Michelle Hoffman, editorial director of Pharmaceutical Technology.

Michelle Hoffman

I have been fortunate in my career to meet and interview many of the scientists who have shaped modern biology and medicine and many more who worked with them. One such witness to history recalled for me his days as a postdoctoral fellow at the National Institutes of Health in the early 1960s. It was the practice at the time for the various research groups to get together on Friday afternoons to report on their work. The topic one Friday struck him as exceptionally dull, centering on the cell-free translation of a synthetic poly-uracil oligonucleotide. "Well, that's eminently missable," he thought as he happily skipped out of the presentation to join friends at a nearby bar. 

 This particular "eminently missable" talk was in fact the announcement by Marshall Nirenberg's laboratory that they had deciphered the first word in the genetic lexicon and so, had begun to "crack the genetic code." The laboratory then went on to translate the rest of the genetic code, a feat that earned Nirenberg a share of the 1968 Nobel Prize in Physiology or Medicine, along with Robert W. Holley of Cornell University and Har Gobind Khorana of the University of Wisconsin at Madison. 

I am reminded of this story because Marshall Nirenberg died on January 19. And while I never met him, it seems fitting to pay tribute in these pages to a scientist whose work is a pillar on which the biopharmaceutical industry rests—not to mention biotechnology and molecular medicine. Equally important to recognize was Nirenberg's social consciousness and his concern that the new science of "biochemical genetics" be used responsibly, ethically, and wisely.  

 in 1967, Nirenberg asked, "Will Society be Prepared?" He wrote, "When man becomes capable of instructing his own cells, he must refrain from doing so until he has sufficient wisdom to use this knowledge for the benefit of mankind" (1). 

 Nirenberg's fear, articulated in his quote from Salvador Luria—himself a Nobel Laureate and contributor to molecular genetics—was that "the progress of science...creates an imbalance between the power it places in the hands of man and the social conditions in which this power is exerted." Luria went on to say that all of the collective wisdom of science and the public is incapable of compensating for "inadequacies of the institutional framework to cope with the new situations." 

Fortunately, none of the extreme scientific abuses Nirenberg and Luria feared have come to pass. Nevertheless, their concern about the lag between technical ability and social policy remains as much an issue today as it was in 1967. Social policy still trails behind technology. For example: Will we or won't we allow the use of embryonic stem cells for regenerative medicine? Will we or won't we allow therapeutic cloning? How about gene therapy? What's the proper way to proceed with follow-on biologics? How will we assess and regulate them? How and when will we decide? 

Nirenberg closed his essay with this prescription, "...decisions concerning the application of this knowledge must ultimately be made by society, and only an informed society can make such decisions wisely." Will society be prepared, indeed? 

 Note: Nirenberg's biographical information is available from the National Library of Medicine, at 

http://profiles.nlm.nih.gov/JJ/Views/Exhibit/narrative/biographical.html

Articles

The death of a pioneer in molecular genetics recalls age-old questions about social fitness to ensure the ethical uses of scientific advances.

Science and Sensibility

Retrospectives of the decade for the pharmaceutical industry will undoubtedly mention US efforts to reform its healthcare policy and the continuing globalization of the pharmaceutical industry. So it's interesting to note the convergence of those two issues in a fact sheet quantifying the price of corruption in the global medicine chain posted in December by the World Health Organization (online Fact Sheet #335).  

Among the more striking conclusions of the WHO posting is that a quarter of the more than $4 trillion spent globally on health services every year (including some $750 billion on pharmaceuticals) —a full trillion dollars—is lost to corruption. Much of this corruption goes unreported, the WHO document claims, out of fear of victimization and retaliation coupled with a lack of incentives for whistle-blowers. Such corrupt and unethical practices reduce the availability of drugs and quality healthcare to patients. Countries with higher incidences of corruption also experience higher child mortality rates. 

Additional WHO statistics shed light on the costs and consequences of various levels of health spending (see Table I). For example, at $6103, the US spends the most per person each year on healthcare, while Burundi spends the least, at $2.90. Although the statistics indicate that $2.90 per person per year is far too little to increase life expectancy, life expectancy does not necessarily rise after a certain spending level is achieved. At $1000, that level falls well below the US annual per capita spend.  

Table I: Costs and consequences of health spending. 

WHO's statistics seem to indicate that life expectancy rises logarithmically from 30 years, when the annual per capita spend is $0, to 70 years at an annual per capita spend of $1000, but levels off at that point. The data do not indicate how the increased spending correlates with an in increase in 

Overall, these statistics suggest that, theoretically, healthcare costs could be cut dramatically around the world by reducing inefficiency and corruption—easier said than done. Also, healthcare around the world might improve significantly if annual spend were readjusted globally so that more people could have access to the $1000 per year that seems to push life expectancy into the upper reaches. At any rate, these statistics indicate that the US may be able to spend a lot less on our health than we now do with no reduction in life expectancy. 

If the past decade has taught us anything, it's that resources—natural or manmade—are not infinite. Hopefully, the next decade will find us chastened, wiser, and better able to make judicious use of our medical and healthcare resources.  

From healthcare to corruption to life expectancy, here's what we can learn from the past decade.

Refocusing Our Resources

Just as indicators are sending mixed messages about the health of the US economy—GDP is up, while job growth is sluggish—the Pharmaceutical Technology 2009 Employment Survey delivers contradictory messages about the pharmaceutical industry. Salaries are up over last year, job security is way down, and almost two-thirds of the 1500-plus respondents have been through some kind of corporate reorganization during the past year. Nevertheless, job satisfaction remains high with employees in the pharmaceutical industry indicating 3 to 1 that they feel valued by their employers, and more than 60% of respondents say it is unlikely or very unlikely that they'll change jobs this year. 

Private industry remains the primary employer to 86% of respondents working for private companies. Academic institutions came in a far-distant second with 4%. The number of respondents who are self-employed, or work for government or nonprofit institutions came in even lower still. Among those who work in private industry, more than a quarter work for companies that employ over 25,000 people, 17% work for companies with 100-500 people, and 11% work for companies with fewer than 50 employees. As a result, most of these responses reflect life at privately held corporations of varying sizes. 

At 17%, quality control and assurance professionals are the best represented job function of survey respondents, as has been the case in years past. Eleven percent are professionals in pharmaceutical development, retaining last year s second-place spot. Rising to third from last year s fourth place position, were production research and development (R&D) professionals, accounting for 8.8% of respondents, and relinquishing its third-place position, were professionals in pharmaceutical analytical development, who now occupy fourth place at 8.3%.  

Table 1:Given the Opportunity, I Would Leave My Job 

On average, workers report they were contracted to work for 27.8 hours, down from last year s average of 32 hours. Actual hours worked also declined from last year s 40 hours to 31 hours. 

Table II: Have the following regulatory guidelines and initiatives changed the manner in which you perform your daily activities at your present job? 

This year, job security is the big story, not unexpectedly in this time of extreme economic turbulence. An all-time low of 51% of respondents reported feeling secure in their jobs, down from last year s low of 55%. 

Table III: Please rate the importance of the following types of knowledge in fulfilling the daily activities of your position 

In contrast, 80% of respondents felt secure about their jobs in 2001. But if workers are feeling insecure, it's with good reason. Sixty-four percent of respondents report their company has gone through some kind of reorganization—a downsizing, restructuring, merger, or acquisition—this year. About 53% of those experienced some kind of job change as a result, primarily a change in function. About 7.4% of respondents left their jobs involuntarily, and about 4% said they left voluntarily. 

Table IV: Please rate the importance of the following skills in fulfilling the daily activities of your position 

Government workers feel the greatest job security, with 92.3% of those feeling sure that their jobs will continue to exist. Among academics, 69.6% feel secure, followed by workers in private industry with 49.5% reporting feeling secure. Least secure are workers in nonprofit organizations; 42.3% of these feel secure in their jobs. Interestingly, 60% of workers at nonprofit organizations say they would leave their jobs given the opportunity.  

PharmTech was interested in knowing how security tracked with job function and found that 75% of educators feel secure in their jobs, which put them at the top of the list. Next most secure are professionals involved in finished dosage-form manufacturing, with 65% reporting feeling secure, followed by about 63% in product management who feel secure. With about 35% feeling secure, workers engaged in pharmaceutical analytical development feel least secure, followed by those working in drug metabolism at 40%.

Most workers feel their work is fully valued by their employers. Most valued are experts in drug stability; almost 100% of these report feeling fully valued. Over 90% of workers in drug delivery and packaging also feel fully valued by their employers. At least 70% of workers in all other job functions feel fully valued, with the exception of two functions. Only 60% of workers in drug metabolism feel fully valued, but the rock bottom position belongs to workers in preformulation, with little more than 30% feeling fully valued by their employers. 

About 65% of preformulation developers say they would leave their jobs if the opportunity presents itself. Forty percent of workers in drug metabolism say they'd choose to leave their jobs. Workers in drug stability are least inclined to leave their jobs. 

Not all workers have the choice to leave. PharmTech asked how many felt circumstances would dictate that they change jobs in the coming year. It should come as no surprise that workers who feel most secure in their jobs are the least likely to foresee a job change in their near futures. In fact, of the more than 70% percent of those who feel it is unlikely that they'll be changing jobs this year also feel secure in their jobs. In contrast, among those who feel they're most likely to change jobs, only 24% feel secure. 

A large number of respondents—almost 70%—feel their jobs make full use of their skills and education, while 12% do not. Interestingly, the best employer in that regard is oneself, as 96% of the self-employed feel they fully use their skills. At the other end, only 57.7% of workers in nonprofit organizations feel that way. Just under 70% of employees of private industry feel their skills are fully used, and just over 70% of academics feel their skills are fully used. Almost 77% of government employees feel their skills are used to the fullest extent.

Figure 2: Respondents possibility of leaving job next year. 

Most important to employees considering a job change is income, as reported by almost 60% of respondents. Other important attributes when considering a new job are work/life balance (33%), intellectual challenge (32%), and geographic location (31%). Least important to job seekers are scientific opportunities (40%), vacation allotment (35%), and pension or retirement benefits (27%). 

Figure 3: Regional distribution of respondents within the US. 

The big surprise this year is that salaries were up universally. Whereas last year's average for workers inside and outside of the US was $85,087; this year's average was $94,079. The rise may be due to several factors, including the weakening dollar, which would make overseas salaries relatively higher than in years past. It may also be that when downsizing does occur, lower paying jobs are preferentially eliminated. 

Figure 4: Organization type of respondents. 

Employees received an additional $14,536 from their principal employers, including income from bonuses, grants, and summer work. Again, this figure represents an increase over last year s average of $10,892. Workers reported earning another $2860 from other professional work, more than $1000 over last year s earnings. 

Not only are salaries on the rise in general, but it appears that the gender gap is closing in the US and abroad. Overall, men earned on average $97, 538, while women earned $85,995. The gap of a little more than $11,000 represents a decline over what has traditionally been a $20,000 gap. Interestingly, the gap is greater inside the US than it is overall. US men earned on average $110,981; women, $97,758. 

Figure 6: Effect of reorganization on respondents. 

The best paid workers in the pharmaceutical industry are not involved with pharmaceuticals at all. They work in information technology and information services and earn on average $123,462. Earning $111,372 on average, the second highest paying function is technology transfer. Other six-figure salary jobs are, in descending order: pharmaceutical development, regulatory compliance, engineering and engineering management, and drug delivery. 			

Figure 7: Respondents experience with downsizing. 

Professionals in drug metabolism and production management saw a decline in their pay. These workers now earn on average less than the $100,000 they did last year. Least remunerative is education; educators earn $65,500 on average. Also toward the bottom are packaging professionals at $71,816, drug stability professionals, with an average salary of $72,287, and workers in preformulation development, with an average annual salary of $78,833. 

Figure 8: Respondents likelihood of changing jobs. 

Pay rose over last year's averages for all regions within the US, with those in the Northeast continuing to garner the highest pay, with an average salary of $117,372, up from last year's regional average of $111,171. As in years past, those in the Southwest come in second with an average of $106,580, which also represents a rise over last year s average of $102,240. With an an average salary of $83,896, employees in the Northwest realized the lowest average pay but also enjoyed the highlest pay raise, reporting on average almost $9,700 over last year s average. 

Figure 9: Respondents salary (US workers) by gender. 

Essential skills, education, training, and knowledge

Respondents with bachelor s and master s degrees are approximately equal in number and each represent about one-third of respondents. At 28.9%, slightly fewer respondents hold doctorates, and a small percentage (4.5%) hold an associate's degree. The most common training was in pharmaceutics or pharmacy, representing 17% of respondents. This was followed by analytical chemistry (14.6%), and fields unrelated to pharmaceutics or science (11%). Over half of respondents were trained in the US (including Puerto Rico), followed by 12.7% trained in the UK, and almost 4% trained in India. 

About one-third of respondents felt their education prepared them extremely well for their current positions, with an additional half feeling their education to have been adequate. Six percent felt their education prepared them poorly for their current positions. In contrast, almost 97% of respondents felt their previous employment experiences prepared them for their current positions. 

Figure 11: Respondents salary by region. 

Among the types of knowledge that respondents rate as important in fulfilling their functions, good manufacturing practices (GMPs) came in highest, at 86%. Next in importance is process validation (74%), followed by the US Food and Drug Administration's quality-by-design initiatives (65.8%). Skills that respondents ranked as most important were computer-based systems, including database management (77.8%), chemistry (69.2%), and automation (52.3%). Least important were aseptic processing and isolation technology (40.4%) and biotechnology (46%). 

Among regulatory guidelines, respondents are most aware of 21 

Part 11, FDA's Rule on Electronic Records and Signatures (91.5%), follwed by 89% who are aware of FDA's "Pharmaceutical CGMPs for the 21st Century." Finally, 80% are aware of FDA's process analytical technology (PAT) guidance for industry. Respondents also report that these regulatory initiatives have changed the manner in which they perform their daily activities at their present jobs in the same order: 21 

Part 11 (50.8%), CGMPs (48.4%), and PAT (28%). 

Figure 13: Job seekers least important considerations. 

Results from our annual employment survey.

Headed Up or Down? Pharma's Position in the Current Economy

Knowledge is power, so the saying goes. And so the Internet must  be the most empowering tool of all. But is all knowledge equally empowering in all hands under all conditions? More specifically, when it comes to medical and pharmaceutical knowledge, are people really better off having access to the bounty of medical and pharmaceutical sites?  

The US Food and Drug Administration seems to be wondering just that. In mid-November, it held a public hearing on "Promotion of FDA-Regulated Medical Products Using the Internet and Social Media Tools." The purpose of the hearing, according to an agency announcement, is to help guide FDA "in making policy decisions on the promotion of human and animal prescription drugs and biologics and medical devices using the Internet and social media tools."  

The transcript of this hearing will not be available until sometime in December, so I do not know what FDA is proposing. But the Pharmaceutical Research and Manufacturers of America (PhRMA), welcomed the initiative, calling the hearing a "new and exciting step toward ensuring that patients can easily access truthful and reliable information about medical products online," according to a published transcript of a press briefing held by the trade organization in advance of the FDA hearing. In the transcript, Jeffrey Francer, PhRMA's assistant general counsel, offers PhRMA's suggestion that FDA develop a "single, universal symbol that would, in a single click, take users directly to pages displaying FDA-regulated prescribing information as well as patient medication guides." Such a symbol, he suggests would serve as an "unambiguous sign that an ad or Web site contains reliable information about medicine that is regulated by the government."   

In what seems to be a related initiative, FDA announced a collaboration with the website EverydayHealth.com, onto which FDA will deliver consumer health information. The goal, said FDA Commissioner Margaret Hamburg in a Nov. 17 agency press release, is to "reach millions more consumers with accurate, science-based information that can help them make decisions about their health."  

In another era, these initiatives would seem like an uncomfortable incursion of government into the press. But I think there's a case to be made for this initiative. 

The first thing to consider is that the Internet offers information, which is not at all the same as knowledge. Yet, some people could easily confuse the two, especially if they thought the medical information sites they visit are legitimate sources of health information.  

In the old days—that is, before the Internet—that function was largely the job of physicians and other professional healthcare providers. But the Internet can cut out that middleman, leaving many information-seekers to decide for themselves which sites offer reliable information. Of course, health-related information has always been available in newspapers, on TV, and in magazines. While many health communicators in these venues were not specialists, they almost always consulted people who were. Furthermore, people still relied on professional healthcare providers to prescribe drugs. But that's not the case today. Internet users now have the means to take their therapeutic regimen into their own hands. 

Patients now have direct access to prescription drugs through online pharmacies, many of which don't require prescriptions. So, it's possible for someone to diagnose and treat themselves. And there's a good chance that drugs purchased over the Internet are adulterated, counterfeit, contaminated, expired, or all of the above. In her Oct. 2, 2009 blog post, Assistant Editor Alexis Pellek cited a study (see blog.PharmTech.com) in which only four of the 2930 online pharmacies investigated carried the Verified Internet Pharmacy Practice Sites (VIPPS) certification. (The VIPPS program is governed by the National Association of Boards of Pharmacy. FDA advises consumers to confirm VIPPS certification of online pharmacies.)  

By eliminating the middleman of a professional healthcare provider, the Internet may have, in fact, created a credibility vacuum. The health and well-being of many people may benefit if someone filled that vacuum, and FDA may be the right agency to do it.  

is editor-in-chief of Pharmaceutical Technology. Send your thoughts and story ideas to 

With so many healthcare and pharmacy websites, consumers could use the agency's nod of support.

An FDA Seal of Approval for Online Information?

The healthcare reform debate rages on, with more opinions than opinion-makers it seems, and more variations than there are members of Congress to introduce bills. So if you're confused about the options—and let's face it, who's not?—I propose a different approach. Why not do it yourself? What follows is a handy worksheet to help you formulate your own healthcare proposal—just circle your preferred options.  

should; should not; should with an exemption for people who can't afford it; should with an exemption for people with religious or moral objections; should with exemptions for people with incomes lower than 133% of the poverty level or for those individuals who would have to pay more than 8% of their income to buy the lowest cost plan available to them

US citizens; citizens and legal US residents; legal and illegal residents

) carry health insurance. Individuals who violate the mandate (

0; 2.5% of adjusted gross income; up to $750 a person per year) 

that will be phased in gradually over the next eight years. 

under all circumstances; under no circumstances; if their annual payroll exceeds $250,000; under all circumstances unless the company can demonstrate that paying for health insurance would lead to job losses or have other negative effects; if they employ more than 25 people

0; $750 for each full-time employee, and half that for each part-time employee

national; exchange; state-based exchange; private insurers

government-run insurance plan; nonprofit cooperative

) be set up to compete with private plans.  

under no circumstances; if they have fewer than [25; 50; 100)] workers; on a sliding scale based on the size of the company and the level of worker pay, with larger companies and better-paid workers receiving few or no credits; if they are considered a small business)

a basic package of preventive services, mental health, dental, and vision benefits; at least ambulatory patient services, emergency services, hospitalization, maternity and newborn care, mental health and substance-abuse services, rehabilitation services as well as devices, laboratory tests, preventive and wellness services, and pediatric services; four levels of coverage, with an escalating number of services and increasing percentage of costs covered as one ascends the levels

) be prevented from denying coverage to individuals with pre-exising conditions. Plans (

) include prescription drug coverage, and if a public plan is put into effect, the government (

) use its purchasing power to negotiate lower drug costs. In addition (

) take into account comparative-effectiveness research when constructing their formularies. The plan (

) also take into account follow-on biologics and (

) years of data exclusivity for innovator drugs. 

$1 trillion; $829 billion; not so much as to add to the federal debt

) over the next 10 years. The plan will be paid for by (

slowing the growth of health spending in the long term; income surtaxes on families earning over $350,000 and individuals earning more than $280,000; surtaxes on families earning over $1 million and individuals earning more than $500,000; fees on insurance companies, medical-device manufacturers, and drugmakers; limiting tax deductions on charitable contributions; mortgage interest for families earning more than $250,000; taxing money spent by drugmakers on advertising; tax money for direct-to-consumer advertising; raising taxes

) be raised by trimming Medicare payments to hospitals and subsidies through Medicare Advantage. Hospital associations (

) give up some proportion of Medicare and Medicaid payments to offset the cost of insurance, and drugmakers (

reduce the costs of drugs for individuals who fall into the Medicare "doughnut hole." 

Now wasn't that was easy? Next month, we'll tackle the economy. (For more information, the

 website has an interactive graphic on healthcare proposal comparisons.) 

While Congress debates hundreds of healthcare plan proposals, perhaps we, the public, can get in the game too.

DIY Healthcare Reform

The rise in novel biopharmaceuticals has injected new life into the injectable delivery market. The demand for injectable technologies is growing, says George Perros, managing director for Greystone Associates, a technology consultancy based in New Hampshire, which in September 2009 published an analysis on 

Drug Delivery for Self-Adminstration: Devices, Drugs, Product Strategies and Forecasts. 

The following interview with Perros describes this evolving market and recent innovations. 

What is your overall assessment of the future for injectables? 

The advent of protein and peptide drugs has spurred the development of new delivery devices. Newer more fragile drug substances present a delivery challenge. Nevertheless, we see not so much a revolution in injectable devices, as an evolution, as these devices become increasingly more sophisticated, cost-effective, and safe.  

Table I: Global historical volume and forecast for prefilled syringes (Greystone Associates). 

What are the main drivers of this evolution? 

Typically, when these biological drugs are first released onto the market, they are administered by infusion by professional healthcare providers in a healthcare facility or an outpatient setting. This is an expensive way to administer drugs, but it allows these drugs to be used in a controlled setting until enough data are available to establish a safety profile for the drug that can be used to determine whether it should be approved in a form for self-administration.  

Table II: Current and forecast global market share for pen injector segments (Greystone Associates). 

The challenge that keeps driving device evolution focuses on how to get these drugs into the hands of the patients for self-administration in a way that is safe, reliable, and economical. For drug products designed for self-injection, this means injection devices that are prefilled (also referred to as combination products). 

Another issue for biological drug developers is the fragile nature of the drugs themselves, which necessitates they be transported and stored at low temperature—the so-called 'cold chain'—which adds to the cost of distribution. To avoid the problem of temperature-dependent stability, proteins and peptides are often processed and packaged in dry or powder form. These lyophilized drugs must be reconstituted prior to injection. Special injection devices have been developed that contain two chambers, one with the lyophilized active ingredient, and the second for the formulation liquid or diluent. Upon activation, the powder and liquid are allowed to mix in the correct proportions, before being injected. 

The ability of patients to self-medicate reduces the economic and resource pressure of having a healthcare professional administer the drug to the patient. So the technology challenge is to design a delivery device that ensures that the drug is preserved properly, reconstituted properly if necessary, and administered at the right dose by a person who may have little or no experience with injectable devices. 

What kind of innovations are you seeing? 

The growth of reusable injectors with replaceable cartridges has been significant, particularly for drugs indicated for chronic conditions. Some of these devices allow the patient to adjust the dose. These are most often used for insulin administration, where the patient is adjusting the dose after measuring their blood glucose levels. 

The arrival of disposable autoinjectors is an exciting development. Autoinjectors are pen-like devices that allow the user to insert a prefilled syringe and simplify the injection event. For years, this segment was dominated by reusable autoinjectors, which are made of durable materials but are a bit pricey. Recently, disposable autoinjectors have begun to appear. These less-expensive devices are providing drug marketers with new opportunities because they can be bundled or paired with a prefilled syringe. It's extending the utility and user-friendliness of autoinjectors to a growing number of patients who would otherwise need to master the art of injection with a naked prefilled syringe. 

There have also been improvements in safety features for syringes used by healthcare providers. Retractable safety syringes, which are designed with needles that retract after injection to minimize the risk of needlestick injuries to care-givers, are starting to find traction in North America, and to a lesser degree, in Europe. 

I see that the market for antivirals seems to have plateaued since 2007. Can you explain that trend? Which antivirals in particular are you focusing on? 

Interferons for infectious diseases, particularly Hepatitis C, are designed to boost the immune response to an infection. Because of difficulty with patient compliance due to side effects, this segment has experienced uneven growth. We expect that trend to continue. 

The global market for pens containing insulin is trending up gradually. Do you see that growth coming from domestic or international growth primarily? 

Pens are already the most popular way to self-administer insulin in Europe. These devices are becoming more popular among diabetics in the US and this popularity will help overall growth in the near-term. 

Are there any technologies that seem to be losing traction? 

Needle-free injectors continue to struggle. We think that this is because the current generation of pen injectors—with their quick and relatively painless operation and user friendly features—to a large extent obviate the need for needle-free devices. 

A Conversation with Greystone Associates' George Perros. This article contains bonus online-exclusive material.