Category Archives: Biotechnology

Sartorius and Repligen collaborate on perfusion enabled bioreactors

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Designing the bioreactors to control cell growth, fluid management and cell retention to ultimately simplify the development and cGMP manufacture of biological drugs.

Sartorius Stedim Biotech (SSB) and Repligen Corporation have partnered to integrate Repligen’s XCell ATF cell retention control technology into SSB’s BIOSTAT STR large-scale single-use bioreactors to create novel perfusion-enabled bioreactors.

SSB is an international supplier for the biopharmaceutical industry and Repligen Corporation is a global life sciences company focused on bioprocessing technologies.

Christine Gebski, VP of Product Management at Repligen, said: “We are excited to partner with SSB, a global innovator in bioreactor technology. The integration of our market-leading XCell ATF control technology with SSB’s high-performance bioreactors offers a simplified perfusion-enabled bioreactor solution for end users to develop cell culture processes more quickly and implement perfusion more efficiently.”

As a result of this collaboration, end users will stand to benefit from a single control system for 50–2000 litre bioreactors used in perfusion cell culture applications. This single interface is designed to control cell growth, fluid management and cell retention in continuous and intensified bioprocessing and ultimately, simplify the development and cGMP manufacture of biological drugs.

Through the partnership, SSB and Repligen will further collaborate to equip SSB’s recently launched ambr 250ht perfusion single-use mini bioreactor system with Repligen’s KrosFlo hollow fibre filter technology.

The bioreactor system will be sold by SSB as a complete single-use assembly. This optimal design conserves the hollow fibre filter technology across scales, enabling customers to fast track development and scale up their cell culture perfusion processes.

“Sartorius Stedim Biotech has continuously expanded its integrated upstream portfolio for the past years with a focus on robust and scalable, automated single-use solutions, optimized for high-cell-density applications. The collaboration with Repligen will result in easy-to-implement, high-performance and perfusion-ready bioreactors ranging from process development to commercial manufacturing scale,” commented Stefan Schlack, Head of Marketing at SSB.

SOURCE: www.manufacturingchemist.com/news

NICE rejects Gilead’s CAR-T, immediately after EU approval

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Novartis and Gilead’s CAR-T therapies have been approved in Europe – and the UK’s NICE immediately slapped down the latter, saying it is too expensive for regular NHS use in England and Wales.

Novartis’ CAR-T, Kymriah (tisagenlecleucel) has not yet been reviewed by NICE’s committees, as the cost-effectiveness body received the manufacturer’s dossier much later.

But if NICE’s decision on Gilead’s CAR-T (chimeric antigen receptor T-cell) therapy, Yescarta (axicabtagene ciloleucel) is anything to go by, Novartis may also have difficulties securing market access on England’s NHS.

In its document summarising its assessment of Gilead’s drug, NICE noted the good response rates, overall survival and progression-free survival data from clinical trials of Yescarta in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma in people who have had two or more systemic therapies.

But NICE said there was a lack of comparator data with standard care of salvage chemotherapy, so it was unable to quantify the exact size of the drug’s benefit.

Gilead has kept the list price a secret, and NICE merely said that the cost per Quality Adjusted Life Year was in excess of £50,000, its upper limit for medicines given to patients at the end of their lives.

However the medicine does not come cheaply – in the US Gilead set a list price of $373,000, for the therapy, a single shot of a patient’s own T-cells, harvested and genetically modified to destroy certain blood cancer.

NICE’s independent assessment committee also considered whether Yescarta could be reimbursed on an interim basis by the Cancer Drugs Fund until new clinical data comes to light.

But the committee said Yescarta does not have plausible potential to be cost-effective.

Meindert Boysen, director of the centre for health technology evaluation at NICE, said: “CAR-T is an exciting innovation in very difficult to treat cancers, with a promise of cure for some patients.”

“We have been working with the companies involved, and with NHS England, with the aim of ensuring that patients in England are among the first to have access to these new treatments in Europe.”

“Although promising, there is still much more we need to know about CAR-T, and unfortunately, in this case, we are not able to recommend axicabtagene ciloleucel for use in the NHS in England at the cost per patient set by (Gilead’s subsidiary) Kite Pharma.”

However in the long term, it looks likely that CAR-T therapies will be available for NHS patients: as revealed by pharmaphorum earlier this year, the NHS has been doing extensive groundwork ahead of their approval, including setting up specialist centres.

The approved indications for Yescarta are adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.

Kymriah has been approved for the treatment of paediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

SOURCE: www.pharmaphorum.com/news

Europe’s first allogeneic stem cell therapy rejected by NICE

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Cost regulators for the NHS in England and Wales have not approved funding for TiGenix and Takeda’s Alofisel – the first allogeneic stem cell therapy to be approved for use across the European Union – for use in Crohn’s patients.

The therapy (previously referred to as Cx601) was approved in March to treat complex perianal fistulas in adult patients with nonactive/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy.

Perianal fistulas, a common complication of Crohn’s disease, occur when an abnormal passageway develops between the rectum and the outside of the body, potentially leading to incontinence and sepsis. Complex fistulas, which are rare, are more treatment resistant than simple fistulas.

Alofisel (darvadstrocel) is a local administration of allogeneic (donor derived) expanded adipose-derived stem cells (eASCs).

In clinical trials underpinning the drug’s approval, patients receiving the treatment showing a 44 percent greater probability of achieving combined remission compared to placebo, while a follow-up analysis (at 52 weeks and 104 weeks post-treatment) confirmed sustained efficacy and safety, according to the firms.

However, in draft guidelines, the National Institute for Health and Care Excellence said Alofisel showed only a modest improvement in the proportion of people with complex perianal fistulas achieving complete remission compared with placebo in one clinical trial.

“Reliable follow-up results are only available for up to one year, so it is unclear how long the treatment benefit will last,” according to the guidelines.

Because of this, cost-effectiveness estimates are “highly uncertain” and the committee was unable to conclude on the most plausible cost-effectiveness estimate, NICE said.

SOURCE: www.pharmatimes.com/news

From molecule to medicine, the importance of persistence

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Here, Dr Sheuli Porkess, deputy chief scientific officer, Association of the British Pharmaceutical Industry (ABPI), outlines how the pharmaceutical industry takes a substance from molecule to medicine and how the process requires persistence.

A report last week from the Office of Health Economics (OHE) shows the amazing impact medicines have had on the NHS and more widely. The antipsychotic chlorpromazine, first used in the NHS in 1954, paved the way for deinstitutionalisation and community-based care for people with mental illness. In 1948, there were almost 400,000 cases of measles in England and Wales, and 327 people died. By 2015 the number of cases of measles in England and Wales had fallen below 1,200.

These medicines, and others, had a variety of benefits including better clinical outcomes, saving lives, improving quality of life, greater health service efficiency and wider societal impacts. But making medicines is a complicated and costly business. It costs billions of pounds and can take decades. Successes can change the world; failures are an inevitable part of the discovery and development process. But when medicines get through the development process, they can clearly change millions of lives.

There are broadly three stages to creating a new medicine: research, development and approval. Here’s how it works:

Drug discovery and development

The process usually starts with chemical compounds or biological molecules. With advances in technology over the last few years, we can screen compounds that have the potential to become treatments faster than ever before. AstraZeneca — a British pharmaceutical company — launched a new screening robot in 2016 called ‘NiCoLA-B’ which is able to test 300,000 compounds a day. Its job is to find those chemicals that show the slightest potential of being useful as a medicine.

The research stage benefits hugely from collaborative partnerships between the pharmaceutical industry, charities and universities, all working together to find a potential medicine. This stage can take four to five years and takes about 22% of the total budget it takes to find a treatment. Each compound has a less than 0.01% chance of success.

Preclinical research

From a batch of about 10,000 compounds screened in the drug discovery phase, only about 10–20 go into the pre-clinical phase, where scientists determine how safe a medicine might be through testing in cells and animals as well as using computational models.

Clinical research

If any of those 10-20 compounds show real potential of being turned into something useful, they’re developed in to a medicine that will move into clinical trial stage. There are three steps: Phase I involves about 20 to 100 volunteers. If medicines are successful here, they will move onto Phase II where they are tested in people with the disease.

Phase III can include up to 5,000 patients. Going through the three phases can take six or seven years. Over half, or about 65%, of the money it takes to make a medicine is spent in the development stage.

Phase IV clinical trials are after the medicine has a licence and are there to help monitor the medicine’s safety and help clinicians better understand how the medicine works in everyday life, not just in clinical trials.

Approval

The final stage is when regulators review the medicine and it can get ‘market authorisation’ — which shows the medicine is safe and effective. By this point, the manufacturing of the medicine has been scaled up. Only one medicine of 5,000–10,000 compounds discovered will make it to this stage.

The approval processes last anywhere from six months to two years. The medicine is continually monitored once it starts being prescribed for patients.

Researching and developing medicines takes a lot of time and work along the way; there is no guarantee that any particular medicine will make it through the various stages of this highly regulated process. The process is fascinating and once medicines get through this system, their impact can be huge.

Of course, the pharmaceutical industry is pioneering new ways to find treatments. The future looks exciting and how we detect, diagnose and treat disease is set to change significantly.

Advances in medical technology and the miniaturisation of diagnostics, wearables and devices will have a huge impact on our lives and could help people with chronic diseases to remain out of hospital.

Advances in understanding how cells monitor and repair damaged DNA enables us to develop game-changing treatments for cancer. Progress in immuno-oncology sees patients own immune cells used to attack cancer cells, and stem cell therapy is treating rare sight conditions.

We see AI and synthetic biology used for treating malaria, HIV and hepatitis. Gene-editing technology is happening in labs right now, identifying new disease targets, accelerating the discovery of novel treatments.

Passionate pioneers, such as those who invented the groundbreaking treatments in the report, have always been at the heart of our industry and it’s exciting to imagine what their successors could achieve in the next 70 years.

SOURCE: www.epmmagazine.com/opinion

Demographic shifts create biotechnology opportunities

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Ageing populations which are increasingly wealthy means opportunities for biotech and healthcare investors.

Globally, populations are rapidly growing, ageing and becoming richer. It is estimated that within 25 years, the number of over 65s in Asia will exceed the total populations of the eurozone and US combined.

This progression, accompanied by declining birth rates in the developed world, is creating a growing demographic imbalance. Simultaneously, incomes are rising in developing economies, so emerging market consumers are increasingly entering the global middle class.

When populations become wealthier, healthcare spending infallibly increases and pockets of new healthcare needs (in response to lifestyle changes) often emerge. The consequences of these demographic shifts – both current and emerging – include far greater pressures on healthcare and a greater reliance on the private sector to provide care solutions.

Against this backdrop, biotechnology (or biotech) businesses can minimise the strain of (and theoretically profit from) global demographic adjustment. The biotech sector is broad-based, but primarily seeks to improve healthcare and treat disease through clinical research and drug development. Crucially for long-term investors, the sector also benefits from the relatively non-discretionary nature of demand for its products and services.

We have been taking advantage of these opportunities since 2016, when we began investing in an actively managed healthcare and biotech investment trust. We see high growth potential and strong structural tailwinds in the industry, and have since added to our exposure by investing in a passive exchange-traded fund (ETF) tracking the Nasdaq Biotechnology Index.

Having fallen sharply between late 2014 and 2016, the Nasdaq Biotechnology Index has been tracking steadily upward ever since. Despite its considerable growth potential and solid performance since 2017, the sector continues to trade at relatively attractive valuations; since the 2014-2016 sell-off, the sector’s price-to-earnings ratio has languished below that of the broader market for the first time in history.

As any excess capital is generally reinvested into further research and development, the majority of returns from the biotech sector are driven by mergers and acquisition activity and – crucially – the number of new drug approvals in a given year. The latter is positive news for investors, as approvals are on track for near-record levels in 2018, backing up strong years in 2015 and 2017.

For the sector’s world leaders in the US, biotech activities are tightly regulated by the Food and Drugs Agency (FDA). However, in a characteristically controversial manoeuvre, President Trump recently found himself on the biotech frontline when signing the ‘Right-to-try’ law – legislation permitting terminally ill patients to bypass the FDA to gain faster, unhindered access to experimental treatments. While not universally supported, and not without ethical constraints, the act should widen the pipeline of information on the effectiveness of potential new treatments. In turn, this could accelerate decision making over the fate of these new drugs. 

As with all sectors, biotech has its weaknesses. The most commonly highlighted risks are the binary nature of research results and the subsequent price movements in individual companies. More recently, political pressure to address fears around drug pricing is also mounting.

Mindful of these risks, but also seeking to harness biotech’s many compelling opportunities, our diversified positioning aims to limit the portfolios’ exposure to stock-specific risk, while allowing access to the benefits of powerful demographic shifts.

SOURCE: www.moneyobserver.com/demographic-shifts-create-biotechnology-opportunities

A majority of Americans support using biotechnology to grow human organs in animals for transplants

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Almost six-in-ten Americans (57%) consider it an appropriate use of technology to genetically engineer animals to grow organs or tissues that could be used for humans needing a transplant, while 41% say this would be going too far, according to a new survey by Pew Research Center.

The findings are part of a larger pattern that reveals Americans are more likely to support the bioengineering of animals if it benefits human health.

Demand for transplantable organs and tissues continues to grow in the United States. Last year saw the most organ transplants ever performed in the country. Organs were recovered from more than 10,000 donors – an increase of more than 25% over the past 10 years. Health experts attribute this increase, in part, to breakthroughs in medical technology that have made it possible to recover organs that previously would have been unsuitable for transplants. But, despite these advances, the U.S. Department of Health and Human Services reports that the gap between supply and demand remains wide.

Researchers are hoping to close that gap through the development of new medical technologies. One such approach is 3D organ printing– a process that uses “bio-ink” to print layers of cells that grow to form transplantable tissue.

Another method under development uses genetic engineering to grow human organs and tissues in animals. There was a breakthrough with this technique earlier this year, when scientists used gene editing to create hybrid embryos containing both human and sheep cells.

When the survey – conducted April 23-May 6 – asked the 41% of respondents who opposed this application of genetic engineering to explain, in their own words, the main reason behind their view, the objections included concerns about the use of animals in this way for human benefit (21% of those asked) and the potential risks for human health (16% of those asked).

The responses included:

“In manufacturing organs, the existence of these animals would be miserable … I can’t ethically say that I would agree with such a practice.”

“Factory farming already as an industry unethically treats animals. I imagine organ growing wouldn’t treat the animals any differently.”

“When you mix human and non-human genetics I believe that will cause extreme problems down the road.”

“Even human-to-human organ transplants often reject, so I can only imagine the bad side effects that an animal-to-human transplant would cause. Keep things simple and the way nature intended.”

Majority supports bioengineering animals to grow human organs

SOURCE: www.pewresearch.org/fact-tank

Seven million euros for research into chronic inflammatory bowel conditions

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A new collaborative research centre/Transregio 241 ‘Immune-epithelial communication in inflammatory bowel diseases’ is due to commence its research at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) in July 2018.

In conjunction with the Charité hospital in Berlin, doctors and biotechnologists at FAU will be conducting research in order to better understand the interaction between cells in mucous membranes and immune cells in the bowel and to develop more effective therapy methods for chronic inflammation. The German Research Foundation (DFG) is providing funding worth 11.5 million euros for the first funding period until 2022, and FAU has been allocated nearly 7 million euros of this amount.

Number of patients with IBD is increasing

Severe diarrhoea, stomach pain, cramps – these are the most common symptoms of inflammatory bowel disease (IBD) such as Morbus Crohn or Colitis ulcerosa. Around 40,000 people in Germany suffer from IBD and this number continues to rise. Patients of IBD often suffer from flare-ups of their condition, which severely affects their quality of life and physical capabilities. ‘Despite the use of strong medication, chronic inflammatory bowel conditions remain difficult to treat’, says Prof. Dr. Christoph Becker, lead researcher at the Department of Medicine 1 at FAU’s Universitätsklinikum Erlangen and spokesperson of the collaborative research centre. ‘Acute flare-ups are often treated with corticosteroids that ease symptoms only in some cases. Many patients have to take several immunosuppressive substances.’ In addition, their symptoms are often accompanied by other conditions such as arthritis, acute inflammation of fatty tissue and chronic inflammation of the biliary tract in the liver.

Little research to date on molecular and cellular mechanisms

IBD is difficult to treat because the interactions between various cell populations in the bowel are not yet fully understood. ‘Newer findings show that the intestinal mucosa cannot be regarded as merely a physical barrier. In fact, it is highly-dynamic tissue that reacts to a large number of environmental stimuli including intestinal flora and local or systemic signals,’ explains Christoph Becker. ‘The immune system in the intestine regulates the barrier function of the intestinal wall and the composition of intestinal flora and vice versa as the intestinal barrier influences the immune system.’ However, there is a lack of knowledge of how the interactions between the epithelium and immune cells influence the long-term cellular reactions that contribute to controlling chronic inflammation processes.

New concept for new therapies

This is the starting point for the researchers from Erlangen and Berlin. During the next few years, they aim to integrate findings about the regulation and function of the immune system in the bowel and current data about anti-microbial defence on the mucous membrane barrier into a new concept. The individual projects will focus in particular on the role of misdirected communication between epithelium and immune cells during the pathogenesis of IBD. The researchers’ long-term aim is to develop medication that targets the causes of bowel inflammation while retaining the ability of the immune system to fight infections and cancer cells. In addition, they hope to find diagnostic methods that predict patients’ response to therapies – a goal that not only serves to relieve symptoms quickly, but should also contribute to lowering treatment costs.

Researchers from Erlangen involved in 14 projects

The scientific programme of CRC/TRR 241 is divided into three research areas: Area A ‘Immune regulation of intestinal barrier functions’, comprises projects focusing on the effects of acute and chronic inflammation on epithelial cells, in particular on their cell homeostasis and barrier-forming functions. Area B ‘The epithelium as a regulator of immunity and inflammation in the bowel’ examines the effects of disruptions to the barrier function and antigen translocation on the mucosal immune system. The objective of research area C ‘Diagnosis and therapeutic intervention of IBD’ is to develop innovative therapeutic and diagnostic approaches and evaluate them in a clinical setting. CRC/TRR 241 comprises a total of 22 projects, 14 of which are either based in Erlangen or involve researchers from Erlangen. The Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology, Department of Medicine 3 – Rheumatology and Immunology, the Department of Surgery and the Department of Dermatology and the Institute for Medical Biotechnology are all involved. 23 jobs and 9 scholarships are being funded during the next four years with the nearly 7 million euros allocated to the FAU.

SOURCE: www.eurekalert.org/pub_releases

Prothena guts workforce by more than half, after trial failure

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Prothena Therapeutics has acted drastically by slashing staff numbers by more than half, after the failure of two pivotal trials for its lead candidate.

The company subsequently ditched NEOD001, when trials revealed that placebo treatment outperformed the drug candidate in the treatment of AL amyloidosis.

The reorganisation sees 63 positions cut away from the Dublin-based company, representing a shedding of 57% of the entire staff at the company.

As is usually the case, the process was necessitated to stymie cash losses during 2018 – it projected its estimated net cash burn for the year to be $40 million to $50 million, driven by a net loss of $170 million to $185 million.

Luckily for the biotech, it’s had some backers that were betting that its work would produce results and so estimates that it still have a relatively healthy $421 million in cash to end the year on.

One notable backer is renowned UK investor, Neil Woodford, who had to defend his investment in biotech in a blog post immediately after the trial failures were announced – pointing out strengths from within the Prothena’s pipeline and suggesting its partnership with Roche was one reason to keep faith with the biotech.

In the announcement regarding its restructuring, Prothena followed suit, with Gene Kinney, President and Chief Executive Officer of Prothena, saying: “As we move forward, we have the resources to support the advancement of our pipeline through meaningful milestones and we will focus on developing neuroscience programs that we believe have a potential to offer significant benefit to patients. This includes our two clinical-stage programs PRX002/RG7935, currently in Phase 2 development in the PASADENA study in patients with early Parkinson’s disease, and PRX004, which recently initiated a Phase 1 study in patients with ATTR amyloidosis.”

PRX002/RG7935 is both being developed in collaboration with Roche and there will be significant hopes placed on this candidate to pull the biotech out of a tricky spot; however, with the treatment being for patients with Parkinson’s disease, it’s a fairly risky bet given the dearth of disease-modifying treatments for the condition.

SOURCE: www.pharmafile.com/news/517476

Life Sciences sector responds to report on the impact of Brexit

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

The Business, Energy and Industrial Strategy (BEIS) Committee report calls on the Government to secure a post-Brexit deal to protect patients and the UK’s pharmaceutical industry.

“The impact of Brexit on the pharmaceutical sector’ makes several recommendations which industry welcomes. This includes the need to secure the closest possible regulatory alignment with the EU as well as minimum border friction. Patients are at risk of harm and the UK pharmaceutical sector could lose its status as a world leader,” the report says.

The Committee also concluded that “what little benefits there may be from regulatory divergence, these would be greatly overshadowed by the costs and loss of markets and influence the UK would face.”

A joint statement by the Association of the British Pharmaceutical Industry (ABPI) and the UK BioIndustry Association (BIA) – whose chief executives, Mike Thompson and Steve Bates, provided evidence to the Committee – said:

“Every month, 45 million packs of medicine move from the UK to the EU, with 37 million moving the other way.

Today’s Select Committee Report is right – a Brexit ‘no deal’ would significantly damage public health, patient access to medicines and the UK’s leading pharmaceutical sector. This must be avoided at all costs.

“Securing cooperation on the regulation, trade and supply of medicines must be a priority for both the UK Government and the EU.”

The ABPI represents innovative research-based biopharmaceutical companies and is recognised by government as the industry body negotiating on behalf of the branded pharmaceutical industry, which supplies more than 80% of all branded medicines used by the NHS.

SOURCE: www.manufacturingchemist.com/news

Daiichi Sankyo to restructure vaccines subsidiary

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Daiichi Sankyo is set to restructure its wholly owned Kitasato Daiichi Sankyo Vaccine subsidiary into a specialised manufacturing division to enhance stable production and quality.

In August this year, Daiichi Sankyo will establish Daiichi Sankyo Biotech as a wholly owned subsidiary.

The change will be effective from 1 April next year, and all of the subsidiary’s functions, except manufacturing and production technologies and marketing approvals, will be shifted to Daiichi Sankyo.

The subsidary will be involved in contract manufacturing of vaccines, biologics and investigational drugs.

“All of the subsidiary’s functions, except manufacturing and production technologies and marketing approvals, will be shifted to Daiichi Sankyo.”

Kitasato Daiichi Sankyo Vaccine was founded in 2011 as a joint venture (JV) between Daiichi Sankyo and the Kitasato Institute.

The JV’s operations include research and development (R&D), production and the sale of vaccines to prevent and treat verioud infectious diseases in humans.

Kitasato Vaccine was created as a wholly owned subsidary in November last year during a review of its vaccine business structure.

After the integration, the division focussed on the quality and stable supply of vaccines, along with the R&D and commercialisation of new products.

Daiichi Sankyo is a research-based pharmaceutical company involved in making generic pharmaceuticals, vaccines and over-the-counter medicines.

With operations across the US, Japan and Europe, the company has various other subsidiaries, including Luitpold Pharmaceuticals, Plexxikon, Daiichi Sankyo Ilac Ticaret, Daiichi Sankyo UK and Daiichi Sankyo RD Novare.

SOURCE: www.pharmaceutical-technology.com/news