Statistics are currently available for January–September 2011. So far, the EMA has issued 74 positive opinions on marketing authorisation applications. Overall, the agency has started 76 marketing authorisation applications and finalised a further 79. So, what kind of picture do these statistics paint? Quite a bright one, actually, particularly in comparison to the bleakness of 2010 when the EMA issued only 51 positive opinions for marketing authorisation applications.

2011’s number of finalised marketing authorisation applications (79) has overtaken 2010’s low figure of 54; indeed, the year has also beaten 2008’s 72 finalised applications. However, there’s still a long way to go to outdo 2009’s 125 finalised applications, which were partly driven by a high number of applications (51) for generic products. This year, there has once again been a considerable number of marketing authorisation applications for generic products, with 28 finalised compared with only 20 in 2008.

There has also been a noticeable increase in the number of applications for new products, which is positive considering the amount of criticism that has been directed at the pharma industry’s innovative pipeline. So far, the agency has finalised 32 applications for new drugs compared with just 21 last year. New orphan medicinal products are also on the rise: 11 applications have already been finalised this year compared with six in 2010.

For started marketing authorisation applications, it’s a little different: 76 started applications in 2011 compared with 90 in 2010. Breaking down the numbers, however, the EMA starts roughly 8 applications per month, so the total could theoretically rise to 100 or more. We’ll have to wait until the end of the year to find out. Importantly, however, the number of started applications for new products is high at 36 applications compared with 2010’s 34.

There’s still a long way to go before anyone can safely say that the innovation drought is over, but given that the US has also seen greater drug approval rates this year compared with last, perhaps 2011 marks an important step towards this goal.

Related articles

An upward trajectory for new drug approvals

Is pharma’s innovation slump over?

The final ruling goes further than the preliminary ruling, laying down broad restrictions on patenting any procedure or process that requires the destruction of an embryo. Included in the ban are patents on scientific research entailing the use of human embryos, and patents of procedures and processes using embryonic stem cells derived by processes that result in destruction of an embryo. In the press release accompanying the ruling, the court states “In conclusion, the Court holds that an invention is excluded from patentability where the implementation of the process requires either the prior destruction of human embryos or their prior use as base material, even if, in the patent application, the description of that process, as in the present case, does not refer to the use of human embryos.”

While the European research community is not banned from conducting embryonic stem cell research, the climate for commercializing any discoveries is now decidedly unfriendly. IP protection can still be obtained for embryonic stem cells in the US, but Europeans wishing to pursue research on stem cells with the ultimate goal of developing therapeutics might be better off switching to stem cells derived from adults, or must adopt ways of obtaining embryonic stem cells without destroying embryos. The scientific community generally does not view adult-derived stem cells as being equivalent to embryonic stem cells, and therapeutics derived from either are not numerous or far enough along in development to know which class will prove to be safer or more effective in the clinic. However, this seems to be a case where drug development will have to accommodate the wishes of society.

See related posts:

New Challenges for Use of Embryonic Stem Cells

Embryonic stem cells: the moral dilemma of patentability and funding

Federal Appeals Court Lifts Ban on Funding for Embryonic Stem Cell Research

The move by the EC this week will somewhat relax the stringent control, but it’s important to differentiate between providing information and full-blown DTCA. For a start, television, radio and general print media will not be allowed and the information will be factual rather than promotional.

Further, only certain information can be conveyed, including information on the label and packaging leaflets, pricing information, clinical trials and instructions for use. The information will have to conform to recognised quality criteria by being unbiased, factually correct and non-misleading, and will also need to be verified by competent authorities prior to use. Companies will be able to disseminate the information on sources such as officially registered websites or printed information that will be made available only when specifically requested by members of the public.

In general, the move has been welcomed by industry stakeholders, including the European Federation of Pharmaceutical Industries and Associations (EFPIA), which believes the approach is constructive and pragmatic. However, the European Public Health Alliance (EPHA), while welcoming the EC announcement, adds that the Internet is a sticking point.

“EPHA agrees that the Internet can be a useful place to provide information, however in the case of medicines information, this should be limited to the Patient Information Leaflet and other medicines safety information. This should be accessed though a portal or database with a single point of entry so as to avoid confusion and the proliferation of misleading information. Unfortunately, this is not the approach chosen by the European Commission which still prefers ‘information’ to be provided by pharmaceutical companies directly on their website,” said a statement from the EPHA.

Another issue with the Internet is that, although the DTCA of prescription-only medicines is banned in Europe, we are exposed to it all the time. I’ve often clicked on a link in Google to be taken to a US website that bombards me with banner advertisements about Alzheimer’s medications. It’s always made me uncomfortable; the first time I was exposed to medicines ‘advertising’ was when I fourteen and began receiving spam emails about Viagra (which, as a teenager, I found vastly amusing). Ever since then, all medicine advertisements have put me in mind of those spam emails. It’s a harsh generalisation, but DTCA is very strange when you’re not used to it!

It’s also not hard to find extensive information about a medicine—either accidentally or simply by clicking on the “I am based in the US” option on global websites.

However, the adoption of the EC proposal, which obliges pharma companies to provide medicines information, will enable Europeans to access this data without having to find a way into a US site, in their own language and without having to be exposed to DTCA.

So is DTCA next on the agenda for Europe? Unlikely. DTCA is perceived rather negatively by both the European public and industry associations alike, and previous attempts to instate it have always been rejected quickly. EFPIA has also made it clear that it does not wish to see information on prescription medicines on television, print mass media or radio.

If you want to look at DTCA from the other side of the fence, then take a look at a related blog on our sister site Pharmaceutical Executive where Pfizer’s CEO argues that DTCA is a fundamental right!

Other recommended articles

Will DTC advertising appear in Europe?

Google’s worldwide woes

No clear benefit predicted from an extended moratorium on direct-to-consumer advertising

DTCA: beneficial or harmful?

Innate immunity refers to the body’s first line of defense against infection.  When a pathogen enters the body, the body must recognize that a foreign body has entered, then mount an immune response that will destroy the pathogen.  Hoffman, working in fruit flies, identified a gene called Toll that was required for innate immunity. He found that the product of the Toll gene helped detect the presence of pathogenic microorganisms and that Toll activation was required for successful defense against them.

In parallel, Beutler was searching for a receptor that would recognize the bacterial product lipopolysaccharide (LPS), which can cause septic shock.  The gene for the LPS receptor that he identified turned out to have a high degree of homology to the fruit fly Toll gene.  He went on to show that this Toll-like receptor activated inflammatory responses after binding LPS.  Other researchers have identified around a dozen different Toll-like receptors in humans and mice, each of which recognizes certain molecules common in microorganisms. Individuals with certain mutations in these receptors carry an increased risk of infections while other genetic variants of Toll-like receptors are associated with an increased risk for chronic inflammatory diseases.

Adaptive immunity refers to ability of the immune system to acquire a long-term memory of pathogens it has seen before, allowing a more rapid and stronger activation of the immune system the next time that pathogen is encountered.  Steinman is honored for his discovery of the dendritic cell, an important intermediary in the development of adaptive immunity.  Work by Steinman and others showed that dendritic cells capture and present antigens and can powerfully activate T-cells.  Dendritic cells also play an important role in the control of tolerance and immunity, processes by which the body differentiates “self” from others.

The understanding of the immune system embodied by this work has laid the foundation for new therapies that attempt to harness the immune system to fight diseases such as cancer, and for new strategies for vaccine development.   As an example, Dendreon’s cell-based therapy Provenge for prostate cancer takes a patient’s own dendritic cells, cultures them, then re-introduces them into to the patient to reinforce the immune response to the cancer cells.

Sadly, Steinman passed away on September 30, 2011, days before the announcement of the prize.  The Nobel committee was unaware of his death at the time of the announcement. Although the Nobel Prize is not granted posthumously, the committee has decided to nevertheless award the prize to Steinman, because he was alive at the time of the selection.  Steinman was suffering from pancreatic cancer, and was being treated with a therapy based on his own discoveries of dendritic cell activation.

I’ve been reading a lot about CPhI this week as companies prepare their media campaigns and with the start of October looming, I thought I’d take a brief look at where the behemoth event started and where it’s going.

CPhI debuted in 1990 in Frankfurt as a small international convention for ingredients and intermediates, with only 16 exhibitors and 250 delegates. The event has been held annually ever since and I wonder if the original delegates from 1990 would even recognise it. 2011’s event will run for three days (25–27 October) and is expected to see 1900 exhibitors and 28,500 industry professionals from more than 120 countries.

Although this year’s event, like the inaugural show, will be held in Frankfurt, CPhI has visited many European cities over the years including Amsterdam, Belgium, London, Madrid, Milan and Paris. Frankfurt is a popular location for European trade shows, but hasn’t hosted CPhI since 2008. With Germany being one of the leading pharmaceutical markets in Europe, it’s safe to say that it’s a fitting setting for a pharmaceutical event.

Even twenty two-years after its debut, ingredients and intermediates are still a huge part of CPhI. Over the years, however, the event has begun to include several collocated events dedicated to contract services (ICSE — debuted in 2001), pharmaceutical machinery and equipment (P-MEC — debuted in 2006), and biopharmaceuticals (BioPh — debuted in 2009). This year will also see the debut of a new collocated event called InnoPack dedicated to (you guessed it) packaging.

As big and important as CPhI is, however, its location in Europe inevitably makes it trickier for visitors to attend from regions such as Asia and South America. In the last decade, CPhI has expanded its global reach by initiating events in China (2001), Japan (2002), India (2006) and South America (2008). In particular, the Indian and Chinese events are growing fast, which is a testament to the growing pharma industries in these developing markets, as well as the increasing interest of Western companies looking to emerging markets for new opportunities.

The next CPhI China event, due to be held in June 2012 in Shanghai, is expected to attract 1700 exhibitors and 27000 attendees, which is close to the numbers of the worldwide show. CPhI India 2011, due to be held this November, is also expected to see attendee numbers in excess of 26,000, which is remarkable considering that the event only debuted in 2006. The event was met with strong interest from the beginning when the inaugural show featured 325 exhibitors and 11,000 attendees — the largest ever debut for a CPhI show.

Of course, it’s not just pharma companies that will be descending on Frankfurt at the end of October — members of the Pharmaceutical Technology Europe team will be attending too. My colleagues will be at booth 51F53 and would love to hear any thought from you about our website or magazine so please do come and say hello. As for me, I’ll be in the office keeping a close eye on the latest CPhI trends and discussions on Twitter and LinkedIn.

Looking to next year, the organisers are already outlining plans for CPhI 2012. The event will be held in Madrid (Spain) at the Feria de Madrid.  The show will run from 9–11 October so keep these dates free!

Concern about pharmaceuticals in our water supply has been in the public consciousness for a few years now. In 2009, the Environmental Protection Agency found traces of various drugs in fish caught in rivers that receive effluent from wastewater-treatment plants. The drugs were believed to come from doses that people had excreted or flushed down the toilet. In response, FDA updated its guidelines for disposing of drugs. New research, however, shows another potential source of drugs in our waterways.

French scientists investigated fish called wild gudgeon that lived upstream and downstream of a steroid-manufacturing facility owned by sanofi. About 60% of the fish downstream of the facility had both male and female sexual characteristics, as opposed to 5% of the population upstream. Researchers identified pollutants such as diuretics and anti-inflammatory agents in the river. The fish’s abnormalities could prevent them from breeding and also signal problems in other species.

“People think drug release is regulated, but it’s not,” said Joakim Larsson, a pharmacologist at the University of Gothenburg in Sweden, to Nature. But this lack of oversight may end: the European Commission is now considering whether to set limits on common drugs (e.g., ibuprofen and the contraceptive ethinylestradiol) in waterways.

Setting limits might prove difficult, however. Scientists have not yet determined safe limits for many pharmaceuticals in the aquatic environment, or how widespread the problem is, according to Susan Jobling, an aquatic ecotoxicologist at Brunel University in London who spoke to Nature.

The French researchers’ findings certainly are alarming, but regulators won’t have a solid basis for any decisions until more information comes to light. I’m encouraged that sanofi is cooperating with regulatory agencies, researchers, and ecological associations to investigate the scope and root of the problem. In the meantime, the pharmaceutical industry would do well to keep this story in mind, and perhaps review whether it can reduce the potential risks of its waste-disposal procedures.

Also see my previous posts about pharmaceuticals in water:

“Water without Side Effects”

“Hope for Bipolar Fish”

I like cars, and I like fast cars even more. So too, it would seem, does GlaxoSmithKline’s CEO Andrew Witty as the company is embarking on a long-term strategic partnership with the McLaren group, which is best known for its Formula 1 racing cars. The phrase “best of British” really does sum up the partnership and both companies seem extremely proud of it. The aim for GSK? Applying McLaren’s engineering and technical expertise to production lines to reduce breakdowns and improve costs, amongst other things.

“I am delighted to announce this partnership with McLaren which brings together two British companies whose continued success hinges on the ability to innovate and rapidly respond to change and competitor activity.” said Witty in a GSK press release. Witty considers the unusual pairing to be “looking outside its sector for inspiration and fresh perspectives” – and where better to look than a sport with 720 bph engines and grid girls? What the McLaren Group stands to gain, I can only guess…

Reading the joint press releases, it really does seem to make some sense; in particular, the state-of-the-art facility planned for 2013 to be called The McLaren GSK Centre for Applied Performance sounds like a novel way of breathing a little fresh air into pharma’s slightly sagging sails. Scientists, engineers and technologists from both camps will be able to share ideas and collaborate on innovative, dynamic and exciting joint working projects. And let’s face it, sometimes a fresh outlook is exactly what is required to make real progress. In some ways, it puts me in mind of the Novartis-MIT Center for Continuous Manufacturing – though admittedly, this collaboration is more readily justifiable and the aim a lot less vague…

Having said that, there are some defined goals. Alongside the aforementioned application of McLaren’s modelling system to the GSK production line, the R&D organisation will examine whether real-time monitoring technologies can be applied to human studies and the GSK Consumer Healthcare business will work with McLaren’s “Mission Control” unit to enable faster responses to competitor activity and customer needs.

Some might say that it smacks of a marketing stunt, and certainly it will do GSK no harm to be associated with such a fast-paced, exciting, technologically advanced, continually improving world—aren’t these all qualities that we would like to see demonstrated by pharma companies? I guess the level of investment that GSK pumps into the project may answer any critics and I look forward to seeing what comes into fruition.

The news has left me wondering what else the future may hold… Sanofi and Red Bull Racing? Merck and Merc? The race to the chequered flag is on!

No matter the real reasons behind the partnership, I will certainly be settling down on the sofa this weekend to see the top F1 drivers battle it out in Singapore—the perfect accompaniment to a traditional home-cooked Sunday lunch – another best of British.

…and sometimes, entirely the wrong drug is found in the packet. In a case that has had UK media reports aflame, a prescription only antipsychotic drug was found in certain packets of a common pain medication that was manufactured by a completely different company. Is it a repackaging mistake? Or are more sinister intentions at work? Either way, it’s clear there are could be a few security holes in pharma’s distribution chains.

Late yesterday afternoon, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) issued a statement warning the public to be cautious when using Neruofen Plus (made by Reckitt Benckiser) because AstraZeneca’s Seroquel XL 50 mg, had been found in certain packets. Seroquel XL is indicated for the treatment of schizophrenia and bipolar disorder.

It’s a pretty big mistake. In fact, it’s so major that some media reports led themselves to the conclusion that it could be sabotage. In its own statement, the MHRA also believes that a manufacturing error is unlikely. “Seroquel XL tablets are made by a different company (AstraZeneca) at a different site. Manufacturing errors by Reckitt Benckiser and AstraZeneca are not considered to be part of the cause at this stage.”

Three packets have been identified so far—all in south London. The MHRA believes that three different batches may be affected, which equates to anywhere between 4000–7500 packs, according to a report from the UK’s BBC. The MHRA statement says that the packs contained “rogue” cut-down blisters of Seroquel that included both parallel-imported tablets (from different companies) and originator product.

Several media reports have claimed that the swap may have happened in a wholesale warehouse. Whatever the cause, the situation raises issues about the integrity of pharmaceutical packaging. For instance, in the UK, many non-prescription medicines are not wrapped in cellophane and do not have protective seals, which means that anyone can open them and, if their intentions are malicious, tamper with the contents. Should these packages be more secure? And, in the event that medicines are swapped, should blister packs be more clearly labelled?

According to the MHRA, there is a clear difference in the design of the blister packaging of Nurofen (silver and black) and Seroquel (gold and black). But the question is, how many people out there actually double-check that they’re taking the right medicine after they’ve opened the carton? In addition, text on blister packaging can often be small, which doesn’t encourage people to take notice.

The case also raises issues about the distribution and wholesale chain. In particular, if parallel importing was involved, it will reinforce long-cited concerns about this “grey market”. Parallel trade and the repackaging of drugs—to the frustration of many stakeholders—is legal in the EU. If you’re unfamiliar with parallel trade then the article “Who’s afraid of parallel trade?” is a good introduction, or you can take a look at the EUROPA website.

At the moment, there’s no solid information as to the exact cause, and the MHRA has warned that we may never know the full story, saying: “We have some information to suggest possible links between these cases. It is possible that these problems are linked to product consolidation and/or erroneous examination of returns. Work is ongoing to obtain more information but the full facts may never be fully established.”

However, the situation has also highlighted something that pharma companies are reluctant to use in this kind of situation: communication.

I’ve read reports on The Drum and PRWeek suggesting that Reckitt Benckiser could have provided more information to consumers.

Writing for The Drum, Jonathan Hemus said: “Crucial to effective reputation protection is filling the information vacuum and reassuring your stakeholders… But Reckitt Benckiser – parent company of Nurofen Plus – has appeared slow to activate these communication channels. Hours after the Medicines and Healthcare products Regulatory Agency (MHRA) had issued its announcement about the issue, there was:

no information on the Nurofen website
no information on the Reckitt Benckiser website
no information on the Nurofen Facebook page
no one manning the consumer helpline.”

At the time of writing this blog, there was still very little information available outside of the MHRA and third-party news sites, but this may change.

Unfortunately, mistakes do happen and product recalls will continue. And in the EU, at least for the foreseeable future, there will be continued concerns over parallel trade and repackaging. But in comparison to the complexity of these issues, you’d think that disseminating information to the public was relatively easy.

Allergan’s Botox was in the news again recently, and this time not over a debate of whether a C-list (and unknown to me) celebrity had or hadn’t been for treatment, but because it received a positive opinion from 14 European countries for a new indication: urinary incontinence. The DIGNITY programme (Double-blind InvestiGation of purified Neurotoxin complex In neurogenic deTrusor overactivitY—this must be some new form of acronym creation technique… admittedly memorable and appropriate) consisted of two successful trials involving nearly 700 patients with either spinal cord injury or muscular schlerosis, according to an Allergan press release. The positive opinion from the Irish Medicines Board, under the Mutual Recognition Procedure, is a key step in securing national licenses in the 14 countries involved.

This got me thinking about indications on a wider scale. A recent BBC report discussed a study that claimed that ordinary painkillers could be more effective at treating dementia than the antipsychotic drugs often prescribed, which have powerful sedative effects and can sometimes make dementia worse. On the other side of the coin, the FDA recently withdrew approval for Roche’s Avastin for use in the treatment of metastatic breast cancer because there is not enough data to support the conclusion that the benefits outweigh the risks…

Clearly, research is ongoing in terms of New Drug Applications, and meanwhile, off-label use continues (and punishment off-label marketing continues also). But there is an issue here, and patients’ lives are potentially at risk (read our previous blog). In 2009, the FDA finalised guidance regarding the distribution of medical or scientific journal articles that involve unapproved uses of FDA-approved drugs, but perhaps this only increases the grey area rather than define it. Nevertheless and despite the risk, there is huge potential out there—potential for existing drugs to improve patients’ lives in new ways, especially when thorough research has proved the benefits and opened regulatory doors.

Reports on the joint pilot programs note that continued collaboration will require innovative tools that allow for real-time information exchange. These tools could help the agencies avoid duplication of efforts. Said FDA’s Deborah Autor about the programs via a press release, “It is imperative that FDA work closely with its counterparts in order to ensure the safety and quality of products and the integrity of clinical trials. We cannot do it alone.”

Industry seems to have come to the same conclusion. Rx-360, the international pharmaceutical supply-chain consortium, has been promoting the idea of shared audits for a few years now. In 2011, a few companies completed audits as part of the consortium’s own pilot program. Avantor (formerly Mallinckrodt Baker), for example, participated in the pilot and has written about its experience in the August Outsourcing issue of PharmTech.

“The audit was beneficial because it allowed Avantor to view its manufacturing processes through a lens that combined most industry audit standards into one comprehensive and stringent audit,” wrote Avantor. The end goal of Rx-360’s program is to amass a repository of audits for the industry to share so that manufacturers can reduce the number of individual audits they have to perform. Reducing individual audits based on shared data can be a huge money-saver considering that regulators expect manufacturers to audit every single supplier, contract organization, and distributor in their supply chain.

Giving up ownership of something can be difficult, but it seems that industry is beginning to realize the benefits of collaboration. Let’s hope it continues.