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Sandeep Singh Dhillon
FDA Pilot to Sign Off on Low-Risk Digital Health Products Without Pre market Review –
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By Zachary Brennan

US Food and Drug Administration (FDA) Commissioner Scott Gottlieb on Thursday announced an upcoming pilot program that would create a third-party certification program under which lower-risk digital health products could be marketed without FDA premarket review and higher-risk products could be marketed with a streamlined FDA review.

The pilot, part of a new approach to regulating digital health tools, would help to certify, according to Gottlieb, whether a company “consistently and reliably engages in high quality software design and testing (validation) and ongoing maintenance of its software products. Employing a unique pre-certification program for software as a medical device (SaMD) could reduce the time and cost of market entry for digital health technologies.”

FDA also will provide guidance clarifying its stance on products that contain multiple software functions and which currently fall outside FDA regulations.

“In addition, FDA will provide new guidance on other technologies that, although not addressed in the 21st Century Cures Act, present low enough risks that FDA does not intend to subject them to certain pre-market regulatory requirements,” Gottlieb wrote in FDA’s Voice Blog.

The push into digital health comes as Bakul Patel, ‎associate center director for digital health at FDA, recently told conference attendees that guidance related to software as a medical device, and a new dedicated unit to digital health are coming to FDA’s Center for Devices and Radiological Health (CDRH).

Gottlieb also noted that the postmarket collection of real-world data might be able to be used to support new and evolving product functions.

“For example, product developers could leverage real-world data gathered through the National Evaluation System for health Technology (NEST) to expedite market entry and subsequent expansion of indications more efficiently … The Medical Device Innovation Consortium (MDIC), a 501(c)(3) public-private partnership, is serving as an independent coordinating center that operates NEST. In the coming weeks, MDIC will announce the establishment of a Governing Committee for the NEST Coordinating Center comprised of stakeholder representatives of the ecosystem, such as patients, health care professionals, health care organizations, payers, industry, and government,” Gottlieb wrote.

NEST’s fully operational system is expected to come by the end of 2019.

Full article at

Sandeep Singh Dhillon
What Would Steve Jobs Tell The Pharma/Biotech Industry? – Bioprocess Online
Pharma Extra, Pharma Notables

By Martin Lush, Global VP, NSF Health Sciences

Whether you’re a fan of Steve Jobs and his products or not, two things are undeniable: He was very successful and very different. Now you can relax; this short article will not provide a blow-by-blow account of the man and his methods. “What would Steve Jobs tell the pharma/biotech industry?” is just a metaphor to encourage our industry to radically change — not by reinventing the wheel, but by copying the success of others.

Why Maintaining The Status Quo Is No Longer Good Enough

Please take a look at my last article, “Brexit, Trump, What Next? 6 Rules to Succeed in an Era of ‘Brutal Disruption”, for a reminder of the challenges and opportunities facing the pharma/biotech industry. This article reaffirms the sentiments of the great Albert Einstein:
“The definition of insanity is doing the same thing over and over again, but expecting different results.”
We live in an era of “new” everything — new science, new regulations, new presidents, new governments, and new challenges. To prosper in this era of brutal disruption, we have to think differently.
Like some of you, I have read a lot about Jobs and his methods, and what made Apple so successful.1-4 In writing this article, I simply imagined asking Jobs the question: “Based on your experience, successes, and failures, what would you tell the pharma/biotech industry?” Since he was a man who liked to get straight to the point, I’ve kept my imagined list of his recommendations to just five.
Steve’s Top Five Recommendations
1. Simplification Is Survival
Jobs was a complex man driven by a simple belief: Simplification is survival. For the pharma/biotech industry, this means drastically simplifying everything. Let’s start with the simple stuff first.
Your call to action:
Simplify documentation systems, particularly SOPs. For many companies, SOPs are out of control. They have become overly complex and impossible to follow. Instead of improving consistency, they increase the risk of errors and mistakes. Instead of being written for the user, they have been written for the auditor or regulator. This must stop. If you want guidance on how to write a good SOP, just look at a recipe book! You’ll see lots of pictures and simple diagrams! So, the answer to better documentation systems is in your kitchen.
Simplify batch manufacturing records (BMRs). Excessively detailed instructions, poorly designed documents, and excessive check signatures (most of which are not required) all contribute to user overload, stress, and mistakes. The purpose of the BMR is to provide essential guidance to the user, and provide an accurate and reliable history of events — the who, what, when, and how. Unnecessary complexity slows everything down, dilutes essential accountability, and increases risk. Here’s a helpful white paper on batch record simplification: Improving Human Reliability – Batch Record Simplification.
2. No, No, No, And No: Less Is More
Jobs believed success is determined by what you STOP doing. He would be telling us, “Just focus on doing the basics exceptionally well, and forget the rest. If you try to do everything [which translates to initiative overload], you will fail.”
Your call to action:
Tune up your change control system. If your change control system approves everything, it’s dangerous. A good change control systems works on the tried and tested principles of Pareto. A good system only approves the 20% of changes that provide 80% of benefit — those vital few. For more on change management, check out the free webinar Change Management – Best Industry Practices.
Hone your risk management skills. “Less is more” requires good judgment. Whether your change control system approves or rejects planned changes, one thing remains constant: RISK. To make the right decisions, you must have excellent risk management skills and competencies. Take a look at this short video for guidance: Risk Based Decision Making.
3. Hire People Who Break The Rules
Steve Jobs liked to challenge convention — and, on occasion, break the rules. This recommendation will have many industry veterans running for the hills. Employing rule-breakers in an industry that prides itself on “compliance”? Are you kidding? Think about it another way: Rule-breakers are simply those who keep pushing the boundaries. They keep challenging. They keep asking “why”… and they never give up. History proves Jobs was right.
Your call to action:
Rethink your recruiting practices. If companies recruit the same types of employees, they get just that: the “same” in everything. The same decisions and the same outcomes; and, ultimately, maintenance of the status quo. But, in an era of “brutal disruption,” the status quo is no longer good enough. The pharma/biotech industry desperately needs people who think differently — more “why?” people
Allow rule-breakers to do what they do. Progress, in every walk of life, is usually made by rule-breakers; those who are always looking for a different way.
Don’t just recruit people from the traditional sources, such as the pharma/biotech company next door — unless you want more of the same. Try attracting candidates from the automobile and microelectronics sectors. They have been practicing “total quality management (TQM)” for over 50 years!
If you want a lesson in how to manage quality, keep things simple and be laser focused on the end user. Hire people with backgrounds in fast-moving consumable goods. Instead of taking on graduates with “traditional” science degrees, take a walk on the wild side. Recruit a few with degrees in philosophy — people who think differently.
Hire people who know how to think. My Dad, who came from very humble beginnings, used to say, “We don’t have much money, so we have to really think.” The upside of falling prices for our medicines and rising manufacturing costs is that we all have to think differently. So, remember to hire based on two things: character and creative thinking ability.
4. Become Obsessed With …
… finishing and following up! Jobs was a “details person.” A recent survey conducted by Harvard Business Review found that a large percentage of changes and new initiatives fail because of poor implementation and follow-up.5 At NSF, we’ve found the same. For example, most deviation and CAPA (corrective and preventive action) systems have no “effectiveness checks” to make sure the corrective and preventive actions have been implemented correctly and are working. The same goes for many audit and self-inspection programs.
Your call to action:
Become obsessed with disciplined execution, implementation, and follow-up! The pharma industry is populated with very bright people who come up with lots of very bright ideas … that usually fail. The root cause? Poor (ill-disciplined) implementation. This is compounded by no follow-up to see what has worked and what hasn’t. We just need to apply Deming’s PDCA (Plan – Do – Check [measure and follow up] – Adjust).
5. Keep The Main Thing, The Main Thing … Or Die
Jobs was obsessed with satisfying his customers, the end users of his products and services. If you’ve ever been in an Apple Store for repairs or service to your Apple device, you know what I mean. From the minute you enter the store, you are “the main thing.”
Whenever I visit companies, I always ask the people I meet — from the warehouse supervisor to the CEO — about their products and patients. Do they really understand how their products work? Do they really understand every one of their products’ key quality attributes? Crucially, do they really understand how their products improve patients’ quality of life?
Over the last 37 years working in the pharma/biotech industry, I’ve consistently observed one thing: Those who put more focus on the monthly “P&L” (profit and loss) spreadsheet and forget patients’ struggles falter, and, in extreme cases, go out of business. In contrast, companies who keep their patients at the center of everything they do flourish, going from strength to strength.
Your call to action:
Simply conduct the “patient test.” Ask everyone you meet about the products you make and the impact they have on your patients. Ensure that everyone is emotionally connected to the patient. If not, you really are in trouble. Many companies put the “patient first,” using posters and slogans that, in time, become meaningless words; invisible and soon forgotten. One of the most important jobs of leaders at the ground level is to keep people motivated by giving them a reason to care about what they do. This means constant reminders that the patient is at the center of every decision — and this must be communicated not by using flashy posters or slogans, but through the actions of leadership
Don’t allow stress to eat away at your motivation. I am continually amazed by the quality, integrity, and commitment of the people I meet in the pharma/biotech industry. However, the “routine” of working in a highly pressurized, 24/7 world can be dangerous. The hours consumed by emails and meetings; the obsession with measuring things that don’t really matter; the pressure to hit manufacturing, testing, and product release deadlines can cause our patients, “the main thing,” to be forgotten.
Should Pharma Become More Like Apple?
Well, that’s a yes and a no. One thing is for sure: The pharma/biotech industry must get better at “stealing with pride,” rather than reinventing the wheel. Many of the challenges and problems we face are not new. In fact, the answers are already out there. The solutions are waiting to be stolen. Want to know about human error reduction? Study the solutions generated by the aviation industry. Want to know how to write user-friendly, error-free SOPs? Take a look at the IKEA process for designing instructions for furniture assembly. Want best-in-class practices for problem solving, deviation, and CAPA? Take a look at a Toyota car assembly line. Want to know how to use “Big Data”? Look no further than Amazon. So, whether it’s from Apple, Amazon, or anyone else, start stealing with pride!

Sandeep Singh Dhillon
Former Pharma Rep Now Helps Doctors Save Money on Drugs –
Pharma Extra, Pharma Notables
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As a drug salesman, Mike Courtney worked hard to make health care expensive. He wined and dined doctors, golfed with them and bought lunch for their entire staffs — all to promote pills often costing thousands of dollars a year.

Now he’s on a different mission. When Courtney calls on doctors these days, he champions generic drugs that frequently cost pennies and work just as well as the kinds of pricey brands he used to push.

Instead of big pharma, he works for Capital District Physicians’ Health Plan (CDPHP), an Albany, N.Y., insurer. Instead of maximizing pill profits, his job is to save millions of dollars by educating doctors about expensive prescriptions and the stratagems used to sell them.

“Having come from big pharma, I do really feel my soul has been cleansed,” laughs Courtney, who formerly worked for Pfizer and Johnson & Johnson. “I do feel like I’m more in touch with the physicians” and plan members, he added.

As a drug salesman, Mike Courtney worked hard to make health care expensive. He wined and dined doctors, golfed with them and bought lunch for their entire staffs — all to promote pills often costing thousands of dollars a year.

Now he’s on a different mission. When Courtney calls on doctors these days, he champions generic drugs that frequently cost pennies and work just as well as the kinds of pricey brands he used to push.

A pharmacist works at a pharmacy in Toronto
Instead of big pharma, he works for Capital District Physicians’ Health Plan (CDPHP), an Albany, N.Y., insurer. Instead of maximizing pill profits, his job is to save millions of dollars by educating doctors about expensive prescriptions and the stratagems used to sell them.

“Having come from big pharma, I do really feel my soul has been cleansed,” laughs Courtney, who formerly worked for Pfizer and Johnson & Johnson. “I do feel like I’m more in touch with the physicians” and plan members, he added.

Costs for prescription drugs have been rising faster than those for any other health segment, marked by high-profile cases such as the reported 400 percent increase for Mylan’s EpiPen and 5,000 percent spike for Turing Pharmaceuticals’ Daraprim.

Health plans and others paying those costs are fighting back. Many have tried to give doctors academic research on pill effectiveness or simply removed high-cost drugs from coverage lists.

Consumer groups and medical societies have tried to spread the word about expensive drugs. Startup GoodRx lets patients compare retail prices online.

CDPHP is one of the few insurers to have taken the battle against pricey pills a step further. It is recruiting across enemy lines, hiring former pharma representatives and staffing what may be a new job category: a sales force for cost-effective medicine.

“Insurers are taking matters into their own hands,” said Lea Prevel Katsanis, a marketing professor at Canada’s Concordia University who specializes in the pharmaceutical industry. “They’re saying, ‘We can’t really rely on drug companies to talk to doctors about what’s cost-efficient.’”

If insurance companies can curb drug costs, premiums paid by employers, taxpayers and consumers need not rise as fast.

Two years ago, when one company increased the cost of a common diabetes medicine to 20 times what it had been a few years earlier, Courtney and five other former pharma and medical-device reps working for CDPHP knew what to do.

Valeant Pharmaceuticals had cranked up the price of one common dosage of its Glumetza medicine for lowering blood sugar to an astonishing $81,270 a year, according to Truven Health Analytics, a data firm. Meanwhile a similar, generic version can be bought for as little as a penny a pill.

Because Glumetza was on CDPHP’s list of approved drugs, the insurer and its members had to pay for it when doctors prescribed it, resulting in millions in extra costs and stinging copayments for patients.

Dr. Eric Schnakenberg, an upstate New York family medicine doctor, was shocked when patients began complaining about what he assumed was an inexpensive prescription. Doctors are famously unaware about the cost of the care they order, a situation exploited by drug sellers and other vendors.

While physicians’ electronic prescribing programs and even pharmaceutical guides like the Physicians’ Desk Reference contain prescribing information — some are even peppered with ads — they contain no specific information about prices. Drug sales reps who visit their offices don’t highlight high prices as they drop off free samples, and drugmakers can quietly, but substantially, hike the price of a drug from one year to the next.

“As physicians, we’re blindsided by that,” Schnakenberg said. “We get patient complaints saying, ‘Hey, I can’t afford this,’ and we say: ‘It’s cheap!’”

After Courtney and his colleagues alerted doctors to what Valeant was up to, all but a handful of the 60 plan members who were taking Glumetza switched to metformin, the generic alternative. That saved about $5 million in a year.

Following an outcry over its practices, Valeant agreed last year to raise annual prices by no more than single-digit percentages, the company said through a spokesman. But such hikes could still outpace the inflation rate.

Cardiologist John Bennett got the idea to hire pharma reps a few years ago, after he became CDPHP’s chief executive. He knew reps are smart, genial and motivated. Overhiring by pharma had put many back on the job market.

His sales pitch to them, he says half-jokingly, was: “You know everything they taught you in big pharma? How would you like to use those powers for good?”

Pharma companies spend billions on TV ads, doctor blandishments and expensive salespeople to keep prescriptions flowing.

Pfizer, Johnson & Johnson and other sellers responded to critics a few years ago by restricting gifts of entertainment, coffee mugs and some meals. But the industry’s ethics code still allows lavish consulting contracts for doctors and sponsorship of physician conferences as well as meals for doctors and their staffs who listen to an “informational presentation” from sales reps touting expensive pills.

“When those products go generic, nobody’s promoting them anymore,” Courtney said. Generics makers lack big marketing budgets. CDPHP’s remedy: The insurer promotes generics with its own reps.

“It’s a great idea,” said Alan Sorensen, an economist at the University of Wisconsin who has studied drug prices. “Even a small moving of the needle on their [doctors’] prescribing behavior can have a pretty big impact on costs.”

At first the team concentrated on educating doctors about cheaper alternatives to Lipitor, a widely prescribed cholesterol-lowering medicine, and Nexium, for stomach problems. That saved around $10 million the first year, much in the form of copayments that would have been owed by plan members.

Recently the plan has focused on Seroquel, a branded antipsychotic that costs far more than a similar generic. Switching to the generic saves $600 to $1,000 a month, estimates Eileen Wood, the insurer’s vice president of pharmacy and health quality.

CDPHP’s repurposed reps have helped keep the insurer’s annual drug-cost increases to single-digit percentages, whereas without them and other measures “we would certainly be well into double-digit” increases, she said.

Educating doctors about drug costs is part of a larger push for “transparency” in an industry where Princeton economist Uwe Reinhardt says consumers face the same experience as somebody shopping in Macy’s blindfolded.

Current research by the University of Wisconsin’s Sorensen finds physicians with access to data about drug prices and insurance coverage are more likely to prescribe generics.

That gives Courtney and his colleagues a fighting chance, even if, he said, “we don’t have the freewheeling, unlimited green Amex card like I did back in the day.”

Sandeep Singh Dhillon
Sun Pharma share price falls 3% after Dadra unit gets 11 observations from USFDA
Pharma Extra, Pharma News

Sun Pharmaceutical Industries share price fell nearly 3 percent intraday Friday after CNBC-TV18 reports quoting agencies that the company has received 11 observations from the US health regulator for its Dadra unit.

While inspecting the plant, the US Food & Drug Administration found incomplete lab records at the pharma major’s Dadra plant.

These observations include failure to produce appropriate master or control record for each batch of drugs and failure to properly investigate batches that don’t meet specifications.

CNBC-TV18, quoting sources, had reported this news of Sun Pharma getting 11 observations on April 14.

Inspection of the plant by USFDA was concluded in the first week of this month.

Dadra site is the biggest unit for the company after Halol plant, for supplying drug in the United States.

Analysts say with these observations, the problem for the company may aggravate as its Halol plant has already been under import alert, which contributed 40 percent to US sales in FY16.

Meanwhile, in the first week of current month, the US Food & Drug Administration had said it would lift the import alert imposed on Mohali (Punjab) manufacturing facility and would also remove the facility from official action initiated (OAI) status.

Mohali, which had been under import alert since September 2013, is an oral solids plant and capacity-wise is understood to be as big as Ranbaxy’s Ohm Labs facility in the US.

At 09:38 hours IST, the stock was quoting at Rs 643.35, down Rs 12.50, or 1.91 percent on the BSE.

Sandeep Singh Dhillon
Drugmakers pose Brexit Britain withdrawal risk – Reuters
Pharma Extra, Pharma News

Neil Unmack

Drugmakers could lump Britain with a withdrawal problem. They aren’t publicly threatening to pull staff out of the UK, as the automotive and financial industries have done. But Britain’s looming exit from the European Union gives them renewed negotiating power – especially after Prime Minister Theresa May’s gushing endorsements of the industry.

Britain’s life sciences sector is a success story. It employs over 100,000 people, and generates 40 billion pounds of sales – and is at the heart of a fuzzy industrial strategy outlined by the Conservative government on Jan. 23. Yet apart from locally listed companies like GSK and AstraZeneca, there’s nothing inherently British about it: global companies can move research and manufacturing easily to other countries.

That might happen. Years of austerity mean the health service is not a big market to sell to. Britain invests less in healthcare than counties like Denmark or Belgium, according to the Organisation for Economic Co-operation and Development. Some clinical trials are already being shifted to other countries more likely to use the drugs, according to one pharmaceutical company executive.

Brexit makes things worse in several ways. Border controls could deprive hospitals of staff, and laboratories of scientists. If Britain can’t persuade Europe’s regulator, the European Medicines Agency, to see it as equivalent, pharma groups might have to undergo a separate process to get drugs licensed – and such a small market would be far down the list of priorities.

The government, which announces its annual budget on March 8, can throw money at the problem. It could buy more innovative high-priced drugs, and make procurement quicker. It could simply give tax breaks to drug companies. Yet Europe may be even less tolerant of aggressive tax practices when the UK has left: it recently clamped down on the so-called “patent box” introduced by the last government.

Paying for drugs is less politically toxic than helping bankers. But in any case, Theresa May could have little choice if they decide to exploit their advantageous position. One of her first moves as leader was to complain that AstraZeneca was almost bought by U.S. group Pfizer, threatening – in words that may come back to haunt her – to defend an “important” sector. She cannot easily go cold turkey.

Zydus announces settlement of patent litigation !
Pharma Extra, Pharma News

Sandeep Singh Dhillon
Is a Donald Trump Presidency a Black Swan Event for Pharma Stocks? – The Motley Fool
Pharma Extra, Pharma News
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Pharma stocks, so far, are reacting positively to the news the Donald Trump has upended Hillary Clinton to become the 45th President of the United States of America. However, a Donald Trump presidency may, in fact, be a black swan for this multi-billion industry. Here are 3 reasons why.

Reason No. 1: The Trans-Pacific Partnership would be beneficial to American pharma giants
Donald Trump is a champion of the bold idea of withdrawing from the Trans-Pacific Partnership (TPP). While this dramatic shift in trade policy may sound pro-American, it would unquestionably cause serious damage to the growth prospects of big pharma companies like Pfizer (NYSE:PFE) and Gilead Sciences (NASDAQ:GILD) that are based inside the United States.

The heart of the matter is that the TPP was set up in part to help U.S. drugmakers improve their profit margins abroad by increasing the patent life of top-selling medications and making drug prices more uniform across the globe. Although the evergreening of patents and modestly higher drug prices worldwide are two issues that have drawn the ire of global healthcare advocates, these core tenets of the TPP are without a doubt a huge benefit for U.S. pharmaceutical companies.

Reason No. 2: A pivot toward isolationist trade policies will negatively impact foreign exchange rates
A Trump presidency is almost certainly going to drive the U.S. dollar upwards against major world currencies, whereby negatively impacting foreign exchange rates. After all, a key part of his trade platform centered around new tariffs, renegotiating long-standing trade deals like NAFTA, and an attempt to label China a currency manipulator. The point is that capital is probably going to get sucked out of top emerging markets like China, driving unfavorable exchange rates for U.S. pharma companies moving forward.

How does this issue directly impact pharma companies? One of the few bright spots in Pfizer’s Q3 earnings report was the company’s continued strength in emerging markets. The drugmaker’s Essential Health revenues, for instance, rose by 9% year over year in the third-quarter in emerging markets.

Turning to Gilead, this blue-chip biotech derives around 7% of its total antiviral sales from global markets outside of Europe and Japan. That number could grow substantially if foreign exchange rates remained stable and the TPP was ratified. However, that rosy growth scenario now appears to be off the table.

The big picture issue is that a rising dollar stemming from isolationist trade policies is going to be detrimental to the profit margins of U.S. pharma companies.

Reason No. 3: Obamacare is now in jeopardy
With the Republicans taking control of both houses of Congress, Trump now has the political firepower — and arguably, the mandate — to dismantle the Affordable Care Act, or Obamacare. Whether you agreed with Obamacare or not, this crown jewel of Obama’s presidency coincided with an unprecedented rally among biopharmaceutical stocks as a whole, shown by the 200% rise in the iShares Nasdaq Biotechnology ETF (NASDAQ:IBB). To put this dramatic rise into context, the iShares Nasdaq Biotechnology ETF was actually down by more than 6% since its inception until the ACA become law on March 23, 2010.

Take-home message

A Donald Trump presidency, along with a Republican Congress, may spell disaster for U.S. pharmaceutical companies that have benefited from favorable exchanges rates and from wider insurance coverage that was part and parcel of Obamacare over the last six years. Say what you want about Obama, but there’s no doubt that the pharmaceutical industry flourished under his administration, thanks in no small part to Obamacare.

To be fair, a Trump administration may attempt to deal with the outstanding tax issues that drove companies like Pfizer to seek asylum abroad of late. Even so, these tax headaches are minor issues compared to the potential headwinds that could be stirred up by nixing the TPP and a strong dollar. That’s why I plan to remain cautious with this industry for the time being — that is, until Trump’s actual policies take shape.

Sandeep Singh Dhillon
Exposure to mould increases asthma risk – MIMS Malaysia
Pharma Extra

Exposure to mould or dampness in the home may increase the risk of asthma, according to two studies presented at the European Respiratory Society (ERS) International Congress 2016 held in London, UK.

In the multinational MeDALL* study, exposure to dampness and/or mould in early childhood (from birth to one year) was associated with an increased risk of developing asthma up to adolescence (adjusted odds ratio [adjOR], 1.14, 95 percent confidence interval [CI], 0.99‒1.31; borderline significance). Continual exposure also significantly increased the risk for asthma (adjOR, 1.24, 95 percent CI, 1.02‒1.51). [ERS 2016, abstract OA 3319]

In the Telemark study, a population-based study of asthma in Telemark, Norway, 3,090 individuals reported exposure to dampness or mould at home, 37 percent (n=1,128) of whom reported atopy while 1,895 were nonatopics.

Atopics had an increased risk of (ever) asthma (adjOR, 1.2, 95 percent CI, 1.0‒1.4), wheezing (adjOR, 1.4, 95 percent CI, 1.2‒1.6), chronic cough (adjOR, 1.5, 95 percent CI, 1.3‒1.8), and productive cough (adjOR, 1.4, 95 percent CI, 1.0‒1.8), as well as a higher incidence of asthma medication use in the previous 12 months (adjOR, 1.2, 95 percent CI, 1.0‒1.4; p<0.05 for all). Nonatopics had a higher risk of (ever) wheezing (adjOR, 1.7, 95 percent CI, 1.5‒1.9), chronic cough (adjOR, 1.6, 95 percent CI, 1.4‒1.9), and productive cough (adjOR, 1.6, 95 percent CI, 1.3‒2.1). [ERS 2016, abstract PA 4289] The Telemark study comprised 16,099 participants aged 16‒50 years who responded to questionnaires on mould or dampness exposure and respiratory health. The MeDALL study included 14,384 individuals from seven European birth cohorts. Data on the incidence of asthma and allergic rhinitis as well as exposure to mould and dampness from childhood through to adolescence were provided by parents of the study subjects via questionnaires. “Out of numerous suggested risk factors for asthma onset, the risk for living in a damp home is one of the most consistent findings, alongside exposure to secondhand smoke,” said Dr Joachim Heinrich from the University Hospital, Ludwig Maximilians University, Munich, Germany, author of the MeDALL study. According to Dr Regine Abrahamsen from the Department of Occupational and Environmental Medicine at Telemark Hospital who authored the Telemark study, these findings should draw attention to the association between dampness and mould and respiratory symptoms. “Making people more aware of the risks will hopefully mean more action is taken to prevent them living in these conditions,” she said. *MeDALL: Mechanisms of the Development of ALLergy

Sandeep Singh Dhillon
How Pacira Pharma Is Working To Help Curb The Opioid Epidemic – Pharmaceutical Online Newsletter
Formulation Discussion, Pharma Extra
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Poorly managed postoperative pain can have a significant impact on a patient’s recovery. For example, it can put them at risk for medical complications, including deep vein thrombosis, pulmonary embolus, and pneumonia.1 In addition, today’s methods for drug delivery often introduce a drug into the body in large quantities where it must then systematically travel until it reaches the intended area. This wide-scale distribution increases the potential for harmful side effects and requires a higher cost for care due to the amount of drug needed.

Another concern about the impact of poorly managed postoperative pain is related to the use of opioids for pain relief and a rise in the misuse and abuse of these drugs by patients. In a recent study from Stanford University, researchers found that patients undergoing 11 of the most common types of surgery were at increased risk for chronic opioid use.2 The increased use of opioids after surgery has caused a cascade into the abuse of prescription painkillers, and opioid dependence rose more than 3,000 percent from 2007 to 2014.3 According to, there are an estimated 4.7 million people in the United States dependent on painkillers.4

To address this epidemic, the FDA assembled a task force in 2013, which, among other efforts, encouraged the development of abuse-deterrent formulations of opioids. However, the most effective way to stop opioid dependence is to eliminate the use of these highly addictive drugs after surgery altogether. This was the goal of Pacira Pharmaceuticals, Inc., a specialty pharmaceutical company focused on the development of non-opioid products for postsurgical pain control, when it developed its injectable suspension, EXPAREL® (bupivacain liposome injectable suspension).

Changing The Standard Of Care

EXPAREL is a local analgesic utilizing bupivacaine in combination with the product delivery platform DepoFoam®. DepoFoam is made of microscopic polyhedral particles composed of numerous nonconcentric internal chambers that encapsulate a drug. These discrete chambers are separated by lipid membranes and filled with an aqueous solution of a drug. Once the drug is inside the DepoFoam technology and injected into the patient, the body begins to break down the lipid membranes. This is a naturally occurring process that releases the drug without altering its molecular structure.

DepoFoam permits both systemic and local delivery, which means the platform can release drugs into the bloodstream via the interstitial space or into a body compartment, such as a joint. This targeted delivery system allows the injection of drugs into the areas of the body where pain receptors exist, focusing the administration of EXPAREL to only the areas where it is needed.

The delivery of the non-opioid drug, EXPAREL, through the DepoFoam technology provides physicians and patients with the tools necessary to overcome the challenges associated with managing postoperative pain. “EXPAREL limits the amount of [opioid] drug needed after surgery, and, as a result, the potential for adverse effects is reduced dramatically,” says Ray Kaczmarek, Vice President of Commercial Manufacturing and Supply Operations at Pacira. “Most importantly, it empowers physicians to change the standard of care for postsurgical pain and ultimately gets the patient back up on their feet without the severe adverse events or the side effects of an opioid.” After it is infiltrated into the surgical wound prior to closure, EXPAREL can deliver up to 72 hours of postsurgical analgesia, Kaczmarek says. This significantly reduces pain during the first 24 to 48 hours after surgery, when it is often the most severe.

Addressing The Challenges Of EXPAREL Manufacturing

Beyond the composition of lipid components and the need for aqueous excipients, the effectiveness of the DepoFoam delivery platform is dependent on the manufacturing process used to develop it. Kaczmarek says one challenge is the critical need to properly handle EXPAREL in its sterile state. “Once we start the process of creating the liposome, we have to maintain sterility assurance all the way through to the patient,” he explains. “That means the bulking process, the filling process, and everything done until the point where the physician begins to utilize the drug.” Other important factors for the successful manufacturing of EXPAREL include temperature, agitation, and the design of the sterility assurance package around the drug.

What also makes the manufacturing process for EXPAREL challenging is the need for a manufacturer to understand the complexity of the drug’s critical process parameters and how they interrelate to each one of its attributes. If any one of the parameters is changed, the drug product will either fall apart or will not work in an appropriate way. Additionally, the limitations of today’s downstream technologies create a manufacturing bottleneck that makes the scale up of EXPAREL difficult. “The sooner the industry starts improving downstream technologies, the sooner we will be able to maximize the technologies, such as TFF [tangential flow filtration], to improve our manufacturing scale,” explains Kaczmarek. “Until then, we’re creating newer platforms and utilizing different technologies to allow the maximization of scaling by limiting exposure in the downstream process and implementing continuous batch processing.”

It was these challenges, as well as the need for global exposure and regulatory compliance, that caused Pacira to seek a partner who could provide them with the resources and experience necessary to build upon their existing manufacturing capacity to successfully manufacture and globally commercialize EXPAREL. After vetting other prospects, Pacira decided on Patheon. Kaczmarek says what was particularly appealing about Patheon is that the relationship between the two companies is not a typical CDMO/sponsor relationship. “I’m not just handing the drug product over and then hoping they manufacture and provide the supply to me,” he explains. “We’re working together to transfer a complex manufacturing process into one of their suites, and then, within that work, expanding the process out and training their personnel on how to run it. We will monitor the process as a partner as they manufacture the drug product.” This is accomplished through the use of Patheon’s condominium manufacturing model. The “condo” model is one of six adaptable manufacturing arrangements the CDMO offers its clients. Through multiple options, Patheon provides sponsors with a variety of flexible and scalable manufacturing approaches to create the optimal solution to fit a client’s needs.

A Stronger Partnership Through Collaboration And Communication

Patheon’s condo model is designed for companies either expanding their current manufacturing capacity or introducing new product with unique characteristics that cannot be manufactured on a conventional manufacturing line, such as EXPAREL. In addition to providing manufacturing design services, Patheon works with equipment suppliers, validates the processes, builds the line, and manages operations on behalf of the client. Overhead is shared, and the line can operate as needed to meet demand.

Kaczmarek says Pacira personnel support the manufacturing and quality assurance processes in Patheon’s UK facility. “This gives us the ability to utilize the facility, the staffing, and the support structure Patheon brings to the table,” he says. “They also have multiple areas outside of the U.K. facility where we can continue to grow strategically.” Kaczmarek adds that Pacira wanted a manufacturing agreement and strategic partner, not just a one-time partner for one product. They potentially want to utilize Patheon for their pipeline. “We want to take the new technologies we are developing and place them into Patheon’s facilities, so they can be co-located with the people who are learning the processes and understanding our drug. Patheon provides the ability for us to do that through the condo model and the footprint design they have in their U.K. facility.”

The condo model design coupled with the manufacturing agreement gave Pacira a high level of confidence that they not only picked the right partner, but they would also be able to control the intellectual property of their drug product design and formulation. “Other potential manufacturing groups we were looking at did not have the same type of model, nor did they have the same ability to provide that type of an operational environment where we could transfer a very complex process to them with the understanding of how they would actually be able to manufacture moving forward,” says Kaczmarek.

As the next step toward creating an even stronger relationship, Pacira and Patheon are establishing a governance relationship, where both companies speak on a regular basis about topics like how the U.K. facility is being utilized and whether the product is being fully commercialized in an appropriate way. “Patheon’s openness to the integration of these types of technologies into their network maximizes Pacira’s ability to supply EXPAREL to patients, as well as our future pipeline,” says Kaczmarek. “By having these strategic discussions and agreements, it minimizes the cost of manufacturing for both companies and it maximizes the ability to provide patients the quality drug products in a very timely manner. Ultimately, that’s what we want to be able to do, and both companies are coming together to make that possible.”

Sandeep Singh Dhillon
Pfizer bets $14 bln it knows better than market – Reuters
Pharma Extra, Pharma News, Pharma Notables

Pfizer seems to know something others don’t about Medivation. It’s betting $14 billion on the biotech, a 120 percent premium to the undisturbed market value. It’s a good fit and Medivation’s cancer blockbuster is a rare gem. But a heated auction and back-of-the-envelope math hint that the buyer is overpaying.

Big drug companies are always on the lookout for new drugs to sell. Among the most appealing are cancer therapies with fat margins. The concentrated market means few salespeople are needed, and drugs with a proven benefit over rival treatments can command sky-high prices. Medivation’s Xtandi for prostate cancer costs well over $100,000 per year.

Worldwide sales of Xtandi were $595 million in the second quarter. Even this gem has flaws, however. Pfizer will have to share rights to the drug with Japanese company Astellas Pharma. Medivation currently receives half of U.S. profits and a royalty from overseas sales.

Despite these limitations, Pfizer is paying more than 11 times Medivation’s estimated sales for 2017. The market values Pfizer at 4.5 times its revenue. There are big caveats to this comparison, but at the very least it suggests that Pfizer expects sales to grow sharply in future years. Yet Xtandi’s U.S. sales are leveling off, with growth running at an 11 percent annual rate in the second quarter. Extending treatment with the drug and expanding into new cancers may boost growth again, but that remains to be proven.

Redemption might come from Medivation’s potential drug for breast and other cancers. The company’s management recently said the new category of cancer treatment concerned could produce sales of $30 billion a year, with its drug capturing a big chunk. That sounds like part of the company’s sales pitch, though. Medivation paid just $410 million for it a year ago, with a promise of up to another $160 million as approvals are achieved. Analysts are mostly projecting annual sales of around $300 million from this drug.

Pfizer may believe in a far more lucrative outcome. But it also had to outbid multiple savvy rivals including Astellas, Medivation’s natural partner, and Sanofi. The most probable explanation for the heady price is that Pfizer has once again paid more than it should have done.

By Robert Cyran