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
[Powerpoint]
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.
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.
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.
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 '88) to FDA.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
Reagent / Instrument Validation Protocols
- Reagents protocols are assay specific.
- Instrument protocols are method specific.
- Protocols are based on studies performed in the original submission.
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.
Software Validation Protocol
- CDRH is concerned that software controlled medical devices introduced into
the market are manufactured under well-developed software lifecycle processes.
- The software documentation in the original family clearance serves new family
member software validation protocol and should be certified to.
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
Process
[Accessibility]
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.
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.
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.
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.
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
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.
CLIA '88 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.
CLIA '88 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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