Medtech Industry Groups Spend Millions In 2019 Lobbying ... · 10 Former FDA Coronary Device...

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October 14, 2019 Issue 165

R&D

BD, VIVA data show lower paclitaxel mortality risk, p. 18

POLICY & REGULATION

FTC warns on misleading tv ads by personal injury lawyers, p. 5

COMMERCIAL

Lantheus buys Progenics to combine radiopharmaceuticals with precision diagnostics, p. 17

Medtech Industry Groups Spend Millions In 2019 Lobbying For Device-Tax Repeal – And Much MoreSUE DARCEY [email protected]

T hree medtech industry groups spent roughly $4.9m to lobby Con-gress in the first half of 2019 – and

not only to persuade legislators to repeal the 2.3% device tax, say lobbying reports made available by the Senate Office of Public Records to a public interest group, and analyzed by Medtech Insight.

Lobbying records for AdvaMed, the Medical Device Manufacturers Associa-tion (MDMA), and NEMA (the National Electric Manufacturers Association) and its subsidiary MITA (the Medical Imaging Technology Alliance) were examined for the analysis in this story.

According to the lobby reports, which were captured by the Center for Respon-sive Politics (CRP) and made available on the group’s Open Secrets database, Ad-vaMed spent $2.05m in first and second quarters of 2019, while the MDMA spent $740,000 and NEMA/MITA spent $1.09m – either on their own, in-house lobbying efforts, or in payments for hired lobby-ing guns at Washington, DC, govern-ment-affairs firms.

Perhaps the biggest surprise shown by the reports is that while all the industry trade groups spent a significant chunk of their lobbying dollars and time trying to persuade Congress to repeal or delay im-plementation of the medical device tax, they also lobbied hard on other issues.

Among non-tax repeal issues that the trade groups lobbied hard for in 2019 were cybersecurity concerns with medi-cal devices, trade issues – particularly with China and for passage of the US-Mexico-Canada free-trade agreement – and for better coverage and reimbursement by the US Centers for Medicare and Medic-aid Services (CMS) for medtech products.

Other issues mentioned in the lobby re-ports that the groups pressed Congress to limit or improve, were group purchasing organizations (GPOs) and gainsharing ar-rangements (by the MDMA). For example, in years past, MDMA president and CEO Mark Leahey has given testimony to the

Senate Finance Committee, and continues to lobby Finance panel staff, to be certain that GPOs in their purchasing arrange-ments for hospitals do not favor a small number of medtech firms’ products over others. “Nothing should compromise the physician-patient relationship, including eliminating any financial incentives to use a particular brand or product,” Leahey told the committee in 2015. (Also see “Physicians Failing To Disclose Supplier, POD Arrange-ments Fuel Kickback Concerns, Senators Say” - Medtech Insight, 21 Mar, 2019.)

Further, AdvaMed was concerned about price caps on medtech set by the

CONTINUED ON PAGE 8

AdvaMed was concerned about price caps on medtech set by the Indian government, so it lobbied Congress to intervene on that issue

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inside:Cover / Medtech Industry Groups Spend Millions Lobbying

For Device-Tax Repeal – Public interest group reports show what the medtech industry paid out to hire legislative experts to lobby the US Congress in the first half of 2019.

EDITORS’ PICKS 5 MD Anderson Oncologist Stephen Hahn Is Trump’s First

Choice For FDA Commissioner: Reports – Media reports say President Trump will nominate Stephen Hahn, as chief medical executive of MD Anderson Cancer Center, as the next US FDA commissioner.

5 FTC Warns On Misleading TV Ads By Personal Injury Lawyers – Legal service ads that attempt to recruit patient plaintiffs for product-safety lawsuits against drug and device companies by resembling official medical alerts or recall notices may be deceptive or unfair, the US Federal Trade Commission warned in a recent set of letters.

6 86% Rise In GMDN Usage Heralds New Era Of Postmarket Data Analytics – The Global Medical Device Nomenclature is emblematic of the global trend toward building high-quality datasets.

POLICY & REGULATION 10 Former FDA Coronary Device Officer Hops To Gore –

John Laschinger spoke to Medtech Insight about his work at the agency and his move to device-maker W.L. Gore.

11 Work With Specialty Societies Before Taking Hip And Knee Procedures Off IPO-Only List, MDMA Advises CMS – The US Medicare agency wants to move total hip arthroplasty and knee arthroplasty procedures from an “inpatient only” list to outpatient facilities.

12 US FDA Toying With Idea Of ‘Regulatory Legos’ In MDUFA – FDA device center head Jeff Shuren recently floated the idea of developing statutory building blocks that would allow the agency to keep up with rapidly advancing medtech products.

18 12 14

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13 AdvaMed Pans CMS Plan To Mandate Publicizing Hospital Rates, But Likes Pay Path For Breakthrough Devices Commercial – AdvaMed and MDMA support CMS’ Medicare coverage and payment proposal for breakthrough devices and requested only minor tweaks to the plan.

14 Australia Suspends Breast Implants Over Cancer Risk – The Therapeutic Goods Administration has taken action on breast implants and tissue expanders following its review into the link between these products and a rare type of cancer.

16 Australia Reviews Ban On Many Self-Testing IVDs – A new public consultation is looking at whether Australia’s rules prohibiting the supply of many types of self-testing IVDs are still fit for purpose.

COMMERCIAL 17 Lantheus Buys Progenics To Combine

Radiopharmaceuticals With Precision Diagnostics – Lantheus says the all-stock drug-diagnostics deal brings together complementary portfolios of ultrasound and radiopharmaceutical diagnostics with oncology therapeutics.

R&D 18 BD, VIVA Data Show Lower Paclitaxel Mortality Risk – BD

said an independent Lutonix review found no significant link to deaths, while further meta-analysis from trade group VIVA showed a decline in the risk.

19 Portico TAVR Crosses Non-Inferiority Threshold – Abbott’s Portico transcatheter aortic valve performed well enough to meet the statistical criteria for non-inferiority to surgery in the PORTICO IDE trial. The company will likely look to its next generation of Portico for more impressive results.

19 TRILUMINATE Six-Month Results Support Abbott’s TriClip – Six-month results from a feasibility trial support the safety and efficacy of Abbott’s TriClip, a version of the company’s established MitraClip mitral valve repair device.

20 Five-Year Results Support TAVR In Most Intermediate Risk Patients – A new update from the PARTNER 2A trial shows transcatheter aortic valve replacement with Edwards Lifesciences’ Sapien XT yields similar outcomes to valve surgery in intermediate risk patients.

20 One-Year PARTNER 3 Outcomes Show Better Quality Of Life With TAVR – A new analysis shows transcatheter aortic replacement with Edwards Sapien 3 yields better health status outcomes than surgical valve replacement after one year.

21 Market Intel: 3D Bioprinting Forges Ahead With Mini Human Heart, Human Tissue – Research organizations and companies worldwide are in various states of development of breakthroughs in regenerative medicine, from bioprinting skin to a mini human heart.


� E D I T O R S ’ P I C K S �

MD Anderson Oncologist Stephen Hahn Is Trump’s First Choice For FDA Commissioner: ReportsSUE DARCEY [email protected]

S tephen Hahn, chief medical execu-tive at MD Anderson Cancer Cen-ter, will be Trump’s pick to run the

US Food and Drug Administration as long as he can complete the necessary FBI background checks and other vetting processes, media reports say.

A radiation oncologist at the cancer center – part of the University of Texas system in Houston – Hahn is an active clinician specializing in treatment of tho-racic and genitourinary cancers, and in the use of photodynamic therapy.

So far, he is the only candidate to have met personally with Trump, according to Stat online news and Politico Pro,and is the president’s top pick among three candi-dates – acting chief Sharpless, Hahn, and Harvard University dermatologist Alex-andra Boer Kimball, BioCentury reported on 1 October. (Also see “Three Candidates In Running To Become FDA Commissioner, Including Acting Chief Ned Sharpless” - Medtech Insight, 5 Sep, 2019.)

In a 3 September letter to the president and US Health and Human Services secre-tary Alex Azar, former FDA commissioners Robert Califf, Margaret Hamburg, Andrew von Eschenbach and Mark McClellan ad-vocated for Sharpless, who formerly led the National Institutes of Health’s Nation-al Cancer Institute, to become permanent commissioner.

But it appears Trump prefers Hahn.Sharpless had been criticized by US

Sen. Richard Durbin, D-IL, in a sharply-worded letter in May for not taking swift enough action against the sale of e-cig-arettes to minors. Sharpless’ nomination was also opposed by two North Caro-lina Republican senators, Richard Burr and Thom Tillis, who objected to giving the commissioner position to someone who has contributed to Democratic cam-paigns. Burr sits on a Senate committee – Health, Education, Labor and Pensions – that will preside over the next agency commissioner’s confirmation process.

(Also see “US FDA Commissioner Search: Did Sharpless’ Hopes Just Go Up In Smoke?” - Pink Sheet, 10 Sep, 2019.)

Under the Federal Vacancies Reform Act, the Trump administration is required to nominate a permanent commissioner – or name a new acting commissioner – by 1 November.

Published online 2 October 2019

FTC Warns On Misleading TV Ads By Personal Injury LawyersELIZABETH ORR [email protected]

A recent Federal Trade Commission (FTC) warning against mislead-ing advertisements that attempt

to recruit plaintiffs for medical product-safety lawsuits has drawn applause from device industry observers.

Seven legal practitioners or plaintiff referral services drew FTC letters warn-ing that ads soliciting clients for personal injury lawsuits against drug manufactur-ers could be deceptive or unfair under the FTC Act, the commission announced on 24 September. The commission declined to name the recipients of the letters.

Specifically, the commission says the lawsuit ads “may make deceptive or un-substantiated claims about the risks of taking blood thinners and drugs for dia-betes, acid reflux, and high blood pres-sure.” Any such claims made in advertise-ments should be supported by reliable scientific evidence, the FTC says.

The FTC is concerned that the ads may encourage patients to stop taking medi-cations without consulting physicians, or may easily be confused for government-sanctioned medical alerts or public-service announcements. Some reports concerning

patients who stopped taking prescribed medications after seeing the ads have al-ready been filed with the US Food and Drug Administration’s Adverse Event Reporting System (FAERS), the commission stated.

The move drew cheers from device in-dustry trade group AdvaMed, which has previously expressed concerns about the risks these ads may pose to both patients and the device industry. While the specif-ic advertising called out by the FTC con-cerned drug lawsuits, similar tactics have been used against device manufacturers

“These predatory legal advertisements are disguised to look like FDA safety alerts, recalls or other critical medical warnings in an effort to bundle as many claims as possible for plaintiff lawyer,” said Christopher White, AdvaMed’s chief operating officer and general counsel.

One example comes from lawsuits




against pelvic mesh manufacturers, White wrote in a July blog post. In that case, le-gal services companies directed some pa-tients to have mesh removal surgery even if it wasn’t necessary as a way to maximize any payout from the device manufacturer. And at least one surgeon is under indict-ment for having allegedly performed unnecessary mesh removal surgeries at above-market rates and falsely testified

as to patient symptoms. The patients, physician, lawyers and an outside funding source all conspired to make money from the device manufacturer, White contends.

In addition to recognizing the FTC en-forcement action, White also urged state lawmakers to follow the lead of Texas and Tennessee by blocking the ads at issue. For example, a Tennessee law that went into effect on 1 July says advertising for le-

gal services cannot pose as a health alert, falsely use the word “recall,” or solicit po-tential clients who may allege injury from FDA-cleared drugs or devices without warning patients to talk to a doctor before they stop taking prescribed medication, and stating if the drug or medical device is still approved by the FDA.


86% Rise In GMDN Usage Heralds New Era Of Postmarket Data Analytics AMANDA MAXWELL [email protected]

I t may be “down in the engine room of the EU regulatory system,” and very focused on operational issues, but the

Global Medical Device Nomenclature (GMDN) is now “very slick” and highly rele-vant in the context of the EU’s Medical De-vice Directives and the forthcoming regu-lations that will replace them. It also has applications in global regulatory systems.

Use of the nomenclature is reaching a critical mass. The “exciting potential” it holds in pinpointing the real value of devices is about to be exploited, said John Wilkinson,

who took up the position of chair desig-nate of the agency in May 2019, having al-ready been a trustee. Wilkinson has just two weeks until he steps down from his position as director of devices at the UK Medicines and Healthcare products Regulatory Agen-cy (MHRA) to assume his GMDN role.

GMDN is now used by more than 5,200 registered member organizations around the world. Usage has increased by a stag-gering 86% in the last five months, follow-ing the introduction on 1 April of a new free membership category for manufacturers.

This grants access to core GMDN data only, and was introduced as regulators are in-creasingly insisting that all medical devic-es use GMDN. Charges remain for manu-facturers wanting an enhanced service. GMDN has always been free for regulators and academics. “I am looking forward to developing the offering of GMDN, which has great potential as a globally useful, unambiguous and highly developed op-erational nomenclature for the medtech sector, and for the benefit of patients too,” Wilkinson told Medtech Insight ahead of moving into the hotseat at the agency.

Where the real value of the GMDN lies, who uses it, and why was it not chosen by the European Commission to be the nomenclature for the EU MDR and IVDR were among the themes broached by Wilkinson in the interview below.

Medtech Insight: Where is the biggest value in the service that is provided by GMDN?

John Wilkinson: Globally we are seeing an increased emphasis on postmarket surveillance and postmarket data development.

In the past, there was limited pre- and postmarket data, and much of it was not appropriate for higher-risk products. What we need now is to collect data on a systematic basis; GMDN files information into consistent categories and is a crucial as-set in such analytics.

We can pool this information so that we can see the products that work well and accelerate the adoption of those products. Problems that show up can be analyzed in a timelier manner. The information can also be shared in unambiguous ways.

Where does GMDN fit in globally, and which regulators use it?

Wilkinson: GMDN remains a hugely important global ser-vice. It is embedded in US legislation and has been taken up

by the Australia’s Therapeutic Goods Administration (TGA); it allows regulators to ensure they are comparing like for like. In Canada, Russia and the UK, too, there have been recent an-nouncements by regulators requiring its use.

The UK’s MHRA downloads GMDN data every day to ensure it has up-to-date information on products on its markets. Oth-er regulators download updates less frequently; in all cases, those who use it do not need to build their own datasets and collective terms. We work with all such stakeholders to help them get the full value operationally and strategically.

Who else uses GMDN?

Wilkinson: GMDN is used by not-for-profit organizations and health-care providers, as well as by regulators and manu-facturers. It has many potential uses – we have barely touched the surface of its enormous potential.

While its membership is free for the basic service offered, there is ongoing interest among many manufacturers to pay



for additional services – they appreciate some of the tools we offer to manage large datasets.

You say GMDN is also used by not-for-profit organizations. Can you give an example?

Wilkinson: It is also used in almost a hundred countries and by non-for-profit organizations, such as Médecins Sans Fron-tières, to help them choose the devices that they need in de-veloping countries and define exactly what they want.

What is the role of GMDN given the European Commission’s de-cision to use Italy’s free-of-charge medtech classification codes (CND) as the basis for the future EU medical device database – Eudamed – instead of GMDN?

Wilkinson: To say that we were disappointed that the Euro-pean Commission decided to hand this to CND of Italy is an understatement.

GMDN was established under the jurisdiction and steering of the Global Harmonization Task Force [GHTF], effectively the predecessor of the International Medical Device Regula-tors Forum [IMDRF]. It is a globally harmonized nomenclature that has been designed to avoid ambiguity.

In our view, the commission decision will add a cost burden to manufacturers who are able to use the GMDN free of charge, and having stakeholders use different nomenclatures – ie, GMDN

and CND – is not in patients’ interests either. We are struggling to understand what merits the commission’s decision would have.

Is there a chance that the commission’s decision might be reversed?

Wilkinson: I am not the person to answer that. We certainly see that regulators are using and are committed to GMDN, and are supporting our plans to develop our services.

The importance of GMDN is recognized by the European Commission, which has suggested they will map GMDN to CND – although we do not know how that will work. We are asking a lot of questions, though, and are prepared to work with the commission to see if we can help resolve any issues.

Where does the GMDN fit with UDI?

Wilkinson: GMDN is one part of the device identification system and sits alongside Unique Device Identification [UDI], a requirement in the context of the EU’s MDR and IVDR.

UDI is specific to the actual device itself, whereas GMDN al-lows devices to be accurately categorized according to col-lective terms for the unambiguous exchange of information.

To give one important example, we recently introduced differ-ent collective terms for breast implants to differentiate between implants with different surface textures. This is helping in ana-lyzing the potential link between breast implants and anaplastic large cell lymphoma (ALCL), a rare type of non-Hodgkin lympho-ma (NHL). UDI would specify the implant and its manufacturer.

When UDI becomes fully operational in the context of the EU MDR and IVDR, GMDN utility will go through the roof as GMDN helps to group products in ways that help to analyze characteristics associated with categories of products, rather than at individual product level, such as comparing bare- metal stents with drug-eluting stents. We are already respond-ing to opportunities that relate to UDI implementation. The more rapidly UDI opens up worldwide, the more it will open up GMDN possibilities too.

What changes do you hope to bring about at the GMDN? And how do you see the GMDN in five years’ time?

Wilkinson: As chairman of the GMDN, I want to further build operational performance. My primary goal is to help stakehold-ers realize the full value of our system and exploit it, as its po-tential is currently underutilized. We have the tools to sort criti-cal information in an era where big data is opening up new and faster ways of understanding products. Within five years, I ex-pect GMDN to have penetrated the market significantly further. I expect a high level of engagement and involvement among stakeholders in the nomenclature. I foresee health systems and regulators globally seeing us as a go-to place for information that they can integrate into their systems.


GMDN ExplainedGMDN is a global authority for naming and grouping medical devices and a master data source. It defines boundaries between technologies in an objective and disciplined way and offers a free basic service to customers, as well as a charging service with more functionality – useful for customers who are dealing with large numbers of products.

GMDN is a list of generic names used to identify all medical device products. The GMDN agency is a nonprofit organization responsible for the ongoing maintenance of GMDN.

The main purpose of GMDN is to provide health authorities and regulators, health-care providers, manufacturers, and others with a naming system that can be used to exchange medical device information and support patient safety.

Currently it lists more than 25,000 categories of medical devices, with around 700 new categories created in 2018.

GMDN is used for data exchange between manufactur-ers, regulators and health-care authorities; exchange and analysis of market surveillance and vigilance infor-mation; supporting inventory control in hospitals; and purchasing and supply chain management.



� C O V E R S T O R Y �

Indian government, so it lobbied Con-gress to intervene on that issue, while the MITA pressed Congress and the CMS for better reimbursement of diagnostic radiopharmaceuticals.

AdvaMed, the MDMA and the NEMA/MITA do not limit their lobbying efforts to press for medtech-tax repeal or other issues to conversations with federal leg-islators and their staff members behind closed doors. The groups also appeal to legislative staff and congressional lead-ers for votes favoring medtech causes through splashy advertising campaigns via TV ads in legislators’ home districts, or large advertisements at public bus stops in the greater Washington, DC, area, where congressional staffers can see them. (Also see “Medtech Groups To Blitz Congress Before Expected House Device Tax Vote” - Medtech Insight, 2 Jul, 2018.)

For example, on 24 September, Ad-vaMed, the MDMA and the MITA put to-gether a letter signed by more than 600 medical innovators, physician inventors, patient groups and device firms, and sent it to congressional leaders, appealing to them to permanently repeal the device tax. (Also see “AdvaMed Chair: Another De-vice Tax Moratorium More Likely Than A Full Repeal” - Medtech Insight, 24 Sep, 2019.)

Also, judging by the mentions of differ-ent topics lobbied on in each of the three trade groups’ reports filed with Senate officials, each group focused on a unique mix of hot-button political interests.

ADVAMED RELIES ON HIRED FIRMS TO SPREAD MEDTECH-TAX REPEAL MESSAGEAdvaMed, like the other trade groups, used hired government-affairs experts like Andrew Kauders, David Adams and Claudia James of Cogent Strategies LLC, spending $110,000 to have the firm’s top guns help persuade members and congressional staffers of the necessity of device-tax repeal, according to the lobby reports. (See Exhibit 1, above.)

Most of the working lobbyists in each of the firms paid by AdvaMed and other trade groups to advocate for them are former congressional staffers themselves;

for example, Kauders served as an execu-tive director of the US House Democratic Caucus, where he developed political, legislative and message strategies, and as senior advisor for Sen. Robert Menendez, D-NJ, when the senator sat on the Senate Finance Committee.

Similarly, AdvaMed paid lobbyists at Simmons & Russell Group LLC to bend legislators’ ears on how the device tax might impact innovation within the in-dustry – according to the lobby records – or cause job losses in congressional dis-tricts. The trade group also paid Williams and Jensen PLC $110,000 to lobby solely for them on the Senate version of medi-cal-device-tax repeal, S. 692.

However, when it hired other groups, including Olsson, Frank, Weeda, Terman & Matz PC (for $100,000) and BGR Gov-ernment Affairs (for $100,000), AdvaMed had the groups lobby on CMS reimburse-ment for medtech, device-tax repeal and reauthorization of the device user-fee program at the FDA.

The lobby reports also revealed that Ad-vaMed has been lobbying on a new front – to influence environmental rules. For example, one of the reports say AdvaMed paid CGCN Group LLC $15,000 in the sec-ond quarter of 2019 to lobby on “environ-mental regulations related to commercial sterilizers for medical equipment,” an issue that first came to the fore in March when

the US Environmental Protection Agency closed two medtech plants that used ethyl-ene oxide (EtO) to sterilize devices. (Also see “Sterilization Facility Shutdowns Could Spell Medical Device Shortage; FDA Urges Firms To Assess ‘Downstream Impacts’” - Medtech In-sight, 26 Mar, 2019.) Problems with EtO use is an ongoing issue, most recently in the state of Georgia. (Also see “Industry, AJC Duke It Out In Georgia Over Ethylene Oxide Risk” - Medtech Insight, 23 Sep, 2019.)

ADVAMED LOBBYISTS FOCUS ON MEDICARE COVERAGE, FRAUD AND ABUSE LAWSIn total, AdvaMed’s in-house lobbyists – Riley Swinehart, Duane Wright, Amanda Walsh and Greg Crist – identified at least 22 discrete medtech and diagnostic causes they lobbied for between 1 Janu-ary and 30 June, in the Senate reports, in-cluding medical-device-tax repeal.

Crist, AdvaMed’s chief advocacy officer, previously served as press secretary for former House Majority Leader Dick Armey, R-TX, and also as communications direc-tor for the House Republicans, so he has developed a strong network of Capitol Hill contacts.(Also see “ AdvaMed’s Top Hill Strategist JC Scott Departs; Greg Crist Will Fill Role” - Medtech Insight, 20 Sep, 2018.)

AdvaMed’s in-house experts lobbied for medtech causes as diverse as device cyber-security protections, Medicare coverage

CONTINUED FROM PAGE 1 EXHIBIT 1

AdvaMed Dollars Spent Lobbying In 2019

AdvaMed (own lobbyists)

Cogent Strategies LLC

The Simmons & Russell Group LLC

Olsson, Frank, Weeda, Terman & MatzPC

BGR Government Affairs

Williams and Jensen PLC

CGCN Group LLC

0.2M 0.4M 0.6M 0.8M 1M 1.2M 1.4M 1.6M

Lobb

y Fi

rm

Dollars Spent ($)

Total Spent By AdvaMed: $2.05 million Source: Center for Responsive Politics OpenSecrets.org database

Total Spent By AdvaMed: $2.05m



and reimbursement, third-party servicing of devices, and diagnostics-payment reforms.

A breakdown of the money and time spent by AdvaMed lobbying for specific issues is summarized in Exhibit 2, at right.

The group’s government-relations ex-perts also talked to legislators and congres-sional staff about modernization of fraud and abuse laws, such as the Anti-Kickback Statute, which industry has proposed safe harbors from to shelter value-based pric-ing deals and risk-sharing arrangements that its members favor. (Also see “Industry Requests Three Additional Safe Harbors Un-der Anti-Kickback Statutes” - Medtech In-sight, 29 Oct, 2018.)

MDMA FOCUSES ON TAX REPEAL, MDUFA, PATENT REFORM ACT Meanwhile, the MDMA spent S170,000 of its in-house government affairs expertise and hired-firm lobbying dollars – out of a total of $600,000 in Q1 and Q2 2019 – on medical-device-tax repeal issues.

For example, the MDMA paid policy experts at The McManus Group $60,000 and at O’Rourke & Nappi LLP $40,000 to lobby exclusively on medtech-tax repeal, while spending about 10%, or $60,000, of its own in-house lobbyists’ time on the ef-fort. (See Exhibit 3, at right.)

The MDMA also pushed hard for patent law reform this year, to make the intel-lectual property (IP) protection process fairer for small- to moderate-sized device companies, and that is reflected in the trade group’s $60,000 spend on the issue. For example, Leahey, the MDMA CEO and a top lobbyist for industry, told Medtech Insight in a March podcast interview that patent trolls, who can infringe on IP, need to be controlled, and that at some points in the past, Congress has looked at overarch-ing, sweeping changes that would make it much easier and cheaper to infringe on IP.

“For medical technology companies, par-ticularly the small innovative companies we work with, strong IP is critical to ensur-ing that your technology is uninfringed,” Leahey said at the time. (Also see “Podcast: MDMA CEO Mark Leahey On Industry’s Hot Topics” - Medtech Insight, 18 Mar, 2019.)

The MDMA also sees implementation of the Medical Device User Fee Act in its

most recent, 2017 enactment (MDUFA IV) as a high priority, Leahey said in the same interview. The group spent roughly $60,000 – or 10% – of its lobbying dollars in 2019 on that issue, as well as in prepa-ration for future device user-fee negotia-tions with the FDA and Congress.

Another lobbying effort supported by the MDMA (and AdvaMed) that has borne fruit this year was getting Congress and the CMS to agree to remove barriers to ac-cess for medtech products on the market

by allowing coverage under Medicare for breakthrough devices. Lobby reports on behalf of the group shows it paid in-house lobbyists and Thorn Run Partners about $70,000 in total to lobby for better Medi-care coverage. The announcement about the coverage for breakthrough devices was made by CMS chief Seema Verma at the MDMA’s annual meeting in April. (Also see “Breakthrough Devices To Get Special US Medicare Reimbursement Under CMS Pro-posal” - Medtech Insight, 24 Apr, 2019.)

EXHIBIT 2

Dollars Spent By AdvaMed Lobbying Specific Issues In Early 2019, In Percents Of Total Lobbying Dollars

Other issues combined: Cures Act, Dxregs, ACA, Medtech innovation, etc. 29%

Device tax repeal, S.692, H.R.2207(AdvaMed + hir 19%

Tradeissues(USMCAtrade deal,Indiamedtechprice caps) 6%

Diagnosticspaymentreform, PAMAimplementation 6%

Cybersecurityfor medtech 6%

Medtechandopioidusereduction,SUPPORTAct 6%

Medicarecoverage andreimbursementissues 5%

Stark law andAnti-KickbackStatute reforms 5%

Improving FDAmedtechregulations 4%

Third party servicing ofdevices 3%

Tele

heal

thse

rvic

es

3%

FDAR

A (d

evic

eus

er-fe

e bi

ll)im

plem

enta

tion

3%

Appropriationsbill lapses(H.R.1362) 3%

Source: Center for Responsive Politics OpenSecrets.org database

EXHIBIT 3

MDMA Dollars Spent Lobbying In 2019

MDMA (own lobbyists)

The McManus Group

O'Rourke & Nappi LLP

Thorn Run Partners

50K 100K 150K 200K 250K 300K 350K 400K 450K 500K 550K 600K

Lobb

y Fi

rm

Dollars Spent ($)

Total Spent By MDMA: $740,000 Source: Center for Responsive Politics OpenSecrets.org database

Total Spent By MDMA: $740,000




NEMA LOBBIES ON MEDICAL DEVICE SERVICING, TRADE ISSUES, CYBERSECURITYIn 2019, the NEMA and the MITA, which pri-marily focus their lobbying time on issues of importance to the advanced imaging industry, spent roughly $1.09m on device-tax repeal, third-party servicing of devices, and a big chunk of dollars (about 15% of its total) pushing Congress and federal agencies for medical device cybersecurity reforms. (See Exhibit 4, at right.)

The NEMA spent $87,490 on its own in-house lobbyists and paid the Capitol Hill lobbying firm Kountoupes Denham Carr & Reid LLC around $16,000 (about 10% of $160,000 paid to the firm) to lobby for device-tax repeal, according to lobby re-ports. It also paid Tarplin, Downs & Young LLC – another government relations firm – $7,616 to also lobby for repeal of the tax.

Other dollars spent by the NEMA and its hired lobbying guns were devoted to “cy-bersecurity issues,” (around 13% of the total NEMA spent), medical device servicing and

CMS coverage of devices (including for con-trast agents used during imaging processes).

Reimbursement of diagnostic radio-pharmaceuticals was also an important lobbying push by the NEMA, and it paid

its subsidiary group, the MITA, about $100,000 in 2019 to lobby Congress and the CMS exclusively on that topic.


Q&A: Former FDA Coronary Device Officer Hops To GoreELIZABETH ORR [email protected]

D evice-maker W.L. Gore & Associ-ates is putting new focus on its structural heart product pipeline

with the recruitment of a former US Food and Drug Administration cardiac devices medical officer.

John Laschinger began his career as a car-diac surgeon and cardiovascular researcher at Johns Hopkins University and the Univer-sity of Maryland School of Medicine before joining the FDA in 2010. At the agency, he

served as a medical officer in the coronary and structural hart device areas before ris-ing to chief medical officer in the Office of Clinical Evidence and Analysis. The FDA re-peatedly recognized Laschinger for his work on considering patient populations and use of the total product life cycle approach to device review. He also collaborated on the American College of Cardiology’s National Cardiovascular Data Registry.

Laschinger’s responsibilities as cardiac

chief medical advisor at Gore will include ad-vising on the firm’s clinical device develop-ment priorities and pipeline strategy, lead-ing cross-industry collaborative efforts on medical and regulatory issues, and increas-ing the company’s use of patient input. He will be based in Gore’s Flagstaff, AZ, office.

Medtech Insight spoke with Laschinger on 30 September. A transcript of the con-versation is below, and has been lightly edited and condensed for clarity.

Medtech Insight: What are you proudest of from your time at the FDA?

John Laschinger: There are three different areas. I think that first and foremost, as a medical officer I was involved in the approval of various medical devices that really covered the entire field of the percutaneous treatment of heart dis-ease, such as Edwards’ Sapien family of transcatheter valves and Medtronic’s CoreValve family of transcatheter valves. I

was also involved in the approval of devices for the treatment of heart failure and drug-coated stents for the treatment of coronary artery disease. The second thing that I was most proud of was working as a key participant with outside orga-nizations to provide definitions, or endpoints and outcomes, in the structural heart disease area. And then finally, I was on the writing team for several of the guidances that have come out of the FDA related to the use of real-world evidence in the pre- and postmarket evaluation of medical devices.

EXHIBIT 4

NEMA/MITA Dollars Spent Lobbying In 2019

NEMA (own lobbyists)

Kountoupes Denham Carr & Reid LLC

Tarplin, Downs & Young LLC

Capitol Counsel LLC

100K 200K 300K 400K 500K 600K 700K

Lobb

y Fi

rm

Dollars Spent ($)

Total Spent By NEMA: $1.09 million

Source: Center for Responsive Politics OpenSecrets.org database

Total Spent By NEMA: $1.09m

� P O L I C Y & R E G U L A T I O N �



What changes did you notice at the FDA during your time there?

Laschinger: I think the FDA became much more centered on unmet clinical needs and trying to bring devices to market that would be useful in treating those. They became much more aware of patient perspectives, and patient-reported or patient-centered outcomes, and also began to focus more on the use of real-world evidence for both premarket and postmarket uses. Overall, it became a much more patient-centered organization.

Is there any advice you would give device manufacturers about working with the FDA?

Laschinger: The most important advice is that the FDA is very open to innovation. They want you to come to them early. They want you to come to them often. They want to in-teract with you and then really work with you to make sure that whatever device you’re working on is the best possible device for patients. And really the best way to achieve that is by working cooperatively with the FDA to attain those goals.

You haven’t worked for a device manufacturer before. What made this seem like a good time to move to the industry?

Laschinger: I got to a point at the FDA where I really was in-terested in taking my career in another direction, but staying in the medical device field. Obviously the clinical in my career was on the user end and at the FDA, I was at the regulatory side, and this is really the development side of devices, and I really wanted to get some experience in that area as well.

What are some of your goals at Gore?

Laschinger: We’re trying to watch for new areas in the cardiac-device field where we can apply the differentiat-ing technologies that Gore has and innovate breakthrough devices that physicians can use to provide meaningful, long-term benefits to the patients. We’re focusing on the structural heart field, which involves new and innovative technologies for treatment of structural disease and heart failure primarily, as well as everything from stroke preven-tion to migraine headaches, to closure of holes in the heart with devices. So it’s really a broad spectrum of things that we’re focusing on at Gore.

What do you think are some of the most exciting recent trends or developments in the cardiac device field?

Laschinger: Obviously from a surgeon’s perspective it’s the shift to percutaneous treatment of essentially everything. The thing about percutaneous treatment is, not only is it safer for the patient and less invasive for the patient, but it gets them back to their life quicker with shorter recoveries. But also, as the field develops and as safety is improved, you attack dis-ease at an earlier stage in its life cycle than would be recom-mended with surgery because of its invasiveness and morbid-ity and mortality risks. So it’s really changing the whole way we’re looking at structural heart disease and heart failure, and allowing us to reimagine the way we treat these diseases.


Work With Specialty Societies Before Taking Hip And Knee Procedures Off IPO-Only List, MDMA Advises CMSSUE DARCEY [email protected]

T he Medical Device Manufacturers Association (MDMA) has advised the Centers for Medicare and Medicaid Services (CMS) to consult closely with orthopedic societies before fi-

nalizing a proposal to permit outpatient facilities and ambulatory surgery centers (ASCs) from performing knee and hip procedures.

“MDMA recommends that CMS consult closely with surgeons and their representative organizations regarding the clinical suit-ability of both of these proposals,” commented MDMA president and CEO Mark Leahey. The Medicare agency has proposed allow-ing total hip arthroplasty (THA) and total knee arthroplasty (TKA) to be performed in outpatient settings in proposed Outpatient Prospective Patients System (OPPS) rules released in early July.

Leahey added, “it is imperative that surgeons continue to have the option to select the appropriate [surgical] setting,” after care-fully assessing the needs of the individual patient.




He pointed to a joint statement by the American Association of Hip and Knee Surgeons, the American Academy of Ortho-paedic Surgeons, and The Hip Society and The Knee Society, that highlights a number of factors to be considered before surgeons should discharge on the same-day outpatient basis for the surgeries. Among these is the need to minimize compli-cations and to consult evidence-based protocols for pain man-agement, Leahey said.

CMS MUST INFORM PATIENTS ON RISKS OF SAME-DAY DISCHARGEThe MDMA also recommended that the CMS provide guid-ance on provider use of a predictive tool to inform discharg-

ing hip and knee surgery patients, and on fully informing pa-tients and their families as to the potential risks and benefits of same-day discharge.

In its comments on the proposal, AdvaMed also advocated that physician discretion must apply for patients undergoing hip and knee arthroplasties.

The group further said if the agency does finalize the proposal, “we recommend that CMS monitor the results of the ASC-17 [stan-dard], ‘Hospital Visits After Orthopedic Ambulatory Surgical Cen-ter Procedures,’ to assess any changes in complication rates as TKA and THA procedures are introduced into the ASC setting.”


US FDA Toying With Idea Of ‘Regulatory Legos’ In MDUFA VFERDOUS AL-FARUQUE [email protected]

A s the US Food and Drug Administration begins gearing up for user-fee negotiations with the medtech industry starting next year, the head of the agency’s Center for

Devices and Radiological Health (CDRH) has floated the idea of developing so-called regulatory building blocks. He says the concept would be to give the FDA broader powers, thereby re-ducing its need to constantly ask Congress to authorize specific programs that are not explicitly stated under statute.

On 25 September, top officials from the device center spoke at a town hall meeting with industry at the 2019 MedTech Con-ference in Boston, MA. In his closing remarks, CDRH director Jeff Shuren noted that negotiations under the Medical Device User Fee Amendments (MDUFA) were on the horizon and said industry should begin thinking about the future of medtech regulations.

“I would like to put a little bit of a bug in folks’ ears,” Shuren said. “We are going to, believe it or not, have to start thinking about MDUFA V soon, like next year… and we’ll start with a pub-lic meeting to make sure the public has an opportunity to weigh in, as well.”

In 2002 Congress passed the Medical Device User Fee and Modernization Act, which allowed the FDA to collect user fees for reviewing devices and diagnostic tests, while also setting standards on how those reviews are conducted and the time-frames for the reviews. Since then the act has been renewed three times and industry is currently operating under MDUFA IV. (Also see “MDUFA IV (And More) Is Law: Trump Signs A Health-Care Bill” - Medtech Insight, 18 Aug, 2017.)

During the previous MDUFA negotiations, the operative phrase was real-world evidence (RWE). At the time, Shuren called for a massive paradigm shift in the US regulatory system, where certain medical devices could come to market sooner with less premarket data but with guarantees that the manufacturer would provide more postmarket data on safety and efficacy, or RWE. This meant companies could get devices to patients sooner

while also continuing to grow the RWE data to allow the FDA to make sure the product meets its standard of safety and efficacy. (Also see “Real-World Evidence User-Fee Funding Praised At FDA Meeting” - Medtech Insight, 2 Nov, 2016.)

“This go-around, we’ll be thinking about where do we want to be as an ecosystem at the end of MDUFA V, or maybe even at the end of MDUFA VI,” Shuren said.

He said the goal is to think about what is best for patients, and then set goals in MDUFA V to support those goals.

Shuren noted that the medtech industry is moving at a rapid pace with more complex science and technologies coming to the forefront, which means the industry is moving a lot faster than the current regulatory framework which was put in place

“Should we have building blocks,

something we call ‘regulatory Legos’?”

– Jeff Shuren



decades ago. He said the FDA and industry need to rethink the regulatory process.

“Do we want to have regulatory frameworks in which every few years we’re running back to Congress to make changes be-cause that is a multiyear process?” Shuren asked. “Should we re-ally have cookie-cutter pathways? Or should we have building blocks, something we call ‘regulatory Legos,’ where we have enough tools to put it together to best meet those new technol-ogies that are going to come both today and in the future, so we don’t have to keep going back to Congress to make changes?”

One example he gave of the hurdles the FDA is currently fac-ing is how it is allowed to regulate certain medical software, known as software as a medical device, or SaMDs. The agency has released a number of guidances outlining how it will use a risk-based regulatory oversight to allow such product on the market and is currently working on a precertification program where manufacturers could get their digital health product on the market based on a level of trust from the FDA. (Also see “One Small Step For US FDA, But Maybe A Giant Leap For SaMDs” - Medtech Insight, 23 Jul, 2019.)

However, because of the current statutory constraints on how the FDA can regulate such products, Shuren said, it will take the agency years to get the regulatory pathway up and running. He said this means the agency will continue to lag behind technol-ogy, when really the agency needs to be out in front to help get new technologies to patients.

Over the years, Shuren has proudly said that the CDRH is the “gold standard” of global medical device regulations. But he now wants to move away from that concept, noting that while he appreciates the idea of being the regulatory regime that other countries can look up to, he’d like for the phrase “to fall away from our lexicon” in an effort to embrace a more global view of medtech regulations.

“I would not view us as the gold standard; we’re merely a standard out there,” Shuren said.

Since he joined the FDA, Shuren has also been a strong advo-cate of the concept of global harmonization, where products can be regulated in a more standardized way, allowing them to enter multiple markets at the same time. To make this happen, he said industry and regulators need to do away with the idea of a gold standard and instead be willing to look to other countries for how their regulations may be helpful in advancing better regulations.

“We have to recognize that there is a lot of innovative things going on in other countries, there are a lot of experts sitting in other countries, there’s data sitting in other countries, and we have to really think about we’re members of a global commu-nity and not about everything with the US first,” Shuren said. “Let’s focus on being international citizens [and] having an in-ternational system – and maybe that is one of the places where we should be going as we look to MDUFA V and beyond.”

If past is prologue, MDUFA V negotiations will likely to begin sometime in the middle of 2020.


SUE DARCEY [email protected]

A dvaMed has criticized a 2020 Medicare Outpatient Pro-spective Payment System (OPPS) proposal mandating that hospitals publicly post prices for their 300 most-

frequently used procedure costs and lab tests. The medtech industry advocacy group commented that the

transparency plan laid out in the draft OPPS rule issued by the US Centers for Medicare and Medicaid Services (CMS) could provoke anticompetitive responses from insurers, and warned it would limit patient choice and run afoul of confidentiality re-quirements for disclosure of laboratory service rates. (Also see “Device-Related Procedure Costs To Be Revealed Under CMS Pro-posed Payment Rule” - Medtech Insight, 31 Jul, 2019.)

Under the proposed transparency rule that would take effect on 1 January 2020, the CMS would mandate that each hospi-tal in the US post its charges and negotiated prices for hospital procedures, advanced imaging scans, supplies and laboratory tests on a publicly available website. Hospital and insurance companies have protested the plan, and now AdvaMed is rais-ing doubts about it in written comments, although the group does agree with the general concept of providing patients with information to let them make informed decisions regarding their health-care choices.

On a different matter, AdvaMed and Medical Device Manu-facturers Association (MDMA) endorsed and encouraged the CMS to go forward with an alternative payments pathway for 2020 covering breakthrough devices for three years. (Also see “Breakthrough Devices To Get Special US Medicare Reimburse-ment Under CMS Proposal” - Medtech Insight, 24 Apr, 2019.)

Both groups made suggestions for improvements to the breakthrough passthrough payment plan, however.

ADVAMED: TRANSPARENCY RULE COULD PROVE ANTICOMPETITIVEAdvaMed said it “urges CMS to proceed cautiously as it considers policies that could be detrimental to existing competitive health-care markets.” The group’s executive VP for payment and health, Don May, cited the American Hospital Association, which said earlier this year that the CMS proposal could seriously limit the choices available to patients and fuel anticompetitive behavior.

May also commented that laboratories, and hospitals that contract with labs, may be violating other regulatory require-ments by disclosing their rates. In the agency’s initial transpar-

AdvaMed Pans CMS Plan To Mandate Publicizing Hospital Rates, But Likes Pay Path For Breakthrough Devices




ency proposal on 29 July, it spelled out a preliminary list of labo-ratory and pathology services for which it wants every hospital to disclose prices. The lab services list included at least 14 differ-ent diagnostic tests, among them “basic metabolic panel,” “kid-ney function panel” and “complete blood count, automated.”

However, “Section 1834 of the Social Security Act requires pri-vate-payer rates reported by applicable laboratories to be kept confidential by CMS,” May noted, adding that the logic under-girding the provision “should apply to the disclosure of similar information by hospitals.”

EXPEDITED ACCESS DEVICES ELIGIBLE FOR SAME BREAKTHROUGH PAYMENTS?While throwing its support behind the Medicare agency’s pro-posal to provide a streamlined pathway for approving alternative payments for breakthrough technologies, AdvaMed also argued that slightly older devices under an FDA expedited access pro-gram be granted the same Medicare payments.

“AdvaMed recommends that CMS also consider devices that had previously entered the FDA’s Expedited Access Pathway pro-gram … as breakthrough for purposes of the proposed alterna-tive pass-through program,” the group wrote.

Further, the group says applicants with breakthrough prod-ucts should not have to hold off on applying for CMS payment passthrough status until 1 January 2020, but should be able to

apply by the first business day in September 2019 to be eligible for passthrough payments starting on 1 January.

MDMA: REMOVE THE SINGLE-USE DEVICE CRITERIAThe MDMA also made several requests surrounding the passthrough payment program in its comments. First, it recom-mended that the CMS expand the proposal by removing the single-use device criteria for obtaining passthrough payments so additional breakthrough devices could qualify.

In addition, because the innovative products that go through the Food and Drug Administration’s breakthrough device pro-gram provide effective treatment or diagnosis of debilitating diseases or conditions, the CMS “should create new categories for them,” MDMA wrote, a step that would be analogous to the agency’s decision to treatment breakthrough devices as “new” for purposes of new technology add-on payments.

The group also suggested that information about the clinical use and efficacy of breakthrough device services – such as peer-reviewed articles – should not be required to be submitted to the CMS in support of the passthrough payments. Such a change would “ensure Medicare beneficiaries have access to critical and lifesaving new cures and technologies,” MDMA president and CEO Mark Leahey wrote.


Australia Suspends Breast Implants Over Cancer Risk FearsNEENA BRIZMOHUN [email protected]

A ustralia’s Therapeutic Goods Administration has sus-pended the sale of eight breast implant models and im-posed strict conditions on all other breast implants and

tissue expander devices that remain available.The move is based on findings from the review the TGA carried

out this year into the link between such products and breast im-plant associated anaplastic large cell lymphoma (BIA-ALCL).

The latest suspensions follow breast implant bans this year in France and Canada in response to the rare but serious risk of de-veloping BIA-ALCL. Other countries are also keeping a close eye on the situation, including the US and the UK.

The TGA had recommended taking regulatory action in July when the results of its review first became available, and has now issued a formal decision.

The products suspended are macrotextured (grade 3 and 4) and microtextured implants that are manufactured by four companies: Allied Scientific Products, Emagin, Euro Implants and JT Medical.

They will not be available on the Australian market for the next six months, the TGA said. During this time, the manufacturer will be given the chance to provide additional information to the agency about their implant’s safety and performance.

Any stock of these un-implanted devices in the market will also

be recalled during the suspension period. No models of breast tissue expanders have been suspended.

The TGA said that a suspension can be revoked if concerns about the devices are addressed to its satisfaction. If concerns persist, the suspension may be extended or the entries of the devices on the Australian Register of Therapeutic Goods may be cancelled, it warned.

The agency also noted that since starting its review in May, two



sponsors have chosen to withdraw their products from the mar-ket. Allergan recalled its Biocell macro-textured breast implants and tissue expanders (the company also recalled its Biocell im-plant globally), and AirXpanders’ local sponsor, Emergo Austra-lia, pulled the company’s Aeroform tissue expanders. (Also see “Worldwide Recall On Allergan Textured Breast Implants” - Medtech Insight, 24 Jul, 2019.)

According to the TGA, the suspensions and cancellations affect 13% of the supply of breast implant devices on the Australian market by volume (based on 2018 data).

STRICT CONDITIONSRegarding the newly introduced conditions for those implants and tissue expanders that are still on the market, sponsors now have increased requirements for providing information to practi-tioners and consumers, and for reporting adverse events:

• All cases of BIA-ALCL must be reported to the TGA within 10 working days of the sponsor being aware of the case;

• Six monthly reports of Australian and world-wide supply data, complaints and adverse events are to be provided to the TGA; and

• Clear, written information about the risk of BIA-ALCL must be provided with all devices, to both clinicians and patients.

If a sponsor fails to comply with any condition of inclusion, the device may be removed from the Australian Register of Thera-peutic Goods, the TGA warned.

Australia is among a host of countries that have been investi-gating the link between certain breast implants and the develop-ment of ALCL.

As previously noted by the TGA, BIA-ALCL does not seem to occur with smooth implants but rather with textured or polyure-thane devices. In addition, expert opinion has put the risk of ALCL at between 1-in-1,000 and 1-in-10,000. In Australia, there have been around a hundred cases of the disease, including four deaths.

The TGA’s decision to take regulatory action on the implants and tissue expanders follows recommendations the agency is-

sued in July when the results of its review first became available. At that time the regulator had given the affected sponsors until 24 July to provide it with additional information before it reached a final decision.

The agency’s review involved laboratory testing of the prod-ucts concerned and a full statistical review of all BIA-ALCL cases reported up to the end of May 2019. In addition, the TGA took into account information from industry sponsors and manufac-turers, advice from its Breast Implant Expert Working Group, and submissions and information from stakeholders and patients.

MOVES ELSEWHEREAs for regulatory action overseas, in April France’s regulator, ANSM, withdrew from the market macro-textured implants that have a texture equivalent to the Allergan Biocell envelope, as well as polyurethane implants, as a precautionary measure. Its decision related to products made by Allergan and five other manufacturers.

Health Canada on 27 May suspended the licences for Allergan’s Biocell breast implants, which were the only macro-textured im-plants available in Canada.

Certain other countries are not ready to ban the implants just yet. In the UK, for example, the regulator has put in place mea-sures to track the situation and to ensure that women receiving breast implants are warned about the risks of BIA-ALCL.

In the US, the Food and Drug Administration asked Allergan to recall its Biocell textured breast implants and tissue expanders, and released a safety communication citing additional data link-ing the implants with ALCL.

Meanwhile, in the Netherlands, the regulators have said there is not enough evidence to merit withdrawing currently available textured implants. They noted that that cases of BIA-ALCL oc-curred primarily with Allergan’s Biocell implants but that these products were no longer on the market in the Netherlands.


Intelligence with a Global PerspectiveThe Premier Resource in the Life Sciences Industry

To find out more, visit: www.pharmaintelligence.informa.com




Australia Reviews Ban On Many Self-Testing IVDs NEENA BRIZMOHUN [email protected]

A ustralian regulators are consider-ing whether to relax or otherwise change their rules prohibiting the

supply of certain IVDs designed for self-testing at home.

The rules are set out in the Therapeu-tics Goods Administration’s Excluded Purposes Specification, which came into force in July 2010.

They cover a range of self-testing IVDs, such as genetic tests and those for most infectious diseases, that the regulators were worried might cause more prob-lems than they solved if they were made available for home use by lay people. For example, there have been concerns about the accuracy of such tests and the ability of users to interpret their results.

In accordance with Australian legisla-tion, the Excluded Purposes Specification is due to sunset on 1 October 2020. The TGA has therefore launched a public con-sultation gauge whether the provision is still fit for purpose and whether there is still a need to prohibit the supply of cer-tain self-tests in Australia.

The regulators say that there “may be benefits to wider availability of IVDs for self-testing which outweigh the risks associated with their use depending on the steps that can be taken to mitigate concerns.”

It notes that the Excluded Purposes Specification was amended in 2014 to al-low for the supply of HIV self-tests in Aus-tralia. Here, it was said that the benefits of making HIV self-tests available included an increase in the overall rate of testing for HIV and a reduction in the number of undiagnosed cases of HIV in Australia. Measures were also put in place to miti-gate the risks associated with the use of HIV self-tests.

At the moment, the types of self-test-ing IVDs prohibited from supply include tests for the presence of, or exposure to, pathogenic organisms or transmissible agents (other than HIV), and genetic tests to determine the presence of, or suscepti-bility to, diseases. They also include tests

to diagnose, aid in diagnosis or indicate the presence of a serious disease or con-dition, such as cancer or myocardial in-farction, and tests for markers that are precursors to a serious disease or condi-tion, such as Pap smear tests or prostate specific antigen tests.

In the new consultation, the TGA wants to know whether any of the prohibited self-tests for infectious diseases, genetic testing or determining the presence of other seri-ous diseases should be permitted for sup-ply. It is also seeking comments on whether there are any tests that should not be made available in Australia, and why, and inviting suggestions on how potential risks to con-sumers could be mitigated.

It says that technological develop-ments in recent years have made IVDs for self-testing less expensive and more readily available. There is also a growing desire by consumers to have more say in their health-care decisions.

In addition, the TGA says that“self-testing devices may have a role to play in early screening for certain diseases and making testing available to consumers who would not otherwise be tested.”

Nevertheless, the regulators note that there are concerns regarding the accu-racy of these tests, which may not be of the same standard as a laboratory test. Poor test accuracy could mean that the test gives a false-negative or false-posi-tive result.

It is also important to ensure that self-tests can be easily performed by inex-perienced users and that the user can interpret the results correctly. Access to appropriate support services and follow-up testing may also be an important consideration.

The deadline for submitting comments to the consultation is 22 November.

The TGA then plans to review the feedback received and make recom-mendations to the government on whether the Excluded Purposes Speci-fication should be remade and, if so, whether it should be amended in any way. It would then notify stakeholders of any changes in the operation of the Excluded Purposes Specification that are agreed by government.



� C O M M E R C I A L �

Lantheus Buys Progenics To Combine Radiopharmaceuticals With Precision DiagnosticsREED MILLER [email protected]

D iagnostic imaging agent company Lantheus Holdings Inc. will acquire Progenics Pharmaceuticals Inc., the developer of radiotherapeutics and imaging agents to

treat cancer, in an all-stock deal announced on 2 October.During a 2 October conference call announcing the deal, Lantheus

CEO Mary Anne Heino said she expects Progenics’ line of radiophar-maceuticals to complement Lantheus’ line of imaging products for neuroendocrine tumors and prostate cancer. “The combination of Lantheus and Progenics has a clear and compelling rationale,” she said. “This transaction leverages our core capabilities, including proven commercial and operational expertise while diversifying our revenue streams by broadening our presence in emerging uses of radioisotopes in precision diagnostics, as well as the exciting field of radiopharmaceuticals in oncology treatment.”

Progenics CEO Mark Baker said Lantheus’ manufacturing ca-pabilities and supply-chain expertise will allow Progenics’ prod-ucts to maximize their commercial potential. “We will unlock additional value for our stakeholders as we leverage Lantheus’ enhanced resources and R&D capabilities and complementary portfolio of products,” he said.

Under the terms of the deal, Progenics shareholders will receive 0.2502 shares of Lantheus stock for each share of Progenics stock, so the Progenics shareholders will hold roughly 35% of the combined company. The companies did not specify the total value of the deal, but Wells Fargo analysts estimate the deal is worth about $403m.

The exchange ratio implies a 21.5% premium over Progenics’ 30-day volume weighted average closing stock price.

The two companies had combined revenue of $370.1m for the 12 months ending on 30 June. Lantheus recorded $343.4m in revenue in 2018 while Progenics’ 2018 revenue was $15.6m. The merger to generate approximately $15m to $20m in annual cost savings by 2022, mostly from eliminating duplication in general and administrative expenses, as well as improved process and scale efficiencies, Lantheus CFO Robert Marshall said on the call.

DIAGNOSTICS COMPLEMENTING THERAPEUTICSLantheus markets nine products for diagnostic imaging and nuclear medicine, led by Definity, an injectable cardiovascular ultrasound contrast agent made of lipid-coated echogenic mi-crobubbles filled with octafluoropropane gas.

Progenics develops targeted medicines and artificial intelli-gence-based imaging technology for cancer, including the radio-pharmaceutical Azedra (iobenguane I-131), which the company recently launched in the US. The Food and Drug Administration approved it in 2018 as the first drug indicated to treat children and adults with pheochromocytoma and paraganglioma, rare types of cancer afflicting the adrenal gland. Baker said the com-

bined company will evaluate the potential of Azedra to treat other kinds of neuroendocrine tumors.

Progenics’ other approved products include oral and subcutane-ous formulations of Relistor (methylnaltrexone bromide) for opioid-induced constipation in adult patients with chronic non-cancer pain. Progenics licenses Relistor to Bausch Health Companies Inc.

The company is also developing PyL, an F-18 diagnostic imag-ing agent for visualization of bone and soft tissue metastases, and a prostate specific membrane antigen (PSMA) artificial intel-ligence imaging analysis technology for automating the reading and interpretation of prostate cancer PET scans.

BENEFITS OF THE MERGER MAY TAKE A FEW YEARS TO DEVELOPCommenting on the deal in a 2 October note, Credit Suisse ana-lyst Martin Auster wrote: “Given the niche nature of the assets, the potential acquirer universe [for Progenics] is somewhat lim-ited, with Lantheus providing a logical strategic fit.”

Auster concluded: “While the premium is generally on the light-er side of biotech transactions, we believe the combined entity has the adequate resources to continue investment into the combined pipeline and the Azedra launch, and potentially a value inflection point, with lower downside risk for Progenics shareholders.”

In a 2 October note, Wells Fargo analyst Larry Biegelsen wrote: “We see the deal accelerating Lantheus’ top-line growth and improving its gross margin.” Biegelsen projected that the com-bined companies will have revenues exceeding $650m annually by 2023 with Progenics adding about 8 points to the combined company’s growth by 2022.

However, the deal will likely be dilutive until 2022, and because this is the largest deal in Lantheus’ 60-year history, “investors will likely remain skeptical on the deal execution and integration pro-cess,” Biegelsen wrote. Following the announcement, Lantheus’ share price on Nasdaq dropped from $24 to around $19. Progenics shares opened on 2 October at $4.80 and finished the day at $5.48.

The transaction is expected to close in the first quarter of 2020, sub-ject to approval by Lantheus and Progenics stockholders, govern-ment regulatory approvals, and other standard closing conditions.

Heino will be the CEO of the combined company. Bradley Campbell, currently a member of Progenics’ board of directors, will join Lantheus’ board.

Progenics is currently headquartered in New York City. The combined company will be headquartered in Lantheus’ home of North Billerica, MA, and will continue to trade on Nasdaq under Lantheus’ ticker symbol, LNTH.




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TCT 2019: BD, VIVA Data Show Lower Paclitaxel Mortality RiskELIZABETH ORR [email protected]

T wo new studies presented at the Transcatheter Cardiovascular Ther-apeutics (TCT) conference in San

Francisco show a low mortality risk with balloons and stents coated with the drug paclitaxel.

A meta-analysis published in the Jour-nal of the American Heart Association (JAHA) in December 2018 found that pe-ripheral arterial disease (PAD) patients who received devices coated with the drug had a 90% greater risk of death within five years than patients treated in other ways. But the risk was much lower in the patient-level data reviewed by the US Food and Drug Administration and other researchers. (Also see “Newer Data Fades Paclitaxel Risk, Physician Group Says” - Medtech Insight, 11 Sep, 2019.)

Physician group VIVA announced on 26 September that its ongoing meta-analysis now shows an increased mortality risk of about 27%, MedPage Today reported. That’s a modest decrease from data VIVA shared during a June meeting of the FDA’s coro-

nary devices advisory panel, which showed a 38% increase in the mortality risk.

Like other studies, VIVA’s review has not found any mechanism to explain the deaths.

“This updated meta-analysis, which rep-resents the most comprehensive analysis of available individual patient data to date, demonstrated a modest and consistent mortality signal in patients exposed to paclitaxel. However, it did not identify any explanation,” Krishna Rocha-Singh, chief scientific officer at the Prairie Heart Insti-tute in Springfield, IL, said at the meeting.

Meanwhile, an analysis of Becton Dick-inson & Co. (BD)’s Lutonix drug-coated balloon found no statistical difference in mortality rates for PAD patients com-pared to standard percutaneous translu-minal angioplasty. The study, which was funded by BD but conducted by clinical research firm Syntactx, examined patient outcomes from three randomized trials of the Lutonix balloon, with follow-ups ranging up to five years. The reviewers found an 85% survival rate at five years

for Lutonix patients as compared to 86% for standard PTA patients. The difference is not considered statistically significant.

The BD analysis also included a review of causes of death in two of the trials, which found no deaths linked to paclitax-el. There was also no pattern of deaths in any specific category that could indicate a link to paclitaxel, BD said.

BD unveiled the research during a late-breaking session at TCT on 28 September. It was simultaneously published in the Jour-nal of the American College of Cardiology.

“The published patient-level analysis from Syntactx provides important information that health-care providers can use to make an informed decision on the use of pacli-taxel devices until additional long-term data are available,” J.D. Meler, VP of medical and clinical affairs for BD’s peripheral interven-tion business, said in a statement.

The FDA has instructed physicians to dis-cuss potential risks tied to paclitaxel with PAD patients and urged additional research in the area. It plans to update to device la-beling and clinical trial informed consent documents, but has no plans to take the devices off the market. (Also see “FDA An-nounces More Actions On Drug-Coated De-vices” - Medtech Insight, 7 Aug, 2019.)


“This updated meta-analysis ... demonstrated a modest and consistent mortality signal in patients exposed to paclitaxel. However, it did not identify any explanation.”

– Krishna Rocha-Singh


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TCT 2019: Abbott’s Portico TAVR Crosses Non-Inferiority ThresholdREED MILLER [email protected]

O ne-year outcomes from the 750-patient, randomized PORTICO IDE trial show Abbott Laboratories Inc.’s Por-tico TAVR system is non-inferior to Edwards Lifesciences

Corp.’s Sapien and Medtronic PLC’s CoreValve TAVR systems in patients with high or extreme surgical risk.

Greg Fontana of the Cardiovascular Institute of Los Robles in Thousand Oaks, CA, presented the results at the Transcatheter Car-diovascular Therapeutics (TCT) conference in San Francisco on 27 September.

The primary safety endpoint for the trial was all-cause mortal-ity, disabling stroke, life-threatening bleeding requiring blood transfusion, acute kidney injury requiring dialysis or major vascu-lar complications at 30 days. (Also see “EuroPCR 2018: Real-World TAVR Data Show Consistent Performance With Edwards, Abbott, And Medtronic’s Systems” - Medtech Insight, 23 May, 2018.)

In the Portico group, 13.8% of patients suffered at least one of these events compared with 9.6% of patients in the group ran-domized to one of the other valves.

The rates of all-cause mortality or disabling stroke at one year, the trial’s primary endpoint, were 14.9% in the Portico group and 13.4% in the CoreValve/Sapien group.

The differences for both the safety and efficacy endpoints met the prespecified criteria for statistical noninferiority, Fontana reported.

About 28% of patients in the Portico group needed a new pace-maker, compared with about 12% in the CoreValve/Sapien group, and moderate to severe paravalvular leaks were seen in 6.3% of the Portico group and 2.1% of the CoreValve/Sapien group.

Fontana pointed out that the Portico group included a hun-dred patients implanted with the Portico system with Abbott’s FlexNav delivery system. This group showed no deaths or strokes and a 7% rate of major vascular complications. The rate of the composite safety outcome was 8% in this subset of patients.

In a 29 September note, Wells Fargo analyst Larry Biegelsen wrote that Abbott’s next-generation version of Portico will likely perform better than the version tested in PORTICO IDE because it has a better skirt technology to prevent leaks. The company hopes to launch Portico in the US in the second half of 2020, but “we don’t expect Portico to get much traction until the next gen-eration version is launched in the US in 2021 and even then, Por-tico’s role in clinical practice remains unclear,” Biegelsen said.


TCT 2019: TRILUMINATE Six-Month Results Support Abbott’s TriClipREED MILLER [email protected]

T he six-month results from the single-arm TRILUMINATE Feasibility trial confirm Abbott Laboratories Inc.’s TriClip, a tricuspid version of Abbott’s MitraClip mitral valve repair

device, improves both clinical endpoints and quality of life for patients with tricuspid regurgitation.

Lead investigator Georg Nickenig of University Hospital in Bonn, Germany, presented the data at the Transcatheter Cardiovascular Therapeutics (TCT) conference in San Francisco on 28 September.

The 85 patients in the trial treated with TriClip entered the trial with moderate or severe tricuspid regurgitation. Six months after being treated with TriClip, 87% of patients showed a reduction in tricuspid regurgitation, including 57% of patients with moderate or better tricuspid regurgitation. Only 6% of patients showed no im-provement in tricuspid regurgitation classification after six months.

The six-month results from the TRILUMINATE Feasibility trial, confirm the 30-day results announced in May. (Also see “Tricuspid Version of Abbott’s MitraClip Improves Short-Term Outcomes In TRI-

LUMINATE” - Medtech Insight, 31 May, 2019.)The patients treated with TriClip also showed reduction in

heart-failure symptoms, with 87% of patients showing no symp-toms or mild symptoms of heart failure at six months, compared with 25% of patients at baseline. The patients’ quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire, also showed significant improvement over six months.

Currently, there are no commercially available devices for minimal-ly invasive treatment of tricuspid regurgitation, according to Abbott.

The company recently launched the 700-patient TRILUMINATE Pivotal trial comparing TriClip with medical therapy only in patients in patients with severe tricuspid regurgitation who would be at inter-mediate or high risk for death if they underwent tricuspid valve sur-gery. (Also see “Abbott Launches US Pivotal Trial Of TriClip Transcatheter Tricuspid Valve Repair System” - Medtech Insight, 6 Sep, 2019.)




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TCT 2019: One-Year PARTNER 3 Outcomes Show Better Quality Of Life With TAVRREED MILLER [email protected]

A new analysis of the one-year PARTNER 3 results show TAVR with Edwards Lifesciences Corp.’s Sapien 3 offers a modest disease-specific health status advantage over

surgical valve replacement.The one-year results from PARTNER 3, published in May, showed

TAVR with Sapien 3 resulted in lower rates of death and rehospital-ization at one year compared with surgery in patients with severe aortic stenosis at low surgical risk. The PARTNER 3 results led the US Food and Drug Administration to expand the approved labeling for Sapien 3 to include these low-risk patients. (Also see “FDA Expands TAVR Indication To Low-Risk Patients” - Medtech Insight, 16 Aug, 2019.)

On 29 September at the Transcatheter Cardiovascular Therapeu-tics (TCT) conference in San Francisco, Suzanne Baron from the Lahey Hospital and Medical Center in Burlington, MA, presented results of a substudy of PARTNER 3 comparing patients’ health status at one, six and 12 months.

Baron et al.’s analysis showed that over the one-year follow-up period, both TAVR and surgery created substantial improvements in both disease-specific and generic health status measurements com-pared with baseline.

Consistent with previous studies of transfemoral TAVR, PARTNER 3 showed TAVR is associated with significantly better health status, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary, than surgery one month after the procedure.

However, in contrast to several prior TAVR studies, this anal-ysis showed a persistent, but modest, benefit of TAVR over surgery in disease-specific health status scores at six and 12 months, Baron explained.

The TAVR patients in PARTNER 3 showed better health status than the surgery patients at all time points in the trial and the difference is at least partly due to the differential rates of post-procedural com-plications between TAVR and surgery, Baron said.“This is the first randomized trial to demonstrate a persistent, albeit modest, disease-specific health status advantage with TAVR at six and 12 months – time points at which patients are assumed to have recovered fully from surgery,” Baron said. “Further studies are needed to evaluate the durability of health status benefits with TAVR compared with [surgery] beyond one year in this low-risk population.”


TCT 2019: Five-Year PARTNER 2A Results Support TAVR In Most Intermediate Risk PatientsREED MILLER [email protected]

F ive-year results from the PARTNER 2A shows patients with aortic stenosis and intermediate surgical risk have similar rates of death and disabling stroke with either surgical

valve replacement or transcatheter aortic valve replacement (TAVR) with Edwards Lifesciences Corp.’s Sapien XT.

However, patients who underwent TAVR with the transthoracic access approach had poorer outcomes compared to surgery in PARTNER 2A. The two-year results from the PARTNER 2A showed that TAVR with Sapien XT was similar to surgery for the primary endpoint of death or disabling stroke in patients with severe aor-tic stenosis and intermediate surgical risk.

Vinod Thourani of MedStar Health in Washington, DC, presented the five-year results from PARTNER 2A at the Transcatheter Cardio-vascular Therapeutics (TCT) conference in San Francisco on 28 Sep-tember. Prior to the five-year PARTNER 2A results, there was little longer-term data on TAVR in intermediate risk patients, he explained.

At five years, the rates for the primary endpoint of death or dis-

abling stroke were 47.9% in the TAVR group and 43.4% in the sur-gery group, representing a statistically insignificant difference. Improvements in functional status and quality of life seen in the two-year PARTNER 2A results were maintained through five years for both TAVR and surgery patients.

About a quarter of the TAVR patients could not be treated with the standard transfemoral approach, so the valve had to be delivered through a transthoracic access route. In the transthoracic cohort, the rate of death or disabling stroke was significantly higher than the rate in the surgery group – 59.3% versus 48.3%.

“Therefore, TAVR should be considered as an alternative to sur-gery in intermediate-risk patients with severe aortic stenosis,” Thourani said. “However, in patients without acceptable trans-femoral access, surgery may be the preferred alternative.”



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Market Intel: 3D Bioprinting Forges Ahead With Mini Human Heart, Human Tissue BOB KRONEMYER [email protected]

T hree-dimensional (3D) bioprinting represents the future of medicine for organ and tissue replacements, ac-

cording to Shahram Seyedin-Noor, founder and general partner of Civilization Ventures, a San Francisco-based venture capital firm that has invested in the space.

“Although a lot of start-ups have come to market in the bioprinting space, we believe there is a big difference between the viable innovators that can operate at scale with proprietary platforms and the myriad lab projects that focus on niche bioprinting applications for academic purposes and publications,” Seyedin-Noor told Medtech Insight.

Seyedin-Noor points to the fate of San Diego-based Organovo Holdings Inc., a Nasdaq-listed company that has recently plummeted in value (on 23 September, the company’s shares fell 5.89% to close at $0.26) amid a lack of scientific data to support continued development of its bioprinted liver tissue as an example of an early bird that got eaten in the space.

“We believe that one or two leading platforms will emerge that integrate the most relevant bleeding-edge science in the space into their commercially viable platforms in the same way that Google today integrates or ‘buys up’ the best sci-ence in search,” Seyedin-Noor said. “But as of now, we are still in the nascent, frag-mented stage of the industry where dif-ferent approaches are being tested.”

Civilization Ventures has invested in Ca-nadian-based Aspect Biosystems and Prel-lis Biologics in the Bay Area because of the novelty of their non-overlapping approach-es to bioprinting, the passion and pedigrees of their founders, and their early traction.

Specifically, Aspect employs an extru-sion approach that optimizes fine-resolu-tion printing of heterogeneous cells with its microfluidics and cell-containing bio-inks, enabling it to precisely control the tissue microenvironment.

Prellis, on the other hand, has pioneered 3D laser-based bioprinting for solving the microvascularization challenge associated with creating viable organs.

Seyedin-Noor anticipates that the first meaningful clinical trials will begin in bio-printing over the next decade, leading to approvals over the next 15 years.

The biggest winner in 3D bioprinting will be the first company to achieve the milestone of filing an Investigational New Drug (IND) application and initiating clini-cal trials for an actual organ replacement, according to Seyedin-Noor.

He also predicts that bioengineered replacement tissues will completely re-place artificial organs and transplants within 20 years.

DRUG SCREENING, TISSUE, DEPOSITS In September, Boston-based Cellink launched the BIO X6, a six-printhead bioprinting platform that combines more materials, cells and tools than any other system on the market, according to Cellink’s CEO and co-founder Erik Gatenholm.

Users can mix the cells in each print-head with a tailored bioink, providing the

cells with the biological environment they need to achieve the desired architecture.

“The BIO X6 can be used for drug screening because it aids the fabrication of complex metabolic tissue models and deposits cardiac, liver, renal and pancre-atic tissue in a single print,” Gatenholm told Medtech Insight. “With this printer, us-ers can connect several models through perfusable channels.”

The original BIO X also now has the func-tionality to print complex structures with multi-layers/channels without needing to use G code, the most widely used numeri-cal control (NC) programming language.

Cellink and its partner, the Uppsala Uni-versity in Sweden, achieved a major mile-stone in June when it successfully sent bio-printed neural crest stem cells into space to study the influence of microgravity and hypergravity on living systems.

This comes after Cellink teamed up with Sweden’s Umeå University and GE Healthcare in May to develop alternative transplants that promote nerve regenera-tion and reduce patient suffering at the source in burn victims.

“The new bioprinted transplants will contain sebaceous glands or the types of cells that can regenerate dermal lay-ers, nerves and vasculature, providing an innovative solution to improve patients’ quality of life,” Gatenholm said.

DERMAL REGENERATIONSeoul, Korea-based ROKIT Healthcare Inc., formerly known as ROKIT, introduced a 3D bioprinting method to treat scared lesions.

The technology uses a patient’s au-tologous tissue and cells to form a patch graft that can be placed on partial or full-thickness wounds, from burns and diabetic foot ulcers, according to Da-Yae Lee, ROKIT Healthcare’s project manager for global business development.

The patient’s cell and ECM fractions are derived from liposuction, which is then

Mini human heart

BIOLIFE4D



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mixed with a hydrogel already approved by the US Food and Drug Administration to create a printable bioink.

“Commercially available bioinks have lim-itations in their applications to the clinic, so we focus on developing a bioprinting strat-egy employing patients’ own cell fractions as the bioink,” Lee told Medtech Insight.

Between August and September 2019, ROKIT joined forces with a hospital in India to conduct a clinical study of its dermis regeneration patch in diabetic foot ulcer (DFU) patients. The company expects the technology to become com-mercially available by early next year.

The global population affected by dia-betic foot ulcers is estimated to be 474 mil-lion, with a prevalence rate of 6.3%, accord-ing to a 2016 review in Annals of Medicine.

“Thus, a regenerative solution that would salvage a patient from amputation is an im-portant treatment strategy for diabetic foot ulcer patients,” he said.

ROKIT is also developing bioprinting for knee cartilage regeneration in arthri-tis patients, a heart patch for patients re-quiring localized heart tissue repair and a retinal epithelial patch for age-related macular degeneration (ADM).

COMMERCIALLY AVAILABLE HYDROGEL-BASED INKSBiogelx Ltd. in Scotland identified the need for new bioink biomaterials that can offer the biocompatibility of a collagen matrix aligned with the printability of commonly used natural hydrogels such as alginate with the reproducibility and safety of non-animal derived, chemically defined, synthetic materials.

“Balancing these desired properties into our new peptide-based bioinks has been our biggest challenge,” said Sandy Bulloch, Biogelx’s head of strategic alliances. “Fortu-nately, our materials are very versatile.”

The company has developed a bioprint-able nanofibrous network based on a two-peptide system: a hydrophobic “gelator” peptide (Fmoc-diphenylalanine) and a hy-drophilic “surfactant” (Fmoc-serine).

“The peptides self-assemble to form nanofibers in aqueous environments,” Bulloch told Medtech Insight. “In the pres-ence of calcium ions, these fibers cross-

link to form a hydrogel.” The result is a nanofibrous network

with a similar nanoscale matrix structure to that of the native extracellular matrix (ECM) in human tissue.

Due to the dynamic fibrous nature of the materials, the porosity is not defined and the materials reorganize, therefore allowing cells to migrate through the ma-terials by displacing fibers.

“By changing the concentration of the gel, the network properties can be altered, which effectively controls the average po-rosity and stiffness of the gel,” Bulloch said.

The gel composition enables the nano-fibrous network to emulate specific phys-ical properties of a wide range of different tissue types for development of tailored 3D models for biomedical and pharma-ceutical applications.

“There is a lot of interest from the me-dia about printed transplantable human organs – however, this will undeniably take many years to achieve,” Bulloch said. “While we definitely want to be part of that journey, we are primarily focused on more immediate opportunities for 3D bioprinting and bioinks, such as the development of more accurate disease models and cell-based assays for the screening and testing of new drugs.”

The company’s hydrogel-based inks were commercially launched in the US and Europe in April 2019.

Biogelx expects to capture roughly 5% of the global bioprinting market over the next five years, which for the company would conservatively represent annual sales of $17.5m by 2024.

MINI HUMAN HEARTChicago-based BIOLIFE4D has been able to 3D-bioprint a mini human heart, a sig-nificant step toward the company’s goal to create a full-sized human heart viable for transplant. “While the mini heart has not been bioengineered to replace a heart for a patient, it has been designed to be used for cardiotoxicity screening by pharma and drug discovery companies,” said BIO-LIFE4D’s chief science officer Ravi Birla.

Birla said current animal models have drawbacks including their inability to rep-resent an accurate model of predicting hu-

man cardiotoxicity.“We believe our mini heart will provide a

better predictive model; after all, what is a better predictor of how a human heart will react than another human heart, albeit a scaled-down version,” Birla told Medtech Insight.

The bioprinting process for the full-sized heart will consist of several steps, starting with a patient MRI and a blood sample for collecting cells. A computer software pro-gram will then construct a digital model of a new heart for the patient, which will match the original size and shape.

Next, a bioink will be created, comprised of the patient’s own specialized heart cells that have been reprogrammed and con-verted from normal blood cells.

Nutrients and other materials will be add-ed to help the cells survive the bioprinting process. And a custom-made 3D printer will protect the viable living cells throughout the process. After the printing process, the heart will mature in a bioreactor, in prepara-tion for patient transplant.

“The MRI and blood sample should allow the new heart to be a precise fit and genetic match, hence leaving the patient free from the risk of rejection or immunosuppressant therapy,” Birla said.

BIOLIFE4D is also tweaking the functional-ity of its mini-heart so it can provide optimal predictive value for cardiotoxicity testing.

“Beyond the mini heart, our lifesaving technology has the potential to save mil-lions of lives globally,” said Birla, noting that the addressable market for the mini-heart alone is likely in the billions of dollars.

To create a human heart viable for trans-plantation billions of cells are needed. It also requires a complex vascularization network to keep the bioengineered organ viable.

ARTIFICIAL TISSUEA research team at the University Medical Center Utrecht in the Netherlands and at the École polytechnique fédérale de Lausanne (EPFL) in Switzerland is developing volumet-ric bioprinting for artificial tissues in which a photocross-linkable, hydrogel-forming ma-terial based on gelatin is mixed with living cells. This suspension is then loaded onto a glass reservoir placed onto a rotating vessel.

Swiss-based Readily3D, spun out of the


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technical university EPFL, is currently de-veloping prototypes of the volumetric bioprinting, with hopes to commercialize the product in 2020.

Riccardo Levato, an assistant professor of biofabrication in regenerative medicine at the university, explained the process to Medtech Insight.

“Using a combination of a visible light laser source and a digital micromirror device, tomographic projections of the object to be printed are cast onto the photopolymer,” Levato said. “The combi-nation of these projections crosslinks the cell-laden hydrogel into the desired three-dimensional [3D] object, as the cumulative light absorbance selectively activates the photopolymerization process.”

A main initial interest will be to supply printers to research facilities to create in vitro tissue models, such as for drug testing, and eventually tissues for medical applications like bone, cartilage and heart repair.

“Given the rapid fabrication process pro-vided by volumetric bioprinting, this tech-nology holds clear potential to upscale the generation of living grafts,” Levato said.

Levato admits that many challenges re-main, including identifying an adequate supply of biocompatible materials for safe printing and creating a sterile envi-ronment for print. The regulatory frame-work for constructs with bioprinted cells is also still unclear, as the long-term per-formance of printed constructs has yet to be proven, both in vitro and in vivo.

PRINT COLLAGENCarnegie Mellon University in Pittsburgh has developed a 3D bioprinting technol-ogy called Freeform Reversible Embed-ding of Suspended Hydrogels (FRESH).

Adam Feinberg, a professor of biomedi-cal engineering and materials science & engineering at the university, touted FRESH as being first worldwide to 3D-print collagen and other biological ma-terials with resolution and fidelity that matches or exceeds what 3D printers can do with plastics and metals.

“Collagen is exciting because it is the major structural protein in the body and makes up nearly all tissues and organs,” Feinberg told Medtech Insight. Printing

functional parts of the heart is an ex-ample of what can be accomplished with FRESH printing of collagen and cells.

FRESH prints into a support gel com-posed of gelatin microparticles, akin to the air bubbles that are “stuck” in hair gel.

By dropping a needle into the support gel and extruding collagen, collagen be-comes stuck in place.

“Then when that needle is connected to a 3D bioprinter, we can extrude pre-cisely in 3D space to build whatever we want out of collagen,” Feinberg said.

After the entire collagen structure is print-ed, the support gel is warmed up from room temperature to body temperature, at which point the gelatin microparticles that make up the support gel melt, releasing the print.

“The collagen is able to be printed this way because as it is extruded into the sup-port gel, there is a sudden change in pH to cause the collagen to assemble into a solid network, very similar to collagen in our own bodies,” Feinberg said.

Perhaps the greatest challenge with FRESH is what to actually print; in other words, what is the best combination of structure, cells and materials to produce functional tissues.

“3D bioprinting is also intrinsically 4D, for which the fourth dimension is time,” Feinberg said. “Placing constructs into bioreactors that provide appropriate con-ditioning is also an active research area to create tissues with improved function.”

Currently there is no cost-effective way to generate the 2 to 3 billion heart cells required.

The researchers have also formed a start-up company, called FluidForm, that is collaborating with existing 3D bioprint-er companies to make “FRESH-printing” widely available.

TISSUE SCAFFOLDSThe Fraunhofer Institute for Interfacial En-gineering and Biotechnology IGB in Stutt-gart, Germany, is doing applied research on tissue scaffolds with a focus on devel-oping materials of hydrogel pre-cursor solutions based on derivates of gelatin.

Achim Weber, deputy head of the De-partment of Interfacial Engineering and Materials Science at the institute, told

Medtech Insight: “Bioprinting technol-ogy is the automated deposition of various cell types and cell type-specific hydrogels for the layer-by-layer genera-tion of tissue models or progenitors of biological tissues.”

The material development adds tech-nical requirements to the necessary components of bioscaffolding, whereas the printability of the bioinks depends on the viscoelastic properties of the flu-id, which is influenced by viscosity, gel formation, shear thinning and recovery time, Weber explained.

The deposited materials also need to maintain their form until chemical cross-linking achieves final stabilization. Treat-ment indications will likely include car-tilage defect, fatty tissue replacement and bone replacement. “Some visionary people envision a future where other or-gans like the pancreas and heart will be bioprinted as well,” Weber said.

He also pointed to uncertainties on the regulatory side.

In addition, “legal requirements are also complicated and vary from region to region,” Weber said. He anticipates it will take longer than 10 years for approval of bioscaffolding in humans, noting that the number of bioprinted pieces that is pro-duced for a patient is always one and that testing before implantation will destroy the printed “organ.”

“If you produce an organ for an individual patient, you have to ensure that this ‘one’ organ works and does no harm to the per-son,” Weber explained. Printing an individ-ual organ only once and using additional cells requires tests for regulatory approval before implanting, which may affect the organ or alter the functionality of the organ.

Quality testing is therefore a major hur-dle, he said.

“Bioprinting technologies provide ba-sic architectural tissue structures,” Weber said. “But 3D bioprinting is a technology of the future, especially if you look at the proposed vision of organ replacement. Besides the material printing of tissue and cells, cells grow and exhibit different behaviors during their lifespan.”



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