MDDI Online is part of the Informa Markets Division of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC's registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 8860726.

4 Regulatory Challenges Facing IVD Companies Today

In vitro diagnostics companies are struggling to navigate an increasingly complex regulatory environment fraught with uncertainty.

In vitro diagnostics companies are struggling to navigate an increasingly complex regulatory environment fraught with uncertainty.

By Allyson B. Mullen

Allyson MullenIn vitro diagnostics (IVD) companies today are facing a number of challenges related to FDA regulation of their products and tests. And many of these challenges can be summed up with just one word: uncertainty. 

Many regulatory challenges for IVD companies relate to issues that are evolving and changing. Even where there appear to be clear regulatory requirements, it is not yet known—or not always reasonably foreseeable—how FDA will implement those requirements. In this article, we will examine four significant regulatory challenges facing IVD companies today.

1.  Regulation of laboratory-developed tests (LDTs). For more than twenty years, FDA has asserted that it has regulatory authority over LDTs, but it has chosen to exercise enforcement discretion over such tests. In recent years, however, FDA officials have publicly stated that more oversight of LDTs is needed, and that the agency plans to issue a guidance document on this topic. In fact, just last month at the Food and Drug Law Institute’s Annual Conference, Jeffery Shuren, director of CDRH, indicated that the draft guidance document is currently under administrative review. 

But we shouldn’t hold our collective breath waiting for the release and implementation of the final LDT guidance. After all, FDA will need to provide Congress with at least 60 days notice in advance of releasing a draft guidance document intending to regulate LDTs. The draft is expected to draw heavy criticism, which will further prolong the process. Even once an LDT final guidance document is issued, there will likely be a grace period for companies to achieve compliance. 

Still, even the issuance of a draft guidance is sure to raise questions and create new issues, such as what types of controls providers of LDTs should place on their suppliers. 

Without a solid understanding of how the regulatory environment in the LDT sector may change in the future, companies may find themselves facing the challenge of the unknown—unsure of how to plan for their regulatory future. The issuance of a draft guidance will undoubtedly heighten these anxieties. 

Keep up to date on the latest regulatory affairs issues at the MD&M East conference, June 9-12, in New York City.

2.  Enforcement action against RUO/IUO manufacturers. On November 25, 2013, CDRH issued the final guidance, “Distribution of In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions,” also known as the “RUO guidance.” This guidance is intended to aid companies in determining whether their product is properly labeled as being for research use only (RUO), investigational use only (IUO), or IVD use. RUO and IUO products are commonly sold to researchers and to laboratories developing LDTs. 

The RUO guidance emphasizes that FDA will review the totality of the circumstances when it comes to assessing whether a product is properly labeled as RUO or IUO. This approach is consistent with FDA’s traditional approach to enforcement. But we do not yet know how FDA will interpret the restrictions in the RUO guidance. For example, the guidance says that, “a manufacturer who produces only products labeled RUO whose sales force makes routine calls to clinical laboratories that do not perform research or clinical studies may be viewed as demonstrating its intent that its products be used for clinical purposes.” 

Until FDA provides clarity, we are not likely to know how FDA will try to enforce these limitations. Without an understanding of how FDA will enforce the RUO guidance, RUO and IUO product manufacturers may also find themselves in a state of uncertainty, unsure of whether or not they are in compliance.

3. Regulation of new and advancing technology. Historically, diagnostic tests were relatively simple and used well-established technology, such as immunoassays. Next-generation sequencing (NGS) and other novel genetic tests, however, are beginning to play an increasing role in diagnostic testing. Yet it is not clear how these new technologies will be regulated. 

Unlike older diagnostic tests, which produced a single result for a single analyte or disease, NGS results hold limitless possibilities with regard to diagnostic and prognostic information. Further, as new variants are identified, the genetic sequences can continue to be used to guide patient diagnosis and care. This flexibility, though, bumps up against a more rigid, fixed, regulatory system. 

Given the variety of regulatory pathways available to companies—including the ability to not be regulated by FDA as an LDT or RUO—FDA will need to give companies confidence that it has a plan for regulating these emerging technologies in order for companies to voluntarily seek premarket clearance or approval for their new tests. In particular, FDA will need to convince companies that there is a clear regulatory pathway and expectations that are not unduly burdensome or fraught with uncertainties. 

4.  Inconsistent requirements for IVD premarket submissions. For many IVD manufacturers, the path to clearance or approval has been marred by changing requirements and delays, including the need to educate FDA on their products and technologies. Over the past few years, FDA’s requirements, particularly with regard to 510(k) notifications, have increased, requiring more data and detail than in the past. This change has resulted in unpredictable premarket submission requirements. 

In addition, FDA’s data requirements for IVD submissions have not always been reasonable. Take liquid chromatography and mass spectrometry (LC/MS), for example. LC/MS is gaining popularity in clinical diagnostic labs because it does not suffer from metabolite interference issues like traditional immunoassays. In light of the basic scientific difference in the technology between LC/MS and immunoassays, it would seem logical that certain tests may not be required for new LC/MS assays. However, we are aware of instances in which FDA requested that testing be performed for assays when it was scientifically meaningless, such as metabolite interference testing for LC/MS assays. 

Further, FDA has struggled when there is no standardized method or cut-off for an analyte. These issues can cause difficulty for companies that wish to go down the path of 510(k) clearance, but find themselves at a loss trying to anticipate FDA’s requirements or respond to FDA’s questions.

It is difficult enough from a business perspective for a company to decide whether it wants to be in the business of diagnostics, RUOs, or LDTs. When regulatory uncertainly is added to the business decision, IVD companies are facing a daunting and challenging time. Only time will tell how FDA will regulate LDTs and how it will enforce the RUO guidance. 

Keep up to date on the latest regulatory affairs issues at the MD&M East conference, June 9-12, in New York City.

 Allyson B. Mullen is an associate at the law firm of Hyman, Phelps & McNamara, P.C., where she provides counsel to medical device and IVD manufacturers.


[Image courtesy of Stuart Miles/FREEDIGITALPHOTOS.NET]

500 characters remaining