“Modernization” is a popular word right now in food safety circles. The word “modernization” was introduced into the American lexicon in the mid-1700s and is commonly used to imply upgrading, refurbishing, reinventing and reimagining. From a popular cultural standpoint, a vivid example of modernization involves historic Wrigley Field, the home of baseball’s Chicago Cubs. Built in 1914, the ballpark is undergoing a 5-year, $750 million renovation—replete with Jumbotron scoreboards, LED screens, elevators, a five-star hotel and refurbished bleachers—that will bring the stadium into the 21st century.

The Food Safety Modernization Act (FSMA), often described as the nation’s most sweeping food safety reform in more than 70 years,[1] aims to shift the U.S. mindset from response to prevention in the ongoing battle against food contamination. In light of this new era in food safety, it is critical for suppliers and manufacturers to reshape, reinvent and reimagine their approach to ensuring the safety of food ingredients.

The modern toolbox for food ingredient safety may soon include a revamped GRAS (generally recognized as safe) process, new analytical targets detectable with new technologies and an overarching drive to improve transparency and consensus among industry stakeholders to verify the safety of new ingredients before and after they are brought to market.

Is GRAS Obsolete?
The U.S. Food and Drug Administration (FDA) is responsible for premarket safety evaluations of new food ingredients and additives based on a 1958 amendment to the Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act. However, to avoid the costly and time-prohibitive processes, some new food ingredients were eligible for GRAS notification or even “self-determination.”  

For nearly four decades, the agency affirmed each request for GRAS status, but stopped after 1997, replacing it with a simpler notification process. Companies wishing to notify FDA about a new ingredient provide the agency with datasets. Such data include details about the chemical structure, purity and other technical specifications for the compound, as well as data that allow FDA to estimate the EDI (estimated daily intake) as well as the ADI (acceptable daily intake). These datasets include a variety of safety tests including animal feeding studies as well as clinical studies using healthy subjects to assess human reactions in a controlled setting. Under certain circumstances, other scientific data, as well as analytical methods, methods of manufacture and/or accepted scientific principles, could be relied upon as part of the technical information.[2]

The number of companies using this process increased, but did this streamlined process come at a price?

One drawback of the GRAS notification process was the lack of public notice and the option for public comment. When FDA was affirming GRAS requests, there was a mandatory notification and comment period because FDA was essentially issuing a new rule to allow for the use of the proposed ingredient. Critics of the GRAS process claim that the reduced public notice has lowered the transparency of the process. A recent article documented potential conflicts of interest, as well as a reliance on a small pool of consultants for the GRAS panels.[3]

The self-determination process has drawn even more controversy. Called a loophole by some, it allows many ingredient companies to bypass the notification process altogether. While datasets are not turned in to FDA, the petitioner collects the same type of data, convenes an expert panel and documents the findings, in case FDA asks to review.

Some consumer groups have characterized the self-determination process as rife with conflicts of interest, stating that lenient rules allow food companies to add potentially harmful chemicals to the GRAS list without oversight or consequences. Not surprisingly, these groups are pressuring FDA to increase its scrutiny of the program.

Is there evidence that the current GRAS notification and self-determination processes have allowed harmful ingredients to enter our food system?

While some ingredients are controversial, some experts concede that there do not seem to be specific examples of harmful ingredients. “The existence of some controversy does not disqualify a GRAS conclusion.”[2] Further, “the concept of consensus among qualified experts does not mean there must be unanimity of opinion about the safety of the use of a GRAS substance.”[2]

FDA will move to rescind a specific GRAS status should new data be generated that call the safety of a previously certified ingredient into question, but the new data would be considered along with all relevant data before making this decision. Claire Kruger, Ph.D., president of Spherix Consulting, concludes, “Fortunately, the GRAS procedure is by its very nature a flexible process, able to encompass scientific advances in a robust, comprehensive and transparent safety evaluation process. The GRAS process allows the rapid inclusion of new scientific advances into the risk-assessment process.”[4]

Despite potential drawbacks to the current pathways to GRAS, the track record of the industry has been good. But there are initiatives afoot that will likely bring changes to the GRAS process, thereby modernizing this tool for food ingredient safety determinations.

One driving force seems to be FSMA itself. The rule mandates more strenuous supplier management verification, which is spurring companies to perform “due diligence to make sure their GRAS determinations will pass muster with the FDA.”[5]

In fact, the Grocery Manufacturers Association (GMA) has a task force focused on modernizing GRAS. “Before the dust settles, we anticipate more ingredient manufacturers will opt to submit notices to FDA rather than make independent self-GRAS determinations,” says Ed Steele, Chairman and CEO of EAS Consulting Group. Steele adds, “These manufacturers will be turning to reputable consulting firms like ours for assistance.”[6]

Along with the move to make GRAS more transparent, more data on the human impact of new ingredients are also on the horizon. Animal studies provide key pieces of the GRAS dataset, but safety and tolerance data from controlled human studies are also needed to round out the body of knowledge about new proposed ingredients. 

Market Approach
The safety of food ingredients once they are in the marketplace is an ongoing concern and challenge to our industry. As new ingredients are launched, the R&D team becomes less involved, largely giving way to the quality assurance (QA)/food safety team. Food scientists, QA experts and food safety leaders work together to create systems to assess the risk level for each ingredient across a wide range of potential hazards.

Included in this toolbox are a number of components, such as environmental monitoring of the processing plant and equipment, incoming test protocols to determine level of contamination preprocessing, and postprocessing verification of the ingredient before sale. Physical, chemical and microbiological methods are utilized ubiquitously, although for each ingredient type, customized tests are often employed.

For some ingredients, the processing step plays a huge role in improving their safety. Many processes provide a lethal heat treatment or other means, such as nonthermal, high-pressure processing, to reduce the microbial load of the ingredient, most notably the reduction of the pathogen level. Research studies, such as challenge studies, are not a new tool, but there is growing emphasis under FSMA to use these and other accepted scientific tools to verify the effectiveness of lethal processes for new ingredients in specific facilities.

The National Advisory Committee on Microbiological Criteria for Foods advises that several factors should be taken into consideration when conducting challenge studies either internally or externally via a contract laboratory. First and foremost, challenge studies must be designed and evaluated by an expert food microbiologist.[7]

Choosing an outside laboratory requires careful consideration because not all labs possess the expertise to design challenge studies and the quality control procedures necessary to produce valid results that will be accepted by regulatory authorities or other reviewers. Laboratories may be certified by various organizations and state or federal agencies for various types of testing. However, these certifications do not necessarily qualify a laboratory to design and conduct microbiological challenge studies. Some laboratory groups publish scientific papers on food safety-focused research studies, so this can be used as one potential indicator of expertise.

If a new ingredient cannot be processed to achieve a sufficient level of food safety, then this ingredient would be considered a high-risk ingredient, leading to ramifications for any subsequent use in a finished product. 

A Question of Fraud
Food fraud is a problem that has captured the attention of industry stakeholders throughout the food chain. This topic is not new and stretches back centuries. In 1820, Friedrich Accum, a German chemist whose most important achievements included advances in gas lighting, wrote a book, Treatise on Adulteration of Food and Culinary Poisons.[8]

GMA estimates that fraud may cost the global food industry between $10 billion and $15 billion per year, affecting approximately 10 percent of all commercially sold food products. Fraud resulting in a food safety or public health risk event could have significant financial or public relations consequences for the food industry as a whole or a food company specifically.

Analytical tools and technologies to detect food fraud have made significant leaps and bounds since the early 20th century. From simple tests to detect added starches in milk to state-of-the-art methods to detect melamine in meat, today’s analytical procedures are precise and highly sophisticated. Technologies such as liquid chromatography-mass spectrometry and DNA sequencing have made it possible to identify melamine and other harmful chemical adulterants at very low detection limits.

While melamine has largely become the poster child for adulterants in the minds of many consumers, the European Commission recently published a top-10 list of the most frequently adulterated foods: olive oil, fish, organic foods, grains, honey, coffee, spices, wines and fruit juices. Furthermore, there are two types of adulteration, which can typically be grouped into two categories: where and what.

Where applies to geographic origin, as in, for example, basmati rice (which should come from the foothills of the Himalayas), extra-virgin Italian olive oil, Swiss cheese and Black Forest ham. What applies to adulterants. Examples again include basmati rice, extra-virgin olive oil and coffee.

For basmati rice, the question is related to not only where the rice comes from but also which variety the rice is. By definition, at least one of the parents has to be a historical basmati landrace variety. If none of the parents is, the rice cannot be called basmati, even if it originates in the foothills of the Himalayas.

For extra-virgin Italian olive oil, it must be determined whether it is 100 percent extra virgin and whether it is 100 percent olive oil. Incredibly, there have been times when more “Italian olive oil” has been on the world market than could have been produced from all the olive trees in Italy. There are a number of methods to identify this type of fraud. One of the most promising is the principal component analysis approach. Employing a number of authentic samples from places such as Italy and other olive oil-producing countries, it is possible to distinguish different types of oils. In addition, powerful computers and algorithms make it easier to make distinctions. DNA-based methods for verification of authenticity are becoming more common as a tool in the fight against food fraud.
Virus Detection
Viruses are a leading cause of foodborne illness in the United States. According to the U.S. Centers for Disease Control and Prevention (CDC), viruses account for more than 50 percent of foodborne disease. Annually, norovirus causes about 5 million illnesses and contributes to about 15,000 hospitalizations and 150 deaths in the U.S. alone based on CDC estimates just from domestically produced products.[9] Norovirus and hepatitis A are the two main viruses of concern for the food industry for imported products as well.

Despite an abundant amount of evidence of the large role played by foodborne viruses in the number of illnesses each year, testing methods to address this issue have not been readily available. This situation is rapidly changing and, as a result, the knowledge gap is shrinking around which food ingredients are susceptible to foodborne virus contamination.

Typically, viruses are present in foods in low numbers, making their detection in traditional cell cultures difficult. Recent diagnostic advances, such as real-time reverse transcription-polymerase chain reaction (RT-PCR), have greatly advanced the detection of foodborne viruses. With RT-PCR, the detection limit of norovirus (GI and GII) and hepatitis A is 1–10 copies, depending on the quality of the RNA purification from the food matrix.

Currently, a fruit mixture sourced from Asia was implicated in an Australian outbreak of hepatitis A.[10] An ISO method drafted and approved in Europe in 2013 offers the best-known tool for detecting this virus in food products.[11

While many food ingredients are not at risk for foodborne virus contamination, the ingredients that can pose this risk should be evaluated for a focused monitoring program as well as preventive control measures. Recent advances in methodology allow for more opportunities to reduce this risk.

Expansive Toolbox
The challenges confronting ingredient safety are diverse, making it nearly impossible to cover every relevant topic in this important issue. To meet the many challenges posed by the global food chain, it is incumbent upon food companies to modernize and expand their food safety and quality toolbox. By doing so, manufacturers and processors will be better prepared to address one of the most complex and pressing issues facing the food industry today. Modernization is more than just a buzzword. By using new tools to achieve better transparency, our science-based efforts to improve food ingredient safety will move forward.  

Pamela Coleman, M.B.A., CFS, is vice president of research services for the Silliker Food Science Center and president of Biofortis, Mérieux NutriSciences’ global research organization servicing innovation in food, nutrition, health, cosmetics and consumer goods. She can be reached at info@mxns.com.

1. www.fda.gov/food/guidanceregulation/default.htm.
2. Rulis, AM and JA Levitt. 2009. FDA’s food ingredient approval process. Regul Toxicol Pharmacol 53(1):20–31.
3. Neltner, T et al. 2013. Conflicts of interest in approvals of additives to food determined to be generally recognized as safe: out of balance. JAMA Intern Med 173(22):2032–2036.
4. Claire Kruger, Ph.D., personal communication.
5. Schiff, D. 2013. GRAS self-affirmation fades as sound strategy under FSMA. The Tan Sheet February 11.
6. Ed Steele, personal communication.
7. National Advisory Committee on Microbiological Criteria for Foods. 2011. Parameters for determining inoculated pack/challenge study protocols. J Food Prot 74(4):522.
8. www.rsc.org/education/eic/issues/2005Mar/Thefightagainstfoodadulteration.asp.
9. www.cdc.gov/foodborneburden/2011-foodborne-estimates.html.
10. www.foodsafetynews.com/2015/02/
11. www.iso.org/iso/home/store/catalogue_tc/catalogue_detail.htm?csnumber=60297.