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Dr. Stephen Spiegelberg

Author Archives: Dr. Stephen Spiegelberg

  1. Caliente Chromatography: Quantitative Analysis of Capsaicin

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    Chromatography: To Quantify or Not to Quantify, That Is the Question

    Our chromatography team is regularly asked to identify compounds in materials. Some projects only require the identification of compounds, while others require the accurate determination of concentration of the identified compounds. The latter, termed quantitative chromatography, requires the preparation of calibration standards suitable for the compound in question. At a recent dinner, one of our scientists recognized, in an acute way, the benefit of concentration assessment over the more qualitative assessment of presence for the compound capsaicin.

    Why Tails Matter

    Molecular Tweaks That Determine Whether You’re Enjoying Salsa or Enduring Spider Toxins

    Capsaicin, or 8-methyl-N-vanillyl-6-nonenamide, is the compound found in chili peppers that provides the burning sensation in tissues with which it comes into contact. Capsaicin is the predominant compound found in the general category of capsaicinoids, shown in Figure 1. These compounds all have the same vanillylamide structure at one end of the molecule (left in the figure) but have differing aliphatic tails. Interestingly, the vanillotoxin of the venom of some tarantulas activate the same pain pathways as capsaicin, although arguably through a much less enjoyable mechanism.

    Vanillylamide

    Figure 1: Capsaicin compound. Common Vanillylamide group marked on the left with the unmarked tail on the right varying between compounds.

    The Scoville Heat Unit

    Scoville Heat Unit

    Consumers of food prepared with chili peppers instinctively know that there are levels of heat in the food that is dependent on the concentration of capsaicin. Around 1912, William Scoville, a pharmacist, developed a subjective scale to provide a ranking of the hotness of chili peppers. In his original test, a known weight of dried pepper was extracted in ethanol and diluted to specific concentrations of solutions of the extract in sugar water.

    These solutions were tasted by a panel of tasters until a majority could no longer detect the heat in the solution. The heat unit was based on the amount of dilution necessary to lose the detectable heat, so a pepper requiring a dilution of 1 million times before no heat was detected would have a Scoville Heat Unit (SHU) of 1 million.

    The hottest pepper tested to date is Pepper X with a SHU of 2,693,000, created in 2023 by crossbreeding the Carolina Reaper with another pepper. For comparison, a Jalapeno pepper has an SHU between 2,500-10,000.

    Scoville aimed to assess capsaicin content for use in muscle salves and related pharmaceutical products. His scale became important for both culinary and pharmaceutical applications, especially in ensuring product consistency, safety, and efficacy.​

    Replacing Tongues with Chromatography Columns

    An obvious weakness of this subjective technique is variability between tasters and sensory fatigue. To remove this subjectivity, the assessment of SHU is now performed with high performance liquid chromatography, which can quantitatively measure the concentration of capsaicinoids directly. Dried pepper samples are extracted in acetonitrile and the peak area associated with the capsaicin compound is compared to calibration curves prepared from standards. The results are free from subjective bias, and the test subjects are much happier. This approach is very similar to the trace compound analysis performed by Cambridge Polymer Group.

    Capsaicin Quantification Applications

    • Food Industry: Manufacturers of spicy foods, sauces, and extracts need precise capsaicin quantification for flavor standardization, product labeling, legal compliance, and quality assurance.
    • Pharmaceutical/Medical Device: Companies developing capsaicin-containing topical creams, patches, or other formulations require accurate quantification during R&D, regulatory submission, and quality control for clinical use.
    • Packaging: In modern packaging science, capsaicin is directly incorporated into biomaterials such as antimicrobial films, coatings, and encapsulation systems to enhance freshness, control microbial growth, and improve barrier properties for food and medical products.[1]

    Capsaicin quantification is crucial not just as a safety and contamination measure, but as a technical quality parameter for new biomaterial products and advanced controlled-release systems.  These advanced delivery systems still depend on robust quantitative chromatography to verify capsaicin loading, release profiles, and shelf-life performance in real formulations.[2]

    Contact Cambridge Polymer Group today for expert chromatography, quantification, and material characterization services. Speak to one of our scientists to help define your product or research needs.

    [1] Qincong Luo, Jinyu Ouyang, Luqi Zhan, Guohuan Liang, Xiaojuan Wang, Development and characterization of capsaicin-enriched Dialdehyde starch-PVA films for antimicrobial food packaging. International Journal of Biological Macromolecules.2025;330(Pt 1):147918. doi: 10.1016/j.ijbiomac.2025.147918.

    [2] Qiu X, Xie J, Mei J. Recent Advances in the Applications and Studies of Polysaccharide-, Protein-, and Lipid-Based Delivery Systems in Enhancing the Bioavailability of Capsaicin-A Review. Polymers (Basel). 2025 Apr 27;17(9):1196. doi: 10.3390/polym17091196. PMID: 40362978; PMCID: PMC12073809.

     

  2. How Long Can a Polymer Last…And What Is Q10?

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    The longevity of polymers in real-world use is a critical importance across industries, from medical devices and packaging to consumer products and infrastructure. While many polymers are engineered to withstand sunlight, heat, moisture, and chemical exposure, nearly everyone has seen a once-flexible product turn brittle, discolored, or cracked over time. Both raw materials (such as pellets or powders) and finished products can slowly degrade in storage or use, leading to cosmetic changes or even complete functional failure.

    Because real-time testing of decades-long product lifespans is rarely practical, manufacturers rely on accelerated aging studies to estimate a polymer’s shelf life and in-use performance. These tests subject materials to elevated stress conditions that replicate the effects of long-term aging within a much shorter timeframe, providing scientifically grounded predictions of stability.

    Accelerated Aging and the Arrhenius Equation

    A common approach to accelerated aging is through heat, exploiting the known exponential relationship between temperature and reaction rates described in the Arrhenius equation, as shown in Equation 1, where k is the reaction rate, E is the activation energy for the reaction, T is the temperature of the storage environment, and R is the universal gas constant (8.314 JK-1mol-1). A is a prefactor term that is usually determined empirically.

    Equation 1

    Equation 1

    In an accelerated aging study, the researcher establishes a property that will be affected by aging and then sets a threshold limit on that property where the material or product no longer meets its specifications.  Experiments can then be conducted at various temperatures over time to determine the time to failure at these temperatures. Equation 1 can be re-written in terms of time to failure t1 at the accelerated temperature T1 relative to the real time conditions (time to failure t0 at real-time temperature T0) as:

    Equation 2

    By determining reaction rate at two different temperatures, the A prefactor is not needed and the only unknown in these equations is the activation energy. This parameter is a function of the material and how it was processed and describes the minimum amount of energy required to initiate a chemical reaction. There are a few ways of experimentally determine the activation energy (or in some cases tabulated values can be used).

    Determining Activation Energy

    ASTM D3045 Approach

    In one method, samples are aged at four or more temperatures for varying amounts of time, and the property of interest, such as tensile strength, is measured for each of these specimens over time (see Figure 1 and Figure 2).

    Figure 1: Property loss as a function of temperature following ASTM D3045 at four different temperatures. The related time to failure values are noted with the downward facing arrows, which are used in Figure 2.

    Figure 2: Determination of activation energy, E, from Figure 1.

    A threshold property value is used to plot a time versus inverse temperature plot (Figure 2), the slope of which yields activation energy. This method is a reliable way of determining the activation energy, which can then be used for assessing property loss at different storage temperatures. The downside of this approach is that many experiments (and time) are required to build a dataset.

    ASTM E1641 Approach

    A quicker approach is to determine the activation energy through ASTM E1641, where a set of thermogravimetric analyses (using a Thermogravimetric Analyzer, or TGA) at different heating rates are used to monitor thermally-driven mass loss. In a simple system, the thermally-driven mass loss is an indication of the resistance of the material to thermal decomposition, and the heating rate provides the kinetic driver for the testing. By testing four samples at different heating rates and selecting a target mass loss (say 5%), a plot of log (heating rate) vs. (1/T), similar to Figure 2, will be generated, with the slope proportional to the activation energy. However, it should be noted that in our experience, the calculated activation energy of these two techniques is rarely identical.

    Dynamic Rheology / Master-Curve Approach

    There is a third common technique for polymers. The dynamic rheological properties of a polymer also generally obey the Arrhenius function and therefore building a so-called master-curve from a set of rheological experiments at different experiments. The shift factor used to create this master-curve is related to the activation energy of the polymer, providing another way to estimate this important parameter.

    Simplifying with the Q10 Factor

    Discussing aging rates in terms of activation energies can be unwieldly. As a result, researchers performing accelerated aging studies often refer to the Q10 value, which is the pre-factor that considers how much the reaction rate Rn with an increase of 10 ºC. The Q10 factor is simply written as:

    Equation 3

    where R1 and R2 are the reaction rates at the respective temperatures. The Q10 can be determined from the activation energy through manipulation of Equation 2 and Equation 3. Knowing a Q10 value for your material or product, you can quickly see real time (RT) shelf-life equivalent values based on accelerated aging temperatures (A) by rearranging Equation 3 to get:

    This process is captured in ASTM F1980. As an example, for a Q10 of 2.0, accelerated aging for 30 days at 50 ºC relative to real time storage conditions at 23 ºC would give a real time equivalence of 195 days. Often this value of Q10 is used as a default value, but selection of the accelerated aging temperatures, and calculation of an accurate Q10, requires detailed knowledge of the materials used.

    Learn More in Our Accelerated Aging Webinar

    To explore these concepts in more depth, including practical limitations and real-world examples, attend our webinar:

    Age ISN’T Just A Number: Accelerated Aging Methods for Material and Product Characterization
    Date: Wed, Jan 21, 2026
    Time: 2:00 – 3:00 PM EST

    In this presentation, we will discuss accelerated aging as a ubiquitous tool used to ensure shelf and in-use stability over long time periods. This powerful collection of techniques allows prediction of potential aging issues that would be time consuming and costly to identify in real time. However, accelerated aging has limitations, and data generated in an accelerated study must not be used blindly.

    CPG Speakers

    • Gavin Braithwaite, Chief Executive Officer
    • Jaimee Robertson, Director of Consulting Services
    • Kalpana Viswanathan, Polymer Chemist

    The webinar will:

    • Review aging mechanisms in polymers and the scientific assumptions that underpin accelerated aging.
    • Discuss analytical techniques that can be used to screen material aging or infer acceleration factors, including their weaknesses.
    • Present a case study comparing accelerated aging techniques to demonstrate the importance of careful experimental design when relying on accelerated methods to predict material performance.

    Attendees will gain an understanding of the processes underpinning accelerated aging and the key considerations for applying these data to material and product decisions.

    Secure your spot.

    Partner with Cambridge Polymer Group

    Selecting effective appropriate accelerated aging conditions requires a solid understanding of your product’s material composition, processing history, and thermal stability.

    Cambridge Polymer Group scientists have decades of experience designing and executing Arrhenius-based and Q10-based shelf-life studies for polymers, medical devices, and specialized materials.

    Our lab can help you:

    • Determine activation energy (via ASTM D3045, E1641, or Dynamic Rheology)
    • Identify realistic accelerated aging conditions
    • Validate shelf-life claims and packaging performance

    Contact us to design an accelerated aging study tailored to your material, product, and regulatory needs.

  3. The Chemistry Behind the Perfect Roast: Understanding the Maillard Reaction

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    Every time you roast a turkey or bake bread, a fascinating chemical reaction gives your food its rich brown color, enticing aroma, and complex flavors. That reaction is called the Maillard reaction (pronounced my-ard), a cornerstone of both food chemistry and polymer science.

    What Is the Maillard Reaction?

    The Maillard reaction occurs when amino acids (from proteins) react with reducing sugars at temperatures above about 140 °C. It is not a single reaction, but a chain of them that unfolds in three general stages: initial, intermediate, and final.

    1. Initial reaction: Carbonyl groups from sugars react with amino groups from amino acids to form Amadori products, also known as glycated proteins.
    2. Intermediate reaction: These products break down into smaller molecules such as reduced sugars, dicarbonyls, and additional amino compounds.

    Final reaction: Polymerization, condensation, and fragmentation reactions produce advanced glycation end products (AGEs), complex, often brown-colored molecules. These compounds have been implicated in diabetes, cardiovascular disease and a host of other potential issues.

    Figure 1: Stages of the Maillard Reaction

    The Role of Melanoidins

    Among the many products of the Maillard reaction are melanoidins, a group of high-molecular-weight nitrogen‑containing polymers that give foods their brown hues. Their structures vary depending on the starting sugars and amino acids but generally include heterocyclic rings such as pyrroles, furans, and pyridines linked to a carbohydrate backbone.

    These same compounds are responsible for the characteristic color of roasted coffee, seared steaks, and baked bread. Melanoidins and other Maillard products also create the familiar flavor molecules that chefs prize:

    • Pyrazines: roasted or toasted notes
    • Thiophenes: rich, meaty flavor
    • Furanones and furans: sweet, caramelized aroma
    • Oxazoles and pyrroles: nutty or sweet nuances

    Beyond the Maillard Reaction: Myoglobin and Color

    Not all browning in cooked meat comes from the Maillard reaction. Another source of the brown color is myoglobin, composed of 150 amino acids found in the muscle tissue of vertebrate animals (see Figure 2) and is used to store oxygen in muscles. Myoglobin has four pyrrole nitrogens that surround a ferrous ion center, as shown below. As meat heats, the heat denatures the protein and the myoglobin. This transition occurs much lower than the Maillard reaction (of the order of 60 °C) and is the driving force for the bulk color change that allows determination of “doneness” in red meat since the form of the converted myoglobin governs the final color of the molecule.

    Figure 2: Myoglobin

    How the Maillard Reaction Differs from Caramelization

    The Maillard reaction should not be confused with caramelization, which involves the direct pyrolysis (thermal breakdown) of sugars without amino acids. Both processes create brown color and complex flavors, but they arise through distinct chemical pathways.

    Let’s Talk Turkey: Maximizing the Maillard Reaction

    When it comes to roasting a turkey, harnessing the chemical reactions involved in cooking makes all the difference in flavor and appearance. Here are a few science-backed tips:

    • Dry the surface. Removing excess moisture by blotting helps the turkey brown more quickly.
    • Use moderate alkalinity. Raising the surface pH with a small amount of baking soda encourages the Maillard reaction.
    • Maintain high heat. A roasting temperature above 140 °C ensures the reaction proceeds effectively.
    • Control heating rate and conditions. Although not relevant for surface browning, the rate of heating, and the oxygen environment (oven versus barbeque) can impact the color of the meat in the way that the myoglobin is degraded.

    So do you need to be a chemist to cook a turkey? Thankfully, the answer is no, as all these reactions occur naturally just by cooking the turkey at the appropriate temperature and for the appropriate duration of time. However, when the author of this blog post was a graduate student in MIT’s Chemical Engineering department, the department secretaries received several phone calls every November from amateur chefs asking questions about how to cook their turkeys. The standard response from the secretaries? “Let us connect you to the Chemistry department.”

  4. From Residues to Risk: Why Medical Device Cleaning Validation Matters in Biocompatibility Assessments

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    Webinar – October 15, 2025, 2 p.m. ET

    Register Here

    Ensuring medical device safety requires a coordinated approach across three critical domains: biocompatibility, cleanliness, and sterility. While each area has its own regulatory and testing requirements, they are deeply interconnected. Overlooking the relationship between these elements can increase patient risk and delay product approvals. This upcoming medical device webinar explores how cleaning validation influences biocompatibility outcomes and overall product safety.

    Cleaning validation is a foundational step in establishing device safety. Surface contaminants left from manufacturing or cleaning processes can directly impact biological evaluation results and compromise sterility assurance. Similarly, certain sterilization methods can alter material chemistry, generating new extractables or leachables that affect the device’s biocompatibility profile.

    When designing and validating a medical device, both manufacturers and regulators should consider:

    • Cleanliness addresses surface residues, which can directly influence biological evaluation results. It’s also essential to achieving reliable sterilization assurance.
    •  A sterile medical device may not necessarily be biocompatible; sterilization methods can alter chemical properties relevant to biological safety.
    • Devices can meet cleaning and sterility standards but still fail biocompatibility due to material selection or design factors.
    • Even if a device is determined to be biocompatible post-manufacture, poor cleaning or sterility assurance can compromise clinical performance and patient safety.

    Join our webinar, From Residues to Risk: The Role of Cleaning Validation in Biocompatibility Assessments, on October 15, 2025, 2 p.m. ET, to learn how cleanliness, sterilization, and biocompatibility testing intersect during medical device validation. Our experts will highlight best practices for integrating cleaning validation into biocompatibility assessment plans, review regulatory expectations, and provide actionable strategies to minimize risk while ensuring compliance with ISO 10993 and related standards.

    Register for free today via the link here.

  5. Hydrogel Water Beads: For Farming Use Only

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    What Are Water Beads?

    “Water beads” are water-absorbent polymer beads that can swell over several hundreds of times their initial dry mass when placed in water, forming hydrogel beads. They are primarily marketed as agricultural products to act as humectants in soil, helping retain and slowly release water into the soil.

    Beyond farming, however, water beads have been marketed as colorful sensory toys for play and decoration. This non-agricultural use has raised safety concerns, especially when the beads are accessible to young children who may accidentally ingest them.

    What Are the Hazards of Water Beads?

    A 2025 case study, published in Pediatrics, documented a 13 month-old who was admitted to the emergency room after a 12 hour stint of vomiting and lethargy[1]. She presented as dehydrated, abdominal distension and tenderness. A radiograph and ultrasound showed a mass in the small intestine, which a laparotomy confirmed to be swollen fragments of water bead material.

    The mass was removed, which resulted in partial recovery. The patient continued to show developmental symptoms, and 9 months after the initial mass was removed, a colonoscopy revealed inflammation of the ascending and sigmoid colons and additional gelatinous fragments consistent with water bead material. The patient’s motor skills and speech skills required early childhood intervention. This case underscores the risk of intestinal obstruction and possible neurotoxic effects associated with water bead ingestion.

    What Are Water Beads Made Of?

    The study author noted that some manufacturers claim the sensory toy water beads are made exclusively of sodium polyacrylate, which is the salt form of polyacrylic acid, a common hydrogel often used as the sorbent in diapers. However, characterization testing performed by Cambridge Polymer Group scientists showed that commercially-available water beads procured by the author and sold as sensory toys, found they were predominantly comprised of polyacrylamide, which is synthesized from acrylamide monomer. Polyacrylamide has a different toxicological risk profile than polyacrylate and hence needed additional scrutiny for its use as a toy.

    What Is the Current Regulation on Water Beads?

    The lead author of the 2025 study collaborated with the Consumer Product Safety Commission (CPSC) to highlight the risks posed by these products. The CPSC’s own testing of 14 water bead toy products revealed:

    • Detectable residual acrylamide monomers in most products
    • Two products exceeding acute oral minimum risk levels
    • Significant batch-to-batch variability in monomer content

    To protect consumers, the CPSC launched public guidance warning parents not to allow children to play with water beads[2]. On August 21, 2025, the Commission approved a new federal safety standard regulating water bead toys. The standard imposes two major restrictions:

    • Limits on permissible concentrations of polyacrylamide
    • Rules on maximum allowable bead size when fully swollen to reduce choking and intestinal obstruction risks[3]

    What Is Next?

    Water beads may have benefits in farming, but as toys, they present serious risks. With new safety standards in place and ongoing research, regulatory science is catching up to protect the most vulnerable consumers.

    At Cambridge Polymer Group, we continue to work with companies to characterize the chemical composition of hydrogel materials in consumer products. Our goal is to help ensure these materials are safe, compliant, and effective—whether in agricultural settings or other approved applications.

    If your company is working with hydrogels—whether for consumer products, agriculture, industrial, or medical applications—Cambridge Polymer Group can help. From material characterization and performance testing to product development and risk assessment, our scientists provide the insights you need to innovate with confidence. Connect with us to see how we can support your next project.

    [1] Haugen A, Friedman E, and Duff I. Intestinal Obstruction and Neurotoxicity Associated With Water Bead Ingestion. Pediatrics. 2025;155(2): e2023065575

    [2] https://www.cpsc.gov/Safety-Education/Safety-Education-Centers/Water-Beads-Information-Center

    [3] https://www.cpsc.gov/Newsroom/News-Releases/2025/CPSC-Approves-New-Federal-Safety-Standard-for-Water-Beads-to-Reduce-the-Risk-of-Injury-and-Death-to-Young-Children

  6. Flamingos Doing Vector Calculus

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    While we’ve previously celebrated the kitschy charm of plastic flamingos, today we turn our attention to the remarkable living birds and the science behind their mesmerizing feeding behaviors. With their beaks and most of their heads submerged near their feet, the birds stomp their feet in a rhythmic manner while chattering their beaks. But what exactly are they doing beneath the surface?

    Unlocking the Flamingo’s Secret Techniques

    Driven by curiosity, Víctor Ortega-Jiménez from the University of Maine, alongside collaborators from Georgia Tech and Kennesaw State University, decided to find out. Using detailed, 3D-printed models of flamingo heads, the team recreated and analyzed the birds’ signature feeding actions. Their findings, published in the Proceedings of the National Academy of Sciences (PNAS) in May 2025, finally unveiled the sophisticated strategies flamingos use to feed—movements that have captivated both bird enthusiasts and scientists for years.

    The Dance That Drives Dinner

    Flamingos perform a sort of underwater ballet: spinning and stomping their webbed feet in circles, stirring up the muck below. Far from random, this “wading dance” is a carefully choreographed routine designed to conjure swirling currents—vortices—that lift shrimp and other tiny morsels from the lakebed. The circular motion funnels these snacks into the water column, right where the flamingo’s beak can reach them.

    Beak Work: Precision and Power

    With their heads submerged, flamingos rapidly chatter their beaks up to a dozen times per second while their tongues pulse in sync. This rapid-fire action generates suction and whirlpools, channeling food particles toward the beak’s tip. As flamingos sweep their beaks backwards, these miniature vortices gather prey, making each mouthful more efficient.

    The Grand Finale: The Head Lift

    Every so often, flamingos abruptly lift their heads, creating a final swirl of water that draws even more food upward. This dynamic combination of footwork, beak action, and sudden head movements transforms the flamingo into an active predator, not just a passive filter feeder. Every part of their anatomy—from flexible feet to uniquely shaped beaks—works in concert to manipulate water and maximize their feeding success. These birds have studied and mastered complex chaotic fluid mechanic predictions, something that engineers sweat in their final years of undergraduate degrees.

    Inspiration for Technology

    The lessons learned from flamingo feeding could spark innovations in water filtration, microplastic collection, and aquatic robotics. By mimicking how flamingos harness fluid dynamics, engineers might develop new ways to capture tiny particles from water, offering nature-inspired solutions to modern challenges.

    See Flamingos in Action

    For those eager to witness these pink mathematicians at work, check out the videos and supplementary materials in the PNAS journal article.

     

  7. Potential Changes to the Generally Recognized as Safe (GRAS) Program

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    Background: The GRAS Framework

    The Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act (FD&C Act) was established by Congress in 1958. In the Code of Federal Regulations, the rules that the FDA applies to food additives are spelled out in sections 21 CFR 170.3 and 170.30. A food additive is considered to be any substance that is intentionally added to food or may reasonably be expected to become a component of food, such as leachable components from packaging. These additives are required to be reviewed and approved by the FDA before the additives can be used in food products as part of a premarket approval process.

    However, there are exceptions to this review requirement. If the substance is Generally Recognized by qualified experts As having been adequately shown to be Safe (GRAS) under the conditions of its intended use, the substance does not require FDA approval and is not considered a food additive. GRAS assessment can be performed through scientific analysis, or from safe historical consumption of the substance if it has been used in food prior to 1958.

    The Self-Affirmation Pathway and Its Controversy

    Since 2016, the FDA has operated a voluntary GRAS notification program.  Under this system, any qualified individual can notify the FDA that a substance is not subject to the premarket approval process as it is considered GRAS. The FDA may not question the basis for the GRAS conclusion, or it may conclude that there is insufficient information to make a GRAS conclusion.

    Although the FDA had a GRAS affirmation process in place around 1972, it was discontinued by 1997 due to lack of resources and was replaced with the notification process. The FDA maintains a GRAS database of notifications. The GRAS list, which is not comprehensive, is located in 21 CFR 182, 184, and 186.[1] Notably, the GRAS notification process is voluntary, and does not require either notification or affirmation from the FDA.

    This self-affirmation pathway has been criticized as a “loophole,” enabling manufacturers to introduce new food ingredients without sufficient safety data or transparency. While the process allows for efficiency and rapid market entry, it also means that the FDA and consumers may be unaware of new substances in the food supply.

    Proposed Changes in 2025

    In March 2025, the Health and Human Services secretary directed the FDA to consider removing the self-affirmation process of the GRAS program.[2] Companies would need to publicly notify the FDA of their intended use of substances in food products, along with safety data, before they could go to market with the substances. This substantial change in legislation would require many companies to re-evaluate their safety data and may require retroactive approval from the FDA.

    Current vs. Proposed GRAS Process

    AspectCurrent GRAS ProgramProposed Changes (2025)
    FDA NotificationVoluntaryMandatory
    Public DisclosureNot requiredRequired
    FDA Premarket ReviewNot requiredRequired
    Industry BurdenLowerHigher
    TransparencyLimitedEnhanced
    Time to MarketShorterLonger

    Implementing these changes will not be immediate. The FDA must conduct formal rulemaking, and because the GRAS exemption is written into federal law, Congressional action may be required. These steps could take years and may face industry resistance and legal challenges.

    Establishing Safety Profiles for Food Additives

    • Deliberately Added Ingredients: Toxicological evaluation of the ingredients based on the chemistry and amount can assist in establishing the safety profile.
    • Inadvertent Additives (e.g., from Packaging): Inadvertent food additives may be introduced from materials contacting food products, including food processing equipment, containers, or food preparation surfaces. In these cases, substances may diffuse into the food from the contact materials, which are often plastic and may contain antioxidants, colorants, plasticizers, and other stabilizers. For these substances, migration testing needs to be performed using food simulants to assess the amount of substance that is anticipated to be incorporated into the food product. This testing is comparable to leachables/extraction testing performed for medical devices.

    Contact Cambridge Polymer Group for questions about migration testing in plastic products used in food contact.

    [1] https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory

    [2] https://www.hhs.gov/press-room/revising-gras-pathway.html

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