how to register a hand-sanitizer with the us fda · using structured product labeling (spl) format...

HOW TO REGISTER A HAND-SANITIZER WITH THE US FDA

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Global Regulatory Partners, Inc

OVERVIEW:

The US FDA considers alcohol-based hand sanitizers as Over the Counter Products (OTC). The OTC are divided into two categories either health care antiseptics or consumer antiseptics. OTC consumer antiseptics are broken down into two groups: washes and rubs while antiseptics for Healthcare use are broken down into Patient Antiseptic Skin Preparation, Healthcare antiseptic hand wash, Healthcare Hand Rub, Surgical Hand rub, Surgical Hand Scrub.

¾ Health Care Antiseptics

• They are primarily used by health careprofessionals in hospitals, clinics,doctors’ offices, outpatient settingsand nursing homes.

• They are not only used to protect theuser but also to protect the patient.

• They are often used more frequentlyby health care workers.

¾ Consumer Antispetics

• They are primarily used in thehome, schools, daycares or otherpublic settings.

• Generally applied to protect theuser.

• They are sold in retailestablishments like drug storesand grocery stores

Figure 1: Health Care Antiseptics Vs. Consumer Antiseptics

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Rubs or Leeave - on products are not rinsed off after use. Rubs include health care personnel hand rubs, surgical hand rubs, and patient antiseptic skin preparations.

Washes also known as anti-bacterial soap are rinsed off with water. They include health care personnel hand washes and surgical hand scrubs They are intended for use with water and are rinsed off after use.

Figure 2: Rubs Vs Washes

HOW TO REGISTER A HAND SANITIZER WITH THE FDA?

Step 1: Assess the list of active ingredients

Step 2: Determine registration pathway

Step 3: Assess of Label Compliance

Step 4: Request of NDC Code and a Labeler Code from FDA.

Step 5: Register the manufacturer establishment with FDA.

Step 6: List the Drug with FDA.

HOW TO REGISTER A HAND-SANITIZER WITH THE US FDA | www.globalregulatorypartners.com

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Table 1: Active Ingredients Eligible for Evaluation For Consumer Use under OTC Drug Review

Active Ingredient Consumer Antiseptic Rub Consumer Antiseptic Wash

Alcohol (ethyl alcohol)ü

60 to 95 percent

Isopropyl alcoholü

70 to 91.3 percent

Benzalkonium Chloride ü

Benzethonium chloride

Chloroxylenol

Chlorhexidine gluconate

Cloflucarban ü

Fluorosalan ü

Hexachlorophene ü

Hexylresorcinol ü

Iodophors (Iodine-containing ingredients)

ü

Iodine Complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate)

ü

Iodine Complex (phosphate ester of alkylaryloxy polyethylene glycol)

ü

1. ASSESS THE LIST OF ACTIVE INGREDIENTS

To Assess the List of active ingredients the applicant must heck if the ingredients belong to the authorized list for consumer use found in Table 1 and healthcare use found in Table 2.

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Active Ingredient Consumer Antiseptic Rub Consumer Antiseptic Wash

Methylbenzethonium Chloride

ü

Nonylphenoxypoly (ethyleneoxy) ethanoliodine

ü

Phenol (equal to or less than 1.5 percent or greater than 1.5 percent)

ü

Poloxamer iodine complex ü

Povidone-iodine 5 to 10 percent

ü

Secondary amyltricresols ü

Sodium oxychlorosene ü

Tribromsalan ü

Triclocarban ü

Triclosan ü

Triple dye ü

Undecoylium chloride iodine complex

ü

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Active IngredientPatient Antiseptic skin reparation

Health care Handwash

Health care Hand Rub

Surgical Hand Scrub

Surgical Hand Rub

Alcohol 60 to 95 percent ü ü ü

Benzalkonium chloride ü ü ü ü

Benzethonium chloride ü ü ü

Chlorhexidine gluconate

Chloroxylenol ü ü ü

Cloflucarban ü ü ü

Fluorosalan ü ü ü

Hexylresorcinol ü ü ü

Iodine complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate)

ü ü

Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol)

ü ü ü

Iodine tincture United States Pharmacopeia (USP)

ü

Iodine topical solution USP ü

Nonylphenoxypoly (ethyleneoxy) ethanoliodine

ü ü ü

Poloxamer-iodine complex ü ü ü

Povidone-iodine 5 to 10 percent

ü ü ü

Undecoylium Chloride Iodine Complex

ü ü ü

Isopropyl alcohol 70-91.3 percent

ü ü ü

Mercufenol Chloride ü

Table 2: Eligibility of Antiseptic Active Ingredients for Health Care Antiseptic Uses

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Active IngredientPatient Antiseptic skin reparation

Health care Handwash

Health care Hand Rub

Surgical Hand Scrub

Surgical Hand Rub

Methylbenzethonium chloride

ü ü ü

Phenol (equal to or less than 1.5 percent)

ü ü ü

Secondary Amyltricresols ü ü ü

Sodium Oxychlorosene ü ü ü

Triclocarban ü ü ü

Triclosan ü ü ü

Combination: Calomel, oxyquinoline benzoate, triethanolamine, and phenol derivative

ü

Combination: Mercufenol chloride and secondary amyltricresols in 50 percent alcohol

ü

Triple dye ü

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2. DETERMINE THE REGISTRATION PATHWAY

The Registration Pathway depends on the list of the active ingredients; if these active ingredients are monograph or non-monograph. See Figure 3 and Figure 4 for more details on the different pathways.

Meet standards of applicable monograph (no marketing pre-clearance

required)

Approval of new drug under section 505(b)(2)

OTC Monograph* Process

*OTC monographs are similar to “recipe books” covering acceptable ingredients,doses, formulations, labeling, and in some cases, testing parameters.

Approval of an abbreviated new drug

application under section 505(j)

Approval of new drug under section 505(b)(1)

Non-Monograph OTC Process (NDA/ANDA)

Regulatory Pathway

Figure 3: OTC monograph vs. Non-monograph pathway based on active ingredients.

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Figure 4: Overview of OTC non-monograph Process Vs. OTC monograph Process

• Pre-market approval

• Confidential filing

• Drug product-specific

• May require a user fee

• Potential for marketing exclusivity

• Mandated FDA review timelines

• May require clinical studies

• Label comprehension

• Actual use

OTC Non-monograph Process (NDA/ANDA)

• No pre-market approval

• Public process

• Active ingredient-specific

• OTC drug category

• No user fees

• No marketing exclusivity

• No mandated timelines

• May require clinical studies

• Label comprehension and actual

use studies not required

OTC Monograph Process

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3. ASSESS LABEL COMPLIANCE

The labeling regulations for all OTC products are covered by 21 CFR 201.66. The information allowed on a drug label is determined by the FDA drug classification. The FDA requires that all OTC drug product labeling contain the following information about the drug product. This information must be organized according to the following headings and must be presented in the following order:

1. Title (Drug Facts or Drug Facts (continued))

2. Active ingredient(s)

3. Purpose(s)

4. Use(s)

5. Warning(s)

6. Directions

7. Other information

8. Inactive ingredients

Figure 5: Example of FDA Label for a drug.

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4. REQUEST NDC CODE AND A LABELER CODE FROM FDA

What is an NDC Code?

NDC Code includes 10 digits. The first five digits are assigned by FDA and they represent labeler code. Labeler code identifies the product “labeler” (brand owner or the company who take ownership of the product), and the last 5 numeric characters identify the drug formulation is known as the Product Code and the segment that identifies the trade package size and type is known as the Package Code.

How to request an NDC Labeler code for FDA?

To obtain an NDC Labeler code from FDA, the manufacturer or local agent must request for one using Structured Product Labeling (SPL) format should be submitted to FDA via FDA’s Electronic Submission Gateway or ESG.

NDC Labeler Code Request Documents :

• The name and DUNS number of the establishment (not one linked to the corporate HQ)

• Contact information of someone responsible for receiving FDA communications related to that

establishment;

• All applicable business operations that establishment performs; and

• For foreign establishments, the name and DUNS of a U.S. agent and all importer

Figure 6: NDC label code

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5. REGISTER THE ESTABLISHMENT WITH FDA

Domestic Manufacturers:Domestic hand sanitizer manufacturers must register their establishment with FDA within 5

calendar days after start manufacturing and complete hand sanitizer listing with 10-digit NDC

Number within 3 days after establishment registration.

Foreign Manufacturers:Foreign Hand Sanitizer manufacturer must complete registration and drug listing before start

marketing in the USA.

Renewal of RegistrationAnnual renewal of registration must occur between October 1 and December 31 of each year.

Information submitted for drug establishment registration:

• name and full address of each establishment

• all trade names used by the establishment

• the kind of ownership or operation

• the name of the owner or operator

Additional information for a foreign establishment:

• the name, address and phone number of the foreign registrant’s US agent

• the name of each importer that is known to the establishment

• the name of each person who imports or offers for import such drugs

Electronic submission registrants submit additional information in SPL file:

• official contact’s name, mailing address, telephone number(s), and email address; and

• the type of operation(s) performed at each establishment

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6. LIST THE DRUG WITH FDA

Registrant must list each drug it manufactures, repacks, relabels, or salvages for commercial

distribution.

Listing information:

1. Appropriate NDCs

2. Package type and volume information corresponding to the package code segment of the NDC

3. The listed drug’s established name and proprietary name, if any;

4. The name and quantity of each active pharmaceutical ingredient in the listed drug;

5. The name of each inactive ingredient, along with any assertion confidentiality associated with

individual inactive ingredient

6. The dosage forms

7. The drug’s approved U.S. application number; if any;

8. The drug type (nonprescription)

9. The route or routes of administration;

10. If bearing an NDC:

• (i) The name and Unique Facility Identifier of the establishment where the registrant who

lists the drug manufactures it and the type of operation performed on the drug at that

establishment, and

• (ii) The name and Unique Facility Identifier of every other establishment where manufacturing

is performed for the drug and the type of operation performed at each such establishment.

This includes all establishments involved in the production of each unfinished drug received

by the registrant for use in the production of the drug being listed. The names, Unique

Facility Identifiers, and type of operations for establishments involved in production of each

unfinished drug received by the registrant for use in the production of the drug being listed

may be provided by including the properly assigned and listed NDC for such unfinished drug.

11. Advertisements

12. Drug bearing NDCs

• Human nonprescription drugs: all current labeling, except that only one representative

container or carton label need be submitted where differences exist only in the quantity of

contents statement or the bar code

13. Additionally, the drug’s OTC monograph reference, if any; and

• The date on which the drug was or will be introduced into commercial distribution

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What are the FDA Timelines for Hand Sanitizer Registration?

Generally, Hand Sanitizer FDA Registration will take approximately 14-20 working days by

completing the above steps . The main delay happens is in getting the first 5 digit of NDC

number from FDA. Once we request, it may take 7-14 working days.

Table 4: Table of Abbreviation

Abbreviation What it means

ANDA Abbreviated New Drug Application

CPSC Consumer Product Safety Commission

FDA Food and Drug Administration

FD&C Act Federal Food, Drug, and Cosmetic Act

FTC Federal Trade Commission

FR Federal Register

FY Fiscal Year

GMP Good Manufacturing Practice

GRAS/GRAEGenerally Recognized as Safe/Generally Recognized as Effective

MBC Minimum Bactericidal Concentration

MIC Minimum Inhibitory Concentration

MUsT Maximal Usage Trial

NDA New Drug Application

NDC National Drug Code

OTC Over-the-counter

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REFERENCES:

Center for Drug Evaluation and Research. (n.d.). Labeling OTC Human Drug Products -- Questions and Answers. Retrieved from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/labeling-otc-human-drug-products-questions-and-answers

Safety and Effectiveness of Health Care Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use. (2017, December 20). Retrieved from https://www.federalregister.gov/documents/2017/12/20/2017-27317/safety-and-effectiveness-of-health-care-antiseptics-topical-antimicrobial-drug-products-for

Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use. (2016, September 6). Retrieved from https://www.federalregister.gov/documents/2016/09/06/2016-21337/safety-and-effectiveness-of-consumer-antiseptics-topical-antimicrobial-drug-products-for

Safety and Effectiveness of Consumer Antiseptic Rubs; Topical Antimicrobial Drug Products for Over-the-Counter Human Use. (2019, April 12). Retrieved from https://www.federalregister.gov/documents/2019/04/12/2019-06791/safety-and-effectiveness-of-consumer-antiseptic-rubs-topical-antimicrobial-drug-products-for

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