureau provides nominations for one member of the Reconsideration Panel be outlined as it is for the Sponsor's nominees. (5)

DRC Discussion and Recommendation: The process by which the review bureau nominates members is similar to the process followed by the sponsor. Adequate information is provided; additional clarification will occur in the SOPs to be drafted.

Line Number(s): 332-333.

Comment Received: One respondent suggested that clarification be given on the requirements in meeting the conflict of interest and security clearance. (7)

DRC Discussion and Recommendation: The Office is reviewing these criteria; when ready, these will be shared as a separate document.

Line Number(s): 338-341.

Comment Received: One respondent requested further elaboration on how to proceed should a sponsor-nominated candidate decline to participate in the Reconsideration Panel. (4)

DRC Discussion and Recommendation: If this situation were to arise, the Office would contact the sponsor for additional nominees. It was not considered necessary to include this level of detail in the guidance.

Line Number(s): 358-359.

Comment Received: One respondent suggested that the telephone or video conferencing option be available for all types of submissions (if agreed upon by both Health Canada and the Sponsor during the planning of the meeting). (5)

One respondent suggested that if the SAC or Reconsideration Panel meeting is held via telephone or video conference, it should be clarified that the Sponsor will still have the opportunity to present to the external panel and the process would remain as described in section 5.3.1 (a). (7)

DRC Discussion and Recommendation: Although this option is suggested primarily for priority submissions, it is available for all types of submissions. The guidance will be clarified.

The sponsor and review bureau/centre will both have the opportunity to present, as they would with a meeting in person. The guidance will be clarified.

5.3.2

Line Number(s): 362-376.

Comment Received: One respondent suggested that when a Request for Reconsideration is reviewed by the office, an official record of the meeting between the Sponsor and the DG/Office should be prepared as is done for an SAC meeting. The respondent further suggested that the Sponsor provide input into the draft record and should receive a copy of the final record within 7 calendar days. (1)

DRC Discussion and Recommendation: This meeting is generally an opportunity for both sides to present their side of the issues to the DG; therefore, the presentations become the minutes. Additional discussions or questions and answers would be captured, as determined at the beginning of the meeting. This is an operational issue and will be addressed in the SOPs to be drafted prior to the implementation of the guidance.

5.3.3

Line Number(s): 383-386.

Comment Received: One respondent suggested that new safety information should be the only type of new information considered during the reconsideration process. (13)

DRC Discussion and Recommendation: As stated in the IAS, new information that is relevant to the issues under dispute should also be considered, to assist with dispute resolution.

5.3.4

Line Number(s): 387-403.

Comment Received: One respondent suggested that the Reconsideration process should allow for the issuance of a Notice of Compliance directly as a result of the Office of Science Review, when justified. (8)

DRC Discussion and Recommendation: The Office review can result in the issuance of a Notice of Compliance; however, often the Product Monograph will need to be finalized. Therefore the review bureau/centre will complete any outstanding activities and prepare the NOC package for DG signature, as a result of the Office review.

Line Number(s): 398-403.

Comment Received: One respondent suggested that the Reconsideration process should allow for the issuance of a Notice of Compliance directly as a result of the Office of Science Review, when justified. (8)

It is difficult to provide specific examples of this exceptional situation. The guidance will be clarified to indicate that this is an exceptional circumstance.

DRC Discussion and Recommendation: One respondent indicated that more clarification is needed as to when the following situation would apply: "The Office recommends, upon reconsideration, that the DG 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 cases where the process was not appropriately applied and/or pertinent information was not appropriately considered". (1)

5.4

Line Number(s): 416.

Comment Received: One respondent suggested that the time for the DG to make the reconsideration decision (i.e. 5 days) be included as per Appendix 2. (5)

DRC Discussion and Recommendation: As discussed earlier, the DRC determined that the inclusion of targets in the text would make the document too complicated and lengthen it unnecessarily.

5.5

Line Number(s): 428-433.

Comment Received: Two respondents suggested that if the reconsideration decision was to refer the submission back to the review bureau/centre for re-evaluation and a new target date is required, it should be set for the earliest possible date by which the submission could reasonably be re-evaluated, and the submission should be assigned priority review status. (2, 9)

DRC Discussion and Recommendation: The submission will not be assigned 'priority review' status according to the Priority Review policy; however, it will be placed in the queue according to its original target date, which means that it will likely be next in the queue. The guidance will be clarified.

Line Number(s): 432-433.

Comment Received: One respondent indicated that more clarification is required in terms of how much time is considered acceptable in extending a target review date. (1)

DRC Discussion and Recommendation: The target date will be set based on the data to be reviewed, the complexity of the issues and the data, the number of issues to be reviewed, etc. Each target date will therefore be set on a case-by-case basis. The guidance will be clarified to indicate the criteria used in setting the target date.

Line Number(s): 431-433.

Comment Received: One respondent suggested that how a "new target date" is set be clarified. (13)

5.7

Line Number(s): 446-551.

Comment Received: One respondent suggested that Health Canada should evaluate other options to satisfy the need to share, learn and increase transparency regarding review decisions. Health Canada may consider instituting an "Issues List" or "Reviewer Bulletin", the function of which is to highlight review issues in a neutral, NON-proprietary medium. (1)

An 'issues list' or 'reviewer bulletin' would not provide enough information to prevent future disputes or to be transparent about review decisions.

It is anticipated that the SBRD would take approximately one month to draft, send to the sponsor for comment, translate, and post.

The Singulair decision was not upheld on appeal.

The indicated area of use provides information that is key to understanding the dispute and the decision made, and will remain. The SBRD template will be revised so that submission milestones will not be included.

The SBRD template will be revised so that the sponsor's name will not be included. As the SBD project moves into subsequent phases, this will be re-evaluated.

One respondent suggested that this section should indicate that the external dissemination of reconsideration decisions will be subject to the provisions and exemptions of the Access to Information Act in order for the sponsor to ensure no proprietary/confidential information is included in the summary prior to it being posted on the website. (11)

The provisions of the Access to Information Act do not apply until an ATI request is made. It is not the intent of the SBRD to disclose proprietary or confidential information, and the removal of the sponsor's name and submission milestones should address these concerns.

If a submission for which an SBD is drafted has gone through a Reconsideration, the details will be included in both the SBRD and the SBD (the documents have different audiences and different purposes and may be drafted for different submissions).

One respondent suggested that the SBRD not be published until the product is made available for sale in Canada (i.e. the DIN is notified to Health Canada). It has been the long-standing policy that all information in a sponsor's submission be subject to the mandatory exemptions from disclosure contained in paragraphs 20(1)(b) and (c) of the Access to Information Act until the launch of the product in Canada and the release of the Product Monograph. (7)

One respondent suggested that SBRD should not be made public if the final decision is a Withdrawal Decision, since that would be in conflict with the approach taken to the SBD, which is only made public in the case of an NOC. (8)

One respondent indicated concerns around the publication of a SBRD around the rejection of a priority review request. A company's rationale and support for obtaining priority review should not be made public as this information may reveal certain unique and strategic approaches to the regulatory process adopted by the sponsor. (7)

There is no reason why the SBRD could not be published if a Notice of Application is filed. At any rate, it is anticipated that the SBRD would take approximately one month to draft, send to the sponsor for comment, translate, and post. If the sponsor wishes to prevent Health Canada from publishing the SBRD it may file a motion with the Notice of Application to delay publication until the matter is resolved.

As discussed above, the SBRD will be published whether or not the product is ultimately granted authorization and whether or not it is marketed in Canada. With the removal of the sponsor's name and submission milestones, the information provided in the SBRD will be neither confidential nor proprietary.

DRC Discussion and Recommendation: An 'issues list' or 'reviewer bulletin' would not provide enough information to prevent future disputes or to be transparent about review decisions.

One respondent suggested that the SBRD not be posted until 30 days following the notification to the Sponsor of the Reconsideration Decision. (9)

One respondent suggested that in light of the recent court decision regarding disclosure of information considered to be proprietary, the SBRD document should not be published. (4)

Two respondents suggested the removal of the indicated area of use and all submission milestones. (1, 7)

Several respondents suggested the removal of the sponsor's name. There was concern that by disclosing the sponsor's name, the product could easily be identified, especially in the case of a small company with few products. (1, 6, 7, 9)

Several respondents suggested that prior to the dissemination of the SBRD, the Sponsor should review the summary to ensure that all confidential information is adequately removed from the document. (1, 2, 5, 7)

The SBRD will be sent to the sponsor for review prior to posting, similar to the process followed for the SBD. However, the Directorates will maintain strict control over the parameters for removing or changing information.

Two respondents suggested that the details regarding the Reconsideration decision of subsequently approved submission be provided in the submission SBD. (1, 8)

The SBRD will be published whether or not the product is ultimately granted authorization and whether or not it is marketed in Canada. With the removal of the sponsor's name and submission milestones, the information provided in the SBRD will be neither confidential nor proprietary.

These are two separate projects with different purposes, different audiences, and different approaches. See above comment re: publication of the SBRD if the product is not marketed.

The DRC disagreed that the publication of an SBRD for a priority review request rejection could jeopardize a company's position or provide proprietary information to a competitor. The SBRD will focus on whether the product met the criteria outlined in the Priority Review policy, and identifying information about the submission (i.e. milestones) and the sponsor will not be included.

One respondent suggested that the SBRD not be posted in the event that the Sponsor is not satisfied with the Reconsideration Decision and notifies TPD/BGTD of its intention to file a Notice of Application to the Federal Court to resolve the matter within 30 days of the Reconsideration Decision. (9)

One respondent suggested that the SBRD not be posted in the event that the Sponsor withdraws a submission further to a Reconsideration Decision. (9)

Line Number(s): 448-451.

Comment Received: One respondent suggested that the external dissemination of the SBRD implementation should undergo the same development process (i.e. three phases) as the external dissemination of the SBD. All phases being followed by an appropriate evaluation time frame. (13)

DRC Discussion and Recommendation: These are two separate projects with different purposes, different audiences, and different approaches. See above comments re: publication of the SBRD if the product is not authorized or marketed.

6. Effective date

General Comments

Comment Received: One respondent requested clarification on the effective date of the guidance document. Will the effective date be applied to a submission filed date or a final decision date? (1)

DRC Discussion and Recommendation:The effective date will be clarified in the Notice to accompany the final guidance for implementation. It will apply to all final decisions issued after the effective date.

APPENDIX 1: Reconsideration Process Map

General Comments

Comment Received: Two respondents suggested that the process map is not legible and appears to be very complicated and therefore a cleaner and less complicated map would be more useful. (5, 7)

DRC Discussion and Recommendation Agreed. The process map will be revised.

APPENDIX 2: Performance Targets: Reconsideration Process

General Comments

Comment Received: One respondent suggested that the proposed chart was too long and complex and recommended a less bureaucratic process with predictable timelines. (11)

One respondent suggested that a time frame within which a reconsideration decision must be completed should be included in the reconsideration process. (12)

DRC Discussion and Recommendation The chart was drafted to be a quick reference for all targets and outputs for the Reconsideration process. The DRC decided that no changes were necessary.

The timelines associated with the process are dependent on factors such as the issues identified, the need for an external panel, the ability of the panel to meet, etc. Therefore, it is impossible to set a date by which the appeal must be completed. This is consistent with other administrative tribunals.

APPENDIX 3: Request for Reconsideration Template

No comments received.

The following is a summary of the comments received with respect to the document entitled Issue Analysis Summary: Alternative Models for Dispute Resolution in TPD and BGTD, together with discussions and recommendations for revisions.

1. Issue

No comments received.

2. Purpose/Objective

No comments received.

3. Background

No comments received.

Options Analysis

Option 1 - Status Quo

General Comments

Comment Received: One respondent suggested the discussion of the status quo in the IAS does not fully describe the deficiencies of the Level 1 Appeal process. Of particular concern is the fact that the review is not independent of the Bureau responsible for the original decision. Additionally, the timelines for the various steps were frequently not met.

In addition, it was suggested that undue weight is given by the appeal reviewers to the reports of the original reviewers, rather than to a re-evaluation of the sponsor's data. This problem is presumed to be less likely if the Reconsideration process occurs outside of the reviewing Bureau as proposed in the new guidance. (8)

One respondent suggested the pilot project implemented in mid-2002, which involved the appeal reviewer making a presentation to five review Directors was unsatisfactory, in that the opportunity did not exist for the sponsor to address this panel. Also of concern was that the process suggested was ineffective due to the absence of Bureau Directors. (8)

Health Canada Discussion and Recommendation: The IAS indicates that timeliness is a concern with the Level 1 appeal process. The IAS will be revised to indicate that the lack of independence is an additional concern related to Level 1 appeals.

The IAS will be revised to indicate that sponsors are concerned that they do not have the opportunity to present to the Directors' panel.
The absence of Bureau Directors may occasionally have delayed the process, however the DRC did not feel that this alone rendered the process ineffective.

Options 2a,b,c

General Comments

Comment Received: One respondent suggested that the reasons for the dismissal (i.e. "it would lead to the perception that sponsors are unduly influencing the Directorates") of the options are not valid. The respondent indicated that it should not matter to whose account the time is charged, provided the efficiency of the overall process is improved. (8)

Health Canada Discussion and Recommendation: The respondent has not indicated whether Options 2a, 2b, or 2c should have been selected. While the Directorates agree that efficiencies to the overall process are important, given recent commitments regarding review on time, this is still an important issue.

Option 9 - TGA

Comment Received: One respondent suggested that allowing the Sponsor to select an external Reconsideration Panel as opposed to going through an internal process would provide both the Directorate and the Sponsor the same benefits as suggested by the option analysis (i.e. better position to defend a decision made on the recommendation of a scientific committee than that made on the recommendation of one evaluator). (9)

Health Canada Discussion and Recommendation: Noted. However, the decision must remain with the Directorate (see comment re: referral of issues to external panel on page 1).

5. Consultations

No comments received.

6. Implementation

No comments received.

7. Evaluation

No comments received.

The following is a summary of the comments received with respect to the document entitled Issue Analysis Summary: Dissemination of Reconsideration Decisions in TPD and BGTD, together with discussions and recommendations for revisions.

General comments

Comment Received: One respondent suggested that the IAS on Dissemination of Reconsideration Decisions contains the notion that the "threat" of publication of the results of the Reconsideration Process will be an incentive for sponsors to resolve disputes, and justifies publication of decisions on that basis. The respondent suggests this be removed from the IAS. (8)

DRC Discussion and Recommendation: Although this was not the intention of the IAS, this has been removed to avoid misinterpretation.

1. Issue

No comments received.

2. Purpose/Objective

No comments received.

3. Background

No comments received.

4. Options Analysis

No comments received.

The following is a summary of the comments received with respect to the document entitled Draft Revised Guidance for Industry: Management of Drug Submissions, together with discussions and recommendations for revisions.

General comment

One respondent suggested Health Canada provide clear guidance on how decisions for DINAs (including administrative and notifiable changes related to DIN products) will be handled. (3)

How changes to DIN submissions are handled is beyond the scope of this project. It would form part of a comprehensive review of the Management of Drug Submissions Guidance and/or the Guideline on the Preparation of DIN Submissions.

1. Purpose

No comments received.

2. Background

No comments received.

3. Scope

No comments received.

4. Definitions

No comments received.

5. Procedures

5.2.6

Line Number(s)286-290

Comment Received: One respondent suggested that either more time is allowed for a response to a clarifax and/or the breadth of any one clarifax needs to be reduced. (8)

DRC Discussion and Recommendation: The issue of clarifaxes is outside the scope of this project, and would form part of a comprehensive review of the Management of Drug Submissions Guidance.

5.5.1

Line Number(s)498

Comment Received: One respondent suggested that a major barrier to dispute prevention and early resolution is TPD's policy of "only one NON/NOD per submission". It was suggested that it would be more efficient to proceed in an iterative fashion, based on responses to a series of Notices, rather than interrupt the review process with re-filing or the reconsideration process, possibly necessitating additional reviewers and perhaps reviewers who are unfamiliar with the issues in the original submission. (8)

DRC Discussion and Recommendation: Significant changes to the submission process itself are outside the scope of this project, and would form part of a comprehensive review of the Management of Drug Submissions Guidance.

Line Number(s)505-507

Comment Received: One respondent suggested that TPD has displayed a clear disregard to the flexibility with respect to the 90 day (or such time as the Director and Sponsor may agree upon) response time. When appropriately justified, and it is in the best interest of the efficient completion of the review process, extra time should be allowed. (8)

DRC Discussion and Recommendation: The issue of response time is outside the scope of this project, and would form part of a comprehensive review of the Management of Drug Submissions Guidance.

5.5.1 D

Line Number(s)553-555

Comment Received: One respondent suggested that the opportunity for Sponsors to contact the RPM to arrange a meeting to explain a NON, is not optimally helpful for the following reasons:

• t usually takes weeks to arrange the conference and therefore valuable time is lost with the 90 day response window; and
• it would be far more beneficial if advance notice of a NON was provided to the sponsor so that a discussion concerning the issues could take place prior to the issuance of the formal NON. (8)

DRC Discussion and Recommendation: Teleconferences can be scheduled within days. In addition, if RPMs are aware of issues during the review process, they will (with the consent of the review division) inform the sponsor of these issues in advance of the issuance of the NON. The pros and cons of a prenotice meeting or discussion are discussed under Option 2 in the IAS entitled: Alternative Models for Dispute Resolution in TPD/BGTD.

6. Accessing Submission Information

6.1

General Comments

Comment Received: Several respondents suggested that there is currently a very poor process for managing the release of reviewer reports to the Sponsor. An explanation is needed as to why the Management of Drug Submission Guidance refers to a 30 day delay after the issuance of the NOD/NON. (1, 5, 8)

One respondent suggested a formal decision on the reasons for not providing clearance for DINAs and notifications pertaining to DINAs would be beneficial for the Sponsor to receive in writing. It was suggested that the guidance address how these will be handled. (3)

One respondent suggested that Health Canada ensure that it is possible for the Sponsor to discuss and negotiate more detailed areas with the reviewer to avoid unnecessary back and forth that may occur when having the RPM act as the middle person. (3)

DRC Discussion and Recommendation: The Management of Drug Submissions Guidance refers to a 30 day delay for review reports that must be requested, not for those automatically issued. The Directorates are aware of the concerns with the issuance of review reports and are working to improve the situation. The Directorates will commit to a more realistic target of 7 calendar days to issue review reports, instead of accompanying the decision.

The Senior Medical Advisor Bureau is working to improve communication with sponsors of NON-prescription drug submissions. Although at this time there is no plan to provide review reports automatically with final decisions for DINAs, as per the Management of Drug Submissions Guidance they are available upon request. In addition, sponsors always have the option of contacting the Directorate for clarification, and they may request a meeting or teleconference to discuss a Notice received. A Regulatory Project Manager has been assigned to the NON-prescription Drug Evaluation Division, and consideration is being given to assigning a similar resource to DIN submissions.

The RPM's role is to facilitate discussions, not to be a barrier; the reviewer still discusses scientific issues with the sponsor.

7. Drug Evaluation Fees

No comments received.

Appendix I

No comments received.

Appendix II

No comments received.

Appendix III

No comments received.

ABBREVIATIONS:

ATI:

Access to Information

BGTD:

Biologics and Genetic Therapies Directorate

CV:

Curriculum vitae

DIN:

Drug Identification Number

DRC:

Dispute Resolution Committee

DG:

Director General

IAS:

Issue Analysis Summary

NOC:

Notice of Compliance

NOC/c-QN:

Notice of Compliance with Conditions - Qualifying Notice

NOD:

Notice of Decision

NON:

Notice of NON-compliance

PIPEDA:

Personal Information Protection and Electronic Documents Act

RAD:

Regulatory Affairs Division

RP:

Reconsideration Panel

RPM:

Regulatory Project Manager

RPMD:

Regulatory Project Management Division

SAC:

Scientific Advisory Committee

SACBB:

Scientific Advisory Committee on Bioavailability and Bioequivalence

SBD:

Summary Basis of Decision

SBRD:

Summary Basis of Reconsideration Decision

SIPD:

Submission and Information Policy Division

SOP:

Standard Operating Procedure

TPD:

Therapeutic Products Directorate