FDA Compliance Simplified Blog

Covering FDA regulations and other topics of interest to FDA-regulated companies

Are Your Test Methods Scientifically Valid?

A respected colleague, Marian Boardley, recently published a blog post that is important for anyone in the dietary supplement industry. I’d like to share some highlights with you.

Ms. Boardley frequently evaluates FDA data on inspections and shares her insights.  In her recent post she shared a table of the 10 most frequent citations in of Dietary Supplement Good Manufacturing Practices from FDA inspection reports:

Specifications – identity, purity, strength, composition 55 (citations)
Written procedures – quality control operations 29
Specifications-component purity, strength, composition 28
Specifications – component identity 24
Written procedures – product complaint 22
Batch record – complete 21
Written procedures – holding 21
Specifications met – verify; finished batch 15
Component –  verify identity, dietary ingredient 15
Master manufacturing record – each batch 14
Tests, examinations – scientifically valid 14

 

It is the last item, Tests, examinations – scientifically valid, that is the key insight in the blog post. Ms. Boardley notes that 21 CFR 111.75(h)(2) has begun to appear in FDA Inspection Observations issued in 483 forms. Section 111.75(h)(2) requires that tests and evaluations to determine whether manufacturing specifications are met must use scientifically valid methods.  As Ms. Boardley states,

“FDA’s focus during inspections is by now firmly fixed on examining the specifications you set for finished dietary supplements and their components, and ensuring that compliance with those specifications is tested using scientifically valid, fit for purpose methods.  What does that mean in practice? It means you must be prepared to do due diligence, whether you use an internal or external third party lab, to ensure that the analytical methods used to test your supplements are scientifically valid for the product under test.  In other words, you can’t just accept whatever method your lab prefers (or the cheapest method). You must understand the methods used and ensure the test will give accurate, reliable results in your particular situation.”

The post notes that “by input” is not an acceptable method of determining whether finished good specifications have been met and quotes FDA warning letters noting that manufacturers must document their choice of test method to demonstrate how/why the method will ensure that a product specification is met.  Recent FDA warning letters also note that manufacturers must “verify that the laboratory examination and testing methodologies are appropriate for their intended use, as required by 21 CFR 111.320(a)”.

The blog post and its insights are a must read so you and your company can avoid an FDA warning letter.

 

Proposed New Definition of Healthy for Food Label Claims

The FDA has proposed a new definition of healthy and related terms for the purpose of food labeling.  The current definition became effective in 1994 and focuses on limited levels of total fat, saturated fat, cholesterol, and sodium to establish a food as “healthy”.  Under this rule unprocessed nuts, seeds, and avocados did not qualify as healthy. In March 2015 Kind, LLC received a warning letter from FDA regarding various nutrient content claims on their nut bar labels, including healthy claims.  In May of the same year, Kind submitted a Citizen Petition to FDA requesting an update to the definition of healthy that would consider the Dietary Guidelines for Americans , which recommended then and continue to recommend consumption of whole foods, including nuts, major components of Kind products. In May of 2016, FDA announced a policy of enforcement discretion  for “healthy” claims. In 2017 FDA held a hearing on use of the term healthy in food labeling.

Now, in 2022, FDA has issued a proposed rule to redefine healthy “to be consistent with current nutrition science and Federal dietary guidance, especially the Dietary Guidelines for Americans.” As noted previously, the current definition of healthy from 1994 only considers the level of specific nutrients; total fat, saturated fat, cholesterol, and sodium in the evaluation of healthy claim eligibility. The newly-proposed rule still considers levels of saturated fat and sodium for processed food products. Added sugars levels are new to the list of nutrients to consider before a “healthy” claim can be made.  There are also two entirely new provisions regarding use of a healthy claim:

  1. Use of the term ‘healthy’ is permitted on all unprocessed fruits, vegetables, nuts and seeds.
  2. Plain water and plain carbonated water may also be labeled as “healthy”.

Interestingly, FDA has included “plant-based milk alternatives and plant-based yogurt alternatives” in the dairy group and will allow those products to be evaluated against the dairy criteria for the purposes of the ‘‘healthy’’ nutrient content claim. Plant based milk and yogurt alternatives could be eligible to bear a “healthy” claim if their ‘overall nutritional content is similar to dairy (e.g., provide similar amounts of protein, calcium, potassium, magnesium, vitamin D, and vitamin A).  Unfortunately, whole milk and other full fat dairy products still are not eligible for healthy claims.

Criteria for claim evaluation:

The proposed rule includes several tables defining products that are eligible to be labeled as ‘healthy’.  Of particular note are the following:

TABLE 1—FOOD GROUP EQUIVALENTS

Food group and/or subgroup      Food group equivalent                                      

Vegetables                                                                                                      

Fruits                                                                                                              

Grains                                                                                                             

Dairy                                                                                                               

Protein Foods                           Game Meats. 1.5 oz equivalent.

………………………………………..Seafood. 1 oz equivalent.

………………………………………..Egg. 1 oz equivalent.

……………………………………….Beans, peas, and soy products. 1 oz equivalent.

.                                                        Nuts and seeds. 1 oz equivalent.                      

Adapted from page 16 of the proposed rule

 

TABLE 2—ELIGIBLE PRODUCTS FOR ‘‘HEALTHY’’ NUTRIENT CONTENT CLAIM

Product                                                                 Criteria for bearing ”healthy” claim                                                                                     

Raw, whole fruits and vegetables           No additional criteria; all raw, whole fruits and vegetables may bear the claim                            

Individual food products                             At least 1 food group equivalent per RACC from 1 food group & Nutrients to limit*               

Mixed products                                                At least 1⁄2 food group equivalent each from at least 2 food groups, and Nutrients to limit*

Main dish per 21 CFR 101.13(m)           At least 1 food group equivalent each from at least 2 food groups, and Nutrients to limit*         

Meal per 21 CFR 101.13(l)                        At least 1 food group equivalent each from at least 3 food groups, and Nutrients to limit*         

Water                                                                     Plain water and plain, carbonated water may bear the claim.                                           

*Nutrients to limit:  Sodium, saturated fat, added sugars                                                                                                                               

Adapted from page 17 of the proposed rule

Under the proposed rule some products that currently bear “healthy” claims will no longer be able to do so. Examples include several breakfast cereals that either do not include sufficient whole grains or that have disqualifying levels of added sugars.  Many other products would become eligible for the claim if the proposed rule is enacted. Determination of eligibility for the claim will involve analysis of the levels of the food groups and the product nutrient breakdown. The proposed rule includes record-keeping requirements to support the claim and a two-year retention period for those records.

The proposed rule is subject to public comment as part of the rule making process.  Comments submitted to FDA by December 28, 2022 will be considered when FDA drafts the final rule.  FDA intends that any resulting final rule would become effective 60 days after the date of the final rule’s publication in the Federal Register with a compliance date 3 years after the effective date. Food companies should consider looking into the eligibility of their products for “healthy” claims and consider whether they can make logical arguments if they wish to object to portions of the proposed rule.  We encourage food companies to review the provisions and make comments.   Contact us with questions or for help with your comments.

 

Letter on proposed changes to GRAS regulations

There is a bill before the Senate Committee on Health, Education, Labor, and Pensions that would drastically alter the path to market for new food ingredients.  As an observer of FDA, I expect that this bill will have ramifications for the dietary supplement industry and the New Dietary Ingredient Notification process.  Here is the text of the letter I sent to the committee members and the sponsoring senators:

Re: Comments on S.4316, Ensuring Safe and Toxic-Free Foods Act of 2022

Honorable Senators Murray, Burr, Markey, Blumenthal, and Warren,

This letter serves to provide comments on the draft of the Ensuring Safe and Toxic-Free Foods Act of 2022 issued by the Senate HELP Committee on May 26, 2022.

I am an FDA regulatory consultant with a focus in the food, dietary supplement, and cosmetic sectors. I have worked in FDA-regulated industry since 1986 as a researcher, pharmacologist, and regulatory affairs specialist.  I started my consulting company, Cadman Consulting Services, LLC, doing business as FDA Compliance Simplified, in 2001.  My company has served hundreds of companies from across the globe with over 250 clients in the food and dietary supplement industries.  I have assisted in the preparation of safety evaluations for many food and dietary ingredients. I have reviewed a number of self-affirmed Generally Recognized as Safe (GRAS) notices to evaluate their scientific rigor and advise as to whether the subject ingredient has been shown to be safe.

I am concerned about several aspects of S.4316. This bill will not achieve its stated goals but will increase costs to the Food and Drug Administration and in turn, American taxpayers.  American taxpayers will be further impacted by increased costs and potential limits to their food supply by some of the implausible and unhelpful provisions in the proposed bill.

The Generally Recognized as Safe Standard, reasonable certainty of no harm, should not be altered, Section 1.

The impact this bill would have is of great concern to my company and the hundreds of food and beverage companies we serve as regulatory affairs consultants since it would greatly alter the already strong standards of safety afforded to the United States food supply.  The United States enjoys a robust, varied, and safe food supply due to the existing reasonable standards for entry of new food ingredients into the marketplace.  The current Generally Recognized as Safe (GRAS) standard of “reasonable certainty of no harm.” provides a mechanism for safety review of new food components within the capacity permitted by the technologies and methods currently available.

Per Section 1, the proposed bill seeks to set a new and implausible standard of “toxic-free” foods, a standard which cannot be met even by many unprocessed, unaltered fruits and vegetables fresh from the fields.  Caffeine, which is known to, and roundly enjoyed by the U.S. population, is both naturally occurring in coffee, tea, and many other plant products but can be toxic[1].  Similarly, many fruits and vegetables contain a wide range of naturally occurring toxins[2].  The term “toxic-free” is not only unreasonable, it is undefined. The proposal of safety legislation without definitions of this key term belies ignorance of the natural chemistry of foodstuff as well as a failure to understand the current GRAS standard and the tools available to researchers to assess safety.

While FDA has authority to prevent unsafe products from being introduced into interstate commerce, the level of safety required by the Ensuring Safe and Toxic-Free Foods Act of 2022 will not advance the safety of the US food supply but will instead limit innovation. It will also very likely lead to an even greater increase in frivolous lawsuits alleging consumer harm where there is none.  The ultimate effect will not be to increase consumer safety; rather, it will be to increase consumer costs.

The proposed conflict of interest provision is implausible, Section 2. 

The many industry sectors regulated by FDA are responsible for providing data that their products are safe for their intended use and, in the case of drugs and medical devices, efficacious. The inventing companies cannot develop a new product without considerable research and testing.  This data is incorporated into their submissions to FDA for approval along with direct studies on the safety and efficacy of the potential new health product.  None of these sectors are barred from presenting data from studies that the inventing company has funded.  In fact, research of any kind requires considerable expenditure of time and capital.  How will safety data be obtained on novel food ingredients if the sponsoring company is prohibited from conducting safety studies?  Such studies are time consuming and expensive. Is it the intention of the writers of this bill that the U.S. government would pay for all the studies that would be required to establish the safety of new food ingredients?  A more reasoned approach would be for FDA to consider all submitted data and that such data be accompanied by conflict of interest statements, a practice which is common for scientific journals across many disciplines.

Review of food additives, Section 3

My clients and I do not object to the concept of reviewing GRAS substances as scientific knowledge is expanded and technologies developed that enable reassessment.  Nevertheless, we are concerned that such reviews will prove to be burdensome and expensive for FDA, the food industry, and American consumers unless the process by which substances are chosen for re-evaluation is based on reasonable and thoughtful criteria.  The current criteria used in the GRAS process appears to be sufficient since harm has not been alleged from the several thousand ingredients that have been the subject of GRAS notices[3].  The majority of GRAS notices, including self-affirmed GRAS notices[4] are for substances that are naturally-occurring in food and are not the result of synthetic chemistry.

It is noteworthy that none of the 10 ingredients proposed for reevaluation in section 3, part (f) of the proposed bill entered the US food or food packaging supply as a result of GRAS notices submitted by industry.  Many of the listed components of interest are already under review by FDA[5],[6].[7],[8] and the use of several has been limited in recent years.

Enforcement of current regulations will do more to protect the American food supply than S.4316

FDA has considerable authority that can be used to protect the US food supply and American consumers.  Timely follow up by the agency to food safety issues identified by consumer reports and the agency’s own inspections will do more for public health without overburdening the agency or American taxpayers than the proposal in the Ensuring Safe and Toxic-Free Foods Act of 2022. On behalf of myself, my company, and hundreds of clients, I urge you not to move this bill out of committee.

Sincerely,

Evelyn Cadman

Owner & Principal Consultant

[1] Beauchamp, G., Amaducci A, and Cook, M., Caffeine Toxicity: A Brief Review and Update, Clinical Pediatric Emergency Medicine, 2017, 18(3), p 197-202. https://www.sciencedirect.com/science/article/abs/pii/S152284011730040X

[2] Dolan, LC, Matulka, RA, and Burdock, GA, Naturally Occurring Food Toxins, Toxins 2010, 2, 2289-2232. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153292/pdf/toxins-02-02289.pdf

[3] FDA Inventory of GRAS Notices https://www.cfsanappsexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&sort=GRN_No&order=DESC&showAll=true&type=basic&search=

[4] AIBMR Life Science, Inc., Independent GRAS Self-Determination Inventory Database  https://docs.google.com/spreadsheets/d/1KdlygCppko64yts1O4ZdpzWWfsZZ3yKp97d4ooHGHdQ/edit#gid=0

[5] Perflouoroalkyl substances https://www.fda.gov/food/chemical-contaminants-food/testing-food-pfas-and-assessing-dietary-exposure, https://www.fda.gov/food/cfsan-constituent-updates/fda-makes-available-pfas-testing-results-first-survey-processed-foods, https://www.fda.gov/food/cfsan-constituent-updates/fda-issues-letter-industry-fluorinated-polyethylene-food-contact-containers

[6] Bisphenols https://www.fda.gov/media/90596/download

[7] Orthophthalates https://www.fda.gov/food/cfsan-constituent-updates/fda-limits-use-certain-phthalates-food-packaging-and-issues-request-information-about-current-food, https://www.fda.gov/food/food-ingredients-packaging/phthalates-food-packaging-and-food-contact-applications

[8] Brominated Vegetable Oil https://www.fda.gov/food/food-additives-petitions/brominated-vegetable-oil-bvo

 

Proposed Enforcement Discretion Policy for New Dietary Ingredient Notifications

On Friday, May 20, 2022, FDA published a policy on enforcement discretion regarding New Dietary Ingredients (NDIs) in the form of a draft guidance.   The Dietary Supplement Health Education Act of 1994 (DSHEA) amended the FD&C Act and set up the dietary supplement regulations we know today.  The requirement that industry submit a 75-day-premarket notification (NDIN) for New Dietary Ingredients (NDIs) has been confusing, argued over, and often ignored ever since.  An historical review of past notifications shows that FDA’s requirements evolved over time.  Initially, perhaps FDA accepted notices with little data but eventually it seemed that FDA’s definition of ‘reasonable expectation of safety’ had shifted to such an extent that very few notices were deemed sufficient.  In addition, industry and FDA have argued over what dietary ingredients are ‘new’ and FDA has rejected industry-complied lists of pre-DSHEA dietary ingredients that would not be subject to the 75-day-premarket notification requirement.  The many twists and turns to the story of the NDIN process are too extensive to review fully in this brief message but please see a past article on the topic here.

The recently-published draft enforcement discretion policy notes that dietary supplements containing NDIs that have not been the subject of a notification are deemed to be adulterated.  The policy also acknowledges that some firms “have the information ready to be submitted, but they are afraid of drawing attention to themselves with a late submission.”  The draft enforcement discretion policy allows companies that are “late submitting” required NDINs to submit them without fearing enforcement action. It is very interesting to read this and to see that FDA is trying to work with industry while still maintaining the regulations as originally written. What can this mean?? Well, in light of this document and recent warning letters that note the lack of NDINs, it seems that FDA plans to enforce the new dietary ingredient notice requirements.  It is also likely that FDA will also finalize the NDIN process, which has been in draft form since 2011.

The draft guidance also contained a very interesting note stating, “FDA recognizes that not every dietary supplement containing an NDI is subject to the notification requirement.”  This is very important because the agency had floated the idea in years past that any new combination of dietary ingredients would be subject to the new dietary ingredient notification requirements. It seems that at least one controversy regarding the NDIN process may have been settled in a manner that is not overly burdensome to industry and catastrophically onerous to FDA.

The comment period for the draft enforcement policy guidance is open until July 19.2022.  The specific provisions for the proposed enforcement discretion are:

The ‘late’ notices will be due within 180 days of publication of a final guidance.

The submission must include the required information specified in 21 CFR 190.6.

The agency also recommends providing “(1) documentation that the NDI-containing dietary supplement described in [the] notification was marketed in the United States as of [May 20, 2022] and (2) a copy of the current label for the dietary supplement.”

While not perfect, I view this as a step in the right direction and look forward to working with others to submit comments.

New for 2022! Bioengineered Food Labeling

Update February 17, 2022:

Please use this link to view the UNPA webinar “In the BEginning”… Dietary Supplements Supply Chain Starts with Ag mentioned in the original post.

The webinar opens with a general introduction and the presentations begin as indicated below.

Good Agricultural and Collection Practices begins at 14:30

Organic Best Practices begins at 32:00

GMO and Pesticide Testing begins at 55:10

Nation Bioengineered Food Disclosure Standard information begins at 1:10:00

Original Post:  I’m late with greetings for the start of the new year.  Not only did 2022 begin on January 1st, so did mandatory compliance with the National Bioengineered Food Disclosure Standard.  We provided an overview in a previous newsletter and next month I will be presenting more details about the standard as part of a webinar sponsored by the United Natural Products Alliance (UNPA).  While the webinar is directed to dietary supplement companies, it applies to food manufacturers as well and will cover topics relevant to quality systems, the Foreign Supplier Verification Program, tracking GMOs and the aforementioned bioengineered food disclosure standard.  There is no cost to take part in the webinar.

In the BEginning”… Dietary Supplements Supply Chain Starts with Ag webinar.
The February 10th 90-minute presentation will start at 10:30 MST.

Register

Quality raw material begins with Good Agricultural Practices to support FSMA Preventive Controls. This webinar will focus on dietary supplement risks beginning with the dirt. Our subject matter experts will cover Good Agricultural and Collection Practices (GACP), heavy metals and pesticides monitoring, organic processing requirements and common mistakes, Genetically Modified Organisms (GMO), and BE Labeling.

Topic: High quality botanical dietary supplements begin with high quality botanical raw materials.  This presentation will focus on Good Agricultural & Collection Practices (GACP), best practices in assessing and qualifying suppliers of botanical materials, and explore AHPA resources and guidance that can be useful in building solid long-lasting transparent supply chain relationships.

Topic: Organic processing requirements such as cleaning, sanitation and sanitizers along with covering allowed raw materials common to natural products / supplements, labels and best practices for maintaining compliance with QAI organic standards.

Topic: GMO’s what are they, who cares, and how do you test and monitor them. The presentation will include a discussion on DNA and pesticide testing.

Topic: The National Bioengineered Food Disclosure Standard is a recent addition to the regulations affecting the business practices and documentation requirements food and dietary supplement companies must adhere to. This presentation will review the requirements of the National Bioengineered Food Disclosure Standard and the resulting labeling requirements.

Register

Whether you join me for the webinar or not, I hope 2022 is a great year for you and yours!

 

Voluntary Sodium Reduction Targets for Foods

Many of you will recall that the 2016 updates to food nutrition labeling included a lower percent daily value for sodium (2300 mg/day).  Along with that, the update proposed that there should be a gradual reduction in sodium levels.  Last week FDA published a final guidance on voluntary sodium reduction in processed foods, including restaurant foods. As noted in the 2016 draft guidance, ”FDA is not conducting rulemaking with regard to sodium, and these goals are voluntary.”

 

The initial sodium reduction goal is modest with an aim to reduce U.S. sodium intake from an average of 3,400 mg per day to 3,000 mg per day in 2.5 years.  The previously-proposed 10-year goal to reduce the mean sodium intake level to 2,200 mg/day has not been finalized. The guidance focuses on average sodium levels in various food categories and does not set upper limits on individual products or product lines.

 

The proposal to encourage sodium reduction in processed foods has been controversial.  While evidence shows that high dietary sodium increases blood pressure, sodium also has functions beyond kicking up flavor in processed food. Added sodium also affects the texture, stability, and safety of many foods.  FDA’s guidance sets targets for both upper bounds and mean sodium levels for various food categories.  The targets were developed by assessing the sodium levels of various food categories and by reviewing sales data on those foods.  These analyses allowed FDA to set target mean sodium levels that are weighted by the sales data.  This means that a greater average reduction in American dietary sodium can be achieved by small changes in high sales categories.

 

The new guidance provides insights into FDA’s strategy:

“We developed the goals with a particular emphasis on maintaining concentrations needed for food safety, given the function of salt as a food preservative. These short-term goals are within the range of concentrations found in currently marketed foods and are feasible using existing technical strategies.”

“The extent of targeted reduction in each food category is influenced by the functions of sodium-containing ingredients in the category, as well as the distribution of sodium concentrations we found in products within that category. These values are FDA’s goals for each food category as a whole, not necessarily for individual manufacturers who choose to pursue these goals voluntarily. These mean target concentrations represent the benchmarks that we will use to assess the impact of any voluntary efforts by members of the food industry on the overall composition of the food supply.”

The goals are detailed as:

  • Support increased food choice for consumers seeking a diverse diet that is consistent with recommendations of the Dietary Guidelines by encouraging food reformulation and new product development for Americans;
  • Support the Dietary Guidelines, and NASEM (National Academies of Sciences, Engineering and Medicine) CDRR (Chronic Disease Risk Reduction Intake) recommendations of limiting sodium intake to 2,300 mg/day by encouraging sodium reduction over the short term to achieve an average intake of 3,000 mg/day;
  • Provide uniform metrics (mg of sodium per 100 g of food) for voluntary sodium reduction for industry stakeholders;
  • Focus on the total amount of sodium in a given food as opposed to individual sodium-containing ingredients; and
  • Support and extend industry’s voluntary efforts to reduce sodium across the range of commercially processed, packaged, and prepared foods.

I did a very crude analysis of the proposed target changes to the sales-weighted mean sodium levels and found that FDA is looking for reductions in sodium levels ranging from less than 2% for shelled nuts and seeds to 35% for gravy served in restaurants. FDA has targeted toddler meals for a 23.7% reduction in sodium.

It appears to be common for the restaurant versions of foods such as cheesecake, tomato-based sauces, gravy, potato side dishes, and even whole muscle meats to be slated for greater sodium reductions than their grocery-store counterparts. Notable exceptions to this trend were the grocery versions of butter, margarine, bacon, and bacon bits. I speculate that the requirement to declare sodium levels in the nutrition facts box may be what drives the consumer version of some foods to be lower in sodium than the restaurant versions in order to avoid ‘sodium sticker shock’ on consumer product labels. This would also seem to make sense for the butter, margarine, and bacon products, which have relatively small serving sizes and therefore declared sodium levels that would appear lower in the facts boxes.  Chips and popcorn are targeted for 12 to 15 percent reductions but nothing was said about the salted rims of margaritas.

 

The guidance notes that the reduction in sodium in products should not be accompanied by other ingredient changes that would offset the health benefit of the lowered sodium level.  For instance, fat and/or sugar content should not be increased when the sodium is lowered in a given food. Some may recall the low-fat food trends of the 1980’s and 1990’s that resulted in higher sugar levels in processed foods that has been credited for increased levels of obesity and diabetes in the U.S. FDA will be monitoring sodium levels as well as changes in other nutrients that may be affected by product reformulations. It may be safe to assume that those findings will inform the development of longer-term guidance on sodium reduction.

Special Regulations for Protein Products

Protein intake is essential to human health.  Concern for the health of our planet has led to great interest in obtaining protein sustainably.  Some, such as the Savory Institute view proper management of continental grasslands as the best route to balancing planetary health.  Others are working to develop of plant, algal, and fungal protein products.  Advancements are being made in methods to culture animal-based meats without growing whole animals. There are also efforts to commercialize insects as food sources.

As interest in novel protein products soars, so do the risks. Each of these solutions to our need to consume proteins leads to regulatory challenges.  Let’s start with insects. A colleague and friend, Katrina Emmel, Ph.D., recently published a great article about insects as food.  As she noted, the European Food Safety Authority approved dried yellow mealworms as a new food ingredient.  However, she also noted that insect proteins have not been deemed Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration (FDA).  Novel food sources, including proteins isolated from plants, as well as animal/insect sources that have not been part of the U.S. food supply must be evaluated for safety prior to market introduction.

The FDA and USDA (United States Department of Agriculture) signed an interagency agreement on how proteins made by cell culture technologies will be regulated in 2019. Under this agreement FDA will have regulatory oversight and inspection authority for the culture/production process pre-harvest.  USDA will have oversight and inspection authority over the products once harvested from cell culture.  Labeling will be regulated by USDA as well.

As mentioned above, plant-based protein ingredients need to establish GRAS status if the plant sources are processed to purify or partially purify the proteins. Plant-based protein products also need to be evaluated for their protein quality.

Animal-derived proteins are considered ‘complete’ in that they deliver the amino acids essential to human health in ratios that are central to good human nutrition.  Most plant proteins lack one or more essential amino acids or provide less than ideal amino acid ratios for human health. FDA requires evaluation of the amino acid ratios for any product presented as a source of protein. The protein quality is used to adjust the protein percent daily value on those products.  Those of you familiar with U.S. labeling regulations will recognize that protein daily values are not declared on most food labels.

Foods and dietary supplements labeled with protein claims, even if they only make that claim by identifying the product as a protein source, must declare a corrected percent daily value for protein (21 CFR 101.9(c)(7)). One method to correct the protein daily value is to use a factor known as Protein Digestibility Corrected Amino Acid Score (PDCAAS).  The PDCAAS score must be determined for each ingredient and accounts for levels of essential amino acids that are deemed to be ‘limiting’ because they are present at lower levels than are best for human nutrition. The digestibility of the protein is also accounted for in the PDCAAS value.  Most legumes are low in the essential amino acids methionine and cysteine, with typical protein quality scores in the range of 50 to 65 percent.  Grains, on the other hand, are low in lysine and threonine with typical protein quality scores in the range of 40 to 50 percent. Very few vegan protein products found in the U.S. market include corrected protein daily values in their nutrition or supplement facts boxes.

FDA has been slow to take enforcement action against the many violative products on the market. However, the agency did reiterate this requirement in the Federal Register Notice regarding the revised final rule for nutrition labeling. The increase in vegan protein products in the marketplace may lead the agency to look into the issue out of concern for public health. Companies that fail to evaluate the protein quality of plant-based products also risk lawsuits, as seen in a recent action against Kodiak Cakes.

Protein is essential to health and proper protein labeling is essential.   Contact us with any questions about these or other FDA regulatory issues.

 

2020 in Review

 

The year 2020 started out ordinarily enough for the FDA Compliance Simplified team.  We had projects related to foods, dietary supplements, over the counter (OTC) drugs, pet foods, and medical devices.  On March 2nd we received our first call regarding a project related to the new virus that was beginning to affect the United States. FDA scrambled to respond to the emergency. Soon we were fielding 5 to 8 calls per day regarding the coronavirus, SARS-CoV-2.  It started with many calls from companies wishing to import medical masks into the U.S.  Fraud was rampant.  Many companies never submitted the safety, efficacy, and quality system paperwork required for Emergency Use Authorization (EUA). Instead, they merely registered their facilities on the FDA website, presenting that as ‘proof’ of quality and began illegally taking orders from U.S. hospitals.  FDA readily granted EUA status to other manufacturers that did submit the required documentation to support their claims that their masks met FDA standards for effectiveness.  Nevertheless, FDA rescinded over 170 of those EUAs in a single day due to quality and compliance issues that were later discovered.  Masks and gowns for health care workers remain in shortage today.

Mixed in with the calls in March and April were dozens regarding hand sanitizer. Companies that previously manufactured automobile lubricants, other OTC drugs, food, beer, and spirits registered with FDA and began production of the World Health Organization (WHO) hand sanitizer formula. The WHO formula differed greatly from what consumers were used to in that it was not to contain fragrance or gelling agents.

No countries were permitting the export of medical grade masks—some more chastised in the news than others. This combined with the aforementioned rescindment of the EUAs for many masks led to calls from companies that were buying old manufacturing equipment to enable domestic production of masks for front-line medical workers.

FDA Compliance Simplified worked with companies with technologies to decontaminate medical masks and environmental air in medical facilities.  We, like counterparts working on diagnostic tests, experienced major changes to the EUA requirements on a weekly or even twice-weekly basis. FDA updated requirements to meet safety and efficacy concerns raised as OSHA tested technologies to ensure worker safety.

Throughout this time we continued to work on more ‘normal’ projects. Most of these were previously ‘back burner’ projects that companies turned to while their normal production was shut down during ‘safer at home’ restrictions and lockdowns. It was interesting to find that once New York City’s restrictions had been largely lifted, we received a number of calls from lawyers, architects, and actors seeking help to launch new food products. It seems that the extra time for reflection, provided while normal work lives were hog-tied, led many to decide to bring their dreams to market. Experienced food entrepreneurs understand the uphill climb those inspired dreamers have to “just sell this recipe I’ve been making for friends and family for years.”

With efforts of industry and FDA focused on the COVID-19 pandemic, shortages of more typical drug products occurred and some continue. FDA’s attention remains so focused on pandemic response that typical business has lapsed.  Presubmission meetings that are supposed to be scheduled within 60 days of request are now being scheduled 8 months out.  FDA has not implemented a virtual inspection system with the result that planned launches of new drugs are on hold for the foreseeable future (read more). It has been heartening to see that despite the extra workload for FDA in 2020, the agency did approve a typical number of new therapies. Some of these were for rare diseases with unmet therapeutic needs such as progeria, neuromyelitis optica spectrum disorder, and neuroblastoma.

In what is perhaps a hopeful sign that FDA will give attention to issues other than COVID-19, the agency issued warnings about weight loss and male enhancement products.  Whether this represents a return to normalcy or a response to the increased market interest in hand sanitizers, on December 31, 2020 FDA issued a final small entity compliance guide on consumer hand sanitizers based on pre-pandemic, non-EUA rules.

What will we see in 2021?  There is no doubt that FDA’s response to the COVID-19 pandemic will continue to evolve as the agency remains focused on programs to ensure public health related to foods, drugs, cosmetics, and the various other regulated industries. Whatever comes, it is my sincere hope that we will see the lives of all us, consumers, industry, and regulators alike, refocused on more typical avenues of innovation, product launches, and daily joy.

All the best to you and yours in 2021.

Prop 65 for FDA-regulated Products

Helping companies comply with FDA regulations is our specialty.  But FDA is not the only regulatory body our clients need to be aware of.  As our readers know, from time to time we invite other experts to provide other regulatory information essential to market success for FDA-regulated products.  This post is from Dr. Derek Drechsel, a toxicologist with CTEH and the topic is California’s Prop 65 regulations.  Unfortunately, many FDA-regulated companies do not learn about these rules until they are sued.  The information below is to help you avoid that sort of surprise.

What is Prop 65?

The Safe Drinking Water and Toxic Enforcement Act of 1986, better known as Proposition 65 (Prop 65), requires businesses operating in California to provide warnings about exposures to chemicals or substances that may cause cancer and/or reproductive and developmental toxicity. The California Office of Environmental Health Hazard Assessment (OEHHA) administers the Prop 65 program and has listed over 900 chemicals to date for consideration. Prop 65 states that a warning is required for these chemicals unless it can be shown that a significant exposure does not occur under reasonable use. To determine what entails a significant exposure, OEHHA has established safe harbor levels for cancer (No Significant Risk Level or NSRL) or developmental and reproductive harm (Maximum Allowable Dose Level or MADL). A business is exempt from Prop 65 warning requirements if demonstrated that exposure to a chemical occurs at or below safe harbor levels.

Penalties for failure to comply with Prop 65 can be substantial, with fines for violations up to $2,500 per day. In addition, according to the California Attorney General’s office, businesses spend millions of dollars ($35 million in 2018) to settle Prop 65 lawsuits. Hundreds of notices are filed with the Attorney General office each month. While the original act was intended to protect the state’s drinking water supplies, the impact of Prop 65 has grown to affect manufacturing and construction industries as well as foods, personal care cosmetics, and consumer products. Common chemicals targeted in notices include lead and other heavy metals (cadmium, arsenic), acrylamide, phthalates, hexavalent chromium, and formaldehyde. While other emerging chemicals and new product categories are continually identified and targeted.

What can I do to protect against Prop 65 claims?

There are several pathways by which companies selling products or conducting business in California can address potential Prop 65 issues. The first is a pro-active approach to determine if a product contains a Prop 65 listed chemical. This can be achieved by a critical review of supply chain materials, product formulations, and manufacturing processes or performing appropriate analytical testing and exposure assessment to determine if a significant exposure may exist. By identifying a potential issue, steps can be taken to reformulate or substitute for the chemical or substance of concern, where possible, or comply with Prop 65 warning requirements. Additionally, regular monitoring of Prop 65 notices, trends, and guidance published by OEHHA can be useful. The purpose of a pro-active approach is to identify and address any potential issues, avoid any future claims or violations, and be prepared to respond to any alleged claims.

In the event that a business receives a notice of violation from a private party, there are several steps they may take to assess the validity of the claim. First, one may contact the notifying party to ask for any relevant information to support the claim. However, it should be noted that the notifying party is not required to provide any such information. Second, one should conduct a scientific evaluation to determine if the claim is valid. This may include (1) laboratory testing of the product to determine the presence and concentration of the chemical or substance at issue, and/or (2) an exposure assessment to compare potential exposure from reasonable use of the product to the safe harbor level. Using proper methodology based on current scientific standards and Prop 65 guidance is critical. For this reason, one should ensure that an analyst and/or scientist experienced in Prop 65 issues are involved in the process.

What Are Some Challenges in Addressing Prop 65?

Of the over 900 chemicals currently listed under Prop 65, hundreds do not have safe harbor levels (NSRL or MADL) established by OEHHA. This presents a challenge to businesses determining warning exemptions or addressing notices of violation for such chemicals. However, experienced scientists can review relevant toxicology information to derive safe harbor levels for such chemicals in accordance with Prop 65 guidance, thus allowing businesses to conduct risk assessments to evaluate potential warning requirements in the absence of established levels.

Another common issue is related to “naturally-occurring” chemicals, or those chemicals that are naturally found in the environment and not intentionally added to a product. Heavy metals, such as lead, cadmium and arsenic, are listed under Prop 65 with stringent safe harbor levels. This creates a particular challenge to manufacturers and distributors of foods and nutritional supplements since soil and water naturally contain these metals. Prop 65 regulations contain a naturally-occurring exemption, although application of this protection has proven difficult and costly to parties attempting to do so. Scientific expertise and knowledge of precedents set forth by OEHHA for specific chemicals and/or products are essential to address such issues.

Am I exempted from Prop 65 Warning Requirements?

Demonstrated exposure below safe harbor levels and the naturally-occurring exemption are two of several means that manufacturers and distributors may be relieved from Prop 65 requirements. For a complete list and answers to frequently asked questions related to Prop 65, one should visit the CA Attorney General Office website.

CTEH scientists have extensive professional experience evaluating potential health hazards and conducting human health risk assessments for numerous commercial and consumer products, including applications to prepare for and respond to Prop 65 issues. For more information on CTEH’s capabilities, please contact Dr. Derek Drechsel.

Contact us with any questions.

Stay well!

A Bit of ‘Normal’ in 2020: Food Facility Registration Renewal

Few events are truly global but the 2020 pandemic has affected every living being on the planet in some way.  It is the rare person whose life and/or business has not been turned upside down this year but I am pleased to bring you a tiny bit of normality:  FDA Food Facility Registrations must be renewed between now and the end of 2020.  For FDA, “Food Facilities” include any domestic or foreign facility that manufactures, processes, packs, or holds food or dietary supplements for human or animal consumption in the United States.  Mobile facilities must also register but farms, transport vehicles and fishing vessels are exempt from the registration requirement.

FDA has been swamped this year with duties relating to the agency’s response to the pandemic. Food manufacturing operations have been greatly impacted by changes in facility operations. As a result FDA has allowed flexibility on egg packaging, ingredient labeling, and sale of foods labeled for use in the restaurant industry directly to consumers.  In addition, the agency announced that it will exercise enforcement discretion regarding the January 1, 2021 deadline for the smallest food manufacturers to comply with the 2016 Food Labeling Regulations.  It could happen that FDA will also defer enforcement of the facility registration renewal requirement and are simply slow to notify industry.  However, since the registration is easily accomplished online, it makes sense to comply.

FDA has published a step-by-step user guide to the registration process. In addition to expected queries about the facility’s name, location, and management, two very important bits of information are required for registration:

  1. A statement in which the owner, operator, or agent in charge provides an assurance that FDA will be permitted to inspect the facility at the times and in the manner permitted by the FD&C Act;
  2. A statement in which the owner, operator, or agent in charge certifies that the information submitted is true and accurate.

These two requirements ensure that FDA will have cause and authority to cancel a facility’s registration if the agency is denied access to the facility or if there is a finding that the information submitted was incorrect.

This year is the first in which use of a ”Unique Facility Identifier” (UFI) is required.  The UFI will have to meet FDA requirements. A Data Universal Numbering System D-U-N-S (DUNS) number is listed as an acceptable UFI.  DUNS numbers are assigned and managed by Dun & Bradstreet.  Information on obtaining a DUNS number can be found here.

My colleagues and I wish you and yours good health.  It has been a true joy to hear from past clients and know they are well.  We have also been privileged to work with new clients this year.  We are ready to assist you with facility registrations or other aspects of compliance with FDA regulations.

FDA and COVID-19

Updated March 30, 2020

The past few weeks have brought disruption to our daily lives in ways large and small.  May we learn what is important and where to spend our energy from this experience.  The FDA is also undergoing extreme disruption as they work to continue to protect the public health and respond to the global COVID-19 pandemic.  We and companies like ours are experiencing a huge increase in calls from companies interested in understanding FDA requirements in order to respond to this emergency. We are always eager to educate, inform, and serve you and hope that you will find this article helpful.  I will list a few basic concepts and then provide links to specific FDA programs enacted in response to COVID-19. Be sure to contact us with any questions.

  1. While some requirements have been reported as ‘loosened’ and some FDA activities characterized as ‘dropped’ in consumer and trade publications, the basic premise that products intended for use in and on the human body must be safe and effective remains in effect.
  2. FDA has issued Emergency Use Authorizations to increase the supply of products required for health care personnel and first responders but a strong regulatory framework is still in place for those products.

Applicable to a variety of products

 Update: Adverse Event Reporting

FDA has issued published guidance on Adverse Event (AE) reporting for medical products and dietary supplements during the COVID-19 pandemic. While normal AE reporting should be maintained whenever possible, the agency notes that workforces may be reduced during a pandemic; therefore, this guidance is intended for firms unable to continue normal reporting operations, where impacted firms are requested to focus reporting on AEs related to medical products indicated for the treatment or prevention of the pathogen causing the pandemic (not limited to influenza or COVID-19), and other reports indicated in the guidance document or specified by FDA. It should be noted this guidance does not extend to monitoring or reporting AEs for investigational use of drugs, biologics, and devices or guidance imposed as a condition for medical products authorized for emergency use.

A number of pandemic preparedness planning resources are available to firms, which can be found here and here. Companies should develop a continuity of operations plan (COOP) that includes instructions for AE reporting and the submission of AE reports at a future time. Should a company be unable to fulfill normal AE reporting activities, documentation should include a formal declaration of the pandemic by a respected regulatory or governing body (i.e., the World Health Organization) and specific factors preventing normal AE reporting requirements (i.e., high absenteeism).

FDA notes that any delayed AE reports should be submitted within 6 months of the restoration of AE reporting activities to the pre-pandemic state. For impacted firms, AE reports should be submitted on a priority basis, where reports with regulatory timeframes of < 30 days should be submitted before periodic safety reports. If FDA has designated a product as presenting special concerns, AE reports must be submitted regardless of the timeframe. For medical devices, the agency notes that priority is specified by the outcome, where a fatal outcome is prioritized over a nonfatal outcome. Further guidance on AE report prioritization is provided in Table 1 of the guidance.

Industry Specific News:

Medical Devices

You have heard that new diagnostic tests are undergoing expedited reviews and being approved almost daily. These devices are the subject of the most far-reaching Emergency Use Authorization (EUA) FDA has issued in response to COVID-19. See also FAQs on diagnostic tests and the section titled, “In Vitro Diagnostics EUAs” on this page.

Personal Protective Equipment (PPE) including N95 masks, surgical masks, gloves, face shields, and gowns are medical devices.  The only change to the regulatory requirements for these products is that FDA has allowed for the use of expired N95 masks.  See details here, here, here, and in a ‘down arrow’ section under Personal Protective Equipment EUA on this page.

FDA has also provided a set of FAQs on gloves with a section specifically for companies that want to start supplying gloves.

All other regulations for GMPs, quality systems, device registration, and 510(k) submissions still apply.

Update:  Ventilators and Other Respiratory Devices

FDA has published guidance on an enforcement policy to expand the availability of Class II ventilators, anesthesia gas machines, and other respiratory devices and their accessories during the COVID-19 pandemic. The agency’s policy provides flexibility for manufacturers to modify devices to reduce manufacturing limitations or prevent supply shortages.  This flexibility does not reduce FDA’s requirements for validation of the safety and efficacy of the ventilators produced under this temporary emergency policy.

While the use of “FDA-cleared conventional/standard full-featured ventilators” is preferred, the agency notes that modification to the indications, claims, functionality, hardware, software, or materials of a device may be required which would ordinarily require a premarket notification submission. Specific examples are outlined in the guidance document. Furthermore, FDA has noted that specific durations of use or shelf life may be extended for various ancillary devices in situations that would not create undue risk.

The agency notes that manufacturers should conduct and document appropriate validation for changes made to hardware, software, materials, or duration of use as outlined in the guidance document. All changes should be recorded in the device master record and change control record. Devices that have been modified should be labeled with: a description of the device’s indications, claims, or functions, and performance and potential risks; instructions for use, environment of use, and details on the design differences and known risks; and delineation of FDA-cleared indications and claims from those which have not been cleared by FDA.  The agency requests that manufacturers work with FDA through its EUA process.

Drugs Including Hand Sanitizers and Therapeutics

Hand sanitizers are regulated as over-the-counter drugs.  The ingredients used in them have been under FDA review for years and the agency has divided the category into products for health care professionals and consumers.  Due to the current need for products in both categories, FDA has temporarily reversed previous decisions and has issued emergency use authorizations for hand sanitizers. These policies allow for companies that do not typically manufacture drugs to make hand sanitizers.  This is a temporary authorization and requires companies making hand sanitizer to follow basic good manufacturing procedures, register their facilities (for inspection purposes), and list these products with FDA.  Please see the policy here.  There is a separate but similar policy for compounding pharmacies.

FDA has published a webpage to help companies with potential COVID-19 therapeutics.  Changes to FDA’s foreign and domestic inspection program are discussed here.

Update:  Alcohol-Based Hand Sanitizer Products

On March 27, 2020, FDA updated a temporary policy regarding the manufacture of ethyl alcohol for incorporation into alcohol-based hand sanitizers. As production of alcohol-based hand sanitizers ramps up, the demand for raw materials, including ethanol, has increased. FDA’s policy allows for manufacturers to produce ethanol (also referred to as ethyl alcohol) for use as the Active Pharmaceutical Ingredient (API) in alcohol-based hand sanitizers for consumer and health care professional use during the COVID-19 public health emergency, as long as: the companies produce ethanol of sufficient purity (as outlined in the guidance document) following basic good manufacturing procedures; denature and label the ethanol following appropriate methods detailed in the guidance document; register their facilities; and list these products with FDA.

Denaturing the ethanol is a critical step to prevent adverse events from unintentional ingestion of hand sanitizer. The ethanol can be denatured by the manufacturer or at the point of manufacture or compounding of the hand sanitizer. While FDA continues to evaluate appropriate denaturing formulas, the agency provides formulas in Appendix C of the guidance document for the use of denatonium benzoate with or without tert-butyl alcohol, sucrose octaacetate with or without tert-butyl alcohol, or isopropyl alcohol as denaturants.

Update:  Drugs Subject to a Risk Evaluation and Mitigation Strategy

A limited number of drugs are subject to a Risk Evaluation and Mitigation Strategy (REMS), which may include a Medication guide, patient package insert, communication plan, and/or certain packaging or safe disposal technologies for drugs. Elements to assure safe use (ETASU) may also be part of the REMS requirements for a drug, which can require laboratory testing or imagining studies. Given that patients may be unwilling or unable to complete the required testing or studies due to self-isolation or quarantine, FDA has published a policy regarding REMS requirements during the COVID-19 pandemic.

The agency states that health care providers prescribing and/or dispensing REMs drugs should consider whether or not compelling reasons exist to not complete the test or studies, and to use their best medical judgment to weight the benefits and risks of completing treatment in the absence of laboratory tests and imaging studies. Health care providers should communicate these considerations to patients. While the REMS requirements remain in effect, FDA does not intend to take action for failure to adhere to certain laboratory testing or image study requirements.

Foods, Dietary Supplements, and Animal Foods

On March 18, 2020, FDA held a briefing for the food industry, including the dietary supplement and animal food industries.  While COVID-19 is not a food-borne illness, FDA discussed the importance of good sanitation and maintenance of standard GMPs in manufacturing activities, which always includes the need to ensure that employees are healthy.  FDA has published a set of FAQs for the food industry.

The agency also discussed changes to their inspection activities. They have postponed routine foreign and domestic facility inspections.  “For cause” domestic inspections will still take place and “mission critical” foreign inspections “will be considered on a case-by-case basis.”

During the March 18 briefing, FDA announced that domestic supplier verification required under the Food Safety Modernization Act (FSMA) and Foreign Supplier Verification Program (FSVP) requirements would not be enforced as a temporary measure.  Food, dietary supplement, and animal food companies must still be diligent to ensure the safety of their products.

Update:  Nutrition Labeling    On March 26, 2020, FDA published guidance regarding a temporary policy for nutrition labeling requirements of specific packaged food during the COVID-19 pandemic. The guidance is intended to provide flexibility in label requirements to restaurants and restaurant-supply food manufactures to enable them to sell specific packaged foods directly to retail consumers. It does not apply to restaurant prepared foods.

The agency has indicated that restaurants and food manufacturing facilities with inventory labeled for restaurant use may sell packaged foods without a Nutrition Facts label as long as the food does not have any nutrition claims and is labeled with: a statement of identity; ingredient statement; the name and place of business of the food manufacturer, packer, or distributor; net quantity of the contents; and allergen information required by the Food Allergen Labeling and Consumer Protection Act (FALCPA). Original packaging labels may be reused or labels may be created to provide the necessary information to the consumer.

Cosmetics

There have been no new policies issued for cosmetic manufacturers due to COVID-19.  The changes to inspection activities discussed above apply to cosmetic companies.

Our team is fortunate to remain healthy and at work, so let us know if you have questions on these or other FDA compliance topics.  Meanwhile stay calm, stay well, and stay put.

30 March 2020 Thanks to Katrina Emmel for assistance with this update.

 

 

New Dietary Ingredient Notifications

The Dietary Supplement Health Education Act of 1994 (DSHEA) defined dietary ingredients as

  • a vitamin;
  • a mineral;
  • an herb or other botanical;
  • an amino acid;
  • a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or
  • a concentrate, metabolite, constituent, extract, or combination of any of the above.

Dietary ingredients in use as of October 15, 1994, the date DSHEA was signed into law, were included in this definition. However, any ingredients introduced for use in dietary supplements after that date are required by law to be the subject of a New Dietary Ingredient Notification (NDIN).  To learn more about NDINs, the results of recent NDIN submissions and what your NDIN should include, please see a recent article my colleagues and I have published: NDIs for dietary supplements: How to proceed in 2020.

Let me know if you have questions.  My colleagues and I would be pleased to help you with your submission.

Hindsight and 2020

Hello and Happy New Year!   FDA was busy in 2019 but we didn’t publish many blog posts: So many topics, so little time. Before looking ahead to 2020, Let’s look back at some interesting things that FDA did in 2019.

Drugs: FDA published a final rule on consumer hand sanitizers. Twenty-eight active ingredients were officially removed from consideration as active ingredients.  One of the banned ingredients is triclosan, which has historically been widely used.  New Drug Applications will be required of companies that wish to continue to use any of the 28 banned ingredients.  In related news, FDA has deferred action on benzalkonium chloride, ethyl alcohol, and isopropyl alcohol to allow industry more time to submit data demonstrating safety and efficacy of those ingredients in hand sanitizers.

The agency also published some helpful guidance documents for drug manufacturers.  One is a guidance on conducting maximal usage trials for assessing the safety of topical over the counter drugs.  FDA continued its response to the 1997 FDA Modernization Act by publishing a draft guidance for demonstrating substantial evidence for effectiveness. This guidance discusses scenarios for new types of data that may be used when clinical endpoints are not clear and the possibility that one clinical trial could be sufficient to demonstrate effectiveness.

Medical Devices: FDA has continued to update medical device regulations and one area that is potentially of wide consumer interest is the publication of a final rule for self-fitting hearing aids.  The first such device was cleared in 2018.  The new guidance, which deems self-fitting hearing aids to be Class II and under special controls, may well usher in a time when hearing aids can be bought over the counter, much like reading glasses are today.

Foods: Protection of public health through regulation of foods continues to be high on FDA’s agenda.  One sign of this was the issuance of the first warning letter pertaining to the Foreign Supplier Verification Program. In this case the importer failed to adequately monitor their supplier allowing a product contaminated with Salmonella into the U.S. food supply.  It is essential that anyone importing foods or food ingredients understands their obligations under this rule. FDA also provided a list of records required under FSVP.  Click here to better understand whether this regulation applies to your operation.

FDA continued its look at per- and polyfluoroalkyl substances (PFAS), which are used in many food contact substances; particularly to make paperboard containers grease and water resistant and for non-stick cooking surfaces. The agency released analytical results on PFAS in the U.S. food supply as well as testing methods to detect these chemicals.

FDA published a supplement to the food code and an online training manual on how to interpret and enforce it.  They also provided an online food defense plan builder and related training videos.

2019 saw FDA working on Standards of Identity.  Consumer demands have led to changes in the U.S. food supply. Many FDA regulations are outdated and do not address technological advances in food production.  Is ultra-filtered milk really milk?  Not according to current standards of identity.  As a result FDA has reopened the comment period on uses of ultra-filtered milk in cheeses.

Related issues were discussed in a Public Meeting held in September.  Participants discussed naming of plant-based ‘milks’ and ‘meats’ as well as issues such as what ingredients must be in French salad dressing and cherry pie.  Another food naming issue is subject to FDA enforcement discretion: The salt substitute, potassium chloride may be listed as “potassium chloride salt” in the ingredient statement on food labels.

Dietary Supplements: In February, then FDA Commissioner, Scott Gottlieb, M.D., announced a plan for policy advancements to modernize dietary supplement regulation. His plan was to communicate concerns about marketed dietary supplements quickly, allow innovation while still ensuring public safety, develop new enforcement strategies, to work with industry partners, and engage in a public dialogue with dietary supplement stakeholders.  In April 2019, FDA announced publication of a dietary supplement ingredient advisory list.  With this list, FDA identifies ingredients that “do not appear to be lawfully included in products marketed as dietary supplements.” First on the list were andarine, higenamine, hordenine and DMAA; all most commonly found in supplements for body builders and others interested in physical performance.

In late May 2019, FDA held a public meeting billed as “Responsible Innovation in Dietary Supplements.” The public comments focused on the New Dietary Ingredient Notification (NDIN) process that has been stalled since 2011.  Industry called on FDA to consider use of master file system that could limit the number of NDINs that would be required and enable companies that invest in rigorous testing to protect their investments. Industry would also like FDA to reconsider how to define ‘chemically altered’ as relates to some botanical components and to allow for synthetic copies of phytochemicals to be considered dietary ingredients.  Central to the NDIN issue is determining what ingredients were sold in the U.S. prior to enactment of the Dietary Supplement Health Education Act (DSHEA) and therefore not subject to the NDIN requirement. On October 3, 2019 FDA held a public meeting on developing a pre-DSHEA list of dietary ingredients.

Something new observed in 2019 was the issuance of warning letters to companies that likely consider themselves dietary supplement manufacturers but that are written from the Center for Drug Evaluation and Research (here) and the Division of Pharmaceutical Quality Operations (here).  The dietary supplement industry should be happy to see this.  Industry has rightfully argued that enforcement actions against products with labeling that includes therapeutic claims should not be classified as dietary supplements in those warning letters when they are actually unapproved new drugs.

The Federal Trade Commission (FTC) assists FDA in their enforcement of dietary supplement regulations and in 2019, a court upheld $40 million dollar in sanctions from FTC to a supplement manufacturer for failing to have “competent and reliable scientific evidence” to support product claims.

Cannabidiol CBD:  Is it a food, dietary supplement, pet treat, or drug?  Whatever the answer is, CBD appears to be the hottest regulatory issue of 2019. FDA and the hemp industry are at odds regarding CBD’s status while consumers are snapping up products they presume to be safe and effective. Congress has asked FDA to deem CBD to be safe and the agency has undertaken research to address safety and regulatory concerns.

 

The Year 2020: What is in store for FDA-regulated industry in 2020? Beginning today food and dietary supplement companies with annual sales of ten million dollars or more are supposed to comply with the 2016 revisions to nutrition labeling regulations.  It should be noted that FDA has announced that “during the first 6 months following the January 1, 2020, compliance date, FDA plans to work cooperatively with manufacturers to meet the new Nutrition Facts label requirements and will not focus on enforcement actions regarding these requirements during that time.”

As of January 4, 2020, all food facility registrations must be completed electronically unless they have been granted a waiver by FDA.  2020 is an even-numbered year and all facilities must renew their registration between October 1 and December 31, 2020.

FDA is subject to a Consent Decree and must meet deadlines to comply with statutory requirements under the Food Safety Modernization Act (FSMA). The agency was sued by the Center for Food Safety and the Center for Environmental Health for failing to publish a list of high-risk foods.  Per the decree, by September 8, 2020, FDA must provide such a list and publish a proposed rule that includes record-keeping requirements for high-risk foods.

Optimistic hopes for 2020 are that FDA would at last define “healthy” and update other nutrient content claims in congruence with the 2016 updates to nutrition labeling regulations. The old definitions do not work with the current regulations.  For now FDA is not taking enforcement action against foods that are labeled as “healthy” but do not meet the old definitions, as long as their fat content is predominantly mono and polyunsaturated or if they contain at least ten percent of the Daily Value (DV) per reference amount customarily consumed (RACC) of potassium or vitamin D.

It may be overly optimistic but the dietary supplement industry would be pleased to see a list of pre-DSHEA dietary ingredients along with a finalized NDIN process. The food industry is eager for updates to many food standards of identity.  Most FDA-regulated industry sectors will be impacted by any rulings FDA makes regarding CBD.  Whatever happens, may 2020 be a year of vision and insight!

 

Are you CBD curious?

We are based in Colorado, a state that has legalized both medicinal and recreational marijuana use.  Colorado’s industrial hemp farming program was initiated through legislation adopted in 2013.

On the national scene, passage of  the 2018 Agriculture Improvement Act removed hemp from the controlled substance list.  Since then, the market has been inundated with CBD-containing products.  Are they legal?  And what should your company understand if you are thinking about launching a product that includes CBD?

To answer those question I invite you to read the first in a series of articles I have co-authored: What is CBD’s regulatory status and how should companies proceed?

There is Nothing Simple About Importing Products into the United States

Here at FDA Compliance Simplified we frequently work with companies that wish to import products into the U.S.  While we can help those companies comply with the U.S. Food and Drug Administration import requirements, those are only part of the regulatory pathway that must be navigated in order to import products into the U.S.  You can find our post about FDA import requirements here.  Below is a description of the import process from the perspective of Customs and Border Protection (CBP) provided by one of our partners, Sean Scarbrough of Taggart International, Ltd., a U.S. Customs Brokerage and freight forwarding firm that specializes in U.S. Customs regulations.

There is nothing simple or easy about importing product legally and properly into the United States, especially if your company has never done it before. This is even more so when the products being imported have U.S. Food & Drug Administration (U.S. FDA) oversight. As background, there is no unalienable right to import products into the U.S., even for U.S. citizens. It is a privilege granted those that agree to do so compliantly – whether the importer understands the rules or not. However, it is the importer’s responsibility to understand the U.S. import regulations and to abide by them. Failure to do either can result in significant fines or penalties and in some cases, criminal prosecution for those involved.

The U.S. Customs Informed Compliance publication entitled, “Reasonable Care” provides some insight into the extent to which CBP holds importers accountable for what they do or is done in their name. Other Customs publications that will help you look further into what is required should you choose to be a U.S. importer can be found here and here.

Required Information for FDA-Regulated Imports

It is best to have an experienced Customs broker help your firm with the process. The information below is required to have a meaningful and specific conversation with your broker about importing goods into the U.S.A.  All of this information is necessary if your firm is ever to either ship commercial quantities to the U.S.A or act as the U.S. importer of record.

  1. Names of all contract manufactures, their full addresses and the manufacturer’s U.S. FDA registration numbers.
  2. Your company’s FDA Registration number, if required.
  3. If the products are going to be held at another facility prior to export to the U.S.A, those facility registration numbers as well.
  4. U.S. service of process agent for FDA purposes, if your company is not setting up a U.S. operation that will have a person that can fulfill that responsibility.
  5. Confirm your product packaging and/or labeling has been approved or registered, or that it is not necessary by a qualified expert.

Information Required by Customs

Once the above preliminary information is in place, there is a set of Customs-related questions or areas of exploration that will need to be addressed including:

  1. What is the Harmonized Tariff Schedule of the United States (HTSUS) of the product(s)?
  2. What are the relevant duty rates?
  3. Are there other Customs-related Harmonized Tariff Schedule matters?
  4. Who will be the U.S. Importer of Record (U.S. IOR)?
  5. If you are shipping in commercial quantities, someone must be the U.S. importer of record.
  6. The U.S. IOR can be a foreign company, but additional requirements and considerations impact.
  7. Will a U.S. Customs continuous bond be purchased or will single transaction bonds be used? This is based upon a number of factors, including estimated import value of the good(s) and the duties, taxes and fees.
  8. What will be the reported value of the merchandise at the time of importation and are those values proper or correct?

Based upon the answers to the above, additional questions or issues will surface that will need to be addressed. Likewise, this is all before discussing the physical movement of the goods from origin location(s) to destination(s). There will likely be questions about those, particularly with the costs for doing it all with providers that satisfy FDA requirements. As stated earlier, there is nothing easy or simple about the process. It is a complicated, exacting and tedious process even with the most mundane of products, which is very time consuming for all parties involved. We understand it is a necessary part of the business case buildout for companies that are entertaining the idea of selling products in the U.S.A and we at Taggart International, Ltd. are happy to help.

Importing FDA Regulated Products into the United States

Successful launch of a product requires more than a good marketing plan.  It is also important to know whether your product is subject to special regulations from various government agencies.  While the Federal Trade Commission, Consumer Product Safety Commission and even the Environmental Protection Agency have regulatory interests in a number of products, it is the Food and Drug Administration (FDA) that is most closely involved in the regulation of products that touch our lives every day.

Foods, cosmetics, dietary supplements, and over the counter drugs account for a considerable percentage of US consumer spending.  Each of these product categories is subject to scores of unique regulations and labeling requirements.  While confusing enough for domestic producers, proper compliance with FDA regulations can be daunting for importers.  Not only do imported products need to comply with the same regulations as those that are domestically-produced, due to the inspection process, imported products are often held to a higher level of compliance due to the inspection process and are also subject to some additional requirements.

Important Steps for Importers

Before bringing a product to the US market, it is crucial for importers to know whether the ingredients are permitted in the US, whether the manufacturing met required guidelines and whether the label is properly formatted.  Products that contain ingredients that are not permitted for use in the US are deemed ‘adulterated’ by FDA and will not be given entry to the US.  Products that are improperly labeled are considered ‘misbranded’ and will likely be detained by FDA.  In either case, the result is lost time and money along with the discovery that those problems have opened the door to future import frustrations.

In 2018 all provisions of the Food Safety Modernization Act came into effect.  One section of the resulting regulations is the Foreign Supplier Verification Program.   Under this set of regulations ingredient importers are obligated to ensure that their suppliers can meet FDA regulations.  At FDA Compliance Simplified we specialize in regulatory compliance for FDA-regulated products.  We can review your proposed import to ensure the ingredients may be used in the US.  We can tell you whether the label is compliant with US regulations and what other regulatory issues you need to be aware of.  Below is a list of FDA import requirements that we can help you with.

Steps for importing products into the US

  1. You must ensure that your product ingredients are permitted in the US.
  2. If the products include animal-derived ingredients (meat, fish, poultry, eggs, milk, cheese, etc.) you will need an animal ingredient import license from USDA and depending upon the amount and type of the animal-derived ingredient, you may have registrations, regulations and labeling requirements in addition to the ones listed below.
  3. Review FDA Food Safety requirements and GMP regulations to ensure that the facility where the product is being produced can comply with the regulations since the next step, registration, puts you on FDA’s inspection list.
  4. Register the facility(ies) where the products are produced and warehoused.
  5. Process registration for shelf-stable products that have certain pH and moisture levels. This generally refers to any product that is not dry and does not have to be refrigerated or frozen to retain freshness
  6. You must ensure that the product label is in compliance with FDA regulations

You must notify the FDA of your shipments so they can be inspected upon import. There are many regulations pertaining to U.S. Customs and Border Protection and you can read more about that here. It is best to engage a US Customs Broker with experience working with FDA-regulated products to do this.

Happy 2019 & Year-End News from 2018

Happy New Year!!!

As we step into 2019 we need to take a brief look back at the last week or so of 2018 to review rule makings published by FDA and USDA.

On December 21st USDA published their final rule on bioengineered food disclosure labeling; what consumers think of as GMO labeling. The rule may be a disappointment to many.  See our discussion here.

Also on December 21, 2018 FDA published technical amendments  to the 2016 food labeling regulations.  These amendments do not change to intent of the rules but correct various errors in the final rule.  For example, entire sections of 21 CFR 101.9 regarding declaration of trans fats as well as mono- and poly-unsaturated fats that were inadvertently omitted are being added back. The amendments also made various corrections to sample nutrition and supplement facts boxes that FDA published with the 2016 rule.  Unfortunately, due to the current government shutdown the changes are not yet available in the electronic Code of Federal Regulations and will not be updated in the version of the CFR on FDA’s website until April.  We will update links to the revised regulations in the web-version of this post once they become available.

Late in 2018 Congress passed the 2018 Farm Bill.  While the bill legalized regulated hemp production, it did not legalize the use of CBD or THC in FDA-regulated products that are not approved drugs.  It is still illegal to add CD or THC to foods, dietary supplements, pet food/treats, or cosmetics.

So many new things to end 2018!  No doubt we can be sure that updates and changes will continue into 2019.  We hope that the new year will be one of joys and successes for you.  We’d love to help you along the way.

 

Highlights of the National Bioengineered Food Disclosure Standard

On December 21, 2018 USDA published their final rule on bioengineered food disclosure labeling, commonly known as “GMO labeling”.  The rule adheres to the stipulations in the enabling legislation and is based on the current science but may not satisfy consumers.

The scope of the labeling requirement is limited by statute and applies only to human food that is subject to FDA labeling requirements and certain USDA Food Safety and Inspection Service (FSIS) regulations.  The new regulations to be published as 7 CFR Part 66 define a bioengineered food as, “A food that contains genetic material that has been modified through in vitro recombinant deoxyribonucleic acid (rDNA) techniques and for which the modification could not otherwise be obtained through conventional breeding or found in nature….”  This is a significant departure from the now preempted 2016 Vermont Law that required labeling of any food “produced with genetic engineering” or that may have been produced with genetic engineering.

Foods exempted from the disclosure requirement include:

  1. Refined foods that do not contain detectable levels of modified genetic material. Most corn starch or soybean oil would not contain detectable levels of modified genetic material even if derived from bioengineered crops.
  2. Pet foods are not covered by the regulations.
  3. Incidental additives as defined in 21 CFR 101.100(a)(3).
  4. Food served in a restaurant or similar retail food establishment.
  5. Food produced by “very small food manufacturers” with less than $2.5 million dollars in annual sales.
  6. Foods with inadvertent or unavoidable bioengineered materials at levels of up to five percent (5%) for each ingredient.
  7. A food derived from an animal that consumed feed produced from, containing, or consisting of a bioengineered substance.
  8. Food certified under the National Organic Program.
  9. Foods subject to USDA FSIS labeling rules unless the predominant ingredient (excluding water, stock, or broth) would be labeled as bioengineered if sold on its own. For example, beef stew containing genetically modified corn but with beef as the predominant ingredient, would not be labeled as bioengineered.
Disclosure methods

The law provides a great deal of flexibility in how bioengineered foods may be labeled.  The disclosures must appear on either the front panel; near the distributor name and address on the information panel, or on an alternate panel likely to be seen by the consumer “under ordinary shopping conditions.”  There are also several disclosure methods:

  1. Text,
    1. ‘‘Bioengineered food’’ a raw agricultural commodity or processed food that contains only bioengineered food ingredients; or
    2. ‘‘Contains a bioengineered food ingredient’’ for multi-ingredient food that contains one or more bioengineered food ingredients.
  2. Symbol: There is also a colored version.
  3. Electronic or digital link accompanied by the statement “Scan here for more food information’’ and a phone number where the consumer can obtain the information.
  4. Text message: The label must include this statement ‘‘Text [command word] to [number] for bioengineered food information.’’

Voluntary labeling is permitted for foods that do not contain detectable levels of bioengineered genetic material but that contain ingredients derived from bioengineered crops.

USDA will maintain a list of bioengineered foods to help food manufacturers with efforts to determine whether their products may be subject to bioengineered food disclosure.  As stated in the Federal Register Notice, “The following foods comprise the List of Bioengineered Foods: alfalfa, apple (Arctic™ varieties), canola, corn, cotton, eggplant (BARI Bt Begun varieties), papaya (ringspot virus-resistant varieties), pineapple (pink flesh), potato, salmon (AquAdvantage™), soybean, squash (summer), and sugarbeet.  Note that not all varieties of these crops are genetically modified but manufacturers must be certain of the bioengineered status of any ingredients they use from this list.

Important Dates:

The rule becomes effective February 19, 2019.

The Implementation Dates are:

January 1, 2020 for all but small manufacturers and

January 1, 2021 for small food manufacturers with annual receipts of at least $2,500,000 but less than $10,000,000.

The Federal Register notice states that “Regulated entities should begin implementing the NBFDS no later than those dates by identifying the foods that will need to bear a BE disclosure, the records necessary to meet the record keeping requirements, and the type of BE disclosure they will use….”

Voluntary Compliance Date: Ends on December 31, 2021.  Up until this date companies may voluntarily disclosure bioengineered foods by methods required by State regulations or using auxiliary marking (ink stamping, stickers, etc.).

All foods subject to this rule must be properly labeled by the Mandatory Compliance Date: January 1, 2022.

It will be interesting to see the response of consumers and food manufacturers to these requirements.  We’ll keep you updated and will start discussing compliance with our clients.

Activist FDA?

The Food and Drug Administration (FDA) has historically worked in a reactionary manner.  The original Pure Food and Drugs Act was passed by Congress on June 30, 1906 in response to studies that showed deleterious effects of food additives that were already in use in foods. Under Commissioner Scott Gottlieb, M.D., FDA has been busy taking on issues new and old that affect consumer products and in the process is showing signs of becoming an activist organization.

In September of this year the Commissioner announced a request for information on how consumers understand the use of dairy terms on plant based dairy substitutes.  This action comes twenty two years after the first market introduction of “soy milk”.  In the Federal Register Notice FDA invited “comments on the labeling of plant-based products with names that include the names of dairy foods such as “milk,” “cultured milk,” “yogurt,” and “cheese.” The agency plans to use the information gathered “to inform our development of an approach to the labeling of plant-based products that consumers may substitute for dairy foods.”

In recent months the agency has taken steps to curb use of nicotine vaping products by teens and children.  Electronic cigarettes entered the US market in the last decade.  At the time it seemed reasonable that the agency would have taken some action to regulate the devices but it did not. There are now laws and regulations in place that provide FDA with clear authority over the products and this month the FDA Commissioner asked the Center for Tobacco Products to revisit compliance dates for such products; presumably to call for earlier compliance with registration and listing as well as for removal of most flavored tobacco and vaping products.

While taking on an issue after 10 or 20 years is not an ‘activist’ move, in the past week FDA has issued warning letters to companies illegally selling the opioid drug tianeptine in products marked as dietary supplements. Commissioner Gottlieb’s statement about this clearly outlines his intentions for FDA to be more proactive than we have seen in the past:

“This action is part of a broader effort we have underway to re-examine our resources and authorities related to products marketed as dietary supplements, and outline a new policy on how we intend to more vigorously fulfill our obligations to protect consumers from dangerous products and unlawful claims.”

The dietary supplement industry is often labeled as ‘unregulated’ in the news media.  People in the supplement industry know that the sector is fully regulated but that FDA has created a bit of a monster by taking 10 years to publish GMPs, failing to finalize rules for New Dietary Ingredient Notifications,  and by being slow to take enforcement action against bad actors.  Dr. Gottlieb’s statement will be welcomed by many dietary supplement companies who often find their products disadvantaged in the marketplace when they are sold next to brands that do not comply with FDA regulations regarding permissible dietary supplement claims.

FDA under Scott Gottlieb is even showing signs of being proactive.  In October FDA and USDA jointly hosted a public meeting on production of cell-cultured food products derived from livestock and poultry cell lines.  After hearing from stakeholders the agencies have decided that they will jointly regulate these future products. This proactive approach should lead to clear naming and labeling regulations for these innovative products.

This month Dr. Gottlieb also made a statement regarding animal testing in drug development research aimed at reducing the use of dogs in such work.  He also announced guidelines on FDA’s recall authority and promised to continue work to swiftly alert the public and activate recalls.  I at least welcome this forward-looking approach to regulation and am optimistic that FDA’s initiatives to seek input from industry and other stakeholders will lead to regulations that allow for innovation and protect public health.

2018 Food and Dietary Supplement Facility Registration and Renewal

All food, pet food and dietary supplement facility registrations must be renewed between October 1st and December 31st of even-numbered years.   2018 is a renewal year and prior to the renewal period FDA published two guidance documents on facility registration (guidance and supplemental guidance).  All domestic facilities as well as foreign facilities that provide products to the US market are subject to this requirement.

These regulations have been on the books for a while but have been updated as a result of passage of the Food Safety Modernization Act.  The most interesting update I noted was that facilities with multiple users will in many cases need to be registered by each user as well as by the owner of the facility.  The determination of who must register is based on who has “physical control” over food in the facility.  Accordingly, any business in a multiple-user commercial kitchen who “manufactures/processes, packs, or holds food” must have a separate registration as a food facility.  In addition, the owner of the facility must register if they have “physical control over the food at any time.”  The supplementary guidance suggests that the facility owner may have control over food if they have responsibility for the food in a common storage area.  Many small producers will be surprised by this tidbit in the supplement to the guidance.

The information needed to register a food facility is part of an online User Guide on FDA’s website and is also listed in the guidance.   The required information includes the facility name and address along with information about the parent company and all trade names the facility uses.  In addition, the name and contact information for the owner, operator or agent in charge, the types of foods handled and the activities carried out at the facility (manufacturing, storage, etc.).  In addition, foreign facilities are required to list a US Agent that has a physical presence in the United States.

Two very important bits of information are also required for registration:

  1.   A statement in which the owner, operator, or agent in charge provides an assurance that FDA will be permitted to inspect the facility at the times and in the manner permitted by the FD&C Act;
  2.   A statement in which the owner, operator, or agent in charge certifies that the information submitted is true and accurate.

These two requirements ensure that FDA will have cause and authority to cancel a facility’s registration if the agency is denied access to the facility or if there is a finding that the information submitted was incorrect.

It is also important to note that beginning with the 2020 registration period facilities must have a ”Unique Facility Identifier” (UFI).  This identifier will have to meet FDA requirements. At this time only a Data Universal Numbering System D-U-N-S (DUNS) number is listed as an acceptable UFI. These numbers are recognized by FDA but at this time there is no place to enter the number on the form.  It is possible that another type of number will be deemed acceptable by the 2020 registration period.  DUNS numbers are assigned and managed by Dun & Bradstreet and you can obtain more information about them on the FDA website.

All the information required to register a facility will be known by the facility manager.  As much as my team and I like to help companies comply with FDA regulations, FDA has changed the registration process so that a third party, such as FDA Compliance Simplified, cannot register a food facility on behalf of another company.  This is an important safeguard for the registering business but doesn’t mean that we won’t try to answer your questions on this or other compliance topics.  Let us know how we can help.

About the Author

About the Author

Evelyn has worked in regulatory affairs and product development for FDA-regulated products since 1997. In addition to her experience with dietary supplement, pharmaceutical, food, pet food and cosmetic products, she authored and edited chapters on dietary supplement, cosmetic and food regulations in Fundamentals of US Regulatory Affairs, 8th Edition.

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