[Federal Register Volume 63, Number 198 (Wednesday, October 14, 1998)]
[Proposed Rules]
[Pages 55067-55069]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-27495]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 315 and 601

[Docket No. 98D-0785]


Draft Guidance for Industry on Developing Medical Imaging Drugs 
and Biologics; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Availability of guidance.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Developing 
Medical Imaging Drugs and Biologics.'' This draft guidance is intended 
to assist developers of drug and biological products used for medical 
imaging, as well as radiopharmaceutical drugs used in disease 
diagnosis, in planning and coordinating the clinical investigations of, 
and submitting various types of applications for, such products. The 
draft guidance also provides information on how the agency will 
interpret and apply provisions in the proposed regulations for in vivo 
radiopharmaceuticals used for diagnosis and monitoring, which published 
in the Federal Register of May 22, 1998 (63 FR 28301).

DATES: Written comments on the draft guidance may be submitted by 
December 14, 1998. General comments on agency guidance documents are 
welcome at any time.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Drug Information Branch (HFD-210), Center for Drug 
Evaluation and Research (CDER), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, or the Office of Communication, 
Training, and Manufacturers Assistance (HFM-40), Center for Biologics 
Evaluation and Research (CBER), 1401

[[Page 55068]]

Rockville Pike, Rockville, MD 20852-1448, FAX 888-CBERFAX or 301-827-
3844. Send two self-addressed adhesive labels to assist the office in 
processing your request. Submit written comments to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852. Requests and comments should be 
identified with the docket number found in brackets in the heading of 
this document. See the Supplementary Information section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Robert K. Leedham, Jr., Center for 
Drug Evaluation and Research (HFD-160), Food and Drug Administration, 
5600 Fishers Lane, Rockville, MD 30857, 301-443-3500, or George Q. 
Mills, Center for Biologics Evaluation and Research (HFM-573), Food and 
Drug Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 
301-827-5097.

SUPPLEMENTARY INFORMATION:

I. Description of the Guidance

     FDA is announcing the availability of a draft guidance document 
entitled ``Developing Medical Imaging Drugs and Biologics.'' It 
references other CDER and CBER guidance documents that relate to the 
development of medical imaging drugs and biologics, including CBER's 
``Points to Consider in the Manufacture and Testing of Monoclonal 
Antibody Products for Human Use'' (62 FR 9196, February 28, 1997). The 
draft guidance is intended to assist developers of drug and biological 
products used for medical imaging, as well as radiopharmaceutical drugs 
used in disease diagnosis, in planning and coordinating the clinical 
investigations of, and submitting various types of applications for, 
such products. The draft guidance applies to medical imaging drugs that 
are used for diagnosis and monitoring and that are administered in 
vivo. Such drugs include contrast agents used with medical imaging 
techniques such as radiography, computed tomography, ultrasonography, 
and magnetic resonance imaging, as well as radiopharmaceuticals used 
with imaging procedures, such as single-photon emission computed 
tomography and positron emission tomography. The draft guidance is not 
intended to apply to possible therapeutic uses of these drugs or to in 
vitro diagnostic products.
    CDER's Division of Medical Imaging and Radiopharmaceutical Drug 
Products presented a preliminary version of this draft guidance 
document to the Medical Imaging Drug Advisory Committee (MIDAC) on 
October 26, 1996. Following that meeting, FDA worked with MIDAC to 
develop this draft guidance. As part of this process, FDA considered 
proposals submitted by an ad hoc group representing contrast agent 
manufacturers and by the Council on Radionuclides and 
Radiopharmaceuticals, Inc.
    On November 21, 1997, President Clinton signed into law the Food 
and Drug Administration Modernization Act of 1997 (the Modernization 
Act). Section 122(a)(1) of the Modernization Act directs FDA to issue 
regulations on the approval of diagnostic radiopharmaceuticals. In the 
Federal Register of May 22, 1998 (63 FR 28301), FDA published a 
proposed rule on the evaluation and approval of in vivo 
radiopharmaceuticals used in the diagnosis and monitoring of diseases. 
The proposed rule describes certain types of indications for which FDA 
would approve diagnostic radiopharmaceuticals and lists factors that 
the agency would consider in evaluating the safety and effectiveness of 
a diagnostic radiopharmaceutical under the Federal Food, Drug, and 
Cosmetic Act (the act) or the Public Health Service Act (the PHS Act). 
This draft guidance document provides information on how FDA intends to 
interpret and apply various sections of the proposed rule.
     In the Federal Register of August 3, 1998 (63 FR 41219), FDA 
published a document extending the comment period on the proposed rule 
on in vivo radiopharmaceuticals from August 5, 1998, to October 15, 
1998. In a separate document published elsewhere in this issue of the 
Federal Register, FDA is further extending the comment period to 
November 16, 1998. FDA hopes that the issuance of this draft guidance 
on medical imaging drugs and biologics, in conjunction with the 
extension of the comment period on the proposed rule, will assist 
interested persons in preparing their comments on the proposed rule. 
Persons will have additional time to submit comments on the draft 
guidance after the comment period on the proposed rule closes.
    This draft level 1 guidance is being issued consistent with FDA's 
good guidance practices (62 FR 8961, February 27, 1997). It represents 
the agency's current thinking on the development of medical imaging 
drugs and biologics. 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, regulations, or both.

II. Comments

    Interested persons may, at any time, submit to the Dockets 
Management Branch (address above) written comments on the draft 
guidance document. Two copies of any comments are to be submitted, 
except that individuals may submit one copy. Comments should be 
identified with the docket number found in brackets in the heading of 
this document. The draft guidance document and received comments may be 
seen in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday 
through Friday.

III. The Paperwork Reduction Act of 1995

    This draft guidance contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). A description of these provisions is provided in the following 
paragraphs with an estimate of the annual reporting burden. Included in 
the estimate is the time for reviewing the instructions, searching 
existing data sources, gathering and maintaining the data needed, and 
completing and reviewing each collection of information.
    FDA invites comment on the following: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection on respondents, including 
through the use of automated collection techniques, when appropriate, 
and other forms of information technology.
    Title: Draft Guidance for Industry on Developing Medical Imaging 
Drugs and Biologics
    Description: FDA is issuing a draft guidance on the development of 
medical imaging drugs and biologics. The draft guidance is intended to 
assist developers of drug and biological products used for medical 
imaging, as well as radiopharmaceutical drugs used in disease 
diagnosis, in planning and coordinating the clinical investigations of, 
and submitting various types of applications for, such products. The 
draft guidance provides information on

[[Page 55069]]

how the agency will interpret and apply provisions of the existing 
regulations regarding the content and format of an application for 
approval of a new drug (21 CFR 314.50) and the content of a biological 
product application (21 CFR 601.25). In addition, the draft guidance 
provides information on how the agency will interpret and apply the 
proposed rule on the evaluation and approval of in vivo 
radiopharmaceuticals used for diagnosis and monitoring (63 FR 28301). 
The proposed rule, by adding part 315, would clarify existing FDA 
requirements for the evaluation and approval of drug and biological 
radiopharmaceuticals already in place under the authority of the act 
and the PHS Act.
    Existing regulations, which appear primarily in parts 314 and 601 
(21 CFR parts 314 and 601), specify the information that manufacturers 
must submit so that FDA may properly evaluate the safety and 
effectiveness of new drugs and biological products. This information is 
usually submitted as part of a new drug application (NDA) or a 
biologics license application (BLA), or as a supplement to an approved 
application. This draft guidance supplements these regulations. Under 
the proposed rule and the draft guidance, information required under 
the act and the PHS Act and needed by FDA to evaluate safety and 
effectiveness would still have to be reported.
    Description of Respondents: Manufacturers of medical imaging drugs 
and biologics, including contrast drug products and diagnostic 
radiopharmaceuticals.
    Burden Estimate: The proposed rule on in vivo radiopharmaceuticals 
used for diagnosis and monitoring sets forth an estimated annual 
reporting burden on the industry that would result from that rulemaking 
(63 FR 28301 at 28305 to 28306). This draft guidance on the development 
of medical imaging drugs and biologics is in part intended to explain 
how FDA will interpret and apply the proposed rule. Thus, the estimated 
annual reporting burden of the draft guidance, as provided in the chart 
below, is the same as that of the proposed rule, with one change. In 
addition to the diagnostic radiopharmaceuticals that are the subject of 
the proposed rule, the draft guidance also addresses the development of 
contrast drug products, which FDA evaluates and approves under part 
314, but which are not affected by the proposed rule.
    The chart below provides an estimate of the annual reporting burden 
for diagnostic radiopharmaceuticals and is based on the estimate 
described in the proposed rule (63 FR 28301 at 28306). The chart also 
provides an estimate for the annual reporting burden for contrast drug 
products. FDA estimates that the potential number of respondents who 
would submit applications or supplements for contrast drug products 
would be one. Although FDA did not approve any NDA's for contrast drugs 
(there are no biological contrast drug products) in fiscal year 1997 
(FY 1997), for purposes of estimating the annual reporting burden, the 
agency assumes that it will approve one contrast drug each fiscal year. 
The annual frequency of responses for contrast drugs is estimated to be 
one response per application or supplement. The hours per response, 
which is the estimated number of hours that an applicant would spend 
preparing the information to be submitted for a contrast drug in 
accordance with this draft guidance, is estimated to be approximately 
2,000 hours.
    The draft guidance would not impose any additional reporting burden 
because safety and effectiveness information is already required by 
existing regulations. In fact, clarification by the draft guidance of 
FDA's standards for evaluation of medical imaging drugs and biologics 
is expected to reduce the overall burden of information collection. FDA 
invites comments on this analysis of information collection burdens.

                                  Table 1.--Estimated Annual Reporting Burden1
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                                      Annual
       No. of Respondents          Frequency per   Total Annual      Hours per      Total Hours
                                     Response        Responses       Response
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Diagnostic Radiopharmaceuticals         8               1               8           2,000          16,000
Contrast Drugs                          1               1               1           2,000           2,000
Total                                                                                              18,000
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    In compliance with section 3507(d) of the PRA (44 U.S.C. 3507(d)), 
the agency has submitted the information collection provisions of this 
draft guidance to OMB for review. Interested persons are requested to 
send comments on this information collection by November 13, 1998, to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Desk Officer for FDA.

IV. Electronic Access

    An electronic version of this draft guidance document is available 
on the Internet using the World Wide Web (WWW) at ``http://www.fda.gov/
cder/guidance/index.htm'' or ``http://www.fda.gov/cber/
guidelines.htm''.

    Dated: October 6, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-27495 Filed 10-13-98; 8:45 am]
BILLING CODE 4160-01-F