Post-Notice of Compliance changes: Guidance for safety and efficacy of veterinary drugs: Reporting categories

On this page

• Level 1 changes: Supplements
• Level 2 changes: Notifiable changes
• Level 3 changes: Annual notifications

This section of the guidance provides criteria and examples to help you classify a safety or efficacy related change. Examples are not exhaustive and are meant to provide guidance on types of acceptable changes.

Contact the Veterinary Drugs Directorate submission office if you have questions or need help.

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

Level 1 changes: Supplements

Criteria

Level 1 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. These are changes to the label of a drug that have the potential to increase the exposure levels of the drug, either by:

• increasing individual exposure or
• expanding the exposed population (market)

Label changes that can result in increased exposure levels of the drug include the:

• addition of a:
  • new strength
  • new dosage form
  • new route of administration
  • change in duration of treatment
  • change in recommended dose or dosing range
• deletion or reduction of existing risk management measures
• addition or expansion of a safety claim or efficacy claim, whether explicit or implied

This level also includes changes that don't meet the above criteria, but require the filing of a Level 1 change as per C.08.003 and C.08.005.1 of the Regulations. Examples include:

• Significant changes exclusive to label design elements.
• A submission for the purpose of obtaining a data protection extension.
• The brand name of the new drug has been changed, but the Drug Identification Number (DIN) remains the same.
• An existing indication has been modified or withdrawn in its entirety for risk or harm management, including a reduction in scope.
• An existing route of administration, dosage form and/or strength has been removed following the cancellation of the DIN(s).
• A submission for the purpose of obtaining data protection extension.

Learn more about:

• Data protection extensions

Examples

Examples of Level 1 changes include but are not limited to the following:

Changes to label text

Health Canada initiated label changes that may include, but are not limited to:

• the addition of a warning or caution
• the addition of a new contraindication
• a change in an existing contraindication
• tightening of clinical monitoring that requires a change to the labels or sections of the package insert

Changes to existing label text that reference any potential benefits of the drug (implied or explicit), including references to:

• possible claims regarding side effects
• claims regarding the safety profile or efficacy
• sub‐populations, such as different age groups (puppies versus dogs) or production types (dairy versus beef cattle)

An existing contraindication, warning or cautionary text anywhere in the package insert that has been:

• deleted in its entirety
• modified to reflect a reduction or diminishment in:
  • risk or harm
  • a risk management measure
  • an existing withdrawal or withholding period

Note: changes from existing contraindications, warnings or cautionary texts may result from a range of supporting data, such as post‐marketing data, safety studies and pharmacokinetic data.

Reordering text on the label necessary for the safe and effective use of the product, such as:

• moving label information to different panels
• changing the order of information presented on the principal display panel, including:
  • warnings
  • population
  • expression of strength
  • product name (proprietary and non‐proprietary)

Examples of other label text changes may also include:

• A response to a Health Canada‐issued advisement letter specifically soliciting a labelling only Supplement to an Abbreviated New Drug Submission.
• Changes regarding an adverse event or set of events to reflect an apparent reduction in risk or harm. This includes changes related to non‐target species data.
• The existing text of the label or package insert has been deleted, reworded or otherwise modified to diminish a risk or harm management measure. This would include any change in the conditions of use as a result of new pharmacokinetic data related to a special or sub‐population or new species.

Changes based on new data

These changes can include, but are not limited to, the addition of:

• a new species
• a delivery device
• a new route of administration
• a new dosage form or strength
• a revision to existing text of a current indication that received a NOC and was subsequently withdrawn
• a new indication or reintroduction of an indication that received a NOC and was subsequently withdrawn
• data from an efficacy or safety study in a special population

Other examples of these changes can also include:

• a change in condition of use from prescription to non‐prescription status
• a change to the safety and efficacy study information of the package insert which results in a new claim, explicit or implied, such as:
  • listing of additional outcome measures
  • revision to the description of study design that implies a new benefit for a specific sub‐population
• a change in the drug's mechanism of action that results in an explicit or implicit claim (as detailed in the clinical pharmacology for veterinary drugs section of the package insert)

Changes to label design

Changes to label design can include, but are not limited to:

• adding an innovative label to a package
• changing the size or colour of text or background in connection with:
  • product name (proprietary and non‐proprietary)
  • dosage and strength
  • population
  • route of administration
  • warnings
  • storage
• changing the package design, where the package is the immediate container
• changes that will impact readability of key elements of the inner or outer label, such as:
  • reducing overall label size
  • increasing the size of company logo or graphics
  • adding new graphics or symbols other than symbols required by regulations
  • changing locations of graphics (such as adding a symbol related to the type of packaging)

Submission filing

File changes included in this reporting category, along with the recommended supporting data, with Health Canada as a:

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

Do not implement Level 1 changes until you receive a NOC.

Level 2 changes: Notifiable changes

Criteria

A Level 2 notifiable change is a change to the label that could improve the management of risks or harms to the population currently indicated for use of the drug, or in any other way exposed to the drug by:

• identifying or characterizing any risk or harms
• identifying subgroups or conditions of use where the benefit or risk profile of the new drug could be less favourable
• adding or strengthening risk management measures, including instructions on dosing or any other conditions of use

Examples

Examples of Level 2 changes include, but are not limited to:

Changes to label text

Text additions that strengthen or clarify information anywhere in these labelling sections:

• cautions
• warnings
• adverse events
• contraindications

These additions may include recommended risk or harm management actions such as:

• ensuring awareness of certain risks
• specific monitoring during product use
• required testing prior to initiation of the drug

These additions may also include the identification that a specific sub‐population is at greater risk, such as:

• a specific age group
• those with a concomitant condition
• those taking concomitant medicine

These changes can also include:

• changes made to these sections of the package insert:
  • toxicology
  • microbiology
  • pharmacology
• changes related to the overdose section, such as additional overdose signs or treatments
• improving the clarity of the information in the animal owners section of the package insert
• revisions to existing label text to add clarity to the safe use of the drug, but without expanding, explicitly or implied, the claims of the drug
• rewording or altering the package insert, including dosage and administration, with respect to risk or harm management to optimize the safe use of the drug

Changes based on new data

Examples of these changes can include, but are not limited to:

• An existing drug interaction has been better characterized.
• Additions or changes to text or data (other than Level 3 changes):
  • for which the sponsor is not seeking a statement that may be interpreted as a new claim
  • that do not result in any other changes to the information provided to the veterinarians or animal owner
• A change to the toxicology data, explicitly or implied, stating an increase in risk or harm to the target population.
• A new drug interaction or pharmacokinetic study has been added and does not expand the claim of the drug, explicitly or implied.

Submission filing

File any changes included in this reporting category to Health Canada as a Level 2 notifiable change. Include your recommended supporting data. Sponsors should not implement Level 2 changes until issued with a No Objection Letter.

Note: Some changes that meet the Level 2 criteria may require sponsors to file a Level 1 change.

Level 3 changes: Annual notifications

Criteria

Level 3 or annual notifications are changes to a label that have minimal potential to impact the safety, efficacy or effective use of the drug. Sponsors can implement changes included in this reporting category without Health Canada reviewing the data supporting such a change beforehand.

Examples

Examples of Level 3 related changes include but are not limited to:

• Any change in spelling of the text of the label, including correcting spelling errors
• Any change to the layout of the label that does not represent a change to the requirements of:
  • the terms of market authorization
  • Sections C.01.004 and A.01.016 of the Regulations (such as font, contrast, artwork and position)
• The existing text of the labels have been revised to add clarity and maintain consistency with common label phrase standards, such as 'Keep out of reach of children'.

For non‐prescription drug products, examples of Level 3 changes include but are not limited to the following non‐significant label changes:

• Correcting spelling errors
• Updating contact information such as:
  • website addresses
  • a customer service number

Submission filing

File your notification of a Level 3 label change:

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

Only submit a copy of revised annotated labels and package inserts when you file the next Level 1 or 2 changes that necessitate a label or quality change as well. Clearly identify the implementation dates for these Level 3 changes.

Do not submit supporting data for Level 3 changes recommended in this guidance document. However, the data should be available to Health Canada within 30 calendar days of a request.

File your changes using the Post-Notice of Compliance changes: Level 3 form.