>> Regan Bailey: firstofficial seminar of the practicum with apresentation by Dr. Sybil Swift from the FDA, and asI mentioned, I’m not going to extensively introduceeach of our talkers, because I don’t want totake time away from the valuable information thatthey are going to be providing. So please assemble me inwelcoming, Dr. Swift.[ cheering] >> Sybil Swift: Thank you forthe opportunity to come and present today, andspeak on the behalf of the Office of DietarySupplement Programs at FDA. So, I’m going to bespeaking about our dietary augment sovereignties, and I’d like to begin with the first. The dominion for dietarysupplement regulation comes from the FederalFood and Drug and Cosmetic Act, which governs all FDAregulated commodities.And then, the first rule, which actually characterized dietary supplementregulation, is the Dietary Supplement Health andEducation Act, or DSHEA, which Dr. Coates mentionedearlier this morning. So next, I’d like toexplain a little about DSHEA, it was incrediblyimportant for the regulation ofdietary complements. It defined the termdietary supplement, it substantiated requirementsfor brand-new dietary part premarket examine, itthen installed the requirements for goodmanufacturing practises, and it included dietarysupplements under the Adulteration Provisions. Now, I’d too like topoint out that although FDA does regulate, wedon’t approve dietary adds-on orproduct labeling. So, before I beginexplaining our regulatory authorities, I wanted togive you a snapshot of service industries that we adjust. And these statistics arefrom NIH ODS, and then from the CRN annualsurvey, so they’re external data, they’renot internal from ODSP.When DSHEA was originallypassed in 1994, there were 600 manufacturerson the market. Today it’s estimated thereare approximately 7,000 registered facilities. Again, there were 4,000 makes forecasted about in 1994, and the markethas now grown to over 75,000 products. And from a$ 4 billionmarket to a $40 billion market, so this is amassive industry which we are attemptingto regulate. And so, ourresponsibilities can be various kinds of delineated down tofacility registration, new dietary ingredientnotification, good manufacturing patterns, dietary add-on labeling, structurefunction notifications, and then finally, harmful phenomenon reporting. And I’d like to begin withfacility enrollment. So, all meat facilitiesmust registry with FDA. And this is facilityregistration , not product enrollment. And this is for bothdomestic and foreign equipment, and therequirement comes from the Bioterrorism Act of 2002, as a result of 9/11. And this was updatedby the Food Safety Modernization Act in 2011, to add a requirement of renewal of theregistration every two years. Fortunately, this can bedone electronically, and this includes basicinformation: the specify, the address, the responsibleparty, and the type of facility. And this is actually a newrequirement, so we want to link the type ofactivity that’s conducted at the equipment meaningis it a liquid, food, dietary complement product to the type of facility itself; car manufacturers, the packager, the warehouse.And then it, likewise, ultimately includes an acknowledgement that FDAcan inspect the equipment. So, Dr. Coates was kindenough to provide a definition of the dietarysupplement earlier, and I’d like to take thatdefinition precisely a little bit further, with provide you with a little bit more detail. So, a dietary supplementis just that: it’s a add-on. It’s meant to augment thediet, to promote health, and reduce therisk of cancer. And when I say supplementI’d like to be clear about that because it’s notmeant to be a sole item of a meal, it’s notrepresented for uses of conventional meat, andit must be labeled as a dietary add-on. It must be intended foringestion, so it has to be taken in through themouth, and I have to be clear about that becauseit’s not internasal, it’s not breath, it’s notsublingual, it’s not an injectable, and we haveseen commodities that attempt to purport to besupplements, that suggest that type of use. It must contain one ormore dietary ingredients, and then I’ve provideda list of those below: vitamins, minerals, herbsand botanicals, amino acids, and then thatcategory that Dr.Coates mentioned that was kindof fun, the others. It’s the dietary substancefor consume by human, to supplement the nutrition byincreasing the total dietary intake, orconcentrate metabolite constituents, obtain acombination of any of the above dietary parts. One of our most, I sayfun and interesting categories, is the newdietary ingredients, this is a category that we geta lot of questions on. So, a brand-new dietaryingredient is an ingredient that was notmarketed in a dietary supplement before October1 5th of 1994, and that was, exactly to remind you, when DSHEA was enacted into law. It’s our only premarketauthority for dietary adds-on. This involves anotification and a review, but it is not an sanction. We is not approve newdietary ingredients. The producers ordistributers required to inform us that they intendto busines this at least 75 epoches prior to introducingit to market.Now, the table that I’veincluded today has four pillars. For the purpose of today’stalk, I’d like to focus on the first three, lookingfrom left to right. I took this counter from ourreviseddraft guidance for brand-new dietary ingredientnotifications. I want to be clear aboutthat, it is draft. So, it clarifies the finedetails of how we can determine if something isa new dietary part, and if it requiresa notification. So virtually anythingthat was marketed in the U.S. before October 15 th, 1994 will most likely not regarded as an newdietary part, and will most likely notrequire a notification. If it wasn’tmarketed in the U.S. before October 15 th, 1994, but it was present in the food supply, and you canprovide evidence that it was provided in the foodsupply for, I belief, at least 25 times. As an section used forfood, then it may be a new dietary ingredient, butit most probably may not require a notification.And that’s the most likelypart for this particular line is has it beenchemically altered or not. If it has not beenchemically altered in any way, influence, or use, thenit will most probably not require a notification. But if it has, then theFDA reviewers and the evaluation research staffwill need to see it, to determine if its function, or its consequence has changed.And then, any ingredientthat wasn’t sold in the U.S. before October 15 th, 1994 and was also not present in the food supply willmost likely require a new dietary ingredientnotification. So, a notification mustinclude some basic information: the mention, theaddress, signature, the name of the ingredient. It must contain adescription of the product that’s containing the newdietary ingredient, the proposed amount of the newdietary ingredient in the produce, and then it alsomust include detailed information about theidentity, and that’s so that the evaluationresearch staff can determine exactly what itis, and then get a better idea of how it mightaffect their own bodies. And then it also mustcontain the conditions of use in order for usto assess prone populations. And, as Dr. Baileymentioned earlier, most of supplement use, if that’sprimarily in some of those more susceptiblepopulations, we definitely need to know if that’swhere these products are intended to be marketed to whom they’re intended to be marketed to.Finally, the history ofuse, or other evidence of safety, establishing thatthe NDI will be reasonably expected to be safe. A notification is themanufacturer’s basis for concluding that thisproduct, containing the NDI, is reasonablyexpected to be safe, therefore we require thatthey provide us with bountiful sign, and so thatadequate history of use, the safety studies thatwill effectively address some of the questions, orboth will most likely requires to. And then, my finalstatement about NDI notifications, I merely wantto reiterate, this is our only process where we havethe ability to perform a premarket evaluation. And again, to reminded participants, the dietary supplement make has at least7 5,000 concoctions. In the 20 years sinceDSHEA was ordained, and new dietary ingredientnotifications is a requirement, FDA has receivedapproximately 1,000 brand-new dietary ingredientnotifications.Of those, less than 600 are peculiar, and annually receive 40 5 0 NDIN’s, soyes, we would like to see more[ humour] >> Sybil Swift: So , now I’mgoing to move on to good manufacturing patterns. So, the Current GoodManufacturing Practices, or CGMP regulations, area large part of FDA’s postmarket regulationof dietary supplements. FDA publicized thefinal govern for good manufacturing practicesin June of 2007. And the present rule was it’sfound in the Code of Federal Regulations at 21 CFR 111, and it applies to all houses who fabricate, container, name, or deem dietary adds-on, andthat’s for both foreign and domestic conglomerates. And then this thespeculation has an emphasis, strong emphasis, on make and process verifies, on buildingquality into the products, as well as therequirements for testing in raw material and in thefinished product stage. And it’s meant to helpinsure the dietary complement product qualityconsistency and safety are consistent throughout. And this is an extensiveregulation, it covers all aspects of manufacturingfrom setting up a equipment, to establishingpersonnel, through product design, creation, testing, to records, and record keeping.And then FDA investigatorsconfirm CGMP compliance through hundreds ofinspections every year, and noncompliance canresult in FDA action. So next, dietarysupplement labeling. Dietary augments are acategory of meat, so they must follow the foodlabeling requirements that are found in the Code ofFederal Regulations at 21 CFR 101. They must be labeled as adietary supplement, and they truly must actuallyhave the word dietary supplement, orsupplement facts on them so that a consumer, andalso FDA, knows that they are meant to be adietary supplement.So, they have theirown unique labeling requirements, and likeI said, they have to be labeled as adietary complement. They must register all ofthe ingredients, but the ingredients need tobe formatted into a add-on facts committee. For those, they don’tnecessarily have to provide all of the weightsand the total content, but they must list everythingthat is supposed to be in that augment. They too must provide thename and the location of the manufacturer, andfinally, they have to provide a domesticcontact, symbolizing the phone number, the address forpeople to refer serious untoward phenomenon is under the responsibility of. Dietary supplements areallowed to fix three categories are allowed tocontain three types of claims. They’re allowed to have anutrient content declare, an example of that would bea product that’s high in calcium, or low-grade in sodium.They’re allowed to have astructure/ gathering demand, and I’m going to provideyou with more information about structure/ functionclaims through the rest of my performance. So, arrangement/ functionclaims simply overview, it describes the role ofa nutrient or dietary ingredient on literallythe structure, or the serve, of their own bodies. And then finally, healthclaims, or prepared state declares, categorizethe relationship of a essence reducing therisk of a disease.Now, there are authorizedhealth claims, or prepared state pretensions, and there is specific language that has beenapproved and that is allowed on names, andnothing other than that specific language formore information about that, it’s availableon our website under qualified health claimsor health claims. So, Structure FunctionNotifications are the only allow affirm, andthey’re unique, because it separates dietarysupplements from food and cosmetics, et cetera. It’s an exception from thedrug clarity, it allows claims that are made inaccordance with section 403( r )( 6) at the FD& C Act. And so, the allowableclaims are nutrient defect say, itdescribes a benefit related to that ingredientfor a classic nutrient defect. There are generalwellbeing claims that describe generalwellbeing from the intake of a nutrientor dietary ingredient, and then finally thestructure/ role allege, that as I mentioned, describes the particular effect of that nutrient onthe structure or perform of the body.And then I’ve included thedefinition of an illness: the damage to an organpart, structure, or method of their own bodies, such thatit does not function properly, or a state ofhealth leading to such dysfunction. Because structure/ functionclaims are allowed to address anythingbut ailment claims. And so now I’m goingexplain that a little bit further. So, a organization/ functionnotification, this is another type of reviewthat the Office of Dietary SupplementPrograms accomplishes. Conglomerates are required to havesubstantiation of their claim. Now, they’re not requiredto submit it with their notification, however theyare required to hold it in their equipment. And its substantiationthat the claim is honest and not misleading, andthere’s specific conversation related to that.So adequate substantiationincludes research, studies, study, studies, orother suggestion based on the expertise ofprofessionals in the relevant area that’s beenconducted, and evaluated in an objective manner bypersons required in order to do so expending procedures generallyaccepted in the profession to yield accurate andreliable develops. So, structure/ functionnotifications are also required to include thesespecific disclaimer language. And so, this is languagethat most of you will have learn on a carton and youwonder why it’s there, it’s because they’remaking some sort of structure/ perform contend. They’re be adopted in order to statethat This statement has not been evaluatedby the Food and Drug Administration.This product is notintended to diagnose, analyse, remedy, orprevent any disease. So, if you be understood that onthere, it’s most likely because they’ve putsomething on their concoction related to thestructure or function. And eventually, they mustnotify FDA no later than 30 eras after marketingthe make, that it contains the claim. Now, similar to NDInotifications, FDA does not approvestructure/ part claims. We re-examine the specificlanguage, the text of the claim, and then thereviewers will determine that it does, or doesnot have a disease claim included in it. And if it does, then aviolative affirm, they receive a courtesy letter, it’s FDA’s notifying them that they haveincluded something on their description that suggeststhat the make is intended to treator cure a disease.And then, FDA fieldoffices will follow up with the houses. Now, the only way thatFDA currently, this is actually a new serve, we have an electronic submission entrance forour organization/ role notifications. So, someone who sendsus a design/ function notification, if theydon’t receive anything from us, that means thatwe didn’t have an issue with it. Now, if a firm is willingto submit through the electronic entrance, theydo actually receive an acknowledgementthat we received it. So, there’s a benefitto doing that. Let’s see, lastly I’dlike to talk about adverse phenomenon reporting. So, creators arerequired to submit a serious adverse eventreport to FDA within 15 business days ofdetermining that this event passed. This reporting systemworks through FDA’s MedWatch program, andsubmissions can be received through ourelectronic entrance on the website, through email, through telephone calls, or through letters, all typesof reports will be entered into the system.Now, I mentioned thatmanufacturers are required to submit, but consumersand health care providers do it willingly, and weopenly encourage them to do so, because it helpsalert us that there are problems with products oringredients out there. And then, ultimately, ifmanufacturers become aware of an issue, then theyhave to follow up a year later with any new, orupdated information. Now, to follow onto this, in speaks with what FDA’s regulatoryauthorities are related to dietary supplements, dietary add-on adverse events are entered intothe CFSAN’s Adverse Event Reporting System, theCAERS database, and then all the cases are reviewedand evaluated by medical officers on staff todetermine if any follow up information is necessary, and to determine if additional informationis needed, hopefully the reviewer will be able todetermine that there is something there that’sactionable, that can cause a initiation for otherFDA action, for cause inspection, consumerwarnings, or recalls.Now, I’d like to mentionthat recently FDA started producing postingCAERS data files available on the website. It’s a searchable databasethat’s reported by consumer and healthcarepractitioners freely reportedby industry, and then mandatory reports fromindustry, and its, will eventually include allinformation from January of 2004 forward. Now, I’d like to finish bydiscussing some of FDA’s activities. So, some of the regulatoryactivities that we have taken in recent historyare against warning letter initiativesagainst acacia rigidula, phenethylamine, DMBA, or AMP citrate, methylsynephrine, Picamilon. We questioned alarming lettersagainst unadulterated pulverized caffeine, and then, ODSPrecently supported an FDA initiative againstcompanies that represented claims that their makes couldprevent, diagnose, give, mitigate, or heal cancer, and that is an ongoing initiative. Now, that’s all that Ihad for you in terms of regulation, if you guyshave any questions. Please.[ clapping] >> Female Speaker: Ihave a question. >> Sybil Swift: Yes. >> Female Speaker: Couldyou help me with what a serious adverse occasion is? I work in a retailpharmacy >> Sybil Swift:[ affirmative] >> Female Speaker: andpeople impart produces back all the time with astomach ache, and we call the manufacturer becausewe want them to replace it, but do they have toreport a stomach ache? >> Sybil Swift: You know, Ihonestly I don’t think that I’m the panel of experts forthat, but I know that we have a large amount ofinformation related to adverse events, andserious adverse events, on the website .>> Female Speaker: Okay. >> Sybil Swift: But byreporting it to the manufacturer, you’veput the onus on them to determine if it wasserious or not. >> Female Speaker: Okay, sothey have to determine that. All freedom. Thank you. >> Sybil Swift: You’re welcome. Yes. >> Female Speaker: Hi, yousaid you had 40 5 0 NDI’s a year. Could you tell us whatsorts of commodities they tend to be? >> Sybil Swift: You convey, forwhat type of ingredient? >> Female Speaker: Yeah. >> Sybil Swift: So, an NDInotification is for a type of ingredient. >> Female Speaker:[ affirmative] >> Sybil Swift: Honestly, they can they’re a wide range, and itreally simply depends.I mean we receivenotifications for concoctions I signify, essentially, anything that Dr. Coates mentioned under hisinitial representation. And then we receivenotifications mistakenly for thematics, and orals, and things like that. And those would receive anot a dietary ingredient letter exactly advising themthat that’s not actually a dietary ingredient. >> Female Speaker: Do youget a lot of them for botanicals? >> Sybil Swift: I don’t knowthat I would definitely say a lot. I mean I think thatit’s fairly represented in the characteristics of notificationsthat we receive, yes. All notifications areposted on regulations.gov, that is in process ofbeing updated, so they should all be represented, especially from the most recent years. If you have a questionabout some of the most recent ones, they’re beinggrouped into submissions by time, so if you’d liketo have a snapshot of say, 2016, or 2015, there, it’s regulations.gov has become more searchable.Also on our website, weoffer hyperlinks for’ 14,’ 15, and’ 16, andnotifications be attributed to, so if you’d like to have alittle bit more specific information pertaining tothe type of notifications, you can find thoseon our website. >> Female Speaker: Thank you. I’m actually thinkingabout botanicals that may have traditional use, but have not have been marketed before >> Sybil Swift:[ affirmative] >> Female Speaker: andhave may not appear in nutrients. >> Sybil Swift: Okay. >> Female Speaker: Yeah. >> Sybil Swift: And I we’ve received some like that. I represent, like I said it’sa full spectrum of things we’ve receivednotifications for. For things like that, and especially if the submitter wasn’tnecessarily certain of how to proceed, our evaluationresearch staff offers prenotifications meetingsfor individuals who are interested in submittingthose, really to kind of help with some of theparticulars, and the details and informationthat might be required in that notification, tofacilitate that process .>> Female Speaker: Thank you. >> Sybil Swift:[ affirmative ]. Yes. >> Female Speaker: Ah, yes, I’m wondering along the same lines, you weretalking a little bit about how the manufacturer hasto demonstrate a biography of evidence of safety. >> Sybil Swift: Yes. >> Female Speaker: Can youtalk a little bit about what some of thatsafety data might be? >> Sybil Swift: Absolutely.So that’s actually acasebycase basis. So, in evidence of safety, first you must you have to look at theconditions of use. What person is thisparticular product suggested for? If it’s advocated foraverage, health adults, then you would hope thatthe animal experiments that were designed inorder to funding this would berepresentative of that. If it was suggested totake this particular product for a specificduration, say a shorter duration, then youwould want to see the experiments designed torepresent that snapshot of period. Now, if you weresuggesting that a concoction should be taken for anextended duration, then the experiments should berepresentative of that. So, I can’t say yes forthis specific instance, because it depends on whatthe conditions of use and the populations are for. Now, the revised draftguidance offers a table following the adjournment of it, which is massive.I didn’t even think that Icould place it on a screen this immensity it’s I thinkit takes two sheets to provide a bettersuggestion of the type of studies that would beappropriate to use as evidence of safety. Now if someone’s trying touse a history of use, then that’s different. That’s commonly a minimumof 25 years, evidence of 25 years of history ofconsumption in human population, to provideample evidence. Did that answeryour question? You’re welcome. Yes. >> Female Speaker: Yeah. So, I’ve done somereading, and it suggests that the average drugevent reporting from the FDA database is mightbe less than 10 percentage what’s actuallyoccurring >> Sybil Swift:[ affirmative ]. >> Female Speaker: I’wondering if there’s anything that you’relooking at in trying to improve pharmacovigilancearound that? >> Sybil Swift: I do haveindications that it is quite low.The specific percent, Ithink is still up for debate, I is a well-known fact that theCAERS database, and FDA’s MedWatch program, they’relooking at ways to amend that notification process, to make it user friendly, and then it’s justword of mouth. It’s, we’re it’sconsumer advocacy. It’s putting informationout there to educate populations that we reallyare looking for that type of information. And then, it’s not onlyanalyzing that serious adverse episode reportinginformation, it’s looking at other databases aswell, that might be useful. >> Male Speaker: I havea question seeing intravenous vitaminsand minerals. >> Sybil Swift: Yes. >> Male Speaker: And, so Isaw I read companionships where they specify theyactually go to your home, or its term of office, and theywould secure you up with an IV and give you 50 grams, plus vitamin C and other minerals. So, I was wondering, whatare the regulations and guidelines for that? >> Sybil Swift: That soundslike a product that the Center for Drug Evaluationand Research would regulate.Because anything thatis not ingested orally, that’s an injectable, would be considered to be a drug, and so that’soutside of our purview. Yes. >> Female Speaker: I’m notsure which loudspeaker if you’re the claim speakerto ask this question. >> Sybil Swift: Okay. >> Female Speaker: But I aminterested in what the FDA’s opinion aboutagricultural or industrial hemp is. >> Sybil Swift: I don’tbelieve I’m the privilege party for that. >> Female Speaker: Okay, all right, thank you. I review I’ll ask all thespeakers and meet who are familiar with.[ laugh] >> Sybil Swift: Okay. >> Female Speaker: Okay, expressed appreciation for .>> Sybil Swift: But I’m happythat I was the first. >> Female Speaker: Yes. >> Male Speaker: Hi. How easy, or onerous isit for the FDA to move up from precaution to recall, say with something like Hyland’s HomeopathicTeething Tablets. Does the agency have togo and gather a lot of evidence to do that, orjust have some sort of tolerable concern? >> Sybil Swift: I thinkit is dependent upon the signal, and depend on thetype of product, that’s another one of thosethat’s casebycase, I would think. >> Male Speaker: So, something with infants and Belladonna alkaloids, it’seasier to go to recall because of therisk, versus >> Sybil Swift: Yeah sothat’s an speciman it’s difficult to sayspecifically for each case.I think I imply, it, genuinely it depends on each case >> Male Speaker:[ affirmative] >> Sybil Swift: as its determined. What elevation of proof isrequired, and then the agency would move forwardas quickly as it could. I think in any instancewhere cancellation might be necessary, but I imply Ican’t tell you exactly how many days it would takefor us to move from point A or pitch B on that. >> Male Speaker: It’svery casebycase. All liberty, thank you. >> Sybil Swift: Yes. >> Male Speaker: Yeah, I have a question. You mentioned thatsublingual’s are not considered dietarysupplements. >> Sybil Swift: That’s correct. >> Male Speaker: Suchas Sublingual B1 2. Where would that beregulated then, if not by the FDA? >> Sybil Swift: That soundslike a homeopathic, and I believe that homeopathicsare regulated by CDER. So, it’s not that it’s notregulated by FDA, it’s just notregulated by ODSP .>> Male Speaker: One question. >> Sybil Swift: Yes. >> Male Speaker: So, thereare concoctions out there in the market, and companiesthat actually, you are well aware, represent kind of a meldbetween a menu and a dietary complement. Things like, you are well aware, concoctions that are either garrisoned, or with someadded compounds that would fit in the category ofdietary augments. As far as myunderstanding, in some scenarios it is up tothe company to decide to market whether, you are well aware, they are going to market that concoction as a nutrient, oras a dietary complement. Can you comment on that, and likewise what would be the regulatory oversight inthis scenario of a meat, you know, sort of withsome supplement inside it? >> Sybil Swift: So, if Iunderstand your question, you’re asking me is it upto the manufacturer to determine how a productshould be sold, if it should be sold as adietary augment or sold as a food product. And so, we govern basedon what the labeling states. And so, if it statesthat it is a dietary supplement, meaning thatthey intended to sell it as a dietary add-on, then we adjust it as such.If they territory on thelabeling that it’s intended to be sold as afood, then that doesn’t fall underneath the Officeof Dietary Supplements Program purview. I’m not saying that wedon’t regulate it, or it’s not governed at all, itjust doesn’t fall under our specific purview. >> Male Speaker: So, thelabel of oversight would be like any otherfood, basically. >> Sybil Swift: That’s correct. >> Male Speaker: Yeah, okay. Like the GMP standardsalso for manufacturing would be implemented? >> Sybil Swift: I can’treally speak to food products and how they’reregulated, that’s actually outside of myknowledge base. But for dietarysupplements, yes. They would be subjectto all of the CGMP regulations. >> Male Speaker: Okay, thanks. >> Sybil Swift:[ affirmative ]. No other questions? Great. Thank you, guys.[ praise ].