Guidance for Industry
Guidance for the Submission of
Premarket Notifications
For Radionuclide Dose Calibrators
Document Issued on: November 20, 1998
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Radiological Devices Branch
Division of Reproductive; Abdominal; Ear, Nose, and Throat;
 and Radiological Devices
Office of Device Evaluation Preface
Public Comment
Comments and suggestions may be submitted at any time for Agency consideration to Robert
Phillips, Ph.D., Radiological Devices Branch, Division of Reproductive; Abdominal; Ear, Nose,
and Throat; and Radiological Devices, 9200 Corporate Blvd, Rockville, MD 20874.  Comments
may not be acted upon by the Agency until the document is next revised or updated.  For
questions regarding the use or interpretation of this guidance contact Robert Phillips, Ph.D., at
(301) 594-1212.
Additional Copies
World Wide Web CDRH page  at http://www.fda.gov/cdrh/ode/radcalibrators.pdf  or CDRH 
Facts on Demand at 1-800-899-0381 or 301-827-0111, specify number 2238 when prompted for
the document shelf number.
2 Table of Contents
Section                                Page
I.  Purpose                               4
II.  Scope                                                                                                                      4
III.  Background                               5
A.  The New 510(k) Paradigm                               5
B.   Standards for Radionuclide Dose Calibrators                               6
IV.  Information Required in a Premarket Notification                               7
A.   General Information                               7
B.   Administrative Information                               7
C.   Device Description                               7
D.   Designation of a Predicate                               8
E.   Software                               8
F.   Electromagnetic Compatibility                               8
G.  Labeling                               9
V.  Appendices
1.  510(k) Safety and Effectiveness or Statement                              10
2.  FDA Indications for Use Form                              11
3.  Truthful and Accurate Statement                              12
4.  Declarations of Conformity                              13
3 I.   Purpose
The purpose of this document is to provide a detailed description of the information which should
be included in a premarket (510(k)) notification for a radionuclide dose calibrator (RDC)
submitted to the Center for Devices and Radiological Health (CDRH).  This information is an
elaboration of the general requirements contained in 21 CFR 807.87.
II.  Scope
This document is applicable to Radionuclide Dose Calibrators as defined in 21 CFR 892.1360:
A radionuclide dose calibrator is a radiation detection device intended to assay radionuclides
before their administration to patients.
RDCs are currently in Class II and require premarket notification and an agency determination of
substantial equivalence prior to marketing.  The product code currently used to identify this
device is KPT.  This guidance covers calibrators used to calibrate doses of radionuclides used in
nuclear medicine and radionuclide sources used in brachytherapy.
The principal components of current RDCs are a measurement chamber (such as a vented or
sealed gas ionization chamber or scintillation detector) and readout (such as an electrometer).
This guidance is applicable to premarket notifications for new RDCs, new components, and
modifications to RDCs and components that have a significant influence on safety or
effectiveness.
III.  Background
In the last few years, a number of legislative changes relating to the authority of the agency have
occurred.  These changes have resulted in the adoption of new regulations and administrative
procedures by CDRH, which affect the 510(k) process.  The Safe Medical Devices Act of 1990
(SMDA) has resulted in new Good Manufacturing Practice (GMP) regulations requiring pre-
production design controls, and several administrative requirements (Truthful and Accurate
statements, Summaries of Safety and Effectiveness, and Statements of Indications for Use) have
been added. The Food and Drug Administration Modernization Act (FDAMA) of 1997 and a re-
engineering effort have resulted in the development of a new 510(k) paradigm that incorporates
alternative approaches to demonstrating substantial equivalence in premarket notifications.  These
approaches are intended to facilitate the marketing clearance of devices for which recognized
standards exist, and for cases in which the new device is a modification of a previously cleared
product.
4 A.  The New 510(k) Paradigm
On March 20, 1998 CDRH issued a document entitled The New 510(k) Paradigm - Alternative
Approaches to Demonstrating Substantial Equivalence in Premarket Notifications.  This
document is available on the CDRH web site (http://www.fda.gov/cdrh/ode/parad510.html).  In
addition to the traditional 510(k), this document describes two alternatives, the Special 510(k):
Device Modification and the Abbreviated 510(k).
1.  Special 510(k)
The Special 510(k) is based on the requirement that manufacturers establish design controls in
accordance with the SMDA and 21 CFR 820.30. A manufacturer uses the FDA guidance
document entitled Deciding When to Submit a 510(k) for a Change to an Existing Device to
decide if a device modification could be implemented without submission of a new 510(k). If a
new 510(k) is needed, and if the modification does not affect the intended use of the device or the
basic fundamental scientific technology, conformance with design controls may form the basis for
clearing the application. Under this option, a manufacturer who is intending to modify a legally
marketed Class II device would conduct the necessary verification and validation activities to
demonstrate that the design output of the modified device meets the design requirements. Once
the company has ensured the satisfactory completion of this process through a design review, a
Special 510(k) may be submitted. While the basic content requirements for the submission are the
same, this type of submission should also reference the cleared 510(k) and contain a Declaration
of Conformity with design control requirements. In the Special 510(k) the manufacturer has the
option of using a third party to assess conformance with design controls (refer to the paradigm
document for details). Special 510(k)s are to be processed by the Office of Device Evaluation
within 30 days of receipt by the Document Mail Center.
2.  Abbreviated 510(k)s
The Abbreviated 510(k) is based on the use of conformance to voluntary standards in place of
data review as the means by which the safety and effectiveness of Class II devices can be assured.
Manufacturers may submit an Abbreviated 510(k) when FDA has recognized an individual or
several voluntary standards that cover aspects of the new device. In addition to the required
elements of a 510(k) as described in 21 CFR 808.87, Abbreviated 510(k) submissions should
include information that describes how conformance to one or several voluntary standards,
recognized by CDRH, have been used to address risks associated with the device, and a
Declaration of Conformity to those standards. The Declaration of Conformity should provide
the information listed in the paradigm. A third party may be used to assess conformance with
these standards (refer to the paradigm document for details). The review of abbreviated 510(k)s is
intended to be more efficient since they are not required to contain the experimental data from
which conformance is determined.
5 B.  Standards for Radionuclide Dose Calibrators
The Food and Drug Administration Modernization Act of 1997 authorizes CDRH to recognize
consensus standards established by national and international standards development
organizations that may be used to satisfy identified portions of device review requirements.  On
February 19, 1998 CDRH issued a Guidance on the Recognition and Use of Consensus
Standards which is intended to provide information relating to the recognition and use of
national and international consensus standards.  It is available on the CDRH web site
(hhtp://www.fda.gov/cdrh/modact/k982.html), and describes how the agency will use information
on conformance with recognized standards to satisfy premarket review requirements.  It also
describes the content of a declaration of conformity.  In the case of 510(k)s, information on
conformance with recognized standards might help establish the substantial equivalence of a new
device to a legally marketed predicate in the areas covered by the standards.  If a premarket
notification contains declarations of conformity, this will in most cases eliminate the need to
review the actual test data for those aspects of the device addressed by the standards.  However,
the results of testing are expected when the standard specifies a test method without the
associated performance limits.  There are currently no consensus standards related to RDCs that
are recognized by CDRH, however, several bodies have published standards and requirements.
Several of these are listed for convenience.
1. 10 CFR 35.50  Possession, use, calibration and check of dose calibrators
The Nuclear Regulatory Commission (NRC) requires a licensee to possess and use a dose
calibrator to measure the activity of dosages of photon-emitting radionuclides prior to
administration to each patient or human research subject.  This requirement specifies when a RDC
will be used and the timing of required quality control checks (constancy, accuracy, linearity, and
geometrical dependence.
2. IEC 61303(1994-10)  Medical Electrical Equipment:  Radionuclide calibrators Particular
methods for describing performance.
This standard covers radionuclide calibrators of the well type, with a gas-filled ionization chamber
as used in the practice of nuclear medicine.  The object of this standard is to identify the most
important characteristics of radionuclide calibrators and lay down associated test methods to
enable manufacturers to declare the characteristics of their devices in a standardized way and
facilitate comparisons between devices.
3.   IEC 61145(1992-05)  Calibration and usage of ionization chamber systems for assay of
radionuclides.
This standard covers the techniques for the quantification of the activity of identified radionuclides
using any of a variety of ionization chambers currently available for this purpose.
 
6  4. ANSI N42.13-1986  Calibration and usage of dose Calibrator ionization chambers for the
assay of radionuclides
 
 This standard covers the techniques for the quantification of the activity of identified radionuclides
using any of a variety of ionization chambers currently available for this purpose.  Application of
the standard is limited to instruments that incorporate well-type ionization chambers as detectors.
IV.   Information Required in a Premarket Notification
Information required under 21 CFR 807.87 for RDC devices is listed and discussed in detail
below.
A.  General Information
1.  Name and address of manufacturer.
2.  Establishment registration number (if not available, registration application should be
submitted).
3.  Name, title, phone number, fax number and E-mail of contact.
4.  Trade name and common name of device.
5.  Type of submission (special, abbreviated or traditional)
6.  Classification and class of device (21 CFR 892.1360, class II),  and product code (KPT)
7.  Intended use (general purpose of device per 21 CFR 892.1360)
8.  Applicable standards (e.g. IEC or ANSI) if used.
B.  Administrative Information
1.  510(k) Summary of Safety and Effectiveness or Statement (see 21 CFR 807.92 and 807.93)
2.  FDA Indications for Use Form (specific use of device, i.e. nuclear medicine or brachytherapy)
3.  Truthful and Accurate Statement (see 21 CFR 807.87(j))
4.  Declarations of Conformity to Consensus Standards (Abbreviated 510(k) only)
5.  Declaration of Conformity to Design Controls (Special 510(k) only)
C.  Device Description
The device description should describe the type of detector (gas, pressurized gas, vented,
scintillator), the principal components of the system, provide a brief description of the purpose of
each component, and provide a diagram illustrating their interconnections.
D. Comparison to a Predicate
A 510(k) submission is a comparison of a new device to a predicate to show that the two devices
are substantially equivalent.  Therefore, the sponsor must identify at least one class II legally
marketed device to which equivalence is claimed.  The following information relating to the
predicate should be supplied:
7 1.  manufacturer, tradename and 510(k) number;
2.  a brief description of the important similarities and differences between the device and
predicate;
3.  promotional material for the predicate and any other relevant labeling; and
4.  a tabular comparison of features and specifications of the new device and predicate including:
a.  type of detector and design
b.  allowable activity ranges;
c.  type of radiation measured;
d.  energy range;
e.  accuracy and reproducibility;
f.  geometry of the sensitive volume;
g.  linearity;
h.  interference from background radiation; and
i.  measurement error to be expected over the calibration range.
Any significant differences should be explained and a rationale given for substantial equivalence.
E.  Other information
1.  Describe the method of initial calibration, the calibration sources used (NIST derivable),
and the strength of these sources.
2.  Describe the common sources of error and their magnitude.
The listed items should be supported (appropriate laboratory data and descriptions of methods).
F.  Software
If the device uses software, computer chips, or other digital components, provide the information
requested in Guidance for the Content of Premarket Submissions for Software Contained in
Medical Devices, May 1998.  This document is available on the WorldWide Web/CDRH home
page: http://www.fda.gov/cdrh/ or CDRH Facts on Demand at 1-800-899-0381 or 301-827-0111
specify number 337 when prompted for the shelf number.
The submission should indicate whether the device is year 2000 compatible and describe how this
was determined.
F.  Electromagnetic Compatibility
The submission should explain whether the device is susceptible to electromagnetic interference
and how this was determined.
8 G.  Labeling
The labeling for an RDC device should consist of a summary specification sheet (i.e. a product
data sheet that includes the information provided in paragraph IV, D, 4 for the device;
promotional material; and instructions for use.
The instructions for use should contain:
a. the indications for use of the device (e.g. types of sources for which RDC is applicable -
nuclear medicine, brachytherapy);
b. any contraindications, warnings, precautions associated with the device;
c. instructions for using the device;
d. a recommended way to calibrate the device for specific isotopes;
e. a recommended way to calibrate the device for a specific isotope for which there is no
calibrated national standard available;
f.  a recommended way to calibrate the device for new isotopes which were not available at
the time of manufacture;
g. the expected uncertainty for each radionuclide for which the RDC is calibrated;
h. the activity range (radionuclide RDC) or air kerma-strength range (brachytherapy RDC)
over which the expected accuracy is achieved;
i. the positioning of the source in the RDC, including distances from a reference point over
which measurements can be made within a specified accuracy;
j. any limitation on source size or orientation in the RDC during measurement of source
output;
k.  if the RDC uses software, the functions that are performed by it;
l. recommended minimum specifications or ranges for power source and environment (e.g.,
temperature, humidity, voltage, etc.);
m. recommended maintenance schedules for the equipment, including a designation of
whether they should be performed by the user or company service personnel;
n. reference to NRC requirements for routine calibration; and
o. a discussion of sources of error; including the effect of source size and geometry; and
encapsulation thickness, and energy difference from the standard.
Warnings should contain any information concerning the limits on environmental factors and any
known sensitivity to electromagnetic interference.
9 Appendix 1
510(k) Summary/Statement Certification
Re: K______________
CHECK ONLY ONE:
1.  510(k) Summary.  Attached is a summary of safety and effectiveness information upon
which an equivalence determination could be based.
2.  510(k) Statement. I certify that, in my capacity as
                                                                                                                                    
of                                                                                                         (company),
I will make available all information included in this premarket notification on safety and
effectiveness within 30 days of request by any person if the device described in the
premarket notification submission is determined to be substantially equivalent.  The
information I agree to make available will be a duplicate of the premarket notification
submission, including any adverse safety and effectiveness information, but excluding all
patient identifiers, and trade secret and confidential commercial information, as defined in
21 CFR 20.61.
                                                                                                                        
[ Signature*]
                                                                                                                        
[Typed or Printed Name]
                                    
[Date]
* Must be signed by a responsible person of the firm required to submit the premarket
notification (e.g., not a consultant for the 510(k) submitter).
10 Appendix 2
Indications for Use Form
Page       of
510(k) Number (if known):
Device Name:
Indications For Use:
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF
NEEDED)
                                                                 
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use        OR Over-The-Counter Use
(Per 21 CFR 801.109)
(Optional Format 1-2-96)
11 Appendix 3
PREMARKET NOTIFICATION TRUTHFUL AND ACCURATE STATEMENT
(as required by 21 CFR 807.87(j))
I certify that, in my capacity as                                                                                                           
of                                                                     (company name), I believe, to the best of my
knowledge, that all data and information submitted in this premarket notification is truthful and
accurate and that no material fact has been omitted.
                                                                                                 
    (Signature*)     (Date)
                                                                                                 
(Typed Name) (510(k) number)
* Must be signed by a responsible person of the firm required to submit the premarket notification
(e.g., not a consultant for the 510(k) submitter).
12 Appendix 4
Declaration of Conformity
Voluntary Standards in 510ks
Reviewers should rely on a declaration of conformity to the recognized consensus standards if the
declaration:
Identifies the applicable recognized consensus standards and specifies those that were met;
Specifies, for each consensus standard, that all requirements were met, except for
inapplicable requirements or deviations noted below;
Identifies for each consensus standard any way(s) the standard may have been tailored or
modified for application to the device under review, e.g., identifies which of an alternative
series of tests were performed;
Identifies, for each consensus standard, any requirements that were not applicable to the
device;
Specifies any deviations from each applicable standard that were applied (e.g., deviations
from international standards which are necessary to meet U.S. infrastructure conventions
such as the National Electrical Code (ANSI/NFPA 70));
Specifies what differences exist, if any, between the tested device and the device to be
marketed and justifies the use of test results in these areas of difference; and
If a test laboratory or certification body was employed, provides the name and address of
each laboratory or certification body that was involved in the determining the conformance
of the device with the applicable consensus standards and a reference to any accreditations
of those organizations.
13