Federal Register / Vol. 70, No. 206 / Wednesday, October 26, 2005 / Notices 61829 

agency is not responsible for providing 

access to electrical outlets. 

FDA welcomes the attendance of the 

public at its advisory committee 

meetings and will make every effort to 

accommodate persons with physical 

disabilities or special needs. If you 

require special accommodations due to 

a disability, please contact Christine 

Walsh or Denise Royster at least 7 days 

in advance of the meeting. 

Notice of this meeting is given under 

the Federal Advisory Committee Act (5 

U.S.C. app. 2). 

Dated: October 18, 2005. 

Jason Brodsky, 

Acting Associate Commissioner for External 

Relations. 

[FR Doc. 05–21350 Filed 10–25–05; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2005D–0392] 

Guidance for Industry and Food and 

Drug Administration Staff; Class II 

Special Controls Guidance Document: 

Cystic Fibrosis Transmembrane 

Conductance Regulator Gene Mutation 

Detection Systems; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of the guidance document 

entitled ‘‘Class II Special Controls 

Guidance Document: CFTR Gene 

Mutation Detection Systems.’’ This 

guidance document describes a means 

by which cystic fibrosis transmembrane 

conductance regulator (CFTR) gene 

mutation detection systems may comply 

with the requirements of special 

controls for class II devices. It includes 

recommendations for validation of 

performance characteristics and 

recommendations for product labeling. 

Elsewhere in this issue of the Federal 

Register, FDA is publishing a final rule 

to classify CFTR gene mutation 

detection systems into class II (special 

controls). This guidance document is 

immediately in effect as the special 

control for CFTR gene mutation 

detection systems, but it remains subject 

to comment in accordance with the 

agency’s good guidance practices 

(GGPs). 

DATES: Submit written or electronic 

comments on this guidance at any time. 

ADDRESSES: Submit written requests for 

single copies on a 3.5′′ diskette of the 

guidance document entitled ‘‘Class II 

Special Controls Guidance Document: 

CFTR Gene Mutation Detection 

Systems’’ to the Division of Small 

Manufacturers, International, and 

Consumer Assistance (HFZ–220), Center 

for Devices and Radiological Health, 

Food and Drug Administration, 1350 

Piccard Dr., Rockville, MD 20850. Send 

one self-addressed adhesive label to 

assist that office in processing your 

request or fax your request to 301–443–

8818. See the SUPPLEMENTARY

INFORMATION section for information on 

electronic access to the guidance. 

Submit written comments concerning 

this 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:// 

www.fda.gov/dockets/ecomments. 

Identify comments with the docket 

number found in brackets in the 

heading of this document. 

FOR FURTHER INFORMATION CONTACT: 

Zivana Tezak, Center for Devices and 

Radiological Health (HFZ–440), Food 

and Drug Administration, 2098 Gaither 

Rd., Rockville, MD 20850, 240–276–

0597. 

SUPPLEMENTARY INFORMATION: 

I. Background 

Elsewhere in this issue of the Federal 

Register, FDA is publishing a final rule 

classifying CFTR gene mutation 

detection systems into class II (special 

controls) under section 513(f)(2) of the 

Federal Food, Drug, and Cosmetic Act 

(the act) (21 U.S.C. 360c(f)(2)). This 

guidance document will serve as the 

special control for CFTR gene mutation 

detection systems. Section 513(f)(2) of 

the act provides that any person who 

submits a premarket notification under 

section 510(k) of the act (21 U.S.C. 

360(k)) for a device that has not 

previously been classified may, within 

30 days after receiving an order 

classifying the device in class III under 

section 513(f)(1) of the act, request FDA 

to classify the device under the criteria 

set forth in section 513(a)(1) of the act. 

FDA shall, within 60 days of receiving 

such a request, classify the device by 

written order. This classification shall 

be the initial classification of the device. 

Within 30 days after the issuance of an 

order classifying the device, FDA must 

publish a notice in the Federal Register 

announcing such classification. Because 

of the timeframes established by section 

513(f)(2) of the act, FDA has 

determined, under § 10.115(g)(2) (21 

CFR 10.115(g)(2)), that it is not feasible 

to allow for public participation before 

issuing this guidance as a final guidance 

document. Therefore, FDA is issuing 

this guidance document as a level 1 

guidance document that is immediately 

in effect. FDA will consider any 

comments that are received in response 

to this notice to determine whether to 

amend the guidance document. 

II. Significance of Guidance 

This guidance is being issued 

consistent with FDA’s GGPs regulation 

(§ 10.115). The guidance represents the 

agency’s current thinking on CFTR gene 

mutation detection 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 statute and regulations. 

III. Electronic Access 

To receive ‘‘Class II Special Controls 

Guidance Document: CFTR Gene 

Mutation Detection Systems’’ by fax 

machine, call the CDRH Facts-OnDemand system at 800–899–0381 or 

301–827–0111 from a touch-tone 

telephone. Press 1 to enter the system. 

At the second voice prompt, press 1 to 

order a document. Enter the document 

number (1564) followed by the pound 

sign (#). Follow the remaining voice 

prompts to complete your request. 

Persons interested in obtaining a copy 

of the guidance may also do so by using 

the Internet. The Center for Devices and 

Radiological Health (CDRH) maintains 

an entry on the Internet for easy access 

to information, including text, graphics, 

and files that may be downloaded to a 

personal computer with Internet access. 

Updated on a regular basis, the CDRH 

home page includes device safety alerts, 

Federal Register reprints, information 

on premarket submissions (including 

lists of approved applications, and 

manufacturers’ addresses), small 

manufacturer’s assistance, information 

on video conferencing and electronic 

submissions, Mammography Matters, 

and other device-oriented information. 

The CDRH Web site may be accessed at 

http://www.fda.gov/cdrh. A search 

capability for all CDRH guidance 

documents is available at http:// 

www.fda.gov/cdrh/guidance.html. 

Guidance documents are also available 

on the Division of Dockets Management 

Internet site at http://www.fda.gov/ 

ohrms/dockets. 

IV. Paperwork Reduction Act of 1995 

This guidance contains information 

collection provisions that are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

61830 Federal Register / Vol. 70, No. 206 / Wednesday, October 26, 2005 / Notices 

Reduction Act of 1995 (the PRA) (44 

U.S.C. 3501–3520). The collections of 

information addressed in the guidance 

document have been approved by OMB 

in accordance with the PRA under the 

regulations governing premarket 

notification submissions (21 CFR part 

807, subpart E, OMB control number 

0910–0120). The labeling provisions 

addressed in the guidance have been 

approved by OMB under OMB control 

number 0910–0485. 

V. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES), written or electronic 

comments regarding this document. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, 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. Comments 

received may be seen in the Division of 

Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

Dated: October 17, 2005. 

Linda S. Kahan, 

Deputy Director, Center for Devices and 

Radiological Health. 

[FR Doc. 05–21349 Filed 10–25–05; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2002D–0307] (formerly 02D–

0307) 

Guidance for Industry on Potassium 

Chloride Modified-Release Tablets and 

Capsules: In Vivo Bioequivalence and 

In Vitro Dissolution Testing; 

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 ‘‘Potassium Chloride ModifiedRelease Tablets and Capsules: In Vivo 

Bioequivalence and In Vitro Dissolution 

Testing.’’ This guidance document 

provides recommendations to sponsors 

of abbreviated new drug applications 

(ANDAs) on the design of 

bioequivalence studies for modifiedrelease dosage forms of potassium 

chloride. 

DATES: Submit written or electronic 

comments on agency guidances at any 

time. 

ADDRESSES: Submit written requests for 

single copies of this 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 selfaddressed adhesive label to assist that 

office in processing your requests. 

Submit written comments on the 

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:// 

www.fda.gov/dockets/ecomments. See 

the SUPPLEMENTARY INFORMATION section 

for electronic access to the guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Lizzie Sanchez, Center for Drug 

Evaluation and Research (HFD–650), 

Food and Drug Administration, 5600 

Fishers Lane, Rockville, MD 20857, 

301–827–5847. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry entitled 

‘‘Potassium Chloride Modified-Release 

Tablets and Capsules: In Vivo 

Bioequivalence and In Vitro Dissolution 

Testing.’’ This guidance is intended to 

provide information to sponsors of 

ANDAs on the design of bioequivalence 

studies for modified-release dosage 

forms of potassium chloride. 

A document entitled ‘‘Guidance for In 

Vivo Bioequivalence Study for SlowRelease Potassium Chloride Tablets/ 

Capsules’’ was issued on May 15, 1987 

(1987 guidance), and revised on June 6, 

1994 (1994 revision). The guidance was 

further revised to incorporate FDA’s 

current thinking on the bioequivalence 

requirements for potassium chloride 

modified-release products and was 

issued in draft on August 7, 2002 (2002 

draft guidance) (67 FR 51284). 

Comments were reviewed and 

incorporated. The most substantive 

changes made are described in the 

following paragraphs. Editorial changes 

were also made and the final guidance 

is now available. 

In the 2002 draft guidance, the agency 

recommended a three-way crossover 

design study comparing the reference 

listed drug (RLD) to both the generic 

product and a solution of potassium 

chloride. The 2002 draft guidance also 

recommended analysis of covariance 

(ANCOVA) for the pharmacokinetic 

parameters. 

The final guidance provides 

recommendations for a two-way 

crossover design comparing the generic 

product to the RLD. This design is 

consistent with the 1994 revision, 

which stated that the potassium 

chloride solution mentioned in the 1987 

guidance was no longer necessary and 

recommended the use of a twotreatment, two-period, single-dose, 

fasting study comparing test product 

with reference product. The FDA 

determined that the potassium chloride 

solution arm is not necessary because 

the objective of the bioequivalence 

study is to directly compare the rate and 

extent of potassium absorption from the 

test product and the reference product. 

Therefore, the potassium chloride 

solution arm is not necessary for the 

test-versus-reference comparison and 

adds unnecessary complexity to the 

statistical bioequivalance analysis. 

We also have decided not to 

recommend the use of ANCOVA in the 

final guidance. Analysis of variance 

(ANOVA) with baseline correction is 

adequate for bioequivalence analysis of 

pharmacokinetic data obtained 

following oral administration of 

potassium chloride drug products. The 

FDA concluded that using ANCOVA 

with baseline as a covariate to analyze 

baseline-uncorrected data was not as 

sensitive to changes in formulation 

performance as using ANOVA to 

analyze baseline-corrected data. 

The dissolution testing and criteria for 

waivers on in vivo testing for lower 

strengths are revised to reflect the 

changes outlined in the guidance 

entitled ‘‘Bioavailability and 

Bioequivalence Studies for Orally 

Administered Drug Products—General 

Considerations,’’ available on the 

Internet at http://www.fda.gov/cder/ 

guidance/index.htm. 

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 studies to 

demonstrate the bioequivalence of 

potassium chloride modified-release 

tablets and capsules. 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) written or electronic 

comments on the guidance at any time. 

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