HEALTH HBW · Asia markets for Horlicks and other nutri-tional beverage brands to Unilever PLC. (Also see “Horlicks Brings Unilever ‘Trans-formative’ Nutritional Deal, Market

Pharma intelligenceinforma

HBW24 December 2018 • No. 02hbw.pharmaintelligence.informa.com

I N S I G H T

HEALTHBEAUTYWELLNESS

F R O M T H E E D I T O R S O F : Rose SheetPharma intelligence

Pink SheetPharma intelligence

WELLNESS

Stada Looks To Take Slice Of Growing Probiotics Market With Launch Of Probielle In Germany, p. 9

HEALTH

Bayer’s Consumer Chief Initiates Turnaround Plan In Bid To Return Troubled Business To Growth, p. 5

BEAUTY

J&J Doing Damage Control Following Reuters Report On Asbestos ‘Lurking’ In Johnson’s Powder, p. 11

GSK And Pfizer Start Consumer JV For Different Reasons, Aim For Similar GoalsMALCOLM SPICER [email protected]

T he consumer health product joint venture Pfizer Inc. has agreed to form with GlaxoSmithKline PLC

could drive each firm toward its goal in the sector, even with GSK holding the upper hand as majority owner with initial control of potentially spinning off the JV.

The agreement announced Dec. 19 by the big pharmas could put consumer health where Pfizer wants it, entirely in the firm’s rear-view mirror, and point both firms toward what they wants, more research and development funding freed up for the pharmaceutical ingredient op-erations that are their chief revenue driv-ers. Glaxo is moving consumer health out

of its division that also includes its vac-cines business.

The all-equity deal, giving GSK 68% control, also could boost investors’ inter-est as both firms have been dogged by pressure to sell, spin-off or otherwise di-vest their consumer businesses, which they say had combined pro-forma global sales of £9.8bn ($12.7bn) in 2017. Pfizer attempted earlier in 2018 to exit the space entirely, but the New York-based firm didn’t receive a satisfactory offer, from suitors including London-based GSK, for all its consumer business.

GSK CEO Emma Walmsley: “We paid Pfizer a premium ... for control of the

operating management but also con-trol of the separation.”

For GSK, the deal marks a return to be-ing majority owner of a consumer health JV with another big pharma after buying earlier in 2018 out Novartis AG’s stake in the venture the firms launched in 2015. Glaxo gained Novartis’ consumer health brands under a provision in the transac-tion that gave it first rights to buy the as-sets, a prerogative it also gains in its agree-ment with Pfizer.

According to the firms, GSK intends to separate the JV, which will be called GSK Consumer Healthcare, though a de-merg-er of its equity interest to shareholders and a listing of the business on the UK market within three years of the transaction’s clos-ing, expected in the second half of 2019.

After five years, both GSK and Pfizer will have the right to decide whether and when to separate and list the JV. Should Pfizer initiate a separation, Glaxo would have “the right to acquire all (but not part)” of its equity interest at fair market value. The firms would have the same rights at the 15th anniversary of the proposed deal’s closing.

GSK and Pfizer each has a large con-sumer health footprint with extensive OTC drug portfolios and also some vitamin, mineral and supplement lines. Glaxo’s consumer lineup, which had revenues of around $9.2bn in 2017, includes Flonase Allergy Relief (fluticasone) intranasal corti-costeroid, Fenbid (ibuprofen) and Panadol (acetaminophen) analgesics, Excedrin Mi-graine (aspirin/paracetamol/caffeine) and Voltaren (diclofenac) topical non-steroidal anti-inflammatory; Pfizer’s portfolio, with sales of around $3.5bn in 2017, includes Advil (ibuprofen) analgesics, Robitussin (dextromethorphan) cough medicine,

CONTINUED ON PAGE 4

hbw.pharmaintelligence.informa.com

mailto:[email protected]

2 | HBW Insight | 24 December 2018 © Informa UK Ltd 2018

I N T H I S I S S U E

from the [email protected], [email protected] & [email protected]

Global Regulatory and Compliance Insight for Fast Regulatory ApprovalSuccessfully navigate the complex world of Pharmaceutical Regulatory and Compliance with access to worldwide intelligence for approved and pipeline drugs.

Tracking product progress from submission to approval, our exclusive network of worldwide analysts and journalists cover critical areas of regulatory insight and analyse the implications of worldwide developments on your business.

Anticipate challenges, minimize risks and maximize opportunities.

Pink SheetPharma intelligence |

To fi nd out more, visit: www. pharmaintelligence.informa.com/pink-sheet

JN1130 OTC Pink Sheet Advert 297x210.indd 1 2018/05/24 19:02




hbw.pharmaintelligence.informa.com 24 December 2018 | HBW Insight | 3

inside:

@HBWInsightHBW-Insight

COVER / GSK And Pfizer Start Consumer JV For Different Reasons, Aim For Similar Goals

5 Bayer’s Consumer Chief Initiates Turnaround Plan In Bid To Return Troubled Business To Growth

7 Warnings Up As FDA Trims Its List Of Uninspected OTC Drug Manufacturers

8 Recruitment Begins For UK Health Claims Committee In Preparation For Brexit

9 Stada Looks To Take Slice Of Growing Probiotics Market With Launch Of Probielle In Germany

10 During Recalls, Prepare For ‘Blood In The Water’ Response From Plaintiffs’ Bar

11 J&J Doing Damage Control Following Reuters Report On Asbestos ‘Lurking’ In Johnson’s Powder

12 Canadian Authorities Say Some Cosmetic Talc Applications May Endanger Human Health

13 CIR Expert Panel Seeks Proper Balance In Respiratory Exposure Doc, Says Particle Size Isn’t All-Important

14 FDA Researchers Analyze OTC Spray, Powder Products, Finding Possible Respiratory Risks

Swiss Regulatory Change Takes Over 500 OTCs Out Of Pharmacyhttps://bit.ly/2EzGLZZ

Swiss medicines authority, Swissmedic, rules that hundreds of non-prescription medicines are safe to be purchased outside pharmacy, following the completion of its review of the country’s medicines classification system.

NeuroMetrix Rceives GSK ‘Bridge’ For Quell Wearable Pain-Relief Developmenthttps://bit.ly/2LsXpvT

Recent modifications accelerated portion of milestones remaining in firms’ agreement over the next 12 months, reduced GSK’s aggregate amount payable and forwarded $2m to NeuroMetrix. Firms are co-funding future development of Quell technology and additional TENS products for chronic pain beginning in 2019.

Reckitt Benckiser Exploring AI With Help Of Israeli Start-Upshttps://bit.ly/2UZZbJh

RB is looking to work with Israeli start-ups that can utilize emerging digital technologies to provide ‘real world’ consumer healthcare solutions.

An Expert’s Guide To Switching In Germany, Part 2: Improving The Reclassification https://bit.ly/2QJTTDk

In Part 2 of this exclusive interview, Elmar Kroth, scientific director of the German Medicines Manufacturers´ Association, the BAH, tells HBW Insight what the association is doing to improve the prescription-to-OTC switch process in Germany.

Surviving The Dark German Winter: Four New Dietary Supplements Containing Vitamin D https://bit.ly/2EAk0W4

To help Germans struggling through the dark winter months, Hevert, Cefak, Stada and Doppelherz have all released vitamin D supplements onto the German market.

Suave ‘Beautiful As’ Bath & Body Works Claim Deemed Puffery In NAD Reviewhttps://bit.ly/2EAtT60

Council of Better Business Bureaus Division review Unilever claims for Suave Essentials on challenge by L Brands, which argued “as beautiful as” is linked to a specific product attribute – fragrance – and expressly compares Unilever’s products to Bath & Body Works products. L Brands contended “as beautiful as” is equivalent to claim “as appealing as,” which NAD concluded was unsubstantiated in 2016.

exclusive online content

The next issue will be on January 14, 2019. For online access please contact [email protected]

SEASON’S GREETINGSSEASON’S GREETINGSWishing our readers a joyful

holiday season and all the best for 2019.


https://bit.ly/2EzGLZZ

https://bit.ly/2LsXpvT

https://bit.ly/2UZZbJh

https://bit.ly/2QJTTDk

https://bit.ly/2EAk0W4

https://bit.ly/2EAtT60


H E A LT H ( O T C D R U G S )

Nexium 24HR (esomeprazole) frequent heartburn remedy, Anbesol (benzocaine) topical pain relief, Centrum multivitamins and Emergen-C vitamins and supplements.

However, the firms say they see little overlap in their product lines and expect to make limited brand divestments to sat-isfy potential regulatory concerns about their JV controlling anti-competitive por-tions of certain marketplace categories.

The two big pharmas say the JV will be the consumer health global leader with 7.3% market share, well ahead of the next competitor, which would be Johnson & Johnson, at 4.1%. They say that between them, they have the top or second-ranked market share “in all key geographies, in-cluding the US and China.”

GSK CEO Emma Walmsley will be chair-woman of the JV, which will be based in London, and Pfizer will appoint three mem-bers to a nine-member board. Glaxo’s con-sumer business executives, CEO Brian Mc-Namara and Chief Financial Officer Tobias Hestler will continue in those posts in the JV.

DIFFERENT REASONS, BUT PATH FAMILIAR TO PFIZER ...Pfizer has been open to selling its consum-er health business since it re-entered the space in 2009 through its acquisition of Wyeth, a deal that brought OTC drug and VMS brands as well as the main attraction, Wyeth’s Rx assets.

Pfizer has invested to move formerly Rx drugs to OTC distribution, including Nex-ium 24HR on license from innovator As-traZeneca PLC, and to study the nonpre-scription chances for the largest-selling Rx drug in pharma history, high cholesterol remedy Lipitor (artovastatin). However, after a trial to simulate OTC use of Lipitor 10 mg did not meet its primary objectives of showing patient compliance with the direction to check their low-density lipo-protein cholesterol level and, after check-ing, to take appropriate action based on test results, Pfizer ended that program in early 2015 and its consumer business out-look has been dim since. (Also see “Light Still On For Switches After Pfizer Pulls Plug On OTC Lipitor” - HBW Insight, 3 Aug, 2015.)

In October 2017, Pfizer announced it would consider selling its consumer busi-ness. After receiving no satisfactory offers and saying it was interested only in selling

the entire business, Pfizer in July said it made its consumer business a separate di-vision within the firm and would continue considering divesting or spinning off the unit. (Also see “With Its Own Home, Pfizer Consumer Health Gets Higher Profile For Sale” - HBW Insight, 11 Jul, 2018.)

Longtime Pfizer CEO Ian Read has main-tained a diplomatic tact about the firm’s interest in consumer health, describing it as a reliable segment but different from the Rx world. With the Glaxo JV announce-ment, Chief Operating Officer Albert Bour-la offered the same sentiment as Read, who Bourla has been tabbed to succeed. (Also see “Pfizer elevates Bourla as Read steps down” - HBW Insight, 19 Oct, 2018.)

“The combination of these leading busi-nesses with distinct regional and category strengths will be more sustainable and broader in scope than either company individually. We believe that this joint ven-ture is a great opportunity to ensure the future success of Pfizer Consumer Health-care while unlocking meaningful after-tax value for Pfizer shareholders,” said Bourla in Pfizer’s announcement.

... AND TO GLAXOGSK, on the other hand, steadfastly has focused on making its consumer business more of a revenue driver, not only by add-ing Novartis’ brands but also by pruning what it considered non-core lines. Most recently, it sold North American rights for five dermatology lines to Crown Labora-tories Inc. (Also see “Crown Labs Spreads Out, GSK Narrows Focus In OTC Skin Care Brand Deal “ - HBW Insight, 9 Dec, 2018.) and the rights in India and other South Asia markets for Horlicks and other nutri-tional beverage brands to Unilever PLC. (Also see “Horlicks Brings Unilever ‘Trans-formative’ Nutritional Deal, Market Chal-lenges” - HBW Insight, 3 Dec, 2018.)

Heading a consumer JV with an option to later acquire its partner’s brands is a logical next step in GSK’s plans. Building a consumer business fit for spinning off also allows it to tighten its focus on supporting its Rx pipeline.

GSK consumer CEO Brian McNamara: “One thing that builds our confidence is our successful integration of the Novartis transaction.”

“I’ve stated very clearly that strength-ening GSK’s Pharma business and pipe-

line is our clear priority. And in evalu-ating this transaction, it was essential that it would support and strengthen this effort, which it does,” said Walmsley during a same-day briefing with media and analysts.

GSK’s experience from the Novartis con-sumer JV, which ended in March with the UK firm paying £9.2bn ($13bn) for the Swiss pharma’s 36.5% stake, also was a fac-tor in choosing the same path with Pfizer. (Also see “Glaxo Opts For Solo Navigation To Boost Control In Consumer Health Mar-ket” - HBW Insight, 27 Mar, 2018.)

“The key is to integrate with excellence while continuing to deliver on our perfor-mance objectives. One thing that builds our confidence is our successful integra-tion of the Novartis transaction,” said Mc-Namara during the briefing.

Outlining the different strengths GSK and Pfizer each bring to the JV, he said Glaxo has “capability in external inno-vation that can be leveraged,” with around 30% of its consumer health pipeline com-ing from external partnerships, and Pfizer has “expertise in VMS, both on innovation and marketing, that has not been a focus for GSK.”

Digital sales also are an area where the firms strengths differ, McNamara said. While Glaxo has an agreement for a plat-form on online search engine Google “to drive efficiencies and effectiveness in our digital marketing, Pfizer has “a very strong e-commerce business in China, one of the fastest-growing e-commerce markets in the world.”

An additional strength for the JV: each firm markets one of the strongest OTC switches launched in the US in the past few years, Pfizer with Nexium 24HR and GSK with Flonase Allergy Spray. Pfizer also markets erectile dysfunction drug Viagra (sildenafil) OTC in the UK. (Also see “Pfizer ED claim is sound, ASA rules” - HBW Insight, 23 Nov, 2018.)

GSK says it plans to reinvest up to 25% of its cost savings generated by the JV back into the business to support inno-vation, brand development and other growth opportunities, though it doesn’t expect much contribution from synergies between the two businesses in 2019. It expects to realize around 40% of the to-tal in 2020, rising to around 80% in 2021 as it reaches the later stages of the syn-

CONTINUED FROM PAGE 1



ergy program, including rationalization of manufacturing sites, and to achieve the full amount in 2022. Costs of the transac-tion will come sooner, with around GBP 0.2bn cash costs in 2019 and $0.5 billion in 2020.

While Glaxo has majority ownership, Pfizer’s stake exceeds the amount of its consumer health revenues, a premium GSK is willing to pay. “We paid Pfizer a premium, but that premium is for control. It’s the control of the operating manage-ment but also control of the separation,” Walmsely said.

Additionally, each firm’s business will move to the JV cash- and debt-free other than “a small cash balance for work-ing capital,” and the venture “will stay debt-free until the point of separation,” explained GSK Chief Financial Officer Si-mon Dingemans.

JV FIRST STEP TOWARD PAYOFFAnalysts posting same-day research notes heralded the pact as a strong move for both firms while forecasting the JV’s likely eventual launch as a standalone business as the biggest payoff.

Morningstar’s Damien Conover says “the potential separation of the new joint venture could unlock value for both Pfizer and Glaxo, as consumer health care com-panies trade at higher valuation multiples than big pharma firms.”

Additionally, the JV partners’ “robust brand power” brings “strong competitive advantages,” Conover wrote. Still, neither will miss the revenues from those brands because “consumer products contributed a smaller amount of profits to the overall companies,” he said.

At Credit Suisse, analyst Vamil Divan says while GSK is in the driver’s seat for the JV, Pfizer also is moving in the right direc-tion. Moving its consumer business to the JV will allow “the leadership of [Pfizer’s new ingredient business]] to better drive that business forward, while allowing the rest of Pfizer to become more concen-trated and focus on prescription human health care products,” Divan wrote.

Divan cautioned, however, that Pfizer’s temporary exit from the consumer busi-ness, when it sold its portfolio to J&J in 2006, didn’t work out well for the firm. The move was “more carefully scrutinized”

when a priority Rx pipeline ingredient for the firm “was discontinued for safety rea-sons just a few months later.”

GSK also could expose its Rx business to the threat of a setback without its con-sumer business should the divestment come, says Deutsche Bank analysts Rich-ard Parkes. Forming the JV likely will “be taken positively by investors given that both companies will benefit from syner-gies and the deal should be accretive to earnings for GSK,” Parkes wrote.

However, the proposed spin-off of the consumer business “is likely to be more divisive,” he added. While a spin-off could unlock value within the con-sumer business , it will leave GSK “more dependent on success in reinvigorating its pharma pipeline.”

The JV announcement sparked trading on the NYSE at a much higher volume than average for both firms’ shares, but not a sharp price rise for either. GSK shares traded in the US were up slightly, 0.84%, to $37.40, while Pfizer’s were down 1.01% to $41.97.

Published online 19 December 2018

Bayer’s Consumer Chief Initiates Turnaround Plan In Bid To Return Troubled Business To GrowthTOM GALLEN [email protected]

“We know where the issues are and we have plans to fix them,” insists Bay-

er AG’s Consumer Health head Heiko Schipper, who has been charged with implementing a wide-ranging turn-around program to return the troubled business to growth.

Speaking at the German firm’s recent capital markets day, Schipper – who took the helm at Consumer Health in March – admitted that the performance of the business in recent years had been “disap-pointing”.

Consumer Health’s sales growth had “really slowed down” from a high of 6.1% in 2015, Schipper admitted, with turnover last year declining by 1.7%.

With sales falling, and costs increasing, margins had “eroded significantly” over

the past two years, he pointed out, from a high 24% in 2015 to 21% in 2017.

“With my management team, we’ve spent a lot of time to understand what the root causes are behind this performance,” Schipper revealed, “and, more important-ly, what we are going to do to fix them.”

Bayer is targeting annual sales growth of around 3%-4% by 2022 driven by port-folio changes, a new sales and marketing approach and a focus on innovation. At the same time, the firm will look to lift the earnings before interest, tax, depreciation and amortization (EBITDA) margin to 24%, by creating a leaner organization and op-timizing costs of goods sold. These chang-es, along with group-wide adjustments to the corporate platform, are expected to generate savings at Consumer Health of around €500m ($567m) by 2022.

KEY PROBLEMS IDENTIFIEDTo effectively turnaround Consumer Health and enable it to reach its “full po-tential”, Schipper said he had to address four “key issues”:● A low level of innovation● An outdated sales and marketing ap-

proach● Regulatory difficulties in China● Temporary supply interruptions

“The level of innovation that came to market in the last couple of years has been disappointing,” Schipper admitted, pointing out that new product develop-ment was a “key driver of growth” in the consumer healthcare industry.

On Bayer’s sales and marketing ap-proach, Schipper claimed that the firm had “missed opportunities” by not effec-tively utilising “new digital technologies”





leading it to fall behind some of its peers. Turning to the issues in China, Schipper

said Bayer had suffered a “very significant” setback when the country’s medicines reg-ulator had unexpectedly reverse-switched to prescription-only status its Kang Wang and Pi Kang Wang products. (Also see “Chinese switch hurts Bayer” - HBW Insight, 23 Mar, 2018.) More recently, a change to regulations related to manufacturing had forced Bayer to temporarily stop supplying Claritin in China, he revealed.

Finally, recent supply interruptions, particularly at its plant in Leverkusen, Germany, had “significantly impacted” Bayer’s ability to meet demand, Schipper said. (Also see “Bayer’s “challenging year” persisting” - HBW Insight, 21 Sep, 2018.) “To give you a feeling of magnitude, some of the supply-related issues kind of took out about 150 to 200 basis points out of the top line in the past two years.”

To address these key issues and other problems facing the business, Bayer had put together a “very comprehensive turn-around plan”, Schipper said, comprising three key building blocks”:

Firstly, Bayer had taken a step back to decide what categories and brands in the Consumer Health portfolio it wanted to focus on, Schipper explained. “We took time over the past month to reflect on what is the right portfolio for us to put our R&D, our marketing and our capex invest-ments behind for the future. We looked at each category evaluating them for their growth potential and their margin poten-tial, but of course also our ability to win in these categories.”

Through this process, Bayer had identi-fied five “core OTC categories” to build its Consumer Health business around: Aller-gy, Cough & Cold; Nutritionals; Dermatol-ogy; Pain & Cardio; and Digestive Health.

“These are the five categories that we are going to accelerate,” Schipper said. “We have good positions here with many key brands,” he insisted, pointing to Clari-tin in Allergy; Elevit in Nutritonals; Bepan-then in Dermatology; Aleve in Pain; and MiraLAX in Digestive.

CONSUMER DIVESTMENTS PLANNEDConsequently, Bayer had decided to di-vest those categories of brands it judged to be ‘non-core’, he explained, namely Sun

Care; Foot Care; and Rx Dermatology.In July, Bayer entered into a deal to sell

its Rx Dermatology operation – which generated sales of €280m in 2017 – to Leo Pharma. (Also see “Deal Watch: LEO Phar-ma Expands Market Reach Through Bayer Dermatology Deal” - Scrip, 31 Jul, 2018.)

The company also recently announced plans to explore options for its Copper-tone sun-care line and Dr Scholl’s foot-care range. (Also see “Coppertone, Dr. Scholl’s On The Block As Bayer Narrows Consumer Health Focus” - HBW Insight, 29 Nov, 2018.)

“We feel that these businesses are in better hands with another owner,” Schip-per said, “so that we can focus on some of the other categories where we are better placed; where we can bring science to the category and combine it with our market-ing capabilities.”

With a “winning portfolio” identified, Schipper said Bayer wanted to use inno-vation to “accelerate growth”.

Firstly, the firm intended to strengthen its “core innovation”, he said, by “constantly re-newing” its brands to “keep them relevant”.

Second, Bayer was looking to acceler-ate “adjacent innovation” – moving brands into adjacent spaces, Schipper said, giv-ing the example of the recently launched Stillzeit line extension to its Elevit range in Germany, which had taken the brand into the breastfeeding space, as part of its goal to “own a mother’s journey”.

Driving new prescription-to-OTC switch opportunities is the final piece of Bayer’s innovation plan. “I still believe [switching] is very key in our category,” Schipper said, “and this is a space where Bayer must be strong. We’ve had tremendous success there in the past”.

Overall, Bayer wanted to double the contribution from innovation to Con-sumer Health’s total growth by 2022, he explained, up from 15% currently to around 30%.

Noting that the firm would keep its in-vestments in R&D “pretty much stable” as a percentage of sales, Schipper said Bayer would trim investments in “structures and people” and look to “tap into more exter-nal innovation opportunities”.

SHAKE UP BRAND BUILDINGSupporting its innovation efforts, Bayer in-tends to modernize its brand building and sales capabilities.

“Building brands today looks very dif-ferent from building brands 10 years ago,” Schipper noted. “The millennial consumer is much more interested to un-derstand what is behind the brand, what is the purpose, what you are contributing to this planet.”

Brand building had become “a much wider exercise than just finding one point of difference and marketing this”, he claimed.

“So, we are going to refresh our brands and bring purpose much higher up the agenda,” Schipper said. “If you look at the efficacy of our brands and what we bring, this can be expressed in a much more comprehensive way than we do today.”

Furthermore, Bayer needed to change its marketing approach to become much more focused on the individual, he in-sisted. “Thanks to all the data that we have available on our target consumers, we can target much more precisely every individual we market to. If we think of the target groups that are fairly narrow in our category – because not everyone has al-lergies for example – to fully make use of that is a tremendous upside for us.”

With a reinvigorated sales and market-ing approach and a more focused port-folio selected, Bayer had put together a “clear roadmap for success” for each of its geographical regions, Schipper noted.

NORTH AMERICA IS ‘KEY’North America was “the key area to fix”, he admitted. It is Consumer Health’s big-gest market – with sales of €2.5bn in 2017 – but its worst performer, recording a compound annual growth rate over the past two years of -2%. (Also see “Bayer ‘All Hands On Deck’ For US Consumer Business Turnaround” - Pink Sheet, 8 Aug, 2017.)

Offloading Coppertone and Dr Scholl’s – “primarily” North American brands – would allow Bayer to have a “much greater focus” on its key brands in the region, such as Claritin, One-A-Day and Aleve. “These are very, very strong brands, but maybe we’ve not given them the right attention in the past,” Schipper noted, “as too many resources were allocated to other brands.”

Bayer intended to “rebuild” its innova-tion pipeline in North America behind these core brands, as its track record in this regard had “not been where it should be in the last couple of years”, he admit-



ted. The firm also hoped to expand its Consumer Health offering in the market with a “clear set of priorities” for pursuing prescription-to-OTC switches.

While the company had been “pretty good” at developing its e-commerce of-fering in North America, it still had a lot to do in terms of direct marketing and preci-sion marketing, Schipper observed. Bayer wanted to “catch up” to those firms that were best-in-class in those areas.

Many changes were already underway in North America, Schipper revealed, with Bayer “right-sizing” the business by around 20% in the fourth quarter alone, resulting in a “leaner organization”.

REVERSE-SWITCH HIT APACAway from North America, the other re-gion which needed special attention, Schipper said, was Asia-Pacific, where sales fell by 2.0% to €738 million in 2017.

“We had very good momentum there but the unfortunate reverse-switch that we had last year in China significantly slowed us down. But we’re going to recover from that,” he insisted, “it’s a matter of time.”

Asia-Pacific was the market where Bayer had the “lowest share”, Schipper pointed

out, “and this is the area where we have to build really the highest growth levels”.

Bayer was “well-placed” to achieve this goal, Schipper said, with those brands not impacted by the reverse-switch growing at “double digits”.

“Nutritionals is a huge category in China and we have a very, very attractive posi-tion there in some of the parts of that market,” he noted. “More specifically, our nutritional brand Elevit is the leader in the pregnant and lactating women space.”

Consumer Health’s other regions – Eu-rope/Middle East/Africa and Latin Amer-ica – had been performing well in recent years, Schipper pointed out. “EMEA is a stronghold for us, we are in the top-three in every single market”, he noted, while Latin America was a region where Bayer was “extremely well placed”. Bayer was confident that it could maintain this strong momentum in both regions, he said.

GROWTH FOUNDATIONS IN PLACESumming up Bayer’s Consumer Health turnaround plan, Schipper explained that 2018 had been about “setting the founda-tion” for future growth, by putting in place

a new leadership team, making “portfolio choices” and initiating “stricter” cost control.

In 2019 and 2020, Bayer would “execute” its portfolio choices, work to right-size the cost base and recover product supply, as well as regain momentum in its Asia-Pacif-ic and EMEA regions.

With these changes in place, 2021-2022 would be Consumer Health’s “acceleration phase”, Schipper said, with Bayer driving a “higher innovation level”, accelerating its US growth momentum and “capitalizing” on its portfolio choices.

Commenting on the Consumer Health turnaround plan, Werner Baumann, Bay-er’s chief executive officer, said the firm was “very well positioned to deliver sig-nificant value creation over the next years to come”.

“The fundamentals and the quality of our business are really, really strong,” Baumann insisted. “We have a highly con-centrated portfolio of big, mega-selling brands, we are in the right markets, and we are doing the right things in terms of bringing value to customers, consumers and patients.”


Warnings Up As FDA Trims Its List Of Uninspected OTC Drug ManufacturersMALCOLM SPICER [email protected]

T here’s a reason for a drastic increase in FDA warning let-ters to OTC drug manufacturers, and it’s not that the number of firms providing nonprescription remedies in

the US has jumped.Hundreds of foreign firms that make OTC drugs marketed in

the US had not been inspected for good manufacturing practices compliance before the FDA Safety and Innovation Act of 2012 pointed the agency’s Center for Drug Evaluation and Research to-ward crossing those facilities off its list.

Of the foreign OTC facilities inspected between June 2016 and Jan. 9, 2018, 75% were found satisfactorily compliant with FDA’s drug GMPs, “so most of the drugs that are coming from overseas are actually pretty good,” said Francis Goodwin, acting director of CDER’s Office of Manufacturing Quality.

However, 25% of the facilities received “official action indicated” inspection results. “That was an issue and what that’s doing, the higher OAI rate, is driving a higher rate of compliance actions, more warning letters land also more import alerts,” Godwin said on Dec. 12 at a Food & Drug Law Institute conference in Washington.

“There’s been a lot more warning letters to OTC manufacturers over the last few years. Four or five years ago, 20 warning letters in a year would be a bellwether. This year we’re on pace to be some-where between 90 and 100 warning letters, which is as striking difference,” he said.

According to CDER OMQ, 71% of FDA’s OAI warning letters fol-lowing drug GMP inspections in the June 2016-January 2018 pe-riod went to OTC drug firms, 21% to active pharmaceutical ingre-dient facilities and 8% to other firms.

Because FDASIA shifted FDA’s GMP “inspection paradigm” to risk-based, OTC drug manufacturers that had not been inspected, even though their products are not as potentially risky as Rx ingredients, became a higher priority. (Also see “FDASIA Study Mandates Focus On Performance, But Could Slow Reviews” - Pink Sheet, 20 Aug, 2012.)

Working with the General Accounting Office for a report pub-lished in January 2017, FDA determined that roughly 1,000 for-eign facilities making OTC drugs available in the US had not been inspected. (Also see “US FDA Crossing Off More Foreign OTC Firms On Globalization Checklist” - HBW Insight, 11 Jun, 2018.)





UNTOUCHED BY FDAThose firms’ products were available because, unlike Rx drugs, the large majority of OTC drugs are monograph products and are not required to have pre-market approval from FDA.

“By definition, all of those [Rx product] firms have been touched by FDA. An FDA inspector has gone through their facility and looked to see if they knew what they were doing,” Godwin said.

Foreign and domestic firms making OTC monograph drugs, on the other hand, can make and start distributing their products be-fore FDA has a chance to inspect their operations. “Yet, they are in the US supply chain providing drugs,” he added.

Until FDASIA directed FDA to bring foreign firms into its inspec-tion schedule, most ex-US OTC monograph drug makers weren’t being inspected.

“That’s why when we’re inspecting the uninspected, a higher portion of them are OTCs. That’s why we’re seeing a whole lot more warning letters,” Godwin said.

CDER OMQ’s goal following the GAO report was to inspect all the uninspected OTC drug manufacturing facilities by the end of fiscal year 2019. “We are currently wrapping up this herculean task. You can imagine the logistics of 1,000 foreign drug inspec-tions, plus the normal work FDA does,” he said.

DELAY TACTICS COMMON The reasons the previously uninspected OTC facilities are receiv-ing warning letters include “probably the scariest” problems FDA finds in pharma manufacturing – failing to test raw materials and finished products, Godwin said.

“Some of them said they didn’t know the product they were shipping were drugs. Never mind they are registered as drug manufacturers and the product label literally said drug product.”

Being unfamiliar with drug manufacturing also showed in some firms’ facilities and equipment. “A lot of these firms

weren’t involved in drug manufacturing before and their facilities were pretty shocking. We’ve seen standing water, we’ve seen open equipment, some pretty crazy issues like that,” Godwin said.

He said probably one-third of FDA compliance actions among the foreign firms inspected since FDASIA were for delaying, deny-ing, limiting or refuse inspections.

“This is typically a firm that starts shipping drugs to the US and triggers an inspection. They email back and say, ‘We don’t want to be inspected.’ We say, ‘Fine, you’re going on import alert and you’re locked out’,” Godwin said.

Some also attempt to keep FDA inspectors out of their facilities. “Those get reported on import alert automatically,” he said.

With FDA approaching checking off all uninspected drug facili-ties off its inspection list, the agency expects that manufacturers inspected for the first time typically will be new entrants to the market, not firms that have supplied OTC drugs in the US without an inspection.

FDA also will return to some inspected facilities. “FDA will be coming back at some point,” Godwin said.


‘Four or five years ago, 20 warning letters in a year would be a bellwether. This year we’re on pace to be somewhere between 900 and 100 warning letters.’ – Francis Godwin, CDER OMQ acting director

Recruitment Begins For UK Health Claims Committee In Preparation For Brexit

Ramping up preparations for the event of a ‘no deal’ Brexit, the UK government has begun recruiting for its new Nu-trition and Health Claims Committee (UKNHCC) which is

standing by to take on the role currently played by the European Food Safety Authority (EFSA).

The government is looking to appoint eight members – one of whom will be chair – to the UKNHCC, which it recently an-nounced would be responsible for the scientific substantiation and provision of advice to the four UK administrations on any new nutrition and health claims made within the UK post-Brexit in a no deal scenario.

These eight “specialist members” will be expected to “assess the validity of scientific evidence underpinning applications for nutrition and health claims made to/in the UK after exit,” the gov-ernment explains. Recruitment has begun for the UKNHCC “in order to have a functional committee in place should the contin-gency need to be enacted.”

The UKNHCC will meet in London “up to six times per year,” with members expected to commit “up to 24 days” per annum to the post.

Outlining the scope of the UKNHCC’s work, the government ex-plains that a member’s role is to:



● Ensure the UK government receive the highest quality, time-ly, advice

● Examine the scientific evidence for substantiation of possible nutrition and health claims in light of the balance of evidence, not just that provided by applicants

● Summarise scientific arguments and draw conclusions on the validity of evidence for substantiation of possible nutrition and health claims

● Adhere to the terms by which members are appointed to UKNHCC, set out in the code of practice for scientific advisory committeesNoting that applicants “directly employed by industry” are ineli-

gible for the committee, the government is seeking expressions of interest from nutritionists, clinicians, and researchers with ex-

pertise in nutrition; nutritional epidemiology; human medicine; infant nutrition; paediatrics; and dietary exposure assessment.

Should the UKNHCC come into being, new nutrition and health claims authorised by the UK “will not be valid on the EU market, and vice versa”, the government makes clear.

There would be an “increased administrative burden” on com-panies, the government admits, “as they would have to submit claims to both the UK and the EU if they wished to make the claim in both areas.”

The government insists this process will not be overly cumber-some, with the application paperwork expected to take around thirty minutes to complete.


Stada Looks To Take Slice Of Growing Probiotics Market With Launch Of Probielle In GermanyDAVID RIDLEY [email protected]

Stada Arzneimittel AG has launched four probiotic supple-ments in Germany under its new Probielle brand.

Based on a variety of different probiotics strains, two of the four supplements – Probielle Balance and Probielle Im-mune – were for the general support of the digestive system, the firm explained, while the other two – Probielle Reizdarm and Probielle ADD – were aimed at helping consumers with specific gut problems.

Probielle Immune supported the intestinal function by strengthening the immune system, Stada pointed out, and contained vitamins A, B6, B12 and C, as well as folic acid, zinc and selenium.

Probielle Balance was designed to help support daily intestinal balance, the firm continued, and was “especially suitable for peo-ple who often feel bloated or have a lethargic digestion”.

Probielle Reizdarm helped consumers suffering from irritable bowel syndrome to “restore calmness to the stomach”, Stada not-ed, while also promoting their “general well-being” and maintain-ing an optimum nutrient intake.

Finally, Probielle ADD was “specially formulated for use during antibiotic treatment”, it added, preventing ‘antibiotic-associated diarrhoea’, as well as generally helping to “restore the natural in-testinal function”.

Probielle Balance, Reizdarm and ADD were all suitable for veg-ans, Stada explained, while Probielle Immune was suitable for

vegetarians. All the capsules in the range – which were to be taken once a day – were lactose and gluten free, the firm added.

Stada is supporting the launch of the Probielle range with a multimedia marketing campaign beginning this month, includ-ing two television advertisements.

The first advertisement shows people walking with their upper body detached from their lower body, with a voiceover asking: “Do you ever get the feeling that you are not in harmony with your stomach?”

“Test the new Probielle range,” the voiceover suggests, as the advertisement ends with a pack of Probielle Balance nudging a person’s lower body back into alignment with their upper body.

“We are never alone,” warns the voiceover at the beginning of the second, longer advertisement, adding that as there are “100 billion bacteria” living in the human body, it is “no wonder that the microbiome has a large impact on our health and wellbeing”.

Created by Magna Mana Production, the advertisement uses digital animation techniques to explain how the human microbi-ome works and how probiotics can positively affect overall health and day-to-day well-being of consumers.

“Inspired by nature,” the voiceover concludes, ”Stada’s new Pro-bielle probiotics support wellbeing with targeted therapies for a range of applications.”


� W E L L N E S S �

Visit https://pharmaintelligence.informa.com/hbw-insight



https://pharmaintelligence.informa.com/hbw


W E L L N E S S ( D I E TA R Y S U P P L E M E N T S )

During Recalls, Prepare For ‘Blood In The Water’ Response From Plaintiffs’ Bar EILEEN FRANCIS [email protected]

Consumer health companies working through product recalls often overlook that their immediate communica-tions and actions provide evidence to plaintiffs’ attorneys

in potential follow-up litigation, says Victoria Calhoon, a product liability litigator.

During a session on “Managing a Recall” during a Food & Drug Law Institute conference in Washington on Dec. 13, Calhoon, of Faegre Baker Daniels LLP in Indianapolis, said top management of a company conducting recalls often are inclined to reach out to customers for damage control or to send an email to staff to manage fallout.

However, they fail to realize that plaintiffs’ lawyers in class action cases targeting recalled products have already “smelled blood in the water” and will eventually access internal and external emails and memos, she said. Language used in the messages will be cit-ed out of context.

“In isolation, these documents can turn into red herrings you are going to have to fight,” said Calhoon, who represents manu-facturers of pharmaceuticals, medical devices and consumer products. “I heard a great quote that summarizes it well, ‘Dance like no body’s watching and email like it may one day be read al-lowed in deposition or trial.’”

As recalls, particularly for dietary supplements and food prod-ucts, grow in number due to global trade and FDA’s increased prevention-focused sampling capabilities, litigators are waiting in the wings, she suggested. “They harness the power of Google to set up alerts and see whenever a recall comes to bear,” she said.

Calhoon noted cases can be individual complaints, multi-dis-trict litigation – comprising multiple plaintiffs from different dis-tricts who combine their complaints during the discovery part of litigation – and class action cases, involving numerous plaintiffs.

FDA gained more authority to test food samples under the Food Safety Modernization Act, which established a risk-based and pre-ventive approach to food safety that gives the agency more tools for sampling to identify hazards before they reach the consumer. In the past five years, numerous recalls of foods products, infant formula and pet food related to 120 multi-state outbreaks have been reported.

In addition to emails and other correspondence, drafts of recall notices and press releases “are fodder too,” Calhoon said.

For example, a plaintiff’s lawyer may compare a draft of a press release with the final release to look for discrepancies. “Was there something in the recall notice that someone later took out that the plaintiff is going to want to glom onto?” she asked.

Plaintiffs also will ask to see correspondence with FDA, including form 483s the agency issues at the conclusion of facility inspections when investigators have observed conditions that may constitute violations of FDA regulations, as well as warning letters, meeting minutes and anything else that can be taken to use as evidence.

Even after the initial shock of the recall has passed and compa-

nies are trying to restore their image, the marketing departments can provide more material for plaintiffs. “Marketing departments are job security for litigators,” she said. Their job particularly after the recall is to make consumers happy, but their claims are dis-sected by litigators.

PROCEDURES ASSESSED, TOOCalhoon said plaintiffs will check whether a company has in place a recall response protocol and whether they follow it. ‘Whatever protocol a company has in place to deal with recalls, that will be looked it. They will bring in FDA experts, to put everything under a microscope,” she said.

By retaining a sample of recalled product, a firm can test claims plaintiffs are making. “If you have a food product, isolate it. Don’t let it contaminate anything else, but make sure you have a sample of the product to make sure the one in the lawsuit is the same one as the one recalled.”

In addition to providing FDA more tools to test samples, FSMA gave it authority to mandate recalls when certain unsafe products are identified. A mandatory recall only applies when there is a rea-sonable probability that exposure to a misbranded or adulterated product will cause serious health consequences.

FDA issued guidance in early November to clear up confu-sion over when it would issue mandatory recalls. (Also see “Mandatory Recall Guidance Positions FDA For ‘Robust’ Use Of Authority” - HBW Insight, 6 Nov, 2018.) So far, it has issued one mandatory recall order – in April 2018 for all products contain-ing powdered kratom manufactured or marketed by Las Ve-gas firm Triangle Pharmanaturals LLC after several products were found to contain salmonella. (Also see “Las Vegas Kratom Marketer Rolls Dice On FDA’s Mandatory Recall Authority” - HBW Insight, 3 Apr, 2018.)


Victoria Calhoon




J&J Doing Damage Control Following Reuters Report On Asbestos ‘Lurking’ In Johnson’s PowderLAUREN NARDELLA [email protected]

Johnson & Johnson suffered a major setback Dec. 14 in its battle to defend the safety of Johnson’s Baby Powder

on the global PR front – in addition to the courts – in the form of a Reuters report suggesting the firm has been concealing asbestos-tainted talc risks from the public for decades.

The firm’s stock plummeted follow-ing the report’s publication and remains down roughly 12% as of mid-morning trading Dec. 19.

According to Reuters, which combed through numerous internal J&J docu-ments that have surfaced in the con-text of litigation proceedings, J&J’s finished powder products and raw talc sporadically tested positive for asbes-tos contamination from 1971 through the early 2000s.

The international news agency says J&J was aware of the problem and made supply-chain investments to address the issue while maneuvering to protect its talc interests from potentially crippling regula-tory crackdowns.

What it did not do was fully disclose the extent of the problem to authorities or noti-fy the public of potential risks, Reuters says.

Plaintiff attorneys have painted a similar picture in liability suits alleging that J&J tal-cum powder use caused their clients’ (or cli-ents’ late family members’) mesothelioma or ovarian cancer, either due to airborne particle exposure in the former case or as a result of perineal dusting in the latter.

In this regard, the Reuters piece brings nothing dramatically new to light, but it throws the central issues of contention into high relief for the news outlet’s glob-al audience.

J&J quickly responded with a same-day statement slamming the Reuters article as “one-sided, false and inflammatory.” The firm maintains that its baby powder is safe and free from asbestos, pointing to “thou-sands” of independent regulatory tests that it says corroborate its position.

Additionally, J&J took out full-page advertisements in national newspapers

to reassure the public about Johnson’s Baby Powder, touting “Science. Not sensationalism.”

It’s a regrettable conversation for John-son’s to be having just months after re-launching with new formulations to culti-vate a cleaner chemistry image.

J&J CEO Alex Gorsky made an appear-ance on CNBC’s “Mad Money,” telling host Jim Cramer, “We unequivocally believe that our talc, our baby powder, does not contain asbestos.”

J&J goes further in the statement post-ed to its website, asserting that Johnson’s Baby Powder has never in its 120+-year history contained asbestos, an important specification considering the decades typically required for cancers to develop following asbestos exposure.

According to a 10-Q quarterly report filed with the Securities and Exchange Commission Oct. 31, J&J currently faces some 11,700 liability suits related to talc-containing body powders. Most of the complaints are pending in Missouri, New Jersey and California courts.

The majority of cases tried to date have alleged that talc itself has carci-nogenic potential when it’s applied to female genitals for antiperspirant/de-odorant purposes and migrates to re-productive organs.

As J&J has shown itself capable of defeat-ing litigation of this nature on shoddy sci-ence grounds, courts increasingly are hear-ing cases that cite asbestos as the culprit.

J&J was on the losing end of one such suit in a Missouri state court that involved 22 plaintiffs and resulted in an eye-pop-ping $4.7bn verdict, which the firm is ap-pealing.

Overall, the company has had mixed success fending off talc liability actions and likely will continue to fare differently from one venue and jury to the next.

A draft talc assessment released Dec. 8 by Canadian public health and environ-mental protection authorities won’t be doing any favors for J&J as new cases go to trial.

CATALYST FOR FDA ACTION? Sen. Ed Markey, D-Mass., responded to Reuters’ findings by firing off a letter to FDA Commissioner Scott Gottlieb asking the agency to investigate the claims and “determine whether Johnson & Johnson’s actions have placed at risk the public’s health and safety.”

He notes, “That they may have con-cealed a potentially serious health and safety risk associated with use of its baby powder is deeply troubling.”

The senator highlights Gottlieb’s com-ments in the Reuters report acknowledging that people are concerned about cosmetic talc safety and that cosmetics oversight in general is an area where FDA could be do-ing more if it had additional resources.

The commissioner told Reuters that FDA intends to hold a forum in early 2019 to explore the development of standards for talc risk evaluation, which would include test methods for asbestos assessment.

Markey says that’s not enough. While the senator recognizes FDA’s limited au-thority when it comes to cosmetics over-sight, he demands the agency immedi-ately look into the J&J allegations using the regulatory powers and investigative resources at its disposal.

FDA has been pressed before to look into the safety of talc in cosmetics, most recently in February by Rep. Frank Pallone, D-N.J., who will soon chair the Energy and Commerce committee. He raised his con-cerns following reports that talc-contain-ing makeup products from specialty girls retailer Claire’s were tainted with asbestos.

FDA said it was actively investigating the issue and would offer more informa-tion when it became available.

The agency’s cosmetics office won fund-ing in 2016 for proposed lab studies to ex-plore the relation, if any, between talc use in cosmetics and ovarian cancer.

FDA surveyed the market a decade ago and detected no asbestos in raw talc or finished talc products.


B E A U T Y ( C O S M E T I C S )





Canadian Authorities Say Some Cosmetic Talc Applications May Endanger Human HealthLAUREN NARDELLA [email protected]

Exposure to cosmetic-grade talc through female genital dusting or in-halation during powder product ap-

plication may pose health risks, according to Canadian regulatory authorities.

Health Canada and Environment and Climate Change Canada published those tentative conclusions Dec. 8 in the form of a draft screening assessment under the country’s Chemicals Management Plan.

Created in 2006, Canada’s CMP is de-signed to assess 4,300 chemicals by 2020 and reduce associated risks to consum-ers. To date, nearly 3,600 substances have been evaluated.

The talc assessment comes at a time of growing public interest in talcum powder safety, in large part due to national media coverage of Johnson & Johnson’s related legal battles, with thousands of plaintiffs lined up in courts around the US alleging a link between their ovarian cancer or me-sothelioma and Johnson’s Baby Powder.

A Dec. 14 Reuters report, which J&J calls “one-sided, false and inflammatory,” sug-gests the company has been sitting on knowledge that its talc can be dangerous for decades. (Also see “J&J Doing Dam-age Control Following Reuters Report On Asbestos ‘Lurking’ In Johnson’s Powder” - HBW Insight, 19 Dec, 2018.)

Reuters’ focus is asbestos-contaminated talc, which it says J&J knew about but was unable to completely eliminate from its massive talc supply, based on internal J&J memos, lab reports and other documents from decades past that liability suits have brought to light.

Plaintiffs have made similar claims, connecting their cancer to asbestos J&J didn’t warn them about, while others say talc itself is to blame. J&J has managed to defeat some of these actions by attack-ing plaintiffs’ evidence as flawed or insuf-ficient, maintaining that its talc poses no threat to consumers.

Presumably that includes women who use its powders daily for antiperspirant/deodorant purposes, as well as those who inadvertently inhale micro-sized talc par-

ticles in the course of powder application. (Also see “J&J Talc Suit Dismissals: Plaintiffs Lack Causation Thread For Proof Quilt” - HBW Insight, 8 Sep, 2016.)

The Canadian authorities would dis-agree, based on their draft assessment.

“The meta-analyses of the available human studies in the peer-reviewed literature indicate a consistent and sta-tistically significant positive associa-tion between perineal exposure to talc and ovarian cancer. Further, available data are indicative of a causal effect,” they say.

Aside from baby and body powders, talc-containing self-care products identi-fied by the authorities as having the po-tential for perineal exposure include body wipes, bath bombs, hair-removal prod-ucts “and to a lesser extent (due to wash off or removal) other bath products (i.e., soap, shower gel).”

Inhalation of talc particles is another area of potential health concern, accord-ing to Canada’s health and environmental departments, which point to evidence linking such exposure to lung damage.

They note that pressed powders, such as eyeshadow and blush, are not consid-ered problematic because their applica-tion generally is not expected to generate the “dust cloud” that can lead to respira-tory exposure.

Rather, cosmetic products of concern include those intended for application to the body, feet, buttocks (in the case of ba-bies) and hair (e.g., dry shampoo).

Overall, talc is present in approximate-ly 6,500 cosmetic products on the Cana-dian market, and most – around 4,000 – are pressed powders, according to the draft assessment. Should the draft talc assessment be finalized in its current

form, it will flag the naturally occurring mineral as “toxic” per the Canadian En-vironmental Protection Act’s definition, based on evidence that “constitute[s] or may constitute a danger in Canada to human life or health.”

Risk management measures will follow, according to Health Canada and the coun-try’s environmental department.

Actions could include revision of Cana-da’s Cosmetic Ingredient Hotlist and Natu-ral Health Products Ingredient Database and monographs to prohibit or restrict talc’s use in certain self-care products, they say.

The Hotlist already lists talc as restrict-ed, requiring its inclusion in products de-signed for use on infants or children to be accompanied by labeled warnings to “keep out of the reach of children” and “keep powder away from child’s face to avoid inhalation that can cause breath-ing problems.”

Comments on the draft assessment, which published in the Canada Gazette, are being accepted for a period of 60 days. A final assessment and risk man-agement approach is expected to issue in winter 2020.


‘The meta-analyses of the available human studies in the peer-reviewed literature indicate a consistent and statistically significant positive association between perineal exposure to talc and ovarian cancer. Further, available data are indicative of a causal effect.’ – Canadian health and environment authorities




CIR Expert Panel Seeks Proper Balance In Respiratory Exposure Doc, Says Particle Size Isn’t All-Important EILEEN FRANCIS & RYAN NELSON

It’s increasingly apparent that any inhala-tion risks posed by ingredients in spray or powder cosmetics will have to be de-

termined by Cosmetic Ingredient Review’s Expert Panel on a case-by-case basis, potentially requiring different data from industry to address different ingredient-specific concerns.

But the group’s Aerosol Precedent, which is undergoing a name change among other updates, should give com-panies a general idea of the panel’s expec-tations in terms of testing that may – or may not – be needed to support such in-gredients’ safety.

Debate on the topic, which continued Dec. 3-4 at the CIR Expert Panel’s meet-ing in Washington, has centered to great extent on particle size data – i.e., just how critical they are to evaluating ingredients in aerosol form. (Also see “Cosmetic Spray Safety Assessment Rarely Needs Particle-Size Data? CIR Expert Panel Weighs NGO Criticism” - HBW Insight, 3 Dec, 2018.)

The draft document at issue has been under consideration since April 2017 when CIR staff made revisions to a previ-ous iteration and presented the changes to the CIR Expert Panel.

NGO Women’s Voices for the Earth (WVE) took the opportunity to enter into the con-versation, raising concerns the panel saw as valid. CIR’s independent experts agreed that a “bit of work” was needed to update the guide. (Also see “WVE Letter Prompts CIR Panel To Rethink Aerosol Cosmetics, In-halation” - HBW Insight, 14 Apr, 2017.)

At the time, the panel acknowledged that the methods and data used to char-acterize particle-size distributions re-leased to the breathing zone during the use of cosmetic sprays and powders were not well characterized in the Aerosols doc-ument, according to a CIR recap.

The panel since has heard from a pair of outside experts, including Yevgen Naz-arenko, a postdoctoral fellow at McGill University and the author of a study cited by WVE as a counterpoint to previous CIR assumptions.

An overview of Nazarenko’s presenta-tion to the group, along with that of inha-lation toxicologist Madhuri Singal, at the time a senior consumer safety associate at Reckitt Benckiser Group PLC, is available from CIR here.

CIR also took recommendations from the Personal Care Products Council’s CIR Science and Support Committee (SSC) and collected updated data from industry on particle size distributions in hairsprays and spray deodorants. According to CIR records, the latter were determined to be aerosols with the largest respirable frac-tions based on data at the panel’s disposal in early 2017.

Drawing on that input, CIR’s experts scrubbed an assumption in the Aerosols document that just 5% of the particles re-leased by propellant deodorant sprays are of respirable size, upping the estimate to a conservative 50%.

At the same time, CIR and its Expert Panel began to advocate a tiered ap-proach to assessing inhalation exposure and risk, in line with SCC recommenda-tions, deemphasizing the importance of particle size data.

Going into the panel’s Dec. 3-4 meet-ing in Washington, the Aerosols docu-ment was updated with language sug-gesting that particle size data are “rarely needed” when conducting inhalation risk assessments for cosmetic spray or powder products.

From the viewpoint of Alexandra Scran-ton, director of science and research at WVE, “this statement appears either to contradict a major tenet of inhalation toxicology (i.e. that particle size is indeed a significant factor) or to imply that the CIR is simply uninterested in investigating particle size data when they assess an in-gredient for inhalation safety.”

EXPOSURE IS KEY, AND COMPLEX The disconnect between CIR and WVE may be attributable in part to their differ-ing ideologies when it comes to chemical safety assessment.

Exposure considerations are central to the CIR Expert Panel’s reviews, consistent with industry practices, whereas WVE tends to wield a more precautionary out-look prejudicial to ingredients with known hazardous properties.

If a suspected hazardous ingredient contained in a spray cosmetic is shown by lab testing to disperse in respirable sizes, WVE may well be inclined to error on the side of caution and object to its use.

But just because particles have the po-tential to be inhaled doesn’t mean they will be in the course of normal product use under anticipated use conditions, or that any incidental exposure is neces-sary toxic.

“We say it very strenuously throughout the document that particle/droplet size data for consumer uses are generally not needed when conducting a risk safety assessment, and I think that’s way too strong language because you do want some particle size [information].” - der-matologist and CIR Expert Panel team leader Donald Belsito

CIR increasingly supports a tiered ap-proach that takes into account the diver-sity of factors that can influence exposure and, ultimately, inhalation risks. As RB’s Singal (now at Honeywell International, Inc.) noted in her presentation to CIR, room volume, room ventilation, discharge rates, spray times, airborne ingredient concentrations and a user’s own respira-tory rate all have bearing on exposure, in addition to particle/droplet size.

Such variables are Tier 2 considerations in the methodology proposed by CIR. In many cases, CIR says, it may be sufficient to assume at the Tier 1 level that all cos-metic product leaving the container is po-tentially respirable and likely to become systemically available. If this extremely conservative possibility compares favor-ably against a systemic toxicity threshold, no additional work is needed.

The proposed tiered system recognizes the complexity of exposure scenarios and associated risk calculations. It also could




save cosmetic manufacturers on the costs and uncertainties of testing products un-der simulated use conditions (Tier 3), pro-vided that lower-tier screening and mod-eling provide the safety assurance they need to proceed.

‘WHOLE SLEW OF THINGS’ TO CONSIDER At its December meeting, CIR’s Expert Panel generally embraced the tiered as-sessment concept and agreed to revise the related document’s name from “Aero-sols Precedent” to “Respiratory Exposure from Cosmetic Ingredients Resource.”

According to CIR, the name change re-flects the demoted importance of particle size data in favor of the tiered approach that focuses attention on spray cosmetic ingredients’ physiochemical properties and “realistic” exposure factors under in-use conditions.

“There’s a whole slew of things in addi-tion [to particle size] that should be con-sidered,” noted Ronald Shank, professor emeritus in the Department of Medicine and Environmental Health Sciences Pro-gram at the University of California, Irvine.

At the same time, Donald Belsito, Leon-ard D. Harber professor of dermatology at Columbia University Medical Center – who leads one of the Expert Panel’s two teams – expressed concern that revisions to the document could go too far in mar-ginalizing particle size data. WVE raised concerns of the same nature.

“We say it very strenuously throughout the document that particle/droplet size data for consumer uses are generally not

needed when conducting a risk safety as-sessment, and I think that’s way too strong language because you do want some par-ticle size [information],” Belsito said. “I think it needs to be toned down, to something like ‘particle size is not the only factor that needs to be looked at.’”

The dermatologist, who also chairs the Expert Panel for Fragrance Safety, an inde-pendent group that reviews the activities of the industry-funded Research Institute for Fragrance Materials (RIFM), held that “more than just minor changes” are need-ed to the document.

He contrasted the resource with oth-er documents from CIR that serve as boilerplates invoked in reviews on an ongoing basis rather than having to re-draft language repeatedly around the same points.

For inhalation, “we can’t just say, here is the document and dismiss everything,” Belsito said. The document will explain the CIR Expert Panel’s outlook on the respira-tory toxicity endpoint, but won’t replace the need for data, which will vary depend-ing on the specific ingredient at issue.

CIR captures his view in its post-meet-ing announcement, noting, “When spray parameters are absent or provide an insuf-ficient basis to support a robust inhalation exposure assessment, the Panel would re-quest additional information from Indus-try and further evaluate the sufficiency of other exposure data that may be available on a case-by-case basis.”

Further, CIR says an additional batch of particle size distribution data will be re-quested from industry to address knowl-

edge gaps for certain types of cosmetic sprays – presumably those other than hairsprays and spray deodorants – anoth-er move in line with WVE’s urging.

Finally, an external expert on inhalation toxicology will be asked to review the re-vised Respiratory Exposure document be-fore its finalization, CIR says.

Scranton told HBW Insight Dec. 13 that she’s pleased with the direction CIR and its experts have taken with the Respiratory Exposure document – a name change she applauds.

It’s encouraging that the Expert Panel is prepared to make data requests of indus-try as specific needs arise from one aero-sol ingredient review to the next, and that CIR will be soliciting particle-distribution data from industry on cosmetic sprays that aren’t well understood at present, Scranton said.

“We made the point that the technolo-gy to obtain data on these other products is readily available and should be used, rather than calculating estimated expo-sures using decades-old data or assum-ing hairsprays are an effective proxy for all other cosmetic sprays.”

She continued, “Women’s Voices for the Earth strongly encourages the CIR to get the most and best data available to inform their assessments. The consequences of underestimating the potential hazards of inhalation from cosmetics are significant, and could lead to the inclusion (or contin-ued use) of cosmetic ingredients that could cause real-long term harm to users.”


FDA Researchers Analyze OTC Spray, Powder Products, Finding Possible Respiratory RisksLAUREN NARDELLA [email protected]

OTC sunscreen and antiperspirant drug products in spray or powder formats are meant to be applied

to skin but could expose users to airborne particles in the same size range as those in metered dose inhalers for asthma and other lung conditions, according to a study from FDA researchers.

Titled “Particle Size Distribution Analysis

of OTC Aerosol or Powder Drug Products with Potential for Inadvertent Inhalation Exposure to Consumers,” the study pub-lished online Nov. 20 in the Journal of Pharmaceutical Sciences.

All five of the study authors, led by Xiao-fei Liu, are researchers within FDA’s Center for Drug Evaluation and Research, and while they note that the article does not

reflect agency views or policy, they say it could be useful to FDA in its mission to protect and promote public health.

The study provides insight into the characteristic particle/droplet size distri-butions generated when OTC aerosol/powder drug products for topical applica-tion are discharged from their containers for use in accordance with labeled direc-




LEADERSHIPPhil Jarvis, Richard Faint

SUBSCRIPTIONSDan Simmons, Shinbo Hidenaga

ADVERTISINGChristopher Keeling, Rob Coulson

DESIGN SUPERVISORGayle Rembold Furbert

PRODUCTIONPaul WilkinsonHBW

InsightEXECUTIVE EDITOR Ryan Nelson

EXECUTIVE EDITOR – US Malcolm Spicer

REPORTER – US Eileen Francis

MANAGING EDITOR – EU Tom Gallen

SENIOR EDITOR – EU David Ridley

EDITORIAL OFFICESChristchurch Court 601 Third Avenue 10-15 Newgate Street New York, NY London, EC1A 7AZ 10158 US

CUSTOMER SERVICESUS Toll-Free: +1 888 670 8900US Toll: +1 908 547 2200UK & Europe: +44 (20) 337 73737Australia: +61 2 8705 6907Japan: +81 3 6273 4260 Email: [email protected]

TO SUBSCRIBE, VISIThbw.pharmaintelligence.informa.com

TO ADVERTISE, [email protected] [email protected]

All stock images in this publication courtesy of www.shutterstock.com unless otherwise stated

HBW Insight is published by Informa UK Limited. ©Informa UK Ltd 2018: All rights reserved. ISSN 0143 7690.

tions, the FDAers say. They analyzed 32 commercially pur-

chased offerings via laser diffraction, including sunscreen aerosol products, sunscreen powder products, aerosol and aerosol powder antiperspirants, a topical analgesic in aerosol dosage form, an anti-microbial and analgesic aerosol, skin pro-tectants and an acne product.

Compared with powders and aerosol powders – the authors define these terms based on delivery mechanisms employed – the aerosol products were less likely to contain significant populations of par-ticles that may penetrate the larynx due to their size (<10 µm).

That said, four aerosol antiperspirants containing aluminum chlorohydrate did fall in this bucket, representing potential respi-ratory concerns, according to the authors.

Two aerosol products contained signifi-cant amounts of particles below 5 µm in aerodynamic diameter, which may reach “deep into the lungs,” being of the same general size as drug particles in metered dose inhalers.

Metered dose inhalers are used to treat lung diseases such as asthma, so their ac-tive drug particles are meant to be inhaled and are sized accordingly.

Liu, et al., say the 15 sunscreen aerosol products they analyzed showed larger particle sizes overall compared with the antiperspirant/deodorant products.

As for the seven powder products and eight aerosol powder products the inves-tigators tested, all of the former had large

portions of relatively small particles, and seven out of eight in the latter category had significant populations of particles in the sub-10 µm range, while six had at least 10% of particles that were smaller than 5 µm.

In the authors’ words, “six powder and eight aerosol powder drug products surveyed had particles in the size range where there is high probability for deposi-tion deep in human lungs.”

They go on to interpret the findings’ potential significance from a toxicity per-spective.

“Particles or droplets produced by OTC drug products under normal usage that reach the lower, unciliated airways of the lung are referred to as ‘respirable’ particles and may cause inhalation toxicity de-pending on their chemical properties as well as their dosage,” the researchers state.

They note that their work was not an “in-depth, exhaustive market survey” and that the size distributions of emitted airborne particles varied greatly from one product to the next, which may signal the need for further explorations.

COSMETIC IMPLICATIONS While Xiu et al.’s study focused exclusively on OTC drug products, it could have impli-cations for the cosmetics industry.

The FDA researchers’ findings represent a timely addition to available data in the context of recent efforts at the Cosmetic Ingredient Review to finalize a “Respira-tory Exposure from Cosmetic Ingredients” resource document. (Also see “CIR Expert

Panel Seeks Proper Balance In Respiratory Exposure Doc, Says Particle Size Isn’t All-Important “ - HBW Insight, 13 Dec, 2018.)

The document is intended to inform the CIR Expert Panel’s reviews of ingredients present in aerosol cosmetics, including hairsprays and spray deodorants.

Much of the debate around the docu-ment’s revision has centered on the im-portance of particle size data in assessing inhalation exposure and, ultimately, respi-ratory risks.

Recent changes have included the in-corporation of a tiered assessment ap-proach that deemphasizes particle size data while highlighting the importance of considering ingredients’ physicochemical properties and “realistic” exposure factors under in-use conditions.

In their study, the FDA researchers acknowledge the important roles that chemical properties and dosage play in determining toxicity – i.e., that exposure is not an evil in itself necessarily.

However, they also stress that “the mea-surement of particle size distribution is an important determinant of the exposure to end users since knowing the mass of re-spirable particles is essential for an inhala-tion exposure assessment.”

Women’s Voices for the Earth has main-tained as much in its comments to CIR, cau-tioning the group against making overly broad generalizations based on potentially faulty assumptions (see story, p. 13).







Intelligence with aGlobal Perspective

The Premier Resource In The Life Sciences Industry

Pharma intelligence

Pharmaintelligence.informa.com

Biomedtracker

Datamonitor Healthcare

In Vivo

Meddevicetracker

Medtrack

Medtech Insight

Pink Sheet

Pharmaprojects

RxScorecard

Scrip

Sitetrove

Trialtrove

Documents

HEALTH HBW · Asia markets for Horlicks and other nutri-tional beverage brands to Unilever PLC. (Also see “Horlicks Brings Unilever ‘Trans-formative’ Nutritional Deal, Market