51038 Federal Register / Vol. 76, No. 159 / Wednesday, August 17, 2011 / Notices 

reports of possible postmarketing 

adverse events. FDA has determined, 

under § 314.161, that Halflytely and 

Bisacodyl Tablets Bowel Prep Kit (10- 

mg bisacodyl) was withdrawn from sale 

for reasons of safety or effectiveness. 

Braintree discontinued this product 

containing a total dose of 10 milligrams 

of bisacodyl from sale after receiving 

approval from FDA on July 16, 2010, for 

NDA 21–551/S–013, Halflytely and 

Bisacodyl Tablets Bowel Prep Kit (PEG– 

3350, sodium chloride, sodium 

bicarbonate, and potassium chloride for 

oral solution and one bisacodyl delayed 

release tablet, 5 mg (5-mg bisacodyl)). 

The data available from a clinical study 

comparing the 10-mg version of 

Halflytely and Bisacodyl Tablets Bowel 

Prep Kit to a 5-mg version of the drug 

product showed that the Halflytley and 

Bisacodyl Tablets Bowl Prep Kit (5-mg 

bisacodyl) has comparable effectiveness 

to the 10-mg product and has a safety 

advantage over the 10-mg product 

because there is less abdominal fullness 

and cramping in the patients treated 

with the 5-mg product. Furthermore, the 

10-mg product may be associated with 

ischemic colitis. 

FDA has also reviewed the latest 

approved labeling for the 10-mg product 

and has determined that it would need 

to be updated with additional safety 

information if Braintree were to 

reintroduce the 10-mg product to the 

market. FDA has determined that 

additional clinical studies of safety and 

efficacy would be necessary before 

Halflytely and Bisacodyl Tablets Bowel 

Prep Kit (10-mg bisacodyl) could be 

considered for reintroduction to the 

market. Accordingly, the Agency will 

remove Halflytely and Bisacodyl Tablets 

Bowel Prep Kit (PEG–3350, sodium 

chloride, sodium bicarbonate, and 

potassium chloride for oral solution and 

two bisacodyl delayed release tablets, 5 

mg) from the list of drug products 

published in the Orange Book. FDA will 

not accept or approve ANDAs that refer 

to this drug product. 

Dated: August 10, 2011. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2011–20853 Filed 8–16–11; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2007–D–0068; formerly 

Docket No. 2007D–0290] 

Draft Guidance for Industry: Cell 

Selection Devices for Point of Care 

Production of Minimally Manipulated 

Autologous Peripheral Blood Stem 

Cells; Withdrawal of Draft Guidance 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice; withdrawal. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

withdrawal of a draft guidance entitled 

‘‘Draft Guidance for Industry: Cell 

Selection Devices for Point of Care 

Production of Minimally Manipulated 

Autologous Peripheral Blood Stem Cells 

(PBSCs)’’ dated July 2007. 

DATES: August 17, 2011. 

FOR FURTHER INFORMATION CONTACT: 

Tami Belouin, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration (HFM–17), 1401 

Rockville Pike, suite 200N, Rockville, 

MD 20852–1448, 301–827–6210. 

SUPPLEMENTARY INFORMATION: In a notice 

published in the Federal Register of 

July 26, 2007 (72 FR 41080), FDA 

announced the availability of a draft 

guidance entitled ‘‘Draft Guidance for 

Industry: Cell Selection Devices for 

Point of Care Production of Minimally 

Manipulated Autologous Peripheral 

Blood Stem Cells (PBSCs).’’ 

FDA has carefully considered the 

comments received on the draft 

guidance and, since that document 

issued in 2007, has gained additional 

experience with point of care devices 

and the autologous cells selected by 

them. Based on these comments and 

experience, FDA believes that the draft 

guidance would not, if finalized in 

current form, reflect FDA’s current 

thinking. For these reasons, FDA is 

withdrawing the draft guidance entitled 

‘‘Draft Guidance for Industry: Cell 

Selection Devices for Point of Care 

Production of Minimally Manipulated 

Autologous Peripheral Blood Stem Cells 

(PBSCs).’’ 

Dated: August 10, 2011. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2011–20862 Filed 8–16–11; 8:45 am] 

BILLING CODE 4160–01–P 

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. 

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: 


Emcdonald on DSK2BSOYB1PROD with NOTICES
Federal Register / Vol. 76, No. 159 / Wednesday, August 17, 2011 / Notices 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 lifecycle 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/Guidance

ComplianceRegulatoryInformation/

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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–N–0013] 

Statement of Organizations, Functions, 

and Delegations of Authority 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that it has reorganized the Center for 

Drug Evaluation and Research (CDER) 

by establishing four new Divisions 

under the Office of Generic Drugs. This 

reorganization includes the organization 

and their substructure components as 

listed in this document. This document 

is announcing the availability of the 

Staff Manual Guide that explains the 

details of this reorganization. 

FOR FURTHER INFORMATION CONTACT: 

Karen Koenick, Center for Drug 

Evaluation and Research (HFD–063), 

Food and Drug Administration, 1919 

Rockville Pike, Rm. 324, Rockville, MD 

20852, 301–796–4422. 

SUPPLEMENTARY INFORMATION: 

I. Summary 

The Statement of Organization, 

Functions, and Delegations of Authority 


Emcdonald on DSK2BSOYB1PROD with NOTICES