September 12, 2016
Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane
Room 1061
Rockville, MD 20852
RE: Docket No. FDA-2016-D-0971: Draft Guidance for Industry and Food and Drug
Administration Staff; Infectious Disease Next Generation Sequencing Based
Diagnostic Devices: Microbial Identification and Detection of Antimicrobial
Resistance and Virulence Markers
Dear Sir/Madam:
On behalf of AdvaMedDx, a Division of the Advanced Medical Technology Association
(AdvaMed), we respectfully submit these comments in response to the FDA’s “Draft
Guidance for Industry and Food and Drug Administration (FDA) Staff: Infectious
Disease Next Generation Sequencing (NGS) Based Diagnostic Devices: Microbial
Identification and Detection of Antimicrobial Resistance and Virulence Markers”
(hereinafter “ID Guidance”).
AdvaMedDx member companies produce advanced, in vitro diagnostic tests that
facilitate evidence-based medicine, improve quality of patient care, enable early detection
of disease and reduce overall health care costs. Functioning as an association within
AdvaMed, AdvaMedDx is the only multi-faceted, policy organization that deals
exclusively with issues facing in vitro diagnostic companies in the United States and
abroad. Our membership includes manufacturers engaged in the development of
innovative diagnostic technologies supporting the advancement of the public health and
personalized medicine from next generation sequencing to complex multi-analyte
technologies to a breadth of advanced molecular diagnostics helping deliver cutting-edge
care to patients worldwide.
GENERAL COMMENTS
AdvaMedDx appreciates the efforts of FDA to share its thinking regarding its regulation
of NGS-based diagnostics. In addition to issuing the ID Guidance, FDA recently
published in the Federal Register two related Draft Guidances for Industry and FDA
Staff: 1) “Use of Standards in FDA Regulatory Oversight of NGS-Based In Vitro
Diagnostic (IVDs) Used for Diagnosing Germline Diseases (July 8, 2016) and 2) “Use of
Public Human Genetic Variant Databases to Support Clinical Validity for NGS-Based In
Vitro Diagnostics” (July 8, 2016).
Division of Dockets Management (HFA-305) September 12, 2016
Page 2 of 14
We applaud the tremendous efforts by FDA to develop these guidances and extensive
communications and outreach for public feedback. Through a series of public
workshops, FDA has proposed and received feedback on a number of innovative
regulatory concepts such as better leveraging of standards to support analytical validity,
use of curated databases for establishing the clinical validity of a test, application of a
representative variant approach to support validation, improved transparency of
information to patients and healthcare professionals, and the use of regulatory-grade
genomic sequences as an alternative comparator for clinical evaluation. We appreciate
FDA efforts to support flexible, risk-based regulatory approaches that help promote
patient access to diagnostic technologies.
FDA has incorporated a number of useful concepts into the ID Guidance. Furthermore,
AdvaMedDx believes that this proposed guidance should be reviewed and further
harmonized in the broader context of FDA regulation of NGS-based diagnostics to ensure
a more consistent and cohesive approach in all three guidances. We generally encourage
consistency in scientific and regulatory recommendations across these guidances where at
all possible. More specifically, we believe FDA should promote this goal of consistency
by incorporating the following concepts into the ID Guidance:
Set forth FDA’s process and criteria when contemplating recognition of standards
developed by the scientific community or standard development organizations
that incorporate analytical validation requirements for infectious disease NGS-
based tests.
Permit use of a declaration of conformity with FDA-recognized standards by
developers of infectious disease NGS-based tests in premarket submissions.
Consider special controls and/or conditions of exemption that could be developed
to provide a reasonable assurance of safety and effectiveness for infectious
disease NGS-based tests without necessarily the need for a 510(k), where
appropriate.
AdvaMedDx appreciates the opportunity to provide our comments, which are intended to
support diagnostics innovation and foster advancement of personalized medicine. Our
specific comments follow with accompanying recommendations to assist FDA. Please
do not hesitate to contact me at 202-434-7230 or [email protected] if you have any
questions.
Respectfully submitted,
/s/
Jamie K. Wolszon, JD
Associate Vice President
Technology and Regulatory Affairs
September 12, 2016 Page 3 of 14 Docket No. FDA-2016-D-0971
AdvaMedDx Comments on Infectious Disease Next Generation Sequencing Based Diagnostic Devices:
Microbial Identification and Detection of Antimicrobial Resistance and Virulence Markers;
Draft Guidance for Industry and Food and Drug Administration Staff
Additions are indicated in underline. Removals are indicated in strike out.
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1. lereneG
Clarify whether the ID Guidance would apply to profiling
applications that consist of characterizing microbial
populations through identification and determination of
relative proportions, and if so, whether different
performance analyses might apply.
It is unclear whether these applications are currently included
within the scope of the ID Guidance.
2. lereneG Add Discussion of Limit of Quantitation (“LOQ”) Sequencing has the potential of delivering quantitative results,
but LoQ is not mentioned in the ID Guidance.
3. General
Define “regulatory grade.”
We understand and appreciate the need for databases to be
populated with “regulatory-grade target sequences” and, given
their importance, would appreciate clarity in how the FDA
defines “regulatory grade.” Although the Appendix provides
some details on the constitution of a “regulatory-grade
database,” we recommend that this term be clearly defined and
articulated in the ID Guidance.
4. lereneG
Add Center for Biologics Evaluation and Research
(“CBER”) to the ID Guidance. In the alternative, clarify
that NGS HIV tests are excluded from the scope of the
ID Guidance.
Per the inter-center agreement between CBER and CDRH,
CBER has lead responsibility for all HIV tests and for tests
intended for use to screen the blood supply or tissue and cellular
products. While the ID Guidance explicitly excludes (lines 143-
146) tests intended for use to screen the blood supply or tissue
and cellular products from its scope, it does not exclude HIV
tests, and in fact mentions HIV tests as an example. Yet, the ID
Guidance makes no reference to CBER.
September 12, 2016 Page 4 of 14 Docket No. FDA-2016-D-0971
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5. 130-132
Revise as follows: “In contrast to human sequencing
diagnostics, infectious disease sequencing diagnostics
generally require rapid and actionable results,
sometimes within hours, as delayed or incorrect initial
diagnoses can result in fatalities.”
Human sequencing diagnostics also generally require rapid and
actionable results.
6. 132-135
Revise as follows: “Furthermore, the broad range of
specimen types (e.g., urine, blood, cerebrospinal fluid
(CSF), stool, sputum, etc.) and the large diversity of the
infectious disease agents that can be present in the
sample do not allow straightforward pre-analytical,
biochemical, or bioinformatics processes.”
Variation in pre-analytical processing steps is not unique to
assays for infectious agents. Moreover, the bioinformatics pre-
analytical processes are the same, i.e., searching against known
databases for nucleic acid sequences.
7. 138
Revise as follows: “The opportunity for repeat testing is
expected to may be limited due to a frequently small
specimen quantity (e.g., Cerebrospinal fluid (CSF)) and
the necessity to make a prompt and timely infectious
disease treatment decision for the patient.”
Small specimen quantity is not unique to ID NGS tests.
Moreover, while the opportunity for repeat testing may be small
for direct tests, for other tests (e.g., gastrointestinal pathogens),
the specimen may be abundant or be cultured (e.g., blood).
September 12, 2016 Page 5 of 14 Docket No. FDA-2016-D-0971
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8. 146-147
Add footnote to: “The inclusion of certain targets (e.g.,
Hepatitis B, Hepatitis C, HPV and HIV*) could elevate
the classification of the device to Class III, and FDA
encourages you to contact the Agency for additional
guidance.” The footnote would state: “CBER has lead
responsibility for HIV tests. For questions about HIV
NGS tests, please contact CBER.”
In the alternative, if CBER does not opt to be a co-
author of the ID Guidance, revise as follows: “The
inclusion of certain targets (e.g., Hepatitis B, Hepatitis C,
and HPV and HIV)…”
As discussed above, CBER has lead responsibility per the inter-
center agreement for HIV tests, yet CBER is not mentioned in
the ID Guidance. We recommend that CBER be included in the
ID Guidance. However, in the alternative, we would remove the
reference to HIV in this example.
9. 148-149
Revise as follows: “In addition, FDA recommends that
sponsors contact the Agency prior to undertaking any
clinical or analytical validation studies to discuss
whether additional recommendations are available due
to new advancements in this fast moving field. We
recommend that the sponsor utilize the Pre-Submission
process outlined in the guidance for Industry and Food
and Drug Administration Staff: “Requests for Feedback
on Medical Device Submissions: The Pre-Submission
Program and Meetings with Food and Drug
Administration Staff.”
The existing FDA Guidance for Industry and Food and Drug
Administration Staff: “Requests for Feedback on Medical Device
Submissions: The Pre-Submission Program and Meetings with
Food and Drug Administration Staff” is utilized heavily by
manufacturers, yet this guidance is not referenced in this section
of the ID Guidance. We recommend adding wording that points
manufacturers to this guidance in this section of the ID
Guidance.
September 12, 2016 Page 6 of 14 Docket No. FDA-2016-D-0971
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10. 175-178
Revise as follows: “An Infectious Disease NGS Dx
device differs from traditional diagnostic devices in that it
may be targeted to detect specific organisms or markers
and could simultaneously detect multiple organisms
present in a sample during a single run.”
This sentence applies equally to any multiplex device. Please
distinguish within the ID Guidance what applies to NGS and
multiplex devices versus what is unique to ID NGS devices.
11. 221-231
Re-title Section IIB. to “Databases as an Alternative
Comparator Method for Clinical Evaluation” and revise
the ensuing paragraph to: “FDA, in collaboration with
various federal agencies, has developed the database
entitled ‘FDA-ARGOS: FDA dAtabase for Regulatory
Grade micrObial Sequences; BioProject 231221.’ “To
promote a least burdensome regulatory approach for
devices that incorporate Infectious Disease NGS Dx
technology, FDA proposes the use of an alternative
comparator method for clinical evaluation that relies
heavily on public databases populated with regulatory-
grade target sequences. Such databases may be public
or proprietary and supply a set of validated regulatory-
grade microbial genomic sequence entries that are near
complete high-quality draft genomes with metadata
requirements. For more information on proprietary
databases, see Sections VI(D) and VIII. FDA, in
collaboration with various federal agencies, has
developed a public database entitled ‘FDA-ARGOS:
FDA dAtabase for Regulatory Grade micrObial
Sequences; BioProject 231221.’ This database supplies
a set of validated regulatory-grade microbial genomic
sequence entries which is available at the National
Center for Biotechnology Information’s (NCBI) website
As written currently, this section focuses on the FDA-ARGOS
database and its use as an alternative comparator method to
clinical evaluation. However, as the FDA clarifies in Section VIII,
“genomic sequence depositions in the public domain or in
proprietary databases can be evaluated and qualified for
regulatory purposes.” In short, both public and proprietary
databases that use regulatory-grade genomic sequences may
be used as an alternative comparator for clinical evaluation. As
such, we recommend revising this section to account for this, as
its focal point should be that regulatory-grade databases,
whether public or proprietary, may be used as an alternative
comparator method for clinical evaluation.
September 12, 2016 Page 7 of 14 Docket No. FDA-2016-D-0971
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(http://www.ncbi.nlm.nih.gov/bioproject/231221
(update with FDA web portal link)). Regulatory-grade
microbial sequences are near complete high quality
draft genomes with metadata requirements. For more
information see Section VIII, Appendix.”
12. 226-229
Clarify the statement: “This database supplies a set of
validated regulatory-grade microbial genomic sequence
entries which is available at the National Center for
Biotechnology Information’s (NCBI) website
(http://www.ncbi.nlm.nih.gov/bioproject/231221 (update
with FDA web portal link)).”
The ID Guidance does not address how the FDA-ARGOS
database information was validated. Please include a reference
or detailed information on the FDA-ARGOS database validation
criteria and process.
13. 229-231 Clarify the statement: “Regulatory-grade microbial
sequences are near complete high-quality draft
genomes with metadata requirements.”
It is unclear what constituted near complete high-quality draft
genomes for the FDA-ARGOS database. It also is unclear what
constituted the metadata requirements.
14. 249-254
Revise as follows:
• “Targeted Infectious Disease NGS sequencing:
Targeted sequencing requires a priori knowledge of the
target sequence; thus, its scope is limited to specific
targets. For the purposes of this document, targeted
sequencing refers to preferential amplification of defined
regions that target a specific organism(s) or marker(s)
selected for analysis a priori by any laboratory or
bioinformatics method (e.g., amplicon sequencing,
whole genome sequencing or a k-mer signature
database) based on the diagnostic device’s intended
use.”
Whole genome sequencing (WGS) could be added in "targeted
sequencing approaches" for the purposes of the ID Guidance.
We are aware of WGS-based tests that use a priori knowledge
of sequence targets and database-driven algorithms to identify
defined infectious agent(s) or marker(s) of interest.
September 12, 2016 Page 8 of 14 Docket No. FDA-2016-D-0971
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15. 280
Address discovery of emerging or novel pathogens or
other research applications in a manner consistent with
human sequencing.
Currently, the ID Guidance explicitly states that it does not cover
discovery of emerging or novel pathogens or other research
applications. However, emerging and novel pathogens are akin
to germline or somatic variants of unknown significance. The
expectations for inclusion of these targets should be clarified and
should be similar to those for NGS for human sequences.
16. 318 – 319
Clarify the following statement: “We note that device
performance should be established prior to using this
alternative comparator.”
It is unclear what the FDA means by this statement. Based on
the discussion throughout the guidance, the FDA-ARGOS
database seems to be most useful as an alternative comparator
method in the clinical evaluation of Infectious Disease NGS Dx
devices. Therefore, it appears that “device performance” in this
context may refer to the analytical performance of the device,
but this needs to be clarified.
17. Section IV.
Re-title Section IV. to “Risk Management.” “Benefit-Risk Analysis” is terminology that, through guidance,
FDA has applied to PMA and De Novo submissions. Given that
the focus of this Draft Guidance is 510(k)s, PMA terminology
such as “Benefit-Risk Analysis” should avoid being used, and
this section should simply be re-titled to “Risk Management.”
18. 386 – 392
Revise as follows: “The guidance document entitled
‘Factors to Consider When Making Benefit-Risk
Determinations in Medical Device Premarket Approvals
and De Novo Classifications’ provides information on
FDA benefit-risk determinations. Premarket
submissions should include a discussion of the potential
benefits and risks associated with the device that is
being assessed, the hazards and consequences
associated with those risks, analytical strengths and
Given the focus on 510(k) products in this ID Guidance, the
wording should be modified to reflect the activities that take
place when a risk analysis is conducted following the principles
outlined in the FDA-recognized consensus standard ISO 14971
“Medical Devices – Application of Risk Management to Medical
Devices.” See also comment above.
September 12, 2016 Page 9 of 14 Docket No. FDA-2016-D-0971
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weaknesses of the technology, and the mitigations that
have been put in place to reduce the risks as much as
possible. ISO 14971 ‘Medical Devices – Application of
Risk Management to Medical Devices’ (FDA recognition
number 5-40) may be a useful resource when
conducting such a risk analysis. clinical information that
is available demonstrating device effectiveness.”
19. 422-461
Revise as follows: “You should describe in detail the
methodology used by your device. You should
describe, at a minimum, the following elements, as
applicable to the device:…
• Design inputs and outputs with a risk analysis
and traceability matrix”
Design inputs and outputs are not typically included in a 510(k),
and we do not believe that information is warranted here. See,
e.g., Federal Food, Drug, and Cosmetic Act (FDCA) §
513((i)(D)(i). FDA can assess this information as part of a post-
market inspection of the company’s compliance with the QSR.
21 C.F.R. § 820.30(c) (design input); 21 C.F.R. § 820.30(d)
(design output).
20. 463-469
Revise as follows: “When applicable, you should include
descriptions of design control specifications that address
or mitigate risks associated with Infectious Disease NGS
Dx devices. For example, design controls may be
needed:
• For manufacturing process procedures that may
affect quality. “
Information related to manufacturing process procedures is not
typically included in a 510(k), and we do not believe that
information is warranted here. See, e.g., FDCA § 513((i)(D)(i).
FDA can assess this information as part of a post-market
inspection of the company’s compliance with the QSR.
21. 513-533
Revise as follows: “A description of how you intend to
use your risk assessment to mitigate risks through
implementation of any necessary controls over ancillary
reagents should be addressed using your risk
assessment. These may include, where applicable:…
It is unclear how an infectious disease NGS device would have
an ancillary reagent that is lot-number controlled.
A company’s complaint-handling protocol or information related
to Corrective and Preventive Action (CAPA) should not be
September 12, 2016 Page 10 of 14 Docket No. FDA-2016-D-0971
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Identification of reagent lots that will allow
appropriate performance of your device.
• Complaint handling protocols.
• Corrective and preventive actions. “
required as part of a 510(k) submission. See, e.g., FDCA §
513((i)(D)(i). FDA can assess this information as part of a post-
market inspection of the company’s compliance with the QSR.
21 C.F.R. §§ 820.100; 820.198.
22. 543 – 544
Revise as follows: “This includes any positive and
negative controls intended for use with the assay as well
as the appropriate internal external controls
recommended, but not necessarily provided, for the
assay.”
Positive and negative controls are external controls, so the use
of “external” is redundant in this sentence. Furthermore, internal
controls are valid and actually control with each patient
specimen (i.e., more frequently than once daily). The ensuing
discussion includes, appropriately, “internal” controls as well as
“external” controls.
23. 781 - 793
Revise as follows: “You should submit your minimum
requirements and cutoffs used as quality control for your
material, including, for example, but not limited to the
following factors…
• Agarose gel or equivalent technologies that
separate DNA fragments based on size…”
• …A specific quantification of DNA versus RNA.
Lines 785 – 793 provide a list of quality control metrics that must
be included in infectious disease NGS submissions. However,
other than sample amount and sample volume, the remaining
QC metrics listed are very likely too low to be measured (for
example, viral RNA yield from a plasma specimen). In another
context, the target(s) to be sequenced is/are not likely to be
distinguishable from other nucleic acids present in the sample
prior to enrichment, so the value obtained from the QC metrics
would be meaningless. For example, a total nucleic acid
extraction from a whole blood sample will likely be >99% human
DNA with very good yield (>500 ng), but little to none of this is
likely to be microbial, so the values are meaningless for a
microbiome assay. Nevertheless, sequencing this sample will
still potentially yield a valid microbial profile. We, therefore,
recommend that these factors be provided as examples rather
than mandatory for inclusion in submissions.
September 12, 2016 Page 11 of 14 Docket No. FDA-2016-D-0971
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Capillary systems with special gels are widely used.
Depending on the target, the specific quantification of DNA
versus RNA may be needed.
24. 836-844
Clarify the statement: “The sequences of the multiple
DNA\RNA fragments that comprise the signal outputs of
the reaction should be stored in a suitable format that
allows subsequent bioinformatics analysis. There are a
number of data formats applied to Infectious Disease
NGS; however, the most common are the text-based
formats FASTA (stores the biological sequence format
used to search National Center for Biotechnology
Information BLAST database) and FASTQ (stores both
the biological sequence and its corresponding quality
scores).”
FASTQ and FASTA files are not signal outputs from the
sequencers but already processed results (by sequencer
provider base-calling programs embedded with the sequencer).
If FDA wants signal outputs stored, then FASTQ and FASTA
files are not the right formats for that storage. FDA should clarify
what data it wants stored, and modify the types of files
accordingly.
25. 999-1004
Revise as follows: “(9) Sample to Result Turn-Around
Instrument Run Time (TAT)
The sample-to-result turn-around instrument run time
should be provided for the Infectious Disease NGS Dx
device. Please include data demonstrating turn-around
times for “locked-down” Infectious Disease NGS Dx for
both: (1) laboratory workflow from clinical sample to
sequence, and (2) the subsequent computational
analysis of Infectious Disease NGS data from sequence
to actionable clinical result.”
In line 1003, FDA is asking for laboratory workflow from clinical
sample to sequence. Since the test is not cleared yet, there is
no way for the manufacturer to know how the test will actually be
implemented for pre- and post-analytical factors (i.e., timing of
results reporting). The only thing the manufacturer can control is
sample processing and instrument run time, and not how
specimens flow through the laboratory (especially if the test is
run on a “batched” system where laboratories wait to accumulate
a minimum number of specimens before running the test).
Likewise, before the test is marketed, there is no way of knowing
how long, on average, it takes laboratories to report out results.
September 12, 2016 Page 12 of 14 Docket No. FDA-2016-D-0971
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26. 1052-1055
Clarify the statement: “Limit of Detection (LoD) provides
a measure of assay analytical sensitivity for a particular
target, and is defined as the lowest concentration of a
target that can be sequenced reliably and distinguished
from negative specimens with consistent detection in
≥95% of the specimen replicates.”
It is unclear what FDA means by “can be sequenced reliably” in
this statement. It may mean “coverage at a minimum of 20X
over 95% of the core genome at Phred like quality score8 =>
Q30” or a lower level of coverage if adequate justification is
provided, as is indicated in lines 926-927, but clarification on this
point is warranted.
27. 1066-1068
Revise as follows: In brief, the LoD determination can be
performed with a pool of different claimed targets in
claimed specimen matrix. This pooled approach is also
applicable for inclusivity and reproducibility studies.
Since all NGS technologies have a limited capacity
within which all DNA molecules are competing to be
processed, the pooled approach should be carefully
designed to avoid the bias possibly introduced by a too
high level of multiplexing.
Added to help avoid potential for bias.
28. 1327
Revise as follows: “Please note that in the majority of
instances only one site may be located outside of the
United States. If additional sites are desired, please
contact the Agency.”
FDA should consider a manufacturer request to include more
than one site outside of the United States, particularly if an
infectious agent is at higher prevalence outside of the United
States, or if the study timing coincides with disease seasonality
(e.g., flu studies).
29. 1362 –
1365
Establish sample requirements more consistent with
prior Agency requests for NGS or PCR diagnostic
products or provide sound statistical rationale for
requiring 1500 prospective samples for the evaluation of
negative percent agreement.
The ID Guidance requests 1500 prospective samples for the
evaluation of negative percent agreement, which is inconsistent
with precedent; FDA required 500 samples to demonstrate
accuracy for NGS diagnostic devices in previous related
submissions and 755 samples were used in a prospective
clinical study to evaluate the performance of recently cleared
PCR assay intended as an aid for infection control in detecting
September 12, 2016 Page 13 of 14 Docket No. FDA-2016-D-0971
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and differentiating genetic markers of resistance. While the
Agency provides statistical rationale to support the need for at
least 50 positive specimens for the evaluation of positive percent
agreement (lines 1427 – 1436), FDA fails to provide a similar
statistical rationale for why this number of samples is needed for
infectious disease NGS diagnostic devices. We urge FDA to
establish sample requirements more consistent with previous
expectations.
30.
Section VI.
E. (1) and
(2)
Allow regulatory-grade genomic target sequence
databases to be used as alternative comparators for
both negative percent agreement and positive percent
agreement evaluations.
The ID Guidance indicates that the use of regulatory-grade
databases as an alternative comparator method in clinical
evaluations is only suitable for negative percent agreement and
not positive percent agreement evaluations. We disagree with
this approach and believe that regulatory-grade databases are
suitable for use as alternative comparator methods in both
negative percent agreement and positive percent agreement
evaluations. The choice of a comparator method for sequencing
applications can be very challenging, particularly for rare
variants. There are few FDA-cleared or approved technologies
from which to choose, and their technology is often inferior to
that of the submitted device. Use of a regulatory-grade
database as an alternative comparator alleviates these
challenges associated with the use of traditional comparator
methods.
31. 1548 –
1549
Revise as follows: “Furthermore, for Class II devices,
modification or an update of a library and bioinformatics
pipeline would require premarket review by the FDA if
the modification has the potential to significantly affect
the safety or effectiveness of the device, as determined
by the manufacturer according to 21 C.F.R. 807.81.”
In their current form, lines 1548 – 1549 indicate that all library
and bioinformatics pipeline updates or modifications should be
communicated to the FDA prior to their use and implementation.
For Class II devices (which are the main focus of this guidance),
this is contrary to the principles provided in the Federal Food,
Drug, and Cosmetic Act and the implementing regulations. In
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should be communicated to FDA prior to use and
implementation
particular, the regulations state that, for Class II devices,
changes or modifications to a device that could significantly
affect its safety or effectiveness would require premarket
notification. 21 C.F.R. § 807.81. Therefore, it should not be
necessary to submit all library and bioinformatics pipelines
updates or modifications to the FDA for premarket review but
only those that could significantly affect the device safety or
effectiveness. For example, a manufacturer may determine that
a modification to a single line of code in a bioinformatics pipeline
does not influence the device’s safety or effectiveness. Such a
modification should, therefore, not be submitted to the FDA for
premarket review or as a notification. The text should be revised
accordingly. Additionally, we encourage the FDA to consider a
more flexible approach to modifications of NGS tests to
encourage innovation while protecting public health.
32. 1590-1592
Clarify the statement: “Extracted gDNA should be of
high quality and purity, and at sufficient concentration to
achieve a suitable yield to assure adequate depth and
breadth of genomic coverage for the type of sequencing
method employed.”
We agree with this statement, but the statement is very
subjective. We recommend that FDA add criteria, for example,
of what constitutes “high quality”, what constitutes “high purity,”
and what is “adequate depth and breadth of genomic coverage”
that was used to establish the “regulatory-grade” database FDA-
ARGOS.
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