[Federal Register: May 31, 2005 (Volume 70, Number 103)]
[Notices]
[Page 30953-30954]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr31my05-42]
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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Draft Guidance on Expiration Dating of Unit-Dose Repackaged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.
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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availability of a draft guidance entitled ``Expiration Dating of Unit-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 The draft guidance is a proposed revision of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DATES: Submit written or electronic comments on the draft guidance by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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information (HFD-240), Center for Drug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on the draft guidance to the Division of Dockets Management (HFA-305),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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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access to the draft guidance document.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We are announcing the availability of a draft guidance on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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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