NIPT Technology Guide

This guide is for organizations interested in bringing noninvasive prenatal testing (NIPT) into their
laboratory. Because each technology provider approaches NIPT differently, this guide is designed
to help you ask the right questions, objectively compare platforms, and choose the best NIPT
technology for your lab.
Foreword
What is the value of NIPT?
Until 2011, the predominant prenatal aneuploidy screening options for trisomies 21, 18, and 13 were measurement of serum
markers and sonographic evaluation of the fetus. The introduction of cell-free DNA (cfDNA) screening created a new
option—NIPT—that facilitates screening for a wider range of fetal aneuploidies. Like traditional serum screening, NIPT is a
screening test and results should be confirmed by diagnostic testing prior to making pregnancy management decisions.

How do NIPT and traditional aneuploidy screening

options compare?
Chromosomal conditions screened
Traditional aneuploidy screening typically provides a risk assessment for trisomy 21 (Down syndrome), trisomy 18 (Edwards
syndrome), and, sometimes, trisomy 13 (Patau syndrome). In the second trimester, traditional screening can also screen for open
neural tube defects (ONTDs). NIPT offers the ability to screen for certain sex chromosome conditions (XO, XXX, XXY, and XYY)
and determine the fetal sex (XX or XY), in addition to common autosomal aneuploidies (trisomies 21, 18, and 13). Some NIPT
assays have expanded their test options to include screening for all rare autosomal aneuploidies (RAAs), partial deletions, and
duplications associated with known syndromes and whole-genome copy number variation (CNV) ≥ 7 Mb in an effort to provide
a more comprehensive view of the fetal genome and enable detection of clinically relevant chromosomal anomalies outside of
standard NIPT.

Accuracy and invasive follow-up

Traditional maternal serum screening and ultrasound has an overall false-positive rate of 5%,1,2 while NIPT has consistently
demonstrated dramatically decreased false-positive rates (higher specificity).3-6 Since a positive screen will likely result in an
invasive follow-up, NIPT offers improved screening performance while reducing the number of unnecessary invasive tests due to
false-positive results. Further, NIPT has also consistently demonstrated increased detection (higher sensitivity) for aneuploidy than
traditional screening.3-6

Positive predictive value (PPV)

PPV refers to the chance that a positive test result is a true positive. It is dependent on the prevalence of the condition being
tested and the specificity of the test. Given the significantly improved specificity of NIPT compared to traditional screening, PPVs
are significantly higher with NIPT at any maternal age.7

Early and easy results

NIPT can be performed after just 10 weeks of gestation and requires only one maternal blood draw. Traditional screening is
typically offered at 11-13 weeks at the earliest. Whereas NIPT requires just one blood draw, traditional screening requires a blood
draw and ultrasound in the 1st trimester.

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NIPT platforms
and approaches
There are two major platforms used to perform NIPT:

Sequencing
Data generation Single-nucleotide
polymorphisms (SNPs)
Sequencing provides information on the sequence of nucleotide bases contained in the A SNP (pronounced “snip”) is a DNA
cfDNA from a maternal sample. There are two types of sequencing: sequence variation occurring when
a single-nucleotide adenine (A),
• Targeted sequencing: A sequencing method that involves a step during sample thymine (T), cytosine (C), or guanine
preparation that preselects only certain portions of the genome for analysis. For (G) in the genome (or other shared
NIPT, this usually means that cfDNA fragments with sequences corresponding to sequence) differs between members
of a species or paired chromosomes
chromosomes of interest (such as chromosome 21) are targeted.
in an individual.
• Whole-genome sequencing (WGS): This sequencing method does not
include a targeting step and sequences all available cfDNA in the sample.
WGS interrogates the DNA sequence across an entire genome.

Data analysis methods

• Counting-based analysis: This method uses genetic information from the sample and performs a “count” of the relative
amount of data aligning to a given chromosome. Aneuploidy is detected when genetic data is proportionally over- or under-
represented on a target chromosome relative to other chromosomes in the sample.
• SNP-based analysis: This method uses single-nucleotide polymorphisms (SNPs) to infer the fetal genotype within a sample.
Aneuploidy can then be determined by assessing the representation of the fetal signal on target chromosomes.

Different providers use different combinations of data generation and data analysis methods in their respective NIPT assays.

Microarrays
Data generation

DNA microarrays use oligo probes to interrogate thousands or millions of SNPs contained in cfDNA in a single sample. Microarrays
are fixed and target the same SNPs in each sample.

Data analysis method

• SNP-based analysis: Non-polymorphic SNPs on a microarray can be used to assess copy number changes on chromosomes
of interest and make a determination of aneuploidy in a sample.

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Evaluating NIPT options
The sensitivity and specificity of NIPT are comparable across all three technology platforms.3 So what attributes
differentiate one NIPT option from another? Which questions should you ask to ensure your confidence when
choosing NIPT technology?

To help you compare your options objectively, this guide outlines the key criteria to consider:

• Test capabilities
• Test performance
• Lab operations
• Total ownership and operating costs
• Test regulatory status

For each criterion, this guide recommends questions to ask so you can select the NIPT option that best meets the needs of
your laboratory.

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Test capabilities
Traditional cfDNA-based NIPT methods focus only on chromosomes 21, 18, 13, X, and Y. This narrow range means that
chromosomal anomalies occurring elsewhere in the genome will be missed unless combined with other options. One possibility is
to use targeted panels to screen for microdeletions with known clinical phenotypes, but this still retains the test focus on a limited
range of conditions. Using a genome-wide screening strategy to analyze all chromosomes can increase detection rates for a broad
range of chromosome conditions, without being restricted to known conditions.8 These three NIPT options, traditional screening,
targeted panel analysis, and genome-wide screening, When deciding on an NIPT method, it is important to understand what the
community you service is looking for and how much genetic information they are seeking. Consider the comprehensiveness of the
test menu, reporting flexibility, and how well the test can accommodate future needs.

Test menu
NIPT enables you to screen for the most common chromosomal aneuploidies, including:

• Trisomy 21 (Down syndrome)

• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)

Expanded screening may include the following:

• Sex chromosome aneuploidies: NIPT can provide information on the status of sex chromosomes and screen for sex
chromosome­–related syndromes such as monosomy X (Turner syndrome) and XXY (Klinefelter syndrome), among others.
• Select microdeletion syndromes: Assessment of specific deletions smaller than 7 Mb with clinical relevance. Microdeletion
syndromes that can be assessed using NIPT include DiGeorge syndrome, Prader–Willi syndrome, and others.
• Aneuploidy status on all autosomes: Determination of rare autosomal trisomies, such as chromosome 22 or 16. While
individually rare, studies suggest that, collectively, rare autosomal trisomies have an incidence rate in early pregnancy of
~ 0.34%,9 which is similar to incidence rates of trisomy 21 in early pregnancy (0.30%).10 Rare autosomal trisomies have been
linked to early miscarriage, intrauterine growth restriction (IUGR), and uniparental disomy (UPD).9
• Copy number variants (CNVs) ≥ 7 Mb: Assessment method for subchromosomal CNVs, duplications, or deletions of the
fetal genome typically ≥ 7 Mb in size. Duplications and deletions ≥ 7 Mb have been associated with fetal anomalies and
developmental delay.

When considering an NIPT platform, it is important to consider the extent of reporting capabilities, as well as the flexibility and
expansibility, that the platform offers. This will ensure that you are set up for the future direction of reporting with the platform
in which you invest.

Considering an expanded menu

Currently, medical societies recommend NIPT only for the standard panel: trisomies 21, 18, and 13. Private insurers and some
national health screening programs follow this guidance and only reimburse for the standard panel.

However, an expanded menu can be a powerful tool for specialists caring for high-risk pregnancies.7 Initial studies indicate
potential benefits for expanded menu testing in average-risk cases as well.6 Use of expanded menu NIPT is in the early phases
with more information expected from ongoing clinical studies. In addition to evaluating clinical utility, these expanded menu
studies will take into consideration any changes to overall test specificity which could lead to a slight increase in rates of invasive
procedures.11

Societies, insurers, and national health programs will continue to evaluate the efficacy of an expanded NIPT menu, and guidelines
may evolve to incorporate more testing options.

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Questions to ask about test menu:
• Which chromosomes are tested?
• Is it possible to exclude specific chromosomes from evaluation prior to running a test?
• How was test performance validated?
• Will it be possible to add an expanded menu with this technology in the future?
• Will the test offer high specificity and sensitivity with an expanded menu?

Reporting flexibility
The information requested from NIPT may vary depending on the requesting lab, patient, or physician. To accommodate a variety
of needs, look for a test option that provides control over the data being reported on.

Questions to ask about reporting flexibility:

• Which chromosomes are reported on?
• Is it possible to exclude specific chromosomes from the final report?
• How easy is it to change the amount of information provided in a report?

Future needs
NIPT requirements may change as more information is discovered about the genome. Consider how easily a test can be adapted
to new findings as they become available or if you will need to invest in a new screening approach or technology.

Questions to ask about future needs:

• What updates will be needed for this test when new discoveries are made or new guidelines introduced?
• How will this method help meet future customer needs?

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Test performance
Several considerations factor into NIPT performance, including sensitivity, and specificity, time to results, failure rates, and
repeat rates.

Sensitivity and specificity Sensitivity (true positives)

As a screening test, NIPT clinical accuracy can be described by sensitivity and Sensitivity measures the proportion
specificity. Sensitivity is the proportion of true positives that are correctly identified of positives that are correctly
identified as such (eg, the
as such; specificity is the proportion of true negatives correctly identified as such.
percentage of sick people who
Fetal aneuploidy for chromosomes 21, 18, 13, X, and Y can be detected with a high are correctly identified as having
degree of accuracy by NIPT. A meta-analysis of multiple clinical studies reported the condition).
the weighted pooled sensitivities and specificities for trisomy 21 and trisomy 18 in
Specificity
singleton pregnancies as follows: trisomy 21, 99.2% and 99.91%; and trisomy 18,
Specificity (also called the true
96.3% and 99.87%, respectively.3
negative rate) measures the
proportion of negatives that are
correctly identified as such (eg, the
Turnaround time (TAT) percentage of healthy people who
are correctly identified as not having
It is essential to match the time to results with the expectations of physicians. TAT the condition).
can depend on multiple factors that are intrinsic to the assay. Factors such as the
number of steps required for sample preparation and data generation and analysis,
as well as the complexity of those steps and length of time required to complete each, all have an impact on TAT. Test failure
rates and repeat rates can also impact TAT at the sample level. In general, automation of an assay will improve both TAT and
throughput. But sample-to-report time can vary considerably among the manual and automated NIPT technologies available.

The major drivers of TAT are the methodologies unique to each technology and the extent of automation versus hands-on time
required.

Questions to ask about TAT:

• What is the expected total TAT from plasma isolation to clinical report?
• How many lab technicians are required to achieve the TAT?
• How many shifts are required to achieve the TAT?

Failure rates
Failure rates are a key consideration, but one of the hardest to compare. Also known as a “no call,” a test failure is defined as the
inability of NIPT to produce a test result for a given sample. Several factors can contribute to test failure, and overall failure rates
can differ significantly between tests. These differences can be clinically very relevant because most society guidelines recommend
that diagnostic testing be done to confirm any positive or failed screen test.11,12

Diagnostic testing for chromosomal aneuploidy involves an invasive procedure. Therefore, increased failure rates increase the
number of invasive procedures offered which, in turn, increase healthcare costs and the potential for adverse events, including risk
of pregnancy loss and patient anxiety. To understand the scope and clinical impact, consider the following factors that make up
the overall failure rate:

• Technical failure rate: The rate at which the NIPT technology fails to provide a result during testing. Reasons for technical
failures can include errors in sample preparation, data processing, and limitations of the test due to biological factors.

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• Fetal fraction failure rate: The rate at which samples don’t generate a result
because they are below a threshold amount of fetal cfDNA in a sample (the percent Fetal fraction
of fetal cfDNA in a sample is known as the fetal fraction). Samples that don’t meet This represents the amount of ‘fetal
signal’ within a given maternal
the fetal fraction threshold produce the same result as a failed test.
sample for performing NIPT. It has
Different methods of addressing fetal fraction include the following: been used as a sample QC metric
for performing NIPT. The ability for
— Strict fetal fraction cutoffs: This ensures that only samples with a high signal NIPT to discriminate fetal aneuploidy
are called by not reporting on samples with a fetal fraction lower than the may decrease as fetal fractions
decrease in a sample. Note that
threshold, often approximately 4%.
there is no gold-standard method
for assessing fetal fraction and that
— Dynamic threshold: Samples with low fetal fraction are only reported if
accuracy can vary widely among
there is sufficient data to make a confident call. The intent is to minimize failure methods used.
rates while ensuring accurate calls.

• Administrative failure rate: A measure of failures that occur outside of test

processing. Examples include underfilled blood collection tubes, damaged blood
collection tubes, and incomplete or incorrect test requisition forms. While not
always resulting directly from the technology, administrative failures may be more
closely associated with some options versus others. It is important to have a good
understanding of the potential causes of administrative failures.

Different vendors approach failure rates differently. To truly understand and accurately compare the performance and clinical
impact of any NIPT technology you may be considering, you should ask the vendor specific questions.

Questions to ask about failure rates:

• What is the overall failure rate of all samples, including those outside of thresholds and excluding repeats?
Characterize each type of failure.
Note: Samples should represent the expected NIPT cohort: average- to high-risk pregnancies with mean
gestational age near 10 weeks.
• What are the causes of the technical failures?
• Does the test use a strict fetal fraction cutoff, a dynamic cutoff, or no cutoff?

Repeat rates Repeat rates

Assess the rate at which samples must be reprocessed after the first pass. Some NIPTs The rate at which samples
allow failed samples to be reprocessed to achieve a result on a second pass, but this don’t return a result and can be
reprocessed a second time to
also increases the cost and expected turnaround time for delivering results.
return a result.
It is also critical to distinguish between repeat rates and redraw rates. By definition, a
repeat sample is one that can be processed using plasma from the same blood draw
event. In contrast, a redraw means that the patient must undergo an additional blood draw event, requiring more of the patient’s
time and a longer delay in achieving a final result. Some NIPT requires high levels of plasma per run, which means a test failure will
likely result in a redraw, not a repeat.

Questions to ask about repeat rates:

• What is the rate of samples that require reprocessing after the first pass?
• Does a repeat require an additional blood draw?

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Workflow operations
The NIPT workflow consists of several steps, and the complexity for each of these steps can vary widely between providers and
the technical approach used. A typical workflow starts with isolating plasma from a maternal blood draw. cfDNA is then extracted
from plasma and prepared for analysis. Data is generated from prepared cfDNA using sequencing, microarray, or other means.
Sophisticated analysis is then applied to the data, producing information on the aneuploidy status of the fetus in a sample. When
assessing NIPT options, consider all key aspects of workflow: throughput, automation, infrastructure, and labor.

Sample Accession Plasma Isolation cfDNA Extraction cfDNA Preparation Data Generation Analysis Reporting

Throughput
Some NIPT technologies are built for industrial-scale processing with very high throughput (> 20K samples per year). These
platforms are well suited for high-throughput labs and able to process a very high number of samples cost-efficiently. However,
these workflows typically require a high number of samples to initiate the processing of a batch. This can be problematic for labs
that do not have a sufficient number of samples to process batches consistently, resulting in long turnaround times for sample
processing. Some high-throughput workflows may allow fewer samples than the maximum to be processed in a batch, but
normally this means excess reagents are consumed, resulting in a higher cost per sample.

Conversely, some NIPT technologies are built for lower-throughput needs (< 2K samples per year). These platforms are best suited
for labs that expect to maintain a modest sample volume, but they can present issues if sample volume begins to grow. Typically,
more and more platforms must be purchased to meet rising sample demands, resulting in higher capital expenditure and inefficient
organization of the lab.

Finally, some NIPT technologies are built to be flexible and may offer different batching solutions on the same platform while
maintaining price-per-sample parity. These flexible options can be ideal for labs starting to offer NIPT and planning for sample
volume growth. Depending on the volume, these solutions may not be well suited for labs with demands on the extreme ends of
the sample throughput spectrum.

It is important to select a platform that meets your lab’s expected sample volume to maintain overall operational efficiency with low
operational costs, but you should also consider whether your sample volume needs may change over time.

Questions to ask about throughput:

• What are the minimum and maximum sample batch sizes that the platform can process?
• How long does it take to process a single batch?
• Does processing time change depending on the number of samples in the batch?

Automation
Preparing a blood sample for analysis can be complex and require numerous steps. Automation can help by significantly reducing
hands-on time for processing samples for NIPT while at the same time increasing total throughput.

NIPT platforms may vary substantially in the extent of automation options offered. When considering automation, look at the labor
demands for the workflow, the fit with your staff’s existing technical skill set, and the impact that required resources would have
on the rest of your lab operations. As with automating any workflow, weigh cost against benefit. High degrees of automation can
simplify and create process efficiencies, but they generally come with higher capital expenditure requirements.

Depending on the type and volume of work you do, you may or may not need the advantages of automation in simplifying
workflow and enhancing efficiency.

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Manual workflow
Manual options do not rely on automated liquid handling for liquid transfer and sample processing. Typically, they are labor intensive,
requiring significant assay “hands-on time” for pipetting and physically moving samples through the lab workflow. As a result,
manual workflows generally have a lower throughput and higher cost of labor per sample processed than automated systems.

Automated workflow
In automated workflows, some or all the steps are completed using automation equipment and automated data transfer. The capital
equipment requirements depend on the technical details of the NIPT assay. Some NIPT workflows only require a single automated
instrument, while others may be more complex and require multiple pieces of equipment to perform different steps of the workflow.
Automated assays generally have higher throughput and enable fewer technicians to process more samples, resulting in lower cost
of labor per sample. Human error can be minimized and sample tracking can be streamlined with an automated process. However,
depending on the instruments required, the initial capital expenditure can be higher.

Labs that are more automated, with NIPT systems that can run without need for monitoring, may achieve two more important
benefits: a reduced cost of labor per sample and reduced chance of human error.

Questions to ask about automation:

• Does the NIPT technology option automate liquid handling or require manual pipetting and physical moving of samples?
• Does the technology automate data transfer?
• Does the technology require multiple pieces of equipment to complete the workflow? How many technicians does the
technology require to process your lab’s volume of samples?

Laboratory infrastructure
Another important consideration when assessing NIPT technology options is the infrastructure required. Each option differs in its
requirements. Examples for consideration include the following:

Ancillary consumables and equipment

In addition to dedicated sample preparation and analysis equipment, NIPT workflows normally rely on general laboratory equipment,
such as centrifuges and freezers, or consumables, such as plasticware and blood collection tubes. A given NIPT workflow may
require that these general use items meet detailed specifications. Be sure to understand the total laboratory equipment and
consumable requirements, including specifications, prior to deciding on workflow.

Footprint
As outlined in previous sections, NIPT workflows have multiple steps that may require several pieces of automation, analysis, or
general laboratory equipment. Equipment can also vary in size, weight, and functional requirements, such as power supply. It
is important to understand the exact equipment required to perform a given NIPT assay, as well as if your available lab space is
sufficient to operate the test safely. Further, understand options for scaling up capacity should NIPT volume grow, as well as how
this would impact available lab space.

PCR room requirements

Polymerase chain reaction
A PCR-based test requires separate pre- and post-PCR lab space. This means (PCR)
separate rooms are required to complete the sample preparation process. Conversely, A technique used to amplify, or
NIPT workflows without a PCR step can be performed in a single workspace. make many copies of, a specific
target region of DNA.

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Assays can be very sensitive to contamination due to PCR products and may require additional countermeasures: for example,
negative or positive pressure, or restrictions on lab technicians who have entered post-PCR processing. These measures may
require significant investments in infrastructure or limit operational staffing flexibility.

Data management
What’s the best way to manage, store, and analyze NIPT data? Available NIPT technology solutions offer either onsite or cloud
data solutions, or both.

NIPT software that you can run in your lab on an onsite server potentially enhances the accessibility of your data. However,
managing data onsite can add administrative tasks, including maintaining the infrastructure to back up data and continually scaling
up as you process more samples and generate larger volumes of genomic data.

Uploading data to a cloud is another option. Cloud-based storage platforms do not require onsite infrastructure. Cloud-based
systems scale easily to meet growing needs. However, before committing to a cloud platform, make sure your institution permits
data storage in the cloud, which some organizations prohibit for security reasons. Some countries also have regulations about
transmission of data across borders or boundaries, so it is important to know what your country/region allows and where the data
storage servers are geographically located.

Laboratory information management system (LIMS)/laboratory information system (LIS) integration should also be considered.
Different NIPT provides different levels of sample tracking support. Systems may provide sample tracking throughout the full
workflow and integrate with existing information management systems. Other systems may rely on existing LISs for full sample
tracking.

Questions to ask about infrastructure:

• Is there a complete list of required equipment and consumables, including specifications?
• What is the minimum lab footprint required to run the assay?
• What are the options for scaling should test volume change in the future?
• Does the technology require PCR to amplify cfDNA? If so, how much additional pre- and post-PCR lab space is required?
• Can you run the NIPT software on your lab’s server? If so, what additional infrastructure is needed to back up data?
• Does the technology offer the ability to upload NIPT data to the cloud? Do your institution’s security guidelines allow
cloud-based storage?
• How does the system manage sample tracking? What are the requirements for LIMS/LIS?

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Total cost
To accurately compare the economics of NIPT options, consider the capital expenditures and operational expenditures—beyond
merely the test purchase price—that drive the total cost.

Additional equipment required

Some technologies require more equipment than others. For example, a PCR-based system requires space for dual robotic
systems to manage pre- and post-PCR processing. Or one system may require more computing and storage equipment
than another.

Infrastructure requirements
The more equipment needed and the larger the footprint, the more demands the system places on your infrastructure, including
the need for additional rooms, increased use of utilities, and added air-handling requirements. Consider what accommodations
you will need to make in your lab.

Number of hands-on full-time employees (FTEs) required

Factors influencing the FTE count include the volume of testing your lab performs and the platform you select. Generally, the
more automated the processing, the fewer FTEs you need. As a result, the balance shifts from operating expenditures to
capital expenditures.

Processing time
Total processing time extends from plasma isolation to cfDNA extraction all the way to result reporting. Assays with faster
processing time can result in less cost of labor or overhead per batch processed.

Test failures and repeat rates

Often, when a test does not return a result, the lab is not reimbursed even though it has incurred the costs associated with running
the test. So labs must account for repeat and failure rates when assessing the overall cost of NIPT options.

Bottom Line: Reagents and consumables account for part—but not all—of the cost of running a test. Similarly, capital
expenditure for equipment may simply be part of the cost of getting up and running, as there may be some reconfiguration
or infrastructure modifications required. Take into account all factors that impact cost when considering an NIPT technology.

Questions to ask about costs:

• What is the purchase price of the testing platform?
• What is the cost of additional equipment required to run the test?
• How much total lab space does the test require?
• What other infrastructure requirements must be met?
• How many FTEs are required to run the test?
• What is the processing time for each run?

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Regulatory status
In the United States, there are different classifications of in vitro diagnostics (IVD). To date, no NIPT IVD test has received Food &
Drug Administration (FDA) approval.

Did you know? There is not yet an FDA-approved NIPT in the US.

In the US, it is important for users to understand which elements of the chosen NIPT solution are IVD-marked and which are not.

The European Union (EU) has its own classification system for the CE marking of IVD devices such as NIPT:

• Other/General: All devices except Annex II and self-certified devices.

• Self-Certified: The manufacturer asserts product conformity with applicable requirements and maintains a file to prove it.
• List B, Annex II: Includes reagents and products for a wide range of tests.
• List A, Annex II: Includes reagents and products for human immunodeficiency virus I and II; hepatitis B, C, and D; and other
blood-related products.

NIPT options in the EU are classified as List B, Annex II. When evaluating an NIPT solution, it is important to understand which
components are CE-IVD marked and which are not. The CE-IVD mark indicates that the component has met rigorous regulatory
requirements. This distinction may be important in institutions with clear regulations stipulating that medical devices and equipment
must meet the most stringent standards.

Questions to ask about test registration level:

• What is the test’s US level of registration?
• What is the test’s EU level of registration?

Further considerations in
selecting an NIPT technology
We hope that you have found this guide helpful in understanding the steps to succeeding with NIPT in your laboratory.

Beyond considering the major criteria outlined in this document—test capabilities, test performance, lab operations, total costs,
and regulatory status—your evaluation of your options should include other, “behind-the-scenes” characteristics as well.

For example, investigate published research on the options you’re considering. Determine if there are extensive published studies
based on the technology. Request published data confirming performance, emphasizing those with large, blinded samples.

Learn how long the technology provider has been serving the community and how widely used their brand is. Understand
whether the provider has secure intellectual property rights for their technology. Seek out other users and ask about performance,
operations, and cost considerations, plus the company’s reputation. Know the full extent of support offered: technical expertise,
training, onboarding, and other tools.

The more you learn, the more confident you will feel about the NIPT you choose. The more confidence you have, the more
success you will have with NIPT in your laboratory.

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NIPT technology checklist
Covering all the bases
Congratulations. You’re getting closer to bringing NIPT into your lab. By now, you likely have a deeper understanding of your
options, as well as the important questions to consider during your buying process. This is the time to reach out to the various
suppliers and schedule an in-person appointment. Use this checklist to guide the conversation and ensure that all your questions
are answered.

Define your performance expectations

Be sure that you have a complete picture of how the NIPT technology performs, what its capabilities are, and
how the performance relates to your overall workflow and cost structure. Consider the following:

• Test menu: Is the technology capable of reporting on common chromosomal aneuploidies (T21, T18,
T13)? Can it report on sex chromosomal aneuploidies? Does it meet current business needs and enable
differentiation from other service providers through the means of expanded test options and customizable
reporting? How easily will it adapt to future changes in reporting guidance or specialists’ needs?
• Failure rates: What is the overall failure rate, inclusive of technical failures, samples that didn’t meet the fetal
fractions cutoff, and administrative failures?
• Repeat rates: What is the rate of samples that require reprocessing after the first pass, and how often do
repeats require an additional blood draw?

Know your TAT

Ensure that the workflow you are considering can consistently deliver results in a timely manner consistent with
the expectations of your clinicians.

• What is the expected total TAT from plasma isolation to clinical report?

Envision your new workflow

To help narrow your choices, define what your needs and requirements are in some key areas.

• Throughput: Determine what your expected sample volume is and how you see it changing over time.
Which technologies can meet your throughput requirements?
• Automation: Understand how different NIPT workflows fit with your current skill set and available FTE
resources. How much equipment is required to automate the workflow?

Assess the fit with your existing lab

How does the NIPT workflow fit with your current laboratory infrastructure?

• Ancillary equipment and consumables: What is the complete list of required equipment and consumables,
including specifications?
• Footprint: What is the minimum lab footprint required to run the assay?
• PCR requirements: Does the workflow require PCR to amplify cfDNA? If so, how much additional pre- and
post-PCR lab space is required?
• Data management: Do you need to run the NIPT software onsite, or is cloud computing an option for you?
What is needed to back up the data?

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Consider all components of “cost”
It is imperative to consider both acquisition and operation when evaluating costs of an NIPT technology.

• Additional equipment: What additional equipment is required to perform the test?

• Infrastructure modifications: What are the space and utility requirements?
• Personnel requirements: How many FTEs are required to run the test?
• Hands-on time: How much of the total processing time is actual hands-on time for laboratory staff?
• Test failures and repeat rates: How many test failures and repeated samples should you expect (and for
which you won’t be reimbursed)?

Be aware of the level of regulatory registration

This distinction may be important in institutions with clear regulations stipulating that medical devices and
equipment must meet the most stringent standards.

• Which of the components (ie, reagents, hardware, and software) in the NIPT solution are cleared by relevant
regulatory bodies?

Factor in research, reputation, and support

Ensure there is an established base of users and responsive service support.

• Published research: Are there extensive published studies based on the technology?
• Reputation: How long has the technology provider been serving the community, and what do other lab
customers say about the technology?
• Rights: Does the provider have intellectual property rights for its technology?
• Support: What type of support do vendors offer, including technical expertise, training, and onboarding?

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References
1. Ryan A, Hunkapiller N, Banjevic M, et al. Validation of an Enhanced Version of a Single-Nucleotide Polymorphism-Based Noninvasive Prenatal Test for Detection of
Fetal Aneuploidies. Fetal Diagn Ther. 2016;(40)3:219–223. doi:10.1159/000442931.
2. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011;31(1):7–15.
3. Gil MM, Quezada MS, Revello R, Akolekar R, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis.
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