[Federal Register Volume 70, Number 103 (Tuesday, May 31, 2005)]
[Notices]
[Pages 30953-30954]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-10702]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005D-0174]


Draft Guidance on Expiration Dating of Unit-Dose Repackaged 
Drugs; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance entitled ``Expiration Dating of Unit-
Dose Repackaged Drugs.'' The draft guidance is a proposed revision of 
section 480.200 of FDA's Compliance Policy Guide (CPG) (CPG 7132b.11). 
We are proposing to revise CPG 7132b.11 so that FDA enforcement policy 
regarding expiration dating of nonsterile unit-dose repackaged drugs 
under the agency's current good manufacturing practice (CGMP) 
regulations is substantially comparable to the expiration dating 
standards for such drugs set forth in the U.S. Pharmacopeia (USP).

DATES: Submit written or electronic comments on the draft guidance by 
August 29, 2005. General comments on agency guidance documents are 
welcome at any time.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857. Send one self-addressed adhesive label to 
assist that office in processing your requests. Submit written comments 
on the draft guidance to the Division of Dockets Management (HFA-305), 
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Barry Rothman, Center for Drug 
Evaluation and Research (HFD-320), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-9026.

SUPPLEMENTARY INFORMATION:

I. Background

    We are announcing the availability of a draft guidance on 
``Expiration Dating of Unit-Dose Repackaged Drugs.'' The document 
provides guidance on FDA's enforcement policy regarding expiration 
dating of repackaged nonsterile solid and liquid unit-dose drugs under 
Sec.  211.137 (21 CFR 211.137). Specifically, the draft guidance states 
certain circumstances under which we intend to exercise enforcement 
discretion and do not intend to take action against repackagers for 
failure to conduct stability studies to support expiration dates for 
drug products in accordance with FDA regulations.
    The draft guidance is a proposed revision of section 480.200 of the 
CPG (CPG 7132b.11), which we issued in February 1984 and revised in 
March 1995. We originally issued CPG 7132b.11 because unit-dose 
packaging systems had become widespread in health care, and questions 
had arisen as to whether drugs that were repackaged into unit-dose 
containers needed expiration dates based on stability data on the drugs 
in the unit-dose containers.
    The CGMP regulations require that each drug product bear an 
expiration date derived from tests conducted on samples stored in the 
immediate container closure system in which the drug is marketed (see 
Sec.  211.137(a), Sec.  211.166(a)(4) (21 CFR 211.166(a)(4))). This 
expiration dating ensures the drugs' safety and efficacy over their 
intended shelf life. CPG 7132b.11 notes that the USP contains standards 
on beyond-use dating of nonsterile solid and liquid unit-dose drug 
products.
    Since its adoption in 1984, the CPG has stated that, in light of 
the USP standards and under certain conditions, the agency does not 
deem it necessary that stability studies be conducted on drugs that are 
repackaged into unit-dose containers. Therefore, the CPG has stated 
that we do not intend to initiate enforcement action against any unit-
dose repackaging firm for failure to have stability studies supporting 
expiration dates, provided certain conditions are met, including that 
the expiration date does not exceed 6 months. At the time the CPG was 
adopted, this recommendation was substantially comparable to the USP 
standards on expiration dating of nonsterile unit-dose repackaged drug 
products.
    In 2000, the USP revised its standards on the beyond-use dating of 
nonsterile solid and liquid dosage forms that are packaged in single-
unit and unit-dose containers. The USP now states that, for such 
products, the beyond-use date must be 1 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 (USP 
27, General Notices and Requirements, at 11).
    We have considered the USP revision to its beyond-use standard and 
believe that similar conditions are appropriate for CPG 7132b.11 for 
expiration dating. We believe that under certain specified conditions, 
it may be appropriate to assign up to a one-year expiration dating 
period to solid and liquid oral dosage form drug products repackaged 
into unit-dose containers, without conducting new stability studies on 
the repackaged drug products. Therefore, we are proposing to revise CPG 
7132b.11 to clarify the agency's exercise of enforcement discretion 
concerning expiration dating of nonsterile solid and liquid oral dosage 
form drug products that are repackaged into unit-dose containers.
    Under draft revised CPG 7132b.11, the expiration date for a 
nonsterile repackaged unit-dose drug would not exceed the following: 
(1) One year from the date of repackaging, or (2) 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 indicated otherwise, and provided certain other 
recommendations specified in CPG 7132b.11 were met. These other 
conditions include, but are not limited to, standards for containers, 
repackaging operations, and the repackaging environment.
    Additionally, because CPG 7132b.11 serves as Attachment B to 
section 430.100 of the CPG (CPG 7132b.10, ``Unit Dose Labeling for 
Solid and Liquid Oral Dosage Forms''), the proposed revision of CPG 
7132b.11 will serve as Attachment B to CPG 7132b.10 when CPG 7132b.11 
is finalized.
    We invite comments on the draft guidance. Additionally, we intend 
to conduct further study of the appropriateness of the proposed 
revision of CPG 7132b.11 regarding expiration dating on the unit-dose 
containers of nonsterile repackaged solid and liquid oral dosage form 
drug

[[Page 30954]]

products. We do not intend to make a final decision on the proposed 
revision of CPG 7132b.11 until we complete further study of the 
expiration dating issue to determine the most scientifically sound 
approach. We invite interested persons to submit data establishing 
appropriate expiration dating for such drug products.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the agency's current thinking on expiration 
dating on nonsterile unit-dose repackaged drug products. It does not 
create or confer any rights for or on any person and does not operate 
to bind FDA or the public. An alternative approach may be used if such 
approach satisfies the current requirements of the applicable statutes 
and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments on the draft guidance. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. The draft guidance and received 
comments may be seen in the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the documents at 
http://www.fda.gov/cder/guidance/index.htm or http://ohrms/dockets/
default.htm.

    Dated: May 19, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-10702 Filed 5-27-05; 8:45 am]
BILLING CODE 4160-01-S