[Federal Register Volume 65, Number 119 (Tuesday, June 20, 2000)]
[Notices]
[Pages 38290-38292]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-15429]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-0726]


Agency Information Collection Activities; Submission for OMB 
Review; Comment Request; General Licensing Provisions: Changes to an 
Approved Application, Labeling, and Revocation and Suspension

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing that the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments on the collection of information by July 
20, 2000.

ADDRESSES: Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Wendy Taylor, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: JonnaLynn P. Capezzuto, Office of 
Information Resources Management (HFA-250), Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

General Licensing Provisions: Changes to an Approved Application, 
Labeling, and Revocation and Suspension (OMB Control Number 0910-
0315)--Extension

    Under Section 351 of the Public Health Services Act (PHS Act) (42 
U.S.C. 262), manufacturers of biological products must submit a license 
application for FDA review and approval prior to marketing a biological 
product in interstate commerce. Licenses may be issued only upon 
showing that the establishment and the products for which a license is 
desired meet standards prescribed in regulations designed to ensure the 
continued safety, purity, and potency of such products. All such 
licenses are issued, suspended, and revoked as prescribed by 
regulations.
    In part 601 (21 CFR part 601), Sec. 601.2(a) requires a 
manufacturer of a biological product to submit an application with 
accompanying information, including labeling information, to FDA for 
approval to market a product in interstate commerce. Section 601.12(b), 
(c), and (d) requires applicants to follow specific procedures in 
informing FDA of each change, established in an approved license 
application, in the product, production process, quality controls, 
equipment, facilities, or responsible personnel depending on the 
potential for the change to have a substantial, moderate, minimal or no 
adverse effect on the safety or effectiveness of the product. Section 
601.12(e) requires applicants to submit a protocol, or change to a 
protocol, as a supplement requiring FDA approval prior to distributing 
the product. Section 601.12(f)(1), (f)(2), and (f)(3) requires 
applicants to follow specific procedures in reporting labeling changes 
to FDA. Section 601.12(f)(4) requires advertising and promotional 
labeling and any changes to be reported to FDA. Section 601.45 requires 
applicants to submit to the agency for consideration, during the 
preapproval review period, copies of all promotional materials, 
including promotional labeling as well as advertisements. In addition 
to Secs. 601.2 and 601.12, there are other regulations that relate to 
certain information submitted in a license application or supplement as 
follows: Part 640 (21 CFR part 640), specifically Secs. 640.6, 640.17, 
640.21(c), 640.22(c), 640.25(c), 640.56(c), 640.64(c), 640.74(a), and 
(b)(2); 21 CFR 660.51(a)(4) and 680.1(b)(2)(iii) and (c). The burden 
associated with the information collection requirements in these 
regulations is included in the burden estimate for Sec. 601.2, reported 
under OMB Control No. 0910-0427, and Sec. 601.12 in table 1 of this 
document. Sections 600.15(b) and 610.53(d) require the submission of a 
request for an exemption or modification regarding the temperature 
requirements during shipment and from dating periods, respectively, for 
certain biological products. Section 601.25(b) requests interested 
persons to submit, for review and evaluation by an advisory review 
panel, published and unpublished data and information pertinent to a 
designated category of biological products that have been licensed 
prior to July 1, 1972. Section 601.26(f) requests that licensees submit 
to FDA a written statement intended to show that studies adequate and 
appropriate to resolve questions raised about a biological product have 
been undertaken for a product if designated as requiring further study 
under the reclassification procedures. Section 601.5(a) requires a 
licensee to give notice of its intention to discontinue manufacture of 
a product or all products. Section 601.6(a) requires the licensee to 
notify selling agents and distributors upon suspension of its license, 
and provide FDA with records of such notification.
    Form FDA 2567 is used by manufacturers of licensed biological 
products to submit labeling (e.g., circulars, package labels, container 
labels, etc.) and labeling changes for FDA review and approval. The 
labeling information is submitted with the form for license 
applications, supplements, or as part of an annual report. Form FDA 
2567 is also used for the transmission of advertisements and 
promotional labeling. Form FDA 2567 serves as an easy guide to assure 
that the manufacturer has provided the information required for 
expeditious handling of their labeling by the Center for Biologics 
Evaluation and Research (CBER). For advertisements and promotional 
labeling, manufacturers of licensed biological products may submit to 
CBER either Form FDA 2567 or 2253. Form FDA 2253 was previously used 
only by drug manufacturers regulated by the Center for Drug Evaluation 
and Research. In August of 1998, FDA revised and harmonized Form FDA 
2253 to enable the form to be used to transmit specimens of promotional 
labeling and advertisements for biological products as well as for 
prescription drugs and antibiotics. The revised, harmonized form 
updates the information about the types of promotional materials and 
the codes that are used to clarify the type of advertisement or 
labeling submitted; clarifies the intended audience for the 
advertisements or promotional labeling (e.g., consumers, professionals, 
news services); and helps ensure that the submission is complete.
    The number of respondents is based on the estimated annual number 
of manufacturers that submitted the required information to FDA. There 
are an estimated 350 licensed biologics manufacturers. However, not all 
manufacturers will have any submissions in a given year and some may 
have multiple submissions. The

[[Page 38291]]

total annual responses is based on the estimated number of submissions 
(i.e., license applications, labeling and other supplements, protocols, 
advertising and promotional labeling, notifications) received annually 
by FDA. The rate of submissions are not expected to change 
significantly in the next few years. The hours per response are based 
on past FDA experience with the various submissions or notifications. 
Additional information regarding these estimates is provided below as 
necessary.
    Under Sec. 601.2(a), the total annual responses is based on the 
numbers of applications submitted to FDA for approval to market a 
biological product. The estimated burden hours include the time 
required to fill out the form and collate the documentation. The 
estimated burden hours to prepare the labeling information submitted 
with a license application are included in the burden hours to submit a 
license application that are reported under OMB Control No. 0910-0427.
    Under Sec. 601.12(f)(1), (f)(2), and (f)(3), the estimated burden 
hours include the time to prepare the supplement, fill out the form, 
and collate the documentation.
    Under Secs. 601.12(f)(4) and 601.45, manufacturers of biological 
products may use either Form FDA 2567 or Form FDA 2253 to submit 
advertising and promotional labeling. In fiscal year 1999, CBER 
received 3,784 submissions of advertising and promotional labeling from 
114 manufacturers. FDA estimates that approximately 55 percent of those 
submissions were received with Form FDA 2567 resulting in an estimated 
2,081 submissions by 63 manufacturers. The estimated burden hours 
include the time to prepare the submission, fill out the form, and 
collate the documentation. The burden hours for the remaining 
submissions received using Form FDA 2253 are reported under OMB Control 
No. 0910-0376.
    Under Secs. 601.12(b) through (d), and 601.12(e), the estimated 
burden hours include the time to prepare the appropriate supplement or 
protocol, respectively, and collate the documentation.
    Under Secs. 600.15(b) (21 CFR 600.15(b)) and 610.53(d), FDA 
receives very few requests for an exemption or modification to the 
requirements, therefore, FDA has estimated one respondent per year in 
table 1 of this document to account for the rare instance in which a 
request may be made. The estimated burden hours include the time to 
prepare the request for modification or exemption.
    Under Sec. 601.25(b)(3), FDA estimates no burden for this 
regulation because all requested data and information had been 
submitted by 1974. Under Sec. 601.26(f), FDA estimates no burden for 
this regulation because there are no products designated to require 
further study and none are predicted in the future. However, based on 
the possible reclassification of a product, the labeling for the 
product may need to be revised, or a manufacturer, on its own 
initiative, may find further study necessary. As a result, any changes 
to product labeling would be reported under Sec. 601.12. The 
information collection requirements for Sec. 601.12 are reported under 
OMB control number 0910-0315.
    Under Sec. 601.5(a), the total annual responses are based on the 
estimated annual number of notifications received by FDA to discontinue 
either an establishment and/or product license(s). The estimated burden 
hours include the time to prepare and submit a letter of 
discontinuance.
    Under Sec. 601.6(a), the number of respondents (21) is based on FDA 
estimates that establishments would need to notify an average of 20 
selling agents and distributors of such suspension, and provide FDA 
with the records of such notification. The number of respondents is 
based on the estimated annual number of suspensions by FDA of an 
establishment or product license(s). The estimated burden hours 
includes the time to prepare a notification letter and submit record of 
such notification to FDA.
    In the Federal Register of March 7, 2000 (65 FR 12011), the agency 
requested comments on the proposed collections of information. No 
significant comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1.--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                        Annual
 21 CFR section   Form FDA No.         No. of        frequency per   Total annual     Hours per     Total hours
                                    respondents        response        responses       response
----------------------------------------------------------------------------------------------------------------
601.2(a)         2567 and 356h   17                 3.71            63              2              126
                  \2\
601.12(f)(1)     2567            12                 1               12              40             480
601.12(f)(2)     2567            10                 1               10              20             200
601.12(f)(3)     2567            70                 1.43            100             10             1,000
601.12(f)(4)     2567            63                 33.03           2,081           10             20,810
 and 601.45
601.12(b)(1)     356h \2\        190                4.75            903             80             72,240
 and (b)(3)
601.12(c)(1)     356h \2\        98                 2.60            255             50             12,750
 and (c)(3)
601.12(c)(5)     356h \2\        34                 1.21            41              50             2,050
601.12(d)        356h \2\        166                1.37            227             10             2,270
601.12(e)        356h \2\        14                 1.43            20              20             400
600.15(b)        356h \2\        1                  1               1               8              8
610.53(d)        356h \2\        1                  1               1               8              8
601.25(b)(3)     NA              0                  0               0               0              0
601.26(f)        NA              0                  0               0               0              0
601.5(a)         NA              33                 1               33              .33            11
601.6(a)         NA              2                  10.50           21              .33            7
Total                                                                                              112,360
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ The burden hours for the use of Form FDA 356h are reported under OMB Control No. 0910-0427.



[[Page 38292]]

    Dated: June 14, 2000.
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 00-15429 Filed 6-20-00; 8:45 am]
BILLING CODE 4160-01-F