A Decade in the Making: The Clinical Landscape and Commercialization of NIPT

One Year After the Pilot Cancellation: What Is the Current Status of This Technology’s Clinical Use, and What Changes Has It Brought to Clinical Prenatal Diagnosis?

At the recently held 6th Academic Conference on Fetal Developmental Abnormalities, Prenatal Diagnosis, and Intrauterine Therapy, alongside the Symposium on the Clinical Application of Genomics Technologies in Reproductive Medicine (hereinafter referred to as the Symposium on Clinical Applications of Prenatal Diagnosis), reporters from VCBeat (WeChat ID: vcbeat) interviewed Huang Shangzhi, a national expert in prenatal diagnosis; Yao Hong, Director of the Prenatal Diagnosis Center at Southwest Hospital; and Zhao Lijian, Vice President of BGI Genomics. Through their insights, we hope to address the questions on our minds.

In 1997, Professor Dennis Lo of The Chinese University of Hong Kong accidentally discovered the presence of cell-free fetal DNA in maternal peripheral blood. Subsequently, many scientists and biologists in the field sought to develop diagnostic products for fetal diseases based on this discovery.

“Many new methods have emerged in this process, but their performance has been suboptimal,” Zhao Lijian, Vice President of BGI Genomics, told VCBeat. “Many detection methods exhibit poor specificity, making them unsuitable for widespread clinical adoption.”

In 2008, BGI began exploring the use of next-generation sequencing (NGS) technology for the detection of cell-free fetal DNA. Between 2008 and 2010, BGI conducted large-scale clinical trials in collaboration with hospitals in Shenzhen and Zhuhai. Over this two-year period, 3,177 cases were enrolled to validate the clinical feasibility of this technology.The results exceeded expectations, with both detection rate and specificity far surpassing those of traditional serological screening techniques.

In 2010, NGS-based non-invasive prenatal screening technology began to enter clinical practice.

Prior to the advent of next-generation sequencing (NGS), clinical screening for Down syndrome primarily relied on two methods: serological screening and amniocentesis. Although amniocentesis is considered the gold standard for diagnosis, it is highly invasive and carries a risk of miscarriage. While serological screening is non-invasive, its detection rate and false-positive rate are less than ideal. The emergence of non-invasive prenatal testing (NIPT) has addressed one of the most pressing needs in clinical prenatal screening.

This technology quickly demonstrated its clinical application potential and began to expand rapidly in clinical practice. During this process, an increasing number of companies entered the industry. Each operated independently, with no unified standards for operational procedures or testing methods.

In February 2014, the National Health and Family Planning Commission and the China Food and Drug Administration (CFDA) jointly issued a directive to halt unauthorized practices, marking the beginning of standardized clinical application of high-throughput sequencing. Services were suspended, and companies were required to cease operations, submit registration applications, conduct new clinical trials, and re-establish their quality systems in accordance with CFDA standards. BGI Genomics’ NIFTY non-invasive prenatal testing (NIPT) became the first product to receive CFDA certification.

In 2015, the National Health and Family Planning Commission issued a notice on pilot programs for the clinical application of high-throughput sequencing. Eight medical testing laboratories, including BGI Genomics, and 108 prenatal diagnosis institutions were granted pilot qualifications. The pilot program was officially terminated in 2016. After one year of small-scale validation by regulatory authorities, non-invasive prenatal genetic testing began to be conditionally permitted nationwide.

The discontinuation of the pilot program signifies regulatory endorsement of NIPT. Now, more than a year since the pilot was discontinued, what changes has it brought to clinical practice?

“The biggest change is that this test was previously only available at Grade A tertiary hospitals, but it now reaches primary care hospitals and remote areas.”Yao Hong, Director of the Prenatal Diagnosis Center at Southwest Hospital, told VCBeat.

In clinical practice, the widespread adoption of a technology depends not only on the technology itself but also on health economic considerations.

Technologically, NIPT is disruptive and meets the dual demands of clinical practice. During the one-year pilot period for its removal from restricted lists, local governments and companies provided varying degrees of subsidies and price concessions for testing. The improvement of regulatory frameworks and the reduction in costs have enabled the technology to reach primary care hospitals, allowing individuals with relatively lower incomes to benefit as well.

Taking Chongqing Municipality as an example, although non-invasive prenatal testing (NIPT) has not yet been included in the medical insurance coverage, free screening has been implemented in two districts and counties—Yubei District and Zhong County—based on the collaboration between BGI Genomics and the local government, while a subsidy of RMB 600 is provided in other districts and counties.

Shenzhen, Guangdong Province, included non-invasive prenatal testing (NIPT) in its medical insurance coverage as early as January 2016, with the test price set at only RMB 855. This year, the city has further implemented fully free NIPT for all pregnant women in Shenzhen through fiscal subsidies and maternity insurance payments.

“Testing in the Hong Kong region costs around 7,000 RMB, while it is completely free in Shenzhen, just across the river.”Zhao Li stated.

“NIPT technology is disruptive, and its ultimate adoption rate will be determined by health economics,” said Yao Hong. “The ideal model would involve the government covering a portion of the cost, enterprises offering concessions, and pregnant women paying a share or even nothing at all, thereby bringing the price down to a reasonable level.”

As the coverage area expands, public acceptance of NIPT is also increasing.

The availability of NIPT is conditional, with stringent requirements imposed on testing institutions and protocols. Strict government regulations have enabled participating companies and institutions to clearly define their roles, while the industry has established standardized procedures for testing, operations, and reporting. Furthermore, endorsement by regulatory authorities has increased acceptance among pregnant women.

“Ninety percent of pregnant women who visit our hospital choose NIPT,” Yao Hong revealed to VCBeat.

He told reporters that many pregnant women directly request NIPT, having learned from media, online sources, friends, or doctors about the test’s high accuracy and its safety for the fetus.

“Once they understand the technology, they will opt for such solutions.”The patients’ acceptance rate is even higher than that of physicians, which is the most reassuring aspect.“Yao Hong said.

On the 10th anniversary of its inception, NIPT has become a routine and widely accepted technology.

These changes stem not only from government initiatives but are also inextricably linked to the efforts made by hospitals and enterprises.

Government Level: Clarify Regulatory Rules and Vigorously Promote the Prevention and Control of Birth Defects

Government-led initiatives are undoubtedly the most efficient. Moreover, government services operate from the grassroots level upward; with such a system in place, both coverage and public acceptance would improve significantly.

The government attaches great importance to the prevention and control of birth defects. In Hubei Province, Chongqing Municipality, and Shenzhen, the government has already assumed the costs for birth defect prevention and control measures. Not only is non-invasive prenatal testing (NIPT) covered, but many newborn screening tests are also provided free of charge.

“During the pilot implementation of NIPT, government leaders would lead teams to hospitals for on-site inspections and supervision, aiming to observe firsthand how the technology was being applied.” Yao Hong recalled, “The government stands in the same trench as hospitals, with the goal of controlling, or even eliminating, birth defects.”

Hospital Level: Undertaking the Function of Grassroots Health Education

The implementation of NIPT was also inseparable from the efforts of hospital experts. Tertiary Grade A hospitals were among the first clinical institutions to adopt this technology, with some even participating in its early trials. It was precisely the endorsement from these leading hospitals that paved the way for this technology to enter the market.

For clinical practitioners, NIPT remains an emerging technology, and physicians at primary-care hospitals may not have a high level of awareness regarding the test. As the technology is introduced into primary-care hospitals, these leading institutions also assume the role of providing public education to lower-tier hospitals and the broader community.

“This year marks the sixth edition of the Symposium on Clinical Applications of Prenatal Diagnosis, although the conference actually took shape nine years ago. It is a highly significant academic event within the industry,” Yao Hong revealed. “This conference is specifically targeted at obstetricians. Physicians themselves must understand birth defects; only by mastering this technology can they effectively educate their patients.”

Furthermore, as the Director of the Prenatal Diagnosis Center at Southwest Hospital, Yao Hong frequently delivers lectures at county- and township-level primary healthcare institutions to disseminate knowledge on birth defects. Physicians from these grassroots hospitals who are interested also have the opportunity to undertake advanced training at his hospital.

“I have also established a communication group for obstetricians, and we are trying every possible measure,” said Yao Hong.

Moreover, hospitals serve as the final point of contact with patients, representing the institutions closest to pregnant and postpartum women and providing the most direct setting for patient education.

Upon entering the floor housing the obstetrics department of a tertiary Grade A hospital, one can see informational display boards lining both sides of the corridor. These boards feature concise illustrated educational materials on birth defects, along with takeaway brochures.

Yao Hong told VCBeat, “Pregnant women undergo numerous tests during prenatal check-ups, such as ultrasound and imaging. At 12 weeks of gestation, we clearly advise them to undergo either non-invasive prenatal testing (NIPT) or serum screening. In addition, through routine health education and informational brochures, we ensure they fully understand the importance of Down syndrome screening.”

He believes that although doctors may not have sufficient time to provide pregnant women with highly detailed explanations, basic health education is essential.

Of course, in addition to science popularization and health education, it is more important to ensure that pregnant women and their families have a clear understanding of the nature of testing during the process: screening is not equivalent to diagnosis; even if the test result is positive, further diagnostic evaluation is required. Testing is not infallible, and its scope is limited.

Although the scope of detection for some companies' NIPT products has expanded to include sex chromosomes and copy number microdeletions/microduplications, the detection rate remains lower compared to that for trisomies.

“We explicitly inform pregnant women that NIPT has a higher detection rate for trisomy syndromes, while other tests serve only as screening alerts,” Yao Hong told reporters. In addition to verbal counseling, pregnant women must sign an informed consent form prior to testing; the hospital may proceed with the test only after both verbal and written disclosures have been completed.

“Testing will involve communication with patients, so it is essential to clarify this concept with them from the outset,” emphasized Yao Hong.

Corporate Level: Rationale and Profit Concession

Certainly, enterprises have also played an indispensable role in this process. The inception, application, and subsequent development of regulatory frameworks for this technology are all closely intertwined with corporate involvement. Data generated by enterprises from the experimental to the clinical stages have provided regulators with a substantial foundation for argumentation and research.

For instance, the “Document No. 45” released in 2016 drew on data from multiple third-party industry companies.

Meanwhile, after the regulatory framework was formally established, these companies also offered concessions, both to promote the adoption and penetration of their technologies and to attract a larger user base.

As previously mentioned, the cost of NIPT in the Hong Kong region is approximately RMB 7,000. In second- and third-tier cities, this price may be unaffordable for some individuals. Internationally, testing prices range from USD 350 to USD 2,900, with an average price of USD 874, equivalent to RMB 5,792. However, under the current pricing schemes issued by various provinces in mainland China, the highest approved price is only RMB 2,400.

In an interview, Zhao Li revealed to reporters that practicing public welfare has always been a crucial component of BGI Genomics’ strategy. Since May 2017, through collaboration with the government and utilizing both fiscal subsidies and maternity insurance coverage, BGI Genomics has enabled all pregnant women in Shenzhen to access free non-invasive prenatal testing (NIPT) services.

“We also plan to gradually implement similar models in places such as Fuyang, Anhui Province, and the Qianxinan Buyei and Miao Autonomous Prefecture in Guizhou Province. This is one of the best ways to make genetic technologies more accessible and beneficial to the public,” said Zhao Lijian.

In the future, there is no doubt that NIPT technology will achieve more comprehensive market penetration, with an increasingly broader population coverage and a continuously expanding market size.

“After the pilot program was discontinued, this technology was rolled out nationwide.”The experience from the pilot program should be implemented more rigorously.“, it doesn’t mean that we’ll disregard regulations once we scale up,” said Huang Shangzhi.

He believes that once technology is fully deployed in clinical practice and the market, regulation should not be solely the government’s responsibility; enterprises should also proactively engage. “Companies must strictly adhere to regulations, and if others violate them, the industry should collectively reject such behavior,” said Huang Shangzhi.

“Meanwhile, the data storage capacity of hospital testing centers is limited; in the case of third-party testing, the data does not return to the hospital.” Huang Shangzhi stated, “How should hospital-generated test data be stored? How can data from third-party testing institutions be returned to hospitals? Is it feasible to leverage third parties to store and consolidate this data? These issues warrant discussion.”

Furthermore, public awareness of NIPT has not yet reached a particularly high level, and market education efforts still need to be intensified. In this process, companies must disseminate accurate information, hospitals should provide proper guidance, and online platforms and media ought to remain objective, fair, factual, and promote positive values—a principle that VCBeat has consistently upheld.

To enable more people to benefit from non-invasive prenatal testing (NIPT), incorporating it into medical insurance coverage would be the most effective measure. As early as 2011, local governments began to successively introduce pricing standards for NIPT.

Currently, the price bureaus of five provinces—Guangdong, Sichuan, Jiangsu, Hubei, Fujian, and Zhejiang—have established pricing standards for non-invasive prenatal testing (NIPT). However, only Shenzhen City and Qianxinan Prefecture in Guizhou Province have included NIPT in their maternity insurance coverage.

Nevertheless, local governments have long assumed the cost of birth defect prevention and control. Beyond non-invasive prenatal testing (NIPT), corresponding subsidy or fee-waiver policies have been implemented for prenatal screening and diagnostic procedures such as serological screening, amniocentesis, and ultrasonography, with some services even provided free of charge nationwide.

“The government attaches great importance to the prevention and control of birth defects, so it won’t be long before NIPT is covered by medical insurance,” said Yao Hong.

For companies, there is a growing expectation for expanded disease coverage in screening. Beyond chromosome-related disorders, prospective research is also being conducted on monogenic diseases. From a technological development perspective, the trend will be toward increasingly broader disease coverage by NIPT in the future.

However, for hospitals, the accuracy of testing is often the most critical factor. To ensure that NIPT covers high-prevalence diseases, substantial R&D investment is required, after which cost and ethical considerations must be addressed.

“We are not waiting for NIPT, but for NIPD—diagnostic-grade technology,” said Yao Hong. “When disease diagnosis can be achieved through maternal peripheral blood, the accuracy of testing for monogenic disorders will naturally improve.”

“Additionally, there should be a designated party to follow up after the testing,” said Huang Shangzhi. He believes that third-party testing laboratories, blood collection agencies, and prenatal testing centers should form a triangular closed loop to enable further management and counseling after screening.

Furthermore, Huang Shangzhi advocates for the early establishment of a genetic counseling system: “Genetic counseling can encompass many aspects of genetic services, such as determining which specialist to consult, selecting appropriate tests, and interpreting test results. Given that physicians are often heavily burdened with clinical duties and may not always keep pace with the latest understanding of gene-disease associations, these tasks can be effectively delegated to genetic counselors.”

In the field of birth defect prevention and control, genetic counseling can serve both prenatal genetic counseling and post-testing services.

“Explaining to patients what heterozygotes and mosaics are, and outlining the next steps, are all services provided by genetic counseling. Additionally, some patients experience significant psychological distress upon learning about their genetic factors; genetic counseling addresses these concerns through scientific explanations and evidence-based approaches to alleviate their anxiety.” Huang Shangzhi stated, “These services can provide substantial support to patients and are of great importance.”

Postscript

In the interview, Yao Hong likened the clinical adoption of NIPT to an act of immeasurable merit.

Indeed, the prevention and control of birth defects are matters of social significance and future consequence. Particularly against the backdrop of China’s national policy on eugenics and healthy childbirth, as well as the trend toward later marriage and childbearing, the disruptive impact of technologies such as NIPT on clinical practice and society at large cannot be adequately summarized in just a few words.

NIPT is merely the beginning of NGS technology’s clinical application. Today, NGS-based tumor detection products have entered the medical device approval process, and this technology is poised to create a new wave in clinical oncology.

Although the potential of NGS technology in the healthcare sector remains difficult to quantify, and it is unclear when new products will receive regulatory approval,But what is destined to come will eventually arrive.