Poland Switches from Rx-To-OTC Mylan's Duspatalin for IBS, Plus Orion's ED Treatment

No. 23 • 10 June 2019

recommended posology is one tablet, three times per day, preferably 20 minutes before meals. The product’s patient information leaflet advises users not to take Duspatalin for more than five days without medical advice, adding that if there is no improve- ment in symptoms in this period, they should consult their doctor. Mebeverine is not widely available OTC across Europe, with the UK, Ireland and Belgium the only countries in the region permitting the non-prescription sale of the drug.

VALINGER SWITCHED TO TREAT ED Alongside Duspatalin, URPL has also approved the Rx-to-OTC switch of Ori- on’s Valinger, making the erectile dys- Poland Switches from Rx-To-OTC function treatment sildenafil available without a prescription in tablet form. Mylan’s Duspatalin For IBS, In 2016, Polish men became the first in the world to have OTC access to sildenafil when URPL switched Adamed’s Plus Orion’s ED Treatment MaxOn Active. TOM GALLEN [email protected] Valinger 25mg is indicated for use in patients over 18 years of age suffering oland’s national medicines regula- In 2016, Polish men from erectile dysfunction, with a maxi- tor, URPL, has approved two pre- mum recommended dose of 1 tablet per Pscription-to-OTC switches to give became the first in the day. The product’s patient information consumers easier access to treatments for leaflet advises users to complete a ques- irritable bowel syndrome (IBS) and erectile world to have OTC access tionnaire supplied with each pack to as- dysfunction. sess their suitability, and educate them Consumers can now purchase without to sildenafil when URPL about sildenafil and its contraindications. a prescription Orion Corp.’s Valinger (silde- switched Adamed’s Sildenafil remains non-prescription nafil), and from 1 July, Mylan NV’s Duspa- in all European countries except Poland talin Gastro (mebeverine hydrochloride). MaxOn Active. and the UK. Last year, Pfizer launched The switch of Mylan’s Duspatalin means Viagra Connect, the first OTC sildenafil- Polish patients will be able to access for based erectile dysfunction treatment the first time without a prescription the available in the UK. (Also see “Viagra Con- antispasmodic mebeverine to treat ab- for use in patients over the age of 10 nect aims to remove ED stigma” - HBW In- dominal pain caused by IBS. years suffering from abdominal pain sight, 11 May, 2018.) Duspatalin 135mg will soon be avail- or discomfort, which may be accompa- able OTC in packs of 15 tablets indicated nied by a change in stool constancy. The Published online 31 May 2019

FOR THE LATEST INSIGHT ON OTC, DIETARY SUPPLEMENTS AND COSMETICS VISIT: HBW.PHARMAINTELLIGENCE.INFORMA.COM

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hbw.pharmaintelligence.informa.com 10 June 2019 | HBW Insight | 3

JN2181 Pink Sheet Advert HBW A4.indd 1 2019/06/05 12:57 HEALTH (OTC DRUGS)

Thinking About Switching? Dr Gauld On The Go-To Markets Today DAVID RIDLEY [email protected]

hen it comes to innovation, prescription-to-OTC switching can be a “holy grail” for pharmaceutical com- Wpanies looking to grab consumer healthcare market share or extend the lives of blockbuster prescription drugs reaching the end of their patent periods. However, reclassification applications are not easy to navigate successfully, with regulators often erring on the side of caution when it comes to making medicines available without a prescription. In this first installment of a three-part series on the state of switching today, switch expert Dr Natalie Gauld talks to HBW Insight about what makes a country an attractive environment for switching and those markets leading the way. Future install- ments will look at the role of pharmacy in making switches successful and the barriers companies face when thinking about prescription-to-OTC reclassifications. As well as publishing numerous studies on switching – including studies on the barriers, enablers and benefits of switching for industry, regulators and consumers – Dr Gauld has cals Ltd.’s Maloff Protect (proguanil hydrochloride and atova- been involved in driving many switches, including the first- quone, 250mg/100mg, in packs of up to 36 tablets), Pfizer’s in-world switch of Pfizer Inc.’s erectile dysfunction drug Viagra Viagra Connect (sildenafil citrate, 50mg, in packs of up to eight Connect(sildenafil) in the UK. tablets) and Leo Pharma AS’s Dovonex Psoriasis (50mcg/g cream in packs of up to 60g). (Also see “Viagra Connect hits Q: Which countries would you say are leading the way with UK shelves” - HBW Insight, 13 Apr, 2018.) So that was exciting, switching today? having three in one year. But now things have slowed down again, and we’ve even seen some reverse switches in the last A: I’m going to stay with the developed countries because they five years, such as diclofenac in the UK, emergency contracep- are the ones leading the way in switching with new products tives in Poland, and dextromethorphan in France. and new therapeutic areas. The UK seems reasonably active at Editor’s Note: Following the decision by Australia’s Therapeu- the moment, but many other countries have had fairly limited tic Goods Administration to reverse-switch codeine in 2017, there numbers of switches. For example, in Australia applicants have has been a wave of similar reclassifications of the drug across the been trying to get many products across the line, such as silde- world, including in France and New Zealand. Poland is considering nafil and also oral contraceptives. But so far these attempts a reverse-switch, and in the UK, the MHRA’s Opioid Expert Working have failed. However, Australia is about to implement a new Group is looking at codeine as part of a review of the risks of opioid system which could enable more switches to get approved. medicines, such as dependence and addiction. (Also see “OTCs Un- Following the path of New Zealand, Australia is seeking to in- der Threat In Europe: Calls To Reverse-Switch Codeine And Others In troduce an Appendix M restriction that introduces additional Poland And Ireland” - HBW Insight, 19 Mar, 2019.) criteria for supply beyond its current pharmacist-only category. (Also see “Australian Industry Welcomes Possible Oral Q: How important is culture in creating a progressive switch Contraceptive Switch” - HBW Insight, 11 Mar, 2019.) I think that environment? that’s going to help switch in Australia but there are still important barriers that remain, particularly with regards to immedi- A: Very important. In Japan, for example, it’s usual to go to ate competition from generic and house medicine brands. your doctor about everything. What they say in Japan is that “if you’re sick, don’t go to the hospital, go to your local doc- Q: Has the rate of switch slowed down over recent years? tor.” That’s the message they try to send out, even for a cold. A consumer I spoke to there couldn’t believe that I might sug- A: Yes, I think it has slowed a bit. The UK, for example, for a gest that people in other countries wouldn’t go to a doctor for few years went through a stage of not having any prescription- a cold. But the fact that it is easy to see a doctor in Japan, as only-to-pharmacy-only (POM-to-P) switches. Then in 2017 you well as the culture of great respect for a doctor’s knowledge, had three POM-to-P re-classifications: Glenmark Pharmaceuti- contribute to this environmental difference. Furthermore, Jap-

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anese doctors get a small payment from the government for general sales environment only, is more difficult. There is a lot each appointment. So, it’s partly about the financial incentives. being done around technology, talking labels, kiosks, smart- phones, but I am not convinced ignoring the pharmacist is the Q: What makes a country attractive for a firm looking to switch its best way to do this. That assumes that consumers will do the blockbuster prescription medicines? necessary reading and make the choices that are in their best interests, and it’s hard to convince a committee of that. (Also A: When firms are looking to switch their prescription medi- see “Innovation In OTC Switches Takes Multimedia Approach In cines they are often looking for a large market that’s progres- US FDA Draft Guidance” - Pink Sheet, 17 Jul, 2018.) Switch takes sive in terms of switching, for example the UK. While the UK’s some bravery as well. I had a really nice quote from an indus- decision to leave the European Union (EU) is frustrating for try participant some years ago, which pointed out that a firm many working in the region’s pharmaceuticals sector, it may needs courage to actually put itself out there and attempt to also provide an opportunity for industry. (Also see “Brexit Could do a switch. There’s a leap of faith involved. Open Up Rx-To-OTC Switch Opportunities In UK, Says MHRA” - HBW Insight, 8 May, 2019.) One of the positives that might come out Q: It sounds like there are a set of minimum conditions for a country of Brexit is that anything that was centrally registered will no to qualify as a “go-to” market for switching? A reclassification has longer need to be switched centrally. That would be quite nice to be worth the cost, for example, in terms of post-switch revenue. and likely to help really cement the UK as the global switch- leader.” New Zealand’s progressive attitude to switching has A: Yeah, of course, there have been a number of switches certainly helped drive a lot of re-classifications over the last that have failed commercially, for example H2 antagonists in few years. Australia was seen as a progressive switch market most countries and simvastatin in the UK. Allergan PLC’s Oxy- for a while. There has been some great work in Germany re- trol over-active bladder treatment was discontinued in the cently by the country’s medicines manufacturers’ association, US. In Australia, Novartis AG initiated the famciclovir switch the BAH, especially by its scientific director Dr Elmar Kroth, for (for cold sores) but most pharmacies do not stock the firm’s example the introduction of annual switch conferences. (Also OTC Famvir brand. But countries also wax and wane when it see “German Industry Wants To Simplify ‘Complicated’ Switch Pro- comes to switching. In the 1990s, New Zealand was a leader. cess” - HBW Insight, 24 May, 2019.) This work could see Germany Australia was very progressive in the early 2000s, whereas become a preferred market for switches, as it was over a de- New Zealand seemed rather conservative at that time. Then cade ago when it led the way with the reclassification of trip- it swapped round again so New Zealand was suddenly the tans. Its large population, consumer interest in self-medication one that was leading the way with switch and Australia the and ability to pay for it will also help. one that was behind. The UK has been very advanced for a very long time, with a Q: You see some countries releasing lists of potential switches, like consistent government interest in switch, but – in part because Ireland for example. But out of 12 ingredients put forward by the of the centralized EU switch system – it then had a five-year Irish medicines agency, the HPRA, only five have made it across the hiatus when nothing important went through until 2017. Look line. Why do you think this is? at Denmark as well, which in the late 1980s, early 1990s was leading the world in switching. Denmark was the first country A: Unfortunately, because the market is so small, companies to put a H2 antagonist on the market as an OTC product, for ex- don’t see a switch as paying off in terms of a simple cost-ben- ample, when it switched cimetidine and ranitidine in 1989. The efit analysis. So, for companies, Ireland is not necessarily going country’s government was doing amazing things for switch, to be a test market, particularly considering that the ingredi- until the EU single market came along and stopped everything ents on the list have been switched elsewhere. If a country that really. So, you do have ups and downs, that’s just the variation had 50m or more people put out a list with some really inter- you get. I think over the last 25 years, the countries which have esting ideas, then there would be a lot more interest I would been the most progressive for the majority of the time have think. Furthermore, many US states allow pharmacists to ad- been the UK and New Zealand. minister vaccines without a prescription – that’s not a federal As mentioned at the beginning of this article, this is the first install- switch but rather uses a different mechanism. Idaho allows ment of a three-part series on the state of switching today. In Part 2, pharmacists to treat urinary tract infections with antibiotics switch expert Dr Natalie Gauld talks about the role of pharmacy in without a prescription. There are some very interesting initia- making switches successful, and Part 3, the barriers companies face tives in that space. While other countries are moving to more when thinking about prescription-to-OTC reclassifications. complex switches, using things like pharmacist-only supply and Appendix M in Australia, the switch model in the US, to a Published online 31 May 2019

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J&J Wants To Inspire A Quitter Movement In The UK With Nicorette Campaign DAVID RIDLEY [email protected]

ou are not alone” is the key message of Johnson & John- son’s new campaign for Nicorette in the UK, which seeks “Yto leverage the power of social media to help “quitters” stay off cigarettes. Featuring a new website – www.nicorette.co.uk – with on- J&J’s Nicorette Range line support materials as well as a Facebook group, the “Join In The UK the Quitters” campaign, J&J explained, sought to create a “critical support network to give people the best chance at quitting smoking for good.” “The campaign will turn what it means to be a ‘quitter’ on its head, highlighting the importance of a support community to inspire a movement,” the firm continued. “As many as 75% of quitters relapse so getting support from others can be crucial to main- showcase all the “Quitters of the Week” featured during the taining smoking abstinence.” course of the campaign. “As Britain’s number one selling nicotine replacement therapy “Quitting smoking is an amazing achievement, but it can also brand, we know whilst having the right products is important, be one of the hardest things you’ll ever do,” the firm explained. building a strong support network can also be a real help in finally “From all the quitters that the team at Nicorette have helped all breaking free from smoking for good,” commented J&J’s Senior over the world for the last 40 years, they know that once you quit, Brand Manager for Nicorette, Anthony Dunn. even more amazing things can become possible.” As well as encouraging quitters to join together via social me- J&J currently offers seven distinct smoking cessation products dia, J&J is also using television, digital media and PR advertising as part of its Nicorette range: Nicorette Nasal Spray, Nicorette In- to celebrate the “brilliant” and “brave” real-life quitters that have visiPatch, Nicorette Microtab, Nicorette Inhalator, Nicorette Gum, successfully given up smoking. Nicorette QuickMist Mouthspray and Nicorette Lozenge. Launched initially in the North of England – an area that These products would all be available to buy directly through “over-indexes in smoking prevalence in the UK” – J&J said its the Nicorette website in the near future, J&J revealed.. “full 360 media campaign” would culminate in a “high-impact” out-of-home advertising push during Stoptober that would Published online 3 June 2019 Pfizer Feels The Heat As ThermaCare Recall Spreads To Europe

TOM GALLEN [email protected]

fizer Inc. has widened the scope of its Like the more recently recalled Ther- ThermaCare Heatwraps recall to out- maCare HeatWraps, the Muscle Joint Pside the US after identifying issues Therapy 8-hour lots were distributed with certain lots distributed in Europe. during parts of 2017 and 2018 to retail- The firm has issued recalls in Germany, ers, wholesalers and distributors in the the UK, Switzerland and Ireland for spe- US, including Puerto Rico and the US cific lots of its ThermaCare Lower Back & Virgin Islands. Hip Heatwraps because heat cells in the Globally, the recall covers five lots OTC transdermal patch could reach higher of the medical device – Lot numbers temperatures than specified. In April, the S23902, N3357, S00639, S97473 and firm voluntarily recalled in the US one lot W37940 – distributed at various pe- of the product – sold under the Therma- Pfizer’s ThermaCare Heatwraps riods from 2017 to 2018. Pfizer has Care Back Pain Therapy HeatWraps name initiated the European recall at the – for the same reason. wholesaler level, but certain regulators,

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Pfizer’s ThermaCare recall by market PRODUCT COUNTRY LOT NUMBER EXPIRY DATE DISTRIBUTION PERIOD 10 March 2017 - ThermaCare Wärmeumschläge bei Rückenschmerzen Germany S00639 31 October 2019 28 April 2017 17 August 2017 - ThermaCare Lower Back and Hip Heatwraps UK S23902 30 April 2020 23 October 2017 2 February 2017 - ThermaCare Wärmeumschläge bei Rückenschmerzen Switzerland S00639 31 October 2019 16 March 2017 ThermaCare Lower Back and Hip 12 September 2017 Ireland S23902 30 April 2020 Heatwraps (2 Count) - 4 October 2017 June 2017 - ThermaCare HeatWraps, Advanced Back Pain Therapy US S97473 Not specified March 2018 Source: Data xyz including Ireland’s Healthcare Products Regulatory Authority, is claimed by Pfizer to provide temporary relief of minor muscular are urging consumers to check if they have purchased one back aches and pains associated with overexertion, joint strains, the affected products. sprains, and arthritis. Pfizer pointed out that the use of a patch with an increased At the time of the US recall, a Pfizer representative told HBW temperature – possibly up to 0.9°C higher – posed a potential risk Insight that the firm had “identified the root cause for both of skin injuries such as burns/blisters and/or skin irritation on the recalls, and [has] implemented the appropriate corrective ac- wrap-applied area. However, the potential risk to consumers was tion.” The firm did not elaborate on the cause or the correction. “considered to be low,” the firm said, as the product’s labeling in- Pfizer also recalled another ThermaCare HeatWraps product in structions – recommending that the user stop use or wear a layer the US in late 2018 due to leaking heat cells. (Also see “Leaking of clothing if the product felt too hot – were intended to mitigate Heat Cells In Pfizer’s ThermaCare HeatWraps Prompt Recall” - HBW risk of serious events. Insight, 26 Nov, 2018.) ThermaCare Heatwraps contain activated charcoal, iron pow- der, sodium chloride, sodium thiosulfate and water. The product Published online 4 June 2019 � BEAUTY� Blood In The Water? L’Oreal Hit With New Keratin Fraud Complaint As Matrix Suit Advances

RYAN NELSON [email protected]

he L’Oreal Paris EverSleek Sulfate Free Keratin Caring line is Illustrating the burden of discovery on defendants in such cases, labeled and advertised to mislead consumers into believ- L’Oreal counsel notes in a 30 April status filing that the defendant T ing they will receive the benefits of keratin when in fact the produced 180 documents and 338 documents in Phase I and Phase products contain no keratin at all. II fact discovery, while plaintiffs produced five and zero documents, Such is the argument put forward by plaintiff Tammy Devane in a respectively. According to the same filing, deposition taken from a proposed class action filed 14 May in New York’s Southern District. L’Oreal representative in September 2018 covered ground including The complaint is closely modeled after another against L’Oreal the company’s intent in using the Keratindose name, as well as its as- USA Inc. in the same federal court, which casts the firm’s Matrix sessment of potential risks and consideration of alternative names. Biolage Keratindose Pro-Keratin + Silk hair-care range as decep- The deposition also sought information on L’Oreal’s decision tively marketed due to the products’ omission of actual keratin. not to include keratin in the products at issue, as well as the iden- (Also see “Where’s The Keratin? L’Oreal/Matrix Hair Line Falsely Ad- tities of individuals and departments responsible for the Matrix vertised – Lawsuit” - HBW Insight, 2 Feb, 2017.) line’s development and marketing. That case is in Phase II expert discovery stages following a June L’Oreal also has provided sworn, out-of-court testimony as to 2017 dismissal motion from L’Oreal that pruned just a couple of the Matrix products’ formulation/ingredients, efficacy and clinical plaintiff Brandi Price’s claims, and an August 2018 court order trials, according to the filing. granting certification to New York and California classes while de- Matrix labeling and advertising claims highlighted by Price in nying Price’s bid for a nationwide class. her complaint include: According to a proposed schedule adopted by the court in Feb- ● “Formulated with Pro-Keratin and Silk, Matrix’s keratin treat- ruary, the parties’ remaining discovery activities will wrap up in ment for damaged hair provides targeted reinforcement for September. over-processed, weak or fragile hair”;

hbw.pharmaintelligence.informa.com 10 June 2019 | HBW Insight | 7 BEAUTY (COSMETICS)

● “Prevent[s] damage”; There’s considerable discussion online ● “Restore[s] overprocessed hair”; as to whether and how keratin-containing ● “90% more conditioned after one appli- hair-care products benefit hair that’s been cation”; and damaged, for example, by heat styling or ● “Matrix’s first advanced system de- environmental factors. Proponents say in- signed to restore lost essentials.” fusing hair with fresh doses of keratin can Devane alleges in her similar complaint, protect and replace hair’s natural keratin filed just weeks ago, that “the EverSleek protein, resulting in smoother, stronger, Keratin Caring Products do not contain healthier-looking locks. any keratin at all and are incapable of pro- Competing brands such as TreSemme viding the claimed benefits of keratin to (Unilever PLC), Keranique and AG Hair the consumer,” notwithstanding represen- offer keratin-themed shampoos and tations such as: other hair products formulated with hy- ● “Keratin Caring”; drolyzed keratin. ● “Reparative Smoothing”; Notably, such brands tend to high- ● “Cares for the essential protein and ker- light their use of keratin ingredients in atin that is found in hair”; product descriptions, while L’Oreal’s ● “Repairs, smoothes, and improves hair’s brands do not. texture”; and L’Oreal defeated a class action earlier ● “Gentle on processed hair.” this year, after two and a half years of liti- At a glance, Devane’s case against Kera- gation, concerning its SoftSheen Carson tin Caring, undertaken on her behalf by The keratin-less L’Oreal Paris EverSleek Amla Legend hair relaxer, which plaintiffs New York-based Heninger Garrison Da- Keratin Sharing Shampoo alleged is deceptively marketed as gen- vis, LLC, may be less compelling than the tler than competing offerings when in Keratindose action that precedes it, led Keratindose, which consumers may be fact it contains caustic ingredients linked by Tampa, Fla.-based Morgan & Morgan more inclined to interpret as a promise of to burns, hair loss and other adverse re- Complex Litigation Group. supplemental keratin infusion. actions. (Also see “L’Oreal’s Gunslinging On the level of product name alone, It remains to be seen whether such dif- Counsel On Killing Amla Hair-Relaxer Class Keratin Caring reasonably could be read ferences are material in the eyes of the Action: ‘We Shot Every Bullet’” - HBW In- as an expression of what the line’s non- court and the extent to which the earlier sight, 27 Mar, 2019.) keratin ingredients do – eg, nourish exist- case’s trajectory and eventual outcome ing keratin in users’ hair – as opposed to bears on the later. Published online 30 May 2019 ICMAD’s New President Is Mary Kay Alum With Globally Recognized Scientific Expertise

RYAN NELSON [email protected]

he Independent Cosmetic Manufac- turers and Distributors has tapped T Ken Marenus as its next president. Announced May 30, Marenus comes to ICMAD with deep industry experience and a global reputation as a leader in the fields of cosmetic science and skin biol- ogy, the trade group says. The highly published biophysicist and active industry advocate has been in specialty consulting since June 2018 after serving 32 years at the Estee Lauder Companies Inc., half of those as senior vice president of regulatory affairs/product integrity, according to his LinkedIn profile.

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Prior to his stretch at Lauder, Marenus ICMAD champions held seats on Cosmetics Europe and Inter- managed research programs at Mary national Cooperation on Cosmetics Regu- Kay, Inc. independently owned lation committees. ICMAD champions independently At ICMAD, he’ll oversee the group’s stra- owned businesses of all sizes, with Mary businesses of all sizes, with tegic plan and head up legislative advo- Kay figuring among its largest members. cacy, marketing and outreach programs. “Dr. Marenus’ expertise in issues that Mary Kay figuring among “Ken brings an unbeatable combination are relevant to regulators and legislators its largest members. of extensive knowledge and a passion to in the US and internationally will be im- encourage grassroots innovation and en- mensely valuable in representing and ed- trepreneurship across the beauty indus- ucating our members,” says ICMAD Chair- try,” Mehra says. man Sanjiv Mehra. others like them are now playing leading ICMAD’s Vice Chairman Chris Hobson “His perspectives on the opportunities roles in the global beauty marketplace,” adds, “With Ken’s leadership we look for- and challenges of entrepreneurship in the Marenus observes. ward to being even more relevant and ef- beauty industry resonate strongly with He continues, “As new business models fective and to fulfilling our mission to sup- our members and tie closely to ICMAD’s are created and barriers to competition port innovative beauty companies.” mission,” Mehra adds. change, we expect the industry to contin- Marenus succeeds Pamela Busiek, who Marenus shares a bit of that perspec- ue to experience strong levels of growth, left ICMAD quietly at the beginning of tive in the release, noting the dramatic innovation and globalization. Through 2019 after serving 12 years at its helm. shifts that have taken place in the in- this period, ICMAD will be a strong voice Among ICMAD’s key priorities is creasingly digitized cosmetics industry to foster creativity and innovation and to right-sized reform of the federal regu- over the past decade, upending tradi- support the entrepreneurial spirit that is latory framework for cosmetics. (Also tional power structures. driving this change.” see “ICMAD Attorney: ‘Bad’ Cosmetics “There has been a significant impact In the trade association domain, Mare- Bill Won’t Get Through Senate, But Next from the emergence of independent nus has chaired the Personal Care Prod- Session Is Less Certain” - HBW Insight, 11 beauty companies as leaders in product ucts Council’s Scientific Executive Com- May, 2019.) innovation and branding over the past de- mittee, as well as Cosmetics Alliance cade and, as a result, ICMAD members and Canada technical committees. He also Published online 30 May 2019

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e71GenBullHBW.indd 1 18.02.19 15:50 hbw.pharmaintelligence.informa.com 10 June 2019 | HBW Insight | 9 BEAUTY (COSMETICS)

EWG Casts FDA’s Proposed Sunscreen Rule As Validation Of Longstanding Concerns LAUREN NARDELLA [email protected]

he Environmental Working Group FDA has arrived at the same conclu- consumers to stay out of the sun. “Sun- has seized on the US Food and sion. In its proposed rule, the agency screen should be your last resort,” it says. T Drug Administration’s proposed cites “substantial” evidence that zinc From industry’s perspective, such as- rule for a final OTC sunscreen drug mono- oxide, including in nano form, does sertions are “dangerous” and run counter graph as verification that its longstand- not penetrate human skin to any great to sunscreen use recommendations from ing concerns about chemical UV filters extent, and trace amounts that may ab- FDA, the Centers for Disease Control and are not misplaced. sorb pose no health risks, it says. The Prevention and the American Academy “The good news is that the FDA has re- same goes for titanium dioxide. of Dermatology. affirmed what EWG has advocated for 13 For its 2019 report, EWG assessed 1,300 The Personal Care Products Council years: Based on the best current science, sunscreen products and determined that and the Consumer Healthcare Products the safest and most effective sunscreen two-thirds of them do not offer enough Association contend the report “irrespon- active ingredients are zinc oxide and tita- protection from the sun or contain haz- sibly misrepresents the evidence base sur- nium dioxide,” says Nneka Leiba, director ardous ingredients, consistent with its rounding sunscreen safety and efficacy,” of EWG’s Healthy Living Science program, previous findings. (Also see “EWG Sun- potentially leading to consumer confu- in a May 22 release. screen Report At Odds With FDA Enforce- sion and abstention from sunscreen use at FDA’s proposed rule for a final OTC sun- ment Guidance On Sprays, SPFs” - HBW a time of epidemic skin cancer rates. screen drug monograph tentatively cat- Insight, 25 May, 2018.) Individuals with EWG’s guide in one egorizes titanium dioxide and zinc oxide Just 40% of products evaluated by the hand and Consumer Reports’ recom- as generally recognized as safe and effec- group rely exclusively on one or both min- mendations in the other may be doubly tive (GRASE), while identifying a dozen eral UV blockers. confused, as the latter continues to pro- currently used active ingredients – all EWG maintains that evidence is incon- mote oxybenzone-containing offerings, chemical sunscreen agents that absorb clusive as to sunscreen’s capacity to re- which it says test best when it comes to rather than deflect ultraviolet rays – as duce skin cancer risk. The group advises broad-spectrum protection and minimal insufficiently supported by existing data. variation from claimed SPF. (Also see “Con- (Also see “’Data Gaps’ Keep 12 Ingredients sumer Reports Issues 2019 Sunscreen Rec- Off FDA’s Proposed OTC Sunscreen Mono- ommendations; All Contain Oxybenzone” graph” - HBW Insight, 21 Feb, 2019.) - HBW Insight, 9 May, 2019.) “It’s long past time that the chemicals PCPC and CHPA are working to provide used in sunscreens were tested to show FDA with comments on the proposed sun- that they will not harm our health,” Lei- The Personal Care screen rule. The organizations requested ba says. a 60-day extension to submit their com- EWG has consistently championed min- Products Council ments, but were granted only an extra 30 eral-based sunscreens over chemical ones days to June 27. (Also see “Industry Groups in its annual sunscreen ratings tracing and the Consumer To Request FDA Rulemaking Deferrals For back to 2007. The nonprofit takes particu- Healthcare Products Sunscreen Ingredients In Question” - HBW lar issue with oxybenzone due to its sus- Insight, 19 Mar, 2019.) pected hormonal effects, allergic poten- Association contend While EWG clearly favors mineral sun- tial and other safety concerns heightened screens, its “best” list includes sunscreens by recently published FDA study results that EWG’s report formulated with chemical filters such as indicating significant systemic absorption. “irresponsibly avobenzone and ecamsule. (Also see “FDA MUsT Shows Sunscreen In- The group says there are fewer data gredient Absorption ‘Not Just A Theoretical misrepresents gaps for avobenzone than other chemical Concern’ “ - HBW Insight, 7 May, 2019.) sunscreen agents. It also is one of only two In the inaugural year of its sunscreen the evidence UV filters available for use in the US that guide, EWG said zinc oxide and titanium base surrounding provide “good UVA shielding,” the other dioxide “appear not to absorb into the being zinc oxide, according to EWG, which skin,” based on information available at sunscreen safety predicts that avobenzone will be deemed that time. (Also see “Environmental Group GRASE by FDA. Urges Rapid Application Of Sunscreen and efficacy.” Rule” - HBW Insight, 3 Sep, 2007.) Published online 3 June 2019

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Wildflower Rep Before FDA Cannabis Panel: CBD’s Functional Purpose In Beauty Products? Er … RYAN NELSON [email protected]

ancouver, Canada-based Wildflower Brands, Inc. sent a rep We’ve had a lot of interaction with customers that – it’s simply to the US Food and Drug Administration’s public hearing more effective as a beauty product when we include that ingredi- Von cannabis May 31, with the message that CBD-contain- ent. I’m not 100% on the scientific research.” ing cosmetics and dietary supplements can be adequately regu- Mettler persisted, “When you say ‘effective,’ what do you mean lated without consigning such products to the drug category. by that?” “While we recognize that CBD has demonstrable medical use Shults hesitated. “It delivers a more … a higher sense of, you when highly refined and used in a controlled clinical setting, we know, of personal attraction … an increase in … it’s more desir- also think there is sufficient evidence to safely regulate plant -ex able to the product. Not through clinical definitions, but through tracts containing CBD in a dietary supplement or cosmetic,” said a consumer-based opinion.” WMI Consulting’s James Shults on Wildflower’s behalf. Despite obviously being put on the spot, Shults managed not He noted the massive increase in public interest around CBD to mention CBD’s purported anti-inflammatory properties or since the 2018 farm bill’s passage. (Also see “CBD Cosmetics Rush acne-fighting powers – benefits that FDA maintains should be Is ‘Fast And Furious,’ But Don’t Skimp On Testing, Experts Say” - HBW exclusive to pre-approved or OTC monograph-compliant drugs Insight, 21 May, 2019.) – nor any other disease-treatment or structure/function effect “And it’s only getting started,” he said. that would exceed the Federal Food, Drug and Cosmetic Act’s Shults continued, “Wildflower understands that the best ap- “cosmetic” definition. proach to establishing public safety and trust in our products Another panelist questioned whether the consultant had infor- is through the FDA regulating CBD for use in a dietary supple- mation to offer on CBD’s absorption potential, a factor of increas- ment or cosmetic. … The public needs to trust that the products ing importance in FDA’s consideration of topical drug ingredients they are buying are safe, are made with the ingredients they are and cosmetics safety issues. (Also see “FDA Final MUsT Guidance promised and don’t contain any misleading information about For Topical OTCs Bolstered By Agency’s Recent Study Results” - HBW benefits or uses.” Insight, 14 May, 2019.) The consultant said he would be submitting a citizen petition Shults answered in the negative, but said he was collecting sci- requesting agency rulemaking to permit use of CBD in dietary entific evidence, including exposure data, in conjunction with the supplements and cosmetics. citizen petition he plans to submit. “Through evidence-based regulation and guidance, the FDA “That is at the root of what we’re trying to figure out and pres- can ensure safe and accurate CBD products are available to the ent to you to provide clear grounds for why you can safely regu- public and that the industry can grow with clear expectations of late this in those products,” he said. what good manufacturing looks like,” he concluded. Titled “Scientific Data and Information about Products Contain- Shults was one of more than 100 stakeholders invited to pro- ing Cannabis or Cannabis-Derived Compounds,” the FDA hearing vide oral testimony at the hearing, each limited to two minutes in also included remarks from the Consumer Healthcare Products order to leave room for almost six hours of formal presentations. Association, Council for Responsible Nutrition and American Reportedly, FDA had to deny more than 300 requests from inter- Herbal Products Association. ested commenters. (Also see “Legalizing Marijuana Would Calm Concerned citizens, health professionals and representatives CBD Regulatory Storm – CV Sciences’ MacKay” - HBW Insight, 22 from academia, the agricultural sector and state government en- May, 2019.) tities weighed in as well. Much of the testimony flowed without interruption from FDA’s FDA is accepting written or electronic comments on the subject panel convened for the occasion, consisting of agency attorneys, through July 2. program directors and top policy advisors. However, panelists had questions for Shults. Published online 31 May 2019 “Can I ask what you view as the functional purpose of CBD in beauty products?” asked Erik Mettler, assistant commissioner for partnerships and policy in FDA’s Office of Regulatory Affairs. (Also see “Interested In Using CBD Or Probiotics In Cosmetics? Ask Your- ’ self Why – FDA’s Linda Katz” - HBW Insight, 15 May, 2019.) LET S GET It was a dicey question for a company already marketing topical CBD products and soap, along with capsules, tinctures SOCIAL and vaporizers. @HBWInsight Shults hemmed and hawed accordingly. “Personally, I don’t have a collection of the evidence to give you a hard claim on that.

hbw.pharmaintelligence.informa.com 10 June 2019 | HBW Insight | 11 WELLNESS (DIETARY SUPPLEMENTS)

VMS Industry Wants Into CBD Market, Plus Enforcement On Firms Already There MALCOLM SPICER [email protected]

level playing field for developing hemp and CBD space? he added. “Every- and launching dietary supplements one is having to make difficult decisions.” Acontaining cannabis-derived ingre- The decisions’ importance grows as the dients should come with any decision to market soars and most of the established deem the substances dietary ingredients, VMS industry stays out. “The gravitational industry stakeholders recommend to the pull to enter the market is increasing,” Is- US Food and Drug Administration. raelsen said. “You’re punished for not en- An FDA policy change should include tering it. Hence, the inequity.” requiring full regulatory compliance by And the unrest in the industry due to companies already marketing food and the inequity won’t be lost on the FDA. supplement products containing hemp “Why not open a public discussion about and cannabidiol, representatives of vita- it? It all leads back to the problem of who min, mineral and supplement product is going to take nest step? FDA, you have firms and industry trade groups said at a NOW Health VP Aaron Secrist: “By not to do something,” he said. public hearing on 31 May. enforcing the current statutes, the agency Natural Products Association President The requirements include submitting is encouraging irresponsible or at best and CEO Daniel Fabricant sees Secrist’s to the agency pre-market notifications of uneducated and uninformed companies suggestion as good not only for the indus- to manufacture hemp and CBD products proof of a reasonable expectation safety try’s future, but also for the FDA to clamp without” complying with FDA regulations. for an ingredient’s intended use. Although down on noncompliant firms that could no new dietary ingredient notifications be selling unsafe products. have been filed for CBD and hemp and the NOW Health also recommends as part of a “He wants to get the agency in the FDA says the substances are not eligible policy change enforcement that is outside game, or stop giving those who are mak- for use as dietary ingredients, the agency’s the agency’s regulatory powers – impos- ing products in their garage an advan- current enforcement policy allows sales of ing financial penalties. tage,” Fabricant told HBW Insight. VMS, food and cosmetic products contain- “Also, ensure the rule of law is upheld by In comments during the hearing, Coun- ing the ingredients without drug or other barring any company illegally marketing cil for Responsible Nutrition President and violative claims and otherwise compliant CBD or hemp-derived dietary ingredients CEO Steve Mister noted that companies with relevant regulations. from submitting [a new dietary ingredient marketing hemp and CBD supplements “The current approach taken by FDA, notification] for the period of time that probably aren’t up on their regulatory what seems to be best described as unof- their products have been illegally mar- burden. Responding to a question from ficial enforcement discretion, does little to keted,” Secrist said. FDA Office of Foods and Veterinary Medi- promote and protect the public’s health “If the FDA simply opens the door to cine Senior Advisor for Policy Sharon Mayl, and safety, the primary mission of the hemp-derived ingredients and products Mister said no compliant firms probably agency,” said Aaron Secrist, NOW Health containing CBD by” deeming the sub- are making or offering the products. Group’s quality and regulatory affairs vice stances dietary ingredients, “it effectually “Typically, when a new ingredient president, at the hearing the FDA con- will encourage companies to flout the law comes to market, it comes through exist- ducted for scientific data and information in the future,” he said. ing companies that are already in the di- about products containing cannabis or etary supplement space and as a result, cannabis-derived compounds. ‘FUNDAMENTAL ISSUE’ FOR they are well-equipped and familiar with “By not enforcing the current statutes, COMPLIANT FIRMS all the requirements. I believe that what’s the agency is encouraging irresponsible Secrist’s recommendation for financial happening in the CBD space is that the or at best uneducated and uninformed penalties may not have relevance to the majority of these companies who are companies to manufacture hemp and FDA’s authorities, says United Natural bringing CBD to market in supplements CBD products without” complying with Products Alliance President Loren Israelen, are not companies that were already in FDA regulations for VMS product manu- but it illustrates the scope of the problem the dietary supplement space,” Mister said. facturing and marketing, Secrist told a for compliant firms. A requirement many are missing is panel of 12 FDA senior officials. “Aaron is raising a fundamental issue, to include on labels a domestic phone While requiring all firms marketing this ‘go, no go’ question that every compa- number or address for reporting adverse hemp and CBD food and supplement ny in our industry faces,” Israelsen said in events to product marketers, to evaluate products is within the FDA’s authority, an interview. “Do we go or not go” into the those reports and to submit to the FDA all

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though cannabis-extract CBD already has been studied as an inves- Docket Follows Farm Bill tigational drug and is approved in one drug marketed in the US. NOW Health, however, wouldn’t expect a rapid process for the The agency sought comment, at the public hearing and FDA clearing an NDI notification for hemp or CBD ingredients sub- to a docket – FDA-2019-N-1482 – open through 2 July, mitted by it or any firm. on questions in the categories of health and safety risks; “It probably would take us some time to survey the market. manufacturing and product quality; and marketing/la- We’ve done that a little bit already, to just know what’s there and beling/sales. It asked for input from across the sectors of know what the different options are,” Secrist said. stakeholders with interest in whether cannabis-derived “We certainly want to figure out what is safe, at what amount ingredients receive its clearance for use in any category of what dose, what are the potential toxic elements that potentially regulated products other than drugs. could be in it. So, finding a clean source certainly would be a top In July 2018, the agency acknowledged its current food priority,” he added. and supplement sector enforcement policy when it approved the first drug available in the US made with a can- COMPEL COMPLIANCE TO LEVEL FIELD nabis-based active ingredient. The docket wasn’t opened Comments from Secrist and others at the hearing not only provid- after Congress in December 2018 passed legislation reau- ed the FDA a wide variety of input, but also confirmed that hemp thorizing spending for US Department of Agriculture pro- and CBD food and supplement products won’t be confiscated grams, the farm bill, that included a provision removing from store shelves. hemp – defined as cannabis plants and derivatives con- “I think everyone realizes that it is embedded in the US” and re- taining no more than 0.3% concentration, on a dry weight moving the products from the market “presents an unclimbable basis, of tetrahydrocannabinol, the psychoactive ingredi- mountain for FDA,” UNPA’s Israelsen said. “Taking them off the ent in cannabis – from the Drug Enforcement Administra- market is not an option.” tion’s schedule of controlled substances Instead, the FDA could compel compliance from firms already marketing hemp and CBD supplements. Failures to respond satis- The farm bill, though, didn’t direct FDA to allow hemp and factorily could lead to some businesses being shut down through CBD as dietary ingredients. While it explicitly preserved litigation conducted for the FDA by the Department of Justice. FDA’s authority to regulate products containing cannabis The agency’s current policy of warning hemp and CBD product or cannabis-derived compounds, it also included language marketers making drug claims won’t produce those results. acknowledging that the agency’s authority to make CBD “Act as if CBD is lawful,” Israelsen said. “When it is labeled as di- and other cannabis-derived ingredients eligible for use in etary supplement and it’s a dietary ingredient, all of the rules apply.” food and supplements. “The reality is it’s not the marketing. Rather than sending warning letters about Alzheimer’s claims, inspect facilities and get to the heart of it and tell those companies that if you’re in violation, reports of serious adverse events. “That is an additional reason the FDA has regulatory authority and can and will take enforce- why the agency needs to be aggressive in enforcing the regula- ment action,” he added. tory requirements for supplements,” Mister said. “I believe that would focus the mind of the industry during this debate.” Part of the reason behind the FDA’s current approach to YEAR-FOR-YEAR PENALTY? hemp and CBD’s use in food and supplements is the agency’s lim- NOW Health will consider submitting NDI notifications to the FDA ited resources. Policing manufacturing and marketing in the gen- before entering the market with hemp or CBD products in the eral food and supplement industries already taxes its staffing and event an agency policy change, Secrist said in an interview. funding, and launching an initiative targeting the hemp and CBD Meanwhile, though, other businesses already are selling hun- space isn’t practical. dreds of hemp and CBD products even though the ingredients, But the FDA and the industry have options. “That’s a solvable under FDA regulations, are unlawfully being used. Those firms problem, if it’s a resource issue,” Israelsen said. have a head start in what obviously is a rapidly growing market. “If that taxes FDA’s resources, I think you would see broad re- “If it’s been five years” that a firm has sold hemp and CBD food ports to members of Congress stating that one thing you can do or supplements, “then they’re barred for five years,” Secrist told is to allocate resources to FDA, your constituents would support HBW Insight. He added, though, those firms’ compliance with that. I would like to believe industry would.” such a penalty wouldn’t be guaranteed. “They already don’t fol- Congress could be pivotal, too, in changing the FDA’s policy low the law. So, are they going to pull the product? Probably not.” on hemp and CBD as dietary ingredients. FDA officials have ac- Food and VMS firms that comply with FDA regulations are “sit- knowledged that a rulemaking would take several years, and ask- ting it out because they’re waiting for regularity clarity. They’re the ing members of Congress for legislation to require the change ones who are going to do what it takes to do the safety studies could be more efficient. “We’re all familiar with the usual pace that and make sure the products are safe,” Secrist said. it would take the FDA to review and then make the decision on Like other manufacturers represented at the hearing, NOW what next to do,” Israelsen said. Health recommends that the FDA use its authority to deem cannabis-derived substances eligible for use as dietary ingredients even Published online 4 June 2019

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FDA Road To Decision On Expanding CBD Uses Starts With Weighing Impact On Existing And Future Use As Drug MALCOLM SPICER [email protected]

S Food and Drug Administration officials are making clear that their consideration of cannabidiol’s use as a dietary Uingredient will prioritize weighing the potential impact of slowing or interrupting the development of drugs using cannabis-derived substances. At a May 31 public hearing, officials starting with acting Com- missioner Norman “Ned” Sharpless emphasized that CBD is approved only as a drug ingredient and deciding whether to allow it use in any other type of FDA-regulated product will be done with potential impact on drug development foremost in the agency’s thinking. Also apparent from questions the 12-member panel of FDA officials asked during the day-long hearing was that a potential regulatory pathway for clearing hemp and CBD as dietary ingredients will require resolving concerns about the substances’ dose or concentration levels in food and dietary supplements, establishing ingredient identity standards and determining whether “FDA treats substances derived from food and supplements already available with the ingredients will be allowed to remain on the market without notifications to the cannabis just like we do any other agency with proof of reasonable expectation of safety for their in- substances, and they are subject to the tended uses. The FDA’s first public hearing on the use of cannabis-derived same authorities as any other substance.” – ingredients in products subject to its oversight revealed, too, that the agency is aware it is behind the market curve on establishing acting FDA Commissioner Ned Sharpless a regulatory scheme allowing hemp and CBD’s use as a dietary ingredient. Hemp-derived ingredients’ use in cosmetics also was discussed at the hearing. FDA is playing catch-up not only because hundreds of food ments and other non-drug products already available with the and supplement products, as well as cosmetics and animal health ingredients also isn’t escaping the agency’s attention. products, containing the ingredients already are available, but “Given the new interest in marketing cannabis products across also because US hemp farmers are moving to using the large ma- the range of areas FDA regulates, we will need to carefully evalu- jority of acreage to grow the botanical for use as a dietary ingredi- ate how all these pieces fit together in terms of how consumers ent. Farmers generate $60,000 to $70,000 per acre raising hemp as might access cannabis products,” said Sharpless. a dietary ingredient compared to $750 for textiles. While Sharpless didn’t remain at the hearing, other agency of- Comments by more than 100 speakers from across all stake- ficials kept front and center the question of how allowing hemp holder communities provided the agency with nearly as many and CBD as dietary ingredients will affect pharmaceutical research viewpoints and suggestions about its path ahead, with numerous and product development using cannabis-derived substances. speakers discussing topics outside the FDA’s oversight such as “How does the availability of CBD and other cannabis-derived some states legalizing sales of medical marijuana or of recreation- ingredients in the marketplace conceptually incentivize or disin- al amounts of cannabis. Several speakers, including an attorney centivize your drug development?” asked Principal Deputy Com- who litigates complaints for damages against opioid drug manu- missioner Amy Abernethy following comments by a represen- facturers as well as cannabis-product firms, offered emotional tative of a firm developing endocannabinoid system-targeting statements about the potential harm from allowing hemp and synthetic drugs to treat inflammatory and fibrotic diseases. CBD as dietary ingredients because the substances are derived “How do you think the commercial availability cannabis and from cannabis. CBD and other cannabis-derived ingredients is affecting Al- Through it all, starting with Sharpless’ hearing-opening com- zheimer’s research?” asked Principal Associate Commissioner for ments, the agency’s representatives reiterated that allowing Policy Lowell Schiller following a presentation by an Alzheimer’s CBD’s use in food, supplements or cosmetics could come with a Association official. spotlight on it already being approved as a drug ingredient and Noting a CV Sciences Inc. executive’s comment about FDA’s ex- studied for additional medicines. And the impact of food, supple- isting regulatory options for allowing CBD and other hemp-de-

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rived extracts as dietary ingredients and the pharmaceutical use and hemp-derived CBD to be used in food and dietary supple- of cannabis-derived CBD, Sharon Mayl, senior advisor for policy in ments and in the meantime demand that products that are mar- the Office of Foods and Veterinary Medicine, asked, “Do you see keted as food and dietary supplements comply with all the re- any of them disincentivizing the other? In other words, does al- quirements” in the agency’s VMS product regulatory framework. lowing a broader use disincentivize clinical trials?” Compliant VMS firms, Mister added, would file NDI notifications before introducing CBD supplements, but they would first need FARM BILL FORCES FDA’S HAND recognition that the FDA considers the ingredient eligible for use CBD and hemp are available in the US in supplements, food and as a dietary ingredient. cosmetics because the FDA, officially for two years and unofficially “Ironically, if a company submits an NDI notification today to for a longer period, has practiced an enforcement policy that al- FDA … it would have that notification returned because the ingre- lows sales of products that are not marketed with drug or other dient is not recognized as legitimate dietary ingredient,” he said. violative claims and that are otherwise compliant with relevant The FDA could find the answer to its regulatory question agency regulations. Additionally, some supplements for dogs and through a lengthy rulemaking, or as former Commissioner Scott other pets contain CBD and veterinarians are prescribing CBD- Gottlieb suggested to members of Congress earlier in 2019, a rule containing remedies off-label for pets and other animals. allowing hemp and CBD’s use a dietary ingredient and potentially In July 2018, the agency acknowledged the food and supple- for other non-drug uses could come more quickly through legisla- ment sector enforcement policy when it approved the first drug tion. (Also see “FDA Clearing CBD As Dietary Ingredient? Legislation available in the US made with a cannabis-based active ingredient. More Likely Than Rulemaking” - HBW Insight, 2 Apr, 2019.) A docket to consider allowing the use of hemp and CBD as dietary FDA panel member Douglas Throckmorton, the Center for Drug ingredients didn’t come until December 2018, after Congress Evaluation and Research’s deputy director for regulatory pro- passed legislation reauthorizing spending for US Department of grams, said the agency will consider comments from the hearing Agriculture programs, the farm bill, that included a provision re- and submitted to the docket and other relevant information to moving hemp – defined as cannabis plants and derivatives con- “decide exactly what course we’re going to take.” taining no more than 0.3% concentration, on a dry weight basis, “We got a large spectrum of voices. That is what we were look- of tetrahydrocannabinol, the psychoactive ingredient in cannabis ing for,” he told HBW Insight. “We heard from people we hadn’t – from the Drug Enforcement Administration’s schedule of con- heard from before. We have new people to talk to. That’s a good trolled substances. (Also see “FDA To Consider Regulatory Shift thing for us.” Making Cannabis Ingredients Officially Eligible For Use In Dietary The course FDA chooses, he added, will determine when this Supplements” - HBW Insight, 28 Dec, 2018.) regulatory question is answered. “If it’s a legislative course, its goes However, the farm bill didn’t direct FDA to allow hemp and CBD on one timetable. If it’s a rulemaking that we decide to do, that’s as dietary ingredients, Sharpless noted in his remarks. The legis- another timetable.” lation “explicitly preserved FDA’s authority to regulate products containing cannabis or cannabis-derived compounds,” he said. DRUG FIRMS VALUE PHARMA POTENTIAL “FDA treats substances derived from cannabis just like we do The drug industry, too, is anxious for the FDA to establish a regu- any other substances, and they are subject to the same authorities lation. That’s especially true for GW Pharmaceuticals PLC which as any other substance,” Sharpless added. markets the only CBD-containing drug the agency has approved, And while the bill also included language that the agency Epidiolex (purified cannabidiol) oral solution for treatment of can make CBD and other cannabis-derived ingredients eligible syndromes of rare forms of pediatric epilepsy. (Also see “Gottlieb: for use in food and supplements, that change wouldn’t come Epidiolex Approval Covers One Specific Cannabidiol Medication, easy, he said. Not Marijuana” - Pink Sheet, 25 Jun, 2018.) “Although the law says that FDA can issue regulations to create Alice Mead, vice president of US public policy and public af- new exceptions to these statutory provisions, FDA has never is- fairs for GW’s subsidiary Greenwich Biosciences Inc. in San Diego, sued a regulation like that for any substance. So, if we were think- pointed out to the FDA panel that GW Pharma conducted clinical ing about doing that for a substance like CBD, it would be new trials with CBD and produced a comprehensive profile of its safety terrain for the FDA,” Sharpless said. as part of its new drug application for Epidiolex. “No one knew CBD was potentially toxic to the liver until we VMS INDUSTRY WANTS ANSWERS conducted” trials, Mead said. New to the agency or not, the vitamin, mineral and supplement “We support a strong regulatory framework for cannabis prod- product industry is anxious for the FDA to embark on a rulemak- ucts that encourage robust research, maintains the integrity for ing. No shortage of hemp- and CBD-containing supplements al- the FDA approval process for medicine and brings more FDA-ap- ready are available, but nearly all are marketed by firms with little proved medicines to patients,” she added. to no presence in other VMS product categories and none of the London-based GW also markets Sativex, a botanical formula- products were subjects of new dietary ingredient notifications to tion in an oral spray to treat multiple sclerosis-related spasticity, in the FDA. countries outside the United States. It is researching other phar- The Council for Responsible Nutrition, said President and CEO maceutical uses for cannabis-derived ingredients, Mead said. Steve Mister, “urges FDA to act quickly and decisively to ... [con- “We’re just scratching the surface … there’s plenty of potential duct] a notice-and-comment rulemaking which will allow hemp in this plant to treat more diseases,” she said.

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GW’s research, Mead said, also cast ents used in food and supplements. The California, San Diego, Center for Medici- doubt on the farm bill’s definition of company, said Chief Scientific Officer nal Cannabis Research, that “rather small hemp ingredients as extracts containing Rosemary Mazanet, is vertically integrated doses of THC appear to produce benefits no more than 0.3% of THC. to control its ingredients from start to fin- for neuropathy.” Proponents for hemp and CBD’s use as ish in testing and development. Grant said while additional studies dietary ingredients assert that the sub- Meanwhile, edibles and supplements are needed on dosing levels and use stances have no psychoactive effect and labeled as containing CBD may contain format to prove CBD’s efficacy, consum- that 0.3% levels will eliminate any effect more or less of the listed ingredients, ers already using food and supplements from THC. which may or may not have been tested made with the ingredient for help with a “It’s a myth that CBD products will before they were used to make a fin- variety of health issues. Consumers have have only trace amounts of THC. The ished product. no reliable sources to guide their deci- 0.3% limit from the farm bill could be “What that shows is people are lazy. sions even as the number of available interposed to allow, for example a small People will do an extraction of whatever products soars. gummy bear [edible or supplement] plant they have and sell it. Until somebody “The public will continue to use these to have as much as 12 mg of THC. That tells them they can’t do that, they will con- products without appropriate informa- means two gummy bears could provide tinue to sell it,” Mazanet said. tion. We need to get the information out more THC than smoking an entire mari- “We’re trying to make a legitimate in a more nimble fashion,” Grant said. juana cigarette,” Mead said. business out of the medical products “In our view, we are rapidly getting be- New York firm Columbia Care Inc. also that might be available from cannabis,” hind the curve in terms of what’s happen- is developing cannabis-based drugs and, she added. ing in the real world.” like GW, is concerned about the absence Cannabis research also shows, said of standards for CBD and similar ingredi- Igor Grant, director of the University of Published online 3 June 2019 FDA’s CBD Puzzle: ‘Criminals’ Continue Or Prohibition Ends And Research Grows

MALCOLM SPICER [email protected]

llowing cannabis-derived ingredi- substances also was recommended dur- Evans told the panel that “anybody ents’ use in any non-drug product ing the hearing at the FDA’s White Oak that’s selling marijuana as a medicine or as Aavailable in the US allows “crimi- campus headquarters in Silver Spring, Md. a food that is not approved by the FDA” is nals” in “the marijuana industry” to profit, The agency sought comment, at part of “the marijuana industry.” the Food and Drug Administration heard the hearing and to a docket – FDA- “The reality is these people are criminals. from speakers at a 31 May public hearing. 2019-N-1482 – open through 2 July, on They are doing this in violation of the fed- On the other hand, speakers during the questions in the categories of health and eral Controlled Substances Act and also agency’s first-ever hearing on the use of safety risks; manufacturing and product the Food, Drug and Cosmetic Act … and cannabis-derived ingredients in products quality; and marketing/labeling/sales. the federal government has allowed for subject to its oversight also suggested And it sought comments from across the this to go on for a long, long time,” he said. that the FDA leverage its authorities to sectors of stakeholders with interest in Rather than moving off its official policy help establish uniform regulations nation- whether cannabis-derived ingredients re- that cannabis-derived ingredients are not wide about access to hemp and cannabi- ceive its clearance for use in any category eligible as dietary ingredients because diol in food and dietary supplements. of regulated products other than drugs. some are approved or are being studied Additionally, a panel of 12 FDA senior (Also see “CBD Public Hearing Could Extend as drugs, Evans said the FDA should in- officials also heard from representatives FDA’s Hand Further For Help From Con- stead begin enforcing the prohibition. of drug development firms who asked gress” - HBW Insight, 29 May, 2019.) “It’s not debatable. There is no regula- the agency to loosen limits on research- David Evans, an attorney active in liti- tory ambiguity. You guys have said, ‘don’t ers’ access to cannabis-based substances. gation targeting pharma firms marketing sell this stuff. It’s illegal’,” he said. Helping drug firms access substances to opioid drugs and also general counsel for “These people have been operating research potential treatments that tar- a group targeting cannabis product firms for years and they’ve ignored you. What get a variety of conditions by reaching –”Cannabis Industry Victims Educating makes you think that anything will be dif- the endocannabinoid system, which is Litigators” – spoke at the FDA hearing to ferent if you come out with something responsible for observable effects seen ask for a prohibition on the use of canna- now? The only way it’s going to be differ- from consuming CBD and other cannabis- bis-derived ingredients in any non-drug ent is if you enforce it and you have not derived ingredients, but are not cannabis product subject to the agency’s oversight. been doing that.”

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CBD and hemp are available in the US in “We suggest that the FDA work hand in supplements, food and cosmetics because hand with the states,” Orlowitz said. the FDA has practiced an enforcement policy that allows sales of products that QUESTIONS FORM are not marketed with drug or other vio- PHARMA, TOO lative claims and that are otherwise com- Drug firms Corbus Pharmaceuticals pliant with relevant agency regulations. Holdings Inc., Full Spectrum Omega Inc. A docket to consider allowing the use of and CV Sciences Inc. also support broader hemp and CBD as dietary ingredients was use of cannabis-derived ingredients un- opened after Congress in December 2018 der the agency’s oversight, but comments passed legislation reauthorizing spend- by their representatives at the hearing ing for US Department of Agriculture reflect how the current regulation of can- programs, the farm bill, that included a Marijuana Policy Project attorney Sheri nabis by the FDA and the Drug Enforce- provision removing hemp from the Drug Orlowitz: De-scheduling hemp “creates an ment Administration create impediments Enforcement Administration’s schedule unprecedented opportunity” for FDA. in their work. of controlled substances; the bill defined Corbus is developing treatments for hemp as cannabis plants and derivatives Justice attorney, she currently works to cystic fibrosis, systemic sclerosis and containing no more than 0.3% concentra- “get rid of the cannabis prohibition.” In ad- other conditions through a non-canna- tion, on a dry weight basis, of tetrahydro- dition to the marijuana remaining a con- bis ingredient that target the endocan- cannabinol, the psychoactive ingredient trolled substance under federal law, an nabinoid system but avoid interaction in cannabis. impediment to wider consumer access to with cannabinoid receptors in the brain However, the farm bill didn’t remove cannabis products, she said, is the variety and focus on the immune system out- exempt hemp and CBD from the FDA’s au- of regulations among the states. side the brain, thority for use in products under its over- For instance, she said, California cur- “It is not medical cannabis nor is it a sight; instead it stated that the agency can rent prohibits using CBD derived from cannabis-derived substance,” said Robert make CBD and other cannabis-derived hemp in food but allows using the sub- Discordia, the Norwalk, Mass.-based firm’s ingredients eligible for use in food and stance derived from marijuana. Those vice president for pharmaceutical devel- supplements. and other rules and regulations that lim- opment and manufacturing. In addition to Evans for CIVEL, represen- it business growth as well as consumer “Yet, because [Corbus’ exploratory tatives for opponents of allowing canna- access could be made more uniform drug] is categorized as a cannabinoid, we bis-derived ingredients in non-drug prod- with FDA’s help. face obstacles that other drug developers ucts including Marijuana Victims Alliance, targeting the same indications with non- Partners in Safety and Smart Approaches cannabinoid, exploratory drugs do not,” to Marijuana Canada wre among the more Discordia told the FDA panel. than 100 speakers during the hearing. He added that same type of restriction delays Corbus from conducting clinical OPPORTUNITY TO EXPAND trials in Canada and Australia but not ACCESS “The reality is these in 27 other countries. “FDA should de- A former federal prosecutor now investing velop a transparent, consistent, fair and through private equity, Sheri Orlowitz, of- people are criminals. practical framework to support the in- fered the FDA a suggestion diametrically They are doing this in vestigation and development of drugs opposed to Evans’. “This creates an un- targeting the endocannabinoid system precedented opportunity,” said Orlowitz, violation of the federal … to have a clinical development path a founding partner at Artemis Holdings that mirrors as closely as possible that of Group LLC and an attorney in the Mari- Controlled Substances other investigational drugs without the juana Policy Project. Act and also the Food, need for unnecessarily onerous regula- The MPP since 1995 has worked to tory barriers.” change federal law to allow states to de- Drug and Cosmetic At Full Spectrum Omega, founder and termine their own marijuana policies, to CEO Richard Brumfield has difficulty ob- allow the medical use of cannabis in all Act.” – David Evans, taining cannabis-derived ingredients for states and territories and to regulate mari- attorney ”Cannabis development of low-THC medicinal can- juana like alcohol. The project will provide nabinoid elixirs and topical products. In a report on states’ marijuana and hemp/ Industry Victims addition to developing products for FDA CBD laws as part of its comments to the approval, the Log Angeles-based firm has FDA docket. Educating Litigators” an agreement with the National Institute of Orlowitz said that while she once pros- Allergy and Infectious Diseases’ Radiation ecuted drug cases as a Department of and Nuclear Countermeasures program to

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test its products in a federal laboratory as a wound healing treat- substances are derived from the same source. The FDA should ac- ment after radiation exposure and is working with a Department of knowledge the difference, too, and recognize that it has multiple Defense on a proposal on pain relief products. options for clearing hemp and CBD’s use as dietary ingredients, Even with those research credentials, Full Spectrum Omega MacKay told the panel. doesn’t have clearance to move its materials from California to The agency has been clear that ingredients approved or studied other states for additional testing and development because the as drugs, such as highly purified and isolated CBD, aren’t allowed 2018 farm bill didn’t left up to states whether to allow interstate for use as dietary ingredients. However, the FDA has “ to separate transportation of hemp and CBD. (Also see “Legalizing Marijuana an agricultural commodity from controlled substance,” he said, Would Calm CBD Regulatory Storm – CV Sciences’ MacKay” - HBW adding that “hemp extract is a significantly different article from Insight, 22 May, 2019.) a highly purified CBD.” Brumfield said tests with ingredients the firm has not main- Existing FDA regulations support the agency’s evaluation and tained control of won’t work. “We need to find a way to bridge approval of GW Pharmaceuticals PLC’s Epidiolex (purified CBD) that gap where innovators like myself are not handicapped and oral solution for treatment of syndromes of rare forms of pediatric have to use a subpar product,” he said. epilepsy, and allowing hemp and CBD’s use as a dietary ingredient “If we don’t have control of our raw material now, how can we can be done, MacKay said. not have a drug shortage later on? It is imperative that we have “A product intended to treat children with epilepsy is a drug control of our own raw materials,” Brumfield added. and it should come with the pre- and post-market rigors re- Unlike Corbus and Full Spectrum Omega, CV Sciences is inter- quired of FDA-approved drugs. ... However, for a food product ested in marketing nutritional products containing hemp and that provides nutrition or a supplement that supports a healthy CBD as well as developing drugs with cannabis-derived ingredi- lifestyle, we have regulatory paradigms that appropriately cor- ents. Duffy MacKay, senior vice president of scientific regulatory respond to those uses.” affairs, said the Las Vegas-based firm recognizes the difference between a dietary ingredient and a drug ingredient even when the Published online 3 June 2019 Full Plate Of Dietary Ingredients In Latest US Tariff Hikes On Chinese Imports

EILEEN FRANCIS [email protected]

he Trump administration’s proposed tariffs on an addi- The additional ingredients comprise a wide swath of foods, es- tional $325bn in imports from China includes the major- sential oils, teas, herbal extracts and infant formulas and include T ity of nutritional product ingredients not subject to tariffs ginseng, turmeric, ginger, green tea, black tea, vanilla, cardamom, imposed in 2018 as stakeholders look for help from an exclusion cumin seeds, coconut seed, linseed oil, soybean oil, dill, chicory option offered for some ingredients already listed. plants, chickpeas and essential oils of orange, grapefruit, citrus The US Trade Representative on May 17 announced plans for a fruit, peppermint, mint and eucalyptus.Some US firms could seek 25% tariff on “essentially all products” imported from China that suppliers outside of China as one option for mitigating higher were not subject to three earlier lists. The increase does not ap- costs caused by the tariff hikes (see sidebar). ply to products exported to the US prior to May 10, if the items The list excludes pharmaceuticals, certain pharmaceutical in- entered the US prior to June 1. puts, select medical goods, rare earth minerals and critical minerals, notes the USTR’s notice on the duties. USTR is soliciting comments on the list until June 10 and will hold a public hearing for feedback on June 17.

AHPA, NPA COMMENTING TO USTR The American Herbal Products Association says it plans to submit comments on the tariff proposal “in an effort to minimize economic harm” to member companies that import ingredients from China. “Numerous herbal product ingredients are impacted by this latest round of tariff increases and the proposed expansion could increase the impact on US herbal products companies. We will continue to evaluate the potential impact of this new round of tariff actions on US-based dietary supplement marketers and seek member and industry input as we prepare recommendations for

USTR,” said AHPA President Michael Mc- duties on US imports – announced it will es to member of Congress urging them Guffin in a May 20 release. increase rates on US products into its to contact the administration to allow for The Natural Products Association also is country worth $60bn, from 5%-10% rates tariff exclusion on certain ingredients that submitting comments and plans to pres- to 20%-25%, effective June 1. Thousands are only sourced from China.” ent during the USTR hearing. NPA said of products targeted include teas, juices NPA says exclusions that industry has en- a May 23 release that the new round list and individual unmixed vitamins A and couraged are for ingredients used in the US of products includes “many new dietary B1, 2 and 12. to manufacture natural products, “many of ingredients used in dietary supplements which are exported back to China.” as well as personal and home care ingre- USTR ACCEPTS NPA’S The USTR has stated it will consider cer- dients and products.” EXCLUSION REVIEW REQUEST tain conditions to allow for excluding par- He noted a recent report from the Beer The USTR had allowed companies to re- ticular items, including whether they are Institute and National Beer Wholesalers quest product exclusions on the rounds of sourced exclusively from China or wheth- Association that asserts the tariffs on met- tariffs imposed in the first half of 2018 and er the tariff would cause severe harm to al products, including 10% on aluminum, so far it has allowed for about 1,500 prod- businesses or to the US economy. have inflated the price of aluminum cans uct exclusions. NPA has for months urged Stephen Mahinka, a partner at Morgan, and resulted in US companies cutting the agency to allow for a similar process Lewis & Backius LLP in Washington who around 40,000 jobs since mid-2018. Read for the third round of duties that kicked in works in areas including FDA regulatory, the full article here in September 2018, highlighting 57 items transactional and compliance matters The White House has said its tariff plan of ingredients it says should qualify. (Also throughout a product’s lifecycle, says is “part of the United States’ continuing see “Proposed Tariffs Threaten Ingredient while stakeholders will understandably response to China theft of American in- Supply Chain For US Supplement Firms” - push for exclusions, they are difficult -ar tellectual property and forced transfer of HBW Insight, 3 Aug, 2018.) guments to win, particularly for dietary American technology.” On May 21, the agency granted NPA’s supplements since few raw materials are In mid-2018, the USTR announced its request, announcing it was opening an available only from China. first two rounds of 25% tariffs on a com- exclusion-review process for products in- As thousands of exclusions are request- bined $50bn worth of Chinese imports. cluded in the round effective in Septem- ed and the USTR has limited staff, Mahinka On Sept. 21, 2018, the USTR implemented ber and would accept requests beginning recommends stakeholders provide spe- a 10% tariff on a third round of imported June 30. The USTR says in a Federal Reg- cific details on how they will be harmed products valued at $200bn, including di- ister notice it expects 60,0000 exclusion by the tariffs. “Saying we’re going to be etary ingredients and active ingredients requests to be submitted. injured, well everyone says that. It’s not and excipients used in OTC drugs. (Also “This process has been long and te- Earth-shattering to know that a particular see “Trump’s Chinese Import Tariff Hike dious. Without exclusions for industry, the importer or importers of a group of prod- Could Take Toll On Consumer Health Sec- tariff proposals will increase costs for small ucts are unhappy about paying more.” tor” - HBW Insight, 25 Sep, 2018.) businesses and the majority of Americans But he says companies that can make As tension with China grows, the USTR who rely on dietary supplements to sup- a bigger case for their business, such as announced on May 9 it would boost tar- port their healthy lifestyles,” NPA says. reducing staffing because of higher costs iffs for the third list of targeted ingredi- The group says it has been the “leading from tariffs, are more likely to be granted ents by 25%. trade” to push the USTR to offer the exclu- an exclusion. In response, China – which had already sion and has sent “thousands of letters responded to each round with its own representing hundreds of small business- Published online 30 May 2019 Supplement Firms Work On Mitigating Import Tariff Costs Before Raising Prices

EILEEN FRANCIS [email protected]

igher raw material costs associated with the US-China Mahinka, who represents clients on FDA regulatory, transac- trade war has some dietary supplement firms seeking tional and compliance matters throughout a product’s lifecycle, Hsuppliers outside of China or haggling with existing sup- said he expects increases in material costs on Chinese goods from pliers and retailers over bearing the brunt of the cost of higher tariffs the Trump administration has implemented to impact the raw materials. vitamin, mineral and supplement industry beginning in the sec- “If you are in the supply chain, your preference is always that ond half of 2019 and in 2020. The timing depends somewhat on someone else pay,” says Stephen Mahinka, a partner at Morgan, the length of supply contracts between manufacturers and retail- Lewis & Bockius LLP in Washington. ers, though most sign one-year contracts.

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On May 17, the White House proposed plans for a 25% tariff on a “It is going to be hard for industry to list of “essentially all products” imported from China not subject to three earlier duties, that includes many nutritional and cosmetic pass along 20% or 25% [price increases] ingredients and is valued at around $325bn (see sidebar). The tariff is on top of the 10% tariff announced in September 2018, that to consumers, if only because retailers has since kicked up to 25%, on items valued at around $200bn and two earlier rounds of 25% tariffs on goods valued at about are not going to be happy with that.”– $50bn. (Also see “Trump’s Chinese Import Tariff Hike Could Take Toll attorney Stephen Mahinka On Consumer Health Sector” - HBW Insight, 25 Sep, 2018.) Many large retailers are resistant to passing on higher costs to consumers, as they have “built their businesses on low prices,” Ma- hinka said. “It is going to be hard for industry to pass along 20% NEW SUPPLIERS, STAFF CUTS ON TABLE or 25% [price increases] to consumers, if only because retailers are Mahinka said supplement firms have efforts “already ongoing not going to be happy with that.” to try to reduce the dependency” on purchasing of Chinese raw materials, but, companies seeking alternative suppliers in other 10%-15% VMS PRICE HIKES LIKELY countries may run the risk of higher costs later if they source from During mass-merchandise retail chain Target Corp.’s May 22 earn- unqualified suppliers. ings briefing, CEO Brian Cornell said the firm is not “reactive” to “With FDA-regulated products, a manufacturer has to be careful the tariffs because of the impact price increases would have on that it is purchasing from a supplier that complies with FDA regu- consumers. “Our teams have done a very good job of trying to lations, so one of the difficulties with switching suppliers when mitigate the impact in the short term,” Cornell said. tariff restrictions are in place is that you want to make sure that, Target’s multi-category portfolio is a “huge advantage,” he said. in attempting to reduce costs by ten, fifteen or twenty percent for “Our ability to flex our focus from category to category is something some input, you are not raising product liability concerns by buy- that’s somewhat unique to Target versus single-category retailers.” ing from a source whose capabilities you are not sure of,” he said. Cost increases likely will be split among Chinese suppliers, The FDA’s capacity is limited for inspecting foreign food facilities manufacturers and retailers, said Mahinka. Manufacturers’ cost for items brought into the US and currently it’s using a “cross-cut- increases will depend on how much product they sell to retailers ting, risk profile” that weighs risks based on potential food-safety and “how important your brand is to them,” he added. risk associated with a commodity, manufacturing processes and Still, VMS product costs will trickle down to consumers. Mahin- compliance history of a facility, the agency notes on its website. ka said he expects consumers will see retail prices of VMS prod- The Food Safety Modernization Act passed in 2011 requires the ucts increase between 10%-15%. How consumers respond will agency to identify high-risk facilities and allocate resources to in- depend on the type of product, its popularity, its current price and spect facilities according to known safety risks and includes sever- how it is used. al other factors it considers when developing a facility risk profile. “Some dietary supplements people want and you can raise the Supplement companies may have to mitigate costs from ma- price 10%-15% and you don’t affect the purchases. Other prod- terials by cutting employees, said Mahinka. “If you are a dietary ucts you try that and people say, ‘I’m going to cut down from tak- supplement company with low margins and the products you are ing two tablets to one, or take them every other day’.” mostly selling are very much affected by these tariffs it is going to Mahinka expects VMS products to be impacted more by the be hard for you to retain all your employees.” tariffs than cosmetics as supplement ingredient costs are more He noted a recent report from the Beer Institute and Nation- reflective of raw material. Prices for cosmetics products, which al Beer Wholesalers Association that asserts the tariffs on metal typically deliver higher margins than supplements, often are in- products, including 10% on aluminum, have inflated the price fluenced more by costs of ornate packaging and brand building of aluminum cans and resulted in US companies cutting around efforts, including advertising, he said. 40,000 jobs since mid-2018. Published online 30 May 2019 FDA Prioritizes Vinpocetine Decison After Animal Study Shows ‘Developmental Toxicity’

MALCOLM SPICER [email protected]

he US Food and Drug Administration will “expedite” decid- The agency announced the plan in a June 3 statement by two ing whether to prohibit vinpocetine’s use as a dietary in- deputy commissioners warning consumers about safety concerns T gredient following a National Institute of Health program regarding vinpocetine, “specifically concerns about the use of this animal study showing consumption of the synthetic botanical ingredient by women of childbearing age.” Recent findings by the derivative is associated with adverse reproductive effects. NIH National Toxicology Program’s study with rats and rabbits in-

second species; all animals survived to the The agency’s 2016 proposal to ban end of the study, the report states. vinpocetine’s use as a dietary ingredient “Under the conditions of this prenatal – docket FDA-2016-N-2523 – prompted study, there was clear evidence of devel- quick industry rebuttals. The Council for opmental toxicity of vinpocetine in rats Responsible Nutrition and the Natural based on increased post-implantation Products Association said in separate loss and increased incidences of ventricu- comments to the FDA that it would es- lar septum defects, thoracolumbar ribs tablish a process outside its regulatory (full), and incomplete ossification of the authority for removing ingredients from thoracic centrum in the absence of overt the supplement marketplace if it followed maternal toxicity,” the researchers said. through on the proposal, which would They described vinpocetine as a semi- render violative an ingredient currently synthetic derivative of vincamine, an al- widely used in supplements. (Also see kaloid extract derived from the periwinkle “FDA Opens Extra-Regulatory Enforcement plant Vinca minor, widely available as a Door On Vinpocetine – CRN, NPA” - HBW In- pharmaceutical in Europe, Russia, China, sight, 8 Nov, 2016.) and Japan for treatment of cerebrovas- NPA also asserted that vinpocetine cular and cognitive disorders. In the US, meets FDA’s criteria for a compliant moi- it has been marketed as a dietary supple- ety of a botanical stated in the agency’s ment, often with cognitive enhancement draft guidance for new dietary ingredient Sales of dietary supplements with claims and targeted for older consumers. notifications. In addition to arguing that vinpocetine could end soon as FDA plans However, memory enhancement market- FDA over-stepped its regulatory author- to “expedite” confirming its 2016 proposal ing also has targeted younger consumes, ity with is proposal to ban vinpocetine’s to ban its use as a dietary ingredient. including women of childbearing poten- use in supplements, NPA’s argued that the tial, according to the NTP study. proposal ignores the science behind the dicate “vinpocetine may cause a miscar- The study states that exposure to vin- botanical’s compliant use. (Also see “FDA riage or harm fetal development,” accord- pocetine during gestation in rats and Guidance Makes Vinpocetine Compliant ing to the statement. rabbits resulted in evidence of develop- Despite Ban Proposal – NPA” - HBW Insight, The FDA in 2016 requested comment mental toxicity as exhibited by embryo- 1 Dec, 2016.) for an administrative proceeding to evalu- fetal death. Additional findings included Vinpocetine also has been used in ate whether vinpocetine is legal for sale as reductions in fetal weight in both groups products marketed by firms the Federal a dietary supplement after receiving mul- and malformations and variations of the Trade Commission has targeted in com- tiple new dietary ingredient notifications heart and skeleton of the rat. plaints alleging false advertising. (Also for the ingredient in 1990s. “These findings are particularly con- see “XXL Impressions Supplement Mem- Following the NTP report, “it was impor- cerning since products containing vin- ory Claims Impress FTC As False” - HBW tant to issue today’s warning because the pocetine are widely available for use by Insight, 23 Feb, 2017.) availability of dietary supplement prod- women of childbearing age,” said FDA’s The FDA’s vinpocetine announcement ucts containing vinpocetine has grown Abernathy and Yiannas. also noted that as steps in an intiative and the labels of vinpocetine products of- launched by former Commissioner Scott ten have no warnings about the dangers PROPOSAL PROMPTS Gottlieb to modernize the agency’s over- of miscarriage and harm to fetal develop- INDUSTRY QUESTIONS sight of VMS product manufacturing and ment. For the same reasons, the FDA will In addition to questioning vinpocetine’s marketing, it created the Botanical Safety expedite completion of the administrative safety as a dietary ingredient in the 2016 Consortium public-private partnership to proceeding that we began in September administrative proceeding, the FDA has promote scientific advances in evaluating 2016,” stated Principal Deputy Commis- included the substance in a list identi- the safety of botanical ingredients and sioner Amy Abernethy and Deputy Com- fying ingredients it has concluded are mixtures; introduced the Dietary Supple- missioner for Food Policy and Response not eligible for use in vitamin, mineral ment Ingredient Advisory List to more Frank Yiannas. or supplement products and on which quickly alert consumers about ingredients The report, made available by NIH as a it already has conducted regulatory ac- that appear to be unlawfully marketed peer review draft, states NTP conducted tions, including warning letters. The list in supplements; and conducted a public its study on rats “based on the possibil- currently comprises DMHA, phenibut, meeting to discuss responsible innova- ity of widespread exposure to pregnant acacia rigidula, BMPEA, DMBA, methyl- tion in the industry. (Also see “’Innovation’ women and [women of childbearing po- synephrine, picamilon and tianeptine Meeting Shows FDA-Industry Gap On NDI tential] and limited literature indicating as well as vinpocetine. (Also see “FDA Guidance Details Remains “ - HBW Insight, that vinpocetine may not be safe for use Debuts List For Rapidly Announcing Non- 20 May, 2019.) during pregnancy.” A study with rabbits compliant Ingredients In Supplements” - was included to see if effects occurred in a HBW Insight, 17 Apr, 2019.) Published online 4 June 2019

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Stada Health Report 2019: A Quarter Of Europeans Take Supplements, France and Germany Sceptical About Health Gadgets DAVID RIDLEY [email protected]

ver a quarter of Europeans take a daily vitamin or nutri- Figure 1: Percentage of Europeans Preferring Home- tional supplement, according to Stada Arzneimittel AG’s Made Remedies Over OTCs O2019 Group Health Report, The Future of Your Health. “Vitamins and nutritional supplements are becoming increasing- ly popular as part of a healthy lifestyle,” Stada explained. “For 28% of Europeans, a daily dose of vitamin pills is part of their routine.” “Poland is Europe’s forerunner in terms of supplement consumption,” the firm added. “Four out of ten [Poles] take them regularly.” Stada’s online study – conducted by market researcher Kantar Health and involving roughly 18,000 people in nine European countries: Belgium, France, Germany, Italy, Poland, Russia, Serbia, Spain and the UK – also looked at the use of e-health technologies, such as smartphone apps and wearables. “On average, four out of ten people are open to health apps and gadgets such as fitness trackers,” Stada found. “Such technical as- sistants are particularly popular in Spain, Italy and Russia.” However, such technologies were not popular with all Europe- ans. The French, Germans, Belgians and Serbians only used them occasionally, Stada said, because “they think they are a waste of time and money.” proportion of people relying on such remedies was 27%, the firm Furthermore, roughly a quarter of French and Germans noted. In Germany, however, the proportion was much higher, were “scared of the possible misuse of their personal data,” with roughly one in two turning to traditional cures (see Figure 1). the firm added. While two out of three Europeans surveyed relied primarily on “In general, the younger the respondents, the more popular classical medicine – three out of every four in the Spain and the those digital features are,” Stada commented. “The Russians are UK, and men more so than women – Stada said that 14% turned setting an example: If you wear a pedometer on your wrist, you instead to alternative medicines such as homeopathy and acu- are also ready for the next step.” puncture, as well as probiotics. “Conversely, this also means that one in seven Europeans DIY OVER OTC? have lost faith in classical medicine largely or completely,” According to Stada’s report, many Europeans, especially those Stada pointed out “The distrust is particularly distinct in Ser- over the age of 50 years old, still rely on “grandmother’s home bia, with 23% of respondents [saying they would rather use remedies” – such as herbal tea, chicken broth or a hot-water alternative medicine].” bottle – rather than OTC medicines at the first signs of a mi- nor illness. Across all of the nine countries surveyed, the average Published online 30 May 2019 House Appropriators’ Report Tracks With FDA Concern About CBD Supplements

EILEEN FRANCIS [email protected]

he US House of Representatives Appropriations Commit- The FY 2020 “Agriculture, Rural Development, Food and Drug tee’s report with its fiscal year 2020 spending bill for the Administration and Related Agencies” appropriation bill, passed TUS Food and Drug Administration states concern over the along party lines in 29-21 vote on June 4, would provide the FDA proliferation of foods and dietary supplements containing canna- with $3.25bn in discretionary funding – $185m above the 2019 bidiols in violation of federal regulations. enacted level.

Businesses marketing hemp and CBD ingredients in violation dietary supplements if such pathways are consistent with protec- of the Food, Drug & Cosmetic Act, which the FDA currently allows, tion of the public health. Such pathways may include necessary “pose potential health and safety risks to consumers through public health and safety parameters that will protect the public unsubstantiated and misleading claims such as treating a wide- health, such as labeling requirements and limits on CBD or other range of life-threatening diseases and conditions; excessive [CBD] cannabis-derived ingredients in products, based upon anticipat- concentrations that can result in harmful drug-drug interactions, ed total exposure levels.” somnolence, and elevated transaminases or liver toxicity; and The committee also notes a priority the agency has stated in its the presence of significant levels of intoxicating compound such consideration of allowing wider uses of hemp and CBD. “It is also as tetrahydrocannabinols,” the committee states in its report re- imperative that any FDA regulation of foods and dietary supple- leased 3 June. ments containing CBD or other cannabis-derived ingredients pre- The committee’s report explains the committee’s thinking serve incentives to invest in robust clinical study of cannabis, so its behind its funding levels for the FDA and other agencies in FY therapeutic value can be more fully understood.” 2020, which begins 1 Oct. The bill itself does not contain lan- FDA officials have emphasized that deciding on allowing hemp guage related to hemp or CBD. A draft of the markup bill was and CBD’s use in other types of FDA-regulated products will be made public May 23, prior to the FDA’s May 31 public hearing done with potential impact of drug development foremost in the for input on the use of cannabis-derived ingredients in prod- agency’s thinking. (Also see “FDA Road To Decision On Expanding ucts subject to its oversight. CBD Uses Starts With Weighing Impact On Existing And Future Use Regarding CBD, the appropriators’ report notes the bill provides As Drug “ - HBW Insight, 2 Jun, 2019.) $16.5m for the US Department of Agriculture’s Hemp Production Program, as authorized by the 2018 farm bill. HOUSE, SENATE IMPASSE AHEAD The committee urges the USDA to use existing resources to is- The FDA would receive $5.85bn in the bill, a 4.7% increase com- sue regulations authorized by the farm bill “as soon as possible,” pared to the FY 2019 funding bill, but significantly less than Presi- as the funding for the hemp program is allocated for use in 2020. dent Trump allocated in his budget request. The farm bill directed the USDA to develop regulations to imple- The bill includes just more than $1.1bn for the Center for Food ment the act’s provisions and promote uniformity in state over- Safety and Applied Nutrition and related field activities in the Of- sight programs, which must be approved by the federal agency. fice of Regulatory Affairs, up nearly $60m from the current budget. The agency aims to publish those regulations later in 2019 to ac- The Center for Drug Evaluation and Research would receive the commodate the 2020 planting season. largest increase within the agency, $98.7m, to $1.98bn. The committee notes in its report the 2018 farm bill expressly The funding is another win for the FDA, but it was not based preserves the FDA’s authority for appropriate actions regarding on budget numbers agreed to by the Senate and White House, a cannabis, including hemp and its derivatives, and recognizes the complaint Republicans made during the mark-up. Until an agree- agency is considering a public regulatory process to evaluate the ment is reached, enactment likely remains in doubt. appropriateness and possible parameters of a regulatory pathway The Senate has not yet released its FY 2020 FDA appropria- that would permit CBD in certain food and dietary supplements. tions bill. “The committee expects the FDA to assert its commitment to identifying lawful federal regulatory pathways for CBD foods and Published online 5 June 2019

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