I always seem to be writing about GSK in my blogs but this is a much more sombre subject compared with the recent news of GSK CEO Andrew Witty’s knighthood. This week’s attention on GSK is focused on the COMPAS (Clinical Otitis Media and PneumoniA Study) study, which involved almost 24 000 children and was completed in Argentina in June 2011. The fine issued by the Argentinean National Administration of Medicines, Food and Medical Technology (ANMAT) related to administrative procedures in place for the study in 2007 and 2008. According to media reports (Sky News, CNN), some consent forms were signed by illiterate parents or people who did not have custody of the children. Claims have also been made that some children feeling unwell after vaccination were not seen by doctors.

Fourteen children are reported to have died during the study. Because the trial involved children, it is an extremely sensitive and emotional topic that has evoked strong reactions from some media sources that accuse GSK of “killing” babies and “experimenting with humans”.

But there are two sides to every story. Personally, I don’t believe that any reputable pharmaceutical company would experiment on humans.

GSK emphasised in a press statement that the fine relates to administrative procedures and “does not question the safety of the study vaccine”. Indeed, according to the statement, any deaths in the study were thoroughly investigated and both an independent data monitoring committee and ANMAT both concluded that none of the deaths were related to the vaccine.

The administration irregularities with obtaining informed consent were identified by GSK in 2007 and 2008 as part of routine monitoring, which takes place at 6-week intervals.

“The company proactively reported these findings to ANMAT and immediately put in place a corrective action plan which involved reconfirming informed consent of patients in the study and retraining doctors… where necessary,” explained GSK’s press statement. “The safety of patients participating in the study was not put at risk and ANMAT agreed that the study could continue as planned.”

Some media sources have also accused GSK — and other Western pharma companies — of taking advantage of developing countries to experiment with new treatments. In the case of GSK’s Synflorix, however, developing countries are a logical choice for a clinical trial. Estimates from the World Health Organisation claim that more than 500,000 young children die each year from pneumococcal infection, with the vast majority of these deaths occurring in developing countries. The GAVI Alliance also explains that although a vaccine against pneumococcal disease has been widely used in Europe and the US since 2000, it was not optimal for developing countries because it lacked different strains of pneumococcal bacteria that are common in developing countries.

Although Argentina is not really considered a developing country, it still has a large number of people living in poverty and pneumococcal disease is a significant health burden.

GSK says that it “respectfully disagrees” with the court ruling in favour of ANMAT and will appeal to the Supreme Court of Argentina. However, if unethical practices did take place during the trial then GSK has said it will pursue the matter.

“We are also concerned by allegations that treatment was delayed for some children in the trial if they were unwell and, if true, these events are shocking… we will be looking into this further,” said the GSK statement.

The National Institutes of Health recently administered cancer vaccine PANVAC to 26 women with breast or ovarian cancer. PANVAC, a recombinant poxviral vaccine, produces two proteins associated with tumor cells to stimulate the body’s immune system to attack the cancer. During the trial, the median time it took for the breast-cancer patients’ condition to progress was 2.5 months, and the patients’ median survival time was 13.7 months. One breast cancer patient was still alive 37 months later. Median survival for the 14 ovarian-cancer patients was 15 months, and one woman went 38 months before her disease progressed. Although the trial was small and did not include a control group, these results seem encouraging.

Researchers from Oxford University also have attempted to fight cancer with the immune system. A team led by Paul Fairchild, codirector of the Oxford Stem Cell Institute, used stem-cell technology to create new dendritic cells from a patient’s skin. The dendritic cells, which organize part of the body’s immune response, carried the marker Melan A so that they would trigger an attack on melanomas. In the study, the team’s dendritic cells activated immune cells that produce antibodies and those that kill other cells. Previous studies using other dendritic cells had stimulated only part of the immune system.

Both of these techniques are still in their early phases. It will be some time before the studies lead to therapies from which patients can benefit, but they add to our knowledge of cancer and underscore the importance of oncology research. I take encouragement from these early steps, which I hope will inspire other drugmakers to take up the challenge of battling cancer.

A few weeks ago, Representative Michele Bachmann (R-MN) made waves by claiming that the vaccine for human papillomavirus could have dangerous side effects. She retreated from her remarks after the American Academy of Pediatrics said that they had no scientific validity. Makers of biopharmaceuticals might feel vindicated, but a recent poll emphasizes that Bachmann is not alone in her views.

About 21% of respondents to an NPR–Thomson Reuters Health Poll believed that autism was linked to vaccines, and 7% believed that diabetes was linked to vaccines. Nearly half of the respondents worried about the side effects of vaccines, and about the same portion were concerned about their long-term effects on health. About a quarter of respondents said that their opinions about vaccines had changed during the past five years.

Patients’ concerns about vaccines’ safety are not supported by the evidence. Federal officials have studied vaccines’ links to side effects 12 times in the past 25 years, and the most recent report from the Institute of Medicine (IOM) found inadequate evidence to accept a causal relationship in the vast majority of cases. IOM did, however, find evidence to reject relationships between the measles–mumps–rubella (MMR) vaccine and autism, and between that vaccine and diabetes.

IOM did find links between vaccines and some adverse events, but the events were either rare or transient. For example, patients vaccinated against chicken pox can develop pneumonia, hepatitis, or meningitis late in life if an unrelated illness (e.g., cancer) compromises their immune system. In addition, the MMR vaccine was linked to temporary joint pain in children and female adults.

Biopharmaceutical manufacturers that are confident of their products’ safety could still benefit by launching a public-education program. Publicizing the many federal studies that have found vaccines to be safe and, as I wrote a few weeks ago, disclosing safety information gained during trials of approved vaccines could help to assuage patients’ fears.

Just last week, Representative Michele Bachmann (R-MN) told Fox News that the vaccine for human papillomavirus “can have very dangerous side effects.” Bachmann, who hopes to be the Republican candidate for president next year, mentioned a mother who claimed that her daughter had suffered mental retardation because of the vaccine.

Bachmann has taken a lot of heat for her remarks. The American Academy of Pediatrics and public-health efforts have denounced them. Arthur Caplan, a bioethicist at the University of Pennsylvania, offered to donate $10,000 to the charity of Bachmann’s choice if she “can produce a case in one week . . . verified by three medical experts that she and I pick of a woman who became ‘retarded’ (her words) due to the vaccine.”

Unfortunately, Bachmann is not the first to question vaccines’ safety. For years, a small but vocal group has been claiming that the vaccine for measles, mumps, and rubella causes autism. Early this year, the research paper that lent credence to this claim was revealed to rely on sloppy science and questionable methods. More recently, a panel assembled by the Institute of Medicine found no evidence that the vaccine causes autism.

Rumors that vaccines are harmful continue to circulate even in the absence of sound evidence. Comments such as Bachmann’s help foster this misperception. The group warning about vaccines’ putative dangers may be small, but it has gained media attention and could potentially influence patients’ decisions about healthcare. The pharmaceutical industry, and public officials such as FDA, would do well to publicly reaffirm that vaccines are safe. Drugmakers could describe the safety information garnered during clinical trials of their now-approved vaccines. And perhaps FDA could include a Q&A about vaccines on its website to dispel doubts. Communicating accurate information about vaccines will help the industry and patients alike.

The patent cliff is beginning to reduce Big Pharma’s sales figures as generic versions of branded drugs enter the market. Although FDA has remarked that pharmaceutical innovation is beginning to increase, not all companies are going to be able to market enough new drugs to make up for lost sales. So how will these vulnerable companies maintain their profits?

Producing vaccines could be a key strategy for firms that have invested in biopharmaceutical manufacturing capacity. Market research firm Kalorama Information reported that the world market for preventative vaccines rose from $22.1 billion in 2009 to $25.3 billion in 2010. It predicts that the market will grow at a compound annual rate of 9.3% during the next five years, thanks partly to sales in emerging markets.

The vaccine market generally is regarded as having two components: adult products and pediatric products. The pediatric market is the bigger of the two—it accounts for more than half of the total market and is growing at a faster rate than the adult market, according to Kalorama.

The growth in pediatric vaccines could spur the development of new drug-delivery methods—another go-to strategy for drugmakers facing the patent cliff. Kalorama predicts that the market for needle-free drug delivery methods will grow at an average rate of 15.1% from 2011 through 2016, when it will be valued at roughly $6.2 billion. More and more children, and needlephobic adults, might benefit from products such as patches and pen injectors.

The search for alternatives to injections could produce surprising results. Arizona Biodesign Institute has concluded three early-stage clinical trials using potatoes that carry vaccines against hepatitis B, E. coli, and the Norwalk virus, according to Kalorama.

These two reports confirm the growing importance of vaccines and new drug-delivery methods for the pharmaceutical industry. Companies with enough manufacturing muscle and scientific knowhow should be able to find creative ways to survive the coming welter of patent expirations. And their ingenuity will make life easier for patients, too.

Sound like a fairy tale? Well, it’s safe to say that the research is definitely in its early days so we’re a long way away from a vaccine, but important progress has been made by the discovery of an antibody that can fight all types of the influenza A virus, which commonly affects humans and some animals. The discovery was made by scientists at the UK’s Medical Research Council (MRC), the Institute for Research in Biomedicine and Humabs BioMed (both in Switzerland), and has been described in a number of media headlines as a “super antibody”.

“Historically, it has been impossible to predict precisely what kind of flu could develop into an epidemic and, as such, it has been necessary to develop new vaccines each year to tackle the different viruses. Our discovery may eventually help to develop a universal vaccine,” Dr Steve Gamblin from the MRC’s National Institute for Medical Research said in a statement.

According to a report from BBC news, the antibody—known as F16— targets the haemagglutinin protein, which is found on the surface of all influenza A viruses. Experiments were conducted on mice to test the antibody’s potential. When the mice were injected with the antibody up to two days after being given a lethal dose of the influenza virus, all of them survived and recovered. The antibody was discovered after the scientists looked at more than 100000samples of immune cells from patients who had flu or had received a flu vaccine.

A report from Reuters added that previous research has found antibodies that work in Group 1 influenza A viruses or against most Group 2 viruses, but not against both.

Sir John Skehel from the MRC’s National Institute for Medical Research explained that knowing the structure of the antibody and how it interacted with haemmagglutin would aid the search for a vaccine, but added that this development would be years away.

“It is estimated that every year millions of people are infected with influenza A viruses and, although the majority of infections are mild, those in vulnerable groups, such as the very old or the very young, may be worse affected and more likely to die or be hospitalised. As we saw with the 2009 pandemic, a comparatively mild strain of influenza can place a significant burden on emergency services. Having a universal treatment which can be given in emergency circumstances would be an invaluable asset,” said Skehel.

This week, for instance, Novartis started shipping its flu vaccine, Fluvirin, across the US, while MedImmune, a unit of AstraZeneca, has been talking about shipments of its three-strain influenza vaccine, FluMist. It’s not unusual for vaccine manufacturers to begin making preparations at this time of year, but one particularly interesting piece of influenza news in the headlines this week concerns a novel breath test that shows promise for measuring an individual’s immune response to the H1N1 virus.

The test, developed by researchers from the Cleveland Clinic and Syft Technologies, measures biomolecules (exhaled nitric oxide) that accumulate in response to H1N1. By identifying people who have already been infected with the virus (and who are thus extremely unlikely to contract the same strain again), the test could reduce unnecessary vaccinations. There’s nothing wrong with being vaccinated against a flu you have already caught, but it does put a bit of a drain on vaccine stocks, which can be scarce depending on public demand.

According to a press statement describing the breath test research, in 2009, more than half of the people in Glasgow (Scotland, UK) who were vaccinated against H1N1 had already been infected with the virus. It’s believed that similar patterns would have been seen throughout the UK. Given the fact that the 2009 swine flu pandemic is still fresh in everyone’s minds, it’s likely that demand for flu vaccines will be high over the next few years so it’s important to make sure that stocks do not go to waste.

There’s still a way to go though before the test can be used commercially. According to the researchers, further work is needed to identify other compounds that are associated with an immune response. It will also be important to identify the exact mechanism that underlies the increase in exhaled nitric oxide triggered by the virus.

It’s definitely an interesting piece of research, but the problem with any influenza R&D is that it can become out of date quickly. By the time an H1N1 breath test is available, it could be that a new strain is filling the headlines and that nobody really remembers H1N1. On a more positive note, though, the research demonstrates the potential benefits that breath analysis can offer to medical diagnostics. And if/when a test does become available for H1N1, perhaps there will be potential to create tests for other strains.

If you’re interested in this research, the full scientific article is available for free (for a limited time) in IOP Publishing’s Journal of Breath Research.

Indeed, many of this week’s price cuts have been made in response to a tender off for the rotavirus vaccine (the world’s second largest killer of children after pneumonia) from the United Nations Children’s Fund (UNICEF), which supplies medicines to children in developing countries. The reductions were detailed in a statement from the GAVI Alliance, a global health partnership that aims to increase access to immunisation programmes in poor countries.

GlaxoSmithKline (GSK) has come forward with an offer of just $2.50 per dose or $5 to fully immunise a child, which is a 67% reduction on the current, lowest available public price. However, GSK isn’t the only company  taking an axe to its prices. Merck has said it will offer its own rotavirus vaccine to UNICEF at a discounted price, and new market entrants in India, including Bharat Biotech, the Serum Institute and Shantha Biotechnics (a subsidiary of Sanofi Pasteur), are also developing rotavirus vaccines for GAVI-eligible countries, although these are not expected to be ready for purchase until 2015. However, these vaccines could encourage further price reductions. On its website, Bharat Biotech has said that it will offer $1 per dose.

According to Helen Evans, GAVI’s interim CEO, if the rotavirus vaccine could be purchased this year at a $2.50 price, the impact on public health could be significant. It would also enable GAVI to save approximately $500 million through to 2020, or about $140 million through to 2015, as measured against GAVI’s current financial estimates.

Cuts have also been made to the prices of other important vaccinations. For instance, the Serum Institute and Panacea Biotec (India) have both lowered the prices of their pentavalent vaccines. GAVI’s statement added, “The price reductions illustrate the key role of emerging market suppliers as new global players, contributing to both innovation and increasing competitiveness in the market place.”

Merck has also offered its human papillomavirus (HPV) vaccine at a reduced price of $5 per dose, while Crucell and Sanofi Pasteur have announced that they will extend GAVI prices on their pentavalent vaccines to the 16 countries expected to graduate from GAVI support. In its statement, GAVI added that these announcements build on similar commitments made to graduating countries by Pfizer and GSK.

“Our market-shaping goal is to achieve the lowest price for currently available products while maintaining supply security,” said Evans. “Looking forward, Alliance members will work to broaden competition and ensure the provision of quality vaccines at sustainable prices. Today’s announcements are a step forward to achieving this goal.”

GAVI’s statement was issued in the lead up to its first pledging conference, which will take place next week.

New Jersey’s pharmaceutical workforce has shrunk as a result of mergers and flagging sales, and observers are searching for a tonic to give the industry new life. One necessary strategy is to form partnerships with international investors or other drugmakers, said David Finegold, dean of Rutgers University’s school of management and labor relations, at the EU–NJ Business Forum. Investors in South Korea, India, and China are putting a lot of money into the industry, but they don’t have people with experience in gaining FDA approval for their products, Finegold said, according to The Record.

Finegold’s model of choice is the partnership between Merck & Co. and the Wellcome Trust medical charity, which is based in the United Kingdom. The partnership aims to prevent diseases that affect poor countries by developing new vaccines and optimizing existing vaccines. Merck and the Wellcome Trust invest equally in the partnership and share decision-making responsibilities.

The partners run the venture like a business, but according to a not-for-profit model, which is a foreign concept to most drugmakers. Yet the pharmaceutical industry will have to get used to this idea. To survive, firms will have to abandon their high profit-margin business models, Finegold said.

Give him credit for trying to get risk-averse drug companies to adopt new and creative ways of thinking and operating. Although Finegold’s recommendations could help stimulate the industry, I wonder whether they would increase domestic employment. The Merck–Wellcome Trust partnership, Finegold’s template, is based in India. An ideal business model would foster international cooperation, create domestic jobs, and encourage the development of needed therapies. If nothing else, Finegold’s remarks will help start discussions that could lead the industry toward this ideal.

On Tuesday morning, representatives of Shire and Honeywell will explain how the former rapidly designed and completed a biopharmaceutical manufacturing facility that relies heavily on single-use equipment. Shire say they set themselves an ambitious timeline for completing the facility, and the company apparently finished it earlier than it had planned. I’m curious to learn how the crew managed to design, equip, commission, and validate the facility in a seemingly short period. I’d also like to know which of the plant’s operations use disposable components, and how Shire decides when single-use items can take the place of traditional stainless steel.

A session about designing modular vaccine facilities on Wednesday promises to be interesting, too. Modular facility design has been touted as a way to reduce operating costs and make a manufacturing plant more flexible. A representative of NNE Pharmaplan will describe how standardization and single-use equipment helped to lower the costs of BSL2 and BSL3 vaccine facilities. He’ll also describe how these techniques can speed up the completion of a facility, and it will be instructive to compare his remarks with what Shire says on Tuesday. I’ll also be curious to hear about the challenges that any company must face when they want to design a modular facility.

Several other sessions will relate to large-molecule facilities. Speakers will talk about applying risk assessment to the design of biopharmaceutical manufacturing plants, and also about establishing appropriate microbial controls for these sites. It might be difficult for attendees to choose among the many presentations at a given time. Regardless, I’m sure we’ll walk away with a better understanding of where the industry is headed in the near future.