Frequently Asked Questions related to Health Canada's Guidance Document: Disinfectant Drugs

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Notice

April 27, 2010

Our file number: 10-109675-529

To Disinfectant Drug Sponsors: Release of Frequently Asked Questions related to Health Canada's Guidance Document: Disinfectant Drugs

This Notice contains Frequently Asked Questions (FAQs) related to the information provided in Health Canada's Guidance Document: Disinfectant Drugs (August 29 2007).

The FAQs have been developed by the Therapeutic Products Directorate's Disinfectant Unit and take into account the types of questions and responses this unit has responded to since the posting of the Guidance Document: Disinfectant Drugs.

The release of the FAQs provides an opportunity for disinfectant drug sponsors to refer to this information in addition to the requirements as provided in the applicable Health Canada Guidance Document(s).

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

Bureau of Gastroenterology, Infection and Viral Diseases
Therapeutic Products Directorate
Health Products and Food Branch
Health Canada
Finance Building, Address Locator 0202D1
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0K9

Facsimile: (613) 941-1183

Email: BGIVD_Enquiries@hc-sc.gc.ca

Frequently Asked Questions

• Microbicidal Efficacy Test Performance Criteria
• Testing with Viral Surrogates
• Label Use Directions for Contact Time and Use Dilution
• Towelette Testing
• Mycobactericide Testing
• Organism Specific Disinfectant
• Number of Batches or Lots Required to be Tested
• Number of Cultures or Carriers Required for Testing
• Information Dissemination
• Organisms Required for General Claims
• Requirements for an Application
• Disinfectant Drug Products classified as "New Drugs"

1.0 Microbicidal Efficacy Test Performance Criteria

1.1 What are the log₁₀ reduction performance criteria for microbicidal efficacy?

Bacterial spores: For chemosterilization and high-level disinfection, a minimum 6 log₁₀ reduction is required.

Mycobacteria: For chemosterilization and high-level disinfection, a minimum 6 log₁₀ reduction is required. For intermediate-level disinfection, a minimum 4 log₁₀ reduction is required.

Bacteria: For disinfection, a minimum 5 log₁₀ kill is required. For a disinfectant-sanitizer, a minimum 3 log₁₀ kill is required for sanitization.

Virus: As per Section 5.6 of the Canadian General Standards Board (CAN/CGSB)-2.161, for disinfection the viral "infectivity titer must be reduced by at least 3 log₁₀ beyond the level of cytotoxicity".

Fungi: For disinfection, a minimum of 4 log₁₀ reduction is required.

1.2 Will Health Canada accept data in support of claims against vegetative cells, or the use of vegetative cells, to generate efficacy data in support of claims against spore-forming bacteria?

As indicated in Section 5.2 of the Guidance Document: Disinfectant Drugs, Health Canada will not approve the labelling of a non-sporicidal disinfectant with claims against the vegetative cells of spore-forming bacteria.

1.3 Will Health Canada accept claims against Clostridium difficile spores for hard non-porous surfaces only when tested on hard non-porous surfaces?

All efficacy tests, including Clostridium difficile protocols, are to be conducted on hard non-porous surfaces or acceptable surfaces that generate data equivalent to testing on hard non-porous surfaces.

2.0 Testing with Viral Surrogates

2.1 Does the full validation condition stated in Section 2.1 of the Guidance Document: Disinfectant Drugs for hepatitis B virus (HBV) surrogate testing, apply to all other surrogate microorganisms?

The full validation condition does not apply to all situations. Specifically, testing in only one laboratory is required for the feline calicivirus surrogate, for Norwalk or Norwalk-like viruses and for the bovine viral diarrhea virus surrogate for Hepatitis C. Testing in two laboratories is required for the duck hepatitis B virus surrogate for Hepatitis B.

2.2 Does full validation require surrogate testing in laboratories owned by two different companies in two different locations?

To meet full validation, surrogate testing should be conducted independently (that is [i.e.] by different study directors); however, their laboratories may be located on the same sites and belong to a single company or organization.

2.3 Does full validation require surrogate testing of three lots in each of the two independent laboratories?

Typically, validation of the surrogate testing of three product lots is required in one laboratory and then two product lots, tested in the second laboratory, would suffice for validation purposes.

2.4 Is testing on a single large carrier such as 10 square inches per lot, acceptable to represent microbicidal efficacy of that lot?

Multiple carriers are required to assess variability given that the statistical value and/or the level of confidence obtained from one single carrier per lot cannot be adequately estimated.

2.5 Do the testing requirements differ for bloodborne pathogens versus non-bloodborne pathogens?

The testing requirements do not differ for bloodborne pathogens vs. non-bloodborne pathogens. At present, only the duck hepatitis B virus surrogate requires validation.

3.0 Label Use Directions for Contact Time and Use Dilution

3.1 Can a disinfectant product be labelled with contact times and use dilutions that vary depending on which pathogens are targeted?

As stated in the Guidance Document: Disinfectant Drugs, contact times and use dilutions that vary depending on which pathogens are targeted are unacceptable as the end user is unable to readily determine which microorganisms are present on a target surface. Therefore, a disinfectant product cannot be labeled with contact times and use dilutions that vary depending on which pathogens are targeted. For example, a label may not make reference to a 5 minute contact time for efficacy against bacteria and a 10 minute contact time for efficacy against fungi.

The exception to the above is Human Immunodeficiency Virus (HIV) where a separate contact time is allowed.

3.2 If a product label indicates a contact time of 10 minutes for disinfection, can the sponsor advertise elsewhere (for example [e.g.] in supplemental product literature and/or website) that the product disinfects against bacteria in 5 minutes, fungi in 3 minutes, and viruses in 1 minute?

The contact time, as described on the authorized product label, must be reflected in any communication to the public through websites, technical literature, "1-800" consumer information services and similar media.

4.0 Towelette Testing

4.1 In the absence of data representing actual wipe tests using a towelette on a hard surface, can disinfectant testing using the liquid formulation support the efficacy claims for a towelette product?

As per Section 5.4.5.II of the Guidance Document: Disinfectant Drugs, products marketed as wipes or towelettes are assessed on the basis of the efficacy of the liquid disinfectant itself. Therefore, in the absence of data for a wipe test, a liquid formulation supporting efficacy claims is acceptable as long as the sponsor ensures that the contact time of the liquid disinfectant corresponds to the contact time for the towelette.

4.2 In testing a towelette, is it required to assess the contamination on the towelette that was used to wipe the contaminated surface?

When testing the towelette, it is not necessary to assess the contamination on the towelette provided that an organic load is used in the test methodology and the product is a single-use towelette.

5.0 Mycobactericide Testing

5.1 Section 5.4.6.1 of the Guidance Document: Disinfectant Drugs recommends that an additional quantitative test also be considered as part of the mycobactericida method. What test does this requirement refer to?

Consistent with the recommendation, as provided in this section of the Guidance Document, qualitative tests designed to screen the presence or absence of mycobacteria will not suffice to support a mycobactericidal claim given that it does not provide a quantitative measure of the log reduction. In turn, a quantitative test that provides log₁₀ reduction values is required to be part the protocol.

6.0 Organism Specific Disinfectant

6.1 Will Health Canada grant a Drug Identification Number (DIN) for a product that is intended for sale as a disinfectant, but has no target organism listed on its label?

A DIN for a product that has no target organism listed on its label could be granted; however, as per Section 5.2 of the Guidance Document: Disinfectant Drugs: "A disinfectant without specific target organisms indicated on the product label is regarded only as a bactericide."

6.2 Will Health Canada grant a DIN for a disinfectant that is labelled with a claim of disinfecting only a single microorganism?

Health Canada will grant a DIN for a product which has demonstrated disinfectant efficacy against a single microorganism; however, only a disinfectant claim attesting the effectiveness against the specific microorganism tested can be listed on the product label.

6.3 Will Health Canada grant a DIN for a disinfectant that is labelled with a claim of disinfecting only a single bacterium that is not one of the three required in Section 6.10 of the CAN/CGSB-2.161?

Health Canada will grant a DIN for a product which has demonstrated disinfectant efficacy against a single bacterium; however, only a disinfectant claim attesting the effectiveness against the specific bacterium tested can be listed on the product label.

6.4 Can a single-bacterium disinfectant be labelled with associated claims against other microorganisms, such as fungi and viruses?

A single-bacterium disinfectant could be labeled as being effective against fungi or viruses, as long as data demonstrating effectiveness of the product against all the microorganisms has been provided.

For example, a disinfectant effective against Staphylococcus aureus only, but with data demonstrating its effectiveness against both Trichophyton mentagrophytes and poliovirus type 1 (Sabin), would be eligible to carry three specific claims on its label corresponding to the three microorganisms. Additionally, based on Sections 6.11 and 6.12 of the CAN/CGSB-2.161, this disinfectant could be labelled as both a fungicide and a virucide, two general claims, but not as a bactericide.

6.5 Could a disinfectant product be labelled only as effective against Gram-positive or Gram-negative bacteria?

Given that the end user is unable to readily determine whether the microorganisms present on a surface are Gram positive or Gram negative, the product label must not be labeled only as effective against Gram-positive or Gram-negative bacteria.

7.0 Number of Batches or Lots Required to be Tested

7.1 As per Sections 6.1 of the CAN/CGSB-2.161 and 5.4.6 of the Guidance Document: Disinfectant Drugs, is testing of at least 3 samples, representing 3 separately compounded batches of product, necessary?

The response to this question depends on the type of claims, as described below.

For general claims:
The requirement for testing at least 3 separately compounded product batches reflects the minimum number necessary for statistical purposes. Therefore, for the general claims listed in Sections 6.9 through 6.13 of the CAN/CGSB-2.161, microorganisms should always be tested using at least 3 product batches or lots.

Claims against additional microorganisms:
Once a general claim has been established, testing against 2 separately compounded product batches should suffice to support additional claims against specific microorganisms.

For example, a product with demonstrated efficacy as a bactericide should only require testing of 2 separately compounded product batches against any additional bacteria.

Specific claims in absence of general claims:
If a general claim has not been established, data demonstrating the effectiveness of the product against a specific microorganism requires testing with at least 3 separately compounded product batches.

For example, in the absence of a general claim, such as a virucidal claim established based on efficacy testing against poliovirus, testing is required with at least 3 separately compounded product batches to demonstrate efficacy against a specific microorganism.

7.2 Will Health Canada allow a "Clostridium difficile sporicide" claim without a general sporicidal claim demonstrated by disinfectant efficacy data against Bacillus subtilis and Clostridium sporogenes?

Health Canada will not allow such a claim since making a "Clostridium difficile sporicide" claim is considered to be misleading and unacceptable, as the use of the term "sporicide" on a product label is conditional to proof of efficacy against Bacillus subtilis and Clostridium sporogenes, in accordance with Sections 5.2 and 6.9 of the CAN/CGSB-2.161.

8.0 Number of Cultures or Carriers Required for Testing

8.1 As per Sections 5.2, 5.3, and 5.6 through 5.8 of the CAN/CGSB-2.161, what are the requirements for the number of cultures tested, and for the post-disinfection ratio of acceptable growth per total cultures tested (i.e. growth/cultures ratio)?

With respect to the number of cultures tested, sponsors are required to submit data that meets the following criteria from a statistical and microbiological perspective.

Bacterial sporicide and sterilant: The demonstration of sporicidal activity requires testing of at least 120 cultures per microorganism per batch with a maximum of 2 tolerable failures each (i.e. not more than 2 cultures out of 120 shall show growth in efficacy tests against Bacillus subtilis and Clostridium sporogenes). However, claims for chemosterilization are required to show no growth on any of the cultures (i.e. no failures), as noted in the AOAC official method 966.04.

Bactericide, mycobactericide and fungicide: The demonstration of bactericidal, mycobactericidal or fungicidal activity requires testing of at least 60 cultures per microorganism per batch with a maximum of 2 tolerable failures each (i.e. not more than 2 cultures out of 60 shall show growth in efficacy tests against Salmonella choleraesuis, Pseudomonas aeruginosa, Staphylococcus aureus, Mycobacterium bovis/terrae and Trichophyton mentagrophytes).

Virucide: The demonstration of virucidal activity requires the successful testing of at least 5 cultures (i.e. no carrier shall show less than 3 log₁₀ reduction beyond the level of cytotoxicity on all test cultures).

8.2 If a product has met the criteria as being a general sporicidal (i.e. demonstrated efficacy against Bacillus subtilis and Clostridium sporogenes) how many cultures are required in support of efficacy claims against other spore forming bacteria (e.g. Clostridium difficile)?

Once a general sporicidal claim has been established for a product through testing against B. subtilis and C. sporogenes, a minimum of 60 cultures per microorganism per batch, with not more than 1 failures each, may be found sufficient to support additional claims against specific bacterial spores.

8.3 In the absence of a general sporicidal claim, how many cultures are required to prove efficacy against other spore forming bacteria (e.g. Clostridium difficile)?

Sponsors are required to test, at minimum, 120 cultures per microorganism per batch with a maximum of 2 tolerable failures each.

8.4 If a product has met the criteria as a general bactericide (i.e. demonstrated efficacy against Salmonella choleraesuis, Pseudomonas aeruginosa and Staphylococcus aureus), will Health Canada accept the results of testing of the same product against additional, non-spore forming bacteria, using 10 cultures?

Once a general bactericidal claim has been established, a minimum of 10 cultures per microorganism per batch, with no failures, may be found sufficient to support additional claims against non-spore forming bacteria. Additionally, as indicated in question 7.1, testing against only 2 separately compounded product batches should suffice to support the additional claims.

8.5 In the absence of a general bactericidal claim, how many cultures should be tested to prove efficacy against other non-spore forming bacteria?

Sponsors are required to test, at a minimum, 60 cultures per microorganism per batch with a maximum of 2 tolerable failures each. Additionally, as indicated in question 7.1, testing against at least 3 separately compounded product batches is required.

8.6 If a product has met the criteria as a general fungicide (i.e. demonstrated efficacy against Trichophyton mentagrophytes), what is the minimum acceptable number of cultures per batch for testing against additional fungi?

Once a general fungicidal claim has been established, at a minimum, 10 cultures per fungus per batch, with no failures, may be found sufficient to support additional claims against other fungi. Additionally, as indicated in question 7.1, testing against only 2 separately compounded product batches should suffice to support the additional claims.

8.7 In the absence of a general fungicidal claim, how many cultures are required to prove efficacy against other fungi?

Sponsors are required to test, at minimum, 60 cultures per microorganism per batch with a maximum of 2 tolerable failures. Additionally, as indicated in question 7.1, testing against at least 3 separately compounded product batches is required.

8.8 When demonstrating efficacy testing against a sporicide or bactericide that requires not more than 2 growths per total cultures tested, a small number of additional growths may appear as false positives. Will Health Canada accept the data in support of a DIN application if there is proof that these additional growths are false positives?

The observation of not more than 2 test failures in either sporicidal or bactericidal tests, first and foremost indicates a product's inability to demonstrate the established efficacy requirements against a particular microorganism. Moreover, it also takes into account the "inherent variability" of the test method used and the potential for it to influence results. Therefore, while sponsors could provide a strong scientific rationale in support of additional failures (i.e. an explanation of a false positive), the likelihood of a positive decision, following review and without additional efficacy data, is limited.

9.0 Information Dissemination

9.1 Does Health Canada provide guidance to sponsors for disseminating information to the public about the effectiveness of their disinfectant drugs?

The extent of Health Canada's guidance to sponsors is provided in the applicable guidances, as available on Health Canada's website. In turn, the effectiveness of a disinfectant drug is relayed to the public by the information captured on an authorized product label.

9.2 Does Health Canada have a "general" policy that provides guidance to sponsors for disseminating information to the public about the effectiveness of a particular disinfectant against an emerging pathogen in a timely manner? If not, will it consider developing such a policy?

At this time, Health Canada does not have such a "general" policy nor is it considering developing one. However, Health Canada will assess the nature of various emerging pathogens, on a case-by-case basis, and could consider the development and issuance of specific guidance, in a timely manner, such as what is currently available for the 2009 (H1N1) pandemic influenza A virus.

10.0 Organisms Required for General Claims

10.1 Will Health Canada accept efficacy data against an alterative, non-enveloped virus as a substitute for poliovirus in support of a general virucidal claim?

Health Canada could accept an alternate non-enveloped virus, such as echovirus or adenovirus type 5, as potential substitutes for poliovirus in support of a general virucidal claim.

If a sponsor intends on using these substitutes, Health Canada requests that sponsors clearly communicate this substitution in the cover letter that accompanies a DIN application.

11.0 Requirements for an Application

11.1 What reference material/guidance documents are available for the preparation of a disinfectant drug application?

When preparing a disinfectant drug application, applicants should familiarize themselves with the following reference material:

1. Health Canada's Guidance Document: Disinfectant Drugs;
2. Health Canada's Guidance to Industry: Management of Drug Submissions;
3. Canadian General Standards Board's Document: CGSB-2.161-97, which refers to the microbicidal efficacy test standards; and Health Canada's Health Products and Food Branch Inspectorate's Guide-0049: Standard for the Fabrication, Control, and Distribution of Antimicrobial Agents for Use on Environmental Surfaces and Certain Medical Devices.

11.2 Where can I find the relevant application forms for a disinfectant drug submission?

The application forms are available on the Health Canada website and can also be obtained from:

Submission and Information Policy Division (SIPD)
Therapeutic Products Directorate
Health Canada
Address Locator 0201A1, Finance Building (#2)
101 Tunney's Pasture Driveway
Ottawa, Ontario
K1A 0K9
Facsimile: 613-941-0825

11.3 Is a DIN required to market a disinfectant drug product?

As per the Food and Drugs Act and Regulations, products that are labelled and/or sold as hard surface disinfectants, must be registered and authorized for sale by Health Canada's Therapeutic Products Directorate. Therefore, the receipt of a Drug Identification Number, prior to sale of the product on the Canadian market (which includes any advertisements of the disinfectant drug product), is required.

11.4 Are Good Manufacturing Practices (GMP) required for disinfectant drug products?

Requirements for GMP depend on the type of product. That is, Health Canada's certification forms for DIN submissions and Category IV DIN submissions reflect the exemption applied to some antimicrobial products, such as low-level hard surface disinfectants, with respect to GMP. However, this exemption does not apply to higher risk disinfectant products such as contact lens disinfectants, chemosterilants and high level disinfectants used to sterilize invasive devices or devices used for circulation, reintroduction of a body fluid or for introduction in a body cavity as well as to antimicrobial drug products for use on the skin.

For more information, please refer to the certification form that is available on Health Canada's website.

12.0 Disinfectant Drug Products classified as "New Drugs"

12.1 How do I proceed to commercialize a disinfectant drug product that has been identified as a "New Drug"?

When a disinfectant drug product is determined to meet the requirements of a "new drug", as defined in Division 8 of the Food and Drug Regulations, an applicant must submit a New Drug Submission instead of a DIN application.

Prior to submitting an application, applicants could request for a pre-submission meeting to better understand the submission and evidence requirements necessary to support such a submission.

For information on pre-submission meetings and package requirements, please consult the Guidance to Industry: Management of Drug Submissions.