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  1. 1. Inductively Coupled Plasma Mass Spectrometer ICPMS-2030 Innovation - Industry's first method development and diagnostic assistant functions Accuracy - Newly developed collision cell achieves high sensitivity with low interference Economic - Proprietary technology realizes low running costs, among the industry’s best
  2. 2. BioEdit 4   BioSpectrum | April - May 2016 | | An MM Activ Publication I ndia’s $20 billion pharma indus- try has been shell-shocked by a sudden government announce- ment in mid-March 2016 ban- ning the production and sale of 344 fixed dose combination (FDC) drug production and sale.Analysts estimate that these drugs, some of them very popular brands of cough syrups, anti- infectives, anti-cholesterol treatments, account for at least 10% of the indus- try’s revenue. A High Court in the national capital Del- hi has given a temporary relief to the manufacturers,who are some of the leading global pharma giants as well as domestic ge- nerics drug makers,and is hearing the case on priority.There has been some intense debate within the health community in the past seven years over these FDCs.There are more than 6,000 generic FDC products that have become very popular with patients as well as doctors for their usefulness and efficient treatment proto- col. The Indian government had appointed an ex- pert committee, headed by a pharmacologist, C K Kokate, to study the issue and its recom- mendations were submitted in January 2015. Subsequently, there was no public debate on the expert committee report till the mid-March 2016 announcement on the ban of 344 FDCs. Globally, FDCs are used widely and the US regulator FDA has approved 131 FDC products from 1990 to 2013. The Active Pharmaceutical Ingredients (APIs) that go into making of FDCs are individu- ally approved by regulators around the world. Regulators also provide guidelines on FDC formulations.In an exhaustive study on FDCs done by two Turkish pharmacologists,Timucin Ugurluand Tugce Ozaydin, at the Marmona University, the researchers found not adverse side effects reported by most of the FDC drugs prescribed widely in the world. In fact, they highlighted the beneficial effect of a combination of Amlodipine and Valsar- tan in lowering blood pressure in patients sig- nificantly compared to their individual use. The researchers noted that FDCs are highly successful in treatments related to cardiovas- cular diseases, infectious diseases, diabetes, psychiatric disorders and respiratory illnesses. The only drawback is that it is not very easy to pinpoint quickly which of the APIs contribute to side-effects, if any reported by patients. Metformin is one of the most popular drug in treating diabetes.Inrecent years, metformin has been combined with different dosages of a new class of drugs called gliptins and the com- binations have beenfound to be highly effective in diabetes management. There are many more such examples of combination drugs that are highly effective. While hearing the case, a judge in the Delhi court asked a pertinent question to the govern- ment’s lawyer. When the drug regulator has approved these drugs, APIs and their combina- tions after rigorous scrutiny, how can another expert find fault with these? And how long can the regulatory approval process go on with- out any certainty?The government lawyer just spouted the excuse of ‘public interest’ for the ban on these drugs.The decision of this court will holdsignificance not just for the pharma industry in India but around the world in the near future.It could be trendsetter for this sec- tor in many ways. Meanwhile, the industry and regulators have to share more data on the rationale for use of FDCs and put things in perspective on this con- tentious issue.  BS Narayanan Suresh Group Editor B an on Fixed Dose Combination (FDC) drugs hits India pharma
  3. 3. BioMail An MM Activ Publication | | April - May 2016 | BioSpectrum    5 Excellent read The entire segment called ‘A decade of growth‘ was an excellent read. It revived the entire decade of the bio- tech industry. Refreshing the stories that was burning issues and major happening in the industry, it’s good to know that the biotech sector has evolved substantially in the past 10 years. James,Korea Wonderful wearables This is with reference to the story on wearables in the last issue of the magazine. Wearables are increasingly becoming an important tool to monitor health. How- ever, I believe better policies and a strong regulatory framework,will go a long way in exploiting this new tech- nology in a healthy way. Julie Tan, Malaysia Excellent flashback! I have been an avid reader of BioSpectrum for the past many years and have been reading the yearly round- ups. This is the first time I have read the flashback for the entire decade! Kudos to BioSpectrum for coming up with interesting and informative articles every month. Zack Mathison, Taiwan Big data for healthcare Big data has immense potential for healthcare sector, but un- fortunately the sector has been slow in exploiting the usage of big data. Though the traction has increased in the past few years but not too much. Other sectors are already benefitting from big data, hopefully healthcare will also join the bandwagon soon. Carl Benedict, Singapore Congratulations to BioSpectrum My heartiest congratulations to BioSpectrum Asia and its team as the publication turned 10 in March, celebrat- ing a decade of relentless existence. I’m very impressed by your quality editorial content which is a perfect bal- ance between Science & Technology and Business. The story ‘A Decade of Growth’ in your 10thanniversary edi- tion took me through 10 mind-blowing developments in the bioscience industry. On similar lines, I’m wondering if you could highlight at least one big breakthrough in bioscience in each edition. Overall, job well done! Shalmalee Vaidya, Singapore | March 2016 | BioSpectrum CoverStory BioSpectrum is an publication; MCI (P) 115/10/2014 A DECADE OF GROWTH | ł Ð é Ý Ë ‰ ł ú Ž 1 Publisher: Jagdish Patankar Editorial Chief Editor: Narayanan Suresh Executive Editor: Srinivas Rasoor Senior Assistant Editor: Amrita Tejasvi Senior Correspondent: Raj Gunashekar Production Assistant Editor: Ajay Ghatage Sub-Editor: Ayesha Siddiqui Design Shihab KA Sales and Marketing Associate Vice President (APAC): Kingshuk Sircar ( International Sales: Vikas Monga ( Subscription Services Print Edition: Saradha Mani ( Digital Edition Srinivas Rasoor ( Editorial and Marketing Offices Singapore Manager Admin & Sales Support: Saradha Mani #14-06, High Street Centre, 1 North Bridge Road, Singapore - 179094 Tel: +65-63369142 Fax:+65-63369145 India BioSpectrum MMActiv Sci-Tech Communications, #9, UNI Building, 3rd Floor, Thimmaiah Road, Millers Tank Bund, Vasanthnagar, Bangalore - 560 052 Tel: +91-80-41131912/13 Fax: +91-80-41131914 Australia Media Representative: Mr Anupam Das AtsMedia, PO Box 660, West Ryde, NSW 2114 Email: Tel: +61-430195795 South Korea Media Representative: Young Guk CHO, CEO Global Venture Network 4th fl, Haengwoon bldg., 150-5 Pyungchang-dong, Jongno-Gu, Seoul, Korea Tel./Fax.: +82-70-89504080 Mobile. +82-10-52030716 E-mail: Printed and published by Jagdish Patankar on behalf of MM ACTIV Singapore Pte Ltd. Printed at Times Printers Private Limited 16 Tuas Avenue 5, Singapore 639340 Tel : +65-63112888 Chief Editor: Narayanan Suresh MCI (P) 029/10/2015 Copyright: MM ACTIV Sci-Tech Communications Taiwan Media Representative: Ms Christine Wu Image Media Services Company 2F-2, No. 35, Sec. 2, Fushing South Road, Taipei 10665, Taiwan Tel: +886-2-87734199 Fax:+886-2-87734200 Mobile: 886-937890533 E-mail: website: Europe Media Representative: Mr. Stuart Smith Media Representative: Mr. Stuart Smith Global Media Sales Limited PO BOX 1126, Bromley, Kent, BR1 9TX, UK Tel: +44-(0)20-8464-5577 Fax: +44-(0)20-8464-5588 Email: Website: USA Media Representative: Ms Leslie Hallanan Avani Media, Inc. 80 Liberty Ship Way, Suite 25, Sausalito, CA 94965 USA Tel: +1-415-3312150 Fax: 415-3312151 E-mail: website: Photo: Shutterstock Go Digital: To request subscription email Vol 11; Issue 4; April - May 2016 Vol 11; Issue 3; March 2016
  4. 4. 6   BioSpectrum | April - May 2016 | | An MM Activ Publication Latest BioSupplier Technologies BioContents COVERSTORY16 Siemens Healthcare, India17 ARE YOU READY FOR LABORATORY TRANSFORMATION? Thermo Fisher Scientific20 CRISPR-CAS9 GENOME EDITING – SIMPLE GENOME EDITING STARTS HERE Horizon Discovery23 CRISPR–CAS9: A NEW HOPE FOR DRUG DISCOVERY Eppendorf India26 TRIUMPH OF HIGH PRECISION PARALLEL BIOREACTORS OVER CONVENTIONAL SYSTEMS Sartorius-Stedim Biotech, UK28 SINGLE USE MICRO SCALE BIOREACTOR ENABLES HIGHER PRODUCTIVITY CONVENTIONAL SYSTEMS Waters India32 ACQUITYQDA: SEPARATING BEYOND QUESTION Thermo Fisher Scientific34 EXPLORING NEW FRONTIERS IN BIOLOGICAL SCIENCE USING MASS SPECTROMETRY In the ensuing pages, BioSpectrum is publishing a selection of open invitation articles by the industry captains, highlighting the latest BioSupplier technologies/ products that are enabling the biosciences industry on the course of drug discovery.
  5. 5. An MM Activ Publication | | April - May 2016 | BioSpectrum    7 REGULARS BioEdit�����������������������������������������������������������������������������������������������������������������������04 BioMail����������������������������������������������������������������������������������������������������������������������05 BioNews�������������������������������������������������������������������������������������������������������������38 BioPeople��������������������������������������������������������������������������������������������������������46 10 India’s trillion-dollar opportunities in ICT, IoT BIOIT QE Prize winner Dr Langer shares his success Dr Robert Langer Winner of Queen Elizabeth Prize of Engineering 2015, David H Koch Institute Professor, Massachusetts Institute of Technology (MIT), USA 08 36 Biosimilars are opening up new opportunities Mr Christiaan Engstrom President, Cell Culture Company BIOTALK 47 BIOCOLUMNS Driving public health impact with vaccines The past, present and way forward Dr Joselito Sta Ana Senior Director, Regional Head Dengue, Sanofi Pasteur Asia Pacific BIOANALYSIS 49 Lung cancer burden of Asia
  6. 6. BioTalk 8   BioSpectrum | April - May 2016 | | An MM Activ Publication QE Prize winner Dr Langer shares his success Dr Robert Langer Winner of Queen Elizabeth Prize of Engineering 2015, David H Koch Institute Professor, Massa- chusetts Institute of Technology (MIT), USA T he Queen Elizabeth Prize for Engineering is con- sidered as the highest international accolade for engineering, and recognizes ground-breaking global innovation to inspire next-gen engineers. The award is a global £1 million prize celebrating pio- neering innovations that has had a profound benefit to humanity globally. Dr Langer lab’s work is at the interface of biotechnology and material science. His lab’s major focus is in studying and development of polymers to deliver drugs, particu- larly genetically-engineered proteins, DNA and RNAi, continuously at controlled rates for prolonged periods of time. Dr Langer exclusively spoke to BioSpectrum, where he shared his passion, origins, memories of his childhood laboratory, entrepreneurial tips and his award-winning work on controlled-release drug systems. Excerpts: Dr Robert Samuel Langer was awarded the 2015 Queen Elizabeth Prize (QEPrize) for Engineering in February 2015 at the Royal Academy of Engineering, London, UK. He is a world-renowned American scientist, engineer, inventor and entrepreneur, and David H Koch Institute Professor at the Massachusetts Institute of Technology (MIT), USA.
  7. 7. BioTalk An MM Activ Publication | | April - May 2016 | BioSpectrum    9 Firstly, a hearty congratulations Dr Langer. Tell us about your award-winning work to our Indian readers, and the impact of your controlled-release drug systems. A Thank you. I think engineering is such a wonderful way to contribute to society. The two things that give me the greatest satisfaction are discovering princi- ples or making inventions that enable people to have hap- pier and healthier lives, and seeing the people who train in our lab succeed to become future leaders in engineer- ing themselves. There are times when drugs administered to patients could react after being in the system for more than the required period of time or they might be ineffective by disappearing quickly. To tackle this, controlled drug re- lease helps maintain and sustain the drug release at an effective level for the suitable period of time. The polymer which was invented through my study helps in controlled dissemination of the drug molecules. My work which won the QEPrize is on engineered polymers which control the delivery of large molecular weight drugs for the treatment of diseases such as cancer and mental illness. It is already being used in various countries, including India. I am thrilled to be the recipient of the Queen Elizabeth Prize 2015. The prize celebrates ground-breaking innova- tions in engineering and in addition strives to celebrate stories of engineering successes, raising the international public profile of engineering and inspiring new genera- tions of engineers to take up the challenges of the future. What sparked you to become a scientist? A Some of it started as a child having chemistry, mi- croscope and erector sets. My dad also played a lot of math games with me. All this contributed to my liking science and math. Shed some light about the lab in your home’s basement in Albany. A It was a small basement and I had a Gilbert chem- istry set. I put all the chemicals down there and I loved doing experiments where I would make things like rubber and make solutions change colors via chemical re- actions. You have a background in Chemical Engineering. What made you to shift towards Biomedical Engineering? A I always wanted to learn biology. My PhD thesis was on the enzymatic regeneration of ATP. I did my postdoc in a surgery lab at Boston’s children’s hospital. I was the only engineer in the hospital. It really gave me all For young people, I’d say dream big dreams, dreams that can change the world and make it a better place kinds of ideas as to how chemical engineering could be applied to medicine. You have been researching since the 70s. How difficult or hard has it been for you to achieve what you have achieved today? A Very difficult. My first nine research grants were turned down largely because my research went against conventional wisdom. No chemical engineering department would hire me as a professor. And I ended up joining a nutrition department. The year after I joined, the department head who hired me left. So the associate department heads decided to give me advice. They told me to start looking for another job. Time helped me over- come some of these issues as we proved that conventional wisdom was incorrect. And I just never gave up. You have over 1,000 patents to your credit. How will you define innovation? A A new idea or invention, and its implementation into real life You are also an entrepreneur too. What do you have to say to all the scientists who want to be an entrepreneur? A: I think it’s an attractive career path but not the only career path. Personally I love it because it enables myself and my students to take our ideas into the real world and help people. But science leads to many good career paths. What are the common mistakes committed by scientists while they pursue their entrepreneurial dreams? A Starting a company too early. Not having good in- tellectual property (IPs). What do you advice students who hesitate to become a scientist or pursue a research- oriented career? A I think that’s okay. Everyone should get lots of ad- vice. But they should follow their passion. I think people should do things that make them happy. And they shouldn’t do things just to make money.  BS Raj Gunashekar
  8. 8. BioIT 10   BioSpectrum | April - May 2016 | | An MM Activ Publication In recent years, Internet of Things (IoT) has emerged as a buzzword, with both service providers and businesses, exploring possibilities connected devices can bring to the services they render and the way they conduct their businesses. IoT solutions are impacting the healthcare in a significant manner. Today, enterprises are realizing that the adoption of IoT in their operations will not only lead to increased productivity and process efficiencies, but also a reduction of costs. While IoT is still at its nascent stages in India, the potential is tremendous. India’s trillion-dollar opportunities in ICT, IoT A s a society, we are becoming more connected and the pace at which new technology is im- pacting our every- day lives is increasing at lightning speeds. Over the next decade, the IoT and M2M (machine-to-machine) are ex- pected to bring billions of data-gen- erating devices online, and connect a vast stream of data with people, processes and other devices. There are some niche applications such as sensors record, ambulatory medi- cal record (AMR) modem, and asset tracking. “In the pharma and healthcare in- dustries,” says Mr Sai Pratyush, Ad- ditional VP, Managed Services, Tata Teleservices, “we see the increasing use of IoT in the form of people con-
  9. 9. BioIT An MM Activ Publication | | April - May 2016 | BioSpectrum    11 necting to various healthcare devices. Also the use of wireless technology will allow healthcare workers and pa- tients to rapidly access information. M2M communication connected wirelessly via sensors that transfer data automatically will improve ef- ficiencies.” The healthcare industry has long been overburdened by slow moving innovation due to the complexity of the medical ecosystem that’s chang- ing aggressively, and IoT and M2M solutions are playing a catalyst role in this change and revolutionizing the pharma sector. “It will also be helpful in providing better medication-management and will be the fastest growing segment in the whole IoT market,” predicts Mr Pratyush. Technology is playing a significant role in improving the quality of healthcare, cost efficiency, precision performance, proactive and on-time care, real-time communication and most importantly, saving lives. Tata Teleservices is working with partners to develop scalable ICT (In- formation and Communication Tech- nologies) and IoT solutions across the healthcare value chain which in- cludes hospitals, vendor ecosystem, doctors and individuals. The following are few areas which will see innovation, and will benefit Technology is playing a significant role in improving the quality of healthcare. Mr Sai Pratyush Additional VP, Managed Services, Tata Teleservices
  10. 10. BioIT 12   BioSpectrum | April - May 2016 | | An MM Activ Publication both the industry as well as patients:  Outpatient monitoring  Wearables  Remote monitoring or rural healthcare  mHealth  Location based services ICT Trends In Indian Healthcare ICT and IoT solutions are impacting the healthcare in a significant man- ner. There is the wearables space which is enabling and pushing ordinary peo- ple to maintain a healthy lifestyle, and then, there are those simple in- novations which are enabling the healthcare industry to provide better quality of care to its patients. Outpatient monitoring and telemedi- cine applications are introducing the healthcare industry to newer ways of interaction with patients and en- abling them to not only monitor pa- tients on a continuous basis but also respond more quickly to situations that need their attention. “As an example, a monitoring device is given to the patient at the time of discharge for a limited timeframe, which helps the doctor to continue to monitor the patient and suggest cor- rective actions during the patient’s recovery,” states Mr Pratyush. As per a Deloitte Report, telemedi- cine is witnessing fast adoption in In- dia. In 2012, the telemedicine market in India was worth $7.5 million, and it is expected to rise 20% annually to $18.7 million by 2017. Telemedicine can provide low-cost consultation and diagnostic facilities to the remotest areas via high-speed internet and telecommunications, The major users of ICT include big pharmaceutical companies, cor- porate hospitals and other private health sector institutions, while the public healthcare sector is lagging way behind in IT utilization. But the good news is that the situation is changing. Mr Pratyush mentions, “Though ICT solutions have had a positive im- pact on the healthcare sector, there are some challenges that need to be overcome in order to provide afford- able, high quality healthcare solu- tions, and innovations to hospitals and their vendor ecosystem, doctors, and eventually the citizens of this country.” The government is now cognizant that technology can help overcome challenges arising due to geographi- cal size, high-population density, lack of healthcare infrastructure, in- accessibility in rural India, poor nu- tritional conditions, and low literacy, among others. Furthermore, the National Health Policy endorsed by the Parliament of India encourages the introduction of electronic communication media in health sector. The Government of India also brought in the National Rural Health Mission for delivering the best-in- class healthcare facilities to the rural population. The Ministry of Health and Family Welfare and the Ministry of Com- munication and Information Tech- nology are jointly creating a national health information infrastructure for easy capture and dissemination of health information. Like all new disruptive technolo- gies, IoT deployments face numerous challenges. thus, bridging the rural-urban divide. In addition, India’s extensive mobile technology infrastructure and better connectivity infrastructure is expect- ed to drive mobile health (mHealth) adoption further. He points, “Several people in our country do not have ready access to decent healthcare. There are many challenges to set up a full-fledged hospital at remote and rural loca- tions. However, IoT-based wireless solu- tions are now making it possible for doctors based in cities to monitor patients located in remote villages. Now, villagers need not travel long distances to get a simple diagnosis done.” Mr Pratyush feels that solutions need not involve complex ICT infrastruc- ture. “SMS-based solutions are enabling doctors and hospitals to send re- minders and alerts to their patients on medication or health checkups. “This management of medication through SMS platform ensures doc- tors and hospitals provide best pos- sible care to their patients,” he adds. Challenges to disruption Despite being an IT-enabled servic- es behemoth, the use of ICT in the healthcare sector is limited in India. The government is now cognizant that technology can help overcome challenges arising due to geographical size, high population density
  11. 11. BioIT 14   BioSpectrum | April - May 2016 | | An MM Activ Publication THE CLOUD ADOPTION Though cloud computing is still a concept that exists only in theory for the Indian healthcare industry, the healthcare vertical has made it to the potential list of every cloud vendor and service provider. Mr Pratyush says, “It is not surprising, given the general opinion that healthcare industry is rapidly automating itself, and soon enough, will be leapfrogging towards the cloud.” Research agencies like Zinnov have derived that the healthcare industry currently spends only about 2% of their total budgets on IT. This figure is set to grow to 15 to 20% in 2015, and up to 40% in 2020, purely to- wards adoption of cloud services. This will mean that the cloud opportunity within the healthcare seg- ment could touch $600 million in 2020. At a CAGR growth rate pegged at 25%, healthcare is definitely one of the most promising segments as far as cloud adoption is concerned. “With connected IoT devices, reliable bidirectional signaling is essential for collecting and routing data between devices. You need to be 100% sure that that stream of data is going to arrive at its destination every time,” emphasizes Mr Pratyush. Security is another important factor in IoT connectivity. “What good is a smart home if any- one can unlock your doors, or for that matter anyone can access your health records?” asks Mr Pratyush. “Solutions need to ensure that when sending or receiving a stream of data, the IoT device or server has proper authorization to send or receive that stream of data, and most important- ly, you need end-to-end encryption between devices and servers.” Huge and uninterrupted power consumption is also seen to pose challenges. “Billions of IoT devices which are required to transmit data between one another will require un- interrupted power either through the grid or battery bank,” he stresses. Currently most solutions deployed in the country are based on proprietary technologies which make it difficult for customers to scale or opt out in case the solutions are not working for them. Tata Teleservices is working with partners to create innovative ICT so- lutions for the healthcare industry. These solutions address the basic needs of providing telecom infra- structure as well as more complex IoT solutions such as LBS (Location- based services) or healthcare-related applications. Trillion dollar opportunity As far as the IoT market opportunity is concerned, while findings of market research companies may vary, they are unanimous in their conclusion that this is a trillion dollar opportu- nity in terms of revenue potential. A recent study by a global network- ing major predicted that there will be 25 billion devices connected to the internet by 2015, and 50 billion by 2020, thus highlighting its promi- nence in the coming decade. Mr Pratyush explains, “We have seen IoT and M2M deployments primar- ily in the utilities and transportation space, but that is changing slowly. As the devices, sensors and applica- tion ecosystems grow, we are seeing investments being made across BFSI (Banking, Financial Services and In- surance), retail, healthcare and even the home and building management space. The Government of India is also playing a significant role in adopting ‘smart IoT technologies’. The ‘Smart Cities’ program as well as ‘Digital India’ is leading entre- preneurs to make substantial invest- ments in this space.” Globally, IoT has seen deployment across transport, utilities, retail, logis- tics, home automation and security. “The West is definitely a few steps ahead in terms of use cases and scale of deployments, but it would be in- correct to say that we are ‘very’ far be- hind,” he opines. “The next few years will be critical for India, and I believe we have a good opportunity to bridge the gap. The Government’s ‘Digital India’ program and ‘Smart Cities’ ini- tiatives will further the cause of IoT substantially.” Tata Teleservices has been develop- ing IoT solutions for its customers across a host of use cases and indus- tries which includes the healthcare industry. “Our solutions encompass not only the telecom infrastructure but the de- vices and application as well in select verticals. Healthcare is a key vertical, and we are working with partners to create solutions which will be benefi- cial for our customers,” concludes Mr Pratyush.  BS Raj Gunashekar
  12. 12. Latest BioSupplier Technologies The invention of the microscope is one of the most important scientific development. Since then the development in the laboratory instruments and technologies have grown by leaps and bounds. The Human Genome Project to sequence the human took 13 long years. Today, it is possible to sequence DNA in a couple of hours. As research and development in the biosciences grows, so is the demand for more sophisticated technologies, instruments that are affordable, precise and timely. In the ensuing pages, BioSpectrum is publishing a selection of open invitation articles by the industry captains, highlighting the latest BioSupplier technologies/products that are enabling the biosciences industry on the course of drug discovery. CoverStory 16   BioSpectrum | April - May 2016 | | An MM Activ Publication
  13. 13. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    17 Are you ready for laboratory transformation? Mr Amit Manjure Head-Clinical Marketing, Laboratory Diagnostics, Siemens Healthcare, India The influence of diagnostic tests on clinical decisions is very high. The global in vitro diagnostics market is estimated to reach $75.1 billion by 2020 R ising populations in emerging econ- omies will lead to increased demand for medical de- vices, diagnostic equipment and pharmaceuticals in the near future. At the same time, this demand will leverage tech- nological advances. In vitro diag- nostics (IVD) is one such industry that is witnessing proliferation of technology in terms of new assays, workflow excellence, turnaround time, etc. IVD plays an integral role in health- care and disease management. The influence of diagnostic tests on clinical decisions is very high – almost 75% of clinical decisions are based on a diagnostic test. The global in vitro diagnostics market is estimated to reach $75.1 billion by 2020, growing at a CAGR of 5.8%. The Indian IVD industry, still in the inception stage is valued at more than $500 million and is expected to surpass $1.5 billion by 2018. Growth Drivers for IVD With a population of more than 1 billion, India is world’s second larg- est country and therefore a signifi- cant market to the healthcare pro- viders. The demographic change has led to growth in tier 2 and tier 3 cities creating disposable income ultimately leading to a change in lifestyle patterns and an increase in the lifestyle diseases like cardiovas- cular diseases, lung disease, cancer, obesity, diabetes, etc. One in four Indians is at a risk of non-commu- nicable lifestyle disease. Accurate and quick diagnosis of diseases has thus become a crucial factor in providing quality patient care. Turn-around time (TAT) The diagnostics labs operate in a dynamic environment. In addition to the accurate diagnosis, reduced turnaround time (TAT), consistent delivery and affordability have be- come the need of the hour. Turn-
  14. 14. CoverStory 18   BioSpectrum | April - May 2016 | | An MM Activ Publication around time is the most noteworthy manifestation of laboratory service and a crucial barometer of laboratory performance. As a result, laborato- ries of all sizes are adapting total au- tomation across pre-analytical, ana- lytical and post-analytical processes integrated with information technol- ogy (IT) since information systems are a key differentiator among major healthcare providers. The innovations and discoveries in the IVD market are transforming the healthcare arena. The IVD market in- cludes a variety of advanced and cut- ting edge technologies to project the disease state, choose the right treat- ment and monitor thepatientsresponse to the treatment. An array of assay ca- ters to wide spectrum of diseases. Automation, a unified solution de- veloped expressly for the changing workload and expanding needs of to- day’s clinical laboratory, is playing a key role in the entire diagnostics set up. It provides unlimited potential for lab optimization by combining peak performance, adaptability, and intelligent technology. However, the challenges of implementing lab au- tomation can be formidable. It is a complex undertaking to meet busi- ness objectives and clinical require- ments while managing logistics, timelines, people and technology to achieve workflow excellence. And the operations must continue uninter- rupted during this transition! The work in any laboratory is typi- cally broken in three phases. 1. The pre-analyticalphase: this comprises of patient sample iden- tification, test request registration and billing, sample collection, labeling by barcode, separation followed by transport and sample processing. 2. The analytical phase: this com- prises of properly calibrating the instruments, the quality control process and analysis of samples. 3. The post-analytical phase: This includes all the processes that follow the testing of the samples. Namely, the validation of test re- sults, transcription of results into the records, printing and dispatch of the results. Also, the data so generated needs to be stored. The samples also need to be stored for specified period of time for repeats or add-ons. With this background, it is critical for laboratories to optimize the follow- ing flow across these three phases.  The sample flow has to do with the collection of the samples, to sorting, transportation until their disposal and/or they are sent out.  The data (information) flow goes from order entry to receiving or accessing, quality control, etc. all the way to validation, reporting and billing.  The material flowincludes inven- tory tracking; invoicing and pay- ment etc. Removal of non value-added steps such as reducing sample touch points, manual bench sorting ali- quoting transportation, sample re- run, results review is a key to achiev- ing workflow excellence. Automation – the way ahead! Statistics indicate that there has been an approximately 25 percent increase APTIO AUTOMATION INTELLIGENT, TEST-DRIVEN, TUBE ROUTING ON APTIO PLATFORM
  15. 15. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    19 in laboratory tests due to screening and follow up for lipid profile, blood glucose levels, glycosylated haemo- globin, speciality tests for thyroid hor- mone levels, vitamin levels, infectious serology and basic cancer markers. The diagnostics and pathological lab test market has the potential to grow at a CAGR of 18.9 percent. With automation, labs of all sizes can transform their operations to harness change and drive maximum perfor- mance and efficiency. Laboratories can also customize their automation solutions by identifying the sustain- able workflows. Labs can consolidate multi discipline testing into a single, fully automated solution or improve spatial efficiency, tube utilization, or resource allocation. Siemens has helped diagnostic laboratories lever- age the benefits of automation and information technology since 1998— making workflow more efficient and flexible while improving turnaround times, reducing errors, and cutting costs. Laboratory automation allows for a broader diagnostic scope and in- creased accuracy. Ultimately, labo- ratories will be able to perform more tests in-house and reduce their de- pendency on outsourcing services in addition to the decrease in number of duplicative laboratory process and increase in throughput. This will also allow staff to be better utilized beyond bench testing and routine operation including but not limited to patient interaction,finance, marketing services and strategic planning.  BS Statistics indicate that there has been an approximately 25 percent increase in laboratory tests due to screening and follow up
  16. 16. CoverStory 20   BioSpectrum | April - May 2016 | | An MM Activ Publication CRISPR-Cas9 genome editing – simple genome editing starts here Namritha Ravinder Senior RD Manager, Synthetic biology, Thermo Fisher Scientific The new GeneArt CRISPR Search Design tool allows scientists to search a database of 600,000 pre-designed CRISPR gRNAs in human and mouse genes I ntroducing the only com- plete genome editing solu- tion designed to expedite your research. Our easy- to-use, optimized and val- idated solutions span the entire cell engineering workflow, making genome editing accessible to anyone at any level. We are con- tinuing to expand our suite of ge- nome editing products to span the entire cell engineering workflow, from cell culture reagents, delivery reagents and sample preparation to genome modification, detection and analysis of known genetic vari- ants. We offer our state-of-the-art online CRISPR search and design tool along with CRISPR-Cas9 in four formats: an all-in-one expres- sion vector, Cas9 mRNA, Cas9 pro- tein, and CRISPR libraries services paired with the optimal cell culture reagents, delivery method, and analysis tools based on required application and cell type (Figure 1). Optimal CRISPR design at the touch of afinger The new GeneArt CRISPR Search Design tool allows scientists to search a database of 600,000 pre- designed CRISPR gRNAs in human and mouse genes or analyze their sequence of interest for de novo gRNA designs using Thermo Fish- er’s proprietary algorithms. The tool is designed to analyze genes of interest, identify gRNA sequences adjacent to protospacer adjacent motif (PAM) sites, and rank order resulting gRNAs based on potential off-target effects. Up to 25 gRNA sequences per gene are provided with recommendations based on potential off-target effects for each CRISPR sequence. Invitrogen GeneArt Platinum Cas9 Nuclease is wild type Cas9 in pro- tein form for genome editing with CRISPR-Cas9 technology. Cas9 protein and guide RNA (gRNA) form a very stable ribonucleo pro-
  17. 17. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    21 NamrithaRavinderisaseniorRDmanageratThermoFisherScientificinCarlsbad,California.Sheleads productdevelopmentactivitieswithintheSyntheticBiologyandSamplePrepteam,withprimaryfocus onbuildingproducts,screeningtoolsandworkflowsforgenomeeditingandcellengineeringapplications. Priortohercurrentrole, she was a technical lead for a wide variety of synthetic biology custom service offerings including cDNA library generation; high-throughput gene expression and miRNA profiling for biomarker discovery; lentivirus production; and next-generation sequencing libraries. She did her postdoctoral research at Children’s hospital in Los Angeles in HIV virology and doctoral research in plant molecular biology and biotechnology at University of Alabama inHuntsville. BRIEF PROFILENAMRITHA RAVINDER tein (RNP) complex that provides the next level of cleavage efficien- cy over CRISPR-Cas9 vector and mRNA-based systems when paired with Invitrogen Lipofectamine CRIS- PRMAX Cas9 Transfection Reagent. The Cas9 RNP complex can act im- mediately after it enters the cell, since transcription and translation are not required (Figure 2). More- over, the complex is rapidly cleared from the cell, minimizing the chance for off-target cleavage events when compared to vector-based systems. GeneArt Platinum Cas9 Nuclease is the recombinant Streptococcus pyogenes Cas9 (wt) protein purified from E.coli that can be used for ge- nome editing with CRISPR technol- ogy. Features and benefits include:  Two available concentrations  1µg/µL(B25640) for use instan- dardediting scenarios, including cell lines such as HEK293 or HCT116  3 µg/µL (B25641) for optimiza- tion of editing conditions in more difficult scenarios such as in primary or embryonic cell lines, or when screening multiple gRNA sequences at a time  Streamlined cell engineering by eliminating transcription and translation in the cell  Elimination of time-consuming cloning steps  Minimization off-target cleavage due to rapid clearance of the pro- tein complex from the cell The GeneArt Precision gRNA Synthe- sis Kit is a complete system for rapid synthesis of guide RNA (gRNA), ready to complex with GeneArt Plati- num Cas9 Nuclease for transfection- ready Cas9 protein/gRNA ribonu- cleoprotein (Cas9 RNP). Features and benefits include:  Fast assembly and synthesis of any gRNA target in as little as four hours, including template assembly  High yield (10 µg) and concen- tration ( 200 ng/µL) of gRNA The Lipofectamine CRISPRMAX Cas9 Transfection Reagent is the first optimized lipid nanoparticle trans- fection reagent for CRISPR-Cas9 protein delivery, providing the cleav- age efficiency of electroporation with the simplicity and scalability of a re- agent. Lipofectamine CRISPRMAX transfection reagent is an ideal al- THE PERFECTPAIRING We have paired the CRISPR-Cas9 format and delivery method for scientists to ensure the highestefficiencies.
  18. 18. CoverStory 22   BioSpectrum | April - May 2016 | | An MM Activ Publication ternative to electroporation as it is gentleron cells and more cost effec- tive overall (Figure 3). Features and benefits include:  Demonstrated cleavage efficiency tested in more than 20 cell types including iPSC, mESC, N2A, CHO, A549, HCT116, HeLa, HEK293, and several others  Low cell toxicity—fewer cells needed to initiate your experi- ment  Cost savings—including both cost- per-reaction and initial invest- ment  Easy scalability—an ideal deliv- ery solution for high-throughput experiments Advances in genome modulation and editing have the potential to change the way we create energy, produce food, optimize industrial processing, and detect, prevent, and cure diseas- es — improving the human condition and the world around us. Thermo Fisher’s trusted products harness the power of science to transform lives. Its instruments, routine tools, and services offer high-quality, innova- tive life science solutions for every- lab. BS WORKFLOW Advances in genome moudulation and editing have the potential to change the way we create energy, produce food, oprtimize industrial processing, and cure diseases
  19. 19. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    23 CRISPR–Cas9: a new hope for drug discovery Dr Ceri Wiggins Team Leader, Horizon Discovery Thought to be devoid of the caveats associated with siRNA and shRNA reagents the hope is that novel targets can be uncovered T he repurposing of a primitive adap- tive immune re- sponse in bacteria, known as CRISPR (clustered regularly interspaced short palindromic re- peat), has revolutionized gene edit- ing and provides a new and power- ful tool to interrogate gene function on a genome-wide level. Indeed, the contribution of this technology to drug discovery looks, from our current vantage point, to be sub- stantial. The application CRISPR– Cas9 technology to whole genome screening is transforming our abil- ity to perform target identification experiments and to understand complex biological processes, such as drug resistance. Thought to be devoid of the caveats associated with siRNA and shRNA reagents, the hope is that novel targets can be uncovered and rigorously validated using CRISPR–Cas9, and that a pipeline of innovative and validat- ed targets will enter drug discovery programs. Indels are crucial: CRIS- PR–Cas9 screens make use ofshort guide RNAs (sgRNAs) and Cas9 nuclease, two components of the CRISPR machinery in bacteria. The sgRNA, which Cas9 binds to, con- tains a protospacer adjacent motif (PAM) site and this enables the tar- geting of Cas9 to the RNA:DNA hy- brid. Once bound, the Cas9 nucle- ase generates DNA double strand breaks precisely 3 base pairs away from the PAM site. These double strand breaks are repaired by non- Dr Steffen Lawo Senior Scientist, Horizon Discovery Narinder Singh commercial contact, Country Head-India-Horizon Discovery.
  20. 20. CoverStory 24   BioSpectrum | April - May 2016 | | An MM Activ Publication Ceri Wiggins is a Team Leader at Horizon Discovery, currently responsible for the internal synthetic lethal CRISPR screening and target identification/validation team. Steffen Lawo joined Horizon Discovery GroupasSenior Scientist in 2013. As Country Head at Horizon Discovery, Narinder is responsible for business development of Horizon’s product and service portfolioacross India and Middle East. BRIEF PROFILE BRIEF PROFILE BRIEF PROFILE DR CERI WIGGINS DR STEFFEN LAWO NARINDER SINGH homologous end joining (NHEJ), which frequently results in small nu- cleotide insertions and or deletions (indels) that can lead to the inter- ruption of the normal reading frame, thereby disrupting gene function. Pooling resources: Using lentiviral transduction to deliver both the Cas9 nuclease and sgRNAs into cells, Horizon Discovery has adapted a pool-based screening protocol to examine the effect on cell survival of knocking out thousands of individual genes. The sgRNAs are designed to direct Cas9 to exons at the start of the open reading frame, such that any out-of-frame indels will result in gene disruption. The screen analysis is based on data from cells collected at the start of the screen (3–5 days after transduction) compared with cells collected at the end of a screen that have been exposed to a drug of interest, for example. The next gen- eration sequencing (NGS) data from the initial time point acts as a com- parator for the NGS data collected at the end of the screen, such that sgRNA loss and gain over the time of the screen can be established. We use a dedicated CRISPR–Cas9 screening analysis platform, adapted from the MAGeCK workflow (Li et al., 2014), which enables individual sgRNAs and gene hits to be ranked. Resistance discovery ahead of the clinic Many of the initial screens that Ho- rizon Discovery has undertaken for a number of clients from the phar- maceutical industry have examined mechanisms of drug sensitivity and resistance. Indeed, for our initial proof of concept studies we, like oth- ers, examined mechanisms of resis- tance to vemurafenib, a drug that targets the BRAFV600E activating mutation. The GeCKOv2 genome wide library, which contains 6 guide RNAs against 19,050 genes (San- janaet al., 2014), was transduced into BRAFV600EmutantA375melanoma cells and the cells were treated with vemurafenib. A comparison of the abundance of each guide RNA at the start and end of the screen was used to assess whether drop out or enrich- ment of guide RNAs had occurred over the course of the screen. Over 228 guides were shown to be 100- fold enriched, with several sgRNAs targeting the same genes. Using our analysis platform, the highest rank- ing targeted genes (MED12, NF1, CUL3, NF2, TADA2B and TADA1) were those whose loss is known to confer resistance. These findings repeated previously published data (Shalemet al., 2013, Huang et al., 2012, Whittaker et al., 2013). Interestingly, when the sgRNAs for each of these hits were evaluated individually, it was clear that not all guides performed equally well in the screen. This emphasises that for suc- cessful screening, the library compo- sition and complexity are key consid- erations. Increasing the odds with a haploid approach Engineered from KBM7 fibroblasts, eHAP cells are a fully haploid cell line and are particularly suited to CRISPR–Cas9 screens because there is only one copy of any given gene to edit. We used the eHAP cells to ex- amine the mechanisms of resistance to 6-thioguanine (6-TG), a purine an- timetabolite that is used in the treat- ment of leukaemia. The biology of the DNA mismatch repair (MMR) system and factors that mediate resistance to 6-TG have been extensively studied and as such provide an excellent par-
  21. 21. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    25 adigm to test the power of CRISPR– Cas9 resistance screens in haploid cells. eHAP cells were infected with the whole genome GeCKOv2 library and were exposed to either 500 nM 6-TG or vehicle control and main- tained in culture to allow sgRNA en- richment and depletion to occur. As expected, NGS analysis revealed that sgRNAs targeting MLH1, MSH2 and MSH6, three genes that encode MMR proteins, were enriched in the screen (Branch et al., 1993; de Wind et al., 1995, Abuinet al., 2000, Buermeyer- et al., 1999). To validate these targets as 6-TG resistance factors, MLH1 and MSH6 knockout HAP1 cells were generated using a CRISPR–Cas9 approach. These cells were able to proliferate in the presence of 6-TG unlike the parental cell line. Thus, CRISPR–Cas9 approaches were used to both identify the mechanisms of resistance and to validate them. The future looks bright CRISPR–Cas9 is a fast moving technology that has been embraced across the board. As discussed above, it has been used to successfully iden- tify mechanisms of drug resistance in whole genome screens, but its applications extend further into ani- mal model generation and genetic therapies. Its use, particularly in hu- mans, is the subject of much debate that looks set to continue for years to come. However, in terms of drug discovery, CRISPR–Cas9 technolo- gies look poised to replace RNAi as a new avenue for more effective drug discovery. Thanks to NGS, we are starting to catalogue the plethora of mutational changes that occur in the genome of any cancer cell. With this knowledge comes potential – novel mutated genes and the proteins that they encode, are candidates for prog- nostic markers and/or new drug tar- gets. With the ability to rapidly engi- neer cells (and animal models) using CRISPR–Cas9 technologies, the gen- eration of robust models needed for improved target identification and validation promise to be attainable.  BS The generation of robust models needed for improved target identification and validation promise to be attainable.
  22. 22. CoverStory 26   BioSpectrum | April - May 2016 | | An MM Activ Publication Triumph of high precision parallel bioreactors over conventional systems D. Muruganand PhD., Vice President – Marketing, Eppendorf India, Chennai Scientists and investors are looking forward to shorter timeframes in getting results and the product of interest launched in the market respectively T he biopharma in- dustry is growing steadily at a sig- nificant pace and so are their invest- ments in research and development. Investment in biologics like vaccine, biosimilars, novel biopharmaceuticals, cell and gene-based therapeutic products are seeing a never before trend. The stakeholders, both scientists and investors, are looking forward to shorter timeframes in getting results and the product of interest launched in the market respec- tively. As these processes involve cell culture or microbial fermenta- tion, the need for dedicated mini- bioreactor systems for process de- velopment and critical parameter optimizations in low volume ranges are certainly creating interest com- pared to the conventional fermen- ters and bioreactors. With time being very critical, the single use vessels are also gaining more at- tention over autoclavable formats among the biopharma users. From conventional shake flasks to parallel bioreactors While initial bioprocess develop- ment involving microbial or cell culture involves several steps like cell line optimization, clone selec- tion, screening for media and feed components along with other pro- cess conditions, conventional shake flasks are still used foroptimizing these early steps. Though widely used, shake flask formats only al- low identifying temperature, am- bientgas mix and agitation rates- but pose limitation upon reaching scalable levels with respect to the industry standard monitoring and control requirements. Critical pro- cess parameters like pH, dissolved
  23. 23. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    27 oxygen (DO), gas flow rates and feed schedules of media components are beyond the capabilities of shake flask format. Moreover equipment used for screening or optimization in the earlier steps should mimic the physi- cal and mechanical characteristics of production scale reactors to the greatest degree possible, to ensure consistency throughout development phases. The parallel bioreactor sys- tem provides all essential features in a compact and comprehensive design with flexibility to optimize and un- derstand parameters that influence growth kinetics, productivity, prod- uct quality and stability. Parallel bioreactors over the micro/mini bioreactor Though micro and mini bioreac- tor systems address the basic needs of media selection and optimiza- tions they still do not support when it comes to scalable proportions and concerns over unconventional formats are not uncommon. Lower volume by itself seems to limit for applications where the processes requirements are not flexible. Feed rates, sampling volumes to mention a few could be mandatory in these critical steps of characterization or optimization. Hence selection of an ideal system for lower volumes is no different from the standard volumes when it comes to the expectations of the process outcome. Expectations in a parallel bioreactor system With more manufacturers getting into this space expectations also grow from the user end. Hence the demand for compact, comprehensive and flexible system to adapt to pres- ent and future needs is on the cards. While deciding the number of vessels the primary requirement starts with a compact and less space occupying system. But when coming to the pro- cess needs features like flexibility for upgrades to enhance or extend the configuration to meet evolving needs, minimum level of scalability in work- ing volumes to establish proof of concepts, possibility for seamless in- tegration to downstream equipmen- tare certainly the priorities. Above all a simple and user friendly superviso- ry control and data acquisition (SCA- DA) software convenient for data ac- quisition, monitoring and processing becomes mandatory. Parallel bioreactors from Eppendorf DASGIP parallel bioreactor systems for microbial or cell culture applica- tions from Eppendorf combine the advantages of small working volumes with the full functionality of indus- trial bioreactors. The modular design allows expanding the system capa- bilities in 4,8,12 or 16 parallel vessels format controlled by single operating system. The vessels are the industry standard stirred tank reactors with different workings volumes ranging from 60 mL to 3.8 L. The modular system provides the flexibility to configure to the needs of user with respect to number of pumps, gases and their flow rates. The availability of single use vessels of different volumes have provided users the flexibility to choose be- tween autoclavable and single use vessels in both microbial and cell cul- ture applications. DASBOX parallel mini bioreactor sys- tem for microbial or cell culture has the option to use a dedicated vessel volume with working volume rang- ing from 60-250 mL. These systems are also designed to operate in mod- ules of 4, 8, 12 or more vessels.With both autoclavable and single use ves- sel formats available, the user has the choice to select. Availability of Photo- synthetic light module can make it a convenient choice for users working either with plant cells or for biofuel. Both DASGIP and DASBOX sys- tems can be calibrated in parallel for pumps and sensors making the ves- sels perform as replicates. Though designed for parallel reactions, these can also be controlled independently for maintaining completely different parameters. DASGIP control software allows par- allel monitoring, data capture with online analysis options. Combined with other software options, the system can be integrated with third party equipment like metabolite ana- lyzer, Raman spectrometer etc. The DAS ware software platform pro- vides larger integration and analysis flexibilities like Design of Experi- ment (DoE), remote monitoring and controlling, communicating with third party OPC compliant systems and morwwe. BS PARALLEL BIOREACTOR SYSTEMS
  24. 24. CoverStory 28   BioSpectrum | April - May 2016 | | An MM Activ Publication Single use micro scale bioreactor enables higher productivity Dr Barney Zoro ambr 15 Product Manager, Sartorius-Stedim Biotech, Royston, UK A strategy for reducing manufacturing COGs is to use advanced automated micro and mini bioreactor models to improve upstream cell culture productivity W o r l d w i d e sales of bio- logic drugs, including monoclonal antibodies (mAbs), fusion proteins and thera- peutic enzymes now exceeds $120 billion per year. These therapies cost more than small molecules, in part because they are more ex- pensive to manufacture. A strategy for reducing manufacturing COGs (cost of goods) is to use advanced automated micro and mini biore- actor models to improve upstream cell culture productivity by select- ing better clones and enabling more efficient optimisation of media, feed and culture conditions. Traditionally, cell culture develop- ment for bioprocessing begins with screening to find clones that express the most protein. This is usually per- formed in small volumes of 0.1mL to 6mL using a multiwell plate for- mat. Because of the need to conduct large numbers of experiments this has resulted in the development of systems based on 24 well single- use multiwell plate. These have the advantage of being quick and easy to set up and use and because the multiwell plate are pre-sterilised there is no pre-process preparation and as they are single-use there is no post-run cleaning. Some of these multiwell plate systems do provide monitoring and some control of dissolved oxygen (DO) and pH but have the drawback that they do not mimic the sparging or stirring ac- tion of a large scale bioreactor as they rely on shaking for mixing. Ad- ditionally, they do not provide auto- mated feeding and have a working volume of less than 6mL, which lim- its the amount of analytical testing possible. Clone selection and early process development to identify the most productive clones and define op-
  25. 25. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    29 timal media or culture conditions is typically performed in shake flasks with two or three top clones carried forward for evaluation in bench top bioreactors. Using shake flasks and bench top bioreactors is very labour intensive and as they are generally made of glass, require time consum- ing pre and post-process cleaning and sterilisation for every experi- mental run. Shake flasks provide no active control of pH and DO, relying on the buffer- ing capacity of the media and the gas environment of the incubator. The mixing environment is unlike that in a bioreactor as there is no impeller. Ad- ditionally, shake flasks are often ma- nipulated by hand, making it difficult to perform nutrient feeding or sam- pling without introducing variability. Hence, the use of shake flasks can of- ten result in different cell growth and titre profiles to those seen after scale- up in a bioreactor. Data published in Cytology of a study at Genentech demonstrates that when cultured in shake flasks, Chinese Hamster Ovary (CHO) clones expressing mAbs do not show comparable culture perfor- mance with those grown in 2L bench top bioreactors. Using bench top bioreactors does mimic the sparging and stirring ac- tion of a large scale bioreactor but they require considerable amount of time for set-up, operation and post-experimental cleaning and ster- ilisation. Therefore, the amount of available resource often limits use of bench top bioreactors requiring that researchers have to select only their top clones to test in this way. This can lead to the final choice of clone sometimes performing sub- optimally upon scale-up, adversely affecting yield and titre. If a larger number of runs could be performed during clone selection under condi- tions which are representative of the scale-up bioreactor environment, then it should be possible to isolate a better performing clone for use in manufacturing and potentially save thousands of dollars in manufactur- ing COGs. To meet the need for a single-use bio- reactor model that provides compa- rable mixing, gassing and sampling parameters to be used in place of shake flasks and bench top bioreac- tors, the advanced micro and mini scale bioreactor systems, ambr 15 and ambr 250 (Sartorius-Stedim Biotech) have been developed. These integrat- ed systems combine 10-15mL or 100- 250mL single-use bioreactor, with an automated liquid handling work- station and dedi- cated control and analysis soft- ware. Critical to the use of these systems as bio- reactor models is the geometric similarity to larg- er bioreactors and that their contents are stirred by an im- peller and gases can be supplied by sparging. In addition, the software control systems and integrated single use sensors enable these systems to control the culture conditions in a similar way to large scale systems en- suring scalability. Each workstation maintains aseptic conditions using a HEPPA filtered environment (ambr 15 can be in- stalled in a standard biological safety cabinet and the ambr 250 includes an integrated system) and provides independent parallel control of either 12 or 24 (ambr 250), 24 or 48 (ambr 15) bioreactors. The workstation con- trols the stir speed, gas supply and temperature and also provides liquid handling automation functions for the bioreactors, each of which can have its own medium, feed, inoculum and sampling strategy. Each bioreac- tor also incorporates sensors for real- time measurement and bioreactor- specific automated control of DO and pH and set points. A major contract research organisa- tion (CRO) compared the timelines for clone selection and early process development of a mAb expressing (CHO) clone using shake flasks and bench top bioreactors with the auto- mated micro bioreactor. The results showed that with reusable shake
  26. 26. CoverStory 30   BioSpectrum | April - May 2016 | | An MM Activ Publication flasks and bench top bioreactors, clone selection and early process development took around 22 weeks, whereas using the single-use micro bioreactors and a confirmatory run in a reusable bench top bioreactor ambr15 operators examining full 96 well plate Picture this was reduced to six weeks. Single-use micro and mini bioreac- tor technology can provide an ac- curate prediction of cell growth and protein titre achieved in bench top bioreactors. Setting up and running reusable shake flasks and bench top bioreactors is manually intensive, while the fully automated single-use micro and mini bioreactor is more convenient, taking much less time to set-up and run, as well as requiring no time consuming post run cleaning and sterilising. Thus clone selection and early process development can be performed rapidly and efficiently, increasing the number of clones that can be evaluated by up to ten fold. This improves the chances of select- ing a clone with optimal growth and protein expression. The automated system makes it easy to implement DoE into the work flow and the geo- metric similarity of the platforms re- duces the risks for scale-up to larger single-use pilot and manufacturing scale stirred bioreactors, reducing time-lines and saving cost.  BS
  27. 27. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    31 • One Mega Event • Complete Pharma Value Chain • Over 6,000 Selected Suppliers 健康产业领袖峰会 The Health Industry Summit Where the World of Pharmaceutical and Medical Industries Converge 17-20 APR . 2016 National Exhibition and Convention Center, Shanghai CMEF, ICMD: open 17-20 April ∙ 2016 API China, PHARMEX: PHARMCHINA, NHNE open 18-20 April ∙ 2016
  28. 28. CoverStory 32   BioSpectrum | April - May 2016 | | An MM Activ Publication AcquityQDa: Separating beyond question Manu Grover Product Manager-Pharmaceutical Market, Waters India. One of the complicated process in analytical industry was handling of Mass detection technologies. The research is still on to find the most sensitive Mass spectrometer or detector. W hen Albert E i n s t e i n forged the b e d r o c k t h e o r y of mod- ern physics 100 years ago, he had no computer,nointernet and few homes had telephones. Yet it took one of the most sophisticated sci- ence tools ever built, at a cost of hundreds of millions of dollars, to prove an idea the scientist had crafted with little more than paper, a fountain pen, hard work and a mind sharper than most. Recently physicists announced they had de- tected gravitational waves, hitherto a key unproven element of Ein- stein’s general theory of relativity. It is not always the complicated pro- cess work better but simple tools and process are faster and accurate too. Waters also with same philoso- phy started searching for simple answers for complicated questions. One of the complicated process in analytical industry was handling of Mass detection technologies. The research is still on, to find the most sensitive Mass spectrometer or de- tector. Waters thought differently and focussed on simplifying the usage of the Mass detector tech- nology so that it reaches to masses and today we have world’s smallest, sensitive enough, very robust, and highly user friendly Mass detector – AcquityQDa. The product istrulyan industry changing technology. The idea was to empower and enable chromatog-
  29. 29. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    33 ra- phers with ac- cessible mass data, without the training, without the complex- ity, without extensive compound- specific optimisation. This is realised through the AcquityQDa detector which is now revolutionizing prac- tices within laboratories in India and globally. Within India we have more than 20 companies using the technology in different areas of RD, Quality Control, Drug Discovery etc. The vision of the AcquityQDa was born through the unmet need of the analytical scientists. Today many prestigious scientists and multi-na- tional companies are thrilled with its impact on quality of data. The QDa has been recognized throughout the industry both in India and globally garnering very positive reviews and winning multiple awards for innova- tion. AcquityQDa was listed as one of the top 15 innovative products of the year. Increased efficiency is coming from dramatic innovation. The result of over 30 patented Waters innovations, this the only mass detector that fits on top of your instrument stack. Us- ing less bench space and less energy than a traditional mass spectrometer, it fits easily within your existing lab set up as part of your regular workflow. Even most cleaning and routine mainte- nance have been innovated away, maximizing your uptime. This is fun- damentally different from any expe- rience one would have had with MS. In any analytical development we majorly rely on UV/PDA detector as detector of choice and live with the limitations of same. To have more confidence in data, to understand the development process better and to resolve the complex cases of mass balance we need to have orthogonal analytical detectors like AcquityQDa in our development process. The usage of the detector ensures confi- dence in the data and hence ‘Right time-first time’. The challenges in UV/PDA based developments can be resolved using this orthogonal detector AcquityQDa Mass Detector, which have been pur- posefully designed to enable analysts to readily incorporate mass detection within a UV/PDA chromatographic workflow. The simplicity of this Sin- gle Quadrapole Mass detector is such that it can be handled easily by the chromatographers who have no MS training and are only UV/PDA users. AcquityQDa has the quickest start time, once switched on, the detector is ready to use in less than 25 min- utes. AcquityQDa through Empower CDS software can enable scientists to do tasks like peak tracking, identify- impurities/peaks, analyze non-chro- mophoric impurities, understand- mass-balance related issues, perform MS finger printing, confirm peak pu- rity data, etc. With recent interest of many organi- zations in Biologics and Biopharma- ceuticals, AcquityQDa has emerged to be quite useful in these areas as well. AcquityQDa enables greater selectivity, faster – high throughput methods, and mass confirmation for greater certainty and productivity in routine ‘Glycan monitoring’. AcquityQDa is being utilized by many organizations to monitor pep- tides over a wide molecular weight range. The addition of mass detec- tion allowed scientists to monitor and quantify peptides with greater specificity. AcquityQDa expands the sensitivity currently available with optical only workflows. The addition of AcquityQDa to existing workflows allows scientists to selectively detect and monitor co-elution species. And perhaps most importantly, Acqui- tyQDa works with both TFA and FA based separations. Recent publications like “HILIC-MS Determination of Genotoxic Impu- rity of 2-Chloro-N-(2-Chloroethyl) Ethanamine in the Vortioxetine Manufacturing Process” by Zentiva (Sanofi), “Implemenation of a single quad MS detector in high-through- put transdermal research of plant extracts” by University of Ghent and ‘‘A novel compact mass detection tool for the open access (OA) envi- ronment in drug discovery and early development” by Merck use Acquity- QDa technology and hence exhibiting the potential of this simple and pow- erful tool.  BS
  30. 30. CoverStory 34   BioSpectrum | April - May 2016 | | An MM Activ Publication Exploring new frontiers in biological science using Mass Spectrometry Sharad Mishra Sr. Product Manager, life sciences mass spectrometry, Thermo Fisher ScientificScientists and biologists face many challenges in functional biology studies that require the observation of proteomes over many time points F uture of bioscience through its potential utility in RD where pharmaceutical in- dustries increase in- vestment to achieve discovery of novel compounds. This technology will continue to drive high-throughput screening of candidate molecules together with advances in ‘omics’ technologies (genomics, transcriptomics, pro- teomics, metabolomics) and bio- marker identification. Innovation is shrinking industrial machines and medical devices to the scale of atoms and molecules. Mass spec- trometry is one of the important and versatile tools that will drive the Mass Spectrometry is used in in- dustrial and academic fields for both routine and research purpos- es. Today, there is no single area of experimental science where mass spectroscopy is not being used. It is used to understand the fundamen- tal atomic and molecular processes and, at the same time, those of im- mediate relevance to events within cells. As a technique, it helps to control processes in chemical and biological industries, diagnose dis- eases, discover new drugs, protect the environment and explore mys- teries of nature. Scientists and biologists face many challenges in functional biology studies that require the observa- tion of proteomes over many time points, precise spatial distribution of proteins and different cellular
  31. 31. CoverStory An MM Activ Publication | | April - May 2016 | BioSpectrum    35 states. These issues translated into the analytical challenge of perform- ing reproducible and precise quan- tification of a few selected biological components in the presence of very complex background. One of the major challenges in pro- teomics is the quantification of low abundance proteins and peptides of biological relevance such as tran- scription factors or low stoichiometry post translational modified proteins. The quantification of these analytes of interest is complicated by the very large dynamic range observed for cel- lular protein expression, especially in humans. With the development of new generations of mass spectrom- etry platforms providing high resolu- tion and multiple detector versatility, new strategies are available to push the limits of quantification. This new technology ensures that scientists don’t miss anything in their area of research and provides a strong platform, combining next- generation screening techniques with advanced targeted methods for protein quantitation. It is designed to expand researchers’ capabilities in advanced proteomics and me- This new technology ensures that scientists don’t miss anything in their area of research and provides a strong platform tabolomics applications, including targeted, data-independent acquisi- tion (DIA) and top-down analyses with the industry’s highest level of sensitivity. This delivers more com- plete sequence coverage and allows scientists to perform more inclusive analyses. On January 27, 2016, Thermo Fisher Scientific’s Orbitrap Fusion Lumos Tribrid Mass Spectrometer received the SelectScience Scientists’ Choice Award for Best New Drug Discov- ery Product of 2015. This award cel- ebrates the new technologies that made the biggest impact in drug dis- covery and development research in 2015. The awards are unique in this industry as they empower scientists to nominate and vote for their favor- ite new product, allowing them to have their say about which manufac- turers have truly enabled their work. We’re seeing first hand how Orbi- trap mass spectrometry is driving the future of bioscience, helping scien- tists push the limits of quantitation and protein characterization further and faster. It is ideal for laborato- ries that require more extensive and more profound analytical informa- tion from their sample, especially lower limits of detection and better sequence coverage when characteriz- ing proteoforms, which was not pos- sible with other high-resolution mass spectrometry systems. This technology also enables scien- tists to:  Confidently quantify low-level analytes, low atomic LOQ in nLC analysis and fg in high flow analysis;  Be more selective about which instruments they perform their MS/MS experiments on;  Characterize intact proteins with top down on LC time scale, which means lower detection limits and higher throughput; and  Elucidate structures more thor- oughly and easily by using any fragmentation mode, at any stage of MSn analysis, with detection by either analyzer, which maxi- mizes structural information from metabolites, glycans, PTMs, and sequence polymorphisms.  BS
  32. 32. BioTalk 36   BioSpectrum | April - May 2016 | | An MM Activ Publication C ell Culture Company is a US based Contract Manufacturing Organisation that manufactures automated single-use perfusion bioreactor sys- tems and provide custom manufacturing ser- vices for diagnostic and therapeutic mammalian protein production.Christiaan Engstrom, in an e-mail interview with BioSpectrum Asia, shares his thought on the pros- pects of biologics manufacturing. What are new opportunities in biologics manufacturing for CMOs? A Biosimilars are opening up new opportunities for CMOs as hundreds of drugs have already come off patent and will continue to do so over the next decade or so.This transition has changed the focus of many drug manufacturers back to innovation and has augmented traditional manufacturing facility needs as multi-product facilities trend upwards. Pharma companies are definitely interested in investing in biologics, especially as the patient population is taking a more active interest in their treatment.The population is demanding new, more targeted therapies,which means that large molecule drugs will remain on an upward tra- jectory.Additionally, patients and physicians will be able to choose from multiple commercial sources for drug products,which will add a new element of competition. What are the benefits of single-use technology and is it getting more popular? A As manufacturers look to increase productivity and decrease facility footprint and cost,single-use tech- nologiespresent an easy to implement solution.Whenever a facility is producing multiple products, cross-contami- nation becomes a serious risk.Single use nearly elimi- nates this risk through the disposal of all product contact material.Users can also expand the footprint of their fa- cilities more drastically and rapidly,because of the flexi- ble skids, and eliminate clean-in-place or steam-in-place stainless steel piping—not to mention the tonnesofwaste that come with them. Single-use technologies have already made a huge impact on the way this industry operates over the last decade. Biosimilars are opening up new opportunities Mr Christiaan Engstrom President, Cell Culture Company Interview
  33. 33. BioTalk An MM Activ Publication | | April - May 2016 | BioSpectrum    37 We fully expect that the trend towards multi-product fa- cilities will eventually become a standard,meaning that single-use technologies will continue to be a solution of choice for the industry. Do you have plans to expand customer base in Asia? A Definitely, and, in fact, we already work on certain levels in this market.AtCell Culture Company, our goal is to ensure that customers have a reliable, global partner.Asia is a critical market of focus for us,and one that we look forward to expandinginoverthe next five years. What are the challenges in supply chain and cross-border shipments? A Most biologics are living and highly perishable— unless they are lyophilized—sotimely delivery by couriers is critical to ensure the product is not lost due to improper cold handling. Global distribution of living products further complicates this challenge.The level of cold and supply chain support needs to be exceptional to ensure product viability. Right now, we see that most countries or unions are en- forcing individual established policies, but this is not enough.Webelieve that the industry will continue driving towards harmonisation of global importation to address this critical challenge that has now become industry-wide with the uptick in large molecule drug production. As a new entity, what are the immediate plans of Cell Culture Company? A We see many opportunities for growth, which is why we are launching C3. Our initial focus will be on enhancing and growing our core businesses:our cus- tom GMP contract production BioServices, single-use perfusion bioreactor portfolio,and National Cell Culture Center offerings.Our goal is to leverage our30+years of experience in delivering custom GMP production servic- es from preclinical to commercial stages to the diagnostic,therapeutic and animal healthcare industries. We want to be recognised for being a trusted partner that delivers innovative, high quality products and services that control costs and increase speed to market. What are the factors do you attribute to for the growth of outsourcing industry in biopharma sector? A As the drug industry shifts back to innovation, with a greater focus on large molecule development, manufacturing outsourcing has almost become a neces- sity.Drug makers have to focus their resources on devel- oping the lifesavingtherapies that the market is demand- ing. And, as biologics become more popular, batch sizes have drastically decreased since the days of the block- buster drugs. A traditional, highvolume manufacturing facility no lon- ger retains the same value for many drug manufacturers. And, as technology advances continue to extend the shelf life of biologics, onsite manufacturing becomes even less attractive.There are numerous other advantages to out- sourcing, including decreased risk and cost by removing operators from the equation. Of course, that makes the importance of selecting the right contract manufacturing partner crucial. This is where C3 sees our greatest opportunity—in being an ex- ceptional, long-term instruments and bioservices partner to our customers. How should a CMO ensure the interest of the sponsor companies at the available infrastructure and capacity? A This is an everevolving question as outsourcing be- comes more commonplace.Eventually, it all comes down to having proper documentation and full manufac- turing transparency—not only between partners,but also to meet and exceed the various regulatory expectations. Beyond that, there is such a great element of trust in an outsourcing partnership.The most successful CMOs will have clearly defined supply agreements,including agreedupon transfer methods and details of how the sup- plier plans to deliver exceptional supply chain security. At the end of the day, the value of your product does not matter if your customer cannot get it. There is a great deal of responsibility placed on the CMO to really know their market and act as a guide for the cus- tomer every step of the way.  BS Amrita Tejasvi
  34. 34. BioNews 38   BioSpectrum | April - May 2016 | | An MM Activ Publication Korea’s ImmunoMet raises $5.2 mn Korea-based ImmunoMet Therapeutics, a biotech- nology company developing innovative drugs for the treatment of cancer, has raised $5.2 million in a Se- ries A financing led by Mirae Asset Venture Invest- ments with participation from Aju Tech, GNTech, and MetaVest. ImmunoMet Therapeutics is a development-stage biotechnology company, focused on the development of innovative oncology products.The company’s novel technology is designed to disrupt cancer cell growth and enhance anti-cancer immunity and may be used in a broad range of difficult-to-treat cancers.The com- pany’s lead compound, IM156, for the treatment of glioblastoma (brain cancer) is expected to enter Phase 1 clinical development in the second half of 2016. The primary use of these proceeds will be to fund the company’s research and clinical development pro- grams, establish its worldwide headquarters in Hous- ton and for general corporate purposes. Biovest to spin off CMO business Biovest International has decided to spin off its in- strument and contract manufacturing offerings into a single wholly-owned subsidiary named Cell Culture Company. Cell Culture Company will supply automated single- use perfusion bioreactor systems and custom mam- malian cell and protein manufacturing services to the diagnostic, therapeutic, and animal healthcare indus- tries. Since the late 1990s, Biovest’s primary focus has been the commercialization of personalized immu- notherapies. That work will continue under the Bio- vest name.”The spin-off of Cell Culture Company will ensure that our instrument and CMO customers will be better served through increased focus and invest- ment,” said ChristiaanEngstrom, president, Cell Cul- ture Company President. Medical device firms open to invest on RD: KPMG survey Medical device manufacturers are investing heavily in re- search and development (RD), and are shifting their in- novation strategies from incremental innovation towards achieving breakthrough innovation, according to Global Manufacturing Outlook survey conducted by KPMG. Almost a quarter of all respondents say they spend more than 6 percent of revenueon RD in the last two years, according to a further analysis of a recent KPMG Inter- national Global Manufacturing Outlook 2015 survey.This level of investment and distinct drive for breakthrough innovation is in contrast to the other manufacturers polled in other sectors. In fact, leading medical devices manufacturers are also collaborating with a much broader range of players than before.The report found 80 percent of respondents seek- ing “partnerships rather than in-house efforts” in the pur- suit of innovations. Tan WahYeow, Head of Asia Pacific Healthcare practice at KPMG in Singapore said, “More than other manufac- turing sectors,medical devices have a special stake in in- novation. The nature of the business requires companies to elevate their performance to offer better life-enhancing and life-saving technologies. Medical devices companies need to embrace collabora- tive innovation with a broader range of partners such as suppliers, development partners and healthcare provid- ers to develop product customisation to markets for an ‘in-country, for-country’ business model. Ajay Kumar Sanganeria, Life Sciences Partner at KPMG in Singapore said, “It is imperative that medical device companies, especially smaller, low-cost manufacturers in Singapore develop breakthrough products through col- laboration to stimulate growth and remain competitive in the industry. Compared to larger companies, these com- panies are more adaptable, better able to identify market niches and have more innovative potential.”
  35. 35. BioNews An MM Activ Publication | | April - May 2016 | BioSpectrum    39 China to account for half of Hep B drug sales by 2024 China will remain the largest ma- jor hepatitis B market over the next decade, rising from just under $923 million in 2014 to over $1.4 billion by 2024, representing a Compound An- nual Growth Rate (CAGR) of 4.4%, according to research and consulting firm GlobalData. The company’s report, which cov- ers the eight major markets (8MM) of the US, France, Germany, Italy, Spain, the UK, Japan and China, states that China will continue to dominate the hepatitis B treatment space, as its market share rises from 38.8% in 2014 to 47.2% by 2024. DrDaian Cheng, GlobalData’s Ana- lyst covering Infectious Disease, says this hepatitis B market trend will be largely down to natural popula- tion growth and China’s huge and increasing drug-treated population, which currently makes up 80% of treated cases across the 8MM. Dr Cheng adds: “China’s proportion of treated cases is much higher than its market share because hepatitis B therapeutics cost much less com- pared with other regions.Indeed, it is the sheer increase in the number of drug-treated patients that will drive market growth. “The projected increase of patients alone, nearly 3,00,000 between 2014 and 2024, is much more than the to- tal number of treated patients in the US, which is around 1,00,000. Thus, the increase in therapeutic sales will be considerable and China will hang on to its market dominance, even with lower drug prices.” Despite the relatively high rates of hepatitis B among the Chinese popula- tion, infants are screened for the infec- tion as part of health checks at birth, and at various points throughout their lives, a practice which is mostly orga- nized by schools and employers. APAC’s Alzheimer’s market to surpass $5 bn by 2021 The Asia-Pacific (APAC) Alzheim- er’s disease market will grow from $3 billion in 2014 to $5.1 billion in 2021,representing a robust Com- pound Annual Growth Rate of 7.9%, according to business intelligence provider GBI Research. The company’s latest report states that the main driver of this im- pressive growth,which will oc- cur across the APAC countries of India,China,Australia and Japan,will be rising and aging populations, as Alzheimer’s disease is significantly more prevalent among the elderly. Additional market drivers include bet- ter diagnostic techniques, improving health awareness, special healthcare programs, health insurance coverage, and increasing treatment affordability. MsGayathriKanika, Analyst for GBI Research, says: “An example of healthcare reforms is the Japanese govern- ment’s recently approved plan to increase the number of nurses and care workers in the country’s healthcare sys- tem by 2025,in order to help patients access and inter- pret information about their health, thereby improving knowledge and diagnoses of Alzheimer’s. “Across the APAC region, the expansion of health insur- ance coverage will increase access to healthcare, also leading to a rise in Alzheimer’s diagnosis and higher treatment rates.” In terms of the cur- rent Alzheimer’s pipeline, there are a number of latestage products with the potential to be approved and launched in APAC countries during the forecast period. These include first-in-class Beta-site Amyloid precursor protein Cleaving Enzyme (BACE)1 inhibitors and pas- sive immunotherapies. Bio Classified… Broadcast events and conferences here @ less than $10 per day Reach more than 60,000 readers monthly Contact: Kingshuk Sircar Sales Marketing - APAC Mobile: +65 9272 2676 E-mail: GetNoticed SMS “Bioclassified” to +65 9272 2676
  36. 36. BioNews 40   BioSpectrum | April - May 2016 | | An MM Activ Publication Baxter initiates clinical trial for home hemodialysis system Baxter International has announced the enrollment of the first patient in a US clini- cal trial for VIVIA, an investigational home hemodialysis (HD) system being devel- oped by Baxter and DEKA Research Development Corpo- ration. The trial is designed to study more frequent, extended dura- tion nocturnal home HD therapy (High Dose HD), which will be performed in dialysis facilities as well as the home setting. The study is assessing safety of the product and adequacy of dialysis. The VIVIA investigational home hemodialysis system in- cludes an integrated water purification module, safety sensors and one-button fluid infusion. The investigational system also features SHARESOURCE, Baxter’s two-way connectivity plat- form that allows physicians and nurses to monitor patients’ historical treatment results remotely. Synbiosis introduces the aCOLyte 3 HD high resolution colony counter Synbiosis manufacturer of auto- mated microbiological systems has introduced the aCOLyte 3 HD automated colony counter for microbiologists to quickly and ac- curately count colonies of all sizes and colours. The new aCOLyte 3 HD colony counter, features a high resolution megapixel CCD camera for accu- rate detection of different coloured microbial colonies,even those as small as 0.1mm.The system’s software can analyse pour, spread andspiral plates of up to 90mm, gen- erating full-colour plate images and precise count in seconds.The results can be directly transferred to Excel and other software packages to avoid keying and scanning errors, guar- anteeing accurate GLP compliant reporting and full data traceability every time. “Countinghundreds of micro- bial colonies is time consuming and can generate data that var- ies between different microbi- ologists as it is a tiring and er- ror prone task,”comments Kate George, Divisional Manager at Synbiosis,”we’re confident this new colony counter provides af- fordable automation, which will improve count accuracy, as well as increase productivity in any wa- ter, food or environmental lab that installs an aCOLyte 3 HD.” Gilead’s cancer drug under FDA scrutiny US Food and Drug Administration has raised alarm for Gilead Science’s cancer medicine Zydelig (idelalisib) due to incoming reports of an increased rate of adverse events, including deaths. According to FDA, Gilead Sciences has decided to halt six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lym- phoma and indolent non-Hodgkin lymphomas. Zydelig is currently approved by the FDA for the treatment of relapsed chronic lymphocytic leuke- mia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies; relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies.
  37. 37. BioNews An MM Activ Publication | | April - May 2016 | BioSpectrum    41 Celsion launches cancer drug trial in China Celsion Corporation, a fully-integrat- ed oncology company focused on the development of a portfolio of innova- tive cancer treatments,has launched OPTIMA Study in China. The OPTIMA Study is the company’s global pivotal, double-blind, place- bo-controlled trial, evaluating Ther- moDox, Celsion’s proprietary heat- activated liposomal encapsulation of doxorubicin, in combination with radiofrequency ablation standard- ized to 45 minutes (sRFA) versus sRFA alone to treat newly diagnosed patients with (hepatocellular carci- noma) HCC. The Phase III OPTIMA Study is ex- pected to enroll up to 550 patients globally, and has been successfully enrolling patients at 50 clinical sites in 12 different countries in North America, Europe and Asia Pacific. In December 2015, the company an- nounced that it had received a Clini- cal Trial Application (CTA) approval from the China Food and Drug Ad- ministration (CFDA) to conduct the ongoing Phase III OPTIMA Study at up to 20 additional clinical sites in China. The company aims to enroll more than 200 patients in the Chi- na territory, the minimum number required by the CFDA to file a New Drug Application (NDA), assuming positive clinical results. Pharma Engine gets TFDA nod for pancreatic cancer drug Taiwan based PharmaEngine has receivedTaiwan Food and Drug Ad- ministration (TFDA) approval of the product license of ONIVYDE (irino- tecan liposome injection, nal-IRI). ONIVYDE is indicated, in combina- tion with fluorouracil (5-FU) and leucovorin (LV), for the treatment of patients with metastatic adenocarci- noma of the pancreas after disease progression following gemcitabine- based therapy. There are two steps for the market- ing approval of new drugs in Taiwan. The first step is to assess whether the chemistry, manufacturing and controls,preclinical and clinical data regarding the quality, safety and effi- cacy are sufficient to issue the regula- tory approval letter; and the second step is to assess whether the product labeling and package insert are sup- ported by the new drug application dossiers. Both steps are essential for product sales in the Taiwan market. “We are very grateful that the TFDA accelerated the approval of the prod- uct license in such an expedited man- ner,” said CGrace Yeh, president and CEO of PharmaEngine. “In addition, we highly appreciate our license part- ner, Merrimack Pharmaceuticals for their total support during the review period. Today marks a new era that transforms PharmaEngine from a re- search and development company to a commercial pharma company.” BioAgilytix acquires IPM Biotech BioAgilytix, a leading provider of contract bioanalytical testing ser- vices specializing in large molecule bioanalysis, has announced the ac- quisition of IPM Biotech, a German- based bioanalytical contract research laboratory renowned for its expertise in large molecule bioanalysis, partic- ularly in the area of immunogenicity. The transaction not only expands BioAgilytix’saglobal footprint, with IPM’s newly planned GLP and GMP laboratory facility, but also brings on board IPM’s rich immunogenicity, pharmacokinetics (PK), and pharma- codynamics (PD) expertise to com- plement BioAgilytix’s world-class capabilities in biomarkers, cell-based assays, and immunogenicity phar- macokinetics. Each company has experienced at- tractive organic growth through a strong commitment to scientific qual- ity and attentive customer service.To- gether, they will offer this same rigor of science and service to customers across continents, with expanded capabilities to support all phases of large molecule global studies.
  38. 38. BioNews 42   BioSpectrum | April - May 2016 | | An MM Activ Publication Lupin completes its acquisition of GAVIS Pharmamajor Lupin announced that it has completed its acquisition of pri- vately held US based GAVIS Pharmaceuticalsand Novel Laboratories(GAVIS). Lupin had announced the acquisition on July 23rd 2015. GAVIS brings to Lupin a highly skilled US-based manufacturing and research organization which would complement Lupin’s Coral Springs, Florida, based RD center for Inhalation. GAVIS’s New Jersey based manufacturing facility also becomes Lupin’s first manufacturing site in the US. New Jersey based GAVIS is a privately held company specializing in formu- lation development, manufacturing, packaging, sales, marketing, and dis- tribution of pharmaceuticals products. GAVIS has 62 ANDA filings pending approval with the US FDA and a pipeline of over 65+ products under develop- ment. Seventy two percent of these filings pending approvals represent niche dosage forms with 18 Para IVs and 8 FTFs products.GAVIS’s pending approv- als address a market of over $9 billion. The combined company will have a portfolio of over 120 in-market products, over 185 cumulative filings pending approval and a deep pipeline of products under development for the US. The acquisition creates the 5thlargest pipeline of ANDA filings with the US FDA, addressing a $63.8 billion market. AZ pact with China Medical System for hypertension medicine AstraZeneca announced it has entered into a licensing agreement with China Medical System (CMS) Holdings for the commercialization rights in China to its calcium channel blocker, Plendil (felodipine). Plendil was first approved in China in 1995 for the treatment of hypertension or high blood pressure and in 2015 achieved product sales of $189 million. Under the terms of the agreement,CMS will pay AstraZeneca $310 million for the license to sell Plendil in China.AstraZeneca will maintain a significant, long term interest in the future value derived from Plendil sales in China and will manufacture and supply the medicine to CMS.AstraZeneca will retain the global rights to Plendil outside China.The transaction does not include the transfer of any AstraZeneca employees or facilities. The licensing agreement for Plendil will close at signing and revenue from the agreement will be reported as externalization Revenue in AstraZeneca’s financial statements. The agreement does not impact AstraZeneca’s financial guidance for 2016. AstraZeneca has also entered into an agreement with CMS and its associated company, Tibet Rhodiola Pharmaceutical Holding for the divestment of the global rights to Imdur outside the US. IBM, New York Genome Center to create cancer data repository At White House Precision Medicine Initiative Summit, the New York Ge- nome Center and IBM announced that they are collaborating to create a comprehensive and open repository of genetic data to accelerate cancer research and scale access to preci- sion medicine using cognitive in- sights from IBM Watson. Analyzing this data alongside the medical com- munity’s growing knowledge about cancer could help accelerate the abil- ity of doctors to deliver personalized treatment to individual patients. IBM and New York Genome Center are working together to build the ca- pacity to house the contributed data, train Watson’s cognitive computing capabilities for genomic analysis and enable the Center’s member institu- tions and other research collabora- tors to sequence and analyze DNA and RNA from patients’ tumors. In the first phase of the project, the two organizations will examine genet- ic information from 200 cancer pa- tients to compare how different types of sequencing might impact possible treatment options - examining whole genome and whole exome sequenc- ing as well as clinical panels currently in wide use. Sequencing and clinical data will be fed into Watson to ac- celerate and focus reviews of massive amounts of medical evidence.