Ensuring food safety in this "New Era of Smarter Food Safety" amid the increasing use of whole genome sequencing (WGS) provides many new challenges for food safety professionals, including how to apply new tools and interpret findings obtained with them in the context of laws and regulations that have been around for decades. While these challenges are many and multi-faceted, it is helpful to look back to the "old" era of food safety, to some of the foundational concepts and definitions established in the initial 1938 Food, Drug, and Cosmetic Act (21 U.S.C. §331); hereafter referred to as the "FD&C Act") that are still in full force today.

This article focuses on one of many important legal terms housed in the FD&C Act that is extremely important and often misunderstood—the definition of "adulteration."

What Constitutes Adulteration?

The concepts of adulteration and misbranding appear in several U.S. regulations. The key regulations pertaining to food are the FD&C Act mentioned above, the Federal Meat Inspection Act (FMIA) (21 U.S.C. §610; 9 C.F.R. 301.2), the Poultry Products Inspection Act (PPIA) (21 U.S.C. §458; 9 C.F.R. 381.1) and the Egg Products Inspection Act (EPIA) (21 U.S.C. §1037; 9 C.F.R. 590.5).

This article takes a closer look at the definition of adulteration found in the FD&C Act, given its broad application to most of the food produced in the U.S. The majority of these foods are regulated by the U.S. Food and Drug Administration (FDA). The article will also touch on USDA relevant definitions of adulteration to illustrate the broad impact of changing technologies on how adulteration is defined.

By gaining a deeper understanding of what constitutes an adulterated food, food safety professionals will be better equipped to tackle the challenges that lay ahead in "FSMA 2.0" (the authors' reference to 2021–2031—the second decade after FSMA, coupled with the FDA's New Era of Smarter Food Safety Blueprint).

What may be surprising to learn is that a food is defined by FDA as "adulterated" if it meets any one of seven primary definitions of adulteration. A number of these definitions will be determined, or at least influenced, by the use of modern tools and technology, such as WGS. Each of these primary seven definitions (per FDA regulation) will be cited, followed by an overview as to how these definitions have been applied in the past and how they will be impacted by the application of new tools, such as WGS, in the future.

Each definition of "adulterated food" is taken verbatim from its source in 21 U.S.C. §342: Adulterated Food, and then discussed in context of its impact on the New Era of Smarter Food Safety and new tools. Note: While the authors base much of the analysis on FDA's definitions of adulteration, the definition of adulteration for the purposes of USDA-regulated product is nearly identical to FDA's definitions (see 9 C.F.R. §301.2). Hence, this analysis applies equally to meat, poultry, and eggs (regulated by USDA), and is prone to new importance and new interpretations with the use of WGS.

Dissecting the Definition of Adulteration

First Definition

Definition 1 of adulteration comes from 21 U.S.C. §342 (a)(1): Poisonous or Deleterious Which May Be Injurious to Health: "A food shall be deemed to be adulterated (1) If it bears or contains any poisonous or deleterious substance which may render it injurious to health; but in case the substance is not an added substance, such food shall not be considered adulterated under this clause if the quantity of such substance in such food does not ordinarily render it injurious to health."

This may be the clause that most people think about first when considering whether a food may be deemed adulterated. This clause is most often cited in regulatory violations and is essentially what is applied when defining a ready-to-eat (RTE) food that contains a pathogen (e.g., Listeria monocytogenes or Salmonella) as adulterated. The second part of this definition, on the other hand, is one where WGS and improved detection of outbreaks have a larger impact. The phrase "not an added substance" refers to foods where it could be argued that a given pathogen is naturally present (for the sake of argument, let us use the example of Salmonella on raw poultry and, hence, on the raw meat derived from a slaughtered animal), which would mean raw chicken with Salmonella that was present in the live animal is, at least currently, not considered adulterated.  

The challenge, however, comes with the phrase, "…if the quantity of such substance in such food does not ordinarily render it injurious to health." With improved outbreak detection methods, more and smaller outbreaks are being detected and linked to products such as raw meat and poultry. Detection of such an outbreak could then be interpreted as indicating that the quantity of the organism present was sufficient to make the food in question injurious to health. This essentially leaves the determination of whether the food is adulterated up to the interpretation of "ordinarily." 

What "ordinarily" makes food injurious to health? This phrasing is open to debate and potential litigation. (And we thought dealing with standards such as "reasonable" and "credible evidence" were difficult to interpret! Enter "ordinarily"—yet another subjective, vague term that lacks substantive case law or other precedent to aid understanding.)  

While admittedly subjective, let us consider this term in light of the increasing use of WGS. With the use of WGS, we may start to see that certain pathogens "naturally found" in non-RTE (n-RTE), raw products, and specifically raw meat and poultry may be more often present in quantities that can cause human illness than previously assumed. If we can quantify pathogens at a level that has caused illness in the past, is it a leap to think that finding those similar levels again would rise to being viewed as "ordinarily" injurious?

As detection tools advance and become more sensitive, the ability to quantify what was historically next to impossible to detect is now a reality, sparking some unique debates. For example, WGS may detect one outbreak with a few cases arising once every 10 years that is caused by a product that is consumed at extremely high volumes (e.g., hundreds of millions of pounds in a year). Does this mean that the levels of pathogens found "ordinarily" cause disease? The larger policy implications of these findings (e.g., whether certain Salmonella subtypes should be considered adulterants in raw poultry) will likely be a topic of intense debate. Regardless, as these technologies advance, it may mean that we see an increase in the number of cases where these types of products are considered to be adulterated.  

Second Definition

Definition 2 of adulteration comes from 21 U.SC. §342 (a)(1)(2)(A)-(2)(C): Added Poisonous or Added Deleterious Substance; Unsafe Pesticide Chemicals and Food Additives: "A food shall be deemed to be adulterated [….] (2)(A) if it bears or contains any added poisonous or added deleterious substance (other than a substance that is a pesticide chemical residue in or on a raw agricultural commodity or processed food, a food additive, a color additive, or a new animal drug) that is unsafe within the meaning of section 346 of this title; or (B) if it bears or contains a pesticide chemical residue that is unsafe within the meaning of section 346a(a) of this title; or (C) if it is or if it bears or contains (i) any food additive that is unsafe within the meaning of section 348 of this title; or (ii) a new animal drug (or conversion product thereof) that is unsafe within the meaning of section 360b of this title."

Note this subsection lists a plethora of vehicles that may render a food adulterated—pathogens, pesticides, food additives, and animal drugs. This illustrates the reality that there are far more than the initial seven definitions outlined in section 342 when all of the sub-subsections are considered! This article, however, will examine only sub-subsection 2(A), which applies to foodborne pathogens and represents a provision where WGS could have a considerable impact on the number of products that are classified as adulterated.  

This can be best illustrated with the case of Salmonella presence in raw meat and poultry—the assumption typically is that contamination was introduced with the live animals and was "naturally present" at levels not ordinarily injurious to health. However, with increasing use of subtyping methods (particularly WGS), it will be easier and more common for regulatory agencies to find evidence that a specific Salmonella subtype was persistently present in a slaughterhouse, with this contamination leading to Salmonella contamination of raw meats in the slaughterhouse, meaning Salmonella was added to the raw meat and poultry. Under this provision, the product is classified as adulterated. Hence, it may be prudent for industry to further enhance control of Salmonella persistence in slaughterhouses and to prevent cross-contamination to reduce the risk of product being declared adulterated.

“A transparent roadmap of how WGS will be used by regulatory agencies to define insanitary conditions would be of tremendous help to industry and could even drive increased use of WGS…"

Third Definition

Definition 3 of adulteration comes from 21 U.S.C. §342 (a)(1)(3) and (a)(1)(4): Unfit for Food, Filth, Insanitary Conditions: "A food shall be deemed to be adulterated [….] (3) if it consists in whole or in part of any filthy, putrid, or decomposed substance, or if it is otherwise unfit for food; or (4) if it has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health."

Provision (4) is one that may have been most impacted by subtyping methods and specifically WGS. In the distant and not-so-distant past, insanitary conditions in a food processing facility typically would mean presence of pests (think rodents) or other visually observable issues. However, WGS data is being used more often to define (or help define) a facility as operating under insanitary conditions. WGS can provide evidence that a pathogen (e.g., Listeria monocytogenes, Salmonella) survives in a facility over months or years, as supported by isolation of "identical" or "closely related" pathogens from processing plant environments and finished product over time, which can be interpretated as indicating failure of sanitation and hence "insanitary conditions."

This is not just theory; a number of FDA warning letters use WGS data to support that a facility appears to operate under insanitary conditions. While the nuances of WGS interpretation can, and sometimes should, be argued (e.g., when are two isolates closely related, and could closely related isolates be found in two different locations? etc.), the use of WGS data to identify insanitary conditions is here to stay, and food safety professionals must consider it.

A transparent roadmap of how WGS will be used by regulatory agencies to define insanitary conditions would be of tremendous help to industry and could even drive increased use of WGS by industry if there were some assurance (e.g., safe harbor) that WGS data generated by industry will not be requested and used by regulatory agencies against industry when they lack their own evidence for insanitary conditions.

Fourth Definition

Definition 4 of adulteration comes from 21 U.S.C. §342 (a)(5)-(a)(7): Diseased Animals, Packaging, Radiation. For completeness, we also list the adulteration provisions (5), (6), and (7) below: "A food shall be deemed to be adulterated [….] (5) if it is, in whole or in part, the product of a diseased animal or of an animal which has died otherwise than by slaughter; or (6) if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health; or (7) if it has been intentionally subjected to radiation, unless the use of the radiation was in conformity with a regulation or exemption in effect pursuant to section 348 of this title."

For these three provisions, there is no clear indication for how WGS and other new technologies used as part of the New Era of Smarter Food Safety and similar initiatives may impact the frequency with which foods are considered adulterated, with the possible exception of (5) where new technologies may make it more likely and easier to identify a product as coming from a diseased animal.

Consequences: Are They Real, or is it Fear-Mongering?

A natural question at this stage may be: "What are the consequences of violating one of the definitions of adulteration?" Is there a real adverse risk to business, or are these definitions mainly "academic" (often used to mean practically irrelevant)? While this topic could warrant its own, dedicated article, a summary is provided to indicate the importance of this topic.

Per 21 U.S.C. §331 (summarized by the authors): The following acts ... are prohibited: (a) The introduction ... into interstate commerce ... of any food ... that is adulterated or misbranded. (b) The adulteration or misbranding of any food ... in interstate commerce... (c) The receipt in interstate commerce of any food ... that is adulterated or misbranded… (e) The refusal to permit access to or copying of any record as required… (f) The refusal to permit entry or inspection.

Note to meat, poultry and egg producers: The concept of "prohibited acts" applies to you, too. Additional descriptions of prohibited acts are:

• No person ... shall, with respect to any cattle, sheep, swine, goats, horses, mules, or other equines, or ... meat or meat food products of any such animals ... sell ... any such articles ... which ... are adulterated or misbranded … (21 U.S.C. §610).
• No person shall ... sell ... any poultry products which ... are adulterated or misbranded ... (21 U.S.C. §458).
• No operator of any official plant shall allow any egg products to be moved from such plant if they are adulterated or misbranded … (21 U.S.C. §1037).

Penalties for committing a prohibited act range from product seizures and injunctions against operating, to fines (some in very large sums) and imprisonment. See 21 U.S.C. §333 and a summary of FDA enforcement actions,¹ and do not forget the Parnells from the Peanut Corporation of America incident!

Takeaway

In summary, it is important for food safety professionals to understand the details of both the old and new regulatory frameworks to protect public health and to proactively identify enterprise risks that may result from interpretation of "old" laws with evidence generated by "new" tools and "new" regulatory vision.

While existing definitions of adulteration may be viewed as solely "hazard"-based and not consistent with the idea of "risk"-based food safety management, for now the current legal definition of adulteration is the reality of food safety. Long term, however, we hope and expect that the definition of adulteration will adjust to allow for a more risk-based approach to food safety.

References

1. U.S. Food and Drug Administration. "Types of FDA Enforcement Actions." November 6, 2017. https://www.fda.gov/animal-veterinary/resources-you/types-fda-enforcement-actions.