Reader's Guide to the Phase II Summary Basis of Decision (SBD) - Drugs

(PDF Version - 111 K)

Date: June 29, 2012

The Reader's Guide to the Phase II Summary Basis of Decision (SBD) - Drugs describes the new Phase II question and answer format of the SBD documents. It includes a summary of information found in the response to each question.

For more information related to the SBD Project, please refer to the Frequently Asked Questions: Summary Basis of Decision Phase II.

Title

The introductory lines of the SBD list the brand name of the product, along with the active ingredient(s), strength(s), dosage form(s), route(s) of administration, and the Drug Identification Number(s) (DIN).  The sponsor to which the Notice of Compliance (NOC) was issued is listed, as is the Health Canada control number for the new drug submission.

Introduction

The first paragraph of the SBD describes the authorization issued to the drug product, including whether the submission was reviewed as per the Priority Review Guidance and whether the NOC was issued under the Notice of Compliance with Conditions (NOC/c) Guidance.

The second paragraph gives a very high-level description of the data submitted, and links to Questions 2 (Why was <Brand Name> approved?) and 7 (What was the scientific rationale for Health Canada's decision?). The approved indication is given in plain language, as per the Product Monograph Part III: Consumer Information.

Q1. What was approved?

The answer to this question first gives a description of the therapeutic classification of the product as well as the approved indication, in more technical language (as per the Product Monograph Part I: Health Professional Information). This is followed by a description of contraindications associated with the product.

A description of the product itself follows, including the strength(s), active ingredient(s) and dosage form(s). A list of non-medicinal ingredients is provided.

This answer will then link to Question 7 (What was the scientific rationale for Health Canada's decision?).

A link to the Drug Product Database (DPD) is provided so the reader can access the Product Monograph (PM) for more detailed product information approved by Health Canada. The PM is a factual, scientific document on a drug product that, devoid of promotional material, describes the properties, claims, indications and conditions of use for the drug and contains any other information that may be required for optimal, safe and effective use of the drug. Health Canada reviews this Product Monograph as part of the drug review process. Please note that the DPD contains information on products that have been approved for use in Canada and have been market notified (that is, the company has told Health Canada the product is being marketed). Therefore the product may not yet be listed in the DPD and the PM may not yet be available online.

Q2. Why was <Brand Name> approved?

The answer to this question provides an outline of the benefit/risk assessment that was conducted by Health Canada prior to issuing the NOC for the product.

Included in this section is a description of the nature and severity of the disease or condition and its consequences. The analysis of the benefits of the product with respect to this disease or condition includes a description of the efficacy information collected from the pivotal trials and may include information related to specific subpopulations expected to receive particular benefit.

Also included in this answer is a description of the potential risks inherent with the use of the drug, including a summary of the most important adverse events and reactions, and strategies for mitigating the risks.

If the product was reviewed as per the Priority Review Guidance or authorized as per the Notice of Compliance with Conditions (NOC/c) Guidance, the rationale for applicability of the relevant guidance will be discussed.

The next paragraph(s) will consist of an overall conclusion about the balance of benefits and risks associated with the use of the product, which may take into account treatment effects, disease, targeted population and existing therapies. An outline of risk mitigation strategies will be described, which may include specific text in the PM, a Risk Management Plan (RMP), etc.

This section will conclude with a reference to the authorization of the product as per the Food and Drug Regulations and a link to Question 7 (What was the scientific rationale for Health Canada's decision?) for more detailed scientific information.

Q3. What steps led to the approval of <Brand Name>?

This answer will describe the submission process that led to the authorization of the product. It will include a description of (as applicable) negative decisions issued prior to NOC issuance, requests for reconsideration, and re-filed submissions. It will also describe the process Health Canada followed in reviewing this submission, including if the submission was granted or denied priority review status, whether issues were referred to an external committee for deliberation, whether a foreign review was used in the decision-making process, etc.

A table describing the submission milestones is included in this section, along with applicable dates. Included in this table are pre-submission activities such as meetings, dates of filing and decision for requests for priority review status or advance consideration under the Notice of Compliance with Conditions (NOC/c) Guidance, and the date of submission filing. Notices issued during the process (including screening deficiency notice, rejection letter, notice of deficiency, notice of non-compliance, etc.) will be described with the associated dates. Significant review milestones such as the completion of clinical, quality, biostatistics, labelling, and RMP review will be included as appropriate.

This answer concludes with a link to the Management of Drug Submissions Guidance for more information about the drug submission process.

Q4. What follow-up measures will the company take?

At a minimum, this answer will include a link to the Food and Drug Regulations to describe the post-authorization requirements for the sponsor. In addition, the conditions the sponsor has agreed to meet post-authorization will be described including a description of follow-up measures described in the Letter of Undertaking for products authorized under the Notice of Compliance with Conditions (NOC/c) Guidance.

Q5. What post-authorization activity has taken place for <Brand Name>?

The answer to this question will include a link to the post-authorization activity table (PAAT) for the product, once one has been made available. The PAAT will include brief summaries (normally one paragraph) of activities that impact the safe and effective use of the product. Examples of information found in the PAAT include a submission for a new use of the product (whether Health Canada's decision was positive or negative), changes to the labelling or the Product Monograph, as well as regulatory decisions such as the cancellation of the Drug Identification Number (DIN). Also included will be post-authorization submissions filed to fulfil conditions for drugs authorized under the Notice of Compliance with Conditions (NOC/c) Guidance. Links will be provided to appropriate regulations and guidance documents so that readers will better understand the terminology used in the PAAT.

Q6. What other information is available about <Brand Name>?

The answer to this question includes a link back to the introductory page for the product, which contains links to a number of Health Canada webpages, including:

Q7. What was the scientific rationale for Health Canada's decision?

The answer to this question provides scientific information in support of Health Canada's decision to authorize the product on the basis of the clinical, non-clinical, and quality information submitted.

Clinical Basis for Decision

Clinical Pharmacology

This section includes a very brief description of the disease, the mechanism of action of the drug, and a brief analysis of the clinical pharmacology results. Safety concerns that were identified in the pharmacology studies are discussed, as well as any actions taken to confirm or dismiss the concerns.

If Health Canada used a foreign review in its evaluation of the clinical pharmacology studies (in accordance with the Draft Guidance Document - The Use of Foreign Reviews by Health Canada), this will be discussed.

A link to the Drug Product Database is provided so the reader can access the PM for more detailed product information approved by Health Canada.

Clinical Efficacy

This section includes the total number of studies (pivotal and non-pivotal) conducted to support authorization as well as the total number of subjects followed by the study design. Each pivotal study is described, including study design, number of subjects, demographics and baseline characteristics of patients, primary and secondary endpoints, secondary objective(s), and results.

The majority of this section will contain Health Canada's analysis of the results of the studies that figured significantly in Health Canada's decision. An overall analysis of the clinical efficacy, including any information that has been amended to the PM is also included.

If the product was reviewed under the Priority Review Guidance, the rationale for applicability of the guidance will be discussed as it relates to clinical efficacy.

If Health Canada used a foreign review in its evaluation of the clinical efficacy (in accordance with the Draft Guidance Document - The Use of Foreign Reviews by Health Canada), this will be discussed.

Bioequivalence studies, clinical studies in special populations, supportive studies, and microbiology studies are also discussed if they figured significantly in Health Canada's decision.

Limitations of the efficacy data are discussed, along with Health Canada's assessment of the data submitted by the sponsor to address the concerns. If the submission was evaluated under the Notice of Compliance with Conditions Guidance, a discussion of the limitations of the efficacy data that required further confirmatory studies is included.

If, throughout the course of the submission the indication as originally submitted by the company changed, this will be discussed along with the rationale. In addition, if the submission was previously rejected, this section will include a discussion of the rationale for the rejection along with how the sponsor has addressed Health Canada's concerns within the current submission. A link to the Drug Product Database is provided so the reader can access the PM for more detailed product information approved by Health Canada.

Clinical Safety

This section includes the total number of studies (pivotal and non-pivotal) conducted to support authorization as well as the total number of subjects followed by the study design (note this may be linked to the Clinical Efficacy section to avoid repetition).

The majority of this section will contain Health Canada's analysis of the results of the studies that figured significantly in Health Canada's decision. This will include a description of patient exposure, description of adverse events and serious adverse events/deaths, discontinuations due to adverse events, laboratory findings, safety in special populations, etc. Special considerations may also be discussed, for example QT prolongation.

An overall analysis of the clinical safety, including any precautions, contraindications, etc. that have been added to the labelling/PM, is also included.

If the product was reviewed under the Priority Review Guidance, the rationale for applicability of the guidance will be discussed as it relates to clinical safety.

If Health Canada used a foreign review in its evaluation of the clinical safety (in accordance with the Draft Guidance Document - The Use of Foreign Reviews by Health Canada), this will be discussed.

An outline of risk mitigation strategies will be described, which may include specific text in the PM, RMP, etc.

Post-market safety information from other jurisdictions may be included in this section if it was considered as part of the basis for decision.

If the submission was rejected previously for safety concerns, the limitations of the safety data are discussed, along with Health Canada's assessment of the data submitted by the sponsor to address the concerns.

A link to the Drug Product Database is provided so the reader can access the PM for more detailed product information approved by Health Canada.

Non-Clinical Basis for Decision

This section will include a summary of the results of the non-clinical studies and Health Canada's assessment. There may be additional information if there were concerns identified from the non-clinical studies, particularly if they could have clinical relevance.

An overall analysis of the non-clinical assessment, including any information added to the labelling/PM, is also included.

If Health Canada used a foreign review in its evaluation of the non-clinical studies (in accordance with the Draft Guidance Document - The Use of Foreign Reviews by Health Canada), this will be discussed.

A link to the Drug Product Database is provided so the reader can access the PM for more detailed product information approved by Health Canada.

Quality Basis for Decision

This section will have different information depending on whether the product is a pharmaceutical or a biological drug. The submissions that will be the subject of an SBD are described in the Frequently Asked Questions: Summary Basis of Decision Phase II. Pharmaceuticals are mostly synthetic products made from chemicals for therapeutic use. Biologicals are products derived from living sources; some examples are vaccines, enzymes, monoclonal antibodies, and radiopharmaceuticals.

If Health Canada used a foreign review in its evaluation of the quality studies (in accordance with the Draft Guidance Document - The Use of Foreign Reviews by Health Canada), this will be discussed.

Pharmaceutical:
This section will include a summary of the types of studies conducted to verify the quality of the drug substance (medicinal ingredient) and drug product (final dosage form), and Health Canada's assessment. A statement about the compliance of the production sites with Good Manufacturing Practices is included, as is a statement about the compliance of the non-medicinal ingredients with the Food and Drug Regulations. If applicable, an assessment of whether the excipients are of animal origin and from a bovine spongiform encephalopathy and transmissible spongiform encephalopathy (BSE/TSE) affected country/area is included.

Biologics
This section will include a more detailed description of the studies conducted to verify the quality of the drug substance (medicinal ingredient) and drug product (final dosage form), and Health Canada's assessment. Headings may include:

  • Characterization of the Drug Substance (including Health Canada's assessment of the structural and physico-chemical, biological and/or immunological characterization studies of the medicinal ingredient, and an assessment of impurities arising from the manufacturing process);
  • Manufacturing Process and Process Controls of the Drug Substance and Drug Product (including Health Canada's assessment of the method of manufacture for the drug substance and final product);
  • Control of the Drug Substance and Drug Product (including Health Canada's assessment of the tests conducted to verify that the drug substance and drug product can be manufactured consistently);
  • Stability of the Drug Substance and Drug Product (including Health Canada's assessment of the stability testing conducted to verify the proposed shelf-life for the drug substance and drug product);
  • Facilities and Equipment (including Health Canada's assessment of the facilities and equipment involved in production, and On-Site Evaluation(s) conducted);
  • Adventitious Agents Safety Evaluation (including Health Canada's assessment of measures taken to avoid and control non-viral adventitious agents during manufacture).
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