The Honorable Robert Califf Comissioner U.S. Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, Md. 20852

Response to Docket No. FDA-2023-D-5365: Draft Guidance entitled “Consideration of Enforcement Policies for Tests During a Section 564 Declared Emergency” and “Enforcement Policy for Certain In Vitro Diagnostic Devices for Immediate Public Health Response in the Absence of a Declaration under Section 564”

Dear Commissioner Califf:

The American Society for Microbiology (ASM), one of the oldest and largest single life science societies with 36,000 members in the United States and around the world, whose mission is to promote and advance the microbial sciences, is pleased to comment on the 2 proposed draft guidance documents, entitled “Consideration of Enforcement Policies for Tests During a Section 564 Declared Emergency” and “Enforcement Policy for Certain In Vitro Diagnostic Devices for Immediate Public Health Response in the Absence of a Declaration under Section 564” stemming from FDA’s Final Rule on Medical Devices; Laboratory Developed Tests [Docket No. FDA-2023-N-2177]. 

ASM members perform testing for the diagnosis of infectious diseases in clinical, commercial and public health laboratories in a range of urban and rural settings, including, but not limited to, academic and university-based medical centers, large health care systems, private and public community hospitals, independent laboratories and public health departments. ASM shares the FDA’s goal of protecting public health by ensuring the safety and accuracy of laboratory developed tests (LDTs) and health equity. We appreciate the opportunity to comment on factors the FDA will consider when deciding to issue enforcement policies for unapproved tests and unapproved uses of approved tests both during and in the absence of a public health emergency (PHE). Our comments focus on the FDA’s use of enforcement discretion in the lead up to a possible PHE and the time needed for test development, the need to include non-governmental laboratories in response to local health issues or outbreaks, the importance of consulting with stakeholders in the lead up to a PHE and eliminating gaps in rapid testing that impact patient care. 

FDA should carefully consider the timing needed for test development in the lead up to the declaration of a PHE. While FDA does not directly declare a PHE, they play an important role in ensuring laboratory testing capacity is ready and in compliance when needed. Therefore, FDA must carefully consider when enforcement discretion should be used as new public health situations arise. Each pathogen with potential for significant public health impact requires careful monitoring and rapid response. However, the response approach and timing vary by the pathogen, with factors including its transmission mode (e.g., airborne vs. fecal-oral route) and rate, as well as associated mortality and morbidity and potential to disrupt society (e.g., exceeding medical resources). While it is appropriate for FDA to have discretion, FDA should carefully consider the time needed for test development with the timing of a declared PHE and additional flexibility for emergency use authorization (EUA) submission when relevant. In the case of COVID-19 and mpox, the PHE was declared too late, leading to a significant delay in widespread accurate testing, which led to further transmission, infections and death, while straining health care systems and resources. FDA should consider these examples in the future and allow for enforcement discretion in cases like this before a formal PHE is declared. 

Sentinel laboratories are critical to combating outbreaks and responding to local and national emergencies and should explicitly be covered under enforcement discretion in order to best serve their patient populations. Patients initially present to their local health care systems and these laboratories serve them as the first line for diagnostic testing. The draft guidelines state that laboratories operating under an agreement (formal or informal) with the U.S. government are under enforcement discretion during a declared PHE, but “an agreement” needs to be clearly defined. While all labs are required to report nationally notifiable diseases to their local public health entities and thus have working relationships with public health labs (PHLs) (e.g., clinical laboratories are part of the laboratory response network), it is unclear whether this relationship would qualify labs to operate under enforcement discretion in the absence of a declared PHE as outlined in the guideline. 

FDA should consult with stakeholders in the lead up to a possible emergency and in the absence of one to determine if labs outside of PHLs need to be developing tests. Keeping clinical and commercial labs on the sidelines causes delays and testing restrictions that are costly and cause confusion. The proposed policy for emergent situations will lead to many of the most skilled and innovative labs being forced to sit on their hands. 

In the absence of a declared PHE, testing is restricted to government labs. While public health labs in larger states, counties or municipalities may be more capable, those in smaller states and counties may have more limited capacity. This can negatively impact rural or underserved communities that experience local infectious disease outbreaks such as mpox, hantavirus and measles. PHLs need to be able to utilize assays developed by their state and regional labs to facilitate appropriate widespread testing. As states vary in the number of PHLs within their network, with some having dozens of regional PHLs, it is not feasible for each PHL within a state to submit individual applications for FDA approval of the same assay. ASM recommends that FDA consider a mechanism that would provide conditional reciprocity. Moreover, many CLIA high complexity clinical labs are well-positioned to support their locale and employ scientists with the knowledge needed to develop diagnostic tests and enhance PHL capacity. 

The factors that FDA plans to consider during a PHE are not comprehensive and will lead to gaps in accurate, rapid testing impacting patient care. While the FDA provides a list of items to consider in an emergent situation, ASM recommends that the FDA include these additional considerations: specimen type (some tests or diseases involve sampling of low-risk specimens such as nasal swabs, while other tests may require serum sampling), volume of tests submitted and performance of available diagnostics. High-volume tests can easily and quickly overwhelm the public health system as seen with mpox and COVID-19. This leads to clinically significant delays in testing. In the absence of a 564 declaration, laboratories need guidance on what qualifies as an emergent situation (e.g., clarity on whether a non-novel pathogen causing a regional outbreak of a non-endemic disease or if there is an increase in vaccine preventable diseases constitutes as emergent).

Important non-emergency ongoing public health issues are not covered in these guidelines, creating a substantial deficit in necessary diagnostics. Many public health conditions are diagnosed using LDTs (e.g., vaccine preventable diseases, such as measles; vector-borne diseases, such as Dengue, and other communicable diseases of public health concern, such as tuberculosis; and detection of drug resistance). This testing is typically performed by the PHLs after consultation with the care provider, clinical laboratory and infectious disease experts in health departments, and results are utilized in both patient and outbreak management. Without continued enforcement discretion, PHLs are unable to continue to provide critical diagnostic testing for which there is limited or no capability/capacity in the private sector. PHLs are essential in supporting specialized populations and those who would otherwise lack the testing to receive an accurate diagnosis. 

Conclusion

ASM agrees that ensuring accuracy of diagnostic tests is essential to patient safety, high-quality patient care and the effectiveness of public health interventions. However, these guidelines as written do not fully account for the uniqueness of each situation and the integral and complementary roles of public health/clinical laboratories and commercial manufacturers in combating both local and national public health issues. As demonstrated by the COVID-19 pandemic, delays in declaring a PHE and stringent restrictions placed on both commercial manufacturers and clinical laboratories prevented widespread accurate testing. The ability of both clinical and public health laboratories as well as commercial manufacturers to respond to emerging or ongoing infectious disease issues within their patient populations is essential for accurate, timely and accessible diagnostics to improve patient care.

We appreciate your consideration of our views. If you have questions, you may contact Allen Segal, Chief Strategy and Public Affairs Officer, at asegal@asmusa.org.

Sincerely,



Linoj P. Samuel, Ph.D., D(ABMM) 
Chair, ASM Clinical and Public Health Microbiology Committee