From FCC e-Newsletter (Summer 2010)

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United States Pharmacopeial Convention (USP) and the Food Chemicals Codex (FCC) at Institute of Food Technologists (IFT) 10th Annual Meeting and Food Expo, July 18–20, 2010 in Chicago

At the IFT 10th Annual 2010 Meeting and Food Expo, USP was represented on the exhibition floor at booth #3373 and hosted three symposia and presented four posters as described below.
Symposium: Compendial quality standards for food ingredients – an efficient first-line defense against economically motivated adulteration
(Session 105; Monday, July 19; 8:30–10:00 a.m., Room S501cd)
Compendial standards set acceptance criteria and describe test methods to define what a food ingredient is, rather than focusing on compounds that are not supposed to be present. Thus, compendial standards define the purity, identity, and quality – in short the authenticity – of food ingredients, and they can be used to tightly define any food ingredient in commerce. Recent incidences of food ingredients that have been adulterated for economic gain highlight the necessity of applying tighter standards to keep the food supply chain safe. Wherever economically motivated adulteration occurs, the safety of the adulterated product is determined exclusively by the ethics and knowledge of the adulterer, thus bypassing all other safety considerations by governmental organizations. The development and use of compendial standards can help to provide a first line of defense against the potential adulteration of food ingredients, especially newer standards that have been dev! eloped with a specific emphasis on detecting adulteration.

• "Fake foods: the analytical challenges presented by economic adulteration" – Shannon Cole, PMP, Director of Science Operations, Chemistry/Biochemistry, Grocery Manufacturers Association (GMA); Economically motivated adulteration presents a huge challenge in the marketplace and threatens the integrity of the food supply chain. Its analytical detection is not always straightforward, and an example on the authentication of the exotic juice acai is given to demonstrate the analytical challenges that can be encountered in an effort to prevent adulteration.
• "Challenges in authenticating naturally derived food products" – Eric Jamin, Ph.D., Authenticity Analytical Unit Manager, Eurofins Scientific Analytics; The authentication of naturally derived foods and food ingredients poses a huge challenge to the analyst. The benefits and limitations of novel approaches utilizing advanced molecular biological techniques will be presented and discussed on real-life examples.
• "A food manufacturer's perspective on the prevention of economically motivated adulteration" – John Spink, Ph.D., MSU/A-CAPPP; Food manufacturers are the pivotal point between consumers and ingredients producers. It is their name that consumers associate with the product. Food manufacturers go to considerable length to ensure the quality, purity, and identity of the food ingredients used for the production of their goods in order to protect consumers' health and their brands from adverse effects.
• "Compendial standards in the Food Chemicals Codex – how quality standards can lead to increased food safety" – Markus Lipp, Ph.D., Director Food Standards, U.S. Pharmacopeial Convention; The FCC is a compendium of quality standards for food ingredients, providing acceptance criteria, suitable and validated detection methods, and reference materials to all stakeholders of the food supply chain.

Symposium: Quality and safety of functional foods – from naturals to designer molecules, new challenges to keep the food supply chain safe
(Session 215; Tuesday, July 20, 8:30–10:00 a.m., Room S503ab)
More and more functional foods are incorporated into mainstream foods as consumers are appreciating their benefits. New frontiers are opened through the development of new sources and ultimately the design of molecules according to desired specifications. This session will highlight some of the latest innovations in the development of functional foods and discuss the challenges that long supply chains may have. The special product of today with well-controlled supply chains may transform into a common commodity of tomorrow. A quality standard defining the authenticity, identity, and purity of such an ingredient will be an essential tool to maintain its quality and ultimately its safety throughout such a transition.

• "Designer ingredients" – David Land, Medisyn Technologies; A unique platform technology that brings a new way of looking at compounds and their associated functions (bioactivity) will be discussed. Top-tier companies like Kraft Foods are engaging in Research and License Collaborations with Medisyn Technologies. These companies share a common goal of accelerating product innovation at lower cost and higher probability of success – by incorporating bioactive functionality in the product design at the start of a research project.
• "Botanical quality – a case study on cocoa flavonoids" – Brian Schaneberg, Ph.D., Mars Botanical; This talk will look at the concepts of "scientifically valid" and "fit for purpose," using cocoa extract as a case study. Nonspecific and specific methods of analysis will be discussed detailing their strengths and weaknesses and an insight into the supply chain management for cocoa flavonoids will be presented.
• "Supply chain integrity" – Edward Fletcher, Ph.D., Strategic Sourcing, Inc.; The complexity and challenges of supply chains for food ingredients will be discussed using examples of naturally derived ingredients. The focus of this presentation will be on challenges faced by the food industry and its suppliers to maintain the integrity of naturally derived products with complex compositions.
• "Quality standards and global compendia" – Roger Clemens, Ph.D., Director of Analytical Research at USC and President-elect, IFT; Quality standards for food ingredients, providing acceptance criteria, suitable and validated detection methods, and reference materials to all stakeholders of the food supply chain, is critical. An overview of the existing compendia and other sources of quality standards will be given.

Symposium: Dietary supplement safety assessment: past, present, and future
(Session 119; Monday, July 19; 10:30 a.m.–12:00 p.m., Room S501cd)
With the growth in dietary supplement use in many countries, there is an increasing need to assess the safety of such products; this is not an easy task. Both the quantity and quality of information with respect to toxicological and clinical effects are challenging. Adverse reactions are typically underreported, and the interpretation of reported cases is often difficult. Challenges also exist due to the complex nature of many dietary supplements. Many dietary supplements are obtained from raw/crude botanical or other natural (marine, mineral, etc.) sources; they are not singular, highly purified moieties. Further, many are presented to the public as complex mixtures incorporating an ever-increasing number of individual ingredients, such as herbs, vitamins, and minerals. In the U.S. under DSHEA, dietary supplements are assessed by the manufacturer/distributor and held to a lesser safety standard than food, i.e., the "reasonable expectation of no harm." This symposium will not only address some of the historical and continuing challenges faced when assessing dietary supplement safety, but will also highlight emerging initiatives and toxicological methods aimed at overcoming these challenges.

• "Dietary supplement safety assessments: overview of challenges" – Scott A. Jordan, Ph.D., Evaluator, Health Canada; The safety assessment for dietary supplements (DS) can involve the assessment of human adverse reaction cases, as well as the review of published toxicity data. Both of these information sources present challenges in terms of the quantity and quality of information available. Adverse reactions suspected to be associated with DS are under-reported, and the quality of reported reactions may be less than ideal, making the assessment of causality challenging. In addition, toxicological studies on single chemicals may not always relate to herbal or multi-ingredient DS, where interactions may occur between various components. There is also a general lack of information on the toxicity of many DS ingredients. Despite challenges, opportunities exist to capitalize on newer information to increase the current body of scientific evidence regarding the safety of DS.
• "Practical use and analysis of spontaneously reported adverse event data involving botanicals and other dietary supplements" – Richard Kingston, Pharm.D., President, Regulatory & Scientific Affairs, SafetyCall International; It is critical to analyze spontaneously conveyed adverse event report (AER) data involving botanicals and other dietary supplements. The Dietary Supplement and Nonprescription Drug Consumer Protection Act of December 2007 requires companies to document all reports of adverse incidents, maintain and archive records of AERs for a period of six years, and submit serious AERs to the FDA within 15 days. SafetyCall responds to adverse event calls from consumers or health professionals on behalf of the manufacturer. Experiences in asking the right questions while receiving AERs, analyzing reports, and reporting complete information to MedWatch are discussed.
• "Application of microarray in studying herbal dietary supplement induced toxicity" – Lei Guo, Ph.D., Research Biologist, U.S. FDA; Gene expression is an innovative avenue to explore herbal/ botanical toxicities. This toxicogenomic approach provides a path forward in this field. The evolving "omics" approaches to identify safety concerns are discussed.
• "U.S. Pharmacopeial Convention (USP) approaches to safety and quality of dietary supplements: the need for quality standards and relevant specifications" – Nandakumara Sarma, Ph.D., Scientific Liaison, U.S. Pharmacopeia; The presentation will discuss dietary supplement safety from the perspective of U.S. regulatory paradigms and the value of publicly developed, non-governmental quality standards that address authenticity, purity, and strength. USP is a scientific, nonprofit, standards-setting organization that advances public health through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods. USP's standards are widely used worldwide. Since safety and quality are closely related parameters, the USP monograph development process involves a safety evaluation of the monograph articles as a part of the compendial admission criteria process, and validation of quality parameters, including identity, ! purity, strength, and composition, and limits on contaminants. Approaches used by USP to conduct a safety evaluation as a part of USP's compendial admission criteria are discussed.

Poster: Opportunities to modernize the compendial quality standard for food-grade glycerin to reduce the risk of adulteration
(#142-14; Monday, July 19; 11:00 a.m.–1:30 p.m.)
[Moore, J.C.*; DeVries, J.W.**; Lipp, M.*; Holloway, G.*; Griffiths, J.C.*; * = U.S. Pharmacopeia Staff; ** = Medallion Labs/USP Food Ingredients Expert Committee]
Human consumption of adulterated glycerin includes many tragedies over the past century involving hundreds of deaths. In the United States, recent revisions to the compendial standard for excipient-grade glycerin have been implemented to reduce the risk for adulteration of medicines (both prescription and over-the-counter) with diethylene glycol (DEG) and ethylene glycol (EG). The objectives for this study were to characterize the risks of potential dietary exposure to DEG adulterated glycerin, to assess the likelihood of economic adulteration and supply chain issues, and to identify opportunities to modernize the Food Chemicals Codex (FCC) standard for glycerin to mitigate the risk for adulteration with DEG and other potential adulterants. Results indicate that economic incentive and supply chain confusion could lead to gross adulteration of food-grade glycerin, and that low-level adulteration from supply chain contamination is possible. Dietary exposure to DEG/EG adulterat! ed glycerin would pose a serious food safety concern even when adulterated at low levels. The current FCC standard for glycerin is capable of only detecting materials adulterated with significant (5–10%) levels of DEG, and flagrant replacement with other potential adulterants. To prevent the risk of low-level DEG/EG adulteration of glycerin, the addition of a GC method capable of detecting such adulterants is recommended for the FCC. Investigation into new quantitative assay methods capable of distinguishing glycerin from other potential economic adulterants is also recommended.
Poster: Current regulatory challenges surrounding "inactive ingredient (excipient)" use in dietary supplement applications
(#142-13: Monday, July 19; 11:00 a.m.–1:30 p.m.)
[Catherine Sheehan*; Ranga Velagaleti**; James Griffiths*; * = U.S. Pharmacopeia Staff; ** = BASF]
Excipients are by definition inert substances often used as a diluents or vehicles in dosage forms. They may have "functional" roles that can make a pharmaceutical and/or dietary supplement dosage form achieve a desired performance. The purpose or role (e.g., functionality) of a given excipient(s) in a dietary supplement dosage form (e.g., tablets, capsules) is similar to the traditional role of a given excipient(s) added to achieve the delivery and thus therapeutic effect of an active pharmaceutical ingredient in a final drug product. The performance requirements or critical material attributes (e.g., particle size, size distribution, surface area) of the selected excipient(s) ensures consistent performance throughout the product life-cycle, whether that product be a pharmaceutical or a dietary supplement. The similarity lies in ensuring the dosage form retains its targeted physical form, consistency, and palatability for human consumption, bioavailability, and adsorption/desorption of the active ingredient(s) within the human body. The history of excipients use in dietary supplements and current pharmacopeial and regulatory expectations for their continued use will be covered. The pre-DSHEA "grandfathered" excipients will be reviewed and their use in current dietary supplement manufacturing explained. FDA's Food Additive Status list provides a resource for those needing traditional dietary supplement excipients approved uses. For those potential excipients neither grandfathered through historical use nor appearing on the Food Additive Status list, approaches wi! ll be reviewed to determine their requirements for classification as Generally Recognized As Safe (GRAS) to enable them to be used in dietary supplement dosage forms, including potentially via FDA-approved drug products, and consequent listing in the FDA Inactive Ingredient (IIG) database.
Poster: Protein adulteration with non-declared potential allergenic proteins: can quality standards play a role?
(#142-26, Monday, July 19; 11:00 a.m.–1:30 p.m.)
[Moore, J.C.; Griffiths, J.C.; Lipp, M.]
Allergenic proteins are an important food safety issue, yet most of the routine testing for allergens occurs in finished food products. High-value, protein-based ingredients have historically been susceptible to economically motivated adulteration with alternative (cheaper) proteinaceous materials. The fraudulent substitution of presumed non-allergenic proteins with allergenic proteins could cause significant adverse public health consequences and/or lead to product recalls. Testing of protein-containing ingredients for authenticity/identity and purity early in the supply chain may be a potential option to reduce the risk of allergen safety issues and help prevent the need to recall finished products for the presence of undeclared allergens. Compendial quality standards can provide more selective analytical methods to better identify and distinguish authentic protein ingredients from those that may be contaminated with non-authentic, potentially allergenic proteins.
Poster: Limits for elemental contaminants in dietary supplements: compendial perspectives
(#142-21, Monday, July 19; 11:00 a.m.–1:30 p.m.)
[Tokiwa, Y.; Giancaspro, G.I.; Griffiths, J.C.; and Sarma, D.]
Elemental contamination in some dietary supplements is a well-recognized problem. The natural origin of some dietary supplement ingredients (such as herbals, or natural calcium) might contribute heavy metals, in some cases depending on the part of the plant used, the geographical location of cultivation, or the way they are processed. USP is an official public standards-setting authority for all prescription products and also sets widely recognized standards for food ingredients and dietary supplements. Recently, an informational General Chapter, <2232> Elemental Contaminants in Dietary Supplements, was developed, which proposes daily exposure limits for inorganic arsenic (15 μg/day), cadmium (5 μg/day ), lead (10 μg/day ), mercury (15 μg/day), and methyl mercury (2 μg/day). The proposed limits for elemental contamination in dietary supplements are derived by subtracting their average exposures from air, food, water, and prescription drugs, from the Joint FAO/WHO Expert Committee on Food Additives (JECFA) provisional tolerable weekly intake (PTWI) levels. A safety factor ranging between 5% and 15% was used to calculate the suggested limits. Using this safety range, the resulting values are consistent with proposed Pharmeuropa limits and Health Canada and! WHO proposals. Dietary supplements, especially those of a botanical or marine raw material stock, may be contaminated with high levels of arsenic, cadmium, lead, mercury, and methyl mercury. Compendial monographs need to take these compounds into consideration when setting quality specifications.

USP's First-ever Nomenclature Workshop Addresses Food Ingredient Naming Challenges

What: Compendial nomenclature: overview and challenges
When: Monday–Tuesday, July 27–28, 2010
Where: USP Headquarters, Rockville, Maryland
Highlights of this first-ever Nomenclature Workshop include

• Exploring the current and emerging nomenclature initiatives of the USP, FDA (including the Center for Food Science and Nutrition), other pharmacopeias, and international bodies
• Presentations on drug substance, drug product, and food ingredient nomenclature
• A special breakout session on food ingredient naming challenges, moderated by Grady Chism III, Ph.D.
• Learning about the Work Plan of the 2010–2015 USP Nomenclature, Safety, and Labeling Expert Committee and the proposed concept of a nomenclature guideline as it relates to food ingredients and other nomenclature issues

In addition, participants will learn about the United States Adopted Names (USAN) Council, International Nonproprietary Names (INN), ISO, and other drug product naming initiatives. Participants also will be able to provide input on implementation and communication issues related to the USP Monograph Naming Policy for Salt Drug Substances in Drug Products and Compounded Preparations.