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ANDA Labeling

Question Based Review

September 11, 2013

GPhA/FDA ANDA Labeling Workshop/USP User Forum

Sarah Park, PharmD Jeanne Skanchy, RPh.

Labeling Reviewers

Office of Generic Drugs/Division of Labeling and Program Support

Center for Drug Evaluation and Research

Food and Drug Administration

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Labeling QbR

Questions follow the contents and flow of the

Labeling Review Template.

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Labeling Review Template

1. MODEL LABELING

2. USP & PF 3. PATENT AND EXCLUSIVITY

4. INACTIVE INGREDIENTS 5. MANUFACTURING FACILITY

6. FINISHED PRODUCT DESCRIPTION

7. S TORAGE STATEMENT AND DISPENSING RECOMMENDATIONS

8. PRODUCT LINE 9. CO NTAINER/CLOSURE 10. MEDICATION GUIDES/PATIENT PACKAGE INSERT 11. RELATED APPLICATIONS 12. SPL DATA ELEMENTS

13. CITIZEN PETITIONS/PROPRIETARY NAME/CONSULTS

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Introduction

ANDA Number ######

Date of Submission September 11, 2013

Applicant’s Name Company X

Established Name of the Drug Product Drug A Tablets USP, 20 mg

Proprietary Name of the Drug Product Name B (proposed September 11, 2013)

Labeling Submissions Container, Carton, Insert, Medication Guide, SPL

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Model Labeling

What model labeling(s) is your product labeling

based upon?

Example Answer:

RLD Drug Name, NDA 123456/S-123 approved Date

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USP Monograph

Is there a USP Drug Product Monograph? Does

your product’s labeling meet the USP

requirements?

Example Answer:

Drug X is not the subject of a USP monograph

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USP Monograph

Example Answer:

Drug X is now the subject of a USP monograph and the

official compendial name is “Drug X Tablets”. We have

included the designation “USP” in association with the

drug product name on all labeling pieces. In the insert

labeling, we have included the designation “USP” in

association with the drug product name in the TITLE,

INDICATIONS AND USAGE, DESCRIPTION and

HOW SUPPLIED/STORAGE AND HANDLING

sections.

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USP Monograph

Example Answer:

The USP 36 Drug Product Monograph states: “When

more than one Dissolution test is given, the labeling states

the Dissolution test used only if Test 1 is not used.”

Drug X utilizes Dissolution Test 2. The insert labeling

includes the statement “Meets USP Dissolution Test 2” in

the last paragraph of the DESCRIPTION section.

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USP Monograph

Example Answer:

The USP monograph for Drug X states “Preserve in well-

closed containers, protected from light.” The container

label and insert labeling include the statement “Preserve

in well-closed containers, protected from light.”

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USP Monograph

Example Answer:

The USP 36 Drug Product Monograph states: “If a test for

Organic Impurities other than Procedure 1 is used, then

the labeling states with which Organic Impurities test the

article complies.”

Company X’s Drug A complies with Procedure 2. The

insert labeling includes that statement “Meets Organic

Impurities Test Procedure 2” in the last paragraph of the

DESCRIPTION section.

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Patents and Exclusivities

What are the currently approved patents and

exclusivities for the reference listed drug as listed

in the Approved Drug Products with Therapeutic

Equivalence Evaluation (Orange Book), and what

impact do they have on the labeling submitted?

What are the certifications and labeling impacts

for each patent and exclusivity?

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Patents and Exclusivities

Example Answer:

Patent Data:

Appl No Prod No Patent No Patent

Expiration

Patent Use

Code

Patent

Certification

Labeling

Impact

N###### 001 ####### Sep 1, 2021 U - #### PIV Carved out

Code Definition

U - ####

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Patents and Exclusivities

Example Answer:

Exclusivity Data:

Appl No Prod No Exclusivity

Code

Exclusivity

Expiration

Exclusivity

Statement

Labeling

Impact

N###### 001 NPP Mar 1, 2016 Will not market

until expiry

None

N###### 001 PED Sep 1, 2016

Code Definition

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Inactive Ingredients

Is the listing of inactive ingredients in the

DESCRIPTION section of the package insert

consistent with the listing of inactive ingredients

found in the statement of components and

composition and SPL data elements?

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Inactive Ingredients

Example Answer:

The listing of inactive ingredients in the DESCRIPTION

section of the package insert is consistent with the listing

of inactive ingredients found in the statement of

components and composition appearing in section 3.2.P.1.

and SPL data elements.

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Inactive Ingredients

Do any of your inactive ingredients require

special labeling statements or have regulatory

requirements?

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Inactive Ingredients

Example Answer:

Elemental Iron:

The 20 mg tablet contains red and black iron oxides.

(Show calculations.)

The total daily amount of elemental iron in the 20 mg

tablet is #.## mg. Company X confirms that the maximum

daily intake of elemental iron from the tablets based on

the maximum recommended daily dosage of the drug

product is less than 5 mg per day as per 21 CFR 73.1200.

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Manufacturing Facility

Who manufactures the drug product?

Example Answer:

Manufacturing Facility Name

Facility address

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Manufacturing Facility

Who distributes the drug product?

Example Answer:

Distributor Name

Distributor Address

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Product Description

How does your product description in the insert

labeling compare with the product description in

the Finished Product Specifications?

How does your product description compare

with the product description of the RLD?

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Product Description

Example Answer:

Finished Product

Specifications:

White, capsule shaped, biconvex, film-coated tablets

debossed with “XX ##” on one side and plain on

other side.

ANDA insert:

Drug A tablets are white, capsule shaped, biconvex,

film-coated tablets debossed with “XX ##” on one

side and plain on the other side.

RLD:

NDA Drug C tablets are white, capsule-shaped, film-

coated, debossed with “X##” on one side and plain-

faced on the other side.

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Product Description

How does your product’s dimensions compare

with the dimensions of the RLD tablet?

Example Answer:

RLD Tablet Size ANDA Tablet Size

75 mg 9 mm 9 mm

150 mg 14 mm 15 mm

300 mg 17 mm 17 mm

400 mg 19 mm 19 mm

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Product Description

How are the conditions of 21 CFR 206

(Imprinting of Solid Oral Dosage Form) met?

Example Answer:

The tablets have been accurately described in the HOW

SUPPLIED section as required by 21 CFR 206,et al.

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Product Description

Is the RLD tablet strength linked to or generally

recognized by tablet color?

Example Answer:

The RLD tablet strengths are linked to or generally

recognized by tablet color.

The tablet colors of our XXX tablets corresponds to the

tablet colors of the RLD drug product.

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Product Description

RLD ANDA

1 mg Pink Pink

2 mg Lavender Lavender

2.5 mg Green Green

3 mg Tan Tan

4 mg Blue Blue

5 mg Peach Peach

6 mg Teal Teal

7.5 mg Yellow Yellow

10 mg White White

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Storage Conditions

How does your storage temperature statement

compare with the storage temperature statement

of the RLD and USP (if applicable)? Please

justify the differences.

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Storage Conditions

Example Answer:

USP: Store between 15

and 25

C. Protect from light

and moisture.

RLD: Store at 15

to 25

C (59

to 77

F) and protect

from moisture.

ANDA: Store at 20

to 25

C (68

to 77

F). [See USP

Controlled Room Temperature.] Protect from light

and moisture.

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Storage Conditions Is this product light sensitive? If so, do the storage

recommendations and/or special packaging

address light sensitivity?

Example Answer:

The drug product is light sensitive.

The labels and labeling include the statement “Protect

from light.”

The bottles meet requirements for light transmission

per USP <661> .

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Dispensing Recommendations

How do your dispensing recommendation

statements compare with the dispensing

recommendation statements of the RLD?

Example Answer:

RLD: Dispense in original container.

ANDA: Dispense in original container.

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Product Line

How do your packaging configurations compare

with the packaging configurations of the RLD?

Example Answer:

Please provide a table to include the packaging

configurations for the RLD and ANDA.

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Container & Closure System

How does you proposed container/closure system

differ from the container/closure system of the

RLD?

What child-resistant feature(s) are utilized for each

of your proposed packaging configurations?

Example Answer:

Please provide a table to include the container/closure

system of the RLD and ANDA for comparison.

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Container & Closure System

Is your drug product a controlled substance? If

yes, does the labeling meet the regulatory

requirements of 21 CFR 1302.06 for tamper-

evident sealing?

Example Answer:

Please provide a statement that your drug product

meets the requirements of 21 CFR 1302.06 for

tamper-evident sealing.

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Medication Guides

How will the Medication Guide be provided with

the product and how many will accompany each

package size?

Example Answer:

In accordance with 21 CFR 208.24 (b), a

sufficient number of the Medication Guides is

available for distribution to each patient receiving

a prescription for the drug product.

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Medication Guides Do the proposed container labels and carton labeling

direct the health care provider to dispense the

Medication Guide as required by 21 CFR 208.24 (d)

(Distributing and Dispensing a Medication Guide)?

Example Answer:

Yes, the proposed container labels and carton

labeling direct the health care provider to dispense

the Medication Guide as required by 21 CFR

208.24 (d).

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Medication Guides The Agency recommends that you include one of

the following pharmacist dispensing statements:

“Pharmacist: Dispense the enclosed Medication

Guide to each patient.” or

“Pharmacist: Dispense the accompanying

Medication Guide to each patient.” or

“Pharmacist: Dispense the Medication Guide

provided separately to each patient.”

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Medication Guides Is there an FDA toll-free number for reporting

adverse events under “What are the possible side

effects?” in the Medication Guide?

Example Answer:

Yes, an FDA toll-free number for reporting

adverse events under “What are the possible

side effects?” has been provided.

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Related ANDAs Are there any related ANDAs for your drug

product? Yes or No

Example Answer:

If yes, then list any pending and approved

ANDAs that contain the same drug product with

different dosage forms.

If no, then provide a statement that there are no

related ANDAs for the drug product.

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Structured Product Labeling (SPL)

Are the structured product labeling (SPL) data

elements consistent with the information

provided in your application and the insert

labeling?

Example Answer:

Yes, please state that the SPL data elements

are consistent with the information provided

in the application and insert labeling.

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Citizen Petitions

Is your proposed drug product subject to any

pending Citizen Petitions (CP)? Yes or No

Example Answer:

If yes, please state that the drug product is

subject to a pending Citizen Petition. Please

explain or list the CP.

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Disclaimer:

This presentation reflects the views of

the authors should not be construed to

represent FDA’s views or policies.

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Thank You!