That is the question: Whether ’tis nobler to use whole genome sequencing (WGS) and risk the slings and arrows of detecting a resident strain but better protect consumers; Or to attempt to guard against a potential sea of FDA troubles through ignorance? Although it may be better if I leave the drama to Shakespeare, if my humble attempt at updating the famous quote got your attention, I have served my initial purpose. But also realizing that many fine students resort to Cliffs Notes to understand the tragedy of Hamlet, following are my own “TAG Notes” on the current industry drama of whole genome sequencing (WGS): To use or not to use. It’s not the first time we’ve talked about WGS, and it’s unlikely to be the last: In a June newsletter, we discussed FDA’s new inclusion of WGS data in its National Antimicrobial Resistance Monitoring System (NARMS) report; in May we focused on FDA’s increasing use of WGS in its “seek and find” focus on Listeria in ready-to-eat foods; and back in December 2016, we briefly discussed industry use of WGS for environmental monitoring. CDC is using WGS on human isolates of important pathogens, and both FSIS and FDA are doing the same with Listeria monocytogenes (Lm) and Salmonella at a minimum when they find isolates in food or in food facilities. So, it’s obvious that FDA is focused on WGS as a valuable testing and tracking tool, but the question remains as to whether industry should WGS or not. In its discussion of WGS, FDA notes that testing has traditionally been done using methods such as PFGE (a test which produces a DNA fingerprint for a bacterial isolate), but that there are some strains of Salmonella spp. that PFGE is unable to differentiate. WGS, FDA states, “performs the same function as PFGE but has the power to differentiate virtually all strains of foodborne pathogens, no matter what the species. Its ability to differentiate between even closely related organisms allows outbreaks to be detected with fewer clinical cases and provides the opportunity to stop outbreaks sooner and avoid additional illnesses.” So why is there a question about using the latest and greatest technology? Primarily because of the expanded records access and copy authorities given to FDA through FSMA and the question as to whether a facility’s WGS findings can be, not only accessed and copied by regulators, but also added to the national database used by regulators and public health officials and tagged as from your facility. Once it is in the database, the strain can be used for comparison against any former or future WGS positive put into the database, potentially connecting your facility with an outbreak or recall – past or future. It also could be used as an indicator of a resident pathogen in your facility if a second FDA investigation finds the same strain in your plant at a future date. So let’s play out a scenario in which you are using the latest genetic tools – WGS, to identify potential problems in your manufacturing facility. You find a positive for Salmonella in zone 3 in your plant. You sequence it and, at the same time, deal with the issue in the plant. Eighteen months later FDA comes to visit because they have found Salmonella in one of your products at retail. The Agency asks for all your records for the past two years. You wonder if that includes the DNA sequence of the Salmonella from 18 months ago. But you decide to give FDA the WGS data. Questions from my little scenario: Would you be required to give your WGS data to FDA? If you did give FDA your WGS data, would FDA compare the sequence of the Salmonella you found with the one they just found at retail? If FDA did compare their WGS with yours and found them to be the same, would you be facing an issue of a “resident” strain of Salmonella in your plant for 18 months and therefore a potential recall of 18 months worth of production? In fact, a reading of FDA’s discussion of WGS makes it seem rather likely that FDA will, indeed, add any WGS data it gathers – its own or yours – to its open-access GenomeTrakr, as it is “coordinating efforts by public health officials to sequence pathogens collected from foodborne outbreaks, contaminated food products and environmental sources” and is focused on growing the size of the database, “so will its strength as a tool to help focus and speed investigations into the root cause of illnesses.” Additionally, FDA intends to use the data to “find the contamination sources of current and future outbreaks; to better understand the environmental conditions associated with the contamination of agricultural products; and to help develop new rapid methods and culture independent tests.” So, whether the agency can or does add the findings to its database, should fear really keep you from using the latest technology? And, could not doing so actually work against you? For example, if the WGS testing of environmental sampling of an FDA inspection elicits a positive which you did not detect with a different method (e.g., PFGE), could the agency ding you for not using the latest and greatest technology – particularly when it has publicly stated the value of WGS? Does the use of older testing methods negate any possible defense of due diligence? Additionally, should purely ethical and consumer-protection concerns compel you to use the best method possible to find and eliminate a resident pathogen? Just as classroom readings of Shakespeare often leave students with more questions than answers (even with Cliffs Notes), so, too, does WGS continue to leave industry with more questions than answers. It is a topic about which there needs to be continued discussion across the industry and between the public and private sectors. My personal view of this is that it would be a great shame if fear of regulatory action actually resulted in food companies using second best technology. However, there are already new technologies in the works that I was introduced to at IAFP, that will allow companies to get the same, or close to the same, fidelity of WGS without being exposed to the regulatory dilemmas linked to WGS discussed in this newsletter. About The Acheson Group (TAG) Led by Former FDA Associate Commissioner for Foods Dr. David Acheson, TAG is a food safety consulting group that provides guidance and expertise worldwide for companies throughout the food supply chain. With in-depth industry knowledge combined with real-world experience, TAG’s team of food safety experts help companies more effectively mitigate risk, improve operational efficiencies, and ensure regulatory and standards compliance. www.AchesonGroup.com
