[Federal Register Volume 76, Number 159 (Wednesday, August 17, 2011)]
[Notices]
[Pages 51038-51039]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-20852]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-D-0246]


Guidance for Industry on Residual Drug in Transdermal and Related 
Drug Delivery Systems; 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 guidance for industry entitled ``Residual Drug in 
Transdermal and Related Drug Delivery Systems.'' This guidance provides 
recommendations to developers and manufacturers of transdermal drug 
delivery systems (TDDS), transmucosal drug delivery systems (TMDS), and 
topical patch products regarding use of an appropriate scientific 
approach during product design and development--as well as during 
manufacturing and product life-cycle management--to ensure that the 
amount of residual drug substance at the end of the labeled use period 
is minimized. The guidance is applicable to investigational new drug 
applications, new drug applications, abbreviated new drug applications, 
and supplemental new drug applications for TDDS, TMDS, and topical 
patch products.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of this guidance 
to the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, rm. 2201, Silver Spring, MD 20993-0002. Send one self-addressed 
adhesive label to assist that office in processing your requests. See 
the SUPPLEMENTARY INFORMATION section for electronic access to the 
guidance document.
    Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Terrance Ocheltree, Center for Drug 
Evaluation and Research, Food and Drug Administration, Bldg. 21, rm. 
1609, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-
1988.

SUPPLEMENTARY INFORMATION:

[[Page 51039]]

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Residual Drug in Transdermal and Related Drug Delivery 
Systems.'' This guidance provides recommendations to developers and 
manufacturers of TDDS, TMDS, and topical patch products regarding use 
of an appropriate scientific approach during product design and 
development--as well as during manufacturing and product life-cycle 
management--to ensure that the amount of residual drug substance at the 
end of the labeled use period is minimized. In the Federal Register of 
August 3, 2010 (75 FR 45640), FDA announced the availability of the 
draft version of this guidance. The public comment period closed on 
November 1, 2010. A number of comments were received from the public, 
all of which the Agency considered carefully as it finalized the 
guidance and made appropriate changes. Any changes to the guidance were 
minor and made to clarify statements in the draft guidance.
    Existing TDDS, TMDS, and topical patches contain a larger amount of 
the drug substance than what is intended to be delivered to the 
patient. This excess amount of drug substance is needed to facilitate 
delivery of the intended amount of the drug to the patient and remains 
as residual drug in the used system. The amount of residual drug 
substance in TDDS, TMDS, and topical patches has a significant 
potential to impact the products' quality, efficacy, and safety 
(including abuse potential). Consequently, it is necessary to ensure 
that an appropriate scientific approach is used to design and develop 
these products. The approach should ensure that the amount of residual 
drug substance is minimized consistent with the current state of 
technology.
    Currently marketed TDDS, TMDS, and topical patches may retain 10 to 
95 percent of the initial total amount of drug as the residual drug 
after the intended use period. This raises a potential safety issue not 
only to the patient, but also to others, including family members, 
caregivers, children, and pets. For example, adverse events due to a 
patient's failure to remove TDDS at the end of the intended use period 
have been reported and are generally related to an increased or 
prolonged pharmacological effect of the drug. Also, some children have 
died from inadvertent exposure to discarded TDDS. Reported adverse 
events resulting from various quality problems pertaining to TDDS have 
lead to product recalls, withdrawals, and public health advisories.
    To reduce some of these risks, the Agency recommends that a robust 
design and development approach be considered when developing and 
manufacturing TDDS, TMDS, and topical patches. One example of such an 
approach is quality by design, as described in the International 
Conference on Harmonization guidance for industry entitled ``Q8(R2) 
Pharmaceutical Development.'' The Agency also recommends that 
sufficient scientific justification to support the amount of residual 
drug in TDDS, TMDS, or topical patches be included in an application. 
The justification should include an evaluation of the safety risks 
involved with the formulation and system design, as well as support the 
amount of drug load in the TDDS, TMDS, or topical patch based on the 
proposed quality target product profile and formulation studies. Most 
important, the justification for applications of products with known 
safety issues--such as those with fentanyl-containing liquid reservoir 
systems--should demonstrate that the safety risk factors have been 
adequately mitigated.
    In all cases, the level of information in the justification should 
be sufficient to demonstrate product and process understanding and 
ensure that a scientific, risk-based approach has been taken to 
minimize the amount of residual drug in a system after use to the 
lowest possible level. It is expected that the amount of residual drug 
in a newly developed system (including new generic drug products) will 
not exceed that of similar FDA-approved products.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
Agency's current thinking on residual drug in transdermal and related 
drug delivery systems. 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.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

III. The Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). 
Information in an application on the product and process development 
and justification for the final formulation and system design is 
approved under OMB control numbers 0910-0001 and 0910-0014.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: August 10, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-20852 Filed 8-16-11; 8:45 am]
BILLING CODE 4160-01-P