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Guidance

Expiration Dating of Unit-Dose 

Repackaged Drugs:

Compliance Policy Guide

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.

Comments and suggestions regarding this draft document should be submitted within 90 days of 

publication in the Federal Register of the notice announcing the availability of the draft 

guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and 

Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments 

should be identified with the docket number listed in the notice of availability that publishes in 

the Federal Register.

For questions regarding this draft document contact Barry Rothman, 301-827-9026. 

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

May 2005

Compliance
Guidance

Expiration Dating of Unit-Dose 

Repackaged Drugs:

Compliance Policy Guide

Additional copies are available from:

Division of Drug Information, HFD-240

Center for Drug Evaluation and Research

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

(Tel) 301-827-4573

(Internet) http://www.fda.gov/cder/guidance/index.htm

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

May 2005

Compliance
Contains Nonbinding Recommendations

Draft — Not for Implementation

TABLE OF CONTENTS

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

II. BACKGROUND ............................................................................................................... 1

III. DISCUSSION .................................................................................................................... 2
Contains Nonbinding Recommendations

Draft — Not for Implementation

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Guidance1

Expiration Dating of Unit-Dose Repackaged Drugs: 

Compliance Policy Guide

This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA’s) current 

thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 

bind FDA or the public. You can use an alternative approach if it satisfies the requirements of the 

applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff 

responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the 

appropriate number listed on the title page of this guidance.

Sec. 480.200 (CPG 7132b.11)

I. INTRODUCTION 

Many companies repackage solid and liquid oral dosage form drug products into unit-dose 

containers. This guidance states the circumstances under which the Food and Drug 

Administration (FDA) intends to exercise its enforcement discretion and does not intend to take 

enforcement action against such repackagers for failure to conduct stability studies to support 

expiration dates for these unit-dose repackaged products. 

FDA’s guidance documents, including this guidance, 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. 

II. BACKGROUND

Unit-dose packaging systems are widespread in health care. Some unit-dose containers are 

available directly from manufacturers and repackagers; some drug products are repackaged into 

unit-dose containers by hospital or community pharmacies or shared service establishments. A 

shared service repackaging operation is one that exclusively serves one or more hospitals and/or 

related institutions, each having separate or no pharmacy services and each having responsibility 

for restricting distribution of the drug products received from the shared service establishment.

 

1

 This guidance has been prepared by the Office of Compliance in the Center for Drug Evaluation and Research 

(CDER) at the Food and Drug Administration. 
Contains Nonbinding Recommendations

Draft — Not for Implementation

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The nature of drug dispensing within hospitals in particular has made such unit-dose packaging 

useful and convenient in helping to ensure that medications are properly administered to patients. 

However, questions have arisen concerning the appropriate expiration dating for drug products 

repackaged into unit-dose containers. 

FDA’s current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, 

21 CFR Part 211, include § 211.137 on “Expiration dating.” Section 211.137(a) requires that 

each drug product bear an expiration date determined by appropriate stability testing, as 

described in § 211.166. Under § 211.137(b), a drug product’s expiration date must be related to 

any storage conditions stated on the labeling, as determined by stability studies described in 

§ 211.166. Samples used for stability testing must be in the same container-closure system as 

that in which the drug product is marketed (§ 211.166(a)(4)). This is to ensure the drugs’ safety 

and efficacy over their intended shelf life.

The U.S. Pharmacopeia (USP) contains standards on expiration dating and beyond-use dating in 

its General Notices and Requirements section. 2 The USP directs dispensers of prescription drug 

products to place on the label of the prescription container a suitable beyond-use date to limit the 

patient’s use of the product. The beyond-use date cannot be later than the expiration date on the 

manufacturer’s container. The USP states:

For nonsterile solid and liquid dosage forms that are packaged in single-unit and 

unit-dose containers, the beyond-use date shall be one year from the date the drug 

is packaged into the single-unit or unit-dose container or the expiration date on 

the manufacturer’s container, whichever is earlier, unless stability data or the 

manufacturer’s labeling indicates otherwise.

3

 

III. DISCUSSION

FDA has considered the USP beyond-use standard and believes that similar conditions are 

appropriate for FDA’s CPG 7132b.11 for expiration dating. FDA believes that under certain 

specified conditions, it may be possible to assign appropriate expiration dating without 

conducting new stability studies on the nonsterile solid and liquid oral dosage forms repackaged 

into unit-dose containers. Therefore, FDA does not intend to take action against any nonsterile 

unit-dose repackaging firm (including shared services repackaging operations) or drug product in 

a unit-dose container solely on the basis of the failure of the repackaging firm to have stability 

studies supporting the expiration dates used, provided that the repackager meets all other 

regulations applicable to repackaged drug products and:

1. The expiration date does not exceed (a) 1 year from the date of repackaging or 

(b) the expiration date on the container of the original manufacturer’s product, 

whichever is earlier, unless stability data or the original manufacturer’s product 

labeling indicates otherwise. 

 

2

 USP 27 (2004) at 11. 

3

 Id.
Contains Nonbinding Recommendations

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2. If the drug product repackaged is in solid oral dosage form, the formed unit-dose 

container complies with the Class A standard described in the USP, General 

Chapter <671> Containers—Permeation, “Single-Unit Containers and Unit-Dose 

Containers for Capsules and Tablets.”

3. The original bulk container of drug product has not been opened previously and 

the entire contents are repackaged in one operation.

4. The repackaging and storage of the drug product are accomplished in a controlled 

environment that is consistent with the conditions described in the labeling for the 

original drug product and the repackaged drug product. Where no temperature is 

specified in the labeling of the original drug product, a controlled room 

temperature (as defined in the General Notices and Requirements section of the 

USP) should be maintained during repackaging and storage of both solid and 

liquid oral dosage form drug products. Where no humidity is specified in the 

labeling of the original drug product, the relative humidity should not exceed 75 

percent at 23 degrees Celsius for the repackaging and storage of solid oral dosage 

forms.

This CPG applies only to nonsterile solid and liquid oral dosage forms in unit-dose containers. 

Sterile products and other types of dosage forms and packages pose sterility and/or stability 

concerns that this CPG would not adequately address. Thus, this CPG does not apply to sterile 

products, other dosage forms, and other types of packages. 

Liquid oral dosage forms should not be repackaged unless suitable materials are used and 

precautions are taken to prevent evaporation or solvent loss.

This CPG does not apply to nitroglycerin sublingual tablets or any other solid or liquid oral 

dosage form drug product known to have stability problems that preclude the product from being 

repackaged. This group of products generally would include any drug known to be oxygen 

sensitive or that exhibits extreme moisture or light sensitivity. In deciding whether a particular 

drug product is suitable for repackaging, the repackager should take into consideration any 

available information from the manufacturer, published literature, the USP, and FDA.

FDA’s intent to exercise enforcement discretion concerning stability studies for repackaged 

products does not apply to any other requirements of Parts 210 and 211.