[Federal Register Volume 65, Number 208 (Thursday, October 26, 2000)]
[Notices]
[Pages 64225-64226]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-27452]



[[Page 64225]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-1537]


Draft Guidance for Industry on Referencing Discontinued Labeling 
for Listed Drugs in Abbreviated New Drug Applications; 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availability of a draft guidance for industry entitled ``Referencing 
Discontinued Labeling for Listed Drugs in Abbreviated New Drug 
Applications.'' This document is intended to provide guidance to 
applicants on referencing discontinued labeling for listed drugs in 
abbreviated new drug applications (ANDA's) submitted for approval under 
the Federal Food, Drug, and Cosmetic Act (the act). This issue has only 
recently arisen and is not addressed directly in the agency's 
regulations governing the approvals of ANDA's.

DATES: Submit written comments on the draft guidance by January 24, 
2001. General comments on agency guidance documents are welcome at any 
time.

ADDRESSES: Copies of this draft guidance for industry are available on 
the Internet at http://www.fda.gov/cder/guidance/index.htm. Submit 
written requests for single copies of this draft guidance to the Drug 
Information Branch (HFD-210), 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 Submit written comments on the draft guidance 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 Dockets Management Branch (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Cecelia M. Parise, Center for Drug 
Evaluation and Research (HFD-600), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-5845.

SUPPLEMENTARY INFORMATION: The Drug Price Competition and Patent Term 
Restoration Act of 1984 (the Hatch-Waxman amendments) established the 
generic drug approval program used today to ensure that lower price 
generic drugs are made available to the public promptly upon the 
expiration of patent and exclusivity protections covering the innovator 
products. The generic drug approval process generally depends on the 
ANDA applicant establishing that the generic drug is the same as an 
approved innovator product (the listed drug) with respect to active 
ingredients, dosage form, strength, route of administration, conditions 
of use, and labeling.
    During the period when an innovator drug is being marketed, it may 
undergo a number of changes that are approved through supplements to 
new drug applications (NDA's). Such changes can include the addition of 
new indications, changes to the product formulation, and labeling 
changes. In the past, when ANDA's have been submitted, they have 
referenced only the innovator drug product labeling as it appeared at 
the time of ANDA submission. However, recently a question has been 
raised as to whether, in certain circumstances, an ANDA can refer to 
discontinued labeling for the listed drug. The issue of referencing 
discontinued labeling arises when the sponsor of the listed drug 
product has obtained exclusivity or patent protection for a new part of 
product labeling and has removed a part of the previous labeling, 
unprotected by exclusivity or patents, for reasons other than safety or 
effectiveness. When the holder of the listed drug obtains approval and 
market protection for a change to the drug and removes the 
corresponding unprotected information from the current labeling, there 
remains no current labeling for the ANDA applicant to reference. This 
raises the question of whether applicants will be barred from obtaining 
approval for any ANDA referencing that listed drug until the protection 
for the particular aspect of the labeling expires, because relevant 
labeling is either protected or has been removed from the currently 
marketed product.
    FDA has developed an approach to this situation that ensures that 
labeling removed from a drug product for reasons of safety or 
effectiveness cannot be referenced in an ANDA, while at the same time 
permitting approval of generic drugs that reference discontinued 
labeling for safe and effective innovator products. This approach 
ensures that safe and effective generic drug products are made 
available to the public as promptly as possible when relevant market 
protections have expired.
    An ANDA will be permitted to reference discontinued labeling for a 
listed drug when: (1) The holder of the NDA for the innovator drug has 
obtained approval for a change in the drug labeling; (2) the change has 
received either a patent listed in ``Approved Drug Products with 
Therapeutic Equivalence Evaluations'' (the Orange Book) or market 
exclusivity under the act; (3) the NDA sponsor has removed or revised 
the labeling describing the corresponding unprotected aspects of the 
drug; (4) the change to the drug product is not one for which a 
suitability petition may be filed (21 CFR 314.93); (5) the sponsor 
wishing to reference the discontinued labeling has submitted a petition 
requesting that the agency determine whether the previous labeling was 
withdrawn for reasons of safety or effectiveness, or the agency on its 
own initiative, begins the process of determining the reasons for the 
withdrawal of the previous labeling; (6) the agency has determined that 
the previous innovator labeling was not withdrawn for reasons of safety 
or effectiveness; and (7) the agency has determined that omission of 
the protected information will not render the drug product less safe or 
effective than the currently marketed innovator product.
    The draft guidance identifies the provisions of the act and FDA 
regulations relevant to this issue, and provides a detailed description 
of the process an ANDA applicant should follow to refer to discontinued 
labeling for a listed drug. It also describes the actions FDA will take 
to determine whether the use of such labeling is acceptable because the 
labeling was not withdrawn from the market for reasons of safety or 
effectiveness.
    This draft guidance is being issued consistent with FDA's good 
guidance practices (65 FR 56468, September 19, 2000). The draft 
guidance represents the agency's current thinking on referencing 
discontinued labeling for listed drugs in ANDA's. 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 requirements of the applicable statutes and regulations.
    Interested persons may submit to the Dockets Management Branch 
(address above) written comments on the draft guidance. Two copies of 
any comments are to be submitted, except that individuals may submit 
one 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 are available for public examination in the Dockets 
Management Branch between 9 a.m. and 4 p.m., Monday through Friday.


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    Dated: October 13, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-27452 Filed 10-25-00; 8:45 am]
BILLING CODE 4160-01-F