Antiseptic Teat Solutions Monograph

Table of Contents

• 1. Foreword
• 2. Antiseptic Teat Solutions Monograph
  • 2.1 Quality Information
  • 2.2  Ingredient Information
    • 2.2.1 Medicinal Ingredients
    • 2.2.2 Non-medicinal Ingredients
    • 2.2.3 Acceptable Combinations of Medicinal Ingredients with Emollients
  • 2.3 Labelling Information (refer to Appendix 2 for an example of a mock-up label)
    • 2.3.1 Description
    • 2.3.2 Proper/Common Name
    • 2.3.3 Species
    • 2.3.4 Dosage Form
    • 2.3.5 Route of Administration
    • 2.3.6 Indications
    • 2.3.7 Mixing Directions for Products Containing Lactic Acid and Sodium Chlorite Only
    • 2.3.8 Directions for Use
    • 2.3.9 Cautions
    • 2.3.10 Warnings
    • 2.3.11 Storage Conditions
    • 2.3.12 Additional Labelling Information
  • 2.4 Changes to Drug Product Specification
  • 2.5 Reference Tables
  • 2.6 Glossary
• Appendix 1: DIN Submission Package
• Appendix 2: Example of Mock-up Label

1. Foreword

This monograph,

• has been developed for antiseptic teat solutions that have a well characterized safety and efficacy profile under specific conditions of use.
• describes the requirements necessary to receive market authorization for post-milking antiseptic teat solutions with or without a pre-milking indication, such as teat dips. Udder wash solutions and teat/udder wipes will not be considered under this monograph.
• outlines the permissible conditions of use and labelling requirements such as intended use, directions for use, warnings, medicinal (active) ingredients, emollients and combinations thereof.

When the product and its labelling are consistent with the information set out in the monograph,

• the product may be considered as a Not New Drug under Division 1 of the Food and Drugs Regulations.
• a sponsor or manufacturer may reference the monograph in the cover letter of a Drug Identification Number (DIN) submission.
• for more information on the DIN submission process, please refer to Appendix 1: DIN Submission Package.

When the product or its labelling falls outside the scope of this monograph,

• the product may be considered as a New Drug subject to Division 8 of the Food and Drugs Regulations.
• a classification template should be requested from hc.classification.vet.sc@canada.ca for a proper product status decision.
• if classified as a New Drug, the sponsor or manufacturer will have to submit additional evidence to support the safety, efficacy, and quality of the product when used according to the proposed conditions of use. Examples of these situations include, but are not limited to:
  • an ingredient and/or a combination of ingredients not provided for in the monograph;
  • a strength and/or directions for use not provided for in the monograph.
• for more information on the New Drug submission process, please refer to the Guidance for Industry Preparation of Veterinary New Drug submissions.

Please note that all products are subject to Good Manufacturing Practices (GMP) outlined in Part C, Division 2 of the Food and Drug Regulations whether or not the drug submission references a monograph.

It is important to note that Health Canada reserves the right to request information or material, or define conditions not specifically described in this monograph, in order to allow the Department to adequately assess the safety, efficacy or quality of a therapeutic product. Health Canada is committed to ensuring that such requests are justifiable and that decisions are clearly documented.

2. Antiseptic Teat Solutions Monograph

2.1  Quality Information

Data to support the information listed below should be held by the company and be available upon request.

• Formulation: List of all ingredients in the dosage form, their quality standards, and their amounts on a per unit basis;
• Specification(s) for the drug substance: Tests, acceptance criteria and description of the analytical procedures (refer to pharmacopoeial standards where applicable);
• Specification(s) for the dosage form: Tests, acceptance criteria and description of the analytical procedures;
• Certificate of analysis for one lot of the finished product of at least pilot scale batch size;
• Name and address of the fabricator and tester of the drug substance;
• Master formula for a typical batch size of the drug product and detailed description of the manufacturing process;
• Name and address of the fabricator and tester of the drug product; and
• Stability data to justify the proposed shelf life and storage conditions.

2.2  Ingredient Information

The strengths and combinations of medicinal ingredients and emollients are restricted to those specified in this monograph.

2.2.1 Medicinal Ingredients

Medicinal ingredients are considered as such when associated with germicidal activity at the proposed strength, and should be identified on product labelling by the proper/common names provided in Table 1. Some medicinal ingredients cannot be combined with any other medicinal ingredient in a product formulation, while others are only permitted when combined with one or more medicinal ingredient(s) (+/- emollients). The permitted strengths and/or range for all acceptable medicinal ingredients are provided in Table 1.

2.2.2 Non-Medicinal Ingredients

Non-medicinal ingredients should be restricted to the substances (and amounts) that are necessary for the formulation of the particular dosage form. Their concentration should not exceed the minimum required to provide their intended effect. They should not provide any therapeutic effect and should be harmless in the amounts used, their presence should not adversely affect the efficacy or safety of the medicinal ingredients, and they should not interfere with tests for the medicinal ingredients and, if present, antimicrobial preservatives.

• Emollients (Conditioning, Moisturizing Agents): Emollients are considered as such when associated with skin-conditioning activity at the proposed strength, and should be identified on product labelling by the proper/common names provided in Table 2. The permitted strength and/or range for all acceptable emollients are provided in Table 3.

2.2.3 Acceptable Combinations of Medicinal Ingredients with Emollients

Refer to Table 3 for a complete list of acceptable combinations (medicinal ingredients with emollients) within the context of this monograph.

2.3 Labelling Information (refer to Appendix 2 for an example of a mock-up label)

This monograph describes the requirements that are specific to this class of drugs. All other labelling requirements described in the Food and Drugs Act and Regulations must be respected.

2.3.1 Description

• Brand Name: Name assigned by the sponsor or manufacturer and approved by Health Canada in connection with a drug product.
• Product Descriptor: Required statement: [Post-Milking Antiseptic Teat Solution] or [Pre and Post-Milking Antiseptic Teat Solution], as applicable.
  1. A brand name or additional product description may contain one or more product attribute(s) that can serve as a basis for product identification. Product attributes should refer to the quality of the product and should be measurable, i.e. by reference to the product formulation only. Acceptable product attributes include reference to one or more non-medicinal ingredients (e.g. "XX surfactant" or "with emollients").
  2. Comparison and implied comparison terms used to describe the composition of drug products are not considered acceptable; for example, the terms "high" and "low" generally imply unidentified comparisons and standards against which a drug product must be measured. For antiseptic teat solutions, there are no existing standards in what constitutes "high" and "low" (e.g. concentrations of non-medicinal ingredients or product viscosity); therefore, these terms are unacceptable. Similarly, reference terms that describe the method of application or action of the product on application (e.g. foaming action) are not considered acceptable.
  3. When assigning a brand name, please be reminded that subsection 9(1) of the Act prohibits the representation of a drug "in a manner that is false, misleading or deceptive or is likely to create an erroneous impression regarding its character, value, quantity, composition, merit or safety."
  4. To ensure compliance with regulations, Health Canada reserves the right to request a scientific rationale for any brand name qualifier or additional product description associated with a formulation or formulation change which could potentially impact the impression of quality, safety and/or efficacy of the product under labelled conditions of use.

For more information on the use of product attributes, please refer to the Guidance Document: Labelling of Pharmaceutical Drugs for Human Use.

2.3.2 Proper/Common Name

Active ingredient(s) and dosage form

2.3.3 Species

Dairy cattle

2.3.4 Dosage Form 

Teat solution

2.3.5 Route of Administration

Topical

2.3.6 Indications

Required statements as applicable:
BRAND NAME is a [post-milking] or [pre and post-milking] antiseptic teat solution to be used as an aid in reducing the spread of organisms which may cause mastitis in dairy cattle.

2.3.7 Mixing Directions for Products Containing Lactic Acid and Sodium Chlorite Only

Required statements:
Measure equal volumes of BRAND NAME base and BRAND NAME activator into a clean container and mix until the color is uniform throughout. Do not dilute. Mix only enough product for one milking of the herd. Always use freshly mixed, full strength BRAND NAME.

2.3.8 Directions for Use

PRE-MILKING
Required statements:
Use at full strength. Do not dilute.
Before milking, apply BRAND NAME to each teat, ensuring complete coverage of all teats with the solution. After 15 to 30 seconds, dry each teat thoroughly. If the udder and teats are heavily soiled, clean with an antiseptic udder wash and dry thoroughly before application of BRAND NAME.

POST-MILKING
Required statements:
Use at full strength. Do not dilute.
Apply BRAND NAME to each teat immediately after milking. Ensure that the solution thoroughly covers the entire surface of all teats. Allow teats to dry. Do not wipe. If outside temperature is below 0 ᴼC, allow to air dry on the teats before turning cows out to cold weather to prevent freezing.
A fresh solution should always be used at each milking. The application equipment should be cleaned and rinsed properly after each milking session or when the solution becomes contaminated. Do not pour remaining solution back into the original container. Keep container closed to prevent contamination of the product.
Optional statements:
When a cow is being dried off, continue the application of BRAND NAME to all teats once daily for 1 to 2 weeks as required after the last milking. With freshening cows, resume application of BRAND NAME to all teats twice daily for 7 to 10 days before calving.

2.3.9 Cautions

Required statements:
For external use only. If cow's teats are sore, irritated or chapped, consult a veterinarian before starting or continuing to use antiseptic teat solution.

2.3.10 Warnings

Required statements:
No meat withdrawal period or milk withholding time is required when used according to the label. Avoid contact with food. Do not take internally. If accidentally ingested, drink large volumes of water. Avoid contact with skin and eyes. If accidental contact occurs, flush thoroughly with running water. Seek medical attention [immediately] OR [if symptoms occur or persist]^Footnote * after oral exposure or contact with skin and eyes. Avoid breathing vapours. Do not use for cleaning and/or sanitizing milking equipment. Keep out of reach of children.

2.3.11 Storage Conditions

Example:
Store between X °C and XX °C.

Note: Proposed storage conditions should be supported by appropriate stability data. Therefore, it is understood that additional label statements (e.g. Keep from freezing.) will be dependent upon product specifications.

2.3.12 Additional Labelling Information

• The labelling must be bilingual.
• The statement "For Veterinary Use Only" must appear on the principal display (main) panel.
• If used, alternate terms and/or statements must be consistent with those listed under this monograph and may be considered.

2.4 Changes to Drug Product Specification

Any changes that may impact the quality, safety and efficacy of the product should be reported to the VDD and additional information may be requested, including re-submission of the application as a New Drug.

2.5 Reference Tables

Table 1: Medicinal Ingredients (MI)

Proper/Common Name	Acceptable Strength or Range (% w/w)
For Post-Milking Products Only
Chlorhexidine acetateTable 1 footnote *	0.24 – 0.55
Chlorhexidine gluconateTable 1 footnote *	0.35 – 0.79
Iodine (titratable)	0.25 – 1.0
Linear dodecyl benzene sulfonic acid	1.94
For Pre or Post-Milking Products
Hydrogen PeroxideTable 1 footnote **	0.50
Iodine (titratable)	0.25 - 0.50
Lactic acidTable 1 footnote **	1.70 - 2.64
Sodium chloriteTable 1 footnote **	0.64
Sodium linear alkylate sulfonateTable 1 footnote **	0.50

Table 2: Emollients (Conditioning, Moisturizing Agents; Non-Medicinal Ingredients)

Table 3: Complete List of Acceptable Combinations and Strengths of Medicinal Ingredients (Single or Combined) and Emollients^{Table 3 footnote *}

Medicinal Ingredients (% w/w)	Emollients with Acceptable Strength or Range (% w/w)
For Post-Milking Products Only
Chlorhexidine acetate (0.24 –  0.55)	Glycerin (0 – 7)
Chlorhexidine gluconate (0.35 –  0.79)	Glycerin (2)
Iodine (titratable) (0.25 – 1.0)	Glycerin, Lanolin and/or Propylene Glycol (0 – 12)Table 3 footnote **
Linear dodecyl benzene sulfonic acid (1.94)	Glycerin (3)
For Pre and Post-Milking Products
Iodine (titratable) (0.25 – 0.50)	Glycerin (0 – 5)
Lactic acid (2.64) + Sodium chlorite (0.64)	Glycerin (0 – 10)
Lactic acid (1.70) + Hydrogen peroxide (0.50) + Sodium linear alkylate sulfonate (0.50)	Glycerin (5)

Table 4: List of Admissible Iodine Complexes

2.6 Glossary

Good Manufacturing Practices (GMP):

Part of quality assurance that ensures that drugs are consistently produced and controlled in such a way to meet the quality standards appropriate to their intended use, as required by the marketing authorization.

Teat solution:

An antiseptic solution to be applied on all teats of dairy cattle, either after milking (post-milking) or before and after milking (pre and post-milking), as an aid in reducing the spread of organisms which may cause mastitis.

Teat/udder wipe:

A pre-soaked antiseptic wipe to be used prior to milking to clean the teats and udders of dairy cattle as an aid in reducing the spread of organisms that may cause mastitis.

Udder wash solution:

A concentrated antiseptic solution to be used prior to milking to clean the teats and udders of dairy cattle as an aid in reducing the spread of organisms that may cause mastitis.

Appendix 1: DIN Submission Package

To apply for market authorization for a product subject to Division 1 of the Food and Drugs Regulations, a DIN submission should be filed. The following documentation is required:

• A cover letter stating the purpose of the submission.
• An original, signed and dated version of the Drug Submission Application Form.
• Copies of all labelling (package insert, inner labels, outer labels, etc.,) should be submitted in both English and French, in electronic format. It is preferable to save all labelling components and package sizes in one MS Word document. If available, mock-up labels should also be submitted. In addition, please provide an attestation to the complete and accurate translation of the French version of the labelling. Kindly ensure that a version date is included in the footer of each page.
• The Veterinary Drug Submission Application and Fee Form.

All these forms are available on our web page, Forms-Applications and submissions-Veterinary drugs.

The submission can be sent to hc.vdd.skmd.so-dgps.dmv.cp.sc@canada.ca in one single email with attachments, provided that the total attachments are less than 10 megabytes. If it does not meet these criteria, please submit the electronic documents via courier. A paper copy is no longer required.

Appendix 2: Example of Mock-up Label

Net: XX L DIN XXXXXXXX

WARNINGS / MISES EN GARDE: No meat withdrawal period or milk withholding time is required when used according to the label. Avoid contact with food. Do not take internally. If accidentally ingested, drink large volumes of water. Avoid contact with skin and eyes. If accidental contact occurs, flush thoroughly with running water. Seek medical attention immediately after oral exposure or contact with skin and eyes. Avoid breathing vapours. Do not use for cleaning and/or sanitizing milking equipment. Keep out of reach of children./Un délai d'attente pour la viande ou une période de retrait pour le lait n'est pas requis quand utilisé selon les directives de l'étiquette. Éviter tout contact avec la nourriture. Ne pas avaler. En cas d'ingestion accidentelle, boire de grandes quantités d'eau. Éviter le contact avec la peau et les yeux. En cas de contact accidentel, rincer à grande eau. Recevez des soins médicaux immédiatement après une exposition orale ou après un contact avec la peau et/ou les yeux. Éviter d'inhaler les vapeurs. Ne pas utiliser pour le nettoyage et/ou l'assainissement de l'équipement de traite. Garder hors de la portée des enfants.