OTC Drug Registration and Labeling Guidelines in USA

Submitted by : Amit SangwanM.Pharm (DRA) Maharishi Dayanand UniversityRohtak

Submitted to : Mr. Himanshu SharmaRanbaxy Laboratories LimitedGurgaon

Introduction Registration procedure for OTC drugs a) OTC monograph b) OTC NDA Labeling guidelines for OTC drugs a) content of labeling b) format of labeling Conclusion References

CONTENTS

Over the counter drugs are medicines that may be sold directly to a consumer without a prescription from health care professional, compared to prescription drugs, which may be sold to consumers possessing a valid prescription.

They are also called Non-prescription drugs.

Introduction(1)

Some typical characteristics of OTC products:

The product can be safely used without a prescription based on a long history of use.

Consumers can appropriately self-select (or de-select) the product based on the OTC label, supported by label user testing.

Potential for misuse or abuse of the product is low.

The benefits of using the product as OTC clearly outweigh the risks.

Conti..

Two regulatory pathways for OTC drugs registration in USA.

OTC Drug Monograph

OTC New Drug Application (NDA)

Registration procedure(2)

Office of the Non-prescription Products (ONP)

Office of the New Drugs (OND) These are the sub offices of the Centre for

Drug Evaluation and Research of US FDA. These are responsible for review of OTC

NDA and regulations concerning OTC drug monographs.

Regulatory authorities(3)

Conti...

Office of the Non-prescription Products (ONP)

Division of Nonprescription Regulation Development (DNRD)

Division of Nonprescription Clinical Evaluation (DNCE)

Regulates OTC monograph

Regulates OTC NDAs

In 1972: FDA established OTC drug review procedures for designed of OTC monographs(regulatory standards) for registration or marketing of OTC products not covered by NDA.

Final monographs are published in Code of Federal Regulations: 21 CFR parts 331-338.

OTC Monograph(4)

A Recipe book for marketing an OTC drug.

A list and explanation of GRASE conditions GRASE = Generally Recognized As Safe and Effective

What is OTC monograph ?

1) GRASE active ingredients dosage strength dosage form 2) Labeling requirements indications warning & directions for use 3) Final formulation testing

Contents of OTC monograph

Drugs marketed in accordance with a final monograph can go directly to market and do not require FDA approval of a marketing application.

The OTC monograph system is commercially advantageous as it enables rapid entry of conforming products to the marketplace.

Outcomes of OTC monograph

Through the NDA Drug sponsors proposed FDA for market approval of :

a) New drugs direct to OTC b) Already marketed drugs as an OTC drugs. Drug sponsors submits data in an NDA

demonstrating a drug product is safe and effective for use by consumers without the assistance of a healthcare professional. FDA must review the data within an established timeframe, and the data submitted in an NDA remains confidential.

OTC NDA(5)

In January 1997 Manual for policies and procedure (MAPP) 6020.5R Good Review Practice: establishes a procedure for the review of NDAs for OTC Products.

Specific Subject Matter Review Division (SSMRD) of ONP review clinical trials.

Division of Non-prescription Clinical Evaluation (DNCE) of ONP reviews consumer behaviour studies and post marketing safety data.

OTC NDA

Prescription to OTC switcha) full switch (NDA supplement)b) partial switch (new NDA) Direct to OTC NDA deviation Generic (ANDA)

Type of OTC NDAs

Occurs when NDA holder of approved prescription drug files NDA or supplement for approval of OTC product.

The NDA holder may gain 3 years of marketingexclusivity for OTC “conditions of use” if switch is based on:

New clinical investigation(s).Conducted or sponsored by the

applicant.Essential to approval.

OTC switch

NDA 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 a) label comprehension

b) Actual use

OTC monograph No pre market approval Public process Active ingredient specific No user fee No market exclusivity

No mandated timelines

May require clinical studies

but label comprehension and actual use studies not required

NDA vs. OTC monograph(6)

In the Federal Register of March 17,1999,FDA

published a 21 CFR 201.66, establishing standardized content and format for labelling of OTC products.

This labeling regulation cover all OTC drug and drug-cosmetics products, whether marketed under NDA, aNDA, or an OTC drug monograph.

OTC drug Labeling in USA(6,7)

(1) Title (Drug Facts) (2) Active ingredient(s) (3) Purpose(s) (4) Use(s) (5) Warning(s) (6) Directions (7) Other information (8) Inactive ingredients (9) Contact information

Label Information Content Requirements

1) Title: If the Drug Facts labeling appears on more than one panel or side of the labeling, the title Drug Facts (continued) must appear at the top of each subsequent panel containing such information.

2) Active ingredient: followed by the established name of each active ingredient and the quantity of each active ingredient per dosage unit.

[for oral dosage forms] use the dosage unit stated in the directions for use (e.g., tablet, 5 mL teaspoonful)

[for topical dosage forms marketed with discrete dosage units] use gram, as stated .

Drug products marketed without discrete dosage units (e.g., topicals) must state the proportion (rather than the quantity) of each active ingredient (e.g. 1%).

3) Purpose: Its general pharmacological categories The principal intended action of the drug

If two active ingredients in a drug product have the same purpose (e.g., two sunscreen or skin protectant ingredients are present in the drug product), then the purpose can be stated only once as long as the purpose is clearly associated with both active ingredients.The statement of identity that appears in an applicable OTC drug monograph shall be stated as the purpose of the active ingredient.

4) Use: are the specific indications or approved uses for the drug product.

5) Warning: When applicable, the following information must appear under the respective subheadings in the Warnings section.

-“for external use only” for topical drug products.-For “rectal” or “vaginal” use only.-Allergic reaction warnings.-“Allergy alert”.-“Alcohol warning” Do not use : on irritated skin

• on any area that is infected or reddened • if you are a diabetic • if you have poor blood circulation

“Ask a doctor before use if you have”:Information under this subheading includes all warnings for persons with certain pre existing conditions (excluding pregnancy) and all warnings for persons experiencing certain symptoms. diabetes heart disease

• cough that occurs with too much phlegm (mucus) • chronic cough that lasts as occurs with smoking, asthma, chronic bronchitis, or emphysema

“Stop use and ask a doctor if” this subheading followed by any signs of

toxicity that would necessitate immediately discontinuing use of the product.

Pregnancy/breast-feeding warning The labeling for all OTC drug products shall

contain a warning as follows : “If pregnant or breast-feeding, ask a health professional before use.”

Keep out of reach of children

6) Directions: followed by the direction for use described in an applicable OTC drug monograph. For example :

shake well • do not use more than directed

7) Other information: followed by additional information that is required by OTC drug monograph.

8) Inactive ingredients: : the established names of inactive ingredients must be listed in alphabetical order as :colloidal silicon dioxide, hydroxy propyl methylcellulose, lactose, magnesium stearate, polyethylene glycol, povidone, propylene glycol, titanium dioxide.

Use of bold type Type size Font characteristics The use of bullets- solid square or circle, 5 point. Graphic images and Procedures for handling multiple panels

The FDA mandates that a minimum type size of 6.7 point is required to ensure that people over the age of 60 can read the label. And do not reduce the type size below 6.0 point.

Label Information Format Requirement

Minimum type size:a) Headings- at least 8 point or 2 point larger

than text.b) Text and subheading- at least 6 point.

A clear, easy-to-read type style, such as universe, with no more than 39 characters per inch. Leading- at least 0.5 point(minimum space between lines)Kerning- letters cannot touch.

Principal display panel

The declaration shall appear in conspicuous and easily legible boldface print or type in distinct contrast (by typography, layout, color) to other information.

Height: width shall not be greater than 3:1.

Outer label specifications

Letter and numerals on PDP shall be uniform for all package of substantially the same size by complying with the following type specifications:

-Not less than 1/16th inch in height (area of 5 square inches or less).-Not less than 1/8th inch in height (area of more than 5 but not more than 25 square inches).-Not less than 3/16th inch in height (area of more than 25 but not more than 100 square inches).-Not less than 1/4th inch in height (area of more than 100 square inches).Except -Not less than 1/2th inch in height (area of more than 400 square inches).

1) OTCs deliver tremendous value to individual consumers and the US healthcare system as a whole. The general sales status of OTCs in the US marketplace provides the American consumer with convenient access to important self-care options.

2) The OTC monograph process has the advantage of speed to market for qualifying products, since FDA pre-approval is not required. The NDA route is more time-consuming.

conclusion

1) https://en.wikipedia.org/wiki/Over-the-counter_drug2) http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/Manualof

Policies Procedures/ucm082003.pdf3)

http://www.fda.gov/DevelopmentApprovalProcess/HowDrugsareDeveloped and Approved/ucm209647.htm

4) http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsare Developed and Approved/ucm317137.htm

5) http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ucm 148055. pdf

6) http://www.fda.gov/downloads/Drugs/GuidanceCompliance Regulatory Information/ Guidances/ucm150994.pdf

7) http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrug preparedness/ucm133411.htm

References