Category Archives: R & D

Drug Company Spends $100 Billion But Not to Find New Drugs

This could be the headline if the Pfizer acquisition of AstraZeneca comes to fruition.

Pharmaceutical companies continue to remind us that the reason they have to charge outrageously high prices for their drugs is because drug discovery and development is high risk and very expensive. This argument has always been suspect but now there is clear evidence that it isn’t the high risk and high cost of drug development that drives high drug prices.

Here are two examples that totally discredit the premise behind high drug prices being espoused by Big Pharma.  Gilead spent $11 billion and Pfizer is contemplating an acquisition which will cost the company over $100 billion to buy a company.  These acquisition costs represent more than 5 years’ worth of R & D spending by either company.  Unfortunately, no new drugs will be coming from the money spent on these acquisitions. That’s right, no new drugs, not one, come from the money spent on these acquisitions.  Sure the companies will continue to develop some of the compounds that are already in their respective pipelines, but the $11 and $100 billion isn’t going to discovering or developing any new treatments.

Unfortunately, rather than increasing drug discovery and development, these type acquisitions divert money away from drug research. In addition to the cash and stock value used in the acquisition, the acquiring company looks for “redundancy” and “operational synergies” which result in massive cuts in research budgets and staff.   Bottom line?  Billions of dollars spent for less research, fewer drug discoveries.

It is clear that drug companies don’t have to charge outrageously high prices to cover their R & D expenses. In the examples given here, patients are paying for the acquisitions.  Drug companies obviously have more than enough cash to fund even more research than they currently do.  Rather than innovative drug research, their high drug prices are supporting luxurious operating expenses, overpriced acquisitions, and extraordinary executive compensation (Gilead, Pfizer, and several other Big Pharma CEOs are among the top compensated CEOs in Corporate America).

Rationalizing the high prices they charge for medicine with the high cost of R & D is just another reason Big Pharma has lost all credibility with patients, regulators, and the healthcare market.

The Five Types of Biotechnology Companies

Type One:  Big Biotech

Biotech companies with full product lines and significant revenues that rival those of Big Pharma.  They have sufficient cash from operations (profitable) to support healthy, well-funded research pipelines and to acquire technologies that fit their business strategy.

Type Two: One Trick Ponies

Companies with a single major marketed product and sufficient revenues to support some operations with or without profit.  These companies are often acquisition targets for Big Pharma.  With no follow-on products or pipeline, company executives and investors are counting on the company being acquired before they run out of money, lose investor interest, or their product becomes obsolete.  

Type Three:  Prolific Pipelines

Biotech companies with pipelines of high probability technologies.  Their compounds have a sound basic science premise supported by encouraging preclinical and perhaps even Phase II clinical data.  These biotechs focus on developing a strong regulatory package of clinically relevant “proof of concept” data to support optimism for FDA approval and commercial success.   Single product companies might be acquired outright while multiple product companies may sell individual compounds (or technologies) while leaving the discovery research and early clinical development infrastructure in place.  These companies have recently been the source of compounds for Big Pharma looking to replenish and bolster their depleted pipelines.

Type Four:  Too Little, Too Late

These companies have compounds that will probably work, deliver positive clinical results, and even achieve FDA approval.  Unfortunately, their product will provide no meaningful clinical benefit over currently marketed products (some of which might even be generic drugs).  The commercial potential for these products  is limited.   These companies, nevertheless, continue to persuade investors with slick presentations espousing large market size numbers and an insistence that with “a new treatment” even a small percentage of that large market will result in significant revenues for the company.

 Type Five:  “Promises, Promises”

Biotechs that are developing products based on extrapolation of flawed or misinterpreted laboratory-derived conclusions.  This is different from bonafide discovery research based on progressively revealing evidence of potential safety and efficacy.  Unfortunately, while their story may sound plausible, there is little or no evidence to support hope for clinical or commercial success.  These companies thrive on finding investors who are looking for lottery size payouts from picking a winner where nobody else seems to appreciate or understand the medical and scientific techno babble.  These companies require eloquent CEOs who can tell a story and preach the promise of a promising technology.  Unfortunately, the only winners for this type biotech company are the executive teams who continue to be paid Big Pharma salaries and bonuses for prolonging the unfulfillable promise.

So what’s the point?

There are probably in excess of 4000 companies (private or public) worldwide that consider themselves “biotech” companies. 

             Think about the large number of Type Four and Five companies masquerading as Type Three companies.

             Think about the venture capital, investment, and research grant money that Type Four and Five companies wastefully divert from Type One, Two, and Three Biotech companies.

             Think about investor confidence in Biotechnology when Type Four and Five companies fail to deliver.

 mike@pharmareform.com

drugs

Big Pharma R & D Failing

Research and development … innovative new drugs … “the life blood of the pharmaceutical industry.”

Tens of billions spent on research and what does Big Pharma have to show for their investment?  What do the multi-million dollar a year CEO’s and executive teams have to show for their brilliance in delivering the much needed new treatments they keep promising?   Not much, according to the FDA calendar for 2013 drug approval decisions chronicled in a recent article by Seeking Alpha (http://tinyurl.com/qjdyc3m).  Moreover, based on their pay and bonuses (http://tinyurl.com/p57yt5o) CEO performance reviews obviously do not put much importance or weight on drug discovery or approvals. 

Here’s my assessment.

From what I could determine, only five drugs (suvorexant, dabrafenib, tivozanib, dolutegravir, trametinib) discovered and developed by the sponsors are what I would consider “new”.  GlaxoSmithKline developed and sponsors three of those five drugs and one was developed and sponsored by Merck.  Two new drugs (efinaconazole and sofosbuvir) were acquired and then developed by the sponsors, Valeant and Gilead.

Six additional drugs scheduled for FDA decisions in 2013, are merely reformulations or new delivery systems for already approved drugs.

And finally, there are five,  already approved drugs,  awaiting new or expanded indications. 

Think about that for a second.  Tens of billions of dollars spent on R & D and technology acquisitions every year for decades and only seven new drugs.   Every year PhRMA touts the thousands of new compounds in development, several hundred by disease state.  How many Big Pharma company executives get up at the never-ending investor conferences to brag about their pipelines of new drugs coming?  With more than a thousand drug or biotech companies, spending tens of billions of dollars year after year and we only get seven new drugs?

I would also point out that, from my perspective, only Merck and Glaxo qualify as Big Pharma.  Ok, Pfizer is in the joint venture on dolutegravir, but still.  Even if you throw in Cubist and Gilead, where are the rest of the Big Pharmas? 

This is a sad commentary on disastrous pharmaceutical R & D productivity (and the lack thereof). More importantly, it’s a very scary picture for investors and worse for those with diseases for which there are few or no therapeutic options.

Perhaps Pharma will figure out that it is not more money that delivers breakthrough new treatments.  Focused, high-level basic science expertise (not just academic degrees) and a deep multi-disciplinary understanding of the target disease are required to crack the drug discovery code.  Unfortunately, for the past couple of decades, Big Pharma hasn’t valued discovery research. They would rather just write a check than do the hard work.  And the results show.

Drug Developers: Putting on a Show at JPMorgan Healthcare Conference

Each year there is considerable excitement, behind the scenes deal-making, networking, and of course, 4 days of never ending executive presentations at the JPMorgan Healthcare Conference. This year will be no different.  Over 400 company presentations (the overwhelming majority from Biotech and Pharma company executives) proudly highlighting accomplishments of the past and pipeline promises for the future, all with the caveat of “forward looking statements.”  Virtually every company in drug development that comes to JPMorgan each year declares they have strategically honed their pipelines filled with promising new agents for diseases with significant unmet medical needs.

Granted, not all the JP Morgan presenting companies are working on drug development.  Some are medical device companies, healthcare systems, pharmacy chains, distributors, or contract support companies to the biotech and Pharma industry. Without going through and deciphering which of the more than 400 companies are actually working on drug development, it’s at least 200 and probably closer to 300 of the presenting companies.  So what’s my point?

Unfortunately, all the JP Morgan presenting drug companies collectively delivered less than 35 FDA drug approvals in 2012.  In fact, 12 of the approvals came from companies and organizations not even presenting at JP Morgan this year.

35 approvals is not a very impressive number, especially when you consider the tens of billions of dollars spent each year on drug research, the hundreds of thousands of scientists and clinicians engaged in drug development, and the number of companies professing to have promising new drugs in development.

mike@pharmareform.com

What did Big Pharma contribute to 2012 New Drug Approvals?

I’ve read several press releases over the past couple of week announcing and interpreting the significance of FDA drug approvals over the past year.  Most give you the impression that the results are encouraging and suggest Pharma R & D is in recovery mode.  Traditional PhRMA bragging points of spending more than $60 billion per year on R & D, the thousands of compounds in development, and hundreds of innovative new medicines approved over the past couple of decades are, however, somewhat tempered by the reality of the recently reported drug approvals, especially for Big Pharma.  I don’t mean to downplay the challenges of drug discovery and development but it’s important to look beyond the total number of approvals to determine what that number really represents.

A closer look at the list of 35 FDA approved drugs for fiscal 2012 (October 1, 2011 to September 30, 2012) reveals rather dismal R & D productivity and lack of innovation that has haunted Big Pharma for the past several decades.

First let’s put 35 new drug approvals into context.  These new drug approvals were the results of decades of  hundreds of billions of dollars invested in research being done at or by more than a thousand Pharma and Biotech companies as well as thousands of government and university laboratories.  Pharma reminds us frequently of the hundreds of compounds in development for different diseases.   Yet, only 35 new products in 2012 … not very impressive.   Also interesting to note is that there are 31 different sponsors for the 35 New Drugs Approved.  So out of more than 1000 pharma and biotech companies out there, only 31 entities got a drug to the approval list.

The list better reflects the importance of smaller research organizations in discovering and developing new drugs.  Depending on how you define Big Pharma (e.g., are Gilead, Forest Labs, and Astellas Pharma considered Big Pharma?), you may end up with slightly different numbers but Genentech/Roche, Bayer, and Sanofi contributed 4 of the 12 “Priority Drug Approvals”.  More to the point, of the 35 drugs listed, if we’re generous in a definition of Big Pharma, only 13 of 35 drug approvals were “sponsored by” Big Pharma.

What’s more disheartening is the evidence of diminishing drug discovery at Big Pharma.  While celebrating the 35 approvals, a little investigating reveals that the overwhelming number of approved products were not discovered by or at Big Pharma.  You have to dig a little but even where Big Pharma is listed as the sponsor, many of the approved compounds were licensed in or acquired from collaborative work with smaller biotech companies.  Again, being generous in how you might define Big Pharma, only 6 or 7 products on the list were actually discovered at a Big Pharma.   And in this number, two were discovered by Genentech (acquired by Roche), one is an analog of a previously approved biotech product, one is a combination vaccine, and another is a combination of previously approved products.  So much for Big Pharma innovative “discovery research.”

So while the total number may be reassuring in the context of previously disappointing years of smaller numbers of drug approvals, a closer look reveals that drug discovery and drug development are no longer being driven by Big Pharma.  More importantly, despite the investments being made, new drug discoveries remain elusive and approvals are rare regardless of who is doing the work.

mike@pharmareform.com

Mindset Change Needed for Re-Engineering Pharmaceutical/Biotech R & D

In the previous post and in the book Pharmaplasia I suggest a need for a new approach to pharmaceutical R & D.  There are two essential elements to this proposal.

The first has to do with scientific and corporate integrity.  If the research scientists and corporate executives are not honest about what you have and what you have seen in drug development (if their priority is to protect the “potential“ of your compounds), you can’t make good decisions about your pipeline products.  Research scientists or corporate executives trying to preserve compound “potential” by strategically navigating around potentially damaging data, half-truth disclosures, or blatantly ignoring negative results and their implications can easily sabotage any corporate effort to produce a more robust pipeline with a higher probability of success.  The second essential element will be meaningless if this first element is ignored.

The second essential element:

Know more about your compounds before they go into Phase III clinical trials.

A more comprehensive basic science understanding of your compounds before they enter the clinic, especially expensive Phase III trials; can increase the probability of success.

For safety, this requires an aggressive exploratory preclinical program that “looks for toxicity” (going well beyond the regulatory requirements) and understanding what you find and what you see … not just being able to explain it away.

From an efficacy and safety perspective, if your compound affects one biologic system, what other systems does it affect? Have you really looked or have you been focused on “getting an indication?”   Do you have the basic science data to support the premise/hypothesis for efficacy (or comparative superiority)?  Have you scientifically challenged the premise with alternative outcome possibilities with data to support the different probabilities?   Or, is it still just a hypothesis you plan to prove in Phase III?  Are you sure you have the right endpoints for your Phase III trials?  Have they been sufficiently validated (high probability statistics) in Phase II studies?  By this I mean, have you done more than just a couple of regulatory required trials?  Have you looked at design alternatives that could affect outcomes for different endpoints options?

This strategy may take longer.

But, rather than how fast can you get how many compounds into patients and to the market, research teams and corporate executives need to shift their mindset to increasing the probability of success.  You can do this with a more comprehensive approach to preclinical research.  Thoroughly understanding how your products are going to perform in Phase III trials (or comparative trials) before the trials commence.  Eliminate the “surprises” with better, more comprehensive science around the products.  Be exhaustive in exploration, honest about the findings, inclusive of interpretations, and have better data to support the “go forward” premise or hypothesis.  This all may seem like a simplification but if you’re interested in a more elaborate discussion, I invite you to read about the need for pharmaceutical R & D change and recommendations for change in Pharmaplasia.

Sure there will still be failures, but they should be fewer.  But perhaps the biggest benefit from this approach is the potential for new discoveries of safer, more effective products.  Better diagnostics, more definitive efficacy benefits (maybe we are looking at the wrong endpoints), and advances in the understanding of human biology await this new Pharmaceutical R & D model.  Not to mention, less contentious regulatory reviews, renewed hope for patients with difficult to treat diseases, and more certainty for the investment community.  mike@pharmareform.com

Why so many Surprising Disappointments from Pharmaceutical R & D?

FDA rejections of new drug applications (insufficient efficacy or safety data), totally unexpected drug failures in Phase III trials,  bewildering “no significant differences” demonstrated in comparative trials, eye opening safety issues in late stage trials or raised by FDA Advisory Boards.  In many cases, negative results sufficient to delay approval if not “kill the drug.”

Along with these stories come the unscientific rationalizations of failures. “That’s drug development.”  “High risk, high reward.” “Biology is complicated.” “Diseases we are trying to treat today are far more complex.”

These are not new headlines for the pharmaceutical industry.  In fact, and unfortunately, they have almost become a cultural industry expectation. Patients ride the roller-coaster of hope and disappointment while investors, also frustrated, keep hoping for that occasional “big win” that makes it all worthwhile.

The pharmaceutical and biotech industries have to find a better R & D model before patients lose faith and investors no longer feel that the “drug discovery and development lottery” is worth playing.

How many more times can Big Pharma place big bets on “promising“ compounds with limited “proof of concept” only to find out they have been sold worthless technology that can’t even make it through a traditional development program to gain market approval?

How many Pharma pipelines boast the number of compounds in development merely to demonstrate that they have something worth investing in, while knowing full well most of the compounds have little or no chance of really making it to market or producing a profit?

How many compounds in these Pharma pipelines (or biotech compounds for that matter) have been strategically developed so as to embellish the efficacy “potential” without exposing or exploring the design flaws that might compromise this “potential?”  How many of these compounds have been carefully tested so as to avoid any suggestions of toxicity that might be difficult to explain or might raise concerns during a “Big Pharma due diligence” (for biotech) or worse, during a regulatory review?

But many of you might be thinking…well that’s just the way pharmaceutical and biotech R & D is.  Well, you’re right… it is and it has worked for decades when the benefits of drug treatment (versus no treatment) outweighed the risks and the market was far more receptive to paying for mediocre “follow-on” products?

Find a compound with biologic activity (remember “get a hit in high throughput screening?”), see if it causes any “apparent toxicity” (do the regulatory required testing but don’t look too hard beyond that) in a few animal models.  Do a quick Phase I trial to see if it causes any “apparent toxicity” in a few volunteers.  Your objective is to get into and out of Phase II (not to really understand what happens in Phase I or II).  Now, pick a dosage schedule and the easiest, fastest indication to establish a quick proof of concept. Then, if you’re a biotech company, find a Big Pharma to buy your compound and/or your company.  If no buyer, get more investment to start a Phase III trial.  If you’re a Big Pharma, push it into full-blown Phase III clinical trials as fast as possible on a timeline that shows investors your “quick to market” development strategy and then “hope for the best.”

The problem is that this historical Pharmaceutical/Biotech R & D model is no longer viable.  So what has to change?   mike@pharmareform.com

dowser

Divining the Future from JP Morgan Healthcare Conference Presentations

The J P Morgan Healthcare Conference is, among other things, an annual four days of back to back 30 minute presentations by Pharma, biotech, device companies, CROs, and a diversity of healthcare institutions.  C-level presenters, mostly CEOs, trying to persuade analysts and potential investors that they have the business model designed for increasing shareholder value, some bolstered by forward looking statement disclaimed historically based promises for product approvals, revenue and earnings growth,  dividends, and stock buy backs.

The conference is the premiere healthcare conference in the industry and has become “old home week” for industry executives to reconnect, schmooze, and initiate discussions for potential deals.  Getting an invitation is near impossible if you are not among the presenting companies or on the JP Morgan A-list.  I am neither, so I spent last week listening to all the webcasts that are available for the Pharma and biotech company presentations.

Perhaps the single most stunning, yet less obvious (non- investor perspective) “take away” for me was how rapidly Big Pharma is moving away from Primary Care.  With almost 75% of prescriptions now being filled with generic drugs, the trend may not be that surprising.  What is surprising is that the pace of proactive strategic abandonment of Primary Care is far more dramatic than what I believe most people in the industry would want to admit or even realize.

This trend really got my attention when companies with traditional Primary Care portfolios blatantly stated or clearly outlined that they have strategically refocused their pipelines and commercialization efforts to target specialty markets.  With very few exceptions, company presentations were absent references to products or commercial strategies targeting the Primary Care market.  Oncology, neurology, psychiatry, rheumatology, and dermatology seem to be the focus of attention unless you had a Hepatitis C compound in your pipeline.

Again, the interest in specialty products is not surprising.  They command higher prices, yielding higher margins with less onerous managed market intervention into prescribing practices.   From a commercial perspective, specialists represent a smaller, more easily targeted and sales force friendly customer base.   Specialty market physicians and their patients also seek out and are more receptive to disease and treatment information making promotional education a viable and efficient tactic.

The implications of this trend away from Primary Care are clear.  Fewer sales reps needed for calling on Primary Care.  Less need for expensive Primary Care sales and marketing support activities such as purchasing mass market prescription data, coordinating the complexities of territory management and sales reporting, and dealing with sales force related employee relations issues.  It also means fewer industry sponsored educational programs for Primary Care.  Fewer Primary Care clinical trials.   And,  fewer new Primary Care products means Primary Care physicians and their patients will have to be satisfied and content with the treatment options currently available to them.

The real message here is that while Primary Care has been at the foundation of Big Pharma growth and financial success in the past and there may well be exceptions in the future, the importance and interest of Primary Care to Big Pharma is diminishing quickly.  If your expertise or responsibilities include pharmaceutical sales and marketing to the Primary Care market, I believe your days are numbered and you probably have fewer days than you might think.  Specialty products and markets are where the action is and where the industry is headed and it is moving fast.   mike@pharmareform.com

Merck Spending Too Much on R & D

I was recently surprised by my own indifferent response to a couple of recent pharmaceutical industry news reports that should have been shocking, if not mind boggling. One of them was:

 “Merck CEO defends hefty research spending” (Reuters).

Defend research spending?  Since when would investors be concerned about spending too much on R & D,  in any industry for that matter, but for pharmaceuticals? Are you kidding?

There are a couple of underlying issues that make this situation very disconcerting but understandable.  First, the article identifies “investors” as those who have expressed concerns about the amount Merck and other pharmaceutical companies are spending on R & D.   I’m pretty sure they are not talking about individual investors but rather institutional investors and investment analysts.

The problem is that these analysts and the firms they work for are mostly driven by short term financial results.  When long term corporate value-creation compromises short term financial gain opportunities, analyst and investment banking compensation (especially bonuses) can be negatively impacted.   For example, cutting corporate expenses to increase near-term earnings usually creates more positive stock movement and compensation opportunities than any long-term strategic investment will ever create.

Just look at the daily stock price ups and downs for pharmaceutical companies driven by a single piece of clinical data or a letter from the FDA.   For an investor market driven by a short term “make a quick buck” mentality, long term financial consequences become somebody else’s problem.

So why does Merck CEO Kenneth Frazier get so much attention for what is considered by some analysts as a questionably high level of R & D spending?  For most pharmaceutical company executives, their short term incentives are often similar to those of the analysts and investment bankers.   So, in this light, Mr. Frazier’s long-term perspective may be an outlier in not playing to the expectations of Wall Street.

Perhaps Mr. Frazier understands that innovation in prescription drugs is critical for the long term success of Merck.  Perhaps he understands that truly innovative new products are what pharmaceutical companies need to remain relevant and viable in the evolving new healthcare market.  Perhaps he realizes that a reliance on academia and small entrepreneurial ventures for innovative new products carries the risk of a limited supply. This reliance on outside sources of innovation could subject his company to the finite availability of viable drug candidates at any given time which drives up pre-approval (and sometimes before clinical proof-of-concept) prices (think Gilead $11 billion acquisition of Pharmasset) with no assurance the products will ever get approved.

Mr. Frazier gets noticed  and media attention because he’s in the minority of not playing to the investment analysts’ needs for short term financial gains that can drive stock prices up and provide investors with temporary gratification while handsomely rewarding analysts and their firms for being so smart.

It would be one thing for investors to insist on increasing the productivity and output of Merck and pharmaceutical industry R & D.  I have commented before  and the industry has proven that merely spending more doesn’t necessarily get you more innovative new products.   But, to suggest Merck is spending too much on R & D seems to me to be another attempt by analysts to drive for a near-term balance sheet excitement that can help them drive share price, temporarily.

I’m sure there is room for improvement in Merck’s R & D productivity but I believe that to outright suggest they are spending too much money on R & D is not in the best interest of Merck, its shareholders, or patients.   mike@pharmareform.com

How Pharmaceutical Companies can help Increase FDA Productivity

First, I am not going to defend the FDA or ignore its organizational dysfunction and seemingly antiquated review processes.  No doubt, the agency is underfunded and lacking in the necessary expertise to carry out its broad and geographically disperse responsibilities.   At the same time there are steps the pharmaceutical industry could take to help increase FDA productivity.

Historical precedent would suggest that pharmaceutical companies are more interested in getting products to the market than making sure their products are safe, effective, or even needed.  They tend to do the absolute minimum to get through the regulatory approval process (fastest, easiest indication first), hoping to argue there way through questionable safety data and relying on marketing to find expanded revenue opportunities in patients for whom they have little or no proof of efficacy or safety.   Some of the antics reported in the trade and lay press would suggest that pharmaceutical companies are continuously trying to find new ways to “game” the system.  If you need the details, there is a good review of the past forty years of industry missteps and flagrant disregard for regulatory expectations in the book Pharmaplasia™.   It is clear that the FDA has been put on high alert police mode by what historically has appeared to be an out-of-control, intentionally non-compliant, almost defiant pharmaceutical industry that can’t be trusted.

In this context, is it any wonder that the FDA is skeptically cautious, more demanding for proof of claims, and sometimes even slow and seemingly uncommitted when it comes to product approvals and issuance of guidance documents yet deliberate and critical, albeit intermittent and inconsistent in their enforcement?

Here are five steps the pharmaceutical industry could take to help improve the regulatory process and FDA efficiency.

  1. Focus on Innovation
  2. Makes safety issues easy for the FDA to understand
  3. Make manufacturing quality an organizational priority
  4. Commit to ethical and regulatory compliant marketing and sales
  5. Establish a base of credibility

Focus on Innovation

Despite the sunk costs of discovering and developing a product that companies hoped would turn out better than it did, don’t bog down the FDA review process with products that have little or no clinical benefits over what is already available on the market.  If you feel compelled to bring a comparable product to market, don’t try to make it sound better than it really is to substantiate a higher price.  Again, trying to angle for a labeling claim advantage that doesn’t really exist consumes FDA time and resources.

Make safety issues easy for the FDA to understand

It is mind-blowing to me that pharmaceutical companies can get to a final advisory board meeting prior to an expected approval and find out there is a concern and unanswered questions about an animal toxicology study or clinical finding?  Well, maybe the company was hoping it would just slip by and nobody would notice the data or they thought they could argue their way through the questionable or disturbing data.  Why not be proactive, anticipate the concern and just get the data to prove it’s not an issue?  Well, maybe companies still believe in the “don’t look for it unless it is a regulatory requirement” theory because they might find something they don’t like or can’t explain.  I appreciate the need for speed in development but you have at least 3 to 5 years after a product starts clinical studies to sort out any safety issues.  That is, if you really want to take the risk to understand the basic sciences of the concern or potential problem.

Make manufacturing quality an organizational priority

First, the answer to industry manufacturing issues is not lower quality standards, fewer FDA inspections, or less rigorous, less critical inspections.  In fact, I am a proponent of maintaining high quality standards,  more frequent and more rigorous inspections, including of foreign facilities.

As challenging as pharmaceutical manufacturing can be, I don’t see why pharmaceutical companies should expect anything other than a clean slate, no 483′s,  when the FDA inspects their facilities.  With appropriate management manufacturing expertise and robust quality systems in place, avoiding 483’s should not be a matter of chance or wishful thinking but rather a matter of fact.  Clean, high quality, cGMP – compliant manufacturing would make FDA inspections (and follow-up) easier, less laborious, and less time consuming.

Commit to ethical and regulatory compliant marketing and sales

“Pushing the regulatory envelop” and “off-label” promotion can drive revenues and increase your market opportunity but also puts tremendous additional workload on the FDA.   So much so that it is clear that pharmaceutical companies have taken advantage of this burden by trying to be clever in their advertising and promotions knowing full well the FDA can’t police everything and the chances of being caught are remote.  Even if caught, the consequences are minimal (a “slap on the hand” in the form of a letter) unless the Department of Justice pushes for some financial penalty.  And then,  it just becomes a cost of doing business.  Unfortunately, pharmaceutical companies may feel they will be at a significant commercial disadvantage if they don’t “push the regulatory envelop” because “everybody is doing it.”

An industry-wide commitment to ethical and regulatory compliant marketing and selling would make non-compliant outliers more obvious and allow FDA to focus resources  on the more egregious and potentially harmful marketing and sales activities.

Establish a base of credibility

If the pharmaceutical industry were trusted, credible, and committed to regulatory compliance the FDA would not have to spend as much time, effort, and resources trying to sort out the “gamers” from bona fide efforts to bring safe and effective innovative new products to market, to maintain high quality manufacturing standards, and to market products in compliance with the approved label claims.  Yes, I believe there are companies and their CEOs who profess this to be their intent, but the historical record suggests there are few who have been able to deliver or credibly live up to this commitment.

mike@pharmareform.com