Child-Resistant Packaging Statements in Drug Product Labeling

17266044 FNL

Child-Resistant

Packaging Statements

in Drug Product

Labeling

Guidance for Industry

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

August 2019

Labeling

Contains Nonbinding Recommendations

Child-Resistant

Packaging Statements

in Drug Product

Labeling

Guidance for Industry

Additional copies are available from:

Office of Communications,

Division of Drug Information

Center for Drug Evaluation and Research

Food and Drug Administration

10001 New Hampshire Ave., Hillandale Bldg., 4

Floor

Silver Spring, MD 20993-0002

Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353

Email: druginfo@fda.hhs.gov

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

and/or

Office of Communication, Outreach and Development

Center for Biologics Evaluation and Research

Food and Drug Administration

10903 New Hampshire Ave., Bldg. 71, Room 3128

Silver Spring, MD 20993-0002

Phone: 800-835-4709 or 240-402-8010

Email: [email protected].gov

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

August 2019

Labeling

Contains Nonbinding Recommendations

TABLE OF CONTENTS

I. INTRODUCTION............................................................................................................. 1

II. DISCUSSION .................................................................................................................... 2

III. LABELING ....................................................................................................................... 3

A. Prescription Drug Products .......................................................................................................... 4

1. Prescribing Information................................................................................................................... 4

2. Patient Information .......................................................................................................................... 4

3. Carton Labeling and Container Labels ........................................................................................... 5

B. Nonprescription Drug Products ................................................................................................... 5

1. Drug Facts Labeling ........................................................................................................................ 5

2. Carton Labeling and Container Labels ........................................................................................... 6

IV. PROCESS FOR INCLUDING STATEMENTS REGARDING CRP ON THE

LABELING ........................................................................................................................... 6

A. Prescription Drug Products and Nonprescription Drug Products Approved Under an

Application ...................................................................................................................................... 6

1. Original NDA, BLA, or ANDA submission ...................................................................................... 6

2. Postapproval Change....................................................................................................................... 6

B. Nonprescription Drug Products Marketed Under the OTC Drug Review............................... 7

Contains Nonbinding Recommendations

Child-Resistant Packaging Statements in Drug Product Labeling

Guidance for Industry

This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on

this topic. It does not establish any rights for any person and is not binding on FDA or the public. You

can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.

To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the

title page.

I. INTRODUCTION

This guidance is intended to assist applicants, manufacturers, packagers, and distributors

(collectively referred to as firms) who choose to include child-resistant packaging (CRP)

statements in their drug product

labeling. The guidance discusses what information should be

included to support CRP statements in labeling for new drug applications (NDAs), abbreviated

new drug applications (ANDAs), biologics license applications (BLAs), and supplements to

these applications. In addition to recommendations for labeling of prescription drug products,

this guidance also includes recommendations for labeling both for nonprescription drug

products

approved under an NDA or ANDA and those that are marketed under the Over-the-

Counter (OTC) Drug Review.

This guidance is intended to help ensure that such labeling is

clear, useful, informative, and, to the extent possible, consistent in content and format.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities.

Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only

as recommendations, unless specific regulatory or statutory requirements are cited. The use of

the word should in Agency guidances means that something is suggested or recommended, but

not required.

This guidance has been prepared by the Center for Drug Evaluation and Research and the Center for Biologics

Evaluation and Research at the Food and Drug Administration.

References to drugs and biological products include drugs approved under section 505 of the Federal Food, Drug,

and Cosmetic Act (FD&C) and biological products licensed under section 351 of the Public Health Service Act

(PHSA) that are drugs. For the purposes of this guidance, drug product or drug will be used to refer to human

prescription drug and biological products that are regulated as drugs.

For the purposes of this guidance, the term nonprescription drug products refers to over-the-counter (OTC) drug

products.

See 21 CFR 330-358.

This guidance is intended to apply to FDA-regulated drug products that bear CRP statements, regardless of

whether CRP is required for such products under 16 CFR 1700. For example, bulk packages of prescription drugs

that are shipped to pharmacies for repackaging by a pharmacist are not required to utilize CRP, but a firm may

nevertheless choose to use CRP (and a CRP statement) for such drugs. 16 CFR 1701.1.

Contains Nonbinding Recommendations

II. DISCUSSION

In 1970, the Poison Prevention Packaging Act (PPPA) was enacted to protect children (under 5

years of age) from unintentional exposure to household substances including food, drugs, and

cosmetics.

Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), a drug that has

packaging or labeling that is in violation of a regulation issued pursuant to section 3 or 4 of the

PPPA is deemed to be misbranded.

FDA was responsible for enforcing the PPPA until 1973,

when jurisdiction was transferred to the U.S. Consumer Product Safety Commission (CPSC).

Because of FDA’s authority to regulate labeling for prescription and nonprescription drug

products, if firms choose to make statements in their labeling for such products about child-

resistant packaging, such statements must comply with FDA’s statutory and regulatory

requirements.

CPSC’s regulations list “special packaging standards”

10,11

(also referred to herein as child-

resistant packaging, or CRP) for a wide range of household products, including most oral

prescription drugs and many nonprescription drug products.

There are different ways to make

packaging child-resistant, with the most common forms being a child-resistant closure (e.g., a

“safety cap”) and certain unit-dose blister packaging (e.g., puncture-resistant and peel-push

blisters. It should be noted that “child-resistant” should not be equated with “child-proof,”

because CRP is not designed to completely eliminate the possibility of an accidental pediatric

ingestion. It can only impede access to harmful products and is recognized by public health

experts as only one component of preventing these events. Therefore, FDA advocates that all

drugs, irrespective of the type of packaging, be stored safely out of reach and sight of children to

further the overall public health efforts to address this safety issue.

FDA regulates certain aspects of drug products’ container closure systems related to safety and

efficacy as part of the drug application review and approval process.

13,14

During FDA’s review

of an NDA, ANDA, or BLA (and nonprescription drugs marketed under an application), data

related to container closure systems are evaluated, such as the type of closure employed, the

stability of the product in the container closure system, and whether the closure design is suitable

for the product. FDA’s review does not include evaluation of testing reports to determine

whether a product meets the applicable standards for special packaging set forth in the PPPA and

its implementing regulations.

Poison Prevention Packaging Act of 1970 (PPPA), (Pub. L. 91-601, 84 Stat. 1670-74), enacted December 30,

1970.

See FD&C Act, § 502(p).

Consumer Product Safety Act, Public Law 92-573; 86 Stat. 1207, October 27, 1972, Sec. 30.

See, e.g., FD&C Act § 502(a), (c).

See definitions in section 2 (4) of the PPPA.

Special packaging and child-resistant packaging (CRP) are used interchangeably in this guidance.

See 16 CFR 1700 for substances requiring special packaging and the relevant packaging standards and testing

procedures.

FDA generally does not regulate retail pharmacy vials or other containers used by pharmacies to repackage drugs

to dispense to patients.

See FDA guidance for industry Container Closure Systems for Packaging Human Drugs and Biologics, May

1999. This guidance is available on the Internet at

https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

under Guidances

(Drugs).

Contains Nonbinding Recommendations

With respect to nonprescription drug products marketed under the OTC Drug Review, FDA does

not review data related to container closure systems, as applications for individual drug products

under the OTC Drug Review are not submitted to FDA for review or approval. In addition,

although manufacturers of nonprescription products marketed under the OTC Drug Review must

comply with the labeling requirements under 21 CFR 201.66, they are not required to submit

labeling to FDA prior to marketing.

In this guidance, we recommend text that may be appropriate to consider when including CRP

statements in the prescribing information, in the patient information, on carton labeling and

container labels for prescription drug products, and in the drug facts labeling and on carton

labeling and container labels for nonprescription drug products.

III. LABELING

Because health care professionals and consumers may not be able to determine on visual

inspection whether packaging is child-resistant, a labeling statement may help to identify this

attribute. As a general matter, if a drug product is packaged using CRP and the firm elects to

include labeling statements that identify the product as packaged with CRP, the CRP should be

described using words and not abbreviations (e.g., “CRP,” “CRC,” or “CR”) or symbols because

these abbreviations and symbols may not be readily understood. Because it is important to

clarify that CRP statements in labeling describe how the product is supplied from the

manufacturer, versus how the product is dispensed by a pharmacist, the term “supplied” as

opposed to “available” is preferred.

Section 502(a) of the FD&C Act provides that a drug is deemed to be misbranded if its labeling

is false or misleading in any particular. In general, to ensure that CRP statements on labeling are

not false or misleading, such statements should only be used when the drug product packaging

has been shown to comply with CPSC regulatory standards and test procedures for CRP, as

applicable.

15,16

In addition, placement of CRP statements on the labeling must not interfere with

required information on the labeling.

We provide additional recommendations for the labeling of prescription drug products and

nonprescription drug products below.

See 16 CFR 1700.15 for poison prevention packaging standards and 16 CFR 1700.20 for special packaging testing

procedures. In order to make household substances that are subject to the PPPA’s special packaging requirements

readily available to elderly or handicapped persons who are unable to use those substances in special packaging,

section 4(a) of the PPPA authorizes manufacturers and packers to package such substances in non-complying

packaging of a single size provided that: 1) complying packaging is also supplied, and 2) the non-complying

packages are conspicuously labeled to indicate that they should not be used in households where young children are

present. In order to comply with CPSC regulations, any non-complying packages a firm elects to market pursuant to

section 4(a) of the PPPA must bear the labeling described in 16 CFR 1700.5.

We note that if a product is subject to the special packaging requirements of the PPPA, but its packaging or

labeling is in violation of applicable regulations issued pursuant to section 3 or 4 of the PPPA, it may also be

misbranded under section 502(p) of the FD&C Act.

See FD&C Act § 502(c).

Contains Nonbinding Recommendations

A. Prescription Drug Products

1. Prescribing Information

If a firm chooses to include information about CRP in the prescribing information, such

information should appear in the HOW SUPPLIED/STORAGE AND HANDLING section as

this is generally where practitioners look to ascertain information about a product’s packaging.

It is important that the CRP statements be linked clearly to a particular package, especially when

multiple packages are supplied and not all have been demonstrated to be child-resistant.

Examples include the following:

HOW SUPPLIED/STORAGE AND HANDLING

• Drug X is supplied in 30 g, 4 oz tubes with a child-resistant cap.

• Drug X is supplied as child-resistant sachets.

• The 50 mg tablet is film-coated, round, biconvex, pink, scored, and is

debossed with XXX on one side and scored on the other side.

Bottles of 30 with child-resistant closure, NDC xxxx-xxx-xx

Bottles of 60 with child-resistant closure, NDC xxxx-xxx-xx

Bottles of 500, NDC xxxx-xxx-xx”

2. Patient Information

If a firm chooses to include information about CRP for a prescription drug product whose

commercial container bearing the CRP is designed to be dispensed directly to patients, the CRP

information should be included in the patient labeling (e.g., medication guides, patient package

inserts). Information about the CRP in patient labeling should appear under a heading titled

“How should I store Drug X?” The description should be consistent with the CRP statement(s)

included in the HOW SUPPLIED/STORAGE AND HANDLING section of the full prescribing

information.

Examples include the following:

• Drug X comes in a child-resistant package.

• Drug X comes in a sealed child-resistant foil pouch.

The following statement should also appear at the end of the “How should I store

Drug X?’ section:

• Keep Drug X and all medicines out of the reach of children.

Contains Nonbinding Recommendations

3. Carton Labeling and Container Labels

If a firm chooses to include information about the CRP on carton labeling and container labels, it

may do so as long as there is sufficient space to include such information in addition to

information required to be included.

If space permits, a firm may also include, in conjunction

with the CRP statement, a statement to recommend that the package be kept out of reach of

children, particularly for those packages which may be dispensed directly to patients. Statements

about CRP are most appropriately displayed on the side panels of the carton labeling and

container labels in close proximity to storage information.

Examples include the following:

• This package is child-resistant. Store at 20°C-25°C (68°F-77°F); excursions

permitted to 15°C-30°C (59°F-86°F).

• This package is child-resistant. Keep out of reach of children. Store at

20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F).

B. Nonprescription Drug Products

1. Drug Facts Labeling

FDA regulations do not specify where to place CRP statements on labeling for nonprescription

drug products. If firms choose to include the statement in the drug facts labeling (DFL), it

should appear under the subheading “Other information” with the storage statement.

“Other

information” is the subheading used for certain information that is not included under the other

DFL subheadings, including optional information. A CRP statement would be considered to be

optional “Additional information”

under the “Other information” subheading and should

follow any required statements.

The following examples illustrate types of information considered to be “other information,”

including a CRP statement:

• Read the directions and warnings before use.

• Keep the carton. It contains important information.

• This package is child-resistant.

• Store at 20-25°C (68-77°F) and protect from moisture.

If the container label is too small, see 21 CFR 201.10(i).

See § 201.66(c)(7).

See § 201.66(c)(7)(iii).

Contains Nonbinding Recommendations

2. Carton Labeling and Container Labels

Even if the CRP statement(s) are included in the DFL, their placement on the carton labeling

and/or container labeling outside the DFL is optional. Conversely, if the CRP statement is not

included in the DFL, it is still permissible to include a CRP statement(s) on the carton labeling

and/or the container labeling outside the DFL, space permitting.

Appropriate text could read

“this package is child-resistant.” For small containers and/or cartons, appropriate text could read

“child-resistant package.” Although any available panel or part of a panel, outside the DFL, is

appropriate for this use, consumers may find this information to be more useful if displayed on

the principal display panel(s).

IV. PROCESS FOR INCLUDING STATEMENTS REGARDING CRP ON THE

LABELING

If firms choose to include CRP statements on their product labeling, they should verify in writing

for FDA that the CRP meets the standards set forth by the CPSC in 16 CFR 1700, as applicable,

as discussed below.

22,23

FDA also recommends that firms retain the data demonstrating that the

packaging meets applicable CPSC standards.

A. Prescription Drug Products and Nonprescription Drug Products Approved

Under an Application

1. Original NDA, BLA, or ANDA submission

In an original NDA, BLA, or ANDA submission, written verification that the CRP meets the

CPSC’s standards under 16 CFR 1700 should appear in the container closure section of Module

3.2.P.7 Container Closure System (name, dosage form) of the Electronic Common Technical

Document (eCTD). An example of the written verification may be “We verify in this submission

that the following package (or packages) meet CPSC’s standards under 16 CFR 1700.”

2. Postapproval Change

If there is a postapproval change to the package or labeling of a product approved under an

NDA, BLA, or ANDA, refer to appropriate regulations and guidances to determine the

appropriate pathway to implement these changes.

Submissions for changes to add CRP

statements on labeling should verify in writing that the CRP meets the CPSC’s standards under

16 CFR 1700 and the verification should appear in the detailed container closure description

In such circumstances, we encourage applicants to discuss their plans with FDA. When the submission is for an

NDA or BLA, contact the specific drug product’s review division with questions. When the submission is for an

ANDA, submit questions as a General Correspondence to the application.

The written verification discussed in this guidance is intended for FDA only, and is separate from the certification

required to be provided to CPSC under 15 USC 2063 and 16 CFR 1110.

Firms should provide such written verification to FDA to support CRP statements even in circumstances where

they have elected to use CRP for products that are not subject to the special packaging requirements of 16 CFR

1700.

See 21 CFR 314.70 and 601.12 for reporting requirements for changes to approved applications for drug products

and licensed biological products.

Contains Nonbinding Recommendations

section of Module 3.2.P.7 Container Closure System (name, dosage form) in the eCTD. An

example of the written verification may be “We verify in this submission that the following

package (or packages) meet CPSC’s standards under 16 CFR 1700.”

B. Nonprescription Drug Products Marketed Under the OTC Drug Review

There is no defined process for submission of a written verification to FDA that a

nonprescription drug product marketed under an OTC monograph meets CPSC’s standards under

16 CFR 1700. However, if firms elect to include a CRP statement on the labeling of a

nonprescription drug product marketed under an OTC monograph, they should retain the data

demonstrating that the packaging meets applicable CPSC standards and follow the labeling

recommendations in this guidance.