Post-Notice of Compliance (NOC) Changes: Guidance for quality of veterinary drugs: Classification – reporting categories

On this page

• Introduction
• Level I: Supplements
• Level II: Notifiable Changes
• Level III: Annual Notification
• Level IV changes: Record of changes

Introduction

The following criteria are meant to provide guidance with respect to the classification of a quality related change. Specific change examples based on the application of these criteria are provided in the post-NOC change examples sections (for drug substances or drug product ) of this guidance document.

We advise sponsors to exercise caution in classifying a series of changes for the same drug product intended to be implemented simultaneously or to be phased in sequentially. Although the individual changes may be classified at a particular reporting category (such as Notifiable Change), collectively, the changes may warrant a higher risk reporting category (such as Supplement). Refer to the multiple changes section for more information.

If the submission has been inappropriately classified, we will notify the sponsor at the screening stage. Contact the Veterinary Drugs Directorate for assistance in classifying a change or a series of changes.

Email: vdd.skmd.so-dgps.dmv.cp@hc-sc.gc.ca

Level I: Supplements

Level I: Supplements (major quality changes) are changes to a new drug that:

• are "significantly different" as it relates to the matters specified in C.08.003 (2) of the Regulations and
• have the potential to have an adverse effect on certain factors of the drug product, as they may relate to its safety or effectiveness. These factors are:
  • purity
  • quality
  • potency
  • identity
  • strength

In general, a change that is supported by extensive documentation or requiring extensive assessment of the supporting documentation would be considered a Level I: Supplement (major quality change. For example, a change supported by in vivo studies. This gives Health Canada the opportunity to apply the principles of risk management by having the necessary time for an appropriate assessment of the documentation.

This assessment will consider:

• any potential impact upon market availability
• the adverse effects on the drug product's:
  • purity
  • quality
  • potency
  • identity
  • strength

The changes included in this reporting category shall be filed, along with the recommended supporting data, to Health Canada as a:

• Supplement to a New Drug Submission (SNDS) or
• Supplement to an Abbreviated New Drug Submission (SANDS)

The sponsor may not implement the change until a NOC has been issued.

Level II: Notifiable Changes

Level II: Notifiable Changes (moderate quality changes) are changes that have a moderate potential to have an adverse effect on certain factors of the drug product, as they may relate to its safety or effectiveness, but do not require an issuance of NOC. These factors are:

• purity
• quality
• potency
• identity
• strength

File changes included in this reporting category to Health Canada as a Notifiable Change, along with the recommended supporting data. Sponsors should not implement any Level II changes until a No Objection Letter (NOL) has been issued.

Level III: Annual Notification

Level III: Annual Notification (minor quality changes) are changes that have minimal potential to have an adverse effect on certain factors of the drug product, as they may relate to its safety or effectiveness. These factors are:

• purity
• quality
• potency
• identity
• strength

The sponsor may implement the changes included in this reporting category without the prior review of the data supporting such a change by Health Canada. Submit all Level III changes using the Post-Notice of Compliance Changes: Notices of Change of Veterinary Drugs: Level III Form:

• at the time the proposed change is implemented or
• during the annual drug notification period in accordance with C.01.014.5 of the Regulations

Level IV Changes: record of changes

Level IV (Quality only) changes are changes to a new drug that are not:

• Level I, Level II or Level III
• expected to have an adverse effect on certain factors may relate to the safety or effectiveness of the drug product. These factors are:
  • purity
  • quality
  • potency
  • identity
  • strength

The sponsor may implement changes included in this reporting category without prior review by Health Canada. The changes should:

• be retained as part of the drug product's record by either the sponsor or the manufacturer
• comply with Good Manufacturing Practices (GMP) requirements of Division 2 of the Regulations

A list of examples of Level IV changes is provided in Appendix 3 of this guidance document.