Transcript Replacement Reagent Policy

Replacement Reagent Policy
Update
DATA FOR COMMERCIALIZATION OF ORIGINAL
EQUIPMENT MANUFACTURER, SECONDARY and
GENERIC REAGENTS FOR AUTOMATED
ANALYZERS issued 6/10/96
Jim Callaghan
April 22, 2003
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Replacement Reagent Policy
• Well characterized clinical laboratory
testing systems intended for use by
clinical laboratory professionals.
• Previously cleared instruments and
reagents, when a claim is made for a
new reagent/instrument combination.
• Introduction of new instrument family
members of a previously cleared
instrument family.
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Reason for Policy
• Each reagent/instrument combination, or
new instrument family member normally
requires a 510(k).
• A different process was developed
utilizing existing 510(k) notification
procedures to handle the potential for
numerous submissions.
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Rationale Behind The Policy
• There are sufficient controls for these
types of claims and test system
modifications when an acceptable test
system validation protocol is in place.
• “Add-to-file” is an appropriate vehicle to
convey device modification information
to the FDA and comply with the 510(k)
regulatory process.
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Replacement Reagent Policy
• Changes since the policy was first
implemented, such as:
– Quality Systems Regulation (QSR)
– Special 510(k)
– FDAMA
– Clinical Laboratory Improvement
Amendments (CLIA) to FDA.
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Replacement Reagent Policy
• The RR-policy did not and does not
apply to:
– class III devices
– devices intended for use in support of blood
banking practices
– systems intended for over-the-counter (OTC)
use
– exempt general purpose reagents.
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Replacement Reagent Policy
• Consult with the appropriate branch chief on
eligibility for assays that could have serious
health risks associated with their use.
• SPECIAL 510(k) – like the Special 510k the
RR-Policy is intended for modifications to a
previously cleared device.
• Use the Special 510(k), when the modified
test system does not meet acceptance criteria
of the validation protocol.
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REAGENTS
• REAGENTS - necessary substances that
produce reactions allowing an analyte to
be measured.
– Includes calibrator and quality control material.
• GENERIC reagents - are intended to be
used manually, or with any open system.
– Laboratories assume responsibility for
performance validation.
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REAGENTS
• OEM reagents - analyzer manufacturer’s
reagents specifically for their analyzers.
• REPLACEMENT reagents - Generic
reagents produced for use with specified
analyzers by suppliers other than an OEM
supplier.
– Replacement reagents may be marketed and
labeled for one specific analyzer or may claim
multiple analyzers.
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ANALYZERS
• Closed Systems - analyzers and OEM
reagents provided by the same
manufacturer and are configured only to
be used in combination with each other.
• Open Systems - analyzers manufactured
with general-purpose features for use only
with "replacement or generic reagents".
• Partially Closed System - is a
combination of the above
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ANALYZERS
• Device Family - a group of one or more
devices manufactured by or for the
same manufacturer and having the
same:
– Basic design and performance characteristics
related to device safety and effectiveness, that
share a common Design History File (DHF)
– Intended use and function
– Device classification and product code.
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LABELING
• Operator Manual - labeling accompanying
instrument for operating instructions.
• Package Insert - reagent labeling which may
give instructions and also refer to an operator
manual for detailed instruction.
• Application Sheet – typically contains analyzer
settings, volumes, and parameters to assist
laboratories in implementing use of secondary
reagents with a specified open analyzer system.
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OTHER DEFINITIONS
• TEST SYSTEM – is comprised of all test
components required to perform an in vitro
diagnostic test, i.e. clinical laboratory
analyzer, reagents, calibrators and controls.
• ADD-TO-FILE – notification to the original file
of validation protocols and intent to introduce
a reagent on a specific analyzer, or introduce
an new instrument family member based on
passing acceptance criteria in the protocol.
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Equivalent Specifications
• The original policy required the analyzer
to be cleared for each analyte prior to a
replacement reagent claim.
• Use on an analyzer requires the
analyzer to have the capability to run the
method the assay utilizes.
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Clarifications
• Class I instruments –Class I devices
such as many of these analyzers, are
exempt from 510(k).
• These analyzers are not exempt, when
an analytical claim is made for a class I
reserved device, by virtue of the
limitations to exemptions under 862.9,
864.9…, or a class II device.
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Clarifications
• These test systems are considered
combination devices "Guidance on the CDRH
Premarket Notification Review Program
6/30/86 – Blue Book Memo (K86-3)"
http://www.fda.gov/cdrh/k863.html.
• When any of these analyzers are regulated
as a combination device, the accessory is
classified in the highest of the predicate
device classifications of the system
combination.
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Clarifications
• When a replacement reagent claims use on
an open system, the analyzer needs to have
a previous 510(k) clearance.
• We ask that the reagent manufacturer have
the instrument manufacturer submit a 510(k)
for the instrument with a non-exempt reagent.
• The analyzer manufacturer can use any
cleared reagent or can jointly seek clearance
for a new reagent along with the instrument.
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Validation Protocols
• Method comparison, precision, reference
range; etc…
• All studies listed in the table need to be
addressed in the protocol submitted to the FDA.
• If a study is not applicable, a justification needs
to be provided on why the study is not
necessary.
• Protocols are accepted based on one-on-one
with the reviewer and may need to be modified.
– Some higher risk assays may require some sort of data.
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Reagent / Instrument
Validation Protocols
• Reagents protocols are assay specific.
• Instrument protocols are method
specific.
• Protocols are based on studies
performed in the original submission.
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Reagent / Instrument
Validation Protocols
• Both replacement reagent and new family
member protocols need predefined
acceptance criteria.
– Criteria for replacement reagents should be assay
specific, designed to challenge the performance
characteristics.
– Criteria for the introduction of a new family member
should be method specific, general enough to evaluate
all analytes within each method, and designed to
challenge the performance characteristics.
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Software Validation Protocol
• CDRH is concerned that software
controlled medical devices introduced into
the market are manufactured under welldeveloped software lifecycle processes.
• The software documentation in the original
family clearance serves new family
member software validation protocol and
should be certified to.
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Software Validation Protocol
• In order to certify to this protocol you
need to ensure your documentation on
file is current
• “Guidance for the Content of Premarket
Submissions for Software Contained in
Medical Devices “ (May 29, 1998):
http://www.fda.gov/cdrh/ode/57.html
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Process
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Replacement Reagent Process
• Use the “Add-to-file” process and
submit your protocol after you receive
your primary clearance.
• After your protocol is accepted, notify
FDA after each analyzer has been
validated according to the accepted
protocol.
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Replacement Reagent Process
• This notification should include a
statement that “abc” replacement reagent
has been validated on the “XYZ” open
system analyzer using the described
protocol in K######/A### submitted on
mm/dd/yyyy.
• The notification should also include any
application sheets or specific labeling for
the associated analyzer.
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New Family Member Process
• Submit Protocol for all methods to allow
the roll over of reagents to the new
family member.
• Validate your new instrument family
member.
• Notify FDA of your intent to market your
new instrument family member you
validated.
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New Family Member Process
• This notification should include a
statement that “abc” instrument family
member has been validated using the
method and software protocols in
K######/A### submitted mm/dd/yyyy.
• Include a list of all associated reagents
and 510(k) numbers intended to be
rolled over onto the analyzer.
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New Family Member Process
• Enough details on the analyzer so FDA
can concur with your family member
designation.
• These processes can be followed in one
notification for the original 510(k), a
Special 510(k) or an “Add-to-file”.
– issues may come up with protocols
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New Reagents For Family
Members
• Traditional 510(k) on a representative Family
member analyzer.
• Assay specific protocol for this new reagent
on the family member instruments.
• Declare validation for all appropriate family
members.
• Have all the processes complete at the time
of submission in order to introduce the new
reagent on all family members.
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CLIA Categorization
• All new test system combinations are
usually based on historical information
pertaining to the instrument on which the
test system is dependent, or on past
family member categorizations.
• However, it is important that all variables
are considered in categorizing a new test
system.
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CLIA Categorization
• Notifications will need labeling in sufficient
detail to determine categorization.
– Replacement reagents require a package insert.
– New family member require instructions for use
such as an abbreviated operators manual.
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