Stephanie Sutton was an assistant editor at Pharmaceutical Technology Europe.

Stephanie Sutton

	Earlier this year in June, Roche’s name hit the headlines after a pharmacovigilance inspection discovered around 80000 safety reports that had not been evaluated by the company to determine whether they should be reported as adverse drug reactions. Included in the reports were approximately 15161 deaths, although the European Medicines Agency explained at the time that the actual number of reports could be lower once verified. EMA also added that the deaths may not have a casual link to the medicine. Either way, it’s still a huge number of reports that should have been assessed.

	Today, the case accelerated as the European Medicines Agency launched an 

 against Roche to investigate the alleged pharmacovigilance deficiencies.

	The procedure means that EMA will be able to investigate Roche within the legal framework of Europe’s Regulation (EC) No 658/2007, which concerns financial penalties. The case could mean fines or periodic penalty payments being imposed upon Roche if the company is found to have failed to comply with its pharmacovigilance obligations. EMA will report the outcomes of the investigation to the European Commission.

	The reports were originally identified by the UK’s Medicines and Healthcare products Regulatory Agency during a pharmacovigilance inspection. Many of the unevaluated reports came from a US-patient support programme, but MHRA also identified other deficiencies related to evaluating and reporting suspected adverse reactions from Roche’s own reporting systems and clinical trials.

	Following the inspection, Roche was ordered to take corrective actions to ensure the correct processing of reports. EMA’s Pharmacovigialnce Risk Assessment Committee is currently reviewing data to evaluate whether the reports will have any impact on the overall risk–benefit balance for any of the medicines involved. According to an EMA statement, the reports concerned 19 centrally authorised medicines.

Articles

Earlier this year in June, Roche’s name hit the headlines after a pharmacovigilance inspection discovered around 80000 safety reports that had not been evaluated by the company to determine whether they should be reported as adverse drug reactions.

Roche Under EMA Investigation

GlaxoSmithKline (GSK) has outlined the measures it is taking as part of a new open innovation approach to R&D, including opening up its tuberculosis compound library, investing in its open laboratory in Spain, and sharing detailed clinical trial data with researchers.

, GSK has been making “fundamental” changes to its business model during the past few years to become more open about its R&D activities, as well as to encourage the sharing of intellectual property, knowledge, and resources.  

In a statement, Sir Mark Walport, director of the UK’s Wellcome Trust charity, said, “In its commitment towards more openness and collaboration, GSK is setting an example of how the pharmaceutical industry must adapt to help drive forward medical advances. Real breakthroughs do not come out of nowhere, but are born of scientists sharing their knowledge and learning from each other.”


GSK’s compound library includes approximately 200 compounds that may inhibit tuberculosis (TB) bacteria, which the company will make public. According to a statement, this is the first time that a pharmaceutical company has opened up its own library of proprietary TB compounds. GSK hopes the move will provide a new starting point for the discovery of new TB medicines using an open approach to R&D. 


GSK will provide its Open Lab laboratory in Tres Cantos, Spain, with an additional £5-million ($8 million) in funding. The laboratory was established in 2010 to allow independent researchers to access the company’s facilities, resources, and knowledge for their own research projects. Currently, there are 16 research projects in the Open Lab’s portfolio, including projects examining TB, malaria, Chagas disease, leishmaniasis, and sleeping sickness. 


Data from GSK’s clinical trials, whether positive or negative, are already published on a public website and the company is also seeking to publish the results of the trials in peer-reviewed scientific journals. Now, the company has also announced its intention to create a system that will provides researchers with access to detailed anonymised patient-level data and discontinued investigational medicines. Researchers wishing to access the data, which will be available on a website, will need to submit requests, which will be reviewed by an independent panel of experts to ensure that the information will only be used for valid scientific endeavors. According to GSK, researchers will be able to examine the trial data more closely or combine data from different studies for further research. 

Andrew Witty, CEO of GSK, said, “I believe we have a responsibility to do all we can at GSK to use our resources, knowledge and expertise to help tackle serious global health challenges. However, the complexity of the science and the scale of the challenge mean that we cannot solve these problems alone. We need to take a different approach – one focused on partnership, collaboration, and openness. By being more open with our clinical trial data, we also hope to help further scientific understanding.”

GlaxoSmithKline has outlined the measures it is taking as part of a new open innovation approach to R&D, including opening up its tuberculosis compound library, investing in its open laboratory in Spain, and sharing detailed clinical trial data with researchers.

GSK Encourages Open Innovation and R&D

	Recent years of low approvals of new blockbuster products have given rise to the perception that pharmaceutical drug development, in its current format, no longer works. Recent late-stage failures of clinical trials have also served to emphasise the risky nature of drug development. So what’s the alternative?

	At the end of last week, GlaxoSmithKline placed its bets on open innovation as a new way forward for developing medicines.

	GSK announced three measures designed to encourage and facilitate open research. The company is opening up both its compound library of promising TB candidates and detailed clinical trial data. In addition, the company is pumping £5-million in funding to its Tres Cantos (Spain) facility which was established in 2010 as a so-called ‘Open Lab’ facility where researchers could call on GSK’s facilities, resources and knowledge for their own research projects. You can read more about the announcement

	Open innovation is about looking outside of a single company for inspiration. GSK has already explored several open-innovation initiatives. In 2009, the company launched a “patent pool” for neglected tropical diseases by making patents for some of its drugs and manufacturing processes available to the public, inviting other companies to follow suite. Alnylam, South Africa’s Technology Innovation Agency and the Medicines for Malaria Venture have also joined the initiative. Earlier this year in June, GSK and the UK’s University of Cambridge also 

 an open-innovation initiative in the area of bioscience.

	According to the University of Cambridge, one of the key elements of open innovation is to enable for scientific exchange without the need for exclusive research collaboration agreements. At the time of the release, Patrick Vallance, president of Pharmaceuticals R&D at GSK said, “This open innovation approach is enabling scientists who might not ordinarily have interacted to build relationships, share ideas and seek advice. This environment provides us with an opportunity to stimulate research and translate science into the discovery of new medicines for patients.”

	Although GSK is not the only pharmaceutical company to have launched open innovation projects; Eli Lilly, for example, is also supporting open innovation via its 

 program, but efforts from the pharmaceutical industry as a whole have been fairly tentative to date. Indeed, the nature of the pharmaceutical industry means that companies understandably must be protective of their intellectual property rights, which may hinder open innovation.

	However, as more open-innovation projects are announced by pharmaceutical companies and the rewards and benefits began to be seen, perhaps we will see more efforts in this area.

Recent years of low approvals of new blockbuster products have given rise to the perception that pharmaceutical drug development.

Will Pharma Embrace Open Innovation?

 that a generic drug manufactured by Impax Laboratories and marketed by Teva Pharmaceuticals USA was not therapeutically equivalent to its reference product. The drug in question, Budeprion XL 300 mg, was approved in the US in December 2006 as a generic form of GlaxoSmithKline’s antidepressent drug, Wellbutrin XL 300 mg.

	Budeprion XL 300 mg (bupropion hydrochloride extended-release tablets) has been under the watch of the US regulator for several years. Between January 1 and June 30, 2007, FDA received 85 postmarketing reports concerning patients who had switched from the branded product to Budeprion XL 300 mg. Specifically, the concern was that there was a reported loss of efficacy following the switch. In 2008, however, FDA announced the 

 of a review of Budeprion XL 300 mg. The verdict:

	“The FDA considers the generic form of bupropion XL 300 mg (Teva Pharmaceuticals) bioequivalent and therapeutically equivalent to (interchangeable with) Wellbutrin XL 300 mg. Although there are small differences in the pharmacokinetic profiles of these two formulations, they are not outside the established boundaries for equivalence nor are they different from other bupropion products known to be effective.”

	So why did last week see a change in opinion? The u-turn by FDA follows the results of a new bioequivalence study sponsored by FDA that compared Budeprion XL 300 mg to Wellbutrin XL 300 mg. The results, which became available in August 2012, showed that Budeprion XL 300 mg failed to release the active ingredient into the blood at the same rate and to the same extent as GlaxoSmithKline’s original drug. No other new safety data were identified.

	Four other generic-drug alternatives to Wellbutrin XL 300 mg are available on the US market. FDA has not conducted bioequivalence studies with these products, but has asked the manufacturers Anchen, Actavis, Watson and Mylan to conduct their own studies in this regard. Data must be submitted to FDA by March 2013.

	FDA does not currently have data indicating that the other generic drugs will also fail to be to be therapeutically equivalent to Wellbutrin XL 300 mg and it is possible that the issue is unique to the Budeprion XL 300 mg. FDA has said it will provide an update when further information is available.

	The worrying aspect to this news is that it may affect the reputation of generic drugs as a whole, particularly if the other generic forms of Wellbutrin XL 300 mg are also shown not to be therapeutically equivalent. It would raise questions among both patients and physicians as to how comparable a generic drug really is to its reference product.

	Because of the expensive nature of pharmaceutical development, branded medicines always necessitate a high price tag. Generics, on the other hand, are much cheaper and provide huge cost savings for patients and governments. In the US alone, generic drugs were 

to have accounted for cash savings of around $192 billion in 2011.

	Let us hope this incident is unique to the Teva/Impax product and does not affect other generic drugs. FDA will also, no doubt, be more cautious. In its statement on Budeprion XL 300 mg the agency added that it is already in the process of revising its guidance to industry about how to conduct premarket bioequivalency studies in generic bupropon products.

Last week, FDA deemed that a generic drug manufactured by Impax Laboratories and marketed by Teva Pharmaceuticals USA was not therapeutically equivalent to its reference product.

Concerns Raised Over the Comparability of Branded/Generic-Drugs

Takeda’s US subsidiary, Takeda America Holdings, has agreed to acquire the vaccine specialist company LigoCyte Pharmaceuticals for an upfront payment of $60 million in a move intended to bolster and expand the company’s vaccine business. Future payments may also be made depending on the progress of LigoCyte’s development projects.

LigoCyte is a US-based biopharmaceutical company that uses its proprietary virus-like particle (VLP) platform technology to develop new vaccines. The comapny’s lead product is a norovirus vaccine that can prevent multiple varieties of the illness. According to a press statement, the vaccine has been shown to provide protection against the norovirus in an initial human challenge trial. The company intends to seek approval for the vaccine in the US, Europe, and other regions.

LigoCyte has also begun preclinical development of other vaccines against respiratory syncytial virus, influenza, and rotavirus.

, Rajeev Venkayya, the executive vice-president of Takeda’s Vaccine Business Division, said, “Norovirus is the most common cause of outbreaks of gastroenteritis and foodborne illness in the US, and is responsible for 200,000 deaths each year, most of them in developing countries. With the only norovirus vaccine in clinical trials today, Takeda will be in a position to change this picture.”

Takeda intends to continue operating LigoCyte at its current location in Bozeman, Montana, for the foreseeable future and will retain the management team and its employees. Once the acquisition is complete, the management team will become a part of Takeda’s Vaccine Business Division, which was launched in January 2012.

The deal is expected to close by the end of November 2012, pending the satisfactory clearance of closing conditions. 

Takeda's US subsidiary, Takeda America Holdings, has agreed to acquire the vaccine specialist company LigoCyte Pharmaceuticals for an upfront payment of $60 million in a move intended to bolster and expand the company's vaccine business.

Takeda to Acquire LigoCyte Pharmaceuticals

	A new report has forecast that the global biopharmaceutical market will be worth more than $320 billion by 2020, up from just $138 billion in 2011. According to global business intelligence firm GBI Research, annual revenues for biopharmaceuticals have been rising year on year since 2001. In 2011, biopharmaceuticals accounted for 15.6% of the total pharmaceutical market.  

	In the bio/pharma industry, headlines are often dominated by jobs cuts, failed clinical trials or forecasts for poor revenue, so it’s always refreshing to read about something that suggests a brighter future. According to GBI Research, the next decade could see a paradigm shift in biomanufacturing technologies, including improvements in equipment efficiency and the introduction of novel therapies. In particular, disposable bioprocessing equipment and microbial technologies are expected to dominate the manufacturing environment and become the “hallmark” of biopharmaceutical manufacturing. Single-use systems are currently mainly used in upstream processing, but such equipment is also beginning to see increased use in preclinical and clinical trials. Microbial manufacturing, on the other hand, is already well accepted and proven, and has also led to the discovery of new subsidiary technologies. Recombinant proteins produced by mammalian cell culture processes have been successful in generating revenues of more than $1 billion for the biopharmaceutical industry.

	The report also has good news for manufacturers of biosimilar products. GBI Research predicts that biosimilars will grow to take up a “sizeable chunk” of the global biopharmaceuticals market by 2020, aided by the huge growth potential in pharmerging markets in Asia, as well as new US legislation that will enable biosimilars to finally begin entering the US market in 2014. In the US alone, revenues for biosimilars are expected to reach $9 billion by 2020.

	Outside of the US, in emerging pharmaceutical markets such as India, China and South Korea, the emergence of biosimilars is seen as an important macroeconomic factor for generating revenues by attracting foreign investment. India’s biosimilars sector is predicted to treble in value in the next five years, from $481 million in 2011 to $1.4 billion in 2016. More than 20 biosimilar companies are currently operating in India, with around 55 products already on the market. India has the advantage of more lenient intellectual property regulations (although this is not viewed as a benefit for pharmaceutical companies, which means that biosimilars for certain products are already available in India, such as Enbrel and Rituxan, even though they are still under patent exclusivity in many western countries).

	Meanwhile, several Chinese companies are planning large-scale distribution strategies in western countries, while the government in South Korea has announced capital and institutional support to boost biopharmaceutical manufacturing, with the aim of acquiring a 22% share of the global biosimilars market by 2020.

Biopharmaceutical Manufacturing in India, China and South Korea - Regulatory Framework, Infrastructure Support and Discovery Funding Create an Environment Conductive to Growth

EMA Aims to Facilitate Biosimilars Development

Bioosimilars: Market Weaknesses and Strength

Biosimilars - It’s the Differences that Really Matter

A new report has forecast that the global biopharmaceutical market will be worth more than $320 billion by 2020, up from just $138 billion in 2011.