Our contributing editor and resident expert on PAT, Emil Ciurczak, sent a nice follow up to my recent article on Virginia Tech Professor Harold McNair. Ciurczak writes:

Thought you might get a kick out of the fact that I had my first formal GC course with Harold McNair in 1972 at PittCon in Cleveland. A mere 36 years ago ... and he was well-known then! It was more than interesting. The two instructors were McNair and Walt Supina (founder of Supelco ... large GC/LC supply house). After an hour of theory about polarity, etc., etc., etc. by McNair, Walt gets up in front of the class and simply says, "I just shoot my sample into whatever column is in the machine. If it comes out too soon, I increase the polarity; if it comes out too late, I decrease the polarity. Any questions?" The look on McNair's face was priceless.

I'd love to know if others out there have similar memories of Prof. McNair. Please add a comment below to let us know, and encourage others to do the same!

--PWT

Just saw the Obama/Biden "fact sheet for science" outlining some ambitious goals for the incoming Administration.  Its cornerstones:

• Restoring integrity to U.S. science policy to ensure that decisions that can be informed by science are made on the basis of the strongest possible evidence.
  • Doubling over a 10 year period the federal investment in basic research by key science agencies, with a special emphasis on supporting young researchers at the beginning of their careers, and backing high-risk, high-return research.
  • Making a national commitment to science education and training by recruiting some of America’s best minds to teach K-12 math and science and by tripling the number of the National Science Foundation’s Graduate Research Fellowships.
  • Encouraging American innovation to flourish by making the R&D tax credit permanent, streamlining our patent system, eliminating the capital gains tax on start-ups and small businesses, and promoting the deployment of next-generation broadband networks.
  • Addressing the “grand challenges” of the 21st century through accelerating the transition to a lowcarbon, oil-free economy, enabling all Americans to live longer and healthier lives, and protecting our country from emerging threats to our national security.

Amen!  Time will only tell how many of these will come to fruition, but they are sorely needed...and how nice that the phrase "basic research" comes up at all!

 But a new Administration brings with it questions about Federal Agency staffing.  It's easy to picture Al Gore as EPA chief.  But who should take over at FDA?  John Mack is taking a poll on this critical topic.  I think Janet Woodcock would advance the first bullet point most effectively at FDA. She's already been doing this behind the scenes.  (But would she want all the headaches of the job?)  As the Wall Street Journal health blog has noted, she is industry's favored nominee.  Perhaps even pharma companies regulated by FDA have to recognize that she is backing good science (even as some of them mistrust or ignore the Agency's invitation to change established ways of handling drug development and manufacturing)

As if the Agency didn't have enough to contend with, today brought news of an extortion scam in which callers identify themselves as "FDA Special Agents" and pressure customers into buying drugs (which are never delivered) online.  Here's more from the source:

Speaking of FDA, attended a very interesting symposium on Science at FDA's brand new, and sprawling, headquarters in Silver Spring Maryland on Monday, in which senior Agency staffers met with the press and scientists allowed journalists to visit their labs, and talked about what they are doing. and am just getting around to writing up a report.  More on that very soon. Clearly, FDA is getting much more proactive about media relations/outreach, just as it has embraced the whole Web 2.0 phenomenon.  This is a very good thing.  

In the meantime, if you'd like to see some real-life FDA impersonators in action, check this video clip from the not-quite-as-funny-as-they-think-they-are  folks at "Onion"

Press Release from FDA.....
The U.S. Food and Drug Administration is warning consumers about a fraudulent scheme to extort money from consumers by callers who falsely identify themselves as "FDA special agents" or other FDA officials. 
Several instances have been reported to the FDA of calls enticing consumers to purchase discounted prescription drugs by wiring funds to one of several locations in the Dominican Republic. No medications are ever delivered. A subsequent call is received from a fraudulent “FDA special agent” informing the consumer that a fine of several thousand dollars is required to be sent to an address in the Dominican Republic to prevent incarceration or other legal action.
“Impersonating an FDA official is a violation of federal law,” said Michael Chappell, the FDA's acting associate commissioner for regulatory affairs. “The public should note that no FDA official will ever contact a consumer by phone demanding money or any other form of payment. FDA officials always present identification in person when conducting official business.”
Consumers should note that the fraudulent calls appear to be from telephone numbers located within the United States, but are in fact from either ported voice-over-the-Internet-protocol numbers (calls made directly from a computer and moved or “ported” to other computers to avoid detection) or cellular phones. Reports to FDA describe the callers as having Hispanic accents.
The scheme most likely began with the theft of personal information from consumers who previously purchased drugs via the Internet or telephone or who were victims of credit card fraud. 
The FDA is investigating and complaints or information regarding this scheme should be reported to the FDA Office of Criminal Investigations at (800) 521-5783.
The FDA reminds consumers to purchase prescription drugs only from licensed pharmacies located in the United States. Information about the proper purchase of on-line medicine can be found at: http://www.fda.gov/consumer/features/drugsonline0707.html.

Paul D’Eramo—former ISPE chair, a two-decade veteran of FDA, and current head of Quality and Compliance Worldwide for Johnson & Johnson—always has a finger on the pulse of the regulatory environment, and knows that GMPs are fluid, not static. “We are always searching for what the ‘c’ in cGMP is,” he says.

At October’s ISPE 2008 show in Boca Raton, Florida, D’Eramo offered his take on current trends that are shaping GMPs. Though not surprising, his are the words of experience and insight:

1. There’s a new inspection model: FDA has become an international organization, and there is an increasing number of plant inspections being done by many countries’ regulatory authorities, D’Eramo says.

These authorities are sharing inspection, recall and adverse event data to a degree that they never have before. They’re training together, primarily through the PICs sessions that occur two to three times a year. These trends will continue. “Eventually we might see mutual agreements between countries to accept each other’s inspections,” D’Eramo says.

2. Regulators hold manufacturers responsible for quality and safety: Aware of the ever increasingly complex supply chain and the impossibility of keeping track of all plants, regulatory authorities are holding manufacturers—or, to be specific, license holders—ultimately responsible for Quality and Safety. While in the U.S., Congress has allocated more funding for FDA, it has also increased manufacturers’ responsibilities for contamination testing, labeling, and the number of products to which they must apply GMPs.

D’Eramo notes how FDA’s CDER director Janet Woodcock has said that all parties throughout the supply chain have to be responsible for their product. FDA must have the tools to hold these parties accountable, D’Eramo says; in particular, it must build an active, accurate database of pharmaceutical facilities. Yet FDA will continue to be limited in its resources, and thus will wield its authority through legal action. “They haven’t been afraid to do this in the past, but they will do this moreso,” says D’Eramo. “If they feel that management is not taking action [to resolve GMP issues], they’ll go for legal actions.”

In Europe, the EMEA has increasingly placed the burden of drug quality and safety on the “Marketing Authorization Holders,” and the role of the Qualified Person (QP) within each organization. It has also been requiring that drug manufacturers submit their own audit reports to health authorities—for example, EMEA has asked J&J API manufacturers to submit audit reports to verify that they have been visiting suppliers, says D’Eramo.

Japanese authorities are focusing on the Marketing Authorization Holder as well. In addition, Japanese inspectors are starting to inspect facilities outside Japan—and have done this with a few J&J sites, D’Eramo notes.

3. There is the continued trend towards harmonized global standards: This is see chiefly in ICH and its stipulations for GMPs, Quality by Design and Quality Systems. GHTF, ISO, and ASTM are also encouraging this trend. The heparin crisis of the past year has had a broad impact on evolving standards. It caused ICH to beef up sections within Q10 on supplier control and sourcing materials (careful supplier selection, clear documentation, etc.), and has put more of an emphasis on a lifecycle approach to quality within standards.

4. Regulators are promoting innovation . . . and providing regulatory relief: FDA in particular has realized its potential to promote (rather than stifle) innovation, and has made several key changes:

--It has come out with more reasonable Part 11 requirements for electronic documentation.

--New validation guidelines, which are pending approval, will allow manufacturers to facilitate PAT, real-time processing, and other efforts that are being undertaken.

ICH’s focus on Quality by Design will also stimulate new ideas and practices, and the use of tools for risk management, PAT and modern Quality systems.

5. New regulatory/registration requirements are ongoing. One is the trend toward reduced filing requirements for process changes (with fewer supplements)are also a positive sign, D’Eramo says. Merck’s ability to gain approval of Januvia through real-time release data is a great example of what such an environment can enable. “These things are all significant enough to help us all out with the business case” for adapting practices, D’Eramo concludes.

6. There is greater transparency in all manufacturing practices, D’Eramo says. If there are any issues or recalls, “the whole world knows about it.”

--PWT

The Competing Globally track also featured a presentation on Quality by Design, made by Russ Somma, President, SommaTech LLC, who worked for several years at Novartis and is also an editorial advisor on PharmaQbD.com.  Mr. Somma joked that the industry never had quality by accident, "We don't just lumber along and wait to fall apart, but the question is: Did you ask the right questions at the right time?" There's a need to better define process needs and required capacity early on.

"It's not a race to the end of development….we need a clear roadmap for development leading to tech transfer," he noted. Later on he described the need for PAT, but not as an add-on, without sufficient process understanding, or as an excuse to justify doing what you want (more on that later(.

He described the need to set drug product specs as well as the importance of:
a basic knowledge of:

• excipient interactions and process understanding
• raw material characteristics and variability
• a target product profile-a “desired state” for product
• stability of clinical forms, prototypes as well as drug substances.

CMC Project Teams are Critical
Mr. Somma said he was amazed that the CMC Project Team is a new concept for some drug companies ("What did you launch projects with before, a catapult?" he asked.)

He also noted the fact that product changes along the way can spell disaster, for example, if the product picks up moisture.

He suggested the following as some of the key questions to ask and attempt to answer as a starting point:

What are the properties that affect product performance?
What is formulation intended to do given drug substance properties?
What are the special requirements of the drug substance anddrug product?

He mentioned the importance of having a historical database for the product (one may start with broader ranges during early stages, he said, then tighten them.   These require a systematic reporting method referenced during clinical batches,pilot scale, scalup and validation.  This information then becomes  a part of knowledge store for product, and basis for SPC, facility design and maintenance.

It is important to determine the proven acceptable ranges, he noted:

Chart all process steps and controllable parameters
Provide a brief description of the process step and controlled parameter
Include Engineering units that are recorded
Anticipate result for exceeding proven acceptable range
Evaluate the risk of exceeding range

From this one can stablish the operating range to be used for process control, he said. It thus becomes like a staged-gate review process.

Next, one must develop process setpoint and establish equipment tolerances.  "You need narrow limits of values…know what potential failures could be and what you’d have to do about them, he said, noting that process analytical technologies provides a context for defining process-critical control parameters.

Don't Be Linear
"Don’t take linear approach and expect it to work in multidimensional world," he cautioned. "PAT is not a fancy term for getting away with what we want."  Critical sources of variability should be known, variability managed, prior quality attributes predicted, rationale for change

Many firms apply PAT as add on technology, when the underlying process understanding isn’t there, Somma said recalling a company that called him.  They were having trouble with their filling line.  Their IR sensors weren't picking up measurements.  It turned out that the tablet coating was releasing dust, coating the sensors and preventing them from functioning. Somma suggested that the process needed improvement and that it might be overheating. "“But we’re adding PAT to the coating line” was the response he got.  

Moving from Tacit to Explicit Knowledge
Mr. Somma sketched the different types of knowledge, noting that tacit knowledge needs to be replaced with explicit knowledge if scaleup is to proceed correctly and if improvements are to be realized across different functions within a company.  And that knowledge needs to be set forth in a database.

He cited tablet development as an example, since it is time consuming and iterative and scalup is less well understood than other processes.  He summarized new techniques in compression simulation and hybrid continuous process systems singling out MIT's  3DP Process used by the Pennsylvania-based company, Aprecia, and the Glatt Multicell GMC 30, semicontinuous process….

Quick Does Not Equal Cheap
If you want to be quick, Somma noted, you're not necessarily going to be cheap.  "YOu have to throw intelligence rather than money at the problem...and consider the product in its entire life cycle to formulate a proactive rather than reactive submission strategy," and to avoid fishing expeditions for data, and approval delays.

In short, he said, "Know what you do not know." U.S. pharma often fumbles over its own requirements and regulations.  "There are companies [that are already] doing things this way and if you don’t consider changing the way you do things, they’re going to eat your lunch…"  You'll find more about him on www.sommatechconsulting.com

On Monday afternoon, a manufacturing and operations discussion group focused on the topic of global competition.  Session chair Julian Wilkins, Vice President of PharmaConsult US, Inc. and a part-time professor of Pharmaceutical Manufacturing at Stevens Institute set the stage with an introduction spelling out the issues and challenges.

One of the points he made was about education in the U.S. Among OECD countries, he noted, the US has slipped to #16 in high school graduates, and 9th in post secondary enrollments. He also noted that 7 out of 10 U.S. students nationally graduate without completing courses needed to succed in college or the workplace….India and China are rapidly moving ahead of the US and Europe in terms of education, he noted, pointing to his own students at Stevens, most of whom are Indian. Currently, he said, he does not have one U.S.-born student in his pharma manufacturing classes. 

He discussed the need for innovation, which is percolating in Indian life sciences, despite lack of capital and an often chaotic infrastructure.

Innovation Inversely Proportional to R&D Facility Cost
At this point, he introduced the "law of pipeline development": The discovery of NDA candidates is in inverse proportion to the cost and luxuriousness of the R&D facility.  "I’ve seen many [unproductive] palaces, where the innovation is coming from universities and small operations…..remember HP's garage?"

He also challenged the West-centric belief that compliance is necessarily more lax abroad.  Compliance, and noncompliance, know no boundaries, he said, posting FDA 483's from Sandoz in the U.S. and Ranbaxy in India, side by side. and noting the many similarities between them. 

Dangers of Short-Term Thinking
Wilkins criticized the industry's reliance on acquisition, joint ventures and consortia to develop innovative new compounds, emphasized the need for safety and ergonomics, citing studies by Dave Eherts PhD, Medical and Aviation Safety, Sikorsky Aircraft Corp. (For more information on a recent review, click here) He also mentioned the need for green product development.

Failure to think long term, he noted, often shows in a failure to respect the workforce and a management that "flies blind to details that matter."

He then cited a number of statistics and trends from a groundbreaking Regent Atlantic report on changing forces at work within the industry that you can access here.

As a company moves from short-termism and a view of the workforce as the enemy, one sees a shift in employee attitudes, from “rebel or quit” to “malicious obedience” to "willing compliance" to "cheerful cooperation" to "hearfelt commitment" to creative excitement…There is a need for cultural change within the industry, he noted.

John Fielding, Senior Director at Genentech, later expanded some of these points in an extended report on issues facing the industry.  He hinted at the company's Factory of the Future program (which we'll hope to cover in greater detail) as well as its efforts in sustainable design, energy efficiency and environmental safety, as part of the LEED program.

There was no applause from the audience for any of the speakers...until Dr. Afnan's presentation at the end of the session.  Surely, anyone who prepares powerpoints and a talk before a discerning group of engineers and technical people deserves some applause!

AMS

A number of speakers at ISPE's conference referred to the Certified Pharmaceutical Industry Professional (CPIP) program that the organization has rolled out, providing certification that an industry professional has met a certain agreed-upon level of competence in GMPs and other critical subject areas.

A growing number of very sharp people in the industry have signed up for this and are now "certified." I was very surprised to learn, though, that ASQ also offers a GMP certification program for pharma professionals. Last week, I interviewed ASQ Senior member Robert Seltzer of Schering-Plough, who first had the idea for this certification test and program about five years ago.  The first official tests will be given soon, and ASQ expects a large number of people to apply to take the exam.  Mr. Seltzer says that this exam is geared to senior level practitioners, where ISPE's is more for entry-level people.  However, I noticed that quite a few of the CPIPs are mid-level or seniorish level professionals.

Both programs are probably excellent, but isn't it confusing to have two different programs that claim to accomplish the same thing?  I wondered why ISPE and ASQ couldn't work together on this, or at least promote each other's programs...in general, wouldn't it be interesting if ISPE collaborated with ASQ on more projects (and brought more examples from outside pharma, in areas such as continuous quality improvement, PAT, FMEA, etc.). After all, ASQ works across many different industries, each with a different lesson to impart? Just a thought....

In the meantime, here is some very basic information on ASQ's program. The podcast interview with Mr. Seltzer and a sample of mock exam questions will be coming your way on November 11 (if you subscribe to our PharmaManufacturing enews and multimedia alerts).  If not, please contact me around that time for more information or check our web site in the middle of next month.

AMS

________________________________________________

ASQ Certified Pharmaceutical GMP Professional (CPGP)
Proposal for Adopting a New Certification for Pharmaceutical and Allied Industry Professionals to Demonstrate an Intermediate to Advanced Knowledge of Worldwide Pharmaceutical Good Manufacturing Practices (GMP) Laws, Regulations, Guidelines, Standards, and Principles, etc.
 

I.      EXECUTIVE SUMMARY: 

The proposed ASQ Certified Pharmaceutical GMP Professional (CPGP) exam is the revised name and acronym from the earlier proposed name, Certified Pharmaceutical GMP Compliance Professional (CPGMPCP).  This was suggested by both the ASQ Certification Board and by the Board of the Food, Drug and Cosmetic Division of ASQ.  In addition to opting for a shorter name and acronym, it was acknowledged that not all professionals who would sit for the exam are employed in strictly “compliance” but function in many other job titles/categories that make significant use of pharmaceutical Good Manufacturing Practices.

This proposed certification differs from other ASQ sector-specific certifications—CBA (Biomedical) and CHA—in that it would apply to/appeal to professions in addition to auditors: 

CBA =     Medical Device Industry   +        Device Quality Stds              +     Auditors

CHA =     Food Industry                     +         HACCP  Regs/Principles     +     Auditors

VERSUS­

CPGP =  Pharmaceutical Industry   +  Pharma GMP Regs/Principles  +      Professionals

As decided by the committee chartered by the FDC Division Board, namely the PharmCert Committee of FDC, the CPGP exam should be made available to pharmaceutical and allied industry professionals that interpret and implement the GMP laws, regulations, guidelines, standards, and principles enacted and/or published domestically and internationally.  The potential CPGP examinees...would need five (5) or more relevant years of experience in the pharmaceutical or allied industries to sit for the exam, as this is not an entry-level GMP exam.  Such an exam would cover nine Body of Knowledge categories with weights determined via a Job Analysis drafting and survey process. 

The key benefits of obtaining the CPGP Certification by individuals (as well as the benefits accruing to the companies for whom they work) are as follows:

•          Enables company individuals and management to raise the GMP compliance “bar” to a higher level.

•          Supports internal company programs of Continuous Quality Improvement (CQI).

•          It is sector-specific applied knowledge.

•          It’s a source of professional and personal pride.

•          Enhances a professional’s credibility and standing with outside business partners.

.

Body of Knowledge Category/% of Cert. Exam
 
I.        Regulatory Agency Governance 14.1
 
II.       Quality Systems 21.9
 
III.      Laboratory Systems 11.6
 
IV.      Infrastructure (Facilities, Equipment, & Utilities) 9.1
 
V.       Materials Management/Supply Chain 8.8
 
VI.      Sterile and Nonsterile Mf’g Systems 10.1
 
VII.     Filling, Packaging, and Labeling 9.9
 
VIII.    Product Development 7.6
 
IX.     Technology Transfer 6.9
 
Total =
 100.0
 

Janet Woodcock, head of FDA’s CDER, strikes me as the type of person you’d want in charge during a crisis.  And that’s exactly where FDA, and CDER, have found themselves this year, so I’m not surprised that Dr. W. was reassigned from her post of Chief Medical Officer and Deputy Commissioner to head up CDER.  Using the triage imagery of the Emergency Room, running the Critical Path initiative is important, but maintaining control of CDER, drug review and inspections, is urgent.

Woodcock opened her keynote with her usual call for global harmonization, science based manufacturing and control, emphasizing the point that it is the industry’s job to understand and control its processes, even as its supply chains become more complex.

The recent heparin contamination case, she said, was a wakeup call for the industry, and emphasized the need for vigilance throughout the supply chain.  Globalization has made this vigilance difficult, she said, especially since the number of drug products made at foreign sites has more than doubled since 2001, while the site inspection rate has declined by 41%.  Adding more inspectors and inspections as the Agency plans to do, using increases in funding, FDA still won’t be able to catch up with the global outsourcing trend.

Generic drugs, now most widely subscribed in the U.S. pose a particular problem, since distant facilities are increasingly named in ANDA’s. 

FDA has also been hampered by a fragmented global regulatory framework.  “In many ways, [global regulation is]  back in the 1950’s.”  Even though nations are rallying around ICH, there is still variability and fragmentation.  For a U.S. government agency, there has been an erosion of FDA’s ability to “mind the store,” when that store is global.

Dr. Woodcock's use of understatement brought chuckles to the audience. At one point, she mentioned that she had spoken to Congress about these issues several times and “expects to make further appearances.”  “We need to deal with today’s global realities,” she said, “and how we maintain quality in this new environment.”

Dr. Woodcock went on to discuss the issue of counterfeit and substandard drugs in the emerging drug manufacturing centers (or, rather, as Dr. Rosling, described them, the mid and low-income nations).  Local training programs will be critical, she said.  (We’ll be writing about one such program, in Madagascar, that was established by USP and has become a model and template for others of this type). 

Inspection's No Panacea; No Buck-Passing, Please
Dr. Woodcock emphasized that inspection is only one component of regulation.  “Congress is very focused on this, but it won’t be the way to guarantee [safety and quality].”

Instead, she said, manufacturers, brokers, importers and distributors need to take primary responsibility for quality.  Regulators can work more closely with local law enforcement agencies, but it is the duty of manufacturers and suppliers.  “Ours in an audit function.  We need to enable continuous improvement and we cannot impede innovation.”

Role of Professional and Technical Societies
Professional technical societies and standard setting organizations need to set standards, Dr. Woodcock said, mentioning the work that ISPE is doing with the PQLI.  Meanwhile, she said, technical societies need to widen the circle and develop global professional communities.

A critical step for harmonization, she said, will be increasing the presence and effectiveness of local inspectorates, to establish standards for ICH and non ICH regions.

There may be a need to extend cGMP’s to excipients, she noted, to modernize manufacturing and harmonize pharmacopeial standards. “Every time we have fragmentation, we create more barriers for global product quality.”

She mentioned the need for more effective methods for supply chain management and integration as well as better automization of globalinventory management.

Dr. Woodcock touched on the FDA Beyond Our Borders program, and the fact that the Agency will be recruiting new people.

She asked the audience to comment on proposed registration and listing system using structured product labeling.  “We need to prevent any train wrecks, errors on the IT side.”

Tracking and Tracing
FDA is also working to develop unique product identifiers, and evaluating the use of DUNS (Dun and Bradstreet) numbers, and moving to electronic verification of listings.  The Agency, she said, will continue to encourage RFID and technologies like it.

Defining the Design Space, Controlling Excipient and API Quality
Finally, the Agency will release a “regulatory agreement guidance” on QbD and the Design Space and related guidances for filing status on related supplements.  This is at the top of the Center’s priority list, she said.  (This should be welcome for the many people out there who still don't really understand the idea of the Design Space or other key terminology of QbD.  An informal poll during a Webcast we aired this month (click here to view) found that this was a major obstacle for most people contemplating this new model for drug development)

Recent events have highlighted the importance of the quality of excipients and APIs, and the need to identify sources of variability in these components, which is the key to ensuring final product quality.

She mentioned the public’s and regulators concerns about food and drug adulteration and food-borne illnesses, and the fact that a number of draft bills would establish controls for manufacturers and increase FDA’s authority.  “We will expect to see legislation move in late Winter, early Spring” she says.

She mentioned that Critical Path was quietly progressing, but that pharmacovigilance initiatives have moved forward at a faster pace, especially in the area of genomic data submission.  “Some drug labels are even starting to contain genomic data,” she said.  An example of Stevens Johnson syndrome, which has been linked to specific alleles….testing is being required.

The Biomarker Consortium at FNIH is also making progress, she said, as well as the Clinical Trial Improvement initiative with Duke University.

Getting a Handle on Unsuspected Adverse Events
Dr. Woodcock also said that the FDAA has led to improvements in pharmacovigilance, especially the REMS risk management process, as well as a major pediatric drug safety program.  However, she said there is a need for systems to be able to detect unsuspected adverse events more efficiently.  The Agency is now developing IT systems that would be able to use medical claims and other data to better link prescription and purchase data with clinical outcomes.

Also on the IT front, the Agency’s Sentinel system is being shored up, and pilot projects are now ongoing.

The science base, she said, has invigorated drug manufacturing and complementary efforts will be needed in drug development and postmarket surveillance, and all these efforts will need to be much more tightly linked to quality.

End Pharma Parochialism: Think Globally, Act Globally

Anyone who still thinks of the term “third world” or uses “industrialized” vs. “developing” to describe world economies was duly chastised, in a most amusing and good-natured way, by Dr. Hans Rosling, Professor of International Health at the Karolinska Institute in Stockholm, Sweden.  (For a video of Dr. Rosling giving a similarly spirited presentation at an event two years ago, click here). 
Dr. Rosling, who cofounded Physicians Without Borders in Sweden, has worked around the world.  While in Mozambique, he discovered “konzo,” a paralytic disease caused by hunger/malnutrition (and badly processed cassava root). With family members, Dr. Rosling also established the Gapminder Foundation in Sweden three years ago, to continue development of Trendalyzer software, which brings statistical information to vivid life.  Google acquired the software last year, but the software can be seen (and played with) via http://www.gapminder.org/.  Its use should be required for anyone giving a presentation that involves statistics and trends.

This is the kind of keynote speaker one wants to hear at an event of this, or any, sort---someone with a keen intellect whose eye is very much focused on the big picture, and yet who manages to maintain a sense of humor.  At one point, he stopped to admire the technology behind the old-fashioned pointer he used for the talk (“it’s even recyclable”)

New economic models needed for drug development
The underlying theme of his talk was the industry’s urgent need to develop medicines for the world’s most ravaging diseases---without destroying the basic free market principles that drive the industry.

He discussed the preconceived notions that so many of us continue to have, convinced that we are operating on a “fact-based world view,” and dividing the world based on “long life with small family” vs. “short life with large family.”  The nations of the world could be neatly divided that way, he said, but that was back in 1950.

Rosling used Vietnam as an example.  Even though the country is more than a century behind the U.S. economically (its per capita GDP is now about 39, where the U.S. figure was about 50 back in 1900), it now has a higher life expectancy than the U.S. did after the Vietnam war, he said, so it is only one generation behind the “developed nations” as far as health care is concerned. 

Diligent Asians vs. Lazy Americans and Europeans?
He interspersed jokes throughout his talk, commenting, for example, on the work ethic of Asian students vs. Europeans, noting how he often works until midnight, and he and the Asian PhD students are the only ones waiting for the bus (“the Swedish graduate students had gone home hours earlier.”)  This theme was also found in some other presentations by U.S. professionals.

Although he acknowledged that 1.2 billion of the people on earth are now living below the poverty level, most people in the world are now “in between,” Rosling said, quoting the World Bank’s Yuri Dikhanov. (More on Dikhanov’s methods here. For a video program that Dikhanov participated in at MIT, discussing global drug pricing, click here. )

In Latin America, Rosling said, every income level can be found, with Mexico’s richest man outstripping Bill Gates on the Forbes wealth-o-meter last year.

In the 1970s, most of the world’s poverty was in China and India, he recalled, and many concluded at the time that “neither of them would succeed. ”

Three billion people are now coming into the global market economy, he said.  They may be viewed as a threat to pharma professionals in the U.S. and Europe, as they are highly trained and may snap up some industry jobs, but they also make up a huge market for new drug products as the pipeline moves from a focus on infectious diseases to cancer and the diseases of affluence.

He joked about how world views have changed, calling the Vikings the al Qaeda of their time, and sketching the following progression:

Dawn – barbarians vs. empires
1492 - colonies vs. empires
1948  - developing vs. industrialized.

Today, the world is instead divided into low, medium and high income regions (and, tragically, “collapsed nations” such as Afghanistan)

Middle income nations are showing economic growth….a quarter of world economy is already there, he said. The correlation between money and child survival is strong (0.8), he noted, but one can find wide variations within the same income levels. He pointed to Turkey, early in his presentation, as one example.

He also discussed “grandma-certified” statistics, a very nice, personalized way to illustrate the fact that we share more similarities than differences and that all nations are on a growth curve:  When his great great grandmother was born, Rosling said, Sweden’s economic situation was like that of Sierra Leone’s today, his grandmother was born at a time when it was like Egypt’s, he was born when it was like Mexico’s and his daughter was born when it was like Singapore’s today.

He then related income level to access to medical care and pharmaceuticals.

Low income 2 billion, $300 gdp per capita,  health expense $15 per year per capita, drug expense per capita, $10

Mid income 3 billion, $3,000 dollars gdp per capita, $200 per year health expenses per capita, drug expense per capita, $50 per year….

High income 1 billion,  $30,000 dollars gdp per capita, $3,000 per year health expenses per capita, drug expense per capita $300

Each region’s access to diagnosis and treatment (D&T) is different

Disease   Low Income  Mid Income  High Income
Iron deficiency  D&T in all
Pneumonia D   D&T   D&T
(lose millions of children each year)
Cancer    -   D   D&T
Depression   -   -   D&T
ALS    -   -   D

In 10-15 years, Rosling said, the world will likely have solved the problem of lack of treatments for low income areas….he had high praise for the Gates Foundation’s pioneering work in this area.

However, he noted the disparity in access to treatment and diagnosis, summarized above.  Depression, he noticed, was a key cause of death in some middle income nations and among some population groups, for example, women in China; diagnosis and treatment are needed, he said.

Dr. Rosling also discussed recent IMF growth outlooks:  Western Europe and the U.S. are expected to grow by 0.3%, Latin America by 3% and Asia, Africa and the rest of the world by 6%, with Africa growing by 6.3%.

“It really is a new world,” Rosling said, noting that we need to see the world based on new income levels, and discard the idea of “the West and the rest”.

He left the audience with this challenging question:  “How do we make innovations available without forcing people to wait 20 years AND without depriving companies of their profitability?  We need clever business models that will leave a legacy that will say, this was fair, there was return on investment.”

The past few years have seen some innovative ideas from Genzyme and we’re seeing others as well. (Click here for some discussion at BIO this past summer) More ideas, anyone?

-AMS

I’m typing these notes, wedged sideways so that my laptop will fit on an empty middle seat, as I fly home from ISPE’s annual meeting.  (A friendly warning:  if you are over 5’4” tall, don’t travel on Spirit Airlines unless

a. you absolutely have to, or

b. you have one of those “big front seats.”  (Be prepared to pay $3, by credit card, for that horrible cup of coffee or unsatisfying can of soda. And the same amount for the flight as you’d pay on any other airline. )  

The venue for this year’s program was the beautiful Boca Raton resort in Florida.   Florida, with its palm trees and broad avenues, has always seemed to me to exist (for good or bad) in a time warp. Maybe Miami's different....but I remember a visit to St. Augustine during the mid-1980’s when I spotted a family out for dinner, with dad proudly wearing his red Masonic order fez (and I thought the crazy hats and the Royal Order of Raccoons went out with Ed Norton and Ralph Cramden…)

It’s a state known for conservatism, yet both Mc Cain and Obama signs were in evidence on front lawns all over town, and some cars driven by women who might be “Golden Girls” sported Obama bumper stickers.   

Colleagues, divided along political party lines, tried to keep the banter and repartee friendly. As election day draws nearer, the truth has been stranger than fiction, what with a Florida journalist quoting Karl Marx in an interview with Democratic VP candidate Joe Biden and disturbing news of an extremist group plotting an assassination and terrorist acts in the South. Fox News and CNN are vying for Election `08 supremacy, becoming somewhat like our own homegrown versions of Pravda and Izvestia ...all too often, the truth is lost in all the spin. (I confess that I'll take CNN over Fox any day, though)

Outstanding keynotes
The keynotes and even the posters this year were outstanding. Unfortunately, my incoming flight was delayed and I just missed Genentech Executive Vice President Patrick Yang’s presentation. Yang had spoken in Chicago recently on operational excellence in pharma and the essential characteristics of a manufacturing leader (click here for a previous blog post describing Yang's talk by Senior Editor Paul Thomas) 

By the way, Yang isn’t a biochemist or chemical engineer, but has a Ph.D. in electrical engineering and spent 12 years at General Electric, in R&D, engineering and technology management before moving to pharma (Merck) and biopharma at Genentech. 

Perhaps his coming from outside of the pharma world has given Yang a clearer vision of potential ways to improve compliance, operations and supply chain management.   

As several speakers at this year’s conference remarked, notably FDA’s Ali Afnan, from whom we haven’t heard all that much since the heady days of the PAT Missionary Movement, pharma needs to look beyond its borders for inspiration and role models.

Perhaps that may even hold true for ISPE as well (but more on that later).  

For any of you who wanted to attend but couldn’t, here’s a recap of Monday’s events and who said what, interspersed with the usual ramblings.

  Entire tracks are being devoted to QbD and the whole PQLI effort today. No doubt you’ll hear more on them from Paul, who is at conference today and Wednesday.

-AMS