Guidance for Industry - Priority Examination of Drug Applications (2023)

Note

February 6, 2009

Our file number: 09-101263-867

Administrative corrections to Health Canada priority review documents

Administrative changes have been made to the French and English versions of the following Health Canada documents:

On December 20, 2007, administrative changes were made to the English and French versions of the Priority Review Policy and Guidelines documents to ensure consistent communication for both official languages. However, during the adoption of these administrative changes, errors were inadvertently introduced into the documents. As such, Health Canada has made the following corrections to ensure consistent application of terminology.

Questions or concerns regarding the policy and guidance documents should be directed to:

Office for Policy, Science and International Programs
Therapeutic Products Administration
Health Canada
Dutch Cross, Tower B,
Address locator 3102C3
1600 Scott Street
Ottawa, Ontario
K1A 0K9
Tel.: (613) 948-4623
Fax: (613) 941-1812
EMAIL:Fragen des Policy Office

Date of approval: 16.09.2002

Revision: 30.11.2005

Date of entry into force: 01.03.2006

Date of administrative changes: 18.12.2008

Forward

The guides are intended to assist industry and healthcare professionalsHowin accordance with policies and applicable laws and regulations. They also serve to provide employee compliance checks and guidance to ensure that orders are carried out in a fair, consistent and efficient manner.

Guidance documents are administrative tools that do not have the force of law and therefore allow for a flexible approach. Alternative approaches to the principles and practices outlined in this documentit canare acceptable provided they are supported by appropriate scientific reasoning. Alternative approaches should be discussed in advance with the relevant program area to avoid potentially finding that any applicable legal or regulatory requirements have not been met.

As a consequence of the above, it is equally important to note that Health Canada reserves the right to request any information or materials or to impose conditions not expressly described in these guidance documents, in order to provide the Ministry with a reasonable assessment of the safety, efficacy or quality of a therapeutic product. Health Canada is committed to ensuring that such requests are justified and that decisions are clearly documented.

This document should be read in conjunction with the attached notice and relevant sections of other applicable guidance documents.

Document change log

Date of modification: 16.09.2002
Place (section, paragraph):
Type and/or reason for change: Date of first application

Date of change: 01.03.2006
Position (Section, Paragraph): Section 3.6
Nature and/or reason for change: consideration of necessary changes resulting from the finalization of the guidance document. Review of final decisions for the submission of medicinal products for human use

Date of modification: 20.12.2007
Position (section, paragraph): throughout the document
Nature and/or reason for change: address update
Consistent application of terminology

Date of modification: 18.12.2008
Position (section, paragraph): throughout the document
Type and/or reason for change: Consistent application of terminology

Content

1.0 Introduction

1.1 Purpose

This guide is intended to assist sponsors in interpreting the Priority Review Policy and in preparing and submitting requests for priority review status. It should be read together withPriority review of drug submission policy.

All therapeutic products sold in Canada must meet the safety and efficacy requirements listed in Part CFood and drug regulations. Be especially careful with notifications of medicines that fall under a compliance notice (NOC/c) Policies or those sold under C.08.010 and C.08.011Food and drug regulationsA guarantee may be granted for specific access purposes. For more information on the NOC/c policy see"Industry Guidelines? Notice of Compliance (NOC/again)". Information about Health Canada's Special Access Program can be found on the Health Canada website.

The purpose of these guidelines is to articulate the expectations of Health Canada and provide a level of consistency in their interpretationPriority review of drug requestsSubmit your policy and request priority review. Additional clarifications are provided on the evaluation process of priority audit requests.

1.2 Background

On December 13, 1996, the former Therapeutic Products Program issued a policy statement entitledPriority review of drug requests. The policy, which replaces Information Letter 804, allowed for "expedited" delivery of Eligible New Drug Applications (NDS) and Supplemental New Drug Applications (SNDS) are intended for the treatment, prevention or diagnosis of a serious, life-threatening or debilitating disease or condition.

A re-evaluation of this policy was prompted in December 1999 by concerns from industry and the HIV/AIDS community. These groups questioned the criteria by which submissions are assigned priority review status and expressed a desire for greater transparency in the drug review process. In particular, concerns related to the increase in the current backlog of applications within Health Canada, confusion regarding the eligibility criteria for priority review status, and the desire to ensure that relevant advanced therapies fall within the scope of priority review.

Allocating shorter review periods for a select group of submissions affects Health Canada's ability to meet performance targets for other types of submissions. By providing additional clarification of the eligibility criteria and the process for reviewing priority applications, Health Canada seeks to increase the consistency of the prioritization process while continuing to meet the policy objective of providing rapid review of important new drugs and discovery therapies to the extent indicated.

1.3 Definition

Clinical benefit: Outcomes that have an overall positive effect on disease management^{footnote 1}.

Significant increase/decrease: A statistically significant and clinically relevant increase (or decrease) detected in well-controlled clinical trials.

1.4 Scope

This policy applies to new drug applications (NDS) or additional submission of a new drug (S/NDS) for a serious, life-threatening or debilitating disease or condition for which there is significant evidence of the clinical efficacy of the drug:

1.5 time frame

Priority review status allows eligible drug submissions to be included in Health Canada's submission workload based on a reduced review target of 180 calendar days. Therefore, eligible submissions may be reviewed before non-eligible submissions, depending on upcoming target dates.

Filing consists of all types of filing, differentiated by product lines for biological, pharmaceutical and medical devices. Special therapeutic experience in the Directorate for Biological and Genetic Therapies (BGTD) and the Administration for Therapeutic Products (TPD) with the aim of revising the respective submission types if necessary. Therefore, review of the priority submission will begin before review of other pending submissions in the same therapeutic area with a completion date after the priority submission. Submissions with a target review date that is earlier than the priority submission target review date will not be suspended.

Once priority review status is granted, there is an express expectation that a submission:

The performance target for initial review and submission review is 215 calendar days (10-day processing time within the Policy and Information Submissions Department (SIPD), a 25-day review in the Administration for the Management of Submissions (SMD) of the relevant administration, 180 days for the review of the application), and for the subsequent review and verification of the response to the notice of non-compliance with the priority of the application, 125 calendar days (10 days).SIPD, 25 TakeSMDscreening, 90-day review).

Review priority sets review priorities. Both applications and priority review requests are subject to established performance standards. While every effort will be made to begin reviewing priority applications expeditiously, the policy does not prevent staff from working on other projects.

2.0 Priority review submission criteria

To be considered for Priority Review status, a submitted drug must first meet the Department of Canada criteria described in Section 1.4 above.

As with similar programs in other international jurisdictions, priority review designation refers to the combination of the device and the specific indication for which it is being investigated, not the device alone. Therefore, it is applied to a specific drug for specific indications, where the indication includes the condition for which the drug is intended and the expected or proven benefit from its use.

To qualify for priority review status, a device must not only be intended for patients suffering from a serious, life-threatening, or debilitating disease or condition, but also indicated for the treatment, prevention, or diagnosis of a serious symptom of its manifestation condition. For example, a product indicated for the relief of minor skin irritation in cancer patients would not qualify for priority review status even if the disease (cancer) itself is clearly life-threatening.

Sponsors seeking priority review status must make a brief presentation to review committee staff prior to submitting a written request for priority review status. The sponsor may discuss the details of the submission and the submission's potential eligibility for priority review status at this time. See section 3.1 for more information on pre-submission briefings.

Regarding eligibility for priority review, the following section provides guidance on how Health Canada determines whether a condition meets the "severe" criterion. All life-threatening conditions are also considered 'severe' diseases and therefore no special distinction is made. In the following discussion, all references to serious diseases also refer to life-threatening diseases.

2.1 Serious/life-threatening illness

Health Canada believes that discretion is required when determining whether a situation is "serious." Factors such as survival, ability to function in daily activities, or the likelihood that the disease, if left untreated, will progress from a less serious condition to a more serious condition are taken into account. The latter includes, among others:

"Severe" diseases are generally associated with morbidity that has a significant impact on daily functioning. Reversible effects of persistent or recurrent morbidity may also be sufficient to qualify a device for priority status if all additional criteria are met. Alternatively, examples of insufficient morbidity would typically include short-term and/or self-limiting morbidity.

2.2 Serious illness

Eligibility for priority review is extended to drug applications intended to treat a seriously debilitating disease or condition for which there is an unmet medical need or for which a significant improvement in the risk-benefit profile of the treatment can be demonstrated. Many chronic diseases that are generally well controlled with available treatments can have serious debilitating effects. Examples include inflammatory bowel disease, asthma, rheumatoid arthritis, diabetes mellitus, systemic lupus erythematosus, depression and psychosis. Again, Health Canada's decision is discretionary.

2.3"Effective treatment, prevention or diagnosis of disease..." (Section 1.4)

A serious, life-threatening or debilitating disease or condition for which no drug treatment is currently available in Canada represents a clear medical need. Therefore, a new treatment that is effective in treating, preventing, or diagnosing the relevant condition would meet this criterion for priority examination status.

The term "available on the market" means that the sale of the product has begun under C.01.014 and that the product is still available for sale (ie, it has not been discontinued or withdrawn from the market). Note: The above criterion does not ensure eligibility due to drug shortage scenarios. Visit the Health Canada website for more information on drug shortages.

Devices that are approved but not yet on the market at the time a priority review request is evaluated will not affect the decision to accept or deny priority review status. Likewise, the fact that an application is subject to review by Health Canada does not affect the decision to accept or reject another sponsor's priority review application for the same indication. The decision to accept or reject depends solely on whether the requirements for priority trial status are met at the time of application and are accurately reflected in the clinical evaluation package (section 3.2).

2.4"A significant increase in efficiency and/or a significant decrease..." (Section 1.4)

To meet the prioritization criteria above, the sponsor should be able to demonstrate that the treatment provides a statistically significant and clinically relevant improvement in efficacy or risk reduction, such that the overall benefit-risk profile compared to existing treatments on the Canadian market is improved. Claim packages for priority review will be evaluated based on the product and information available at the time of claim review and in the context of the disease for which treatment is indicated. At the start of the main trials, the packages are not compared with comparator treatments.

The benefit-risk assessment is consistent with Health Canada's approach to submission review and may include any of the following:

2.5 Substantial evidence of clinical efficacy

Developments in the science and practice of drug development and clinical evaluation in some cases affect the amount and type of data needed to support efficacy.

In general, Health Canada considers substantial evidence of clinical efficacy to be evidence consisting of at least two adequate and well-controlled clinical trials, each of which is individually convincing of the efficacy of the drug in question. The effectiveness of the treatment is evaluated by experts who have scientific education and experience to evaluate the effectiveness of the drug in the treatment of the indicated indication under the conditions of use prescribed, recommended or proposed in the declaration or proposed labeling.

In some cases, clinical evidence consisting of a single, large, appropriate and well-controlled study or a pivotal study and additional clinical evidence may be considered "substantial". Sponsors seeking priority review status must make a brief presentation to review committee staff prior to submitting a written request for priority review status. Additional explanations can be given at this point.

"Promising" clinical evidence, including the use of unvalidated surrogate markers or phase II studies, is further discussed belowNOC/c directives and specified in the corresponding directives. Special abbreviated schedules forNOC/c submissions are processed within . More information aboutNOC/c rules and guidelines can be found on the Health Canada website.

For more information, see the following resources:

3.0 Request for Priority Review Status

3.1 Preliminary Submission Hearings

Before applying for Priority Review status, sponsors are asked to submit a pre-application.NDSprofessionalS/NDSSubmit to the appropriate Health Canada Authority, indicating the effective dates to be included in the submission.

Pre-registration meeting:

Sponsors should send an information pack to the submissions management unit of the relevant department in advance of the meeting in preparation for the submission meeting. For more information, sponsors are encouraged to contact the submissions management department/unit of the relevant Audit Authority.

3.2 Request packets for priority control status

The sponsor is obliged to deliverbefore applying for the drug, a written request for a priority review to the Director of the relevant Health Canada Office and a complete clinical assessment package (COVER) in a format similar to that described in Appendix 1. See section 4.0 for further instructions on how to complete itCOVER. Incomplete packages and requests received after or at the same time the submission is received will not be accepted.

If the application is accepted, the sponsor submits a complete application for the drug to Health Canada within 60 calendar daysbut not before, the date of issuance of the notice of acceptance. See section 3.3 for information on filing a priority filing.

Requests for priority testing should be sent to the competent administration below:

Department of Biological and Genetic Therapies (select one)

For biotherapeutic and radiopharmaceutical submissions:

Director of the Center for Evaluation of Radiopharmaceuticals and Biotherapeutics
c/o Directorate for Regulatory Affairs - Biotherapy and Quality
Directorate for Biological and Genetic Therapies
Health Canada
Building #7, address search 0701A
200 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0L2
Fax: 613-946-9520

For blood products and vaccines:

Director of the Center for Biological Assessment
c/o Directorate for Regulatory Affairs - Blood, Tissues, Organs and Vaccines
Directorate for Biological and Genetic Therapies
Health Canada
Building #7, address search 0701A
200 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0L2
Fax: 613-941-1708

Die

Therapeutic Products Division (select one)

Director, Institute for Metabolism, Oncology and Reproductive Sciences (BMORS)
c/o Regulatory Administration for Project Management in the service of BMORS
Therapeutic Products Administration
Health Canada
Financial Building #2, address search 0202D2
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 1B9
Fax: 613-941-1365

Director of the Institute for Gastroenterology, Infectology and Infectious Diseases (BGIVD)
c/o Regulatory Administration for Project Management in the service of BGIVD
Therapeutic Products Administration
Health Canada
Financial Building #2, address search 0202B1
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 1B9
Fax: 613-941-1183

Director, Institute of Cardiology, Allergy and Neurological Sciences (BCANS)
c/o BCANS-Service Project Management Regulatory Authority
Therapeutic Products Administration
Health Canada
Financial Building #2, address search 0202A1
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 1B9
Fax: 613-941-1668

Director, Institute of Pharmaceutical Sciences (BPS)
c/o Regulatory Administration for Project Management in the service of BPS
Therapeutic Products Administration
Health Canada
Financial Building #2, address search 0201D
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 1B9
Fax: 613-957-3989

3.3 Review, approval and application submission

Upon receipt,COVER(i.e. request) will be reviewed by the Shipping Administration to ensure that all mandatory sections have been completed. TheCOVERIt is then forwarded to the appropriate research department for assignment to a clinical evaluator.

The clinical investigator may request additional supporting information to support and clarify the information provided in the priority trial request. The sponsor is obliged to submit all additional information necessary for the evaluation within two (2) working days from the submission of the application. In the event that additional information is not received within the above timeframe, the decision to accept or deny the request for priority review status will be based on the information provided in the original request, subject to the interpretation of the Health Canada assessor.

Health Canada will notify the sponsor of the decision to accept or deny priority trial status within 30 calendar days of receipt of the request. If the application is accepted, the sponsor submits a complete application for the drug to Health Canada within 60 calendar daysbut not before, the date of issuance of the notice of acceptance.

Submissions received prior to the acceptance letter are subject to review and, if deemed acceptable, will be queued for review as a non-priority submission. Consideration of the application for priority related to the submission ends immediately upon receipt of the submission.

3.4 Review

If priority review status has been assigned, the submission will be reviewed in accordance with the reduced review goal of 25 days.

The request may be submitted to the appropriate Directorate of Examinations and subject to review while the denial of priority review status is being considered. In the event that priority review status is assigned as a result of a review request, the review objective will be adjusted accordingly from the date of approval of review acceptance.

3.5 Denial of Priority Review Requests

A request for priority review status may be denied for reasons including, but not limited to:

The following reasons are not considered reasons for rejecting a request for priority examination:

3.6 Review Process for Priority Review Requests

In the event that the initial request for priority review is denied, sponsors may apply for a review of the decision in accordance with the process outlined in the Health Canada guidelines:Guidelines for the industrial review of final decisions on the use of medicinal products for human use.

According to section 5.1 of the Health Canada Guideline:Guidelines for the industrial review of final decisions on the use of medicinal products for human use, rejection of the first or second request for rejection of priority examination in accordance withPriority review policyit is suitable for re-examination. However, sponsors may request reconsideration only for a first refusalDiefile a second priority review request – perhaps not both.

The request can be submitted to the competent Directorate for Examinations and submitted to examination while the rejection examination is in progress. In the event that priority review status is assigned as a result of a review request, the review objective will be adjusted accordingly from the date of approval of review acceptance.

3.7 Resubmission of a request for priority review status

Instead of submitting a request for reexamination, sponsors may submit a second request for an additional review of the same indication after a period of 60 days from the date of the first request. New information must be evident to demonstrate the submission's priority review status, ie H. Results of ongoing clinical studies. If no new information is submitted, the application will be rejected. Re-analysis of data to clarify the reasons for rejection of the original application is part of the review process and cannot be used as a basis for a second application.

Sponsors resubmitting Requests for Priority Review must comply with the procedures set forth in Section 4 b) through f) of the Priority Review Policy. In the event that another request for priority status is rejected based on the same statement, further requests will not be accepted. In the event that the status of the second priority request for review is denied, sponsors may submit a request for review of the second decision.

4.0 Completion of the clinical evaluation package (COVER)

Clinical Assessment Package (COVER) must be in a format similar to that described in Appendix 1. The extent must not exceed 20 pages^{footnote 3}long and consists of the following elements:

5.0 Termination of Priority Review Status

Priority review status is reassessed by issuing a non-compliance notice (NO) or notification of defects (NOD). Sponsors will receive formal notification of Health Canada's decision to continue or deny priority trial status, based on whether pre-priority trial status conditions still apply.

If there is more than one submission for medicinal products for the treatment, prevention or diagnosis of the same disease or condition, and a statement of compliance has been issued for one of the submissions, the priority review status of the remaining submissions will remain as one until such timeNODieNODPriority status is assigned and reassessed.

Since it is impractical to stop the review once it has started and in the interest of greater transparency, the review of the submission will continue until the endNO/NODis issued, regardless of version aNOCand subsequent commercialization of products with the same label.

6.0 Related Resources

7.0 Supplements

Appendix - 1 - Clinical Evaluation Package

Date of application:

Sponsor:

Contact information:

Section 1: General information (required)

Own or common name:

Specific information required:

Regulatory status of the drug worldwide:

Section 2: Severe, life-threatening, severely disabling (Mandatory)

**Sponsors must complete Section 3 or 4**

Section 3: "Effective treatment, prevention or diagnosis of a disease or condition for which there is currently no drug on the market in Canada"

Section 4: "A significant increase in efficacy and/or a significant reduction in risk such that the overall benefit-risk profile is insufficient compared with existing treatments, prophylactics or diagnostics for the disease or condition controlled by the drug marketed in Canada." is improved.”

Provide justification for the overall improvement in the benefit-risk profile over treatments currently available on the Canadian market and explain that there is no other drug on the Canadian market that offers the same therapeutic profile.

Section 5: Clinical evidence (mandatory)

This domainmorainclude the following:

Section 6: Additional information (required)

The following question is for informational purposes only.

Appendix - 2 - Frequently Asked Questions/Comments (Questions)