Foodborne Illness: Especially Dangerous for the Vulnerable

Older adults, pregnant woman and young children are among the most vulnerable to foodborne illnesses. People with compromised immune systems are also at risk.

If you've ever become sick after eating a food contaminated with disease-causing bacteria, it's not an experience you want to repeat.

But if you're part of what is called an "at-risk" or "vulnerable" population, a foodborne illness can be extremely dangerous. Symptoms—such as vomiting, diarrhea and fever—can intensify and the illness can become life-threatening.

Which populations are most at risk? According to Food and Drug Administration (FDA) epidemiologist Karl Klontz, M.D., M.P.H., they are the very young (under 1 year); older adults; the immune-compromised (those whose immune systems are less able to fight off harmful bacteria); and women who are pregnant.

For a particular type of bacteria known as Listeria monocytogenes—which causes a serious illness called listeriosis—the list is much the same, according to Vital Signs, a new report from the Centers for Disease Control and Prevention (CDC). The report, which summarizes data on the 1,651 listeriosis cases reported from 2009-2011, shows that older adults, pregnant women, newborns and persons with conditions that hinder the immune system are at a higher risk than others for listeriosis.

Combined, these vulnerable groups accounted for at least 90 percent of the listeriosis cases. CDC reported that 21 percent of the people with listeriosis died.

Immune System Plays a Role

What makes these populations more at risk? In many cases, the problem lies with the immune system, says Klontz. The immune system is the body's natural defense system against "foreign invasion" by pathogens (bacteria or viruses that can cause disease). In healthy people, a properly functioning immune system usually fights off harmful pathogens readily.

As we age, our immune functions and other barriers to infection start to wane, says Klontz. Our bodies less effectively fight off harmful bacteria. For example, the amount of acid in our stomachs, once a powerful barrier to pathogens, decreases. In addition, older people tend to take more medications for problems like heartburn or acid reflux, many of which further reduce the amount of stomach acid, further reducing this barrier against pathogens.

The same goes for people with compromised immune systems, such as those with HIV/AIDS, cancer, liver disease and diabetes. "Not only are their immune systems weakened by the disease," Klontz says, "but the side effects from certain treatments such as chemotherapy may make them weaker still."

On the opposite side of the age spectrum are children. Young children, in particular, are more at risk for foodborne illness because their immune systems are still developing.

As for pregnant women, "I wouldn't say that their immune systems are compromised so much as altered, serving a specific purpose—to enable the mother to co-exist with the fetus throughout the nine months of pregnancy. "Remember that half of the fetus' genes are not the mother's," Klontz says. The body has to work extra hard to avoid rejecting it. But that same alteration makes the body more susceptible to infection, he notes.

In addition, listeriosis in pregnant women can cause miscarriage, still birth, premature labor, and serious illness or death in newborns. Listeria monocytogenes, in particular, can cross the placenta (an organ which links the blood supply of mother to child) and infect the unborn baby.

Prevention is Key

Key to reducing the risk faced by these vulnerable populations is to prevent foodborne illnesses from occurring in the first place, says FDA microbiologist Mickey Parish, Ph.D. Prevention is at the heart of the FDA Food Safety Modernization Act (FSMA) signed into law in 2011.

FDA is working toward putting new measures in place to help keep contaminants out of the harvesting, processing and manufacturing of foods, Parish notes. By establishing safety and cleanliness requirements for farmers, food companies, and importers, FDA expects that implementation of FSMA will reduce the chances that pathogens such as Listeria, Salmonella, and E.coli will reach those most at risk.

There are steps that the people particularly vulnerable to the dangers of foodborne illnesses can take to reduce that risk, says Klontz. These include:

• Avoid eating raw animal products, which include unpasteurized milk (and cheeses made from unpasteurized milk), uncooked or lightly cooked eggs, and raw fish and meat dishes such as sushi or steak tartare.
• Wash fruits and vegetables before eating, especially foods with rinds, such as cantaloupes and other melons. Avoid eating raw sprouts.
• Make sure counters and other food preparation surfaces are adequately cleaned.
• Avoid hot dogs and other deli-style meats unless they are reheated to steaming temperatures. Also avoid deli-prepared salads, such as chicken or seafood salad.
• Keep your refrigerator at 40 degrees F or lower, and your freezer at 0 degrees F or lower.

If you're eating out, notes Klontz, especially if you're in an at-risk group, it's helpful to ask what ingredients are in a prepared dish. Are any raw or uncooked? Is the salad dressing or sauce made with unpasteurized milk or eggs? Does it include any raw animal products?

This article appears on FDA's Consumer Updates page, which features the latest on all FDA-regulated products.

FDA Approves Two Drugs, Companion Diagnostic Test for Advanced Skin Cancer

The U.S. Food and Drug Administration today approved two new drugs,Tafinlar (dabrafenib) and Mekinist (trametinib), for patients with advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma, the most dangerous type of skin cancer.

Melanoma is the leading cause of death from skin disease. The National Cancer Institute estimates 76,690 Americans will be diagnosed with melanoma and 9,480 will die from the disease in 2013.

Tafinlar, a BRAF inhibitor, is approved to treat patients with melanoma whose tumors express the BRAF V600E gene mutation. Mekinist, a MEK inhibitor, is approved to treat patients whose tumors express the BRAF V600E or V600K gene mutations. Approximately half of melanomas arising in the skin have a BRAF gene mutation. Tafinlar and Mekinist are being approved as single agents, not as a combination treatment.

The FDA approved Tafinlar and Mekinist with a genetic test called the THxID BRAF test, a companion diagnostic that will help determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene.

“Advancements in our understanding of the biological pathways of a disease have allowed for the development of Tafinlar and Mekinist, the third and fourth drugs the FDA has approved for treating metastatic melanoma in the past two years,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Zelboraf (vemurafenib) and Yervoy (ipilimumab) were approved in 2011 for the treatment of metastatic or unresectable melanoma.

“The co-approval of Tafinlar and Mekinist and the second companion diagnostic for BRAF mutation detection demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Devices and Radiological Health in the FDA’s Center for Devices and Radiological Health.

The FDA’s approval of the THxID BRAF test is based on data from clinical studies that support the Tafinlar and Mekinist approvals. Samples of patients’ melanoma tissue were collected to test for the mutation.

Tafinlar was studied in 250 patients with BRAF V600E gene mutation-positive metastatic or unresectable melanoma. Patients were randomly assigned to receive Tafinlar or the chemotherapy drug dacarbazine. Patients who took Tafinlar had a delay in tumor growth that was 2.4 months later than those receiving dacarbazine.

The most serious side effects reported in patients receiving Tafinlar included an increased risk of skin cancer (cutaneous squamous cell carcinoma), fevers that may be complicated by hypotension (low blood pressure), severe rigors (shaking chills), dehydration, kidney failure and increased blood sugar levels requiring changes in diabetes medication or the need to start medicines to control diabetes.

The most common side effects reported in patients receiving Tafinlar included thickening of the skin (hyperkeratosis), headache, fever, joint pain, non-cancerous skin tumors, hair loss and hand-foot syndrome.

Mekinist was studied in 322 patients with metastatic or unresectable melanoma with the BRAF V600E or V600K gene mutation. Patients were randomly assigned to receive either Mekinist or chemotherapy. Patients receiving Mekinist had a delay in tumor growth that was 3.3 months later than those on chemotherapy. Patients who previously used Tafinlar or other inhibitors of BRAF did not appear to benefit from Mekinist.

The most serious side effects reported in patients receiving Mekinist included heart failure, lung inflammation, skin infections and loss of vision. Common side effects included rash, diarrhea, tissue swelling (peripheral edema) and skin breakouts that resemble acne.

Women of child bearing years should be advised that Tafinlar and Mekinist carry the potential to cause fetal harm. Men and women should also be advised that Tafinlar and Mekinist carry the potential to cause infertility.

Tafinlar and Mekinist are marketed by GlaxoSmithKline, based in Research Triangle Park, N.C. The THxID BRAF Kit is manufactured by bioMérieux of Grenoble, France. Yervoy is marketed by New York City-based Bristol-Myers Squibb, and Zelboraf is marketed by South San Francisco-based Genentech, a member of the Roche Group.

Drug resistance may make malaria parasites vulnerable to other substances

Malaria parasites that develop resistance to the most effective class of anti-malarial drugs may become susceptible to other treatments as a result, researchers at St George’s, University of London, UK have revealed in a study. The discovery could reveal potential new drug options, which would be essential in the event of resistance to the best anti-malarials.

The researchers have shown how the anti-malarials artemisinins attack the malaria parasite by inhibiting the action of a crucial protein, and that genetic mutations in this protein can reduce the effect of the drugs.

While demonstrating this, they also discovered that a mutation that gives the parasite resistance to artemisinins makes it more sensitive to attack by another substance, cyclopiazonic acid (CPA). CPA is thought to be too toxic to be a suitable anti-malarial treatment, but the findings suggest it could be worth pursuing derivatives of the acid as treatment options.

The research has been published in The Journal of Infectious Diseases.

The yeast model provides a convenient and reliable method to study anti-malarials and this particular mechanism of resistance to them

The artemisinin group of drugs are the most effective and widely used treatments for malaria – used most powerfully with other drugs as artemisinin-based combination therapies – but little is known about their mechanism of action on the malaria parasite. There are signs that the parasite is developing resistance to such therapies, meaning that further understanding of the drugs could be crucial to prevent them from becoming obsolete.

The researchers demonstrated that artemisinins work by acting on a protein within the parasite called a calcium pump, which regulates calcium levels in cells, and if it is not functioning properly the parasite dies.

In previous studies, the team saw the same effect on the calcium pump in genetically engineered malaria parasites. However, in these studies the parasites’ sensitivity to artemisinins fluctuated, so they did not give a clear indication of the drugs’ mechanism of action and the findings could not be confirmed.

To provide more consistent results, the latest study used yeast cells instead of parasite cells.

After confirming that artemisinins inhibited the calcium pump in the yeast model, the researchers mutated the pump to mimic three mutations previously observed to give parasites resistance to the drugs. When they did this, they saw similar resistance.

The latest study used yeast cells instead of parasite cells

Following this, they tested whether these mutations had any effect on the action of another five substances known to have an anti-malarial effect. They found that one particular mutation that gave the pump resistance to artemisinins made it more susceptible to CPA.

Their findings also showed that the yeast model could be used to identify other drugs that harm the parasite.

Lead author Professor Sanjeev Krishna said: ‘CPA is a compound used in science and not in clinical practice in any way. However, it points to a proof of concept that we can look for weaknesses in the more resistant strains of the parasite. The yeast model provides a convenient and reliable method to study anti-malarials and this particular mechanism of resistance to them.’

Capsugel launches Lipidex technology platform

US dosage forms specialist Capsugel will launch its Lipidex technology platform this month (June), which integrates the firm’s lipid, liquid and semi-solid fill technologies, product development expertise, and commercial manufacturing infrastructure.

The Lipidex technology offers three encapsulation approaches, including liquid hard shell, Licaps, pictured.

Capsugel says the technology is the culmination of its acquisition of Encap earlier this year, and will enable the recently formed Capsugel Dosage Form Solutions (DFS) business unit to accelerate and improve the development of innovative products for pharmaceutical and nutraceutical customers.

The Lipidex technology includes Capsugel DFS’ clinical fast track development programme that uses the firm’s Lipid Expert System to streamline various aspects of the development process. It offers three encapsulation approaches, including a soft gel (SGcaps), liquid hard shell (Licaps) (inclusive of vegetarian options) and new solid lipid pellet technology currently under development, and which will be launched later this year.

Our Lipidex technology platform provides tailored solutions for the many challenges our customers face

‘Our Lipidex technology platform provides tailored solutions for the many challenges our customers face, whether it’s development of low solubility drugs in their pipeline, repositioning existing drugs for better therapeutic performance or rebranding them using innovative dosage forms,’ said Amit Patel, President, Capsugel DFS.

‘Through Capsugel’s historical investments and our recent acquisition of Encap Drug Delivery, the Lipidex platform represents the industry’s most comprehensive and vertically integrated offering in the lipid, liquid and semi-solid arena. It spans polymer science and process engineering at the capsule level, as well as API handling, dosage formulation development using expert systems, clinical trial quantity supply and commercial manufacturing.’

Rounding off the Lipidex platform is the company’s network of dedicated small-scale and commercial manufacturing sites in the US, Europe and Japan. The firm says this global manufacturing footprint assures business continuity planning and includes FDA and MHRA accreditation, and specialist capability in high potency actives, controlled substances and hormones.

SEXUAL POWER : Confirmation of Sexual Power intensity of a Human being by Electro Tridosha Graphy - ETG AyurvedaScan system

Many persons are willing to know the intensity of their SEXUAL POWER by any source. Till today no machine and mechanical parameters are available to establish sexual power by any technology.

But it is possible today and sexual power can be measured by mechanical means. By virtue of Electro Tridosha Graphy ; ETG AyurvedaScan system, now it is possible to establish the SEXUAL POWER of any human being in measured intensity.

The ETG system measures many parameters systemwise, sectorwise, traces wise, ayurvedic fundamental-wise and so on . PROSTATE health condition is scanned by ETG system. So is of the SAPTA dhatu. The SAPTA DHATU of Ayurveda is considered , similar to PATHOLOGY of Modern western medicine. Intensity of Prostate value shows the Sexual Power intensity of a human being, how is the person’s sexual drive. One of the Sapta Dhatu SHUKRA is evaluated and this shows the Quality and quantity of Semen. The passion of sexual ability and erotic sensibility can be measured by correlating to Autonomic nervous system and Brain faculties evaluation. .

In our studies, we have found that persons, which have very low intensity of PROSTATE pathophysiology, say below 30 e.v. , they are almost IMPOTENT and have no sexual desire. Upper signification of the above said parameters, shows intensity of Sexual desire in increasing level upto 90 e.v., which we consider a normal level. Sexual potency increases according to touch level of Normal parameters.

Strong sexual passion and erotic sensibility is seen in those persons, who have 95 e.v. to 99 e.v.

Excessive sexual passion and erotism is seen in those , who have beyond the above said parameter. Those who have 120 e.v. to more upper limit causes more passion to sexual behaviour.

We have seen that some persons have temporary IMPOTENCY, Their above given parameters , when comes in normal limit and when we see that person says that he have no sexual desire, we consider it a temporary and circumstantial problem with the person. It may be happen due to long travels by Railway, by Car or by any means. We have observed that some persons are impotent due to their workings both physical and mental. The re is other reasons, which are varying from person to person.

In these persons we have given Ayurvedic medicine and their impotency is restablished and as usual as it was in earliest forms. Now it is possible to treat either less sexual desire or excessive desire for sexual intercourses by Ayurveda.

Process Validation Guidance: A Bad Fit for Aseptic Processing?

When he first assessed FDA’s draft Process Validation guidance a few years ago, consultant James Agalloco, president of Agalloco & Associates, saw the usefulness of the guidance for validating pharma production processes and products. “The life-cycle model will result in development and validation exercises that provide relevant and meaningful information,” he wrote. “The link between the process parameters that influence the critical quality attributes will serve the industry well. The use of statistical methods will add a rigor to the validation efforts that has been sorely lacking” [1].

However, he expressed serious reservations (and shared them with FDA) about whether the PV guidance could easily be applied to processes and systems “less clearly related to end-product quality attributes.” This includes sterilization and aseptic processes.

“There are simply too many independent—and interrelated—variables in aseptic processing, and the most meaningful one of all lacks metrics of any type . . . Aseptic processing performed by human operators is devoid of any measurable variable that could be used to predict the outcome.” He concluded: “The statistical component of the guidance really doesn't work with respect to linking any process parameters directly to performance.”

Now that the guidance is official, we checked in with Agalloco to see if his views have softened. Far from it, it turns out. The guidance is a “terrible fit” for the validation of aseptic processes, he maintains.

“I've seen more confusion than clarity,” Agalloco says. “I've seen no indication in the final guidance or anywhere else that suggests things should be changed to accommodate sterility within the new guidance.”

Agalloco teaches regular courses on validation of aseptic processes, but has not changed them to reflect the new guidance. “There's nothing you can change in the practice of either sterilization or aseptic processing that is of any value to fit the guidance,” he says. “I see no need to adapt, because the adaptation will gain nothing of real value.”

The new guidance reinforces the need for science and process simulation testing—isn’t that a good thing? In general, yes, he says. But, “for aseptic processing its about set-up and interventions, and what the operator does in relation to them. Humans are awful subjects for DoE, QbD and all of the scientific buzz we hear about in relation to the guidance.”

Will the PV guidance dramatically change the way manufacturers approach the validation of sterilization processes—filtration sterilization, for example?

“Not in the least,” Agalloco says. “There's no suggestion that anything can or should be changed to match the guidance. Even FDA (Grace McNally, at PDA in San Antonio in April of this year) has stated that the ‘guidance doesn't specifically apply to sterilization.’ Making changes to fit these processes to the guidance is done at one's peril.”

The PV guidance recommends activities in three stages (process design, process qualification, and continued process verification), which depend on process characterization studies (with Key Process Input Variables, Design Space, etc.). Are most manufacturers able to adequately characterize their aseptic processes and sources of variability?

Says Agalloco: “Not at all. As the article [1] states, there's some possibility with sterilization as it relates to Stage 1, but that's about all that fits. Stage 2 & 3 lack adequate metrics to develop the confidence from what we can routinely measure in the process for sterilization so it's not a good fit there. Aseptic processing is just a horrible fit all around.”

 

We also consulted with Sartorius Stedim’s Maik Jornitz, current chair of the board at PDA, about whether the guidance will make a difference regarding the validation of filtration processes, one of his areas of expertise. “I do not think that the new Process Validation Guidance will change the process validation needs and activities surrounding sterilizing grade filtration,” he says. “The 2004 Aseptic Processing Guidance makes it very clear what is expected by regulators in regard to sterilizing grade filter validation, which is still very valid and unchanged by the new Process Validation Guidance.”

Will this guidance help filter end users to better understand which filter process input variables are "critical to quality"? “I do not know whether it will help, but it will raise the awareness and emphasis that there are critical variables within the filtration process,” Jornitz says. “The 2004 Aseptic Guideline touches upon and PDA Technical Report #26 describes in detail these critical process parameters, if the awareness is not already there.”

Jornitz, a frequent writer, speaker, and lecturer, has long preached a “science-based” approach to filter validation, and so believes the PV guidance will support this trend but is not necessarily a game-changer: “I believe everybody in the industry is working in accordance to a science-based approach,” he adds. “Therefore, guidances are only there to reiterate or support what should and is commonly done—or so I hope . . . I do not think that the Process Validation Guidance states something new here.” 

Green chemistry has ecological, financial benefits for Pfizer

When people hear the word "green" these days, they automatically think "environmentally friendly." But among chemists at Pfizer Inc. in Groton, the word also denotes efficiency, which equals a different type of "green" - money.

And Pfizer's local laboratories have been saving the company plenty of money - millions of dollars, most likely, though the company won't provide specific figures - over the past few years through a relatively new idea called green chemistry. Scientists in Groton are constantly reviewing and revising the chemical processes that go into the manufacture of top-selling medicines such as the cholesterol blockbuster Lipitor and pain reliever Lyrica, making sure new drugs are produced in the most efficient manner possible.

"Pfizer is a leader in both the research and implementation of green-chemistry and green-engineering practices," said S. Stewart Slater, a professor of chemical engineering at Rowan University in Glassboro, N.J.

By going green - which local scientists spearheaded at Pfizer a decade ago, though the chemistry principles date to the early 1990s - the making of pharmaceuticals is being done in a less wasteful, safer and more benign manner.

"By being green chemists, I think we provide a particular benefit to the environment," said John Wong, senior research fellow at Pfizer's Groton labs and leader of the eight-member Green Chemistry Team there. "When you use enzymes to do chemistry, they are not toxic and certainly environmentally friendly."

In the pharmaceutical industry, green chemistry often means the replacement of organic solvents with enzymes, commonly referred to as "nature's catalysts" and naturally occurring in all living organisms. Companies try to implement green chemistry ideas right from the start, because changing drug formulations after a product is out requires additional human testing for safety and effectiveness.

Eric Watters, environmental manager of the Groton facility and a team member, said the use of green-chemistry methods doesn't have a big impact on the local air and water because the pharmaceutical giant no longer has extensive manufacturing facilities here. It's at the company's drug-making plants worldwide that the use of green chemistry is most noticeable on the environment, he said.

The environmental impact is felt most profoundly with reductions in the amount of carbon dioxide released into the atmosphere. Efficiencies and cost savings come largely from reduced use of raw materials and significant cuts in energy use.

To give an example, Wong pointed to a new process for manufacturing Lyrica developed by his team in Groton that reduced carbon-dioxide emissions by 43 percent using one of Pfizer's measurement tools. The company expects a further reduction in emissions of 20 percent as it continues to refine the method through the end of next year, he said.

Avoiding chemical waste

"The pharmaceutical sector has embraced green chemistry most enthusiastically, perhaps because it has the most to gain," according to an article last month in Nature News. "Pharmaceutical plants typically generate 25 to 100 kilograms of waste per kilogram of product, a ratio known as the environmental factor, or 'E-factor.' So there is plenty of room to increase efficiency - and cut costs."

The company expects that green-chemistry processes used to reimagine the production of Lyrica will, over a 13-year period, avoid about 200,000 metric tons of organic chemical waste. Pfizer scientist Peter Dunn, who in 2006 became the pharmaceutical industry's first full-time green chemistry leader, has said the rejiggering of three product lines alone saved the company the cost of 500,000 metric tons of chemicals.

According to Pfizer spokeswoman Sperry Mylott, the company's drugs currently in late-stage development use 24 percent less solvent per kilogram than the most advanced compounds it was testing a few years ago, "thus achieving one of Groton's chemical R&D team's environmental goals two years ahead of schedule."

Chemists do small-scale experiments in Groton before trying out their ideas on a bigger stage with Pfizer's manufacturing partners, said local team leader Wong. The idea is to be as "atom economical" as possible, he added, meaning that less material used up front leads to less waste in the end.

"The company is quite good at implementing process improvements," he said.

Although the pharmaceutical industry in general did not embrace the principles of green chemistry right away - chemical companies faced with outcries after the Love Canal fiasco and the Bhopal disaster had a greater incentive - it now is more motivated, as drug discovery has waned and cost-cutting is getting more attention.

As far back as 1998, Pfizer scientists in Sandwich, England, had worked to improve efficiencies in the manufacture of Viagra, which at that point produced 105 kilograms of waste for every kilogram of product. Pfizer eventually reduced the E-factor to 8, meaning the production of Viagra became more than 90 percent more efficient.

"Ultimately, it's all economics that drives it," said Connecticut College chemistry chair Marc Zimmer. "You can't just let waste go down the drain anymore. You have to dispose of it, and that means you have to pay for it."

Improving production methods of antidepressant Zoloft as well as Viagra and Lyrica have won Pfizer major green chemistry awards. The 2002 Zoloft green chemistry project, conducted at the Groton labs, won the U.S. Environmental Protection Agency's Presidential Green Chemistry Award.

Early stage development

The local labs also have their own internal awards, and winners may designate the prize to an educational institution. In the past year, the prize went to Pfizer scientist Jamison Tuttle, who designated that the $5,000 award be given to his former Connecticut College professor Timo Ovaska, who in turn plans to use it for research stipends for summer students.

"Green chemistry is still in an early stage," Ovaska said, "but it's definitely having more and more of an impact."

Wong said Pfizer doesn't force green chemistry on anyone, but there is a constant effort to educate employees in the science. He added that chemists have been quick to embrace the concept and are always brainstorming and experimenting with new ideas for making pharmaceutical production less costly and easier on the environment.

"It's part of our day-to-day activities," he said.

Ordinary Measures : Everything I needed to know I learned in Freshman Chemistry 101

For Years, pharma has been the villain in most public opinion polls. But now, the tide seems to be turning. Last month brought buzz about the film, Extraordinary Measures. You’ve no doubt heard all about the inspiring story of John Crowley, a pharmaceutical exec who quit his job to fund research into cures for Pompe disease. Not only did he save the lives of his own, and many other, children, he opened up the field of orphan drugs.

Although critics are lukewarm, they say the movie does reveal to the public more of the complexity and challenge of drug development and manufacturing. What could be better than that? But lately I’ve been wondering about the “other” side of manufacturing—the side that could never make it to Hollywood: cGMPs and quality control. Drug recalls in the U.S. have been trending upwards. In the U.K., according to a recent study by Blueview Group, drug and medical device recalls increased 400% between 2004 and 2008, due mainly to manufacturing defects, packaging or labeling issues, or compromised sterility. 

Pharmaceutical quality control reached a climax in the news last summer, after FDA issued Genzyme a 483 for cGMP problems at its Allston Landing plant. This plant manufactures the orphan drugs Cerezyme and Fabrazyme, worth nearly $2 billion in sales each year. A dissident shareholder, Relational Investors, sued the company, its principal alleging that Genzyme overpaid for acquisitions and underinvested in manufacturing. The problems cost Genzyme dearly, as FDA did not approve its improved Pompe disease treatment (which is now being re-evaluated) and reportedly streamlined the approval process for a competitor’s product. Last month, Genzyme hired a new QC chief, and contracted with Hospira to handle filling. Relational withdrew its suit, and hopes to settle its diff erences with the company.

But the question still lingers. Is the industry, in its desperate attempt to acquire innovation and reinvent itself, underinvesting in core quality control operations? Last month saw another major pharma company, J&J, dogged by quality control issues. Th e company has led the industry in Lean Six Sigma and operational excellence initiatives, so this news may have surprised some. But J&J had to recall more lots of Tylenol and other over-thecounter medications, which were tainted with a chemical used to treat wooden pallets. FDA alleged that J&J was aware of the problem a full year before it took action.

It’s easy to point the finger at senior management. But is that the whole story? Is everyone on your team being rigorous about quality? We often lament about pharma’s silos and its “data rich, information poor” problem. But that doesn’t mean that each and every critical data point shouldn’t be recorded, transferred and shared. Last month, we interviewed experts on the topic of tech transfer, and found that people oft en fail to transfer basic information to internal partners, or external CMOs. Information is missing, isn’t recorded, and, in deals involving China and Japan, isn’t translated. And analytical methods and SOPs are the areas where people most often trip up. This has an obvious impact on CAPA and fundamental quality control.

Contributing editor and NIR expert Emil Ciurczak suggests that some have “gotten lazy and stupid” about documenting critical details. “Everything you need to know to pass an FDA inspection you learned in freshman chemistry class,” he says. One industry consultant recalls a consent decree in the 1980s, where a lab technician openly admitted to FDA to taking notes down in pencil, then changing them to ink later on. She also responded to questions about an SOP. “Nobody does it that way,” she said. “Everyone knows it won’t work that way.”

“How could anyone have hired such an incompetent tech?” you ask. But is it really that farfetched? Read any 483’s lately? It’s the ordinary measures, as well as the extraordinary ones, that count.