HOW TO REGISTER A HAND-SANITIZER WITH THE US FDA 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.

¾¾ Health Care Antiseptics

• They are primarily used by health care professionals in hospitals, clinics, doctors’ offices, outpatient settings and nursing homes. • They are not only used to protect the user but also to protect the patient. • They are often used more frequently by health care workers.

¾¾ Consumer Antispetics

• They are primarily used in the home, schools, daycares or other public settings. • Generally applied to protect the user. • They are sold in retail establishments like drug stores and 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 3 Global Regulatory Partners, Inc

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.

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

Active Ingredient Consumer Antiseptic Rub Consumer Antiseptic Wash

ü Alcohol (ethyl alcohol) 60 to 95 percent ü Isopropyl alcohol 70 to 91.3 percent

Benzalkonium Chloride ü

Benzethonium chloride

Chloroxylenol

Chlorhexidine gluconate

Cloflucarban ü

Fluorosalan ü

Hexachlorophene ü

Hexylresorcinol ü

Iodophors (Iodine- ü containing ingredients) Iodine Complex (ammonium ether sulfate and  polyoxyethylene sorbitan monolaurate) Iodine Complex (phosphate ester of alkylaryloxy  polyethylene glycol)

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Active Ingredient Consumer Antiseptic Rub Consumer Antiseptic Wash

Methylbenzethonium  Chloride Nonylphenoxypoly  (ethyleneoxy) ethanoliodine Phenol (equal to or less than 1.5 percent or greater  than 1.5 percent) Poloxamer iodine complex 

Povidone-iodine 5 to 10  percent

Secondary amyltricresols 

Sodium oxychlorosene 

Tribromsalan 

Triclocarban 

Triclosan 

Triple dye 

Undecoylium chloride  iodine complex

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

Patient Health care Health care Surgical Hand Surgical Hand Active Ingredient Antiseptic skin Handwash Hand Rub Scrub Rub reparation Alcohol 60 to 95 percent   

Benzalkonium chloride    

Benzethonium chloride   

Chlorhexidine gluconate

Chloroxylenol   

Cloflucarban   

Fluorosalan   

Hexylresorcinol    Iodine complex (ammonium ether sulfate and   polyoxyethylene sorbitan monolaurate) Iodine complex (phosphate ester of alkylaryloxy    polyethylene glycol) Iodine tincture United  States Pharmacopeia (USP) Iodine topical solution USP  Nonylphenoxypoly    (ethyleneoxy) ethanoliodine Poloxamer-iodine complex    Povidone-iodine 5 to 10    percent Undecoylium Chloride    Iodine Complex Isopropyl alcohol 70-91.3    percent Mercufenol Chloride 

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Patient Health care Health care Surgical Hand Surgical Hand Active Ingredient Antiseptic skin Handwash Hand Rub Scrub Rub reparation Methylbenzethonium    chloride Phenol (equal to or less    than 1.5 percent) Secondary Amyltricresols   

Sodium Oxychlorosene   

Triclocarban   

Triclosan    Combination: Calomel, oxyquinoline benzoate,  triethanolamine, and phenol derivative Combination: Mercufenol chloride and secondary  amyltricresols in 50 percent alcohol Triple dye 

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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.

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

Non-Monograph OTC Approval of new drug Process (NDA/ANDA) under section 505(b)(2)

Approval of an abbreviated new drug Regulatory Pathway application under section 505(j)

Meet standards of applicable monograph (no OTC Monograph* Process marketing pre-clearance required)

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

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

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• Pre-market approval • Confidential filing • Drug product-specific • May require a user fee OTC Non-monograph Process • Potential for marketing exclusivity (NDA/ANDA) • Mandated FDA review timelines • May require clinical studies • Label comprehension • Actual use

• No pre-market approval • Public process • Active ingredient-specific • OTC drug category • No user fees OTC Monograph Process • No marketing exclusivity • No mandated timelines • May require clinical studies • Label comprehension and actual use studies not required

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

Figure 6: NDC label 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

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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 Registration Annual 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

Generally Recognized as Safe/Generally Recognized GRAS/GRAE 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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ABOUT GLOBAL REGULATORY PARTNERS, INC

Global Regulatory Partners Inc, (GRP) provides regulatory affairs, clinical, quality and safety services to medical devices and pharmaceutical companies globally. As a qualified and licensed legal representative with offices in USA, China, Japan, Brazil, Mexico and Argentina, the company can represent life science companies in those countries and help them register their products in compliance with local regulations and in record time.

For additional information, please contact us at [email protected]

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Email: [email protected]

Website: www.globalregulatorypartners.com

Telephone: 781.672.4200

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