Draft guidance on terms and conditions for human and veterinary drugs: Overview

On this page

• Purpose
• Introduction
• Scope and application
• Policy objectives and statements
• Definitions
• Note about guidance documents in general

Purpose

This document provides guidance to manufacturers and Health Canada staff on the use of the terms and conditions (T&Cs) regulatory authority in accordance with Part C, Division 1, section C.01.014.21 of the Food and Drug Regulations (FDR).

Introduction

The Food and Drugs Act (FDA) and its regulations give Health Canada the authority to regulate food, drugs (including natural health products and veterinary health products), medical devices and cosmetics. As a drug regulator, our role is to verify that regulatory requirements for the safety, efficacy and quality of human and veterinary drugs are met through scientific assessments. This includes issuing product and establishment licensing, conducting monitoring and surveillance, and carrying out compliance and enforcement activities.

To be authorized for sale in Canada, drugs for human and veterinary use (excluding natural health products and veterinary health products) must meet certain requirements under the FDR. They must also satisfy all applicable requirements in Part C, Division 1. As well, drugs that meet the definition of a new drug under Part C, Division 8 of the FDR must also satisfy the requirements of Division 8 to be authorized for sale.

When we authorize a drug to be marketed in Canada, we assign a drug identification number (DIN) to the manufacturer, which is printed on the package labels. A DIN indicates that the evaluation of the drug determined that it met the relevant requirements of the FDA and its regulations, and that it has a favourable benefit-risk profile.

Manufacturers of prescription and non-prescription drugs must obtain a DIN before they are marketed in Canada. For new drugs that fall under Division 8 of the FDR, market authorization requires that a notice of compliance (NOC) also be issued.

The DIN assigned to a drug is unique and helps with the post-market activities of products on the market, such as:

• product identification and verification by health care professionals
• recall of products
• inspections
• quality monitoring

For information on DINs, refer to:

• Guidance document: Regulatory requirements for drug identification numbers (DINs)

On December 6, 2013, the Government of Canada introduced the Protecting Canadians from Unsafe Drugs Act (Vanessa's Law). On November 6, 2014, it received Royal Assent.

Vanessa's Law introduced amendments to the FDA that allow implementing a lifecycle approach to regulating drugs and medical devices. These amendments improve our ability to collect post-market safety information and take appropriate action when we identify a serious risk to health. We introduced these amendments to better protect patient health and safety and increase consumer confidence in therapeutic products on the market.

The Vanessa's Law amendments also gave the Governor in Council the authority to make regulations under the FDR and the Medical Devices Regulations (MDR) that support the life-cycle approach to regulating drugs and medical devices.

The rapid pace of innovation in industry can lead to significant uncertainties and risks for therapeutic products. These may not be adequately managed through existing regulatory provisions. For this reason, we amended the FDR to include new authorities that allow T&Cs to be imposed and amended on the DIN of a drug. T&Cs are obligations on the market authorization holder (MAH). These obligations may include conducting activities related to the authorized drug when significant uncertainties about a drug's benefits or risks have been identified or to manage identified or potential risks of a drug.

Scope and application

This draft guidance document applies to drugs regulated under Part C, Division 1 of the FDR that are assigned a DIN and the application of T&Cs. It explains the purpose of T&Cs and the processes that apply for imposing them on a DIN.

For this document, "drug" is for human and veterinary use (excluding biocides, natural health products, veterinary health products and some veterinary biologics) and includes:

• pharmaceuticals
  • prescription
  • non-prescription
• biologics
  • therapeutic products made from living organisms or cells
  • vaccines (for human use which includes prescription and non-prescription)
• radiopharmaceuticals

Policy objectives and statements

For a drug to be considered for market authorization, it must be supported by sufficient information as required by the FDR. Data establishing the safety, efficacy and quality of a drug must demonstrate a favourable benefit-risk profile.

T&Cs are a regulatory authority that can be applied for appropriate oversight of an authorized drug's safety, efficacy and quality throughout its lifecycle. The main objective of imposing T&Cs is to ensure that the drug maintains its favourable benefit-risk profile.

T&Cs may be used to manage a drug's:

• significant uncertainties
• known or anticipated risks

T&Cs are not intended to be used to address deficiencies in a drug submission. They cannot be imposed to gather required information to support a drug submission or application where a manufacturer is seeking authorization to market the drug where the submission does not otherwise meet the requirements for authorization.

Before imposing T&Cs, we will consider if other regulatory mechanisms can address any identified risks or significant uncertainties. We will consider whether the obligations imposed using T&Cs are technically feasible and whether less burdensome means exist to achieve those objectives.

We will impose T&Cs fairly and consistently, and regulated parties will have an opportunity to be heard. T&Cs can be amended at any time during the lifecycle of a drug. MAHs are responsible to fulfill their T&Cs by the date specified in their T&C letter. MAHs that do not comply with their T&Cs may be held criminally liable.

Definitions

Biosimilar drug ("biosimilar")

A biosimilar is a biologic drug that is highly similar to a biologic drug that was already issued market authorization, such that there are no expected clinically meaningful differences in efficacy and safety between the biosimilar and the biologic drug that was already authorized for sale.

Clinical benefit

Outcomes that have positive impact on the course of a disease.

Canadian reference product (CRP)

As per section C.08.001.1 of the Food and Drug Regulations, CRP means:

1. a drug in respect of which a notice of compliance is issued pursuant to section C.08.004 and which is marketed in Canada by the innovator of the drug
2. a drug, acceptable to the Minister, that can be used for the purpose of demonstrating bioequivalence on the basis of pharmaceutical and, where applicable, bioavailability characteristics, where a drug in respect of which a notice of compliance has been issued pursuant to section C.08.004 cannot be used for that purpose because it is no longer marketed in Canada or
3. a drug, acceptable to the Minister, that can be used for the purpose of demonstrating bioequivalence on the basis of pharmaceutical and, where applicable, bioavailability characteristics, in comparison to a drug referred to in paragraph (a)

Canadian reference biologic drug (CRBD)

A biologic drug previously issued market authorization and used as a comparator to support market authorization of a biosimilar biologic drug ("biosimilar"). There are no expected clinically meaningful differences in efficacy and safety between a biosimilar and the biologic drug that was already authorized for sale.

Market authorization holder (MAH)

The market authorization holder (MAH) is also referred to as sponsor or manufacturer. The MAH is the legal entity that holds the NOC and the DIN.

Promising evidence of efficacy

Evidence based on well-designed and well-conducted clinical trials and veterinary studies establishing that the drug product has an effect on an acceptable surrogate or clinical endpoint that is reasonably likely to predict clinical benefit.

SNDS-C

Supplement to a new drug submission (SNDS) - confirmatory is to be filed to provide results from the confirmatory clinical trials and veterinary studies specified in the 'terms and conditions letter'.

Surrogate endpoint

Parameters based on available evidence which predict an effect of a drug on recognized clinical outcomes such as morbidity and mortality. A validated surrogate marker is predictive of the clinical benefit of a drug.

Note about guidance documents in general

Guidance documents provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. They also provide guidance to Health Canada staff on how mandates and objectives should be met fairly, consistently and effectively.

Guidance documents are administrative, not legal, instruments. This means that flexibility can be applied. However, to be acceptable, alternate approaches to the principles and practices described in this document must be supported by adequate justification. They should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As always, Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, to help us adequately assess the safety, efficacy or quality of a therapeutic product. We are committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read along with the relevant sections of the regulations and other applicable guidance documents.