Dietary Supplement Practicum (2 of 21): What the U.S. Food & Drug Administration (FDA) Does

first officials session of the practicum with the presentation by dr. Sibyl swift from the FDA and as I mentioned I'm not going to extensively introduce each of our speakers because they don't want to take time away from the valuable information that they are going to be providing so please join me in welcoming dr. Swift thank you for the opportunity to come and present today and speak on the behalf of the office of dietary supplement programs at FDA so I'm going to be speaking about our dietary supplement authorities and I'd like to begin with the first the authority for dietary supplement regulation comes from the federal Food and Drug and Cosmetic Act which governs all FDA regulated commodities and then the first law which actually defined dietary supplement regulation is the dietary supplement health and education act or Touche which dr. Coates mentioned earlier this morning so next I'd like to explain a little bit about dish a it was incredibly important for the regulation of dietary supplements it defined the term dietary supplement it established requirements for new dietary ingredient premarket review it established the requirements for Good Manufacturing Practices and that it included dietary supplements under the adulteration provisions I also like to point out that although FDA does regulate we don't approve dietary supplements or product labeling so before I began explaining our regulatory authorities I wanted to give you a snapshot of the industry that we regulate and these statistics are from NIH ODS and then from the CRN annual survey so there are external data they're not from internal from ODSP when de chelly was originally passed in 1994 there were 600 manufacturers on the market today it's estimated they're approximately seven thousand registered facilities again there were four thousand products estimated about in 1994 and that market has now grown to over 75 thousand products and from a four billion dollar market to a 40 billion dollar market so this is a massive industry which we are attempting to regulate and so our responsibilities can be kind of delineated down to facility registration new dietary ingredient notification Good Manufacturing Practices dietary supplement labeling structure function notifications and then finally adverse event reporting and I'd like to begin with facility registration so all food facilities must register with FDA and this is facility registration not product registration and this is for both domestic and foreign facilities the requirement comes from the bioterrorism Act of 2002 as a result of 9/11 and this was updated by the food safety and food safety Modernization Act in 2011 it's at a requirement of renewal and the registration of every two years fortunately this can be done electronically and this includes basic information the name the address the responsible party and the type of facility and this is actually a new requirement so you want we want to link the type of activity that's conducted at the facility meaning is it a juice food dietary supplement product to the type of facility itself the manufacturer of the package or the warehouse and then it also finally includes an acknowledgement that FDA can inspect the facility so dr. Coates was kind enough to provide a definition of a dietary supplement earlier and I'd like to take that definition just a little bit further with provide you with a little bit more detail so a dietary supplement is just that it's a supplement it's meant to augment the diet so you promote health and reduce the risk of disease and when I say supplement I'd like to be clear about that because it's not meant to be a sole item of a meal it's not represented for use as a conventional food and it must be labeled as a dietary supplement it must be intended for ingestion so it has to be taken in through the mouth and I have to be clear about that because it's not an intranasal it's not inhaled it's not sublingual it's not an injectable and I've seen products that attempt to purport to be supplements that suggest that type of use it must contain one or more dietary ingredients and then I've provided a list of those below vitamins minerals herbs or botanicals amino acids and then that category that dr. Coates mentioned that was kind of fun the others it's the dietary substance for use by man to supplement the diet by increasing total dietary into intake or a concentrate metabolites constituents extract or combination of any of the above dietary ingredients one of our most I say fun and interesting categories is the new dietary ingredient this is the category that we get a lot of questions on so a new dietary ingredient is an ingredient that was not marketed in a dietary supplement before October 15th of 1994 and that was just remind you when de chelly was enacted into law it's our only pre market authority for dietary supplements this involves a notification and a review but it is not an approval we do not approve new dietary ingredients the manufacturers or distributors required to notify us that they intend to market this at least 75 days prior to introducing it to market now the table that I've included today has four columns for the purpose of today's talk I'd like to focus on the first three looking from left to right I took this table from our revised draft guidance for new dietary ingredient notifications I want to be clear about that it is draft so it explains the fine details of how we can determine if something is a new dietary ingredient and if it requires a notification so essentially anything that was marketed in the US before October 15th 1994 will most likely not be considered to be a new dietary ingredient and will most likely not require a notification if it wasn't marketed in the US before October 15th 1994 but it was present in the food supply and you can provide evidence that it was provided in the food supply for I believe at least 25 years as an article use for food then it may be a new dietary ingredient but it most likely may not require notification and that's the most likely part for this particular line is it's has it been chemically altered or not if it has not been chemically altered in any way shape or form then it will most likely not require a notification but if it has then the FDA reviewers and the evaluation research staff will need to see it to determine if it's function or its effect has changed and then any ingredient that wasn't marketed in the US before October 15 1994 and was also not present in the food supply will most likely require a new dietary ingredient notification so a notification must include some basic information the name the address signature the name of the ingredient it must contain a description of the product that's containing the new dietary ingredients the proposed amount of the new dietary ingredient in the product and then it also must include detailed information about the identity and that's so that the evaluation research staff can determine exactly what it is and then get a better idea of how it might affect the body and then it also must contain the conditions of use in order for us to assess susceptible populations and as dr. Bailey mentioned earlier most of supplement use if that's primarily in some of those more susceptible populations we definitely need to know if that's where these products are intended to be marketed or to whom they're intended to be marketed to and finally the history of use or other evidence of safety establishing that the NDI will be reasonably expected to be safe a notification is the manufacturers basis for concluding that this product continuing in DI is reasonably expected to be safe therefore we require that they provide us with ample evidence and so that adequate history of use the safety studies that will effectively address some of the questions or both or most will most likely be required and then my final statement about in DI notifications I just want to reiterate this is our only process but we have the ability to perform a premarket review and again to remind you it's the dietary supplement market has at least 75,000 products in the 20 years since de chelly was enacted and new dietary ingredient notifications were required FDA has received approximately a thousand new dietary notifications of those less than 600 are unique and annually receive forty to fifty in di ends so yes we would like to see more so now I'm going to move on to Good Manufacturing Practices so the current good manufacturing practices or cGMP regulations are a large part of FDA's post market regulation of dietary supplements FDA published the final rule for good manufacturing practices in June of 2007 this role was it's found in the Code of Federal Regulations at 21 CFR 111 and it applies to all firms who manufacture package label or hold dietary supplements and that's for both foreign and domestic firms and then this this regulation has an emphasis strong emphasis on production and process controls on building quality into the products as well as the requirements for testing and raw material and in the finished product stage and it's meant to help ensure the dietary supplement product quality consistency and safety are consistent throughout and this is an extensive regulation it covers all aspects of manufacturing from setting up a facility to establishing personnel through product design production testing to records and record-keeping and then FDA investigators confirm cGMP compliance through hundreds of inspections each year and non-compliance can result in FDA action so next dietary supplement labeling dietary supplements are a category of foods so they must follow the food labeling requirements that are found in the Code of Federal Regulations at 21 CFR 101 they must be labeled as a dietary supplement and they really must actually have the word dietary supplement or supplement facts on them so that a consumer and also FDA knows that they are meant to be a dietary supplement so they have their own unique labeling requirements and like I said they have to be labeled as a dietary supplement they must list all of the ingredients but the ingredients need to be formatted into a supplement facts panel for those they don't necessarily have to provide all of the weight and the total content but they must list everything is supposed to be in that supplement they also must provide the name in the location the manufacturer and finally they have to provide a domestic contact meaning the phone number of the address for people to submit serious ad the serious Advent adverse event reports to dietary supplements are allowed to make three types are allowed to contain three types of claims they're allowed to have a nutrient content claim an example of that would be a product that's high in calcium or low in sodium they're allowed to have a structure function claim and I'm going to provide you with more information about structure function claims through the rest of my presentation so structure function claims just overview it describes the role of a nutrient or a dietary ingredients on literally the structure or the function of the body and then finally health claims or qualified health health claims categorize the relationship of the substance reducing the risk of a disease now there are authorized health claims or qualified health claims and there a specific language that has been approved and that is allowed on labels and nothing other than that specific language for more information about that it's available on our website under qualified health claims or health claims so structure function notifications are the only allowable claim and they're unique because it separates dietary supplements from food and cosmetics etc it's an exemption from the drug definition and allows claims that are made in accordance with section 403 r6 of the FD&C Act and so the allowable claims are a nutrient deficiency claim it describes a benefit related to that ingredient for a classic nutrient deficiency there are general well-being claims that describe general well-being from the consumption of a nutrient or dietary ingredient and then finally the structure function claim that as I mentioned describes the particular effect of that nutrient on the structure or function of the body and then I've included the definition of a disease the damage to an organ part structure or system the body such that it does not function properly or state state of health leading to such dysfunction because structure-function claims are allowed to address anything but disease claims and so now I'm going to explain that a little bit further so a structure function notification this is another type of review that the office of dietary supplement programs performs firms are required to have substantiation of their claim now they're not required to submit it with their notification however they are required to hold it in their facility and it's substantiation that the claim is truthful and not misleading and there's specific language related to that so adequate substantiation includes tests analyses research studies or other evidence based on the expertise of professionals in the relevant area that's been conducted and evaluated in an objective manner by persons qualified to do so using procedures generally accepted in the profession to yield act at accurate and reliable results so structure function notifications are also required to include the specific disclaimer language and so this is language that most of you will have seen on a package and you wonder why it's there it's because they're making some sort of structure function claim they're required to state that this statement has not been evaluated by the Food and Drug Administration's product is not intended to diagnose treat cure or prevent any disease so if you see that on there it's most likely because they've put something on their products related to the structure of function and finally they must notify FDA no later than 30 days after marketing the product that it contains the claim now similar to in DI notifications FDA does not approve structure function claims we reviewed the specific language the text of the claim and then the reviewers will determine that it does or does not have a disease claim included in it and if it does then a violet of claim they'll receive a courtesy letter its FDA is notifying them that they have included something on their label that suggests that the product is intended to treat or cure a disease and then FDA field offices will follow up with the firms now the way that FDA currently this is actually a new function we have an electronic submission portal for our structure function notifications so someone who sends us a structure function notification if they don't receive anything from us that means that we didn't have an issue with it now if a firm is willing to submit through the electronic portal they do actually receive an acknowledgement that we received it so there's a benefit to doing that let's see if finally I'd like to talk about adverse event reporting so manufacturers are required to submit a serious adverse event report to FDA within 15 business days of determining that this event occurred this reporting system works through FDA's MedWatch program and submissions can be received through our electronic portal on the website through email through phone calls or through letters all types of reports will be entered into the system now I mentioned that manufacturers are required to submit but consumers and health care providers do it voluntarily and we openly encourage them to do so because it helps alert us that there are problems with products or ingredients out there and then finally of manufacturers become aware of an issue then they have to follow up a year later with any new or updated information now to follow on to this and speaking about what FDA's regulatory authorities are related to dietary supplements dietary supplement adverse events are entered into the fifths an adverse event reporting system the cares database and then all of the cases are reviewed evaluated by the medical officers on staff to determine if any follow up information is necessary and to determine if additional information is needed hopefully the reviewer will be able to determine that there's something there that's actionable it can cause a trigger for other FDA action at for cause inspection consumer warnings or recalls now I'd like to mention that recently FDA started publishing posting Kerr's data files available on the website it's a searchable database that's reported by consumer and health care practitioners datas voluntary voluntarily reported by any Street and then mandatory reports from industry and it will eventually include all information from January of 2004 forward now I'd like to finish by discussing some of FDA's activities so some of the regulatory activities that we have taken in recent history are against warning letter initiatives against Keysha Brigid Ulla beta methyl phenyl ethyl amine D MBA or EMP citrate methyl sin Efrain pick a melon we issued warning letters against pure powdered caffeine and then f ODSP recently supported an FDA initiative against companies that made claims that their products could prevent diagnose treat mitigate or cure cancer and that is an ongoing initiative now that's all that I had for you in terms of regulation if you guys have any questions please another question yes could you help me with what a serious adverse event is I work in a retail pharmacy and people bring products back all the time with a stomachache and we call the manufacturer because we want them to replace it but did they have to report a stomachache you know I honestly I don't think that I'm the expert for that but I know that we have a large amount of information related to adverse events and serious adverse events on the website okay but by reporting it to the manufacturer you've put the onus on them to determine if it was serious or not okay so they have to determine that all right thank you you're welcome yes uh-huh you said you had 40 to 50 nd eyes a year can you tell us what sorts of products they tend to be you mean for what type of ingredients so an n di notification is for a type of ingredient honestly they can they're a wide range and it really just depends I mean we receive notifications for products I mean essentially anything that dr. Coates mentioned in his initial presentation and then we received notifications mistakenly for topicals and orals and things like that and those would receive a not a dietary ingredient letter just notifying them that that's not actually a dietary ingredient do you get a lot of them for botanicals I don't know that I would necessarily say a lot I I mean I think that it's fairly represented in the type of notifications that we receive yes all notifications are posted on that is in process of being updated so they they should all be represented especially from the most recent years if you have a question about some of the most recent ones they're being grouped into submissions by year so if you'd like to have a snapshot of say 2016 or 20 fifteen there it's has become more searchable also on our website we offer hyperlinks for 14 15 and 16 and notifications related to so if you'd like to have a little bit more specific information pertaining to the type of notifications you can find those on our website thank you I'm actually thinking about botanicals that may have traditional use but have not been marketed before and are may not may not appear in foods okay yeah and I we've received something like that I mean like I said it's a full spectrum of things that we've received notifications for for things like that and especially if the submitter wasn't necessarily certain of how to proceed our evaluation research staff offers pre notifications meanings for individuals who are interested in submitting those just to kind of help with some of the particulars and the details and information that might be required in that notification to facilitate that process thank you yes yes I'm wondering along the same lines you were talking a little bit about how the manufacturer has to demonstrate a history of evidence of safety can you talk a little bit about what some of that safety data might be absolutely so that's actually a case-by-case basis so an evidence of safety first you must you have to look at the conditions of use what population is this particular product suggested for if it's suggested for average healthy adults then you would hope that the animal experiments that were designed in order to support this would be representative of that if it was suggested to take this particular product for a specific duration say a shorter duration you would want to see the experiments designed to represent that snapshot of time now if you were suggesting that a product should be taken for an extended duration then the experiments should be representative of that so I can't say yes for this specific instance because it depends on what the conditions of use and the populations are for now the drug rise draft guidance offers a table at the end of it which is massive I didn't even think that I could put it on a screen this size it's I think it takes two pages to provide a better suggestion of the type of studies that would be appropriate to use as evidence of safety now if someone's trying to use a history of use then that's different that's typically a minimum of 25 years evidence of 25 years of history of consumption and human population to provide ample evidence did that answer your question yeah so I've done some reading and it suggests that the adverse drug events reporting from the FDA database is might be less than 10% what's actually occurring so I'm wondering if there's anything that you're looking at and trying to improve that pharmacovigilance around that I do have indications that it is quite low the specific percent I think is still up for debate I know that the chairs database and FDA's MedWatch program they're looking at ways to amend that notification process to make it user friendly and then it's just word of mouth it's where it's consumer advocacy it's putting information out there to educate populations that we really are looking for that type of information and then it's not only analyzing that serious adverse adverse event reporting information it's looking at other databases as well that might be useful I have a question regarding intravenous vitamins and minerals yes and so I saw I saw companies where they provide they actually go to your home or your office and they would hook you up with an IV and give you 50 grams plus the vitamin C and other minerals so I was wondering what are the regulations and guidelines with for that that sounds like a product that the Center for Drug Evaluation and Research would regulate because anything that is not ingested orally that's an injectable would be considered to be a drug and so that's outside of our purview yes I'm not sure which speaker if you're the right speaker to ask this question okay but I am interested in what the FDA's opinion about agricultural or industrial hemp is I don't believe I'm the right person for the okay all right thank you I think I'll ask all the speakers and see who knows okay thank you what I'm happy that I was the first yeah okay how easy are onerous is it for the FDA to move up from precaution to recall so say was something like Thailand swimming Pathak teething tablets the agency have to go and gather a lot of evidence to do that or just have some sort of reasonable concern I think it would depend on the signal and depend on the type of product that's another one of those that's case by case I would think so something with infants and belladonna alkaloids there's easier to go to recall because of the risk vs. yeah so that's that's an instance that it's difficult to say specifically for each case I think I mean it really it just it depends on each case as it's determined what level of evidence is required and then the agency would move forward as quickly as it could I think in any instance where recall might be necessary but I I mean I can't tell you exactly how many days it would take for us to move from point A to point B on that very case-by-case all right thinking yes yeah I have a question you mentioned that sublinguals are not considered dietary supplements that's correct less such as sublingual b12 where would that be regulated that if not by the FDA that sounds like a homeopathic and I believe that homeopathics are regulated by cedar so it's not that it's not regulated by FDA it's just not regulated by ODSP what question so there are products out there in the market and companies that actually you know represent sort of AM L between a food and a dietary supplements things like you know a products that are either fortified or with some added compounds that would fit in the category of dietary supplements as far as my understanding in some center it is up to the company to decide to market whether they you know they're gonna market up rather as a food or as a dietary supplement can you comment on that and also what would be the regulatory oversight in this scenario of foods you know sort of with some supplement inside it so if I understand your question you're asking me is it up to the manufacturer just to determine how a product should be sold if it should be sold as a dietary supplement or sold as a food product and so we regulate based upon what the labeling states and so if it's states that it is a dietary supplement meaning that they intended to sell it as a dietary supplement then we regulate it as such if they stayed on the labeling that it's intended to be sold as a food then that doesn't fall underneath the office of dietary supplement programs purview I'm not saying that we don't regulate it I'm sure it's not regulated at all just doesn't fall under our specific purview so the level of oversight would be like any other food basically that's correct yeah okay like the GMP standards also for manufacturing would apply I can't really speak to food products and how they're regulated that's actually outside of my knowledge base but for dietary supplements yes they would be subject to all of DC GMP regulations okay thanks mm-hmm no other questions great thank you guys [Applause]

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