The “Traditional” 510(k)

[
Device Validation Forum.
John E. Lincoln
The “Traditional” 510(k)
John E. Lincoln
“Device Validation Forum” discusses regulatory
requirements, scientific principles, strategies, and
approaches associated with medical device validation
that are useful to practitioners. We intend this column
to be a valuable resource for daily work applications.
The key objective for this column: Useful information.
Reader comments, questions, and suggestions are
needed to help us fulfill our objective for this column.
Case studies illustrating principles associated with
medical devices submitted by readers are most welcome. Please send your comments and suggestions to
column coordinator John E. Lincoln at jel@jelincoln.
com or to journal coordinating editor Susan Haigney
at [email protected].
KEY POINTS
The following key points are discussed:
•This discussion addresses the third 510(k) option,
the “traditional” 510(k)
•This 510(k) option is used when a proposed medical
device submission does not clearly match the criteria of the other two less-involved formats—Special
510(k) Device Modification or Abbreviated 510(k)
•A suggested 510(k) general format is provided that
has been used for many submissions for both simple
and complex devices including electro-mechanical
and hybrid devices
•Submission logistics are provided
•Submission document formats including examples
are discussed.
INTRODUCTION
The previous installment of “Device Validation Forum”
(see Reference) addressed “The 510(k): Its Purpose, Compilation, and Submission.” As previously discussed, medical
device companies must by law meet certain requirements
before marketing a new or substantially modified (physically or in labeled/intended use) device in the US. This
means the manufacturer or specification developer must
seek regulatory clearance prior to marketing by means of
a Premarket Notification, or 510(k), submission. These
submissions are required for Class 2 devices as defined by
the US Food and Drug Administration Code of Federal
Regulations (CFR). The European Union’s Medical Device
Directive (EU MDD) has different definitions. Marketing of the most benign devices (generally US FDA Class
1) or the newest technology (generally Class 3) does not
required 510(k) submissions.
The 510(k) system is currently one of the areas under
review by FDA to ensure it does not allow high-risk products to enter or remain in the US market. Areas of substantial equivalence, intended use, and supporting data
including clinical data (actual or published) are among
the areas under review.
In our previous discussion, three different 510(k)s
were mentioned based on the FDA Center for Devices
and Radiological Health (CDRH) guidance document
New 510(k) Paradigm—Alternate Approaches to Demonstrating
Substantial Equivalence in Premarket Notifications, effective
March 20, 1998. This document presents device manufacturers with additional optional approaches to facilitate
and accelerate review and obtain marketing clearance
for devices subject to the following 510(k) requirements:
•The Special 510(k) Device Modification option
utilizes certain aspects of the new quality system regulation, and a company’s previous 510(k) submission(s)
•The Abbreviated 510(k) option relies on the use
of guidance documents, special controls, and recognized standards
•The Traditional 510(k) method has also been
retained and is still required to be used if either of the
above two new option’s requirements cannot be met.
[
ABOUT THE AUTHOR
For more Author
John E. Lincoln, principal consultant, J. E. Lincoln and Associates LLC, assists companies in the design and implementation of complete 21 CFR 111, 210, 211, 820 and ISO 13485 quality management
systems, fully CGMP-compliant, and which have passed FDA audits. He may be reached by e-mail at
[email protected].
information,
go to
gxpandjvt.com/bios
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THE “TRADITIONAL” 510(K)
Previously we’ve discussed the Special 510(k) and the
Abbreviated 510(k). We’ll now discuss the third option
and the most prevalent, the Traditional 510(k). The traditional 510(k) remains the basic, or “fall-back” option,
especially when a proposed medical device submission
does not clearly match the criteria of the other two lessinvolved formats. Even if a submission qualifies under
one of the other two options, the submitting entity must
be familiar with the requirements under the traditional
510(k) submission and have met those requirements in
their retained documentation. These include a design
history file (DHF), 21 CFR 820.30(j), or device master
record (DMR) with controlled change history, 21 CFR
820.40(b).
FDA CDRH 510(K) COVER LETTER AND
SUBMISSION EXAMPLE
The following is a suggested format. It has successfully
been used for many submissions to FDA for both simple
and complex devices, including electro-mechanical and
hybrid devices. It is provided as a suggested template or
starting point to any person desiring to develop their own
submission. It is recommended that the FDA’s website,
www.fda.gov/cdrh, be consulted for the most current
examples or for indications as to changes in the 510(k)
process, especially given the current dynamic nature of
510(k) issues before FDA.
The information provided is taken from sources and
material that the author believes to be reliable. In such
condensed and generalized form, the material certainly
should not be considered a complete report on the subject matter, or usable “as is” for a specific application.
Conclusions are based solely on available data and the
experiences of a limited number of submissions. The
judgments and analysis of technical factors are not
intended to replace the utilization of appropriate professional counsel.
Submission Format
For fastest processing by FDA, any 510(k) should be submitted as follows:
•Electronic (see the FDA’s website www.fda.gov/cdrh)
or hard copy in triplicate (an original and two copies). The submitter should keep an identical full
copy for reference and when discussing issues with
the FDA’s reviewer.
•With sequential pagination.
•With drawings, schematics, and figures numbered
sequentially, preferably not redundantly, to facilitate
ease of review.
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•Separated, indexed, and tabbed as appropriate.
•Original and copies three-hole punched.
•Mark the original and keep the copies separated
(bindings are not required, because FDA puts them
into their own binder, even when the document is
submitted bound).
Cover Letter Sample Format
The cover letter should be a simple one-page explanation
of the submission and company contact(s), preferably on
the company’s letterhead (see Figure 1).
“Truthful and Accurate” Statement
This is a FDA-supplied form (may be obtained from FDA’s
website) that is completed and signed by an individual
who is a responsible senior member of management
attesting to the truthfulness and completeness of the
contents of the 510(k) submission (see Figure 2).
“Indications For Use” Form
This is another FDA-supplied form that restates the
intended use of the device covered by the 510(k) submission, and is stated in Section 11 of the submission.
All statements of “intended use” must agree completely
throughout the submission (see Figure 3).
510(k) Submission Sample Format
This is the traditional 510(k) submission format, covering
key points required by FDA to enable a determination of
substantially equivalent (SE) or not substantially equivalent (NSE). It is supported by attached documentation
analysis, test data, etc. (see Figure 4). The format includes
the following:
•Name(s) of product, with classification name and
common/usual name derived from FDA’s publication Classification Names for Medical Devices,
obtained from Division of Small Manufacturers,
International and Consumer Assistance (DSMICA).
•Medical device establishment and number. Company name and address and the FDA-assigned Establishment Registration Number, if obtained at time
of 510(k) submission.
•Device class (almost all 510(k)s will be Class II, by
definition), panel number (two numeric followed
by three alpha characters), and regulation number
(consisting of a three-digit prefix corresponding to
the part of the 21 CFR that device is referenced, followed by a period, then four more digits). Obtained
as indicated.
•Performance standards. International or industry
standards, if available, that the product has to meet
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Figure 1: 510(k) cover letter sample format.
[Letterhead or Return Address]
[date]
FOOD AND DRUG ADMINISTRATION
CDRH [if appropriate] (Center for Devices and Radiological Health)
Document Mail Center (HFZ-401)
[verify current address]
1401 Rockville Parkway
Rockville, Maryland 20852
RE: 510(k) Notification
Attention: Document Mail Clerk
The attached 510(k) Premarket Notification is submitted for evaluation and approval under
the requirements of 21 CFR 807.
[additional information]
Should there be any questions or additional information desired to facilitate the evaluation,
please contact me [company representative/submitter] at [phone number with area code],
or [consultant, if used] at [consultant’s phone number with area code].
Thank you for your consideration of this submission.
Sincerely,
[printed name/title]
Enclosures
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Figure 2: 510(k) “Truthful and Accurate Statement” form (Replica only—
official form available from www.fda.gov).
PRE-MARKET NOTIFICATION
TRUTHFUL AND ACCURATE STATEMENT
[As required by 21 CFR 807.87(j)]
I certify that, in my capacity as [position held in company] of [Company name], a [type of
organization, e.g., medical device manufacturer, specification developer], I believe to the
best of my knowledge, that all data and information submitted in the premarket notification are truthful and accurate and that no material fact has been omitted.
___________________________________
[signature]
___________________________________
[typed name]
___________________________________
[date]
__________________________________
Premarket Notification [510(k)] Number]
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Figure 3: 510(k) “Indications for Use” form (Replica only—official form available from FDA).
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)
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Figure 4: 510(k) submission sample format.
[Letterhead or Return Address]
[date]
FOOD AND DRUG ADMINISTRATION
CDRH (Center for Devices and Radiological Health)
Document Mail Center (HFZ-401)
1401 Rockville Parkway
Rockville, Maryland 20852
RE: 510(k) Notification
Attention: Document Mail Clerk:
This is to notify you of the intention of [company information] to manufacture and market
[description] Class [I or II]:
1. CLASSIFICATION NAME
COMMON/USUAL NAME
TRADE/PROPRIETARY NAME
2. MEDICAL DEVICE ESTABLISHMENT
Location of manufacturing facilities [name/address; phone and fax numbers]
ESTABLISHMENT REGISTRATION NUMBER: [must be obtained within 30 days of marketing the device]
3. DEVICE CLASS
[Obtain from FDA “Classification Names for Medical Devices” and/or verify with DSMA]
CLASSIFICATION
PANEL NO.
REGULATION NO.
4. PERFORMANCE STANDARDS
[List, if any]
[Also list any Safety Alerts for this classification, if any]
5. REASON FOR 510(k)
6. LEGALLY MARKETED EQUIVALENT (SE) DEVICES
7.
LABEL/PROMOTIONAL MATERIAL
[Submit draft copies of the individual package labels, instructions, and box labels, as
attachments]
8.CHARACTERISTICS:
8.1. Material Used
[List; or reference attached draft Bills of Material and Material Specifications, annotated
drawings for material/configurations]
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Figure 4: Continued.
8.2. Configuration: [attach assembly sketches, etc.]
9.PACKAGING
[Describe]
10.STERILIZATION
[“N/A” if product is non-sterile]
11. INTENDED USE
[Critical: this statement will determine all subsequent allowable marketing claims and
is one of the determinations as to when another 510(k) submission may be required]
12. DIRECTIONS FOR USE
[State all, or key points. Reference the enclosed “Instructions for Use”]
13.EQUIVALENCY
[Basis for claim of Substantial Equivalency (SE); the basis for filing a 510(k) instead of
a PMA]. Show equivalency in the following areas:
13.1. Materials/components
13.2. Construction and method of manufacture
13.3. Function and use. Include sample information on similar devices for review and
evaluation as part of the attached SE submissions.
14. PERFORMANCE TESTING INFORMATION
[Testing for safety, biocompatability, functionality, and electromagnetic compliance
(EMC), as applicable with results attached].
[Make a statement that the units are being developed in compliance with the Design
Control requirements; and will be manufactured under the new FDA Quality System
Regulations (the revised GMPs)].
[Reference the test/final release SOP, which indicate the company’s final release
requirements]
15. 510(k) SUMMARY:
[Summary or Statement -- See earlier discussion on the pros and cons of submitting
only a statement]
Should there be any questions or additional information desired, please contact me at
[company contact phone number with area code].
Sincerely,
[Signature]
[Printed name and title]
Enclosures
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and to which it has been tested. Also include any
safety alerts for this type of product obtainable from
industry sources or DSMICA.
•Reason for 510(k). State reason for this submission (e.g., new product, changed design, change in
key materials, intended use, etc.) (see “Changes/
Modifications”)
•Legally marketed equivalent (SE) Device(s). List the
510(k) numbers of those devices (one or more) to
which substantial equivalence is claimed.
•Label and promotional material. Describe or reference as “attachments” (see Figure 5) the proposed or
draft labeling and sales literature that will be used
on the product, its packaging, and in its marketing.
Again, this labeling must agree with the “intended
use” claim made in the 510(k).
•Characteristics. Describe the device, its material,
construction, and theory of operation.
•Packaging. Describe unit and shipper packaging. If
sterile, describe packaging capability to allow sterilization to be achieved and subsequently maintained
for the shelf life of the product.
•Sterilization (or N/A if non-sterile). Describe method, the sterility assurance level (SAL) achieved, and
validation method.
•Intended use. This description of the device’s intended use is given careful review by FDA to assure no
unproved claims are made. What is finally cleared
becomes the limit for any future marketing claims
made for the device by the company. Any expansion of intended use claims beyond what has been
cleared in the 510(k) will require the submission of
a new 510(k) with supporting data, or a pre-market
approval (PMA).
•Directions for use. Describe the operating instructions to be supplied with the device and enclose
copies (e.g., labeling, sheets, manuals) (see Figure 5).
•Equivalency. Provide FDA with the evidence to support company’s claim that this device is “substantially equivalent” to devices already in the marketplace.
FDA prefers to see an item-by-item listing/matrix of
the points of similarity or differences comparing the
two (or more) devices.
•Performance testing information. Include the test
results of all relevant testing (see Performance standards). Include supporting data as attachments
(including potential problems identified and their
corrective action). All electrical devices must provide data on electromagnetic compliance (EMC;
both acting upon and being acted upon other electromagnetic devices). A statement that the prodgxpandjv t.com
uct will be manufactured under good manufacturing practice (GMP) quality systems regulations is
advisable.
•510(k) summary. FDA allows a company to state
that data in the 510(k) will be made available to
whomever requests it for the life of the product (the
“Statement”). This is a somewhat onerous responsibility to be assumed by the company, because the
company is responsible for responding to a request
for the summary within 30 days of the request for the
life of the product. Alternatively, the company may
submit a summary as part of the 510(k) submission.
FDA (not the company) then makes this summary
available to those requesting it. A sample summary
is shown in Figure 5.
Optional Forms (For Reference or
Submission)
It is suggested that the CDRH “Premarket Submission
Cover Sheet” and the CDRH “Premarket Notification
for 510(k) Refuse to Accept Checklist” both be obtained
from DSMICA and used to prepare the submission. Even
better, fill out the sheets as completely as possible, and
enclose them as part of the submission (possibly after
the “Cover Letter”, “Truthfulness...”, and “Indications
for Use” pages).
Tabs and Attachments
Where any of the above sections of the submission
require supporting data, an Appendix or cross-referenced
“Tabs” section is recommended to be included in the
submission. Typically, such tabs may include: Product
descriptions, pictures, schematics, drawings; labeling,
including instructions for use; test data, bench, functional, lab, biocompatibility; sterilization test data; and
similar. This section is necessary to provide the FDA
reviewer with a full picture of the product and the efforts
to prove SE (substantial equivalence). Cross-reference
the tab to the corresponding submission section, and
vice versa (see Figure 5).
Safety and Effectiveness (Hazard
Analysis)
This is another area coming under FDA review (see
Figures 6 and 7). The author has routinely provided
a documented review of the FDA Manufacturer’s and
User’s Device Experience (MAUDE) database for similar
product’s adverse events, as well as excerpts from the
device’s Product Risk Management File/Report (under
ISO 14971:2009), generally the FMECA’s as part of the
510(k) submission).
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Figure 5: 510(k) attachments to sample submission format.
ATTACHMENTS
0.Table of Contents
I. Summary of Safety and Effectiveness; and Types of Safety/Effectiveness Problems and
Their Resolution (see Figures 6 and 7)
II.C omponents/Assembly Drawings; and Raw Material/Components Specifications
III.Labeling:
Instructions for Use
Unit Label Blanks, various configurations
Carton Label
Advertising
IV. Test Data
Independent Lab Testing for Safety, Biocompatibility, and EMC (electromagnetic compatibility) [as appropriate]
Other Test Data [as appropriate]
In-coming/Manufacturing QC Testing Procedures
FQA/FQC Testing Procedures
V. Predicate Devices
510(k) citation(s) and labeling.
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Figure 6: 510(k) “Summary of Safety and Effectiveness” sample format.
510(k): [TITLE]
Attachment I-1
SUMMARY OF SAFETY AND EFFECTIVENESS
[ in lieu of a statement ]
1. DEVICE NAME (Trade, common, and classification): [name(s)]
2. PREDICATE DEVICE(s): [list “K” number of SE device(s) here] submissions attached,
which were determined to be SE, and [any pre-amendment device(s)]
3. DESCRIPTION: [brief description from main body of 510(k)]
4. INTENDED USE: [restate intended use from main body of 510(k)]
5. We believe this submission should be found substantially equivalent by virtue of the
following points, expanded upon elsewhere in this submission:
5.1. [list similarities in materials, basic components, or method of manufacture] used
have been used in the medical industry on similar/identical products and for similar/
identical uses since pre-amendment [if true], with no record of any patient problems,
adverse reactions [if verifiable in company documentation]
5.2. No change in basic construction [if true]
5.3. The device and its components have been tested by an independent lab for [list tests
referenced or included as part of this 510(k), e.g., safety and EMC, and will be subjected
to inspection/testing at Incoming QC, and during/after manufacture and prior to release
to the field [if such will be performed]
5.4. The function and use of this product will be no different than that of the predicate
device(s) [and any pre-amendment devices]
6. There are no substantive differences between the products defined in this 510(k) submission and the predicate devices [if careful analysis proves this].
Signed: ___________________________ Date ______________
[printed name and title]
[company name/address/phone]
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Figure 7: Possible abbreviated 510(k) risk analysis summary sample format.
510(k): [TITLE] Attachment I-2
TYPES OF SAFETY AND EFFECTIVENESS PROBLEMS
[perform product-specific analysis and amend matrix below as required]
Based on the submitter’s experience in the medical device industry over the past [years],
and review of [company or industry data, e.g., FDA’s MAUDE, DHR’s (batch/lot records),
Non-Conforming Material Reports, and complaint / CAPA] data, the following is a list of
the type of problems this medical device could be subject to, coupled with the method(s)
of correction/prevention:
ProblemResolution
01. Incorrect ComponentsWritten component specifications; and IQC
sampling of component parts to the specs, per
SOP, and ANSI/ASQ[C] Z1.4-1993. Component drawings, photos, and/or Certificates of
Compliance where required
02. Joint/bond DegradationValidation of [define] equipment/ processes;
inspection of bonded/sealed material interfaces; use of calibrated equipment; in-process
inspection/functional QC testing
03. Damaged Material/ComponentsVisual and functional QC inspection at
incoming, in-process, and at finished assembly. Vendor audits
04. Malfunctions [define]Independent lab testing; Functional Mfg QC/
FQC testing
05. Packaging/Labeling ProblemsShake/drop testing pre-production; Visual
FQC sample inspection
Instruction ProblemsFMEA; Investigate problems for any labeling
component; correction
06. Repeated Non-conformancesUtilize principles of continuous improvement; [list company methods, e.g., trending,
investigation of non-conformances and field
complaints, determination of root causes and
elimination].
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Pagination and Submission
Once the entire 510(k) submission, with “Statements”
and “Attachments and Tabs” has been compiled, each
page is sequentially numbered. Copies are made. A
retain copy is made for the submitter’s files. The submission is made together with proof of payment of user
fees (a voucher obtained upon payment from the FDA
website). Typically the submitter will not hear from, nor
should they attempt to contact, FDA until the 90-day
period has almost expired. Generally the reviewer will
have some questions to be answered. Most can be immediately addressed, so the review “clock” keeps running.
If a response requires some extended time period, then
the submitter should request a time extension from
the reviewer, stopping the “clock.” In rare instances,
the 510(k) will be rejected, “refuse to accept,” and the
deficiencies will have to be addressed as indicated. If
the product is still considered Class 2 by FDA, then a
new 510(k), with new fees, will have to be compiled
and submitted. To minimize such an occurrence as far
as possible, do your homework beforehand.
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REFERENCE
Lincoln, John E., “The 510(k): Its Purpose, Compilation, and
Submission,” Journal of Validation Technology, Volume 16,
No. 3, Summer 2010. JVT
ARTICLE ACRONYM LISTING
CAPA
Corrective and Preventive Action
CDRHCenter for Devices and Radiological Health
CFR
Code of Federal Regulations
DHF
Design History File
DHR
Device History Record
DSMICADivision of Small Manufacturers, International and Consumer Assistance
DMR
Device Master Record
EMC
Electromagnetic Compliance
EU MDDEuropean Union’s Medical Device Directive,
Council Directive 93/42/EEC of 14 June 1993,
as amended
FQC
Final QC
FMECAFailure Mode, Effects and Criticality Analysis
MAUDEFDA’s Manufacturer’s and User’s Device
Experience database
N/A
Not Applicable; Non-Applicable
PMA
Pre-Market Approval
QCQuality Control, usually actual inspection
and/or verification activities
SAL
Sterility Assurance Level
SE
Substantial Equivalence
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