Supporting Statement

Radioactive Drug Research Committee Report

On Research Use of Radioactive Drug;

Membership Summary and Study Summary - 21 CFR Part 361.1

\[Docket No. OON-1682\]

OMB Number 0910-0053

Supporting Statement -

A. [Justification]{.underline}

1\. **[Circumstances Necessitating Information Collection]{.underline}**

The Food and Drug Administration (FDA) is requesting OMB approval of the
information collection requirements contained in 21 CFR Part 361.1 These
information collection are:

> 21 CFR 361.1 (c)(2) - Recordkeeping dictates that a Committee must
> meet each quarter in which research studies have either been approved
> or conducted. Minutes of meetings and results of votes on protocols
> that involve the use of human subjects must be maintained
>
> 21 CFR 3661.1 (c)(3) - Reporting requires that each Committee annually
> report to the FDA its composition, including names and qualifications
> of members and any consultants used on Form FDA 2914. Along with this
> annual report, each Committee must also provide a summary report of
> each research study that was conducted during the year using Form FDA
> 2915.

These regulations implement provisions of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 355 (i)), which require the Secretary, DHHS to
promulgate regulations that permit drugs that have been "generally
recognized as safe and effective" to be used solely for basic
informational research use. Title 21, Code of Federal Regulations, Part
361.1, enacted on July 25, 1975, sets forth specific regulations
regarding the establishement and composition of Radioactive Drug
Research Committees and their role in approving and monitoring research
studies utilizing radiopharmaceuticals. No study involving any
administration of a radioactive drug to research subjects is permitted
without the authorization of a FDA approved Radioactive Drug Research
Committee, (21 CFR 361.1 (d)(7)). The type of research that may be
undertaken with a radiopharmaceutical drug must be intended to obtain
basic information and not to carry out a clinical trial. The types of
basic research permitted are specified in the regulation, and include
studies of metabolism, human physiology, pathophysiology, or
biochemistry.

Part 361.1 of 21 CFR designates certain research uses of radioactive
drugs as "generally recognized as safe and effective" (GRAS). When a
drug is designated as GRAS, it is [not a new drug]{.underline}, as
defined by the Food, Drug, and Cosmetic Act. When a "new drug" is used
in humans and the drug is [not yet approved for]{.underline}
[marketing]{.underline}, a Notice of Claimed Investigational Exemption
for a New Drug (IND) application is required. No IND is needed to study
a drug that is [not a new drug]{.underline}. The Committee can
determine, under the specific requirements set forth in 21 CFR 361.1
that the drug to be used in the research study, under the conditions
specified by the investigator's protocol and approved by the Committee,
is [not a new drug]{.underline}. Approval of these studies by the
Committees circumvents the necessity for a Principle Investigator to
file an IND with the FDA.

Types of research studies not permitted under this regulation are also
specified, and include those "intended for (the) immediate theapeutic,
diagnostic, or similar purposes or to determine the safety and
effectiveness of the drug in humans for such purposes (.e., to carry out
a clinical trial)." These studies require filling of an IND under 21 CFR
312.1 and the associated information collection are covered in OMB
Approval 0910-0014.

2\. **[How, by Whom, and for What Purpose Information
Used]{.underline}**

FDA's approval of a Radioactive Drug Research Committee is based on
assessment of the qualifications of committee members and assurance that
all necessary fields of expertise are covered. (Form FDA 2914.) FDA
periodically reviews the Committee's composition. Approval may be
withdrawn at any time the specified requirements are not met.

The FDA monitors a Committee's activities by reviewing its annual
Summary Reports on Research Use of Radioactive Drugs (Form FDA 2915),
Committee minutes and some protocols, and through on-site inspections.
This is done to determine if the research studies are being conducted in
accordance with required regulations. If these studies were not
reviewed, human subjects could be subjected to inappropriate radiation
and/or safety risks. In addition, without review of the Committee's
activities research studies, those originally meeting the criteria
specified in the regulations, could evolve into a research project or
clinical trial that no longer falls under this regulation nor the
authority of the Committee and requires filing of an IND application.

3\. **[Consideration of Information Technology]{.underline}**

Even though advanced technologies for the gathering and reporting of
data possibly do exist, such technologies are not available to the
majority of the Committees, nor does the expertise to utilize such exist
at this time. Other than accepting facsimile copies of the information,
which would still require a follow-up with hard copy, the Agency does
not currently possess technology nor expertise which would aid in the
evaluation of the study summaries. However, the Agency is amenable to
use of information technologies in the future. The existing format
provides a consistent means for the review of committee activities.
There are no legal obstacles to reducing the burden.

4\. **[Identification of Duplication]{.underline}**

The FDA is the only federal agency responsible for regulating these type
activities.

5\. **[Small Businesses]{.underline}**

Collection of this information does not involve small businesses. Most
Committees are affiliated with large institutions. However, the Document
Management and Reporting Branch, Division of Management and Budget,
Center for Drug Evaluation and Research (CDER), provides general
assistance to the industry. The Division of Medical Imaging and
Radiopharmaceutical Drug Products, CDER, provides assistance to the
respondents of this information collection.

6\. **[Consequences of Less Frequent Information
Collection]{.underline}**

Committee appointments are usually made as the need arises and changes
in membership must be submitted when they occur and on an annual basis
with the annual report. Research studies are proposed and approved as
the need arises within the Committees and active protocols reported on
an annual basis. If reporting were required less frequently, the
Agency's awareness of ongoing studies would be delayed and oversight of
inappropriate studies would be extended resulting in potential risk to
human subjects.

In an effort to reduce the reporting burden, Committees which are not
currently conducting active research or do not anticipate any research
projects in the near future have the option of voluntarily deactivating
until such time appropriate research projects are identified. The
Committees may then request reactivation by submitting form FDA 2914
with Curriculum Vitae of any new members. To date, 72 Committees have
taken this option, thus relieving themselves of the requirements of
submitting an annual membership report.

7\. **[Inconsistencies with 21 CFR 1320.6]{.underline}**

This information collection is consistent with the requirements of 5 CFR
1320.6.

8\. **[Consultation Outside FDA]{.underline}**

In the [Federal Register]{.underline}, of January 5, 2001 (66 FR 1137),
the agency requested comments on the proposed collection of information.
The agency received two responses, which contained a total of six
comments:

> 1\. This comment maintained that FDA has never had any actual
> statutory authority over radioactive drugs used for basic research and
> the extensive paperwork requirements for §361.1 should be completely
> removed.
>
> Response: This comment involves substantive changes to the regulations
> and is beyond the scope of the January 5, 2001, notice. In the
> [Federal Register]{.underline} of November 30, 2000 (65 FR 73799), FDA
> announced as part of the semiannual regulatory agenda that it intends
> to publish a proposed rule to revise §361.1, to update FDA's
> regulations on the use of radioactive drugs for basic research to
> reflect technological changes in the field of radiopharmaceuticals and
> to clarify and correct certain provisions. It would be more
> appropriate to submit this comment in response to the proposed rule
> once FDA publishes it.
>
> 2\. The comment maintained that the term "radiation dose commitment to
> whole body" is unclear and that reporting the "absorbed dose to whole
> body" on Form FDA 2915 is inappropriate. The comment stated that more
> appropriate calculations of body dose involve the summation of
> individual organ doses multiplied by organ weighting factors (e.i.,
> effective dose equivalent or effective dose).
>
> Response. This comment is beyond the scope of the January 5, 2001,
> notice and would more appropriately be submitted as a comment on the
> proposed rule that FDA intends to publish.
>
> 3\. The comment maintained that the instructions and table headings on
> Form FDA 2915 require absorbed doses to be in units of "mR" though
> this is a unit of exposure rather than absorbed dose. The comment
> suggests that the unit of rad or gray should be used.
>
> Response: FDA intends to change Form FDA 2915 to require the total
> radiation doses and dose commitments, expressed in the unit of rem {21
> CFR **§** 361.1 (b}.
>
> 4\. The comment maintained that the reporting requirements for gender
> and age of each human subject over 18 years of age are unnecessary and
> should be deleted.
>
> Response: This comment is beyond the scope of the January 5, 2001,
> notice and would more appropriately be submitted as a comment on the
> proposed rule which FDA intends to publish at a latter date.
>
> 5\. The comment recommends that absorbed doses for individual subjects
> who are also representative subjects, or absorbed doses for individual
> subjects that are less than those estimated for a representative
> subject, be eliminated from the annual reporting requirements.
>
> Response: This comment is beyond the scope of the January 5, 2001,
> notice and would more appropriately be submitted to the proposed rule.
>
> 6\. This comment maintains that the estimated annual reporting burden
> stated in Table 1 of the January 5, 2001, notice underestimates the
> time required for completion of Form FDA 2915 as it currently exists.
> The respondent estimates that the time expended to complete an annual
> summary on Form FDA 2915 is approximately 10 hours, rather than the
> 3.5 hours stated.
>
> Response: FDA appreciates the comment but believes that 3.5 hours is a
> reasonable estimate of the average time it takes to complete the form.
> However, FDA recognizes that the paperwork burden may vary from
> committee to committee. FDA's survey of RDRC chairpersons attempted to
> reflect differences in RDRC membership and scope of activities, Based
> on this comment, the FDA may further examine and evaluate the role,
> functions, and activities of RDRC and its related paperwork burden in
> the future.

Recently, three Committee chairpersons, listed below, were surveyed by
phone and asked for their assessment of time expended, cost and views on
completing the necessary reporting forms. These individuals were
selected randomly from different geographic areas and varying levels of
RDRC membership and activities. The respondents indicated a general
satisfaction with the form contents, therefore, no revision of the
current form other than the change of the expiration date is
contemplated. Their provided estimates of work hours per year and
estimated cost to comply with the Agency mandate for Radioactive Drug
Research Committees is reflected in part 12 of this supporting
statement.

RDRC 0037 RDRC 0174

Marvin Ziskin, M.D. Michael Elson, Ph.D.

Temple University V.A. Medical Center

Richard Fox Center for Nuclear Medicine Service (115)

Biomedical Physics One Veterans Drive

3400 North Broad Street Minneapolis, MN 55417

Philadelphia, PA 19140 (612) 725-2014

\(215\) 707-4259

RDRC 0184

Janet F. Eary, M.D.

University of Washington

Medical Center,

Department of Radiology

Division of Nuclear Medicine

Room N 203/Box 356113

1959 N.E. Pacific Street

Seattle, WA 98195-6113

\(206\) 598-4240

9\. **[Payment or Gift]{.underline}**

No payment or gift was provided to respondents.

10\. **[Confidentiality Provisions]{.underline}**

Contents of the Study and Membership Summaries are available for public
disclosure unless confidentiality is requested by the investigator and
it is evident from the report(s) that the material contains trade secret
or confidential commercial information as defined in 21 CFR 20.61. When
confidentiality is requested and justified, the report will be flagged
as not releasable and will be maintained in a manner similar to other
confidential information. Data will be secured in a locked area with
access limited to appropriate FDA personnel. Applicable confidentiality
will be maintained as long as the data are maintained.

11\. **[Sensitive Questions]{.underline}**

No questions of a private or sensitive nature are asked.

12\. **[Total Hour Burden to Respondents]{.underline}**

The estimated annual burden for this information collection is

2,190 Hours.

+---------+---------+---------+---------+---------+---------+---------+
| Table 1 |         |         |         |         |         |         |
| \--     |         |         |         |         |         |         |
| Es      |         |         |         |         |         |         |
| timated |         |         |         |         |         |         |
| Annual  |         |         |         |         |         |         |
| Re      |         |         |         |         |         |         |
| porting |         |         |         |         |         |         |
| Burden  |         |         |         |         |         |         |
+=========+=========+=========+=========+=========+=========+=========+
| 21 CFR  | Form    | No. Of  | Annual  | Total   | Hours   | Total   |
| Section |         | Resp    | Fr      | Annual  | per     | Hours   |
|         |         | ondents | equency | Re      | R       |         |
|         |         |         | per     | sponses | esponse |         |
|         |         |         | R       |         |         |         |
|         |         |         | esponse |         |         |         |
+---------+---------+---------+---------+---------+---------+---------+
| 361.    | FDA     | 96      | 1.0     | 96      | 1       | 96      |
| 1(c)(3) | 2914    |         |         |         |         |         |
|         |         | 63      | 5       | 315     | 3.5     | 1,103   |
| 361.    | FDA     |         |         |         |         |         |
| 1(c)(3) | 2915    | 63      | 5       | 315     | 0.1     | 31      |
|         |         |         |         |         |         |         |
| 361.    |         | 63      | 5       | 315     | 0       | 0       |
| 1(d)(5) |         |         |         |         |         |         |
|         |         |         |         |         |         |         |
| 361.    |         |         |         |         |         |         |
| 1(d)(8) |         |         |         |         |         |         |
+---------+---------+---------+---------+---------+---------+---------+
| Total   |         |         |         |         |         | 1,230   |
+---------+---------+---------+---------+---------+---------+---------+

There are no capital costs or operating and maintenance costs associated
with this collection

  ----------------------------------------------------------------------------------
  Table 2 \--                                                            
  Estimated                                                              
  Annual                                                                 
  Recordkeeping                                                          
  Burden                                                                 
  --------------- ----------- -------------- ----------- --------------- -----------
  21 CFR Section  Form        Annual         Total       Hours per       Total Hours
                              Frequency per  Annual      Recpordkeeper   
                              Recordkeeper   Records                     

  361.1(c)(2)     FDA 2914 &  96             1 per       10              960
                  2915                       quarter 4                   
                                             per year                    

  Total                                                                  960
  ----------------------------------------------------------------------------------

the information to be entered on the report forms, FDA 2914 and FDA
2915, is extracted from data maintained by the Committees for their
operation and reports to the institutions with which the Committees are
affiliated. The time and resources allocated for collection and
compilation of the data for the FDA consists of clerical, administrative
and minimal professional input. It is estimated to take 96 hours
annually to complete form FDA 2914. There are 96 respondents totaling 96
burden hours.

Patient information requested in the annual summary report, form FDA
2915 (21 CFR 361.1(c)(3)), is extracted from a written order
(prescription) or the patient's medical records. These records are
normally maintained in the practice of medicine (i.e.,patient
identification, diagnostic and therapeutic orders, evidence of informed
consent, tests and test results, etc.). It is estimated to take 3.5
hours per report to complete form FDA 2915. Approximately 315 reports
are submitted annually totaling 1103 burden hours.

The minutes of the meetings, which must be kept in compliance with 21
CFR 361.1 (c)(2), are normal records of Committee proceedings and are
accepted for inspection without any further compilation. The time to
prepare these minutes varies, depending upon the number of protocols a
Committee has to review/discuss and vote on, and depending upon how a
Committee is structured. However, an average time to prepare minutes
(writing/dictating, typing, proofreading) specifically related to
studies conducted under this regulation can be estimated to take about
10 hours annually per record keeper. Records must be kept for 96
Radioactive Drug Research Committees totaling 960 burden hours.

13\. **[Total Annual Cost to Respondent]{.underline}**

The total estimated cost to the respondents is \$87,600. It was
determined by telephone survey of contacted chairpersons. The figures
vary, depending upon the geographic location, type of personnel utilized
in preparing reports, size of the Committee membership and the number of
protocols presented and reviewed by the Committee. Therefore, an average
salary of \$40 per hour, (clerical and professional salaries combined)
was used.

Time Cost Total

[(hrs)]{.underline} ([Per hr.]{.underline}) [Cost]{.underline}

Record keeping 960 \$40.00 \$38,400

Reporting 1230 40.00 [49,200]{.underline}

Total Cost to Respondents **\$87,600**

14\. **[Annualized Cost to FDA]{.underline}**

The estimate of the cost to the government is \$20, 950 per year. It is
based on past experience, a current re-evaluation, and the following
factors:

\(1\) Preparing letters to Committees;

\(2\) Printing the forms FDA 2914 and 2915;

\(3\) Clerical time for processing and mailing documents at

\$12.00 per hour; and

\(4\) Administrative and professional review time at \$38 per

hour

+---------+---------+---------+---------+---------+---------+---------+
| Table   |         |         |         |         |         |         |
| 3 -     |         |         |         |         |         |         |
| Es      |         |         |         |         |         |         |
| timated |         |         |         |         |         |         |
| Cost to |         |         |         |         |         |         |
| the     |         |         |         |         |         |         |
| Federal |         |         |         |         |         |         |
| Gov     |         |         |         |         |         |         |
| ernment |         |         |         |         |         |         |
+=========+=========+=========+=========+=========+=========+=========+
| Item    | P       | C       | C       | Prof.   | Prof.   | Total   |
|         | rinting | lerical | lerical | Time    | Cost    | Cost    |
|         |         | Time    | Cost    |         |         |         |
|         |         | (hrs)   |         |         |         |         |
+---------+---------+---------+---------+---------+---------+---------+
| Letter  | \$0     | 20      | \$240   | 320     | \       | \       |
|         |         |         |         |         | $12,160 | $12,400 |
+---------+---------+---------+---------+---------+---------+---------+
| 2914    | \$20    |         |         | 75      | 2,850   | 2,850   |
|         |         |         |         |         |         |         |
| 2915    | \$100   |         |         | 150     | 5,700   | 5,700   |
+---------+---------+---------+---------+---------+---------+---------+
| Total   | 410.00  | 20 hrs  | \$240   | 425 hrs | \       | \       |
|         |         |         |         |         | $14,450 | $20,950 |
+---------+---------+---------+---------+---------+---------+---------+

15\. **[Explanation for Program Changes or Adjustments]{.underline}**

There are currently 194 approved Committee ( of which approximately 98
are deactivated). The total annual burden for reporting and record
keeping increased slightly since the last supporting statement. The
number of study summaries (FDA 2915) increased from 3.5 to 5.0 reports
per Committee, which accounted for an increase in the total hours for
reporting like burden to the total community. Ten (10) hours per year
per Committee accurately reflects the record keeping burden. For these
reasons the annual burden, as reflected on the OMB 83I, are felt to
depict a reliable estimate.

16\. [**Publication of Information** **Collection Results**]{.underline}

FDA does not intend to publish tabulated results of the information
collection requirements that would be imposed by these regulations.

17\. [Display of OMB Approval Date]{.underline}

FDA is not seeking an exemption, not to display the OMB control number
and date.

18\. [Exceptions to \"Certification for Paperwork Reduction Act
Submissions.]{.underline}\"

There are no exceptions to the certification statement identified in
Item 19. " Certification for Paperwork Reduction Act Submission," of OMB
Form 83-I.