
[Federal Register: August 3, 2010 (Volume 75, Number 148)]
[Notices]               
[Page 45640-45641]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03au10-77]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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

 
Draft Guidance for Industry on Residual Drug in Transdermal and 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availability of a draft guidance for industry entitled ``Residual Drug 
in Transdermal and Related Drug Delivery Systems.'' This draft guidance 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 lifecycle management--to ensure that 
the amount of residual drug substance at the end of the labeled use 
period is minimized. The draft guidance is applicable to 
investigational new drug applications (INDs), new drug applications 
(NDAs), abbreviated new drug applications (ANDAs), and supplemental new 
drug applications (sNDAs) for TDDS, TMDS, and topical patch products.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance, including comments regarding the proposed collection of 
information, by November 1, 2010.

ADDRESSES:  Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://
www.regulations.gov. Submit written comments on the draft guidance to 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.

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:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Residual Drug in Transdermal and Related Drug Delivery 
Systems.'' This draft 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 lifecycle 
management--to ensure that the amount of residual drug substance at the 
end of the labeled use period is minimized.
    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, safety, and efficacy. 
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 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. 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, we recommend that an enhanced design 
and development approach--specifically Quality by Design (QbD), as 
described in the International Conference on Harmonization (ICH) 
guidance for industry Q8(R2) Pharmaceutical Development--be used when 
developing and manufacturing TDDS, TMDS, and topical patches. We also 
recommend that sufficient scientific justification to support the 
amount of residual drug in TDDS, TMDS, or topical patches be included 
in an application. 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. Furthermore, it is expected that the amount of 
residual drug in a newly developed system will not exceed that of 
similar FDA-approved 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 residual 
drug in transdermal and related drug delivery systems. It does not 
create or confer any rights for or on

[[Page 45641]]

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 draft 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 by OMB under 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: July 29, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-19041 Filed 8-2-10; 8:45 am]
BILLING CODE 4160-01-S

