Medical Device Link.

Originally Published IVD Technology May 2003

Commentary

Carolyn D. Jones and Luann Ochs

Carolyn D. Jones, JD, is associate vice president for technology and regulatory affairs, and Luann Ochs is chair of the CLIA working group at AdvaMed (Washington, DC). The authors can be reached via cjones@advamed.org and luann.ochs@roche.com, respectively.

Anyone who has been following the IVD industry for any length of time cannot help but notice the continuing debate among laboratory professionals, IVD manufacturers, and government officials over the Clinical Laboratory Improvement Amendments of 1988 (CLIA), particularly the CLIA waiver criteria. Why has this CLIA debate continued for so long?

The CLIA regulations introduced the concept of categorizing tests based on the complexity of the device as determined by the following criteria: knowledge; training and experience; reagents and materials preparation; characteristics of operational steps; calibration, quality control, and proficiency testing materials; test system troubleshooting and maintenance; and interpretation and judgment. The regulations describe three different categories for tests: high complexity, moderate complexity (including provider-performed microscopy), and waived. Waived tests would require the least amount of government oversight. 

The 1992 regulation (42 CFR sec. 493.15) indicated that waived tests are simple laboratory examinations and procedures that have been approved by FDA for home use or have been determined by the secretary of Health and Human Services (HHS) to have an insignificant risk of an erroneous result. These waived tests include those that employ methodologies that are so simple and accurate as to render the likelihood of erroneous results by users negligible; or the HHS secretary has determined pose no unreasonable risk of harm to patients if performed incorrectly.

This regulation also indicated a laboratory may qualify for a certificate of waiver if it restricts the tests that it performs to these waived tests. The 1992 regulation listed several analytes and test types that automatically qualify for waiver, and indicated that HHS shall decide whether other tests should be added to the waived category. Over the years, initially through CDC and currently through FDA, additional analytes and tests have been added to the list of waived tests.

The waiver criteria have been reconsidered and revisited several times by government officials, IVD industry leaders, and laboratory professionals. Laboratorians, government officials, and industry leaders have not always reached the same conclusions nor proposed the same process improvements when it comes to the waiver criteria.

At issue is whether the waiver criteria from the 1995 proposed rule, and the processes used by the health authorities, are the best available options. Is there another approach available to HHS that may meet the original congressional intent of ensuring reliable clinical lab tests, does not limit broad public access to new technologies, and optimizes the use of government resources? Is there an approach that will address concerns about quality without unnecessarily increasing the requirements for waived tests?

Determining Waived Status

Laboratory professionals, IVD manufacturers, and the government all understand that waived tests must be simple to use and accurate. IVD manufacturers are concerned that by constantly increasing the waiver requirements for a device, waived tests must not only be accurate, but they must be more accurate than tests performed in clinical laboratories. 

Many IVD manufacturers believe that moving the primary responsibility for CLIA categorization, including waiver determinations, to FDA would bring the focus back to the “simple” and “accurate” concepts initially envisioned by Congress. As a result of congressional concern over duplicate efforts within the government, FDA has had separate, but coordinated, responsibility for administering the provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including conducting device reviews and approvals as well as determining CLIA complexity criteria.

Under this act, FDA imposes unique and rigorous requirements on IVD manufacturers that commercially distribute IVD instruments, kits, and test systems. FDA pays particular attention to assuring that manufacturers have statistically proven the reliable performance of their devices and provided adequate instructions for use that are written at the educational level of the intended users. Under CLIA, FDA determines which IVDs are categorized into the moderate- and high-complexity designations, as well as the waiver status of those tests that qualify.

The benefits of this “one-stop shopping” have been realized for moderate- and high-complexity tests. FDA makes such complexity determinations concurrently with premarket reviews, thus giving laboratories access to new products and technology in a timely fashion. However, waiver determinations are performed after a product has completed the 510(k) or PMA/PLA process. 

Spurred on by modifications to CLIA included in the FDA Modernization Act of 1997, FDA has sought to use some out-of-the-box thinking to address waiver issues and has developed a guidance document that outlined an alternative approach to determining waiver criteria. This guidance was not widely accepted by CDC and Centers for Medicare & Medicaid Services (CMS), and was withdrawn as a proposal.

Making a Proposal

The CLIA working group at the Advanced Medical Technology Association (AdvaMed; Washington, DC) has developed a new CLIA waiver criteria proposal and submitted it for consideration to the government. AdvaMed has long been engaged in the debate over the proper interpretation and administration of CLIA. One of the goals of this working group is to ensure that waived laboratories continue to have access to innovative, easy-to-use, and accurate products.

Recently submitted to CDC, CMS, and FDA, this proposal attempts to address the many concerns voiced at FDA’s CLIA waiver workshop in August 2000. The proposal suggests what criteria should be used to assess tests for CLIA waiver and reexamines the definitions of “simple,” “accurate,” and “posing no increased risk of harm due to an erroneous result.” It also provides IVD manufacturers the flexibility needed to implement the waiver criteria and maintain physician and patient access to technology which was intended by Congress. 

Some of the elements of this proposal will be familiar to the laboratory community. For example, the criteria for defining “simple” remain essentially the same as the previous criteria utilized by CDC and FDA in their CLIA waiver reviews. 

However, the criteria for “accurate” have been significantly changed. IVD manufacturers responded to the laboratory community’s concern that waived tests need to have a certain level of accuracy by using new concepts. 

The IVD manufacturers’ proposal offers a study that compares results from the waived test device to results from a higher-order laboratory method. This type of study is consistent with international standards (ISO 17511) that require tests to be traceable to higher-order methods or materials.

The waived test’s performance must also be at a level of accuracy that provides clinically relevant information. It is incumbent upon manufacturers to establish that level, through review of the clinical literature or opinions from clinical experts.

In addition, the proposal institutes a risk assessment and risk mitigation approach to ensure that the likelihood of erroneous results by users is negligible. The term risk mitigation means that the manufacturer has provided a means of reducing the risk of errors to an acceptable level. This can be done through various means, such as onboard quality checks, error messages, or improved instructions for use. As with FDA pre-market requirements, manufacturers must provide proof in their CLIA waiver petition to FDA that their risk mitigation approach is effective.

The new waiver criteria proposal intentionally takes advantage of what is provided to FDA during 510(k) and PMA/PLA reviews to help ensure well-informed CLIA categorization decisions (i.e., risk management and labeling instruction decisions). Much of the debate surrounding the CLIA waiver criteria has been fueled by a lack of understanding as to what IVD manufacturers do to get a product to market and by concerns that waived laboratories may not be meeting their quality assurance obligations. This proposed waiver criteria is intended to establish a clearer roadmap for achieving waiver status.

Conclusion

Everyone must be aware that simply imposing a new set of CLIA waiver criteria will not make the quality problems in waived laboratories just disappear. IVD manufacturers must decide what role they will play in ensuring quality in the waived laboratories. At the same time, CMS acknowledges that the total responsibility for quality assurance in waived laboratories does not rest entirely on the shoulders of the manufacturers. The government, manufacturers, and laboratory community all have an important role to play in improving quality.

While the debate over waiver criteria may continue, IVD manufacturers will continue to develop technologies for waived laboratories. AdvaMed members will also continue to work with government agencies and the laboratory community to refine the CLIA waiver criteria proposal to address any remaining concerns. AdvaMed members are hopeful that an agreement can be reached on the waiver criteria so that waived tests are available to the community while raising the quality of the waived testing laboratory. 

Copyright ©2003 IVD Technology