Antibody Tests and Regulatory Reforms: Why Delegating Pre-Market Control to Private Companies is a Bad Idea

Image: @fusion_medical_animation

Sarah Rozenblum and Holly Jarman

As of early May 2020, the United States continues to struggle with an insufficient level of diagnostic testing. While the number of tests available is increasing, it remains far too low (between 1 and 2 million per week) to provide an adequate response to the COVID-19 pandemic. In the early months of the outbreak, the FDA was criticized for having been too slow to approve coronavirus diagnostic tests. More recently, the FDA has incentivized manufacturers to develop antibody tests—which indicate whether an individual has been exposed to the virus and developed immunity to it—as quickly as possible. Loosening standards for antibody tests seems to be a response to initial critics of the agency’s sluggish approval of diagnostic tests, but this approach is paving the way for further short- and long-term public health problems.

In March 2020, the FDA waived initial quality reviews of antibody tests (serological tests), allowing manufacturers to quickly put tests on the market without agency approval. This new policy allowed manufacturers to validate their own product and bring them to the market without agency review, as long as they included a disclaimer with test results. Dozens of companies developed antibody tests, with 155 different tests available on the market in May 2020. 

The new policy was widely criticized for allowing tests that were not reliable and prompted a congressional investigation. The American Medical Association (AMA) asked the US Department of Health and Human Services (HHS) to restrict the use of antibody tests to health care professionals trained in epidemiology. The FDA consequently reversed its policy on May 4th, asking test manufacturers to apply for emergency use authorization within ten days after their products reach the market. Under this policy, manufacturers must suspend distribution if their test does not meet the FDA’s specificity and sensitivity criteria.

In the US, delegating pre-market controls to private companies generated more problems than it solved. Looking at the European medical devices regulation framework could have helped the US anticipate the type of difficulties that arose in March and April 2020. Indeed, the European experience reveals the problems that emerge from weakening standards for tests or medical devices. In the European Union, there is no equivalent to the FDA’s pre-market evaluations for medical devices. Instead of a process to ensure general standards of safety and effectiveness before they reach the market, stakeholders primarily seek to determine whether medical devices function as intended. 

For the EU’s Class III category of high-risk devices, entities known as Notified Bodies perform all quality assessment before devices are commercialized. Crucially, Notified Bodies are almost exclusively private companies that earn their revenue from the fees they charge manufacturers. Notified Bodies therefore have strong incentives to review devices positively, while government regulators representing the public interest have limited oversight over this process.

In practice, this means that high-risk medical devices (such as hip replacement or pacemakers) tend to be authorized more quickly in the EU than in the US, where clinical trials are required and the FDA plays an active role in evaluating devices before they are commercialized. But the greater speed of authorization has come at the cost of quality and safety.

As a result of these regulatory choices, thousands of patients around the world have been exposed to medical devices with serious adverse effects, including defective breast implants, vaginal mesh and hip replacements. One significant scandal concerns defective breast implants manufactured with unapproved silicone gel. Manufactured in France, they were sold in 65 countries for ten years with official authorization. The FDA, which required tougher standards for implants, had banned them from the US market as early as 2000. They were only withdrawn from the French market in 2010 because of their high rupture rates and because investigations had shown that their manufacturers had used industrial silicone to save money. Limited requirements for pre-market assessment and post-market oversight in the EU failed to reveal the defects in these devices. 

The case of loose medical device regulation in Europe shows that without assessments for quality review by public agencies, there is a serious risk of putting unreliable products into circulation. Furthermore, because of the commercial interest of manufacturers and Notifying Bodies in maintaining the status quo, it took European countries years to address the widely known consequences of the EU’s lax framework. The framework was finally revised in 2017 to be stricter and more transparent. After the revisions, the scale of deficiencies in the system quickly became clear, with many Notified Bodies unable to meet the tougher requirements.

There are already signs that the European experience is repeating itself in the United States, as inaccurate antibody tests are now flooding the market. On April 24th, the House Oversight Committee expressed concern in a report over the “numerous companies [that] appear to be marketing fraudulent tests.” According to the report, the FDA “failed to police the coronavirus serological antibody test market.” A team of researchers at UCSF, seeking to fill the regulatory gap left by the FDA, found that out of 14 tests examined only three generated consistently reliable results. Some of the tests examined produced high numbers of false positives, incorrectly identifying patients as having antibodies for the coronavirus.

From a public health perspective, loosening quality assessment procedures for antibody tests could have a dramatic impact. False positives can easily mislead people into thinking that they have already been infected or are immune, leading them to return to work or socialize without masks and other precautions. Results that exaggerate levels of immunity could also incentivize local and state authorities—particularly those already eager to “reopen” their economies— to relax social distancing restrictions prematurely, exposing their constituents to a violent second wave of infection. Public health officials, already busy containing the epidemic, must now decide which test they want to use. This could lead to investing precious resources in potentially defective tests.

Relying on private companies, as the European example suggests, can generate unintended difficulties. The FDA’s decision to reintroduce quality standards and retain control over antibody test manufacturers will help ensure that states’ transition strategies are grounded in accurate data.