Michelle Hoffman, editorial director of Pharmaceutical Technology.

Michelle Hoffman

Psst. I've got a bit of gossip for you, a piece of news you won't hear on TMZ or Entertainment Tonight. Early reports seem to indicate that a huge celebrity couple, seen everywhere at all the big industry firms is headed for splitsville. That's right. That perennial couple, the so-called jewel in every pharma companies' crown—R&D—looks like they're on the outs. R seems to be leaving D. Or is it getting kicked out?  

An article in the Feb. 10, 2011 issue of 

 reported cuts to the research staffs at both Pfizer and GSK. Pfizer, the article said, is shutting down its Sandwich, UK, facility, thus cutting 2400 mostly research scientists. The company, according to the article, is also eliminating 1100 jobs from its Groton, CT, research facility, and is slashing research budgets from a previously stated target of $8.0 to $8.5 billion down to between $6.5 and $7.0 billion.  

For its part, GSK was quoted in the same article saying that it would be "externalizing parts of early-stage discovery; dismantling development in areas with low financial and scientific return." Judy Slinn, a business historian at Oxford Brooks University in UK was also quoted as saying "Pharma companies will still do development work. They won't do discovery."  

OK. But then who will do discovery? Pharma is looking to small biotechs to fuel its discovery engines. By most accounts, pharma will be shopping among later-stage biotech companies ready for development. Yet there still seems to be a significant funding gap to develop promising technologies out of the universities and into at least proof-of-concept stage; that is, there seems to be little money to develop technologies to the point that they become attractive to large pharma.  

This funding gap—the so-called Valley of Death—is nothing new. It's just that in an environment where everyone is cutting back on research, the problem of developing promising technologies seems more acute. The Biotechnology Industry Organization (BIO) is addressing the problem in what it is calling their "Big Thinking Project." BIO recently commissioned the firm headed by former NIH Director Elias Zerhouni to collect suggestions for optimal government and industry initiatives from key industry leaders. They asked for policy proposals that would support early innovation to a point where risk-averse venture investors and big pharma firms would pick up the tab for continued development. Their responses include a mix of reforms that would reduce regulatory and financial risks.  

The Obama administration is also keen on promoting innovation. In his 2011 State of the Union address, the president wasted little time pinpointing the source of America's future financial security. "The first step in winning the future is encouraging American innovation," he said. And the administration's 2012 budget backs that up with funding increases for biomedical research and FDA activities. But then it curiously sounds a counter-innovative note. The same administration "now proposes to jettison the biotech exclusivity deal," that had previously been approved as part of the healthcare reform package, notes Jill Wechsler in Washington Report this month. In shrinking the exclusivity period from 12 to 7 years, the move threatens to disincent investor support for the very innovation it otherwise hopes to stimulate.  

Interestingly, in the same State of the Union Address, the president warned of competition from overseas. "Meanwhile," he cautioned, "nations like China and India realized that with some changes of their own, they could compete in this new world. And so they started educating their children earlier and longer, with greater emphasis on math and science. They're investing in research and new technologies." Indeed they are. The Chinese government is spending a reported $2.4 billion to support drug development, while it introduces policies to promote its biotech sector, strengthen its intellectual property protection, and strengthen tax and lending policies. In other words, research, jilted by US pharma, may find solace in China's warm embrace.  

Articles

Research and development may be headed for divorce.

Celebrity Couples to Disunite

Every January, the movers and shakers of the pharmaceutical industry convene in San Francisco for JP Morgan's annual Healthcare Conference. There, the pharma industry's corporate leaders articulate their business strategies before an audience of investors and analysts. The emerging themes define strategic trends for the coming year, much as fashion trends are set during New York Fashion week. So what's the vogue in pharma for 2011?  It looks as though follow-on biologics are the new black.

News stories coming out of the conference reported how one pharma major after another announced plans to get into follow-ons, a surprising move for companies that, until now, based their reputations on innovation and not imitation.Maybe it shouldn't come as a great surprise, however, considering that recent technical innovations and regulatory advances are creating fertile ground for follow-on commercialization.  

New analytics are making it possible (or will soon make it possible) to characterize proteins as they're being synthesized in the bioreactor. Advances in chromatography and mass spectroscopy allow manufacturers to detect variations in amino acids and glycan disposition within protein products that might alter their biophysical properties. 

The regulatory agencies are also advancing guidances for commercialization of complex biosimilar molecules, such as monoclonal antibodies (mAbs). But as the US pharma majors state their interest in biosimilars, it's important to note that US regulations lag behind Europe. Whereas the US held its first hearing on regulations for follow-ons in November 2010, the European Medicines Agency (EMA) had already developed a regulatory framework for follow-ons in 2003 and issued its first guidelines in 2005.  

To be accurate, the medicines actually manufactured under the 2005 EMA guidelines are small, very well characterized molecules, such as recombinant human insulin. Recent debates on both sides of the Atlantic center on what constitutes proof of similarity for larger, complex biomolecules.  

With the November 2010 release of two draft guidelines, one on similar biological medicinal products containing monoclonal antibodies, and the other on immunogenicity assessment of monoclonal antibodies intended for 

 clinical use, EMA once again leads the way. The focus of the "biosimilarity exercise," notes the guideline on similar biological medicinal products, "is to demonstrate similar efficacy and safety compared to the reference product, not patient benefit per se, which has already been established by the reference product." And the tests EMA asks for—both 

are aimed at determining "all functional aspects of the mAb even though some may not be considered necessary for the mode of action in the clinic."  

Together, the two guidelines ask manufacturers to evaluate differences between innovator and follow-on mAbs in process-related impurities due to differences in expression systems used by different manufacturers. They also address "less well characterized" impurities, differences in formulation, unusual excipients, post-translational modifications that can affect the conformation, aggregation, and ultimately the immunogenicity of the follow-on product. The guidelines go on to outline tests for pharmacodynamics,  immunogenicity, and suggest an overall risk-based approach to follow-on mAb manufacturing.  

Should EMA enact these regulations before FDA, which seems likely, European Union manufacturers will get a head start over their US counterparts in producing, testing, and marketing the follow-ons, which experience could put firms seeking to do business in the US at a competitive disadvantage in what promises to be a tight and competitive market. In light of pharma's expressed intent to manufacture follow-ons, the pressure is on regulators to get up to speed quickly—certainly before follow-ons are just so last year.  

Follow-ons were all the rage at this year's JP Morgan Healthcare Conference.

Follow-Ons: The New Black?

"The beauty of the world, the paragon of animals," on one hand; a "quintessence of dust," on the other, says Shakespeare's Hamlet of humankind. Human institutions, like their inventors, are also dual-natured, it seems. Take the pharmaceutical industry, for example. 

At its best, the industry produces medicines that have saved the lives of millions and alleviated the suffering of millions more. Better still, many leading pharma companies are working toward sustainable, environmentally friendly manufacturing practices. Many companies are also practicing corporate philanthropy and are working hard to produce drugs to treat diseases in developing nations at affordable prices. Highly laudable activities, all.  

And then there's the other side of the industry, the one reflected in a report released in mid-December by Public Citizen's Health Research Group. The title says it all: 

Rapidly Increasing Criminal and Civil Monetary Penalties Against the Pharmaceutical Industry: 1991 to 2010

. American spending for prescription drugs has increased almost 600%, in the period covered by the report, from $40 billion in 1990 to $234 billion in 2008. The report suggests that a nontrivial part of that increase derived from corporate malfeasance, for which pharma companies paid out nearly $20 billion in fines and penalties over the past 20 years. The rise in illegal off-label promotion of pharmaceuticals accounts for much of the fraud. In fact, according to the report, the pharmaceutical industry now holds the dubious honor of being the biggest of all industrial defrauders of the federal government under the False Claims Act, surpassing the defense industry, which used to hold that title. Pharma companies are equal-opportunity defrauders, the report notes, and deliberately overcharging state health programs, mainly Medicaid. This act "has been the most common violation against state governments and is responsible for the largest amount of financial penalties levied by these governments." Other violations include monopoly practices, kickbacks, concealing study findings, environmental violations, financial violations, and illegal distribution.  

Furthermore, the report notes that these incidents have risen precipitately in recent years. According to the report, approximately three-fourths of all settlements and total dollars paid out during the 20-year study period were made in just the past five years.  

The good news, if there is any, is that of the 20 largest settlements in the past 20 years, only one was for poor manufacturing practices, which the study authors define as "selling drug products that fail to meet FDA standards or specifications (e.g., contaminated or adulterated products, or products that fail to meet size or dosage specifications)." That settlement cost Schering-Plough $500 million in 2002 for GMP violations in the manufacture of Claritin. The single largest settlement was $3.4 billion paid out by GlaxoSmithKline in 2006 for unspecified financial violations, and the smallest was a state settlement of $258 million by Johnson & Johnson in 2010 for unlawful promotion of Risperdal.  

Overall, only 3% of all 184 violations accounted for in the study were for manufacturing violations, for which the industry paid out a total of $1.3 billion in fines to federal and state governments. But the study notes that the data set for all violations may not be complete and therefore "may understate the extent of criminal and civil violations by the pharmaceutical industry." 

The study concludes by saying, "the current system of enforcement is not working," a theme we've heard in many instances—greater enforcement being a cornerstone of the current FDA's new policy as well. In fact, the study quotes Eric Blumberg, FDA's Deputy Chief Counsel for Litigation, as saying "...unless the government shows more resolve to criminally charge individuals—at all levels in the corporate hierarchy—...we can not expect to make progress in deterring ...off-label promotion." The same kind of enforcement might deter any number of the violations appearing in the report. Sadly, an industry that is so often noble in its deeds still falls short from being a paragon of industry.  

Capable of great works, pharma as a whole still yields to the lesser angels of its nature.

What a Piece of Work is Pharma

A few weeks ago, I got a phone call from a producer at "60 Minutes" looking for sources for a story they were working on about quality breaches in the pharmaceutical industry. "Was there a particular breach they were interested in," I asked? When they indicated there was, I started to reel off a list of five or so recent such breaches, when I stopped myself and remarked, "There's enough here to fill a Jeopardy! category. I'll take 'Pharmaceutical Quality Breaches' for $600, Alex." 

But it's really not funny, is it? For the past several years, the pharmaceutical industry has had to combat the public perception in decline. The public is unhappy with the cost of drugs, unhappy that novel drugs for unmet needs are slow to come to market, and now unhappy about a seemingly unending stream of quality breaches. Outsized prices might be forgiven if it means the public has access to high quality and highly effective medicine. The lack of innovation is somewhat more troubling for the health of the industry and the US economy and probably can't be solved by industry alone. Rather true innovation probably requires the concerted efforts of industry, academia, and the government. 

Which leaves us once again with the quality question. And here, the industry is at once solely responsible for the problem and singularly capable of finding a solution. For the past few months, I've been writing about possible causes of quality breaches, starting with lack of qualified quality personnel. Until now, though, evidence for that has been largely anecdotal. But this month, 

 publishes the results of its annual employment survey, the responses to which also provide some hard data to support the allegation that quality professionals have been preferentially downsized as a result of the economic downturn.  

Among those who say they've lost their jobs because of economic hard times, the largest percentage—22%—are in quality control and assurance (followed by nearly 10% each in production management, engineering and engineering management, and consulting). Another 21% who say they have kept their positions while colleagues in their divisions have not are in quality control and assurance, again the highest percentage of respondents. And among those who said their job function was eliminated, a full 40% were in quality control and assurance. So it appears that when the going gets tough, pharmaceutical companies let their quality professionals get going ... with the expected consequences.  

In a time when it's harder to produce and market novel compounds, one would think the industry would take greater care with the compounds it already has on the market. They say it's easier to ask forgiveness than permission, and yet I wonder how much more forgiving the public will be, and how many more times the industry will ask. I keep hoping the industry becomes chastened by the recent spate of quality issues. Perhaps in the New Year, industry will rededicate itself to regaining the trust of the public by doing what consumers hope of it: producing highly effective, high-quality medicines.  

And as long as we're discussing quality control, our publication maintains its own through the good graces and generous time and advice of our editorial advisory board and our peer reviewers, who make sure that everything we publish is of the highest quality. On behalf of the editors, we thank you for making 

 the trusted information source it is and for pushing us, the editors, to do our best. The editors would also like to thank the dozens of expert columnists and contributors who share their considerable and considered insights with us and with you. We have all benefited tremendously by your experience and your willingness to educate us. And the editors thank you, our readers, for continuing to engage us through your emails, for your responses to our (very long and detailed) surveys, for submitting your research papers to us, and for your general support, encouragement, and enthusiasm for our efforts.  

We wish you all happy holidays and the very best wishes for a productive and high-quality New Year. 

I take exception to your statement "...true innovation probably requires the concerted efforts of industry, academia and the government."  Hasn't the government totally mismanaged almost everythingit puts its' hands on?  We do NOT need government intervention for innovation.  They will try to find a way to tax it out of existence. The answer is  - let the people with common sense who are close to the processes figure it out.  Get too many academians involved and the result is analysis paralysis.

Upper management has clearly NOT gotten the Quality message if downsizing so many quality professionals. Maybe the problem is the messengers are not conveying the right message that a quality driven company costs less than one that is not.  Read any issue of Quality Progress, the journal of the American Society for Quality for tips ongetting the message up.  If management "doesn't get it", it's time for them to go.

 Regards,M.MacMurray, Senior Member, ASQ, Dec. 23, 2010

As we get ready to begin the New Year, let's hope some quality resolutions are made.

Quality Issues Redux

A couple of years ago as the US slid into economic recession, many of us looked forward to 2010 as the year when we could hope for business to turn around. Surely, by 2010 companies would regain their footing, and the employment situation would return to something that felt like prerecession conditions. So has it? Well, it depends in part on how well you weathered the storm and where in the world you live.  

OPENING ART: JUPITERIMAGES, GETTY IMAGES. 

Many people have lost their jobs—11.3% of respondents, to be exact—but those that remain employed saw significant salary increases this year. In fact, the overall average salary among respondents climbed to $102,468.79, up from last year's average of $94,079. Nevertheless, more people feel insecure in their jobs now—53% of all respondents—than in any survey we've previously conducted. Moreover, their work day has become longer, they are taking on more responsibilities and performing them with fewer resources, and so their stresses mount. Surprisingly, many respondents seem optimistic about the future—56% expect business to improve in the coming year, and 53% report that their companies plan to expand. More important, 71% say their companies will not be downsizing anymore. So, perhaps we were just a tad premature in our expectation that 2010 would be the year of recovery. As we enter what we hope will truly be a year of economic recovery and growth, we present a snapshot of the year that was in employment.  

Figure 1: Survey respondents answer how they feel about their job. 

As in years past, the majority of respondents—80.2%—work in a company that manufactures pharmaceuticals; 45% (of all respondents) work for a traditional bio/pharmaceutical company; 14.5% for a contract service provider or manufacturer; 11% for a generic-drug manufacturer; and 9.7% for a biotechnology company. Only 2.4% work for an academic institution, down from 4% last year. Another 2.6% work for the government, 2.8% are self-employed, 1.9% work for a nonprofit organization, and 10% identify their organization as "other." At 67%, most of the respondents came from the United States (including Puerto Rico), another 20% came from Western Europe, 2.8% are from Eastern Europe, 3.2% are from Canada, and 1.9% are from India. The remainder are from South and Central America and East Asia.  

Figure 2: Survey respondents address whether they intend to leave their jobs. 

As in previous surveys, the quality control and assurance (QA/QC) professionals constitute the largest number of respondents—19% (up from last year's 17%). Interestingly, women account for about 52% of these (36.8% of all women report their function as QA/QC). Coming in second at 8.6% of total respondents were engineers and engineering managers, but here the demographics skewed in favor of men (10% of men, and 2.6% of women respondents performed this function). The same is true of the 7.9% in production management (10.4% of men, but only 1.7% of women); 7.2% are in process development (9.7% of men, but only .0.9% of women); and the 4.1% in corporate management (5.5% of male respondents, but only 0.9% of female respondents). Formulators and production researchers were somewhat more evenly represented by the sexes: 5.9% of total respondents are in formulation (6.5% of men, and 5.1% of women); and 5.2% are in production research and development (4.9% of men, and 5.1% of women).  

Figure 3: Sources of job satisfaction (multiple responses were allowed). 

Of course being employed is only part of the story. The other part of the story is how secure people feel in their jobs—and people don't feel very secure. While 53% of respondents report feeling insecure as compared with past years, insecurity runs highest in the US, where 55.3% of respondents felt insecure (15% feel more secure than they did in the past). The most secure workers live in India, where 25% of respondents feel insecure, and 37.5% feel more secure now than in years past. Half of the respondents from Western Europe feel insecure, and 54.5% of Canadian respondents feel insecure. Men and women feel almost equally insecure—with 54.2% of men, and 52.6% of women feeling insecure. Interestingly, more women—18.6%—report feeling more secure than they did in the past, as opposed to only 14.2% of men.  

Figure 4: Sources of job stress (multiple responses were allowed). 

Offering the greatest security are contract manufacturers and service providers, as 52.9% of respondents who work for these companies say their jobs are secure. Next most secure are workers in generic-drug firms, where 46.6% of respondents say their jobs are secure, followed by traditional bio/pharmaceutical companies with 39.2% feeling secure about their jobs. Biotech companies trail that with 38.9% of respondents reporting that their jobs are secure. Biotech companies also have the greatest percentage of workers who feel insecure about their jobs—38.9% of respondents from biotech companies said they feel insecure, as did 32.4% of respondents from traditional bio/pharmaceutical companies, and 27.4% of workers in contract service and manufacturing companies. Finally, only 11.1% of workers in generic-drug companies feel insecure in their jobs.  

Of course, this year the economy continued to have profound implications for workers in the pharmaceutical industry, and 11.3% of respondents reported losing their jobs because of it. Canadians suffered the heaviest job losses, as 18.2% of Canadian respondents report losing their jobs, in contrast to 12.2% of US workers, and 6.7% of Western European works. Indian workers reported 0% job losses for themselves and their colleagues due to the economy. Workers in contract service and manufacturing providers lost the most jobs—29.8% of respondents in these companies report losses, followed by 10.1% in traditional bio/pharmaceutical manufacturers, 7.5% in generic companies, and 3% in biotechnology.  

Among respondents that remain employed, 30.1% say their workday has become longer, and 23.5% report that they've taken on additional functions to fill in for lost coworkers.  

If you didn't lose your job, 2010 was a good year. Overall salaries increased 8.9% to $102,468. Men earned more than women: $103,787.55 for men versus an average of $100,469.01 for women. The average industry salary in the US was the highest—$ 113,343, followed by $81,076 in Canada; $74,049 in Western Europe; and $58,833 in India. A full 100% of Indian workers report receiving salary increases this year, followed by 69.2% in Canada, and 65.4% in the US. Least likely to have received a raise this past year were Western Europeans, with only 49.3% reporting salary increases. Canadians were most likely to receive salary cuts—with 7.7% of Canadian respondents reporting decreases, followed by 7.4% of US respondents, and 5.85% of Western Europeans.  

Figure 6: Company expansion plans by location. 

In general, people working in the pharmaceutical industry feel gratified and valued by their employers—64.6% of all respondents said their employers fully valued their work. Employees of generic-drug manufacturing firms feel most valued, 68.9% reported feeling valued, followed by 67.1% of workers in traditional bio/pharmaceutical companies who feel that way. Least valued are workers for contract manufacturers and service providers, where 58.4% feel valued. On average men feel slightly more valued than do women, as 65.2% of men, and 62.4% of women reported feeling their work was valued.  

Figure 7: Job selection factors-most important (multiple responses allowed). 

The feeling may not be entirely mutual, however. Over half—58.5% of respondents from contract manufacturer and service providers—say they would leave their jobs if they could. Almost the same number (58.3%) from biotech companies say they'd leave their companies if they could. Employees at traditional bioo/pharmaceutical companies are least likely to look for new jobs, since only 41.2% say they'd switch jobs if they could.  

Figure 8: Effect of economy on job (multiple responses allowed). 

So what accounts for job satisfaction when it occurs and what would employees in the pharmaceutical sector be looking for in a new job? Intellectual challenge is the number one source of job satisfaction say 61.5% of all respondents, followed by 61.3% who say that relationships with colleagues give them on-the-job satisfaction. Other important factors include intellectual stimulation (59.2%), work/life balance (57.6%), and supportive management (57.3%). Interestingly, relationships with colleagues are slightly more important to employees in Western Europe than in the US or elsewhere. In Canada, 66.7% of respondents say that intellectual stimulation is the most important factor, whereas 75% of Indian workers value challenging projects (but only 37.5% say their relationships with colleagues are sources of satisfaction). Salary matters most to Indian workers, 62.5% of whom cite this as a source of satisfaction versus 50% in Canada, 45.3% in the US, and 38.5% in Western Europe.  

Figure 9: Effect of economy on company (multiple responses allowed). 

On the flip side, 51.4% of respondents say that budgetary and resource constraints are their greatest on-the-job stressors. Also high on their list of stressors are short timelines (42.9%), issues with management (40.2%), and poor infrastructure (31.1%). Looking at the breakdown by company type, 53.2% of workers in traditional bio/pharmaceutical and 60% of those in biotech companies cite budgetary constraints as their most stressful challenge, whereas 51.9% of contract service providers and manufacturers and 48.8% of respondents from generic bio/pharmaceutical companies place short timelines at the top of their lists. Contract providers also cite poor infrastructure as a stressor—40.4%, as opposed to 30% or fewer for respondents in generic companies, biotech companies, and traditional bio/pharmaceutical companies. However, employees in these companies grapple more with management issues and fears about their job security.  

Figure 10: Job decision factors-least important (multiple responses allowed). 

Workers in India are particularly stressed about long commutes and low pay (37.5% of Indian respondents report each of these as stressors), while budgets and resources challenge employees in all regions. Men and women report similar stressors, with the exception that women feel the pressures of juggling work and life (30.9% of women versus 20.1% of men) more acutely than men, and women also have more issues with management (43.6% of women, and 39% of men). On the other hand, 29.3% of men feel the stress of job insecurities, while only 22.3% of women do.  

Figure 11: Job security now compared with two years ago. 

Given the workplace challenges and satisfactions the survey uncovered, what would it take to lure an employee to a new position? The answer was unequivocal—money. A full 63% of respondents said income was the number one feature they'd be looking for in a new job. A good work/life balance came in second at 42.3%, and geographic location was third (40.9%). Men and women were almost equally inclined toward a bigger paycheck, but work/life balance is more important to women job seekers than to men (51.5% of women versus 38.1% of men). Geographic location, on the other hand, matters more to men (42.5%) than to women (36.4%). Retirement benefits will matter more to men, too (14.9%) than to women (8.1%).  

Job attributes that matter less to those considering a move include, surprisingly, scientific opportunities, with 47.2% of respondents placing least importance there. Women are less motivated by scientific opportunity than are men. Tolerance in the work place was also relatively unimportant, as was commuting time.  

Figure 13: Respondents organization by type. 

In spite of 2010's vicissitudes, in spite of the fact that 42.7% of respondents say their companies downsized, that 32.0% say business decreased, and 22.6% say their companies outsourced work, employees in the pharmaceutical industry remain bullish on prospects for the future. More than half (53.4%) say their companies are expanding next year, and 56.1% think business will pick up. Let's hope they're right.  

Figure 14: Additional job decision factors by location (mutliple responses allowed). 

2010 came with pay raises for those still employed and anxiety for all. This article contains bonus online material.

Riding the Employment Roller Coaster

 What type of product(s) are amenable to visual inspection by a fully automated machine vision system? 

 Totally automated systems exist for visual inspection of both solid dosage and parenteral formulations. Parenteral products can be inspected inside their containers; that is in ampules, vials, or syringes. The containers themselves can also be inspected. The drug products can exist as liquids as well as in freeze-dried and powder preparations. 

 Which properties of parenteral formulations can you pick up with the existing fully automated technology?  

 Particulate matter, fill level, as well as any container defects can be detected. 

 The same machine can detect product quality as well as container quality? 

 Yes. That's correct. We can look for cracks in the container as well as particulate matter. Aggregates, on the other hand, present a challenge for current technology. We can identify their presence. We can reject a product with protein aggregates in it. The challenge now is to differentiate a particle from a protein. But that's being investigated by several companies, including ours. 

Besides detecting particulates and container defects, it is also important to detect problems with the container closure. A manufacturer wants to ensure that the container is properly sealed. And container closure can also be assessed by a fully automated system. 

 What properties of solid dosage forms—tablets and capsules—can you detect with a fully automated system? 

 We have an automated, camera-based visual inspection system that scans for length, size, color, shape, and foreign materials on the product (not in). We have two different machines, one for tablets, and one for capsules.  

 At the moment, what are the limitations? 

 Not every product is amenable to automated inspection. Starting with parenteral products: It is not possible to find particulate matter in freeze-dried, lyophilized product, because the particulate is hidden in cake itself. No human or machine vision can see it. Some companies are developing X-ray detectors for that purpose.  

Most of the other applications we've been able to manage successfully. If you can see it with the human visual system, then you should be able to see it with a camera and/or a sensor. But if you can't see it with human eye, then it will be a challenge for a camera. Dense suspensions are also a challenge because of the opacity of product. 

 What type of optical reader do these machines use? 

 Eisai's technology for particulate detection does not use a camera, but uses a static division (SD) sensor. The sensor is made up of an array of photodiodes that measure how much light passes through the product. The machine spins the containers, so that the particles are moving in front of the light source during the inspection process. As particles move in front of light, they block the light and create a voltage variation. Depending on the size of the variation, the machine rejects or accepts the product. The customer sets the spinning speed and determines what size of variation merits rejection. The particle's color and composition are unimportant. The sensor responds to the size of the particle. Any time it sees a particle greater than the threshold level set by operator, it generates a reject signal. 

The machine uses cameras for cosmetic container inspection. Cameras are also used for our capsule and tablet systems. Other firms are using sensors that rely on Raman spectroscopy or near infrared technologies to detect properties of solid dosage forms. 

What's the readout for your parenteral or solid-dosage systems? 

 Each device will produce a printout that gives you the number of particle rejects or cracked containers, for example. 

 Does the customer need any additional software to perform an analysis? 

 Not to analyze results, but often, a customer's MES [manufacturing-execution system] or ERP [enterprise-resource planning] system will be interfaced with the machine and can store and sort data as part of an overall batch analysis.  

 Is there any kind of corrective and preventive action (CAPA) system or feedback loop? 

 No CAPA per se, but for inline systems, you can, say, stop the production line if some specified number of products is rejected. The operator can set limits per camera station based on the number of rejects in order to take some corrective action.  

A conversation with Mike de la Montaigne, president of Eisai Machinery, USA Inc., about the possibilities for conducting fully automated product inspections.