Guidance Document - Human-Use Antiseptic Drugs

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Contact name: NNHPD Client Service Unit

July 31, 2019

Notice

Application of the Guidance Document: Human-Use Antiseptic Drugs

The Human-Use Antiseptic Drugs (HUAD) guidance document applies to professional and commercial use antiseptic skin products, as well as non-monograph personal use products such as those making viral, specific organisms, persistence and/or log reduction claims.

The intent of the guidance is that all such products which explicitly or implicitly claim the mitigation or prevention of disease:

• be supported by the necessary data, and
• provide the user of the product with sufficient labelling information to promote safe use.

The guidance applies to new products and will be used by Health Canada to align previously licensed products with these standards.

For professional healthcare products that meet the efficacy requirements for in vitro and in vivo testing against bacteria, market approval may be obtained by tailoring the indication of use to the specific evidence provided and ensuring that the product includes labelling that further communicates any limitations of the evidence provided.

For example, where the product is shown to not have adequate antifungal activity in vivo, a statement such as “Not shown to be effective against fungi” would be required on the label in addition to the product claim.

Manufacturers of authorized products that are seeking license changes should file according to the relevant sections of the Post-Drug Identification Number (DIN) Changes guidance document or the Post Licensing Guidance Document guidance document as appropriate.

Should you have any questions or comments regarding the content of the guidance, please contact:

Natural and Non Prescription Health Products Directorate
Health Products and Food Branch
Health Canada

250 Lanark Avenue
Ottawa, Ontario
K1A 0K9
E-Mail: nnhpd.consultation-dpsnso@hc-sc.gc.ca

Guidance Document
Human-Use Antiseptic Drugs

Published by authority of the
Minister of Health

Adopted Date: 2009/10/21

Effective Date: 2009/11/27

Foreword

Guidance documents are meant to provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. Guidance documents also provide assistance to staff on how Health Canada mandates and objectives should be implemented in a manner that is fair, consistent and effective.

Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in approach. Alternate approaches to the principles and practices described in this document may be acceptable provided they are supported by adequate justification. Alternate approaches 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 a corollary to the above, it is equally important to note that Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, 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.

This document should be read in conjunction with the accompanying notice and the relevant sections of other applicable guidance documents.

Table of Contents

• 1 Introduction
  • 1.1 Policy Objectives
  • 1.2 Policy Statement
  • 1.3 Scope and Application
  • 1.4 Background
• 2 Acronyms And Definitions
• 3 Guidance For Implementation
  • 3.1 Categories of Antiseptic Products
    • 3.1.1 Personal Domestic Use
      • 3.1.1.1 Monograph Products
      • 3.1.1.2 Non-Monograph Products
    • 3.1.2 Personal Commercial Use
    • 3.1.3 Professional Food Premises
    • 3.1.4 Professional Healthcare Use
  • 3.2 Filing Applications
    • 3.2.1 Related Guidances for Filing
    • 3.2.2 Other Related Guidances
    • 3.2.3 Pre-Submission Enquiries
• 4 Documentation
  • 4.1 Common Information for Antiseptic Applications
    • 4.1.1 Efficacy Tests
    • 4.1.2 Safety Tests
    • 4.1.3 Quality Tests
    • 4.1.4 Additional Data for Professional Food Premise-Use Products
  • 4.2 Test Protocol Recommendations
  • 4.3 Standard Test Methodologies
  • 4.4 Test Organisms
  • 4.5 Label Recommendations
    • 4.5.1 For all labels
• 5 Personal Use Products
  • 5.1 Scope
  • 5.2 Test recommendations
    • 5.2.1 In Vitro
    • 5.2.2 In Vivo
    • 5.2.3 Organism-Specific Claims
  • 5.3 Indications
    • 5.3.1 Highlighting Specific Organisms for Personal Domestic Use Product
    • 5.3.2 Log or % Reduction Claims
    • 5.3.3 Persistence Claims
    • 5.3.4 Time Kill Claims
    • 5.3.5 Sterile
  • 5.4 Labelling
• 6 Commercial Use Products
  • 6.1 Scope
  • 6.2 Test recommendations
    • 6.2.1 In Vitro
    • 6.2.2 In Vivo
    • 6.2.3 Organism-Specific Claims
  • 6.3 Indications
    • 6.3.1 Highlighting Specific Organisms for Personal Commercial Use Product
    • 6.3.2 Log and % Reduction Claims
    • 6.3.3 Persistence Claims
    • 6.3.4 Time Kill Claims
    • 6.3.5 Sterile
  • 6.4 Labelling
• 7 Professional Food Handler Use Products
  • 7.1 Scope
  • 7.2 Test recommendations
    • 7.2.1 In Vitro
    • 7.2.2 In Vivo
  • 7.3 Indications
    • 7.3.1 Log or % Reduction Claims
    • 7.3.2 Persistence Claims
    • 7.3.3 Time Kill Claims
    • 7.3.4 Sterile
  • 7.4 Labelling
• 8 Professional Healthcare Use Products
  • 8.1 Scope
    • 8.1.1 Professional handrubs and handwashes
    • 8.1.2 Surgical handscrubs
    • 8.1.3 Patient preoperative skin preparations
  • 8.2 Test Recommendations
    • 8.2.1 In Vitro
    • 8.2.2 In Vivo
  • 8.3 Indications
    • 8.3.1 Log or % Reduction Claims
    • 8.3.2 Persistence Claims
    • 8.3.3 Time Kill Claims
    • 8.3.4 Sterile
  • 8.4 Labelling
    • 8.4.1 Professional Handwash or Handrub
    • 8.4.2 Surgical handrub
    • 8.4.3 Surgical handwash
    • 8.4.4 Patient preoperative skin preparation
• 9 Effective Date
• 10 Appendices
  • Appendix I: Examples of Precedent Active Ingredients*
  • Appendix II: References

1 Introduction

As per the Food and Drugs Act, any substance that is manufactured, sold or represented for use in the "mitigation or prevention of disease" is a drug. Section 9(1) of the Act also specifies that a drug must not be labelled "…in a manner that is false, misleading or deceptive or is likely to create an erroneous impression…"

An antiseptic product is considered to be one that inactivates, reduces, prevents or arrests growth of microorganisms with the inherent intent to mitigate or prevent disease. This includes antiseptic products whether they are regulated under the Food and Drug Regulations (FDR) or the Natural Health Products Regulations (NHPR). This guidance document provides recommendations regarding the information considered necessary by Health Canada in order to support these types of claims.

1.1 Policy Objectives

Pursuant to Section 9(1) of the Act, it is Health Canada's policy that an application for an antiseptic product explicitly or implicitly claiming that the product mitigates or prevents disease be adequately supported by appropriate data. The supporting data may vary relative to the risk associated with the antiseptic product's environment for use and its specific claims.

1.2 Policy Statement

Sufficient information to support the labelled claim of an antiseptic product for human use should be made available to Health Canada.

This information should include evidence of positive supportive results of in vivo and in vitro testing conducted in accordance with acceptable test methods, and for in vivo studies, under the conditions of use prescribed on the label.

1.3 Scope and Application

This guidance applies to antiseptic skin products for human use that are intended for use in professional and commercial settings. The guidance is applicable to pharmaceutical antiseptic products (both Division 1 and Division 8) as well as to natural health antiseptic products. The guidance does not provide data recommendations to support personal domestic use products, except when such products make claims of efficacy against specific organisms, persistence, log reduction or % reduction and/or antiviral claims.

The guidance does not apply to human-use antiseptic products for burn victims, first aid, or application to sites other than the skin (for example (e.g.) mucous membranes, catheter insertion, etc.). Applicants seeking authorization for such products should request a presubmission meeting to discuss appropriate supporting data. Further, the guidance does not apply to hard surface disinfectants (see Health Canada's Guidance Document: Disinfectant Drugs for more information).

The guidance will outline the categories of antiseptic products, the filing process for antiseptic submissions, the basic documentation required to support the efficacy for all categories of antiseptic products covered in the guidance, and the additional detailed data recommendations for specific claims.

For the purpose of this guidance, microorganisms are defined as bacteria, yeast, fungi, and viruses. Helminths and protozoan parasites are recognized to be organisms of concern for professional use products. Representation that a product reduces parasites will be reviewed on a case by case basis outside of this guidance document and sponsors are encouraged to seek a presubmission meeting to discuss the data recommended to support the application.

1.4 Background

Sponsors of antiseptic products for human use containing ingredients that meet the definition of Schedule 1 of the NHPR are required to submit an application for a Natural Product Number (NPN) with the Natural Health Products Directorate (NHPD) as per Section 5 of the NHPR. Sponsors of antiseptic products for human use containing ingredients other than those that meet the definition of Schedule 1 of the NHPR are required to file an application for a Drug Identification Number (DIN) with the Therapeutic Products Directorate (TPD) as per Part C, Section C.01.014 of the FDR.

A drug is defined in part by the Act as "…any substance or mixture of substances manufactured, sold or represented for use in… mitigation or prevention of a disease." Furthermore, Section 9(1) of the Act states:

No person shall label, package, treat, process, sell or advertise any 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.

A labelled claim may be implicit or explicit with respect to mitigating or preventing disease. For example, a claim stated as "prevents the spread of disease X" would be considered explicit. If the claim were stated as "kills organism Y" and organism Y is known to cause disease X then this claim would be considered as implying "prevents the spread of disease X". Therefore, Health Canada has the responsibility to confirm the validity of such claims either through the evaluation of supportive scientific evidence or by confirming conformance to a prescribed and acceptable standard. A standard has been developed for certain personal domestic use antiseptics in the form of the joint TPD-NHPD Category IV Monograph for Antiseptic Skin Cleansers.

However, the lack of guidance for other types of antiseptic products has resulted in a number of undesirable effects and consequences, impacting Health Canada's ability to regulate antiseptic products appropriately. These include:

• industry confusion on submission recommendations and process, resulting in the possibility of non-compliance and an identified need for clarity;
• a high number of Category IV Monograph rejections issued for submissions for professional-use antiseptic products as no guidance is otherwise available;
• less than optimal use of submission review resources as a result of fielding enquiries in the place of a published document, and in processing unnecessary filings;
• consumer and health professional confusion on the availability of appropriate products for use.

It was recognized that Health Canada requires an appropriate tool to effectively manage drug submission applications for antiseptic products.

2 Acronyms and Definitions

ASTM

International (previously American Society for Testing and Materials)

ATCC

American Type Culture Collection

CDER

Center for Drug Evaluation and Research

CEN

European Committee for Standardization

CFIA

Canadian Food Inspection Agency

CGSB

Canadian General Standards Board

DIN

Drug Identification Number

DINA

Drug Identification Number Application

EN

standard developed by the CEN

FDA

Food and Drug Administration, United States of America

FDR

Food and Drug Regulations

ICH

International Conference on Harmonization

NCTC

National Collection of Type Cultures

NHP

natural health product

NHPD

Natural Health Products Directorate

NHPR

Natural Health Products Regulations

OECD

Organization for Economic Cooperation and Development

TPD

Therapeutic Products Directorate

Persistence:

A reduction in skin flora which maintains an extended and low microbial release from the skin due to slow regrowth of the resident microflora. (Fraise et al, 2004)

Resident Organisms:

Those organisms normally permanently resident on the skin. Under some circumstances, this may include those that are not permanently resident on normal skin but may be increased in number in the presence of certain skin diseases (e.g. Klebsiella spp. on psoriatic skin) or systemic illnesses (diabetes, AIDS, etc). (Fraise et al, 2004)

Transient Organisms:

Those organisms picked up by contact with the environment but may remain in situ long enough to be transferred (e.g. from patient to patient; from surgeon to patient, etc.). (Fraise et al, 2004)

3 Guidance For Implementation

This section describes the:

• different categories of antiseptic products;
• filing processes applicable to antiseptic products;
• general information on filing considerations.

3.1 Categories of Antiseptic Products

The categories of human-use antiseptic products for application on the skin are defined by the intended user and the proposed conditions of use. Such products would be considered drugs under the Act if represented for the reduction and/or inactivation of microorganisms on human skin as this implies its use for the prevention of disease or the prevention of disease transmission. Antiseptic products can include both those to be used with water (referred to as washes) or without water (referred to as rubs), and may be presented in different pharmaceutical forms. Antiseptic skin products also include preoperative skin preparations.

Products may be indicated for multiple use categories, provided that each has sufficient data to support the indication, each indication has been authorized by Health Canada, and the product labels contain appropriate information for each use. The statement identifying the environment of use (e.g. For Food Premise Use) may be amended to incorporate all authorized indications.

Below is a list of the categories recognized by Health Canada. Each category is further defined in the appropriate subsection of this guidance document.

3.1.1 Personal Domestic Use

Personal domestic (or household) use products are those used by an individual in a domestic setting to reduce transient organisms on the skin.

3.1.1.1 Monograph Products

A joint TPD-NHPD Category IV Monograph for Antiseptic Skin Cleansers is available for products self-selected by a consumer from a retail outlet for their own personal household use as part of a daily skin cleansing routine. These types of products are intended to provide a superficial and non-persistent cleaning effect to reduce domestic transient bacterial and fungal load on hands. Consumers are encouraged to use plain soap and water with vigorous scrubbing of the entire surface of both hands, followed by proper rinsing and drying, as their first option in order to cleanse soiled hands adequately. Antiseptic skin cleansers should be recommended for use on lightly soiled hands only as a second-line approach or when soap and water are not available. The medicinal (active) ingredients and their concentrations, indications, and adequate directions for use (including directions, dosage, and warnings) are restricted to those specified in the Monograph.

The Monograph outlines active ingredients and their concentrations generally recognized as safe and effective in the reduction of transient organisms. The sponsor is required to have the data on file which supports that the finished product is effective when considering the permitted Monograph claims and required directions for use. Products which meet the Monograph specifications are excluded from this guidance, and should be filed with NHPD or TPD in keeping with the Monograph process. This guidance does not apply to products complying with the Monograph unless a change in indication is made by the sponsor after authorization has been received under the Monograph system.

The Monograph does not apply to:

1. antimicrobial products intended to be used by health care professionals or food handlers or in institutions including health care facilities; or
2. antimicrobial products intended to be used in commercial settings (e.g. outside of the home/personal use); or
3. products with claims outside those permitted in the Monograph, such as:
   • efficacy against any specific organisms;
   • persistence claims;
   • log reduction or % reduction (kill) claims;
   • antiviral claims.

3.1.1.2 Non-Monograph Products

Products in this category include any personal-use antiseptic product not captured in the above Monograph. This includes, but may not be limited to, consumer-use first aid antiseptic for application in cleansing minor wounds or self-administered pre-injection preparatory cleanser (e.g. for ear piercing or insulin injections). Products which make such claims are considered outside the scope of this guidance, although some of the same basic principles may apply. A drug application (for pharmaceuticals) or non-traditional NPN application (for natural health products) should be filed with the appropriate supporting data to Health Canada.

3.1.2 Personal Commercial Use

Personal commercial use products are those made available to the general public for occasional use and are intended to reduce transient organisms on the skin in a commercial or institutional setting.

3.1.3 Professional Food Premises

Products for professional food premises are those which are indicated for use by food handlers to reduce transient organisms on the skin in a commercial or institutional setting including food processing plants and also includes restaurants, retail supermarkets, and fast food outlets.

3.1.4 Professional Healthcare Use

Products for professional healthcare use are those which are indicated for use by individuals to reduce transient and/or resident organisms on the skin in a healthcare setting (such as hospitals, nursing homes, clinics, dental offices). Such products are to be used in accordance with applicable hospital protocols.

Professional healthcare use antiseptics can be broken down as follows:

Professional hygienic handrub:

product used for post-contamination treatment of lightly-soiled hands that involves rubbing hands without addition of water, and which is designed for frequent use.

Professional hygienic handwash:

product used for post-contamination treatment that involves washing hands, and which is designed for frequent use.

Surgical handrub:

product used for preoperative treatment, which involves rubbing hands without addition of water.

Surgical handwash:

product used for preoperative treatment that involves washing hands, either with or without the use of a scrub brush.

Patient preoperative skin preparations:

product used to prepare patient skin prior to surgical procedures.

3.2 Filing Applications

Instructions on the data recommendations to support applications for antiseptic products are detailed below in the following Sections. Antiseptic products using drugs from a natural source which meet the definition of Schedule 1 of the NHPR are required to submit an application for a Natural Product Number (NPN) to NHPD as per Section 5 of the NHPR. Antiseptic NPN applications are to be submitted to the non-traditional assessment stream in accordance with NHPD's Product Licensing Guidance Document. All other applications should be filed with the Therapeutic Products Directorate. Please note that C.08.001 of the FDR may apply to drug applications when introducing new ingredients, new indications, etc.

3.2.1 Related Guidances for Filing

Information regarding general submission requirements, contact information, and target performance standards may be found in the Health Canada guidance documents: Guidance for Industry: Management of Drug Submissions for pharmaceuticals and Product Licensing Guidance Document for natural health products.

3.2.2 Other Related Guidances

This guidance document should be read in conjunction with other associated Health Canada policies and guidance documents including, but not limited to:

• Preparation of Drug Identification Number Submissions (1995);
• Quality Guidance: Applications for Drug Identification Numbers (DINAs) for Pharmaceuticals (2003);
• Product Licensing Guidance Document (2006);
• Evidence For Quality Of Finished Natural Health Products (2007);
• Evidence for Safety and Efficacy of Finished Natural Health Products (2006).

3.2.3 Pre-Submission Enquiries

The listing of ingredients, data recommendations, and methods in this guidance document is not considered to be exhaustive. Sponsors are advised to contact Health Canada, in writing, if the sponsor wishes to discuss product and/or claim-specific data recommendations, or for applications for products outside the scope of the guidance. Verbal enquiries should be followed-up in writing by the sponsor.

4 Documentation

This section outlines the basic data recommended to support all antiseptic product submissions covered in this guidance, including:

• general data for efficacy claims;
• test protocols.

4.1 Common Information for Antiseptic Applications

The following should be included for each drug submission to support efficacy claims and product safety (for any non-Monograph submission):

4.1.1 Efficacy Tests

1. In vitro tests:^{Footnote 1}
   • For surrogate and non-surrogate test organisms: one independent^{Footnote 2} test report, which proves the antiseptic activity for a product.
   • each test report needs to include only one lot of product;
   • the tests are to be done in triplicate to demonstrate reproducibility.
2. In vivo tests:
   • For non-surrogate test organisms: one independent test report, which proves the antiseptic activity of a product.
   • For surrogate test organisms: two^{Footnote 3} independent test reports, which prove the antiseptic activity for a product.
   • Each in vivo test report should include three separate lots of product.
   • Tests should be performed with sufficient subjects^{Footnote 4} per tested product to satisfy the statistical criteria of the clinical trial design.
3. test reports should include at a minimum:
   • identification of the standard method used to verify the product efficacy;
   • proof of the effectiveness of the neutralizer utilized in the tests for both the reference standard and the test product;
   • the relationship of each test to specific area of application;
   • the type and level of soil load included in the test along with a rationale;
   • the time differential (between application of the test product and the collection of organisms) used in the test and whether the time stated is sufficient to meet the required criteria of specific activity;
   • initial number of the test organisms;
   • information on the lot number, expiry date, and date of manufacture for each lot tested;
   • overview of the statistical plan and assumptions;
   • supporting raw data;
   • results in tabular form;
   • proof of a washout period if a cross-over study is employed, or if a subject is reused;
   • proof of glove compatibility for surgical scrub products;
   • the minimum inhibitory concentration (MIC) for the product, when available; and
   • conclusion, describing whether the product meets the specific criteria relative to the reference method(s) employed.
4. at a minimum, tests must demonstrate that the lower bound of the confidence interval is at the required log reduction; and that a power of 80% and alpha of 5% is used.
5. based on practicality, no product will be accepted if its in vivo time-to-effect upon completion of application^{Footnote 5} is greater than 30 seconds (for a leave on product) or 1 minute (for a wash off product)^{Footnote 6}.

4.1.2 Safety Tests

1. published or unpublished safety data testing local tolerance, such as:
   • irritation and sensitization (in the presence and absence of UV exposure when this is likely to be a risk factor) and preferably conducted in human species;
   • photoallergenicity;
   • photocarcinogenicity, etc.
2. when evidence is not available to show that topically-applied medicinal ingredients are not absorbed systemically to a significant degree, toxicity data should be submitted.
3. safety tests for (a) and (b) should be performed in accordance with relevant internationally-accepted test methods (e.g. OECD, ICH)

4.1.3 Quality Tests

Additional supporting data may be required to support the quality of the finished antiseptic product. The recommended quality data depends on the classification of the proposed product as either a drug or natural health product. Health Canada encourages applicants to verify the quality recommendations with the appropriate Directorate prior to submitting an application.

4.1.4 Additional Data for Professional Food Premise-Use Products

For products that are intended to be used in professional food premises, a duplicate copy of the full submission with the following information should be included:

1. Full disclosure of the chemical formulation of the product. This information should be in the form of a quantitative listing of all ingredients used in its manufacture and in the final product formulation, taking into account that the percentage of the chemical formulation components should add up to 100%. Each ingredient should be identified by its trade name, supplier, and/or proper chemical name and CAS number (if available).
2. Residual data would be requested if necessary: the residual amount of the product that will be found on hands of employees after application of the product and the level that may be expected to be transferred to food products (after precautionary safety approaches were undertaken such as potable water rinse or drainage of excess of product). This information should be in the form of actual analytical data or theoretical estimates based on the proposed use level of the product.
3. Type of foods that are processed in the plants where this product is proposed to be used at (if known).

During the review sponsors may also be asked to provide the following additional information, pending assessment by the Food Directorate (FD):

1. The worst case Estimated Dietary Intake (EDI) resulting from the use of the product. This should include any information that is used to estimate the dietary exposure such as type of foods, residual levels, etc.; and
2. Any available data (full reports) on the mammalian oral toxicity of the product.

4.2 Test Protocol Recommendations

1. In vitro and in vivo studies submitted for review to support the proposed product and/or claim should:
   • utilize the specific microorganism(s) for which antimicrobial claims are to be made (or a suitable surrogate thereof when appropriate);
   • use the proposed Canadian formulation (including same concentration of active ingredients);^{Footnote 7}
   • if a reference standard is not specified in the test method, then the following reference standards should be used:
     • Personal use products: 2-propanol;
     • Professional use products: 1-propanol.
   • if the test method requires that a soap and water prewash be used immediately prior to baseline measurements and there are no test organisms added to the skin (that is [i.e.] assessment of volunteer's personal microbial load), the log reduction value for the test product may be shown to be not significantly worse than the reference product.
2. In vivo studies submitted for review to support the proposed product and/or claim should also:
   • use the proposed Canadian conditions of use recommended in the labelling, including:
     • same pharmaceutical form (e.g. lotion, gel, wipe, etc.);
     • same contact times;
     • volume to be used;
     • directions for use;
     • presence or absence of organic load;
     • surgical scrubs should assess glove compatibility;
     • the determination of infective titre should be performed using a direct method ( e.g. plaque assay technique for plaque-forming viruses); and
     • for all products, any other factor/s which may influence the effectiveness of the product.

4.3 Standard Test Methodologies

The guidance is based on standard European (CEN) and North American (ASTM) test methods and represents current scientific knowledge. The EN and ASTM norms were selected as the basis for the data recommendations because these were deemed to:

• be conducive to determination of a products' efficacy against specific organism claims;
• provide both in vivo and in vitro test methodology;
• allow for virucidal testing;
• use ATCC identifiable organisms.

Each standard test method specifies the recommendations and criteria the product must comply with in order to support the claims of the specific microbiocidal activity, with the purpose of:

• enabling the manufacturers to select appropriate test methodology to furnish data in support of the claims for the specific use;
• ensuring that the users of the antiseptic products will be able to select the most appropriate product for a specific purpose;
• eliminating methodology bias and objectively comparing product efficacies since the testing is performed under identical conditions.

Claims for antiseptic products include statements of efficacy, persistence, organism-specificity, and category of product (e.g. professional use, commercial use, etc.) Each claim must be supported by evidence in the form of specific tests that have been carried out to demonstrate the efficacy of the product. As test results may be formulation-dependent, it cannot be assumed that the presence of an active ingredient confers equal efficacy across a range of products.

It is recommended that a modular approach be taken to first test the formulation in vitro, then proceed to in vivo testing if the in vitro testing is successful. It is not generally considered acceptable to label a product for effectiveness against certain microorganisms based only on in vitro studies as there is not usually a correlation between data generated in vitro and effectiveness observed in vivo. In vitro studies are usually considered only secondary supportive evidence.

For personal domestic and commercial use products, only in vivo data need be submitted for assessment except where otherwise specified for fungal and viral testing (see specifics under Common Information for Antiseptic Applications). Ultimately in vivo studies should be provided as the primary evidence for claims. For professional use products, both in vitro and in vivo tests are required to demonstrate efficacy against a broader range of organisms, however the in vivo tests will be limited to representative organisms only.

Please note that Phase I test methods have not been included in the guidance. Such data may be submitted with an application; however it is only considered secondary supporting evidence and is not sufficient on its own to support a therapeutic indication.

Step 1: In vitro testing

ASTM E 1052-96

Standard Test method for Efficacy of Antimicrobial Agents Against Viruses in Suspension.

EN 13624

Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of fungicidal activity of chemical disinfectants for instruments used in the medical area. Test method and requirements (phase 2, step 1)

EN 13727

Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of bactericidal activity of chemical disinfectants for instruments used in the medical area - Test method and requirements (phase 2, step 1)

EN 14348

Chemical disinfectants and antiseptics Quantitative suspension test for the evaluation of mycobactericidal activity of chemical disinfectants in the medical area including instrument disinfectants Test methods and requirements (phase 2, step 1)

EN 14476

Chemical disinfectants and antiseptics. Virucidal quantitative suspension test for chemical disinfectants and antiseptics used in human medicine. Test method and requirements (phase 2, step 1)

Step 2: In vivo testing on volunteers

EN 1499

Chemical disinfectants and antiseptics. Hygienic handwash. Test method and requirements (phase 2/step 2)

EN 1500

Chemical disinfectants and antiseptics. Hygienic handrub. Test method and requirements (phase 2/step 2)

EN 12791

Chemical disinfectants and antiseptics. Surgical hand disinfection. Test method and requirement (phase 2/step2)

ASTM E 1115-02

Standard Test Method for Evaluation of Surgical Hand Scrub Formulations. USA, 2002.

ASTM E 1173-01e1

Standard Test Method for Evaluation of a Preoperative, Precatheterization, or Preinjection Skin Preparations

ASTM E 1174-06

Standard Test Method for Evaluation of the Effectiveness of Health Care Personnel Handwash Formulations.

ASTM E 2011-09

Standard Test Method for Evaluation of Hygienic Handwash and Handrub Formulations for Virus-Eliminating Activity Using the Entire Hand.

ASTM E 2276-03

Standard Test Method for Determining the Bacteria-Eliminating Effectiveness of Hygienic Handwash and Handrub Agents Using the Fingerpads of Adult Subjects.

ASTM E 2613-08

Standard Test Method for Determining Fungus-Eliminating Effectiveness of Hygienic Handwash and Handrub Agents Using Finger Pads of Adults

Note that the most recent validated test method must be used in case of an update.^{Footnote 8} Alternate test methodologies may also be considered acceptable for an antiseptic product submission application, provided that they are scientifically justified and appropriately validated. The use of alternate approaches should be discussed in advance with Health Canada to ensure that the proposed methodology will generate the required data. In such a case, a presubmission meeting is highly recommended.

4.4 Test Organisms

The test organisms recommended for personal domestic and commercial use products are based on the selected test methods. The test organisms recommended for professional use food premise and healthcare products were selected because these were determined to be common organisms of concern in these environments, including those that are recognized to contribute to nosocomial infections. Surgical use products - including patient preoperative skin preparations - are not required to demonstrate efficacy against mycobacteria and viruses as currently only bacteria and fungi are recognized as frequent causative agents of surgical site infections.

4.5 Label Recommendations

The general recommendations for labelling of drug products are outlined in the Food and Drugs Act as well as the Food and Drug Regulations and Natural Health Products Regulations.

4.5.1 For all labels

Labels which include the authorized claims should also describe the intended area of application and specific attributes of the product, such as: bactericidal, fungicidal, mycobactericidal or virucidal. The label should also clearly reflect the same conditions of use employed in the tests used to demonstrate efficacy (e.g. directions for use, warnings, etc.).

Products may carry more than one indication or claim, as long as each has been authorized by Health Canada. In such an instance, the label must include the full warnings and adequate directions for use for each indication, should these differ.

If surrogates were used in testing this should be stated on the labels (e.g. "murine norovirus used as a surrogate for human norovirus") in order to ensure transparency and clarity for the end user.

Note: dispensing units are also considered labels when they contain a drug product, and should be labelled in accordance with regulatory requirements.

See category-specific sections for detailed labelling recommendations.

5 Personal Use Products

5.1 Scope

Personal use products are those self-selected for use by an individual in a domestic setting. The majority of personal use products are subject to the Antiseptic Skin Cleanser Monograph. This Human-Use Antiseptic Drugs guidance document applies only to those personal use products which do not meet the scope of the Monograph. All personal use products are expected to demonstrate efficacy against bacteria and fungi at a minimum (whether through the Monograph stream or outside), but such data is maintained on file with the sponsor unless additional claims are made (e.g. log reduction) or the product contains a new active ingredient or new combination of active ingredients. Claims for mycobacteria and/or viruses are considered to require additional supporting data.

5.2 Test recommendations

For personal domestic use products, only in vivo data need be submitted for assessment except where otherwise specified for fungal and viral testing (see specifics under Common Information for Antiseptic Applications).

5.2.1 In Vitro

5.2.2 In Vivo

5.2.3 Organism-Specific Claims

The following organisms are recognized as potentially appropriate to be labelled on personal use products, and this list is intended as a reference only for the ATCC/NCTC codes only. The presence in this table does not convey automatic acceptance of the suitability of a highlighted organism for any given product. A rationale and supporting clinical data for highlighting a specific organism is required.

5.3 Indications

5.3.1 Highlighting Specific Organisms for Personal Domestic Use Product

If it has been successfully determined that the proposed formulation is effective against an organism using the recommended test methods, that organism may be named on the labels. A generalized claim that a product is bactericidal/fungicidal/virucidal etc. (or likewise "antibacterial…") cannot be determined by one organism alone nor can this representative class be considered authorization to highlight any other untested or specific organism.

Health Canada reserves the right to determine when an organism-specific claim would likely result in the product being used for professional purposes, for example when claiming for organisms identified to be of high risk in healthcare settings (e.g. severe acute respiratory syndrome (SARS), methicillin-resistant staphylococcus aureus (MRSA), H1N1, etc). In such instances, the sponsor will be expected to meet the recommendations for professional use products. Sponsors are encouraged to verify the applicability of organism-specific claims for personal use products prior to testing and/or submitting an application."

5.3.2 Log or % Reduction Claims

Personal domestic use products claiming log or % reduction values (e.g. kills 99.9% of bacteria) are required to submit data to support the claim for the specific formulation and using the recommended test methods. General log reduction claims need only demonstrate efficacy against bacteria and fungi unless claims are also made against mycobacteria and/or viruses.

5.3.3 Persistence Claims

Persistence is defined as a claim that the product will deliver a longer action than only the immediate reduction of microorganisms on hands (see Definitions). Persistence claims for personal use products can only be made relative to bacteria. Should a sponsor wish to make persistence claims against other organisms, a presubmission meeting with a strong supporting scientific rationale outlining an appropriate test method would be necessary.

5.3.4 Time Kill Claims

Antiseptic products are expected to have a minimum time-to-effect of 30 seconds (for waterless handrubs) to 1 minute (for washes or scrubs using water) upon completion of application according to the proposed directions for use. As this is considered the norm for antiseptics, a claim that a product is fast-acting would have to demonstrate both a significantly shorter time-to-effect and still maintain clinical relevance, and should use the test methods outlined for log reduction testing (organisms dependent on indications, with bacteria/fungi as a minimum).

5.3.5 Sterile

Any pharmaceutical product claiming sterility of any component of an antiseptic product must also undergo a chemistry and manufacturing review. Sponsors are recommended to consult the Health Canada guidance document on supporting data requirements for sterility claims: Stability Testing of Existing Drug Substances and Products and Quality Guidance: Applications for Drug Identification Numbers (DINAs) for Pharmaceuticals.

A product license application for a non-traditional natural health antiseptic product includes a chemistry and manufacturing review portion for all products, including those claiming sterility.

5.4 Labelling

Labelling for personal/domestic use products is restricted to that permitted in the Antiseptic Skin Cleanser Monograph, except where data has been reviewed resulting in Health Canada authorization of altered or additional claims.

6 Commercial Use Products

6.1 Scope

Personal commercial use products are those made available to the general public for occasional use and are intended to reduce transient organisms on the skin in a commercial or institutional setting. This includes, but may not be limited to, antiseptic products dispensed in washrooms in public buildings (such as daycares and schools) or used in workplaces other than healthcare or food-handling premises These products are commonly used to reduce transient organisms on hands, including those organisms that may not necessarily be encountered in a domestic setting. They are intended to provide a superficial and non-persistent cleaning effect to reduce microbial load on hands to either augment the effect of soap and water cleaning or for use when soap and water are not available.

Personal commercial use products do not include those intended to be used by professionals or in healthcare facilities and food processing plants.

Personal commercial products making general statements such as those outlined in the Monograph for Antiseptic Skin Cleansers are not considered Monograph applications as the directions for use are inappropriate; however, they may be filed as a DINA (form) for pharmaceuticals or as a non-compendial application for natural health products. No additional supporting clinical data need be filed if the claims, ingredients, and concentrations are the same as those found in the Monograph for Antiseptic Skin Cleansers.

All personal use products are expected to demonstrate efficacy against bacteria and fungi at a minimum (whether through the Monograph stream or outside) but such data is maintained on file with the sponsor unless additional claims are made (e.g. log reduction) or the product contains a new active ingredient or new combination of active ingredients. Claims for mycobacteria and/or viruses are considered to require additional supporting data.

This guidance outlines the data recommendations for supporting an application for personal commercial use wherein claims are made against a specific organism, antiviral claims, or those relating to persistence, sterility, and/or % or log-reduction.

6.2 Test recommendations

For personal commercial use products, only in vivo data need be submitted for assessment except where otherwise specified for fungal and viral testing.

6.2.2 In Vivo

6.2.3 Organism-Specific Claims

The following organisms are recognized as potentially appropriate to be labelled on personal use products, and this list is intended as a reference only for the ATCC/NCTC codes only. The presence in this table does not convey automatic acceptance of the suitability of a highlighted organism for any given product. A rationale and supporting clinical data for highlighting a specific organism is required.

6.3 Indications

6.3.1 Highlighting Specific Organisms for Personal Commercial Use Product

If it has been successfully determined that the proposed formulation is effective against an organism using the recommended test methods, that organism may be named on the labels. A generalized claim that a product is bactericidal/fungicidal/virucidal etc. (or likewise "antibacterial…") cannot be determined by one organism alone nor can this representative class be considered authorization to highlight any other untested or specific organism.

Health Canada reserves the right to determine when an organism-specific claim would likely result in the product being used for professional purposes, for example when claiming for organisms identified to be of high risk in healthcare settings (e.g. severe acute respiratory syndrome (SARS), methicillin-resistant staphylococcus aureus (MRSA), H1N1, etc). In such instances, the sponsor will be expected to meet the recommendations for professional use products. Sponsors are encouraged to verify the applicability of organism-specific claims for personal use products prior to testing and/or submitting an application."

6.3.2 Log and % Reduction Claims

Personal use products claiming log reduction values (e.g. kills 99.9% of bacteria) are required to submit data to support the claim for the specific formulation and using the recommended test methods. General log reduction claims need only demonstrate efficacy against bacteria and fungi unless claims are also made against mycobacteria and/or viruses.

6.3.3 Persistence Claims

Persistence is defined as a claim that the product will deliver a longer action than only the immediate reduction of microorganisms on hands (see Definitions). Persistence claims for personal use products can only be made relative to bacteria. Should a sponsor wish to make persistence claims against other organisms, a presubmission meeting with a strong supporting scientific rationale outlining an appropriate test method would be necessary.

6.3.4 Time Kill Claims

Antiseptic products are expected to have a minimum time-to-effect of 30 seconds (for waterless handrubs) to 1 minute (for washes or scrubs using water) upon completion of application according to the proposed directions for use. As this is considered the norm for antiseptics, a claim that a product is fast-acting would have to demonstrate both a significantly shorter time-to-effect and still maintain clinical relevance, and should use the test methods outlined for log reduction testing (organisms dependent on indications, with bacteria/fungi as a minimum).

6.3.5 Sterile

Any pharmaceutical product claiming sterility of any component of an antiseptic product must also undergo a chemistry and manufacturing review. Sponsors are recommended to consult the Health Canada guidance document on supporting data requirements for sterility claims: Stability Testing of Existing Drug Substances and Products and Quality Guidance: Applications for Drug Identification Numbers (DINAs) for Pharmaceuticals.

A product license application for a non-traditional natural health antiseptic product includes a chemistry and manufacturing review portion for all products, including those claiming sterility.

6.4 Labelling

All products intended for use in a commercial setting should be labelled "For commercial use" on the front panel of the inner and outer labels, and may only use an acceptable indication from the list outlined in the Monograph for Antiseptic Skin Cleansers unless data is submitted to support additional claims. Further, the inner and outer labels shall also carry the following warning statements and directions for use, clearly identified with appropriate headings:

• For external use only. Do not ingest.
• Avoid contact with the eyes.
• Discontinue use and consult a health care practitioner if irritation and redness develops.
• Keep out of reach of children.
• (For handwash): Use XmL and lather in hands with water for at least 30 seconds. Rinse well.^a
• (For handrub): Use XmL and rub thoroughly into hands for at least 30 seconds. Allow to dry.^a

^a Where "XmL" is equivalent to the dose required to achieve effect, as measured in in vivo efficacy trials.

7 Professional Food Handler Use Products

7.1 Scope

Products for professional food premises are those which are indicated for use by food handlers and are used frequently to reduce transient organisms on the skin in a commercial or institutional setting including food processing plants, restaurants, retail supermarkets, and fast food outlets. The intent of such products is to both protect food handlers as well as to reduce the likelihood of transmission of disease through food.

This guidance provides information regarding the data necessary for Health Canada to conduct a premarket evaluation prior to the authorization of these products for sale in Canada. A product indicated for use by food handlers should be safe and effective when applied (and frequently reapplied) to human skin. When applied to bare hands that will come into direct contact with food, the product's chemical composition is not to be detrimental or transfer residue to the food, when the product is used or stored in a food processing facility, where food is prepared, packed or stored. To this end, the FD will be consulted by NHPD or TPD to carry out the premarket safety assessment of an antiseptic product for use in food processing facilities.

There are additional considerations for federally-registered food establishments. The CFIA requires a further assessment of the acceptability for use in establishments operating under the authority of the Agency prior to marketing the product. FD and the CFIA require full disclosure of product's chemical composition listing its ingredients by percentage or quantitatively and a product label, with specific directions for use in a food plant. The premarket review directorates of Health Canada will be responsible for this assessment, and will inform FD and the CFIA of when a product has been authorized for use in food premises. Further information regarding the Reference Listing of Accepted Construction Materials, Packaging Materials, and Non-Food Chemical Products is available at the  CFIA Web site.

7.2 Test recommendations

For professional use products, both in vitro and in vivo tests are required to demonstrate efficacy against a broader range of organisms, however the in vivo tests will be limited to representative organisms only unless a specific organism is highlighted. Products intended for use by food handlers should also demonstrate efficacy in the presence of organic soil such as food ingredients and fats, in order to adequately represent likely conditions of use. Additional consideration must be given to the proposed product formulation, as these must be appropriate for use in food premises. Given the acknowledged potential for spread of enteric viruses, products for use by food handlers should also demonstrate efficacy against viruses in addition to other microorganisms. All in vivo tests should demonstrate a minimum log reduction in microorganisms.

Products for use in professional food premises should also include the additional data for assessment outlined in Section 4.1.4.

Professional-use antiseptic hand rubs and hand washes for use in food premises should have supporting data demonstrating efficacy against all of the following organisms in using the recommended test methods.

7.2.1 In Vitro

7.2.2 In Vivo

7.3 Indications

7.3.1 Log or % Reduction Claims

Products claiming log reduction values (e.g. kills 99.9% of bacteria) are required to submit data to support the claim. Note that products for use in a professional food premise setting are required to have a minimum log reduction in vivo.

7.3.2 Persistence Claims

Persistence is defined as a claim that the product will deliver a longer action than only the immediate reduction of microorganisms on hands (see Definitions). Persistence claims can only be made relative to bacteria. Should a sponsor wish to make persistence claims against other organisms, a presubmission meeting with a strong supporting scientific rationale outlining an appropriate test method would be necessary.

7.3.3 Time Kill Claims

Antiseptic products are expected to have a minimum time-to-effect of 30 seconds (for waterless handrubs) to 1 minute (for washes or scrubs using water) upon completion of application according to the proposed directions for use. As this is considered the norm for antiseptics, a claim that a product is fast-acting would have to demonstrate both a significantly shorter time-to-effect and still maintain clinical relevance.

7.3.4 Sterile

Any pharmaceutical product claiming sterility of any component of an antiseptic product must also undergo a chemistry and manufacturing review. Sponsors are recommended to consult the Health Canada guidance document on supporting data requirements for sterility claims: Stability Testing of Existing Drug Substances and Products and Quality Guidance: Applications for Drug Identification Numbers (DINAs) for Pharmaceuticals.

A product license application for a non-traditional natural health antiseptic product includes a chemistry and manufacturing review portion for all products, including those claiming sterility.

7.4 Labelling

All products authorized for use in a food premises/food handler setting should be labelled on the front panel of the inner and outer labels with the following indications:

• For use in food premises;
• To reduce bacteria, mycobacteria, fungi, and viruses on skin.

If products were tested with the presence of organic soil, then labels may make such a representation.

Further, the inner and outer labels shall also carry the following warning statements and directions for use, clearly identified with appropriate headings:

• For external use only. Do not ingest.
• Avoid contact with the eyes.
• Discontinue use and consult a health care practitioner if irritation and redness develops.
• Keep out of reach of children.
• Avoid food contamination during use and storage.
• Do not refill container.^b
• This product may not be effective against parasites.⁺⁺
• (For handwash): Use XmL and lather in hands with water for at least 30 seconds. Rinse well.^a
• (For handrub): Use XmL and rub thoroughly into hands for at least 30 seconds. Allow to dry.^a

^a Where "XmL" is equivalent to the dose required to achieve effect, as measured in in vivo efficacy trials.
^b This statement may be excluded if it is demonstrated that the product is not in a refillable container.
⁺⁺ This statement may be removed if a parasite claim has been authorized by Health Canada for the product

Depending on the type of antiseptic product, one of two additional statements is necessary:

1. A product which is comprised of volatile ingredients only and for which there is no evidence of residue left on the hands prior to handling food products, requires a statement:
   • For Food Plant Use: after use of this product, food handlers' hands are to be dry and free of product residue prior to handling food products.
2. A product whose composition includes non- volatile ingredients (i.e. colour concentrates, fragrances, fillers stabilizers and preservatives, etc.) and there is a potential for cross contamination to a food product, requires a statement such as:
   • For Food Plant Use: after use of this product food handlers are to rinse their hands with potable water prior to handling food products.

Note: It is not considered acceptable for products for use in food premises to claim "E1" or "E2" rating, as these are international disinfectant ratings not applicable to human use products nor adopted by Health Canada for disinfectants.

8 Professional Healthcare Use Products

8.1 Scope

Products for professional healthcare use are those which are indicated for use by individuals to reduce transient and/or resident organisms on the skin in a healthcare setting (such as hospitals, nursing homes, clinics, dental offices). Such products are to be used in accordance with applicable hospital protocols.

Healthcare settings typically exhibit a higher presence of transient and/or nosocomial organisms than domestic or other commercial institutions. As such there is an inherently higher safety risk to health if the product is not effective.

Professional healthcare use antiseptics can be broken down as follows:

8.1.1 Professional handrubs and handwashes

Professional-use rubs and washes are to be used on the hands of healthcare personnel and clients with the intention to remove and/or inactivate transient microorganisms on the hands to prevent their transmission regardless of the resident skin flora.

Professional hygienic handrub:

product used for post-contamination treatment of lightly-soiled hands that involves rubbing hands without addition of water, and which is designed for frequent use.

Professional hygienic handwash:

product used for post-contamination treatment that involves washing hands, and which is designed for frequent use.

8.1.2 Surgical handscrubs

Surgical scrubs are to be used on the hands of healthcare personnel prior to performing a surgical/invasive procedure. They are directed against the resident microorganisms on hands to prevent their transmission into the surgical wound. Surgical scrubs should have a persistent effect (minimum of 6 hours).

Surgical handrub:

product used for preoperative treatment, which involves rubbing hands without addition of water.

Surgical handwash:

product used for preoperative treatment that involves washing hands, either with or without the use of a scrubbrush.

8.1.3 Patient preoperative skin preparations

Fast-acting, broad spectrum products used on patients prior to a surgical procedure with the goal of significantly reducing/inactivating transient and resident organisms on skin to prevent their entry into the surgical site. Preoperative products, like surgical scrubs, should have a persistent effect (minimum of 6 hours).

8.2 Test Recommendations

For professional use products, both in vitro and in vivo tests are required to demonstrate efficacy against a broader range of organisms, however the in vivo tests will be limited to representative organisms only unless a specific organism (or an acceptable surrogate in the case of pathogenic organisms) is highlighted.

There are minimum efficacy recommendations for products intended for use in a healthcare setting given concerns with the increased prevalence of nosocomial microorganisms compared with a domestic or commercial setting. As a baseline requirement and to ensure a minimum level of efficacy, all professional-use antiseptic products should have supporting data demonstrating efficacy against all of the organisms outlined in the table below. Surgical scrubs and patient preoperative skin preparations must also demonstrate at least 6 hours of persistence.

Other specialty products for professional healthcare use which necessitate testing of additional organisms not included in this guidance may also be acceptable, provided that in vitro and in vivo tests are performed using these organisms or acceptable surrogates thereof, e.g. a product for use in obstetrics/gynaecology may choose to run trials to assess efficacy against Bacteroides spp. other than Bacteroides fragilis.

8.2.1 In Vitro

8.2.2 In Vivo

8.3 Indications

8.3.1 Log or % Reduction Claims

Products claiming log reduction values (e.g. kills 99.9% of bacteria) are required to submit data to support the claim. Note that products for use in a professional setting and/or those claiming to reduce specific organisms are required to have a minimum log reduction in vivo.

8.3.2 Persistence Claims

Persistence is defined as a claim that the product will deliver a longer action than only the immediate reduction of microorganisms on hand (see Definitions). Professional-use surgical scrubs and preoperative patient skin preparations must demonstrate a minimum persistence of at least six hours.

8.3.3 Time Kill Claims

Antiseptic products are expected to have a minimum time-to-effect of 30 seconds (for waterless handrubs) to 1 minute (for washes or scrubs using water) upon completion of application according to the proposed directions for use. As this is considered the norm for antiseptics, a claim that a product is fast-acting would have to demonstrate both a significantly shorter time-to-effect and still maintain clinical relevance.

8.3.4 Sterile

Any pharmaceutical product claiming sterility of any component of an antiseptic product must also undergo a chemistry and manufacturing review. Sponsors are recommended to consult the Health Canada guidance document on supporting data requirements for sterility claims: Stability Testing of Existing Drug Substances and Products and Quality Guidance: Applications for Drug Identification Numbers (DINAs) for Pharmaceuticals.

A product license application for a non-traditional natural health antiseptic product includes a chemistry and manufacturing review portion for all products, including those claiming sterility.

8.4 Labelling

All products intended for use in a professional setting should be labelled on the front panel of the inner and outer labels with the indications specified for each subcategory (see below).

Further, the inner and outer labels shall also carry the following warning statements and directions for use, clearly identified with appropriate headings:

• For external use only.
• Avoid contact with the eyes.
• Discontinue use if irritation and redness develops.
• Allow product to evaporate completely prior to use in electrocautery procedures [Note: required only for alcohol-based products].
• (For healthcare handwash ONLY): Use XmL and lather in hands with water for at least 30 seconds. Rinse well.^a
• (For healthcare handrub ONLY): Use XmL and rub thoroughly into hands for at least 30 seconds. Allow to dry.^a
• Do not refill container^b
• Meets [insert in vivo test methods].^{Footnote 9}

^a Where "XmL" is equivalent to the dose required to achieve effect, as measured in in vivo efficacy trials.
^b This statement may be excluded if it is demonstrated that the product is not in a refillable container.

Additional recommendations specific to the type of product are as follows:

8.4.1 Professional Handwash or Handrub

The front panels of the inner and outer labels should be labelled with the following indications:

• For Hospital and Healthcare Professional Use.
• To reduce bacteria, mycobacteria, fungi, and viruses on skin.

The directions for use (e.g. quantity, application procedure, etc) must comply with standard procedures as used in the efficacy test methods supporting the application.

8.4.2 Surgical handrub

The front panels of the inner and outer labels should be labelled with the following indications:

• For Hospital and Healthcare Professional Use
• "Preoperative antiseptic handrub" or "Surgical handrub"
• To reduce bacteria and fungi on skin to diminish the risk of surgical site infection.

The directions for use should include the following additional direction:

• Reapply every 6 hours or if hands are recontaminated.

The directions for use (e.g. quantity, application procedure, etc) must comply with standard presurgical procedures as used in the efficacy test methods supporting the application.

8.4.3 Surgical handwash

The front panels of the inner and outer labels should be labelled with the following indications:

• For Hospital and Healthcare Professional Use
• "Preoperative antiseptic handwash" or "Surgical handwash"
• To reduce bacteria and fungi on skin to diminish the risk of surgical site infection.

The directions for use should include the following additional direction:

• Reapply every 6 hours or if hands are recontaminated.

The directions for use (e.g. quantity, application procedure, etc) must comply with standard presurgical procedures as used in the efficacy test methods supporting the application.

8.4.4 Patient preoperative skin preparation

The front panels of the inner and outer labels should be labelled with the following indications:

• For Hospital and Healthcare Professional Use.
• "Preoperative antiseptic skin preparation"
• To reduce bacteria and fungi on skin to diminish the risk of surgical site infection.

The directions for use should include the following additional direction:

• Reapply every 6 hours or if skin is recontaminated.

The directions for use (e.g. quantity, application procedure, etc) must comply with standard presurgical procedures as used in the efficacy test methods supporting the application.

9 Effective Date

This guidance document will come into effect upon publication. All applicable antiseptic product submissions from the effective date of the Human-Use Antiseptic Drugs are expected to be filed with the recommended supporting data.

10 Appendices

Appendix I: Examples of Precedent Active Ingredients

Appendix II: References

ASTM International.

E 1115-02: Standard Test Method for Evaluation of Surgical Hand Scrub Formulations. USA, 2002.

E 1173-01e1: Standard Test Method of a Evaluation of a Preoperative, Precatheterization, or Preinjection Skin Preparations. USA, 2002.

E 1174-06: Standard Test Method for Evaluation of the Effectiveness of Health Care Personnel Handwash Formulations. USA, 2002.

E 2011-09: Standard Test Method for Evaluation of Hygienic Handwash and Handrub Formulations for Virus-Eliminating Activity Using the Entire Hand. USA, 2009.

E 2276-03: Standard Test Method for Determining the Bacteria-Eliminating Effectiveness of Hygienic Handwash and Handrub Agents Using the
Fingerpads of Adult Subjects. USA, 2003.

E 2613-08: Standard Test Method for Determining Fungus-Eliminating Effectiveness of Hygienic Handwash and Handrub Agents Using Finger Pads of Adults. USA, 2008.

CEN.

EN 1499: Chemical disinfectants and antiseptics. Hygienic handwash. Test method and recommendations (phase 2/step 2). Brussels, July 1997.

EN 1500: Chemical disinfectants and antiseptics - Hygienic handrub. Brussels, July 1997.

EN 12791: Chemical disinfectants and antiseptics. Surgical hand disinfection. Test method and requirement (phase 2, step 2). Brussels, 2005.

EN 13624: Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of fungicidal activity of chemical disinfectants for instruments used in the medical area. Test method and recommendations (phase 2, step 1). Brussels, 2003.

EN 13727: Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of bactericidal activity of chemical disinfectants for instruments used in the medical area - Test method and requirements (phase 2, step 1). Brussels, July 2003.

EN 14348: Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of mycobactericidal activity of chemical disinfectants in the medical area including instrument disinfectants. Test methods and recommendations (phase 2, step 1). Brussels, 2005.

EN 14476: Chemical disinfectants and antiseptics - Virucidal quantitative suspension test for chemical disinfectants and antiseptics used in human medicine - Test method and recommendations (phase 2/step 1). Brussels, May 2002.

Centre for Healthcare Related Infection Surveillance and Prevention.

Recommendations for Surgical Skin Antisepsis in Operating Theatres. Queensland Health, Australia, December 2006.

CGSB.

National Standard of Canada: Assessment of Efficacy of Antimicrobial Agents for Use on Environmental Surfaces and Medical Devices. Ottawa, Canada, June 1997.

Edwards P, Lipp A, Holmes A.

Preoperative skin antiseptics for preventing surgical wound infections after clean surgery (Review). The Cochrane Collection: The Cochrane Library, Issue 1, 2009.

FDA.

Topical Antimicrobial Drug Products for Over-the-counter Human Use; Tentative Final Monograph for Health-care Antiseptic Drug Products.333.470 Testing of health-care antiseptic drug products. 21 CFR Parts 333 and 369, June 17, 1994.

Fraise AP, Lambert PA, Maillard, J-Y, eds.

Russell,Hugo and Ayliffe's Principles and Practice of Disinfection, Preservation and Sterilization, 4 ^th Edition. United Kingdom: Blackwell Publishing, 2004.

Fulchiero GJ and Billingsley EM.

"Wound Infections" in Complications in Cutaneous Surgery, Gloster HM Jr, ed. New York: Springer, 2008: pp.46-61.

Gerba, CP.

The Occurrence of Heterotrophic Bacteria, Coliforms and Staphylococcus Aureus in Liquid Soap Samples from Public Restrooms. Unpublished study. University of Arizona. 2006

Health Canada.

Antiseptic Skin Cleansers. Ottawa, December 11, 2006.

Guidance Document: Disinfectant Drugs. Ottawa, April 29, 2007.

Larson E.

APIC Guidelines for Infection Control Practice: Guidelines for use of topical antimicrobial agents. American Journal of Infection Control, 16: 253-266.

Mayhall CG, ed.

Hospital Epidemiology and Infection. USA: Lippincott , Williams and Wilkins, 2004.

McDonnell, GE.

Antisepsis, Disinfection and Sterilization: Types, Action, and Resistance. Washington: ASM Press, 2007.

Paulson DS.

Handbook of Topical Antimicrobials. New York: Marcel Dekker, Inc. 2003.

Weber DJ, Rutala WA, Sickbert Bennet EE.

Outbreaks Associated with Contaminated Antiseptics and Disinfectants. Antimicrobial Agents and Chemotherapy, Dec 2007 (51)12: 4217-4224.

World Health Organization.

WHO Guidelines on Hand Hygiene in Health Care. Switzerland, 2009.