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National Medical Research Policy — The United States versus Asia

Posted in Bio Instrumentation in Experimental Life Sciences Research, FDA Regulatory Affairs, Health Economics and Outcomes Research, Human Immune System in Health and in Disease, International Global Work in Pharmaceutical, Medical and Population Genetics, Medical Devices R&D Investment, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Scientist: Career considerations, Statistical Methods for Research Evaluation, Stem Cells for Regenerative Medicine, Technology Transfer: Biotech and Pharmaceutical, tagged China, India, Medical research, National Institutes of Health, National Science Foundation, NIH, South Korea, United States on August 23, 2012| 2 Comments »

Reporter: Aviva Lev-Ari, PhD, RN

Gordon H. Sun, M.D., Jeffrey D. Steinberg, Ph.D., and Reshma Jagsi, M.D., D.Phil.

N Engl J Med 2012; 367:687-690 August 23, 2012

Since the founding of the National Institutes of Health (NIH) and the National Science Foundation (NSF) more than six decades ago, the United States has maintained a preeminent position as a government sponsor of medical research. That primacy is being tested, however, by potent economic challenges. The NIH’s proposed budget for fiscal year 2013 would freeze baseline funding at 2012 levels, continuing a decade-long failure to keep pace with the rising costs of conducting medical research. Across-the-board cuts mandated by the Budget Control Act (BCA) of 2011 will also affect medical research, with the NIH, NSF, and other federal research sponsors sustaining budgetary reductions of about 8% next year.

Cuts to government-funded research will have adverse long-term effects on the health care system and the economy and may irreversibly compromise the work of laboratories long accustomed to receiving stable federal support. Moreover, many medical researchers could transfer their knowledge and resources abroad. In fact, five emerging Asian economic or technological powers — China, India, South Korea, Taiwan, and Singapore — already have medical research policies in place that are filling the void being created by ever more restrictive U.S. funding.

Several U.S.-based economists have justified increasing research budgets on the premise that medical discoveries have intrinsically high economic value. For example, Murphy and Topel have suggested that eliminating deaths related to heart disease had an estimated worth of $48 trillion, and a 1% reduction in cancer-related mortality could save $500 billion.1 Beyond these ambitious goals, however, are more practical arguments favoring support for medical research.

Local and regional economic benefits are one example. A June 2008 analysis by Families USA showed that during the NIH’s fiscal year 2007, nearly $23 billion in grants and contracts supported more than 350,000 jobs, with each dollar generating more than twice as much in direct state economic output in the form of goods and services. The NIH reported that almost 1 million Americans worked in for-profit medical businesses in 2008, earning $84 billion and generating $90 billion in goods and services, reinforcing the importance of preserving the U.S. position as a “knowledge hub” for medical research.2 Nevertheless, BCA cuts next year could result in at least 2500 fewer NIH grants, 33,000 fewer jobs, and a $4.5 billion loss in economic activity.3 Since the NIH’s budget represents less than 1% of overall federal spending, policymakers must reconsider whether shaving 8% from NIH outlays will have a noticeable positive effect on the national deficit or economy.

Fallout from funding cuts could include shifts in the U.S. medical research workforce. In 2000, the National Research Council noted both an overall shortage of medical researchers and inadequate funding for scientists working in the United States, which coincided with a decline in the number of funded NIH grant applications from 31% in fiscal year 2002 to 19% in 2010. This change is particularly critical for postdoctoral researchers, who represent the majority of the U.S. biomedical science workforce. According to the NSF, nearly half the 14,601 new postdoctoral-level researchers who were trained in the United States in 2009 were not U.S. citizens or permanent residents. If U.S. institutions are willing to devote money, training, and infrastructure to support talented, committed researchers, it would be an illogical waste of resources and poor long-term strategy to reduce federal grant mechanisms and wipe out potential job opportunities. Indeed, declining financial support may well encourage medical researchers to seek employment elsewhere.

As compared with the United States, China, India, South Korea, Taiwan, and Singapore have taken a sharply different view of medical research and have developed policies that foster medical research as an engine for economic growth and intellectual innovation (see table Major Government Agencies in Asia and Their Budgets for Medical Research.). Their national budgets are heavily based on scientific research and development, and funding is increasing, with budgetary targets ranging from 2 to 5% of their gross domestic products (GDPs). India’s funding goal for medical research alone is 2% of its GDP.

Increased funding for research infrastructure attracts scientists and organizations interested in high-quality research, including clinical trials. During the past two decades, increasing numbers of clinical trials have moved overseas, where benefits can include decreased costs of doing business, fewer administrative regulations, and greater enrichment of international relationships among researchers. The average annual rate of growth in clinical trials has been highest in China — 47% — while the number conducted in the United States has decreased by an average of 6.5% annually.4 In addition, the increased attention paid to Asia by private firms and other nongovernmental organizations has spurred rapid policy-level responses to concerns about the lack of informed consent, transparency, and other ethical issues, thus further strengthening the appeal of conducting research in the region.

Asian policies reflect a recognition of the extrinsic economic benefits of medical research. China and India have advocated for more government-funded medical research to improve health-related outcomes. China has espoused increased spending as part of achieving xiaokang, a Confucian term meaning a moderately prosperous society. In 2007, India inaugurated its Department of Health Research, which coordinates biomedical science and health-services research programs and translates their findings to address public health concerns. Since the signing of the Korean War Armistice Agreement in 1953, South Korea has leaned heavily on government-funded research to reduce poverty, allowing the country to gradually acquire advanced technologies and expertise. Medical research is part of at least two core technology areas in South Korea’s “577 Initiative”: medical technologies, such as neuroimaging, to address the needs of an aging population and research on issues pertaining to national safety and public health, such as infectious-disease preparedness and food safety.

National research and development programs have been a fundamental component of Taiwan’s economic policy for at least five decades. In 2005, the country began developing “intelligent medical care” — similar to earlier U.S. initiatives — which integrates medical information technology with quality-improvement measures. In Singapore, medical research and economic oversight are administratively linked. For example, the Biomedical Sciences Group of the Economic Development Board supports researchers financially and designs strategies that enhance Singapore’s status as a knowledge center, and the private firm Bio*One Capital invests directly in promising medical technologies.

The diverse strategies outlined above allow Asian countries to systematically recruit medical researchers from both home and abroad. China is particularly proactive in enticing Chinese-born, U.S.-educated researchers to return to their native country by offering generous financial and material incentives under its Knowledge Innovation Program. As the vice president of the Chinese Academy of Sciences stated more than a decade ago, modern “research and development is actually a war for more talented people.”5 In 2000, Singapore jump-started its Biomedical Sciences Initiative to attract medical researchers worldwide with a direct $2 billion investment, as well as with tax incentives for internal biotechnology start-ups and global pharmaceutical firms. In Singapore and India, English is the primary language for scientific communications, which alleviates concerns about language barriers.

For two decades, emerging Asian countries have been designing long-term strategies to reap the benefits of medical research. Meanwhile, the United States is relying on short-term solutions to support its medical research infrastructure, such as those offered by the Patient Protection and Affordable Care Act and the American Recovery and Reinvestment Act. Decreased investment in U.S. medical research could lead to long-term economic damage for the United States and the loss of its stature as a global leader in the field. Powerful incentives that can retain an elite biomedical-research workforce are necessary to strengthen the U.S. health care system and economy.

The views expressed in this article are those of the authors and do not necessarily reflect those of the Robert Wood Johnson Foundation, the Department of Veterans Affairs, or the Agency for Science, Technology, and Research.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

SOURCE INFORMATION

From the Robert Wood Johnson Foundation Clinical Scholars Program (G.H.S., R.J.), the Department of Otolaryngology (G.H.S.), and the Department of Radiation Oncology (R.J.), University of Michigan, and the Health Services Research and Development Service, VA Ann Arbor Healthcare System (G.H.S.) — both in Ann Arbor, MI; and the Singapore Bioimaging Consortium, Agency for Science, Technology, and Research, Singapore (J.D.S.).

http://www.nejm.org/doi/full/10.1056/NEJMp1206643?query=TOC

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Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes

Posted in Aortic Valve: TAVR, TAVI vs Open Heart Surgery, Cardiac & Vascular Repair Tools Subsegment, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, Massachusetts Niche Suppliers and National Leaders, Medical Devices R&D and Inventions, Mitral Valve: Repair and Replacement, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Stents & Tools, Valves & Tools, tagged CE mark, European Union, FDA, Food and Drug Administration, Health Technology Assessment, Medical device, United States on August 9, 2012| 1 Comment »

Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes

Reporter: Aviva Lev-Ari, PhD, RN

Saptarshi Basu, M.P.A., and John C. Hassenplug, M.Sc.

N Engl J Med 2012; 367:485-488 August 9, 2012

The U.S. process for approving innovative, high-risk medical devices has been criticized for taking longer than the European approval process.1 This contention is often used to support the argument that the Food and Drug Administration (FDA) should lower its standards for approving medical devices, since a slow approval process is delaying Americans’ access to innovative and lifesaving technology. But a review of the data, using appropriate end points, suggests instead that it takes the same amount of time or less for patients to gain access to innovative, high-risk medical devices in the United States as it does in the four largest European markets (Germany, France, Italy, and Britain)2 — largely because patient access is generally delayed until reimbursement decisions are made, which often takes substantially longer in Europe than in the United States.

To compare the United States and Europe fairly on this front, three criteria must be considered: the level of device innovation, equivalent start and end points, and patient access as defined by time to reimbursement. First, we focused on innovative, high-risk devices because in the United States such devices require the strongest evidence of clinical benefit and are the subject of most debates about the relative effectiveness of approval processes in different countries. Furthermore, previous studies have shown that lower-risk devices achieve market access in a similar amount of time in the United States and in Europe.

Second, an accurate comparison of time to market access requires measurement of the total time that elapses between application submission and market access. Previous studies have compared the chronologic dates of application submission and market access, but the date an application is submitted varies from country to country.

Third, patient access should be equated with the availability of reimbursement rather than with device approval, because broad patient access to a new device doesn’t occur until reimbursement by a national or third-party payer is available. Previous comparisons of the U.S. and European systems have used the approval date to measure process duration, but innovative, high-risk devices don’t reach a market where most patients can benefit from them immediately after gaining regulatory approval, though they may be accessible to patients who can afford to pay out of pocket. Rather, there is a second level of review through which public or private insurers decide whether and at what price they will pay for a device. Generally, public systems take longer than private insurers to make reimbursement decisions, and significantly more Europeans than Americans have public insurance. Two thirds of the U.S. population is covered by private health insurance, whereas only a fifth receives publicly funded reimbursement, primarily administered by the Centers for Medicare and Medicaid Services (CMS).

For both private and public systems in the United States, the pathway to patient access to a device starts with the submission of an application to the FDA. The FDA reviews innovative, high-risk devices for safety and effectiveness (clinical benefit) under the premarket approval (PMA) process, and information on the duration of reviews is publicly available. In fiscal year 2011, the FDA approved 40 applications for PMA. The average review time was 13.1 months, with 8.4 months attributed to FDA review time, and 4.7 months to the time the agency waits for the sponsor to address deficiencies in the application (“sponsor time”).3 CMS provides reimbursement for the majority of devices when they earn FDA approval. For a limited number of devices each year, however, CMS conducts a national coverage determination in response to external requests for validation or for devices that have limited or conflicting evidence of clinical benefit. This process averaged 8.6 months over the past 5 fiscal years.4 Although it is difficult to obtain data on how long private insurers take to make coverage decisions, anecdotal information from private insurers suggests that decisions are made within a few weeks to a few months after FDA approval, depending on the amount and quality of evidence of clinical benefit.

In Europe, by contrast, most of the 27 member countries of the European Union (EU) have publicly financed health care systems; such systems cover approximately four fifths of the populations of the four largest device markets. All EU countries require devices to first obtain a Conformité Européenne (CE) marking, which refers to a symbol shown on products that indicates market approval throughout the EU. The CE marking process is conducted by for-profit, third-party “notified bodies” that have been accredited by a member country to assess device safety and performance but do not evaluate effectiveness (which requires more clinical data). Although publicly available data are limited, anecdotal information from notified bodies suggests that the process takes 1 to 3 months, excluding sponsor time.

Most European patients do not have access to innovative, high-risk devices as soon as the devices receive a CE marking. Each country must first make a decision about reimbursement, a process that varies substantially among countries.5 Though a CE marking can be granted on the basis of fewer clinical data than are required for FDA approval, European standards for reimbursement are often similar to or higher than those that the FDA imposes for device approval. European countries may require additional data on the device’s safety and effectiveness, as well as on cost-effectiveness.

In France, a centralized body makes reimbursement decisions after assessing the safety and effectiveness of individual devices. Reimbursement decisions in Italy are devolved to the various regions, and Britain and Germany conduct broader assessments of device types or procedures, rather than of individual devices. Typically, innovative devices not covered under an existing diagnosis-related group (DRG) require review under the lengthier Health Technology Assessment process, which assesses safety, clinical benefit, and cost-effectiveness. Government-provided information on time to reimbursement varies by country. Estimated time frames are an average of 71.3 months in Germany, a range of 36.0 to 48.0 months in France, a range of 16.4 to 26.3 months in Italy, and an estimated 18 months in Britain.

Using this information, we determined that the time it takes to bring innovative, high-risk devices to patients in the United States is similar to or shorter than that in the top four European markets (seefigure Comparison of Time to Market in Premarket Approval and Reimbursement Processes.). The public (CMS) process in the United States takes approximately as long as those in Italy and Britain, approximately half as long as that in France, and less than a third as long as that in Germany. The difference in time to market access is even greater when it comes to private insurers (covering the majority of the U.S. population), which often make reimbursement decisions within a few months after FDA approval.

To further illustrate this point, we compared the time to approval for five innovative, high-risk medical devices available in France, Italy, and the United States (see table Comparison of Time to Market Access for Five Innovative Devices in France, Italy, and the United States.). These case studies indicate that the average time to market access for these devices was 26.3 months in France, 30.8 months in Italy, and 15.3 months in the United States.

These numbers may not fully capture the reasons why a device reaches the market more quickly in one country than in another and do not reflect experiences with all innovative, high-risk devices. However, unless one uses equivalent standards in terms of the level of risk, the start and end points of the process, and the key end point of market access, accurate comparisons cannot be made.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on August 1, 2012, at NEJM.org.

SOURCE INFORMATION

From the Office of Planning, Office of the Commissioner, Food and Drug Administration, White Oak, MD.

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International Conference and Exhibition on Biowaivers and Biosimilars, September 10-12, 2012

Reporter: Aviva Lev-Ari, PhD, RN

“A Synergistic Approach towards Biowaivers & Biosimilars”. Biosimilars-2012 is scheduled on September 10-12, 2012 at Hilton San Antonio Airport, USA.

http://www.omicsonline.org/biosimilars2012/pdfs/Biosimilars-2012_Tentative_Program.pdf

Biosimilars or Follow-on biologics

http://en.wikipedia.org/wiki/Biologic_medical_product are terms used to describe officially-approved subsequent versions of innovator biopharmaceutical http://en.wikipedia.org/wiki/Biopharmaceutical products made by a different sponsor following patent and exclusivity expiry on the innovator product.[1] http://en.wikipedia.org/wiki/Biosimilar#cite_note-biosimilars2012-0 Biosimilars are also referred to as subsequent entry biologics (SEBs) in Canada.[2] http://en.wikipedia.org/wiki/Biosimilar#cite_note-1 Reference to the innovator product is an integral component of the approval.

A Biowaiver is a waiver (exemption) of clinical bioequivalence studies given to a drug product.

Biowaivers and Biosimilars.

The main theme of the conference is “A Synergistic Approach towards Biowaivers & Biosimilars”.

Biosimilars-2012 is scheduled on September 10-12, 2012 at Hilton San Antonio Airport, USA.

Click here to view the downloadable Preliminary Program

http://sm1.mailserv.in/omicsonlinebiz/lt.php?id=eR4DBVEEUA9UUksGBlMKAU4=UQMNDAgNSllRVQgECyUNWAodUg5C

This three day conference will cover the latest trends and challenges in Biowaivers and Biosimilars. Biosimilars-2012 highlights the following topics:

Biosimilars Pathway
Immunogenicity
Skill Set for Biosimilars Development
Biosimilar Therapeutics
Biomedical informatics
BCS and IVIVC based biowaivers
Transgenic animals & plants
In vitro & In vivo Correlations
Bioequivalence Testing
BCS and IVIVC based biowaivers
Oral drug delivery

Conference assets are William Velander (University of Nebraska, USA), Lisa J. Murray (Absorption Systems, PA, USA), Leandro Mieravilla (Biosimilar-Biotech Global Expert, Canada) and David Goodall (Paraytec Limited, UK) who will discuss their novel research on Biosimilars & Biowaivers.

This conference is perfect for researchers and experts, as well as those who require in-depth analysis of the latest trends, technologies, and techniques.

Confirmed Speakers Including

Tentative Scientific Program18:00-19:00Registrations Sep-09-2012

Day 1

Sep-10-2012

07:00-08:00 Registrations

08:00-08:30 Breakfast

Breakout 1

08:30-09:00 Opening Ceremony

Keynote Forum

09:00-09:05 Introduction

09:05-09:30 Lisa J. Murray, Absorption Systems, USA

09:30-09:55 Yet to be Confirmed

09:55-10:20 Yet to be Confirmed

10:20-10:45 Yet to be Confirmed

Coffee Break 10:45-11:00

Track 1: Biosimilars : Innovator Pharmaceutical Products

Track 2: Biosimilars: Regulatory Approach

Session Introduction

11:00-11:20

Title: The role of scientific justification in the nascent us biosimilars approval pathway

Ben Kaspar, MMS Holdings Inc., USA

11:20-11:40

Title: The what million dollar question: Patent litigation and strategy under the biologics

price Competition and Innovation act

Bryan J. Vogel, Robins, Kaplan, Miller & Ciresi L.L.P., USA

11:40-12:00

Title: The role of patents in biosimilars and biobetters

Brian Dorn, Barnes & Thornburg LLP, USA

12:00-12:20

Title: New patent reform litigation options for biosimilars

Paul A. Calvo, Sterne, Kessler, Goldstein & Fox P.L.L.C., USA

12:20-12:40 Title: Regulatory consideration of the assessment of biosimilar products

Jun Wang, Duke University School of Medicine, USA

Lunch Break 12:40-13:20

13:20-13:40

Title: What hath FDA wrought: The February 2012 guidance and their implications for

securing biosimilar approval

Michal Swit, Duane Morris LLP, USA

13:40-14:00

Title: The role of clinical trials in demonstrating similarity of biological medicinal

products in the European Union

Cecil Nick, PARAXEL Consulting, UK

14:00-14:20

Title: Biosimilars panel: Opportunities and challenges to be overcome in the near term

Jennifer Brice, Frost & Sullivan, UK

14:20-14:40

Title: Graphical representation of the assessment of inventive step for patents using the

Problem-Solution-Approach (PSA)

Joachim Stellmach, European Patent Office, Germany

14:40-15:00

Title: IP strategies for the biosimilar arena

Ulrich Storz, Michalski Huettermann Patent Attorneys, Germany

15:00-15:20

Title: Biosimilars in emerging countries: Argentina

Gustavo Helguera, University of Buenos Aires, Argentina

15:20-15:40

Title: Developing biosimilars: Considerations, opportunities and challenges

Ming Wang, Gan & Lee Pharmaceuticals, China

Panel Discussion 15:40-15:55

Coffee Break 15:55-16:10

Track 3: Skill Set for Biosimilars Development

Track 4: Clinical Studies for Biosimilars

Session Introduction

16:10-16:30

Title: Strategies for development and validation of immunogenicity assays to support

preclinical and clinical biosimilar programs

Kelly S. Colletti, Charles River Preclinical Services, USA

16:30-16:50

Title: Transgenic blood proteins: An abundant source for next generation therapies with

worldwide availability

William Velander, University of Nebraska, USA

16:50-17:10

Title: The Danish HNPCC-system – Biomedical support to individual health care in

hereditary colon cancer families

Inge Thomsen Bernstein, Hvidovre University Hospital, Denmark

17:10-17:30

Title: Use of human protein transgenic animal models for immunogenicity testing and

their value for comparative studies of biosimilars

Melody Sauerborn, TNO Triskelion BV, The Netherlands

17:30-17:50

Title: Application of nanotechnology in drug delivery

Rawia Khalil, National Research Centre, Egypt

Panel Discussion 17:50-18:05

18:05-19:05 Cocktails: Sponsored by Journal of Bioequivalence & Bioavailability

Day 2

Sep-11-2012

Breakout 1

Track 5: Biosimilars Therapeutics

Track 6: Commercialization or Globalization of Biosimilars

Session Introduction

09:30-09:50

Title: Development of antibody arrays for measuring biosimilar conformational

comparability at molecular level

Xing Wang, Array Bridge Inc., USA

09:50-10:20

Title: Biosimilar market overview, present and future

Leandro Mieravilla, Biosimilar-Biotech Global Expert, Canada

10:20-10:40

Title: Modified biosimilars: Potential role in the emerging global biosimilar market

Pascal Bailon, Bailon Consultants, USA

Coffee Break 10:40-10:55

10:55-11:15

Title: The application of releasable pegylation linkers to improve the pharmaceutical

properties of biosimilars and biobetters

Hong Zhao, Enzon Pharmaceuticals, USA

11:15-11:35

Title: The clinical development of monoclonal biosimilars

Cecil Nick, PARAXEL Consulting, UK

11:35-11:55

Title: Ghrelin antagonist: Advantages and side-effects

Maria Vlasova, University of Eastern Finland, Finland

11:55-12:15

Title: Biosimilar market growth trends in emerging markets

Syamala Ariyanchira, Independent Consultant, Malaysia

12:15-12:35

Title: Developing of long acting glycoprotein hormones using gene fusion and gene

transfer: From bench to clinics

Fuad Fares, University of Haifa, Israel

Lunch Break 12:35-13:15

13:15-13:35

Title: Th1 immune response induced by Ipr1-PPE68 DNA vaccine in BALB/C mice model

Yang Chun, Chongqing Medical University, China

13:35-13:55

Title: Anticancer noscapinoids: Synthesis to nanomedicine

Ramesh Chandra, University of Delhi, India

Panel Discussion 13:55-14:10

Track 7: Plant Produ ced Biosimilar Products

Track 8: Aggregation and Immunogenicity of Biosimilars

Session Introduction

14:10-14:30

Title: Biosimilars: Lessons learned from development to commercial launch

Niranjan M. Kumar, ABS Inc. USA

14:30-14:50

Title: Plant-based production and preclinical analysis of biosimilar Trastuzumab

Michael D. McLean, PlantForm Corporation, Canada

Coffee Break 14:50-15:05

15:05-15:25

Title: Immunological aspects of formation of anti-drug antibodies against aggregated

protein drugs

Melody Sauerborn, TNO Triskelion BV, The Netherlands

15:25-15:45 Speech Opportunity Available

15:45-16:05 Speech Opportunity Available

Panel Discussion 16:05-16:20

Breakout 2

16:20-19:20

Editorial Board Meeting

Poster Presentations

Scientific Partnering

Cocktails: Sponsored by Pharmaceutica Analytica Acta

Day 3

Sep-12-2012

Breakout 1

Track 9: Biowaivers

Track 10: BCS & IVIVC Based Biowaivers

Track 11: Bioequivalence Assessment

Track 12: Analytical Strategies

Session Introduction

09:30-09:50

Title: Role of process controls in mitigating the risk associated with manufacturing of

biosimilars

Indu S. Javeri, CuriRx Inc., USA

09:50-10:20

Title: Current analytical techniques for analysis of carbohydrate containing biosimilars

Parastoo Azadi, University of Georgia, USA

10:20-10:40

Title: Improving outcomes: A decade of industry and regulatory experience with BCS

based biowaivers

Lisa J. Murray, Absorption Systems, USA

Coffee Break 10:40-10:55

10:55-11:15

Title: Approach for development of w-3 phospholipid dietary supplement to potential lipid

drug

Su Chen, Chainon Neurotrophin Biotechnology Inc., USA

11:15-11:35

Title: Bioanalytical challenges in development of biosimilars

Carmine Lanni, Bioanalytical Development Services, USA

11:35-11:55

Title: Some statistical issues on the evaluation of the similarity and interchangeability of

biologics

Laszlo Endrenyi, University of Toronto, Canada

11:55-12:15

Title: Rapid characterization of formulations: Protein size, aggregate levels and viscosity

David Goodall, Paraytec Limited, UK

12:15-12:35

Title: Taylor dispersion analysis, a rapid, nanolitre method to monitor protein aggregation

behavior

Wendy Louise Hulse, University of Bradford, UK

Lunch Break 12:35-13:15

13:15-13:35

Title: Effects of drying technology and polymers on integrity and biological activity of

proteins

Amal Ali Elkordy, University of Sunderland, UK

13:35-13:55

Title: A global perspective on the challenges of GLP/GCLP-bioanalysis for biosimilars

Aparna Kasinath, Clinigene International Limited, India

13:55-14:15 Speech Opportunity Available

14:15-14:35 Speech Opportunity Available

14:35-14:55 Speech Opportunity Available

14:55-15:15 Speech Opportunity Available

Panel Discussion 15:15-15:30

Editorial Board Meeting

For Biosimilars-2012 Organizing Committee

OMICS Group Conferences
5716 Corsa Ave., Suite110
Westlake, Los Angeles
CA91362-7354, USA
Phone:+1-650-268-9744 <tel:%2B1-650-268-9744>
Fax:+1-650-618-1414 <tel:%2B1-650-618-1414>
Email: biosimilars2012@omicsgroup.com <mailto:biosimilars2012@omicsgroup.com>

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Introducing Career Streams into Academic Research

Posted in International Global Work in Pharmaceutical, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Scientist: Career considerations, Statistical Methods for Research Evaluation, Technology Transfer: Biotech and Pharmaceutical, tagged Canada, Canadian Institutes of Health Research, Harvard Medical School, Job Market for Life Scientists, National Institutes of Health, NIH, Postdoctoral research, United States on August 1, 2012| 3 Comments »

Reporter: Aviva Lev-Ari, PhD, RN

The information below is posted on our Scientific Web Site in solidarity with all the Young Life Sciences Scientists in the US, Canada and around the Globe regarding the discrepancy in the marketplace between high supply of highly qualified young scientists and the low demand for their talent by Academia and by the Pharmaceutical and Biotech Industries as evidenced by few jobs for that valuable talent.

The matter has been address by the NIH and was reported in my post on June 27, 2012

Picturing US-Trained PhDs’ Paths and Pharmaceutical Industry’s Crisis of Productivity: Partnerships between Industry and Academia

http://pharmaceuticalintelligence.com/2012/06/27/picturing-us-trained-phds-paths-pharmaceutical-industrys-crisis-of-productivity-partnerships-between-industry-and-academia/

Related matters on that subject are addressed in the following Posts by Dr. Jonathan Thon

Dr. Thon holds joint appointments within the hematology division at Brigham and Women’s Hospital, and Harvard Medical School in Boston, and is an American Society of Hematology Scholar.

The truly bleak job prospects for young scientists in the life sciences

Posted on July 30, 2012 by Jonathan Thon

The following is my response to a letter from Canada’s federal minister of health, Leona Aglukkaq, who was in turn responding to an earlier letter from me:

Honourable Leona Aglukkaq,

Thank you first and foremost for taking the time to respond to my letter on February 7, 2012, regarding the lack of opportunity for early-career scientists in Canada (see the health minister’s response here). While the Canadian Institutes of Health Research (CIHR) is taking positive steps to meet its stated goals of attracting and retaining the best researchers, the Canadian government is failing to acknowledge how truly bleak the job prospects for young scientists are in the life sciences. While resources will always be limiting, the government needs to appreciate that current federal investment in biomedical science is insufficient to maintain the present rate of scientific advancement and falls short of supporting a sustainable pipeline of talented new health researchers. What’s more, this country’s overabundance of PhDs has kept postdoctoral salaries at a rate of $38,000 per year, which is shockingly low when one considers that a four-year undergraduate degree and five-year graduate program are required to fill the role. Worse still, it has extended postdoctoral fellowships (considered neither “student” nor “faculty” positions in Canada) to between four and eight years, creating a temporary “holding pattern” from which most young scientists ultimately transition to other careers.

If Canada is not prepared to make the necessary investment in academic biomedical research, universities must not be permitted to continue to push PhD students and postdoctoral fellows through the present system blindly, with complete disregard to the lack of academic career opportunities that await them. By failing to adapt to current labour market trends, the Canadian people are investing a significant amount of time and money into training highly-educated life scientists to take up positions that simply do not exist, forcing them into under-employment in the private sector. Not only does this represent a terrible return on investment, but it is stunting economic growth. The number of graduate students being trained for academic science positions that 80 percent of them will never fill needs to decrease significantly and the focus needs to shift from academic professorships to alternative professions as support scientists and consultants in neighbouring industries including medicine, finance, teaching and law.

Recently, both the U.S. National Academies and the National Institutes of Health’s Biomedical Workforce issued reports exhorting universities to “improve the capacity of graduate programs to attract talented students by addressing issues such as attrition rates, time-to-degree, funding, and alignment with both student career opportunities and national interests.” To accomplish this, the U.S. National Academies recommend that institutions “restructure doctoral education to […] shorten time-to-degree and strengthen the preparation of graduates for careers both in and beyond the academy.” The NIH concurred, citing the need to “involve relevant employers in the public and private sector in designing and training paths for students.” Among the reforms called for are:

Information and guidance about career opportunities and training in skills relevant to non-academic jobs to be provided to all graduate students and post-doctoral fellows on fellowships or principal investigator grants as normal parts of their programs.
Limitations to the period any individual can spend as a graduate student of post-doctoral fellow, which must be covered in its entirety under “any combination of training grants, fellowships and research project grants.”
Increasing the proportion of graduate students and post-doctoral fellows that receive support through fellowships and training grants versus faculty research grants, to shift the focus from the principal investigators’ labour needs to young scientists’ professional development. The report emphasizes that the overall number of young scientists supported should not increase.
Institutional tracking over time of career outcomes for all their graduate students and post-doctoral fellows, which should be made publicly available.

The last two recommendations are perhaps the most important and I have separated them here for added emphasis.

To improve career opportunities and limit the overproduction of transient trainees, labs should replace many of their post-doctoral fellow slots with permanent staff scientist positions.
Post-doctoral pay and benefits must improve. The Biomedical Workforce proposes implementing a starting salary of $42,000 (which I still consider to be a discouraging return on the increasingly lengthening 5-year investment necessary to earn a PhD), with a “large jump between [post-doctoral] years 3 and 4” intended “to incentivize principal investigators to move fellows to permanent positions.” Given the current state of academic science, the Biomedical Workforce felt it necessary to add that “all NIH-supported postdoctoral researchers on any form of support (training grants, fellowships, or research project grants) [should] receive benefits that are comparable to other employees at the institution,” including paid vacation, parental leave, healthcare, and retirement plans.

The government of Canada has done little to acknowledge and less to address the current overabundance of highly-trained young PhD scientists in low-paying dead-end jobs whose expertise will ultimately (after a significant period of re-training) be better served in other industries. While the CIHR’s efforts to improve current funding practices are necessary, they will not prove sufficient to resolve this issue. The current approach to training scientists and moving them through the labour force is frighteningly inefficient. Training more research scientists than we have the funds to support is not the solution – it is the problem. Acknowledging that we are facing a crisis and implementing the aforementioned recommendations will dramatically improve working conditions for young scientists while curbing inefficiencies in our labour market that are serving to limit economic growth.

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A response from the health minister on the lack of opportunity for early-career scientists

Posted on July 16, 2012 by Jonathan Thon

In a concerted effort to practice what I preach, I write often to the Office of the Prime Minister to highlight issues facing early-career scientists in Canada. To their credit, I always receive a response. Below is a transcript of the most recent letter I received from the Minister of Health, Leona Aglukkaq. Please see ‘Bring home the scientific troops’ to review previous transcripts.

Dear Dr. Thon:

The office of the Prime Minister has forwarded to me a copy of your correspondence of February 7, 2012, concerning opportunities for young scientists in Canada.

The Canadian Institutes of Health Research (CIHR) recognizes the role that new and early career investigators play in creating a sustainable foundation for Canadian health research. In its second strategic plan entitled Health Research Roadmap: Creating innovative research for better health and health care, the CIHR stated its intention to build capacity to attract and retain the best researchers by working with partners at all levels, including teaching hospitals, other federal funding agencies and federal departments. This will involve, among other things, ensuring that sufficient operational support is provided by rectifying the inconsistencies in postdoctoral funding and reviewing the level and form of financial assistance provided.

As part of the CIHR’s commitment to ensuring the long-term sustainability of its contribution to the Canadian health research enterprise, the CIHR has also initiated a process to design a new open suite of programs and peer review system. The new design responds to concerns such as yours from the health community that we need to be providing more support for new and early career investigators.

In the new open suite of programs, the CIHR is considering specific support to new and early career investigators with excellent training and early career productivity to ensure that these researchers have an opportunity to build promising programs of research and knowledge translation. In a new scheme that focuses on projects, the CIHR is considering giving priority in the first stage of review to the quality of the idea with limited information about the track record of the applicant. This would remove some of the biases or barriers (real or perceived) for new and early career investigators.

The CIHR’s direct training programs are not changing as part of this process and will continue to be a part of the CIHR’s strategy to support a sustainable pipeline of talented new health researchers into the health research enterprise.

It should also be noted that the CIHR’s Strategy for Patient Oriented Research also has a focus on developing the talent pool for clinical research in Canada. You can follow the development of this important strategy on their website athttp://www.cihr-irsc.gc.ca.

With regard to your concern about the low levels of successful applications in the CIHR’s Open Operating Grants Program, it should be noted that in February 2008, the CIHR pledged to create and maintain a stable Open Operating Grant Program. This included a commitment to fund at least 400 new grants per competition (800 per year). This commitment will be maintained with the new program structure.

The CIHR currently funds some 14,000 researchers and trainees. In designing the new funding program, the CIHR’s intent is to continue supporting a similar number of investigators and trainees. Furthermore, the CIHR is committed to ensuring that approximately 70 percent of the grants and awards budget continues to be allocated to support investigator-initiated research.

I appreciate having had this opportunity to respond to your concerns.

Sincerely

Leona Aglukkaq

c.c. Office of the Prime Minister

I will be responding to Ms. Aglukkaq’s letter in my following post – and I encourage you to do the same. You can contact the Honourable Leona Aglukkaq at:

House of Commons
458 Confederation Building
Ottawa, Ontario
K1A 0A6

Tel: (613) 992-2848
Fax: (613) 996-9764
Email: Leona.Aglukkaq@parl.gc.ca

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The research bottleneck – flying blind

Posted on June 25, 2012 by Jonathan Thon

The Bridges to Independence report (NRC, 2005) reveals that the number of PhD-trained life scientists in the United States ages 35 and younger increased by 59 percent between 1993 and 2001 while the number of these scientists in tenure-track positions increased by only 7 percent. At research institutions this number decreased by 12 percent over the same period of time. Studies by Michael S. Teitelbaum (Research funding: structural disequilibria in biomedical research. Science 321, 644-645. 2008) and Cyranoski, D. et al. (The PhD factory: the world is producing more PhDs than ever before. Is it time to stop? Nature 472, 276-279. 2011) support these observations and show that the supply-demand gap continues to grow.

Studies from the National Association of Teachers in Further and Higher Education, the British university and college lecturer’s union, and the BETT Report, published in June 1999 by the Independent Review of Higher Education, Pay and Conditions, paint a similar picture for scientists in the United Kingdom and suggest a similar situation worldwide. With limited employment opportunities in academia as it is (Improving graduate education to support a branching career pipeline: Recommendations based on a survey of doctoral students in the basic biomedical sciences. 2011.), this statistic reflects a bad situation only getting worse.

To better assess the magnitude of this problem and compel academic institutions to address it, I suggest federal departments require universities to submit a detailed account of the placement histories of their recent graduates, which should be made available freely online. Another statistic worth tracking is the percentage of graduate students or research fellows training under principal investigators that now support independent research programs of their own. Comparing these figures to research investment practices that have traditionally focused on graduate and postdoctoral funding while avoiding the larger issue of subsequent employment should let us measure the effect these policies have on the knowledge market and provide the impetus to change them. At the very least, it would let prospective scientists know what they were getting into.

Because I am not the first to suggest that dissatisfaction later in their career has less cogency if students investing in a bioscience research career when they choose graduate training are made aware of the risks pursuant, a recent NRC Committee on Trends in the Early Career Patterns of Life Scientists recommended in 1998 “that accurate and up-to-date information on career prospects … and career outcome information … be made widely available to students and faculty. Every life science department receiving federal funding for research training should be required to provide its prospective graduate students specific information regarding all pre-doctoral students enrolled in the graduate program during the preceding 10 years.”

While this is a clear step in the right direction, a recent survey of 10 leading biology departments (experimental group) and professional schools (control group) in the United States concerning the information available to students considering a career in the biosciences showed striking differences between the two groups (Careers and Rewards in Bio Sciences: the disconnect between scientific progress and career progression). As a rule, biology departments had information about time to degree and percentage of matriculating students who obtained their PhD, but not about job placement. No biology department had a job placement adviser, although career counseling offices at some universities did try to help students leaving academic science find non-academic jobs.

By contrast, all of the professional schools – law, business, medical – tracked the salary and position of their graduates through Student Affairs or Career Services Offices. More often than not this information was advertised on school websites. The inaccessibility of specific information regarding pre-doctoral biosciences students enrolled in graduate programs over the last 10 years means that federal funding agencies regulating scientific development and growth are unequivocally flying blind.

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Introducing career streams into academic research

Posted on June 4, 2012 by Jonathan Thon

In the 1990s the typical PhD in biological sciences entered the job market in their mid 30s, after spending approximately 3.8 years as a postdoctoral fellow (National Academy of Science, Enhancing the Postdoctoral Experience for Scientists and Engineers). This is 3.6 years longer than it was in 1970 (National Research Council, Trends in the Early Careers of Life Scientists) and roughly 10 years shorter than what it is today.

It is not surprising then that so few PhDs continue into academic positions after receiving their graduate degree. A major failing of our graduate school system is that despite their program choices both Master’s and doctoral students are exclusively trained to become academic investigators. This is a problem when only 20 percent of doctoral students will ultimately become professors and the average age of independence in academic research is now in the mid-40s (A deeper look into the 80 percent of PhDs who do not become professors, and A new era of science funding – Part 4: Speaking up in support of federally funded research). Meanwhile, industries such as biotechnology, drug development, policy development, and scientific writing (amongst others) employ the remainder.

Indeed, a recent study by Fuhrmann et al. have found that at the University of California, San Francisco, nearly one-third of students midway through their graduate training intend to pursue a non-research career path (Improving graduate education to support a branching career pipeline: Recommendations based on a survey of doctoral students in the basic biomedical sciences. 2011. In other words, we are training our graduate students to excel at professions they will never hold. To support the growing number of research PhDs universities are graduating yearly for which faculty positions are not available, we have extended the duration of the postdoctoral research fellowship position. Originally intended to allow for furthering expertise in a specialist subject, acquiring new skills and methods, and developing one’s ability to run an independent research program by apprenticing under an established professor, this has become a repository of misallocated talent that delay a scientist’s entry into their first “real” jobs by more than five years (Careers for Postdoctoral Scientists: The Ever-Aging Postdoc).

For the majority of scientists that are forced to transition into other industries, the postdoctoral fellow stage represents a significant waste of time that does not adequately prepare them for the career they will ultimately elect – and yet, because of the enormous number of postdoctoral fellows feeding into these professions, it has become a prerequisite for most of these positions. As with any new profession, employment in an altogether different field carries with it its own learning curve, further delaying the career advancement of the scientist.

A significant departure from the current trend of expanding the supply of research scientists without evidence of imminent shortages in either the private or academic sectors is necessary (Supply Without Demand), and could be addressed by implementing career streams at the graduate and postdoctorate levels. While this is not a new idea (Elizabeth Marincola and Frank Solomon. The career structure in biomedical research: Implications for training and trainees, The American Society for Cell Biology on the State of the Profession. Molecular Biology of the Cell. 9:3003-3006. 1998), research institutions such as Harvard are increasingly deciding to go the other way, creating additional temporary, non-tenure-track Instructor and Research Associate positions that are in every way equivalent to a postdoctoral research fellow designation and meant to follow postdoctoral training.

In my next post I will tell you why this is a problem.

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A call to arms

Posted on May 17, 2012 by Jonathan Thon

Scientific research is a marathon, and if we fall behind now, while we are leaders in health innovation, the cost of recovering our position, in light of emerging economies with which we compete, will become progressively more expensive. Sustained increases in National Institutes of Health and Canadian Institutes of Health Research funding are critical to maintain North America’s innovation engines at a crucial time for research and the economy, and most importantly to improve the health and well-being of our populations.

Now is the time for scientists to advocate most strongly for national investment in biomedical research. Members of Parliament, Members of Provincial Parliament and Members of the Legislative Assembly in Canada, as well as senators and congresspersons in the United States are the decision-makers you elect to represent you – write to them. You can go to http://www.canada.gc.ca/directories-repertoires/direct-eng.html and enter your postal code (in Canada), orhttp://www.house.gov and enter your zip code (in the United States) to access your representative.

Things to remember when composing your letter:

Identify yourself as a constituent and a member of the scientific community
Ask that the legislator support sustainable funding priorities for your federal funding agency.
Briefly explain why these issues are important to you.
Acknowledge the efforts that are being made by their party
Give them your contact information and ask to be informed about the actions their office takes in response to your request.

Letters need to be kept simple and as personal as possible, with tangible examples of actions MPs, MPPs, and MLAs can take to change the landscape of how biomedical research is supported in Canada. These should be provided to the legislator in the form of a one-page cheat-sheet with your contact information included for reference. If dealing with your senator or congressperson in the United States you will need to ask to speak/meet with your representative’s health legislative assistant who handles health care issues in the district or state.

Giving opposition members speaking points against current government policies, emphasizing the economic relevance/importance of your position, and holding legislators accountable for providing examples of and justifying actions they have taken on their own promises are all good ways of having your opinions considered. After the meeting it is important to follow up with your representative within the week, whether or not the representative was supportive of your position. This is your chance to remind them of what you discussed and further emphasize the importance of their involvement on this issue.

Canada-specific:

Major research funding in Canada is done federally, but provinces are responsible for health spending and many provinces (e.g.: BC, Ontario, Quebec) have contributed to major infrastructure projects.

U.S.-specific:

States often put aside money for research into targeted areas (e.g. California’s support of stem cell research) and are generally more independent than Canadian provinces.
Many federal representatives will have specific assistants/aides for health related issues -ask to speak/meet with them

Example speaking points:

Low funding rates (NSERC PDFs, CIHR operating grants, etc.)
Low postdoctoral fellow salaries compared to other countries
Plus, 4 or 5 more good statistics that show why basic health research is a good investment or is currently underinvested.

While the argument for the government to prioritize an industry where the number of clinical advances, drug developments and cures is proportional to total research investment is not a difficult case to make – it needs to be made. I and others at The Black Hole continue to work at concentrating and contextualizing some of the more important issues facing early career scientists in Canada and abroad.

Take advantage of this resource and use hard numbers to emphasize your points. Addressing these concerns forces the issue to light, and commits politicians to publicly defensible positions for which they can subsequently be held accountable. Government agencies cannot lobby for themselves and policy makers do not share your unique perspective. Our health, economy, and the future of scientific progress are at stake, so step up and speak out.

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Show me the money!

Posted on May 4, 2012 by Jonathan Thon

It falls to scientists to speak up in support of federally funding research and in this third installment of a four-part series, I explore the economic cost of doing research in a cash-strapped system and the burden this is placing on young investigators.

To bring yourself up to speed, installements 1 and 2 are referenced below:

As has been discussed here on and off for quite some time, 80% of PhDs in the US will not become professors. For the majority of these scientific investigators, the inability to secure a faculty position has meant that they must languish in a series of post-doctoral positions supported by grant-funded professors who are increasingly finding themselves with limited resources. The average age of independence in research is now in the mid-40s, a testament to the bleak prospects facing young scientists (PDF).

Given this highly unstable state of academic funding, it is not surprising that many investigators have chosen to transition into more secure professions like teaching, medicine or law. For an in-depth review of the career prospects of a post-doctoral research scientist please see Careers and Rewards in the Bio Sciences: The Disconnect Between Scientific Progress and Career Progression(PDF). The loss hurts our competitiveness in biomedical research and forces industry abroad.

Given our current economy, it is imperative that efforts to improve the nation’s fiscal stability be grounded in the long-term competitiveness of industries we currently head, and that we leverage our expertise in medical science and capacity to do high-tech research. This does not need to come from increased government spending alone. Whereas academic medicine cannot build R&D into the pricing of its services, universities profit directly from tuition fees, patents and personal endowments.

Since these revenues are derived from faculty teaching loads, the scientific success of their investigators, and established reputation of their research program, faculty support must be factored into departmental operating budgets, freeing up tax dollars to directly support research innovation. Another idea would be to create tax breaks for private donations to federal funding agencies in an effort to reduce their dependence on public dollars and incentivize industry investment in national research programs. In the United States (the same nation that passed the Bayh-Dole Act to spur commercialization of university research), government funding of university research exceeds business funding by an order of magnitude, and business investment in university research is nearly half that of Canada (PDF).

Finally, limiting the number of federal awards issued per investigator, most of which are held by senior faculty (PDF), would open up more funding opportunities to help support young investigators and significantly lower the age of independence. While the debate of whether to preferentially support established labs with proven track records over younger faculty with new ideas is ongoing, without early career support junior researchers will not succeed.

If we are unwilling to prioritize young faculty and share what wealth there is, perhaps the better question is “Should we continue training so many of them?”

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Medicines in Development for Cancer in 2012: An Excellent Response from America’s Biopharmaceutical Research Companies

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, FDA Regulatory Affairs, Genome Biology, Health Economics and Outcomes Research, Personalized and Precision Medicine & Genomic Research, tagged Acute myeloid leukemia, AML, Biopharmaceutical, biopharmaceutical research, Cancer - General, cancer cells, disease, health, new medicines, research, United States on July 31, 2012| 5 Comments »

Reported by: Dr. Venkat S. Karra, Ph.D.

Cancer remains the second leading cause of death by disease. Hundreds of new medicines to treat cancer are now being developed for lessening the burden of cancer to patients, their families and society.

Biopharmaceutical researchers are now working on 981 medicines for cancer. Many are high-tech weapons to fight the disease, while some involve innovative research into using existing medicines in new ways, the report says.

Recent developments in early detection and a steady stream of new and improved treatments suggesting that cancer is a manageable chronic disease (not a deadly one any more). Families and patients alike are with increasing expectations from the industry for more and better treatment options and America’s biopharmaceutical research companies are responding to that.

America’s biopharmaceutical research companies are working on many new cutting-edge approaches to fight cancer. They include:

• A medicine that interferes with the metabolism of cancer cells by depriving them of the energy provided by glucose.
• A medicine for acute myeloid leukemia (AML) that inhibits cancer cells with a mutation found in about a third of AML sufferers.
• A therapy that uses nanotechnology to target the delivery of medicines to cancer cells, potentially overcoming some limitations of existing treatments.

Biosimilars: Financials 2012 vs. 2008

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 5/9/2026

Biosimilar Sustainability Scorecards for Europe 2026: Overall Summary and Country Scorecards.

DOWNLOAD REPORT

As biosimilars continue to play an expanding role in European healthcare systems, it is increasingly important to understand not only the savings and access gains they generate, but also the market conditions required to maintain those benefits over time.

IQVIA Institute published scorecards on the sustainability of biosimilar markets in 2018. This report aims to review this sustainability and how health care systems have evolved over time highlighting the positive levers and areas of development to ensure market sustainability for Biosimilars.

This report highlights the value of biosimilars and evaluates the structural determinants of biosimilar market sustainability across a diverse set of European countries through a standardized, multi-dimensional assessment framework. It examines sixteen metrics across eight categories—including pricing rules and dynamics, incentives, purchasing mechanisms, dispensing and supply, clinical guidelines and prescribing practices, competitive structure, and healthcare system performance—to identify the policy configurations that support or hinder long-term biosimilar viability.

Key Findings:

Biosimilars have delivered ~€75Bn in savings and broadened access in Europe, but future gains rely on sustaining competitive markets.
Clinical confidence is strong; variation across countries is now driven mainly by pricing, procurement, and incentive structures.
Balanced approaches such as moderate pricing pressure, multi-supplier procurement, and uptake incentives support long-term sustainability.
Aggressive policies (price cuts, reference pricing, clawbacks) may undermine markets by discouraging entry and driving price erosion.
Single-winner tenders and price-only models limit competition, while weak incentives hinder consistent adoption.
With 24 biologics losing exclusivity by 2032, capturing future savings depends on strengthening market conditions today.

DOWNLOAD REPORT

As always, I invite you to join the conversation about this important topic and more on LinkedIn and X. And get the latest news from the Institute by joining our mailing list.

Regards,

Murray Aitken

Executive Director

IQVIA Institute for Human Data Science

SOURCE

From: IQVIA Institute <ma@iqvia.com>
Reply-To: IQVIA <ma@iqvia.com>
Date: Saturday, May 9, 2026 at 10:02 AM
To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu>
Subject: New Report: Biosimilar Sustainability Scorecards for Europe 2026: Overall Summary and Country Scorecards

@@@

For IP and Legal aspects of Biosimilars, go to:

Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers

http://pharmaceuticalintelligence.com/2012/07/30/biosimilars-intellectual-property-creation-and-protection-by-pioneer-and-by-biosimilar-manufacturers/

For CMC and Regulatory Affairs of Biosimilars, go to:

Biosimilars: CMC Issues and Regulatory Requirements

http://pharmaceuticalintelligence.com/2012/07/29/biosimilars-cmc-issues-and-regulatory-requirements/

The patent provisions of the Biosimilar Act, 2009 establish demanding and time-sensitive disclosure requirements. ObamaCare upheld by the Supreme Court is a victory for future development of pathways for biosimilar regulatory approval and eventually biosimilar generic drugs.

With the upheld ObamaCare, critical parts of the PPACA constitutional, and with it the BPCIA giving the FDA authority to approve biosimilars.

Had the PPACA been stricken in part or in its entirety, it would have presented obstacles to the BPCIA surviving in its present form. The US government has been critical of the 12-year data exclusivity period for Pioneer Innovators, calling for it to be shortened to 7 years (12 years is favorable to Pioneer Innovators and less favorable for Biosimilar manufacturers). The upheld ObamaCare, PPACA and BPCIA, constitutional, has prevented a multiyear delay in biosimilar approval. Thus, it was the best scenario for the biologics industry.

Thus, projection of Sales for Biosmilars as % of top 100 U.S. Pharmaceutical will receive a special meaning and an expected enhanced market share for 2012 year end and beyond 2012.

Biosimilars are occupying the Following ranking in the U.S. Pharmacuetical Sales – 2012: Top 100 Drugs for Q1 2012 by Sales: 10, 11, 12 13, 15, 24, 27, 29, 33, 35, 39, 57, 58, 62, 65, 70, 72, 74, 90, 98, 99. In addition the following biosimilars did not make the Top 100 list:

Biosimilar Drugs by US Sales – not included in the Top 100 Drug List

Recombinate $2.9 1998 — Antihemophilic Factor VIII (Recombinant) by Baxter 5.7 Billion in 2012

Cerezyme $1.5 1994 — Gaucher disease and Fabrazyme for Fabry disease by Genzyme 200 millions in sales

TYSABRI(R) (natalizumab) revenues were $280 million, in-line with the second quarter of 2011 by Elan and Biogen

NovoSeven $1.4 1999 — Anti-fibrinolytics by Novo Nordisk – $1.5Billion

Synagis $1.3 1998 — Generic Name: palivizumab Anti-virals by AstraZeneca $570 millions

Humulin $1.1 1992 Insulin Human by Eli Lilly $ 1.2 Billion

Kogenate FS $1.1 1993 — octocog alfa Anti-fibrinolytics By Bayer $1.4 billion

U.S. Pharmacuetical Sales – 2012: Top 100 Drugs for Q1 2012 by Sales – Small Molecule Drugs (in green) and Biosimilars (in red)

The following is a list of the top 100 pharmaceutical drugs by retail sales in 2012, listed by U.S. sales value and drug name. Last updated: July 2012 (updated quarterly)

http://www.drugs.com/stats/top100/sales

Rank	Drug	Sales ($000)
1	PlavixBristol-Myers Squibb Company	1,620,790	Stats
2	NexiumAstraZeneca Pharmaceuticals	1,395,981	Stats
3	AbilifyOtsuka Pharmaceutical Co.	1,340,200	Stats
4	SingulairMerck & Co., Inc.	1,238,134	Stats
5	SeroquelAstraZeneca Pharmaceuticals	1,161,141	Stats
6	Advair DiskusGlaxoSmithKline	1,139,182	Stats
7	CrestorAstraZeneca Pharmaceuticals	1,117,904	Stats
8	CymbaltaEli Lilly and Company	1,029,262	Stats
9	atorvastatinGeneric Drug	952,407	Stats
10	HumiraAbbott Laboratories	928,124	Stats
11	RemicadeCentocor Ortho Biotech, Inc	899,453	Stats
12	EnbrelAmgen Inc.	890,135	Stats
13	NeulastaAmgen Inc.	849,971	Stats
14	LipitorPfizer Inc	840,715	Stats
15	RituxanGenentech, Inc	756,875	Stats
16	CopaxoneTeva Pharmaceuticals	748,585	Stats
17	AtriplaGilead Sciences, Inc.	694,901	Stats
18	OxyContin	662,876	Stats
19	SpirivaBoehringer Ingelheim Pharmaceuticals, Inc	659,818	Stats
20	AvastinGenentech, Inc	632,183	Stats
21	ActosTakeda Pharmaceuticals North America, Inc	630,970	Stats
22	JanuviaMerck & Co., Inc.	583,603	Stats
23	TruvadaGilead Sciences, Inc.	546,098	Stats
24	LantusSanofi-Aventis	520,584	Stats
25	DiovanNovartis Corporation	509,615	Stats
26	LexaproForest Pharmaceuticals, Inc	491,053	Stats
27	EpogenAmgen Inc.	489,570	Stats
28	LyricaPfizer Inc	458,171	Stats
29	Lantus SolostarSanofi-Aventis	448,388	Stats
30	enoxaparinGeneric Drug	442,263	Stats
31	EloxatinSanofi-Aventis	431,928	Stats
32	CelebrexPfizer Inc	430,993	Stats
33	HerceptinGenentech, Inc	425,687	Stats
34	Diovan HCTNovartis Corporation	415,475	Stats
35	LucentisGenentech, Inc	409,547	Stats
36	SynagisMedImmune, Inc	396,556	Stats
37	NamendaForest Pharmaceuticals, Inc	391,638	Stats
38	GleevecNovartis Corporation	391,072	Stats
39	AvonexBiogen Idec	388,623	Stats
40	VyvanseShire US Inc	387,167	Stats
41	olanzapineGeneric Drug	385,867	Stats
42	IncivekVertex Pharmaceuticals	371,349	Stats
43	One Touch Ultra	366,294	Stats
44	SuboxoneReckitt Benckiser Pharmaceuticals Inc.	338,840	Stats
45	methylphenidateGeneric Drug	337,211	Stats
46	ZetiaMerck & Co., Inc.	328,653	Stats
47	AndroGelAbbott Laboratories	311,850	Stats
48	ProvigilCephalon, Inc.	303,029	Stats
49	LidodermEndo Pharmaceuticals	301,354	Stats
50	TriCorAbbott Laboratories	298,834	Stats
51	SymbicortAstraZeneca Pharmaceuticals	290,669	Stats
52	CombiventBoehringer Ingelheim Pharmaceuticals, Inc	285,487	Stats
53	ProAir HFATeva Pharmaceuticals	284,647	Stats
54	Seroquel XRAstraZeneca Pharmaceuticals	282,416	Stats
55	amphetamine/dextroamphetamineGeneric Drug	275,447	Stats
56	NasonexMerck & Co., Inc.	274,748	Stats
57	NovologNovo Nordisk Inc.	266,305	Stats
58	ProcritJanssen Pharmaceuticals, Inc	264,190	Stats
59	AlimtaEli Lilly and Company	263,024	Stats
60	ViagraPfizer Inc	260,678	Stats
61	GeodonPfizer Inc	260,514	Stats
62	Rebif	258,088	Stats
63	budesonideGeneric Drug	257,243	Stats
64	NiaspanAbbott Laboratories	255,383	Stats
65	HumalogEli Lilly and Company	244,587	Stats
66	Flovent HFAGlaxoSmithKline	241,552	Stats
67	LovazaGlaxoSmithKline	239,845	Stats
68	LevemirNovo Nordisk Inc.	239,576	Stats
69	Adderall XRShire US Inc	239,097	Stats
70	NeupogenAmgen Inc.	238,427	Stats
71	ReyatazBristol-Myers Squibb Company	238,151	Stats
72	AranespAmgen Inc.	231,643	Stats
73	metoprololGeneric Drug	231,395	Stats
74	NovoLog FlexPenNovo Nordisk Inc.	227,228	Stats
75	VytorinMerck & Co., Inc.	218,215	Stats
76	JanumetMerck & Co., Inc.	212,596	Stats
77	IsentressMerck & Co., Inc.	211,526	Stats
78	escitalopramGeneric Drug	210,171	Stats
79	CialisEli Lilly and Company	206,996	Stats
80	AciphexEisai Corporation	203,097	Stats
81	PradaxaBoehringer Ingelheim Pharmaceuticals, Inc	201,065	Stats
82	SolodynMedicis Pharmaceutical Corporation	198,909	Stats
83	fentanylGeneric Drug	197,350	Stats
84	ZyprexaEli Lilly and Company	194,460	Stats
85	VelcadeTakeda Pharmaceuticals North America, Inc	188,583	Stats
86	RestasisAllergan, Inc	188,501	Stats
87	LunestaSunovion Pharmaceuticals Inc.	187,941	Stats
88	acetaminophen/hydrocodoneGeneric Drug	185,374	Stats
89	PrezistaJanssen Pharmaceuticals, Inc	182,859	Stats
90	PegasysGenentech, Inc	181,693	Stats
91	ZyvoxPfizer Inc	179,523	Stats
92	Prevnar 13Wyeth	179,085	Stats
93	LovenoxSanofi-Aventis	178,957	Stats
94	BenicarDaiichi Sankyo	174,619	Stats
95	VESIcareAstellas Pharma US	174,524	Stats
96	Ventolin HFAGlaxoSmithKline	172,707	Stats
97	OrenciaBristol-Myers Squibb Company	172,202	Stats
98	BetaseronBayer Healthcare Pharmaceuticals	172,143	Stats
99	ErbituxBristol-Myers Squibb Company	171,513	Stats
100	DexilantTakeda Pharmaceuticals North America, Inc	171,179	Stats

Source: IMS Health (Midas).

Biosimilars Drugs by US Sales – not included in the Top 100 Drug List

Recombinate $2.9 1998 — Antihemophilic Factor VIII (Recombinant) by Baxter 5.7 Billion in 2012

Cerezyme $1.5 1994 — Gaucher disease and Fabrazyme for Fabry disease by Genzyme 200 millions in sales

TYSABRI(R) (natalizumab) revenues were $280 million, in-line with the second quarter of 2011 by Elan and Biogen

NovoSeven $1.4 1999 — Anti-fibrinolytics by Novo Nordisk – $1.5Billion

Synagis $1.3 1998 — Generic Name: palivizumab Anti-virals by AstraZeneca $570 millions

Humulin $1.1 1992 Insulin Human by Eli Lilly $ 1.2 Billion

Kogenate FS $1.1 1993 — octocog alfa Anti-fibrinolytics By Bayer $1.4 billion

2011 US Sales vs. 2008 US Sales (in Billions) for Top Selling Biologics

Source for 2008 Sales

http://www.tbiweb.org/tbi/file_dir/TBI2009/Bao-lu%20Chen.pdf

Source for 20011, Q1 2012 Sales

http://www.drugs.com/stats/top100/sales

Drug Name, 2008 Sales, Year approved , Indication

[i.e. Drug Name Enbrel, 2008 Sales $8.0B, Year approved 1998 , Indication RA]

Enbrel $8.0 1998 — RA, psoriatic arthritis, or ankylosing spondylitis indication

Q1 2012	12 (1)	$890,135	1.92%	823	-4.63%
Q4 2011	11 (1)	$873,343	1.67%	863	1.77%
Q3 2011	12 (1)	$858,997	1.27%	848	-2.97%
Q2 2011	13 (2)	$848,230	3.77%	874	3.19%
Q1 2011	11	$817,401		847

http://www.drugs.com/stats/enbrel

Remicade $7.9 1998 — RA & Chron’s Disease

Q1 2012	11 (2)	$899,453	10.04%	1,556	10.04%
Q4 2011	13 (3)	$817,365	-7.02%	1,414	-9.82%
Q3 2011	10	$879,054	1.52%	1,568	1.03%
Q2 2011	10 (2)	$865,903	7.61%	1,552	7.11%
Q1 2011	12	$804,699		1,449

http://www.drugs.com/stats/remicade

Humira $7.3 2002 — treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis

Q1 2012	10	$928,124	2.50%	546	-2.85%
Q4 2011	10 (1)	$905,527	3.18%	562	2.55%
Q3 2011	11 (3)	$877,641	3.95%	548	3.01%
Q2 2011	14	$844,296	6.32%	532	2.31%
Q1 2011	14	$794,076		520

http://www.drugs.com/stats/humira

Rituxan $7.3 1997 — cancer medicines to treat non-Hodgkin’s lymphoma or chronic lymphocytic leukemia.

Q1 2012	15 (1)	$756,875	-1.91%	547	-0.91%
Q4 2011	14 (2)	$771,622	6.96%	552	4.74%
Q3 2011	16	$721,408	-1.77%	527	-1.86%
Q2 2011	16 (4)	$734,378	7.26%	537	5.09%
Q1 2011	20	$684,666

http://www.drugs.com/stats/rituxan

Second Quarter 2012 Highlights: RITUXAN(R) (rituximab) revenues from our unconsolidated joint business arrangement were $285 million for the quarter, an increase of 31% year-over-year. As previously disclosed, during the second quarter of 2011 our share of RITUXAN revenues from unconsolidated joint business was reduced by approximately $50 million to reflect our share of damages and interest that might be awarded in relation to an intermediate decision in Genentech, Inc.’s ongoing arbitration with Hoechst GmbH

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

Herceptin $5.7 1998 — treat metastatic breast cancer that has progressed after treatment with other chemotherapy

Q1 2012	33	$425,687	-0.06%	155
Q4 2011	33 (2)	$425,931	7.61%	155	4.73%
Q3 2011	31 (1)	$395,804	-0.64%	148	-0.67%
Q2 2011	32 (4)	$398,348	3.62%	149	1.36%
Q1 2011	36	$384,428		147

http://www.drugs.com/stats/herceptin

Lantus $5.1 2000 — long-acting form of the hormone insulin.

Q1 2012	29 (5)	$448,388	9.81%	3,737	7.32%
Q4 2011	34	$408,336	8.54%	3,482	7.07%
Q3 2011	34 (2)	$376,208	4.53%	3,252	6.00%
Q2 2011	36 (5)	$359,907	7.80%	3,068	8.30%
Q1 2011	41	$333,878		2,833

http://www.drugs.com/stats/lantus-solostar

Epogen/Procrit $5.1 1989 — Anemia, low RBC

Worldwide, sales of the two drugs – sold under the brand names Epogen, Procrit and Aranesp – exceeded $9 billion in 2005 for Amgen and Johnson & Johnson, their makers. Johnson & Johnson, which sells epoetin under the brand names Procrit in the United States and Eprex everywhere else, reported sales of $2.4 billion in the first nine months of 2006, down slightly from 2005.

Amgen Recalls Anemia Medications for Glass Fragments

09/24/2010 – Drug-makers Amgen (AMGN) and Johnson & Johnson (JNJ) are voluntarily recalling two brandsof an injectable anemia medication because vials containing the drug may have tiny glass flakes. The drug, Epoetin alfa, is marketed under the brand names Epogen and Procrit.Known as lamellae, the glass fragments are created by the interaction of the drug with glass vials during storage, Amgen said in a statement announcing the recall. The recall is being conducted in cooperation with the Food and Drug Administration, Amgen said.

http://www.dailyfinance.com/2010/09/24/amgen-recalls-epogen-procrit-glass-anemia-drugs/

http://healthfully.org/dnd/id9.html

Latest study shows anemia drugs Epogen, Aranesp and Procrit cause strokes, says FDA

Posted on January 7, 2010

Anemia drugs sold by Amgen and Johnson & Johnson have been reported to cause strokes when prescribed in high doses, according to an article from the FDA, recently published in the The New England Journal of Medicine. The law firm of Aylstock, Witkin, Kreis & Overholtz is investigating the FDA’s recent announcement.

The FDA commentary said the latest study and previous studies “raise major concerns” about the use of these drugs to treat anemia caused by kidney disease. The drugs are also used to treat anemia caused by chemotherapy. Studies over the past several years have revealed a link between the drugs and heart attacks, strokes, and other problems.

Amgen’s anemia drugs include Epogen and Aranesp. Johnson & Johnson sells anemia drug Procrit, which is produced by Amgen. The drugs are designed to raise red blood cell levels, to promote delivery of oxygen to body tissues.

http://www.awkolaw.com/news/heart-attacks/anemia-drugs-epogen-aranesp-procrit-cause-strokes-says-fda/

Epogen / Procrit / Aranesp: The July 2012 News Report Which Tells Story Of Big Pharma Profits Over Patient Safety And Drug Efficacy

Once The FDA Started Paying Attention The Writing On The Wall Became Apparent, Albeit Too Late For Some

(Posted by Tom Lamb at DrugInjuryWatch.com)

This lengthy and well-presented news report, “Anemia drugs made billions, but at what cost?”, written by Peter Whoriskey and published July 19, 2012 by The Washington Post (free registration required), is a must-read for anyone with a concern or interest in how larger pharmaceutical companies might put corporate profits ahead of patient safety and drug efficacy.

Here is an excerpt from this Washington Post article which will give you a sense of what went on that, in hindsight, is so disturbing:

For years, a trio of anemia drugs known as Epogen, Procrit and Aranesp ranked among the best-selling prescription drugs in the United States, generating more than $8 billion a year for two companies, Amgen and Johnson & Johnson. Even compared with other pharmaceutical successes, they were superstars. For several years, Epogen ranked as the single costliest medicine under Medicare: U.S. taxpayers put up as much as $3 billion a year for the drugs.

The trouble, as a growing body of research has shown, is that for about two decades, the benefits of the drug — including “life satisfaction and happiness” according to the FDA-approved label — were wildly overstated, and potentially lethal side effects, such as cancer and strokes, were overlooked.

Last year, Medicare researchers issued an 84-page study declaring that among most kidney patients, the original and largest market for the drugs, there was no solid evidence that they made people feel better, improved their survival or had any “clinical benefit” besides elevating a statistic for red blood cell count.

As for some of the key events which led up to this revelation of sorts, we start with a June 24, 2011 FDA press release, “FDA modifies dosing recommendations for Erythropoiesis-Stimulating Agents — Cites increased risk of cardiovascular events when used to treat chronic kidney disease”, which included the following:

The U.S. Food and Drug Administration today recommended more conservative dosing guidelines for Erythropoiesis-Stimulating Agents (ESAs) when used to treat anemia in patients with chronic kidney disease (CKD) because of the increased risks of cardiovascular events such as stroke, thrombosis, and death….

http://www.drug-injury.com/druginjurycom/2012/07/epogen-procrit-aranesp-stroke-thrombosis-death-side-effects-safety-risks-benefits-efficacy-fda.html

Procrit — (epoetin alfa) is a man-made form of a protein that helps your body produce red blood cells

Q1 2012	58 (3)	$264,190	-2.13%	295	-4.22%
Q4 2011	55 (2)	$269,937	3.58%	308	3.01%
Q3 2011	53 (12)	$260,610	-21.61%	299	-21.32%
Q2 2011	41 (7)	$332,466	7.04%	380	5.56%
Q1 2011	48	$310,606		360

http://www.drugs.com/stats/procrit

Epogen — (epoetin alfa) is a man-made form of a protein that helps your body produce red blood cells

Q1 2012	27 (7)	$489,570	-24.54%	555	-17.04%
Q4 2011	20 (2)	$648,794	4.67%	669	3.40%
Q3 2011	22 (2)	$619,828	-13.96%	647	-18.41%
Q2 2011	20 (1)	$720,376	3.32%	793	4.48%
Q1 2011	19	$697,224		759

http://www.drugs.com/stats/epogen

Neulasta $4.2 2002 — used to prevent neutropenia, a lack of certain white blood cells caused by receiving chemotherapy. stimulates the bone marrow and promotes the growth of white blood cells called neutrophils

Q1 2012	13 (1)	$849,971	3.33%	331	1.53%
Q4 2011	12 (2)	$822,578	4.59%	326	3.49%
Q3 2011	14 (1)	$786,464	-3.86%	315	-5.69%
Q2 2011	15	$818,068	4.04%	334	3.41%
Q1 2011	15	$786,288		323

http://www.drugs.com/stats/neulasta

Novolog $3.7 2000 — Insulin aspart is a fast-acting form of insulin. NovoLog is used to treat type 1 (insulin-dependent) diabetes in adults and children who are at least 2 years old. It is usually given together with a long-acting insulin.

Q1 2012	57 (6)	$266,305	5.67%	2,980	3.72%
Q4 2011	63 (3)	$252,015	0.97%	2,873	-0.48%
Q3 2011	60 (1)	$249,591	-0.96%	2,887	-2.66%
Q2 2011	61 (5)	$252,010	3.16%	2,966	-0.70%
Q1 2011	66	$244,297		2,987

http://www.drugs.com/stats/novolog

Erbitux $3.6 2004 — used to treat cancers of the colon and rectum. It is also used to treat head and neck cancer.

Q1 2012	99 (2)	$171,513	2.30%	266	3.91%
Q4 2011	97 (7)	$167,657	-0.15%	256	0.79%
Q3 2011	90 (3)	$167,909	-2.48%	254	-1.93%
Q2 2011	93 (2)	$172,185	-0.89%	259	-0.38%
Q1 2011	95	$173,735		260

http://www.drugs.com/stats/erbitux

Aranesp $3.2 2001 — Anemia, low RBC, (darbepoetin alfa) is a man-made form of a protein that helps your body produce red blood cells.

Q1 2012	72 (6)	$231,643	-5.86%	293	-7.86%
Q4 2011	66 (15)	$246,056	-6.07%	318	-3.64%
Q3 2011	51 (3)	$261,967	-10.25%	330	-11.29%
Q2 2011	48 (3)	$291,873	-1.03%	372	-1.33%
Q1 2011	51	$294,912		377

http://www.drugs.com/stats/aranesp

The article reports on the decline of worldwide sales of Aranesp drug from Thousand Oaks, California-based Amgen Inc. as of the second quarter of 2007. According to Amgen, the 10% decrease of Aranesp worldwide sales was due to the reimbursement issues related to the anemia drug and the drop of U.S. demand for drug, in which the U.S. Aranesp reported sales in the second quarter of 2007 was only $578 million from $713 million in 2006.

http://connection.ebscohost.com/c/articles/26375335/amgen-posts-lower-aranesp-sales

1/24/2011, Amgen boosts prices to offset Aranesp sales

Amgen is hiking prices to make up for the shrinking sales volume of its anemia drug Aranesp. Bloomberg reports that Amgen raised the price tag on Aranesp itself by 4.4 percent, but also marked up the white-blood-cell-boosting meds Neulasta and Neupogen by 2.9 percent.

http://www.fiercepharma.com/story/amgen-boosts-prices-offset-aranesp-sales/2011-01-24

Recombinate $2.9 1998 — Antihemophilic Factor VIII (Recombinant)

BioScience core franchises include: Hemophilia, Biotherapeutics, BioSurgery and Vaccines. BioScience products represent approximately 45 percent of Baxter’s annual sales, totaling $5.7 billion in 2010.

2007 Outlook – Sales within Baxter’s BioScience business totaled $1.2 billion, an increase of 18 percent from the same period last year. This growth was driven by record sales of ADVATE, Antihemophilic Factor (Recombinant), Plasma/Albumin Free Method (rAHF-PFM) for the treatment of hemophilia A, antibody therapy products, including GAMMAGARD LIQUID(TM) [Immune Globulin Intravenous (Human)] (IVIG) 10% Solution for the treatment of primary immunodeficiencies, specialty plasma therapeutics and biosurgery products. Medication Delivery sales increased 7 percent to $1.0 billion, with increased sales of infusion systems, intraveneous solutions and parenteral nutrition products, along with accelerated growth in the company’s drug delivery business. Renal sales increased 6 percent to $537 million reflecting accelerating gains in peritoneal dialysis patients globally.

http://www.drugs.com/news/baxter-s-fourth-quarter-financial-results-exceed-expectations-5128.html

Lucentis $2.7 2006 intraocular injection. (ranibizumab injection) is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A).

Date Range	Sales Rank	Sales ($000)		Units (000)
Q1 2012	35 (5)	$409,547	-6.89%	224	-5.88%
Q4 2011	30 (2)	$439,867	2.44%	238	2.59%
Q3 2011	28 (2)	$429,393	1.13%	232	0.87%
Q2 2011	30 (3)	$424,611	0.95%	230	1.32%
Q1 2011	33	$420,635		227

http://www.drugs.com/stats/lucentis

http://www.gene.com/gene/about/ir/historical/product-sales/lucentis.html

Lucentis brought in $1.7 billion for Roche last year, according to data compiled by Bloomberg.Alimera Sciences Inc. (ALIM), based in Alpharetta, Georgia, and Psivida Corp. (PSDV) also are developing a diabetic macular edema treatment known as Iluvien. The FDA has twice rejected Iluvien, most recently in November.

The FDA pooled results from two Roche clinical trials and found 39 percent of patients who used the 0.3 milligram dose were able to read three additional lines of letters on an eye chart after two years compared to 41 percent who had the same effect on the 0.5 milligram dose, according to an FDA staff report released July 24.

Genentech recommended approval of the 0.3 milligram dose in its application to the FDA since there isn’t evidence of additional benefit of the higher dose, Terence Hurley, a spokesman for the company, said in an e-mail.

Patients who received the monthly injection also were significantly more likely than those who received fake doses of the drug to achieve 20/40 vision, enough eyesight to drive.

http://www.bloomberg.com/news/2012-07-26/roche-s-lucentis-backed-by-fda-panel-for-diabetic-blindness-1-.html

Avonex $2.6 1996 — Multiple Sclerosis, a form of protein called beta interferon that occurs naturally in the body. Interferons help the body fight viral infections. Avonex is used to treat patients with relapsing forms of multiple sclerosis to slow the accumulation of physical disability. This medication will not cure MS, it will only decrease the frequency of relapse symptoms.

Q1 2012	39 (1)	$388,623	2.22%	130	-3.70%
Q4 2011	38 (5)	$380,189	0.19%	135	-2.17%
Q3 2011	33	$379,457	-0.05%	138	-1.43%
Q2 2011	33 (4)	$379,639	2.45%	140	-1.41%
Q1 2011	37	$370,570		142

http://www.drugs.com/stats/avonex

Second-quarter net income surged 34 percent to $386.8 million, or $1.61 a share, from $288 million, or $1.18, a year earlier, the Weston, Massachusetts-based company said today in a statement. Earnings excluding some items of $1.82 topped by 26 cents the average of 21 analysts’ estimates (BIIB) compiled by Bloomberg. Revenue beat estimates by about $90 million.

Biogen said profit this year is expected to be more than $6.20 a share, 5 cents higher than its May 1 forecast (BIIB). The company has been increasing sales of Avonex, Rituxan and Tysabri, another MS therapy, while developing new medicines to introduce to the market.

http://www.businessweek.com/news/2012-07-24/biogen-second-quarter-profit-rises-as-avonex-sales-increase

AVONEX(R) (interferon beta-1a) revenues increased 16% year-over-year to $762 million.

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

Novolin $2.5 1991 — Novolin R (insulin regular) is a short-acting form of human insulin, Diabetes, Type 1 Type 2

Date Range	Sales Rank	Sales ($000)		Units (000)
Q1 2012	74 (2)	$227,228	8.96%	2,489	13.81%
Q4 2011	76 (4)	$208,552	10.19%	2,187	6.73%
Q3 2011	80 (6)	$189,267	4.15%	2,049	4.92%
Q2 2011	86 (7)	$181,733	3.71%	1,953	29.60%
Q1 2011	93	$175,235		1,507

http://www.drugs.com/stats/novolog-flexpen

Novo Nordisk launches iPhone app Posted 17th September 2010, 15:11:54

An iPhone app has been launched by Novo Nordisk in the US which lets healthcare staff check dosage guidelines for diabetes patients.

Novo Dose provides product-specific data for the company’s insulin analog agents Levemir (insulin detemir), NovoLog (insulin aspart) and NovoLog Mix (insulin aspart protamine/insulin aspart injectable).

Combined sales of the three medications increased by 24% last year, feeding a double-digit growth in Novo Nordisk sales and profits.

Novo Dose, the second diabetes app created by the industry, tells professionals when and how to dose the drugs, how to titrate and provides information on the blood glucose goals of patients.

Commenting on the new technology, Anup Kumar Sabharwal, an endocrinologist at the University of Miami Clinics’ Diabetes Research Institute, said: “This is where modern medicine is headed.”

Humalog $2.2 1996 Humalog is used to treat type 1 (insulin-dependent) diabetes in adults. Insulin lispro is a fast-acting form of insulin. It is usually given together with another long-acting insulin. It works by lowering levels of glucose in the blood. Humalog is also used together with oral (taken by mouth) medications to treat type 2 (non insulin-dependent) diabetes in adults.

Q1 2012	65	$244,587	-2.70%	2,570	-3.85%
Q4 2011	65 (2)	$251,367	3.78%	2,673	2.81%
Q3 2011	63 (4)	$242,208	-0.75%	2,600	-1.78%
Q2 2011	67 (5)	$244,050	4.83%	2,647	1.15%
Q1 2011	72	$232,809		2,617

http://www.drugs.com/stats/humalog

Pegasys $2.0 2002 — (peginterferon alfa-2a) is made from human proteins that help the body fight viral infections. Pegasys is used to treat chronic hepatitis B or C. It is often used together with another medication called ribavirin (Copegus, Rebetol, RibaPak, Ribasphere, RibaTab).

Q1 2012	90 (1)	$181,693	3.92%	87	3.57%
Q4 2011	91 ()	$174,833		84

http://www.drugs.com/stats/pegasys

Rebif $1.7 2002 — (interferon beta-1a) is a protein identical to one found in the body. Interferon beta-1a is made from human proteins. Interferons help the body fight viral infections. Rebif is used to treat relapsing multiple sclerosis (MS). This medication will not cure MS, it will only decrease the frequency of relapse symptoms.

Q1 2012	62 (1)	$258,088	-0.21%	540	-9.09%
Q4 2011	61 (7)	$258,643	0.43%	594	-0.34%
Q3 2011	54 (5)	$257,535	1.48%	596	-1.49%
Q2 2011	59 (2)	$253,780	0.25%	605	-0.66%
Q1 2011	61	$253,143		609

http://www.drugs.com/stats/rebif

Cerezyme $1.5 1994 — Gaucher disease and Fabrazyme for Fabry disease.

Last year Genzyme was forced to temporarily close its manufacturing plant in Boston due to a viral contamination. The interruption lead to shortages of two key drugs: Cerezyme for Gaucher disease and Fabrazyme for Fabry disease.

That crisis sent the company’s stock price plummeting from nearly $84 in 2008 to a low earlier this year of $45.39. Sanofi’s offer to acquire the company for $18.5 billion, or $69 a share — along with a 14 percent rise in the NYSE Arca Biotech Index since late July — have helped the shares rebound.

But Genzyme is now on a mission to prove to shareholders that it is worth more than Sanofi is offering, and executives told investors on a conference call that the third quarter marks the beginning of its financial turnaround.

Third-quarter sales of Cerezyme, the company’s top drug, rose to $179.8 million from $93.6 million a year earlier, beating analysts’ average forecast of $175 million.

“In the third quarter we saw our financial recovery start to take effect, and we expect that this will accelerate during the fourth quarter as Cerezyme patients are able to return to normal dosing levels and we begin to increase shipments of Fabrazyme,” Genzyme CEO Henri Termeer said in a statement.

http://www.reuters.com/article/2010/10/20/us-genzyme-idUSTRE69J2S520101020

Cerezyme is the principal drug for Gaucher patients. In the first quarter of 2012 Genzyme (now part of Sanofi (SNY))reported Cerezyme sales of 149 million euros (approx. $194 million), up 5.8% from the same quarter of the previous year. The other supplier Shire (SHPGY) reported $72 million in Vpriv sales, up 22%. There is now a third supplier, Pfizer (PFE), teamed up with the Israeli company Protalix Biotherapeutics (PLX), whose product was approved by the FDA in May 2012. Elelyso (taliglucerase alfa) is now available in the US.

http://seekingalpha.com/article/694801-gaucher-disease-the-fight-for-market-share

Product	Cerezyme
	2009	2010	2011
Total	793	720	885
Ann. Growth Total		-9%	23%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=15461&componentID=1002

Tysabri $1.4 2004 — Multiple Sclerosis by Elan and Biogen

Global in-market sales of TYSABRI in the second quarter of 2012 were $395 million, an increase of 2% over the second quarter of 2011. The total was comprised of $211 million in U.S. sales and $184 million in sales outside the U.S.

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

TYSABRI(R) (natalizumab) revenues were $280 million, in-line with the second quarter of 2011.

http://www.marketwatch.com/story/correcting-and-replacing-biogen-idec-increases-revenue-18-to-14-billion-in-the-second-quarter-2012-07-24

ITALIAN DISPUTE

Elan derives its revenue almost exclusively from Tysabri and it reported total sales for the three months to June 30 of $288 million, up 6 percent on a year ago once sales from its since-divested drug delivery business are omitted.

That compared to the $299 million forecast by four analysts surveyed by Reuters and was driven by in-market sales of Tysabri that rose 2 percent year-on-year to $395 million, also shy of the $419 million expected by analysts.

Biogen, which detailed the sales numbers when it reported second quarter results on Tuesday, attributed the softer-than-expected Tysabri sales to a dispute with the Italian government over pricing.

The number of patients on Tysabri rose 4 percent to 69,100, maintaining Elan and Biogen’s 10 to 12 percent share of the MS drug market in the face of competition from Swiss drugmaker Novartis AG’s Gilenya treatment, the first multiple sclerosis pill to come on the market.

The average addition of 185 new patients per week was the highest quarterly run-rate since the fourth quarter of 2009.

http://in.reuters.com/article/2012/07/25/elan-idINL6E8IP1VV20120725

NovoSeven $1.4 1999 — Anti-fibrinolytics by Novo Nordisk —

Generic Name:

eptacog alfa

Product	NovoSeven
	2009	2010	2011
Total	1,324	1,431	1,559
Ann. Growth Total		8%	9%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&id=13483&lType=modData&componentID=1002

Synagis $1.3 1998 — Generic Name: palivizumab Anti-virals by AstraZeneca

Product	Synagis
	2009	2010	2011
Total	1,042	906	570
Ann. Growth Total		-13%	-37%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=91&componentID=1002

Neupogen $1.3 1991 — (filgrastim) is a man-made form of a protein that stimulates the growth of whiteblood cells in your body. White blood cells help your body fight against infection. Neupogen is used to treat neutropenia, a lack of certain white blood cells caused by cancer,bone marrow transplant, receiving chemotherapy, or by other conditions.

Q1 2012	70	$238,427	0.06%	170	-2.86%
Q4 2011	70 (5)	$238,289	0.16%	175	10.76%
Q3 2011	65 (5)	$237,915	0.69%	158	0.64%
Q2 2011	70 (4)	$236,294	2.51%	157	0.64%
Q1 2011	74	$230,515		156

http://www.drugs.com/stats/neupogen

Betaseron $1.2 1993 — (interferon) is made from human proteins. Interferons help the body fight viral infections. Betaseron is used to treat relapsing multiple sclerosis (MS). Betaseron will not cure MS, it will only decrease the frequency of relapse symptoms.

Q1 2012	98 (1)	$172,143	2.93%	67	-10.67%
Q4 2011	99 (12)	$167,236	-3.76%	75	-5.06%
Q3 2011	87 (2)	$173,769	-2.89%	79	-2.47%
Q2 2011	89 (4)	$178,938	-2.17%	81	-7.95%
Q1 2011	85	$182,908		88

http://www.drugs.com/stats/betaseron

Humulin $1.1 1992 Insulin Human by Eli Lilly

Product	Humulin R
	2009	2010	2011
Total	1,022	1,089	1,249
Ann. Growth Total		7%	15%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=12399&componentID=1002

Kogenate FS $1.1 1993 — octocog alfa Anti-fibrinolytics By Bayer

Product	Kogenate
	2009	2010	2011
Total	1,238	1,332	1,496
Ann. Growth Total		8%	12%

http://www.evaluatepharma.com/Universal/View.aspx?type=Entity&entityType=Product&lType=modData&id=11681&componentID=1002

Conclusion

Biosimilars are defined as biological products similar, but not identical, to the reference biological products that are submitted for separate marketing approval following patent expiration of the reference biological products. As one of the ICH members, the US needs to catch up with the EU and Japan as those two countries have already issued regulatory guidelines for biosimilars.

Once Congress establishes a legal framework, FDA is expected to set up a biosimilar approval pathway which will be similar to those in the EU and Japan and harmonized under ICH. The biosimilar will need a full CMC development package plus demonstration of comparable quality attributes and comparable efficacy and safety to the innovator’s product. Table 5 provides a comparison summary between small-molecule generics and biosimilars. It will take a much bigger effort to develop a biosimilar than a generic drug. Automatic substitution between the innovator product and a biosimilar is not appropriate as a biosimilar is not a generic version of the innovator product and is approved based on comparability to the innovator product.

REFERENCES

http://www.wolfgreenfield.com/files/2426_biosimilars_2_final_pdf.pdf

Read Full Post »

Biosimilars: CMC Issues and Regulatory Requirements

Reporter: Aviva Lev-Ari, PhD, RN

Updated on 6/30/2015

Biosimilars in the US: How much can we learn from Europe?

http://www.xcenda.com/Insights-Library/HTA-Quarterly-Archive-Insights-to-Bridge-Science-and-Policy/HTA-Quarterly-Spring-2015/Biosimilars-in-the-US-How-much-can-we-learn-from-Europe/#.VY-99uehlRA.mailto

Updated on 2/10/2014

Cambridge Healthtech Institute’s Fifth Annual Biotherapeutics Analytical Summit
Hyatt Regency Baltimore | Baltimore, MD | BiotherapeuticsAnalyticalSummit.com

<http://wec.chi-lifescience.com/t/20344782/1039908871/3650297/1006/>

The Science and Regulation of Process Changes for Biologics (Comparability)
Thursday, March 27, 2014 | 5:30 – 8:30 PM | More Information

http://wec.chi-lifescience.com/t/20344782/1039908871/4704449/1007/?fb8dc108=YXZpdmFsZXYtYXJpQGFsdW0uYmVya2VsZXkuZWR1&x=9c418447

Manufacturing changes can impact on quality attributes of biologics, and may affect efficacy and/or safety of the product. For that reason, a thorough comparability exercise is required, to assess the impact of the change and whether CMC data alone will suffice to support the change. This interactive short course will consider comparability exercises during development, as well as post-approval, addressing regulatory and technical requirements. This should provide the attendee with the knowledge on how to prepare a comparability package for discussion with regulatory agencies, towards acceptance of the proposed change to the process/product. Attendees will be contacted before the event and asked about topics on which they would like to focus.

Topics covered include:

Ways that manufacturing changes can impact on quality attributes
Features of a thorough comparability exercise
Critical evaluation of quality data
The comparability exercise during development
Post-approval comparability, ICH Q5E, Comparability Protocols (US) and Change Management Protocols (EU)
Regulatory requirements in the EU and US: guidelines, their interpretation and application
Discussion with Q&A

Course    Instructors:

Christopher J. Holloway, Ph.D., Group     Director, Regulatory Affairs & CSO, ERA Consulting Group
Kazumi Kobayashi, Ph.D., Director, Bioprocess Development, Biogen Idec,    Inc.
Marjorie Shapiro, Ph.D., Chief, Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies,            FDA/CDER

Comparability and Developability conference program at Biotherapeutics Analytical Summit.

The third track of the Biotherapeutics Analytical Summit focuses on the practical application of analytical characterization for Comparability, Biosimilarity and Development purposes. It covers case studies with a variety of products and a range of analytical technologies. We have invited the FDA and regulatory experts to advise and to discuss regulatory challenges being experienced by the industry. This conference also covers the link between the process and analytical technologies for innovator products and for biosimilars.

BiotherapeuticsAnalyticalSummit.com/Comparability

http://wec.chi-lifescience.com/t/20344782/1039908871/4665296/1009/?fb8dc108=YXZpdmFsZXYtYXJpQGFsdW0uYmVya2VsZXkuZWR1&x=833e704b>

SOURCE

From: Biotherapeutics Analytical Summit Short Course <lauran@healthtech.com>
Date: Mon, 10 Feb 2014 12:40:59 -0500
To: <avivalev-ari@alum.berkeley.edu>
Subject: The Science and Regulation of Process Changes for Biologics (Comparability)

Comparability: The Final Frontier of Protein Therapies

The rapid expansion of protein therapeutics has crossed into all major disease classes (cancer, metabolic disease, inflammatory disease, infectious disease, immune disorders, etc.). Due to the lengthy learning curve and high cost of developing these complex products, the development of therapies has been traditionally limited to highly specialized companies. As protein therapeutics become more mainstream, these products are finding new applications in disease treatment and commercial application beyond the range of the traditional biotech companies. Unfortunately, the expansion of medical applications for these therapies is outpacing the rate of innovation in product development and, as a result, market availability is becoming constrained by the ability to characterize and control product characteristics.

The Future Opportunity:

The key to most effectively and efficiently developing a biopharmaceutical or biologic to marketing approval is to have a clear understanding of the unique properties of proteins and to use that knowledge to design appropriate manufacturing processes, preclinical pharmacology-toxicology and clinical programs. It is essential in dealing with complex comparability issues related to the types of manufacturing processes or changes in manufacturing to understand the scientific reasons for requiring a demonstration of comparability and the relationships between bioanalytical differences or changes in a protein and potential alterations in protein functionality in terms of specificity, potency, pharmacological activity, pharmacokinetics, toxicity and ultimately clinical safety and efficacy. This understanding requires in depth knowledge of protein chemistry, manufacturing processes, pharmacology, immunology and toxicology that comes with extensive training and experience. The same scientific and regulatory expertise and experience that is required for a successful demonstration of comparability is also applicable to the development of a biosimilar. This type of experience and expertise should prove invaluable as the expansion in the area of protein therapies continues and the development of biosimilars grows in the coming years.

How to Get There from Here:

Product developers can begin today to capitalize on this opportunity. A number of technology advancements are being explored that will enhance our understanding of relationships between process, product, and clinical safety and efficacy. One must think through how to integrate the future product comparability into early stage product development. For new product development, these issues will include more in-depth analysis of the product structure and relationship of various structural features to function andin vivo activity, increased knowledge about the effect of process conditions on the types and mix of final product variants, and careful choice of in vitro binding and functional assays that clearly relate to the proposed mechanism of action of the product and can often also be used as a potency assays. New technologies are being developed for these assays, and appropriate in vitro functional assays as relates to pharmacological mechanism of action can be very useful for demonstrating comparability.

A careful determination of appropriate animal models of disease for demonstration of proof-of-concept pharmacology is also important early in development. Identification of appropriate biomarkers of efficacy or safety should also be examined in these early animal models for future use in clinical development as well as demonstration of comparability. The discovery of appropriate biomarkers can sometimes be carried over to the clinic and used in clinical trials with the appropriate validation. Finally, as the safety database for the various classes of biopharmaceuticals and biologics expands, the understanding of safety issues associated with each of these various product classes will make it easier to more efficiently demonstrate comparability as well as to develop biosimilar products.

For developers who are trying to bridge comparability on products that lack a complete process/product history due to legacy issues or as in the case for biosimilar development, companies must think about the pharmacology of the product as relates to the proposed indication of either the previous iteration of the product or the innovator product, depending on whether this is a comparability issue or development of a biosimilar. It is the pharmacological activity of a given protein product that determines the efficacy and to a great extent the toxicity of the product. The pharmacological activity of a product is driven by protein structure, mix of product variants, binding kinetics, dose, dosing regimen, route of administration, and final product formulation, among others.

As the development of biopharmaceuticals and biologics continues to expand, more and more information accrues on potential safety issues related to each of the various product classes, and this information will also prove quite useful to demonstration of comparability and development of biosimilars.

Biologics Consulting Group can assist developers in designing and implementing each of their comparability programs with the greatest chance of rapid regulatory approval. Our staff has both FDA and industry experience, with a track record of success in helping academic institutions, start-ups, and established biotech and pharma companies. Our direct knowledge and contemporary experience with all possible regulatory pathways – and every associated nuance — and can provide the requisite preclinical, clinical, quality, analytical, and manufacturing support to increase your chances for success.

Contributors: T. Carrier, D. Barngrover, J. Jessop, V. Narbut, J. Humphries, B. Fraser, R. Wolff, N. Ritter, L. Winberry

SOURCE

http://www.biologicsconsulting.com/perspectives/comparability-protein-therapies/

For IP and Legal aspects of Biosimilars, go to:

Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers

http://pharmaceuticalintelligence.com/2012/07/30/biosimilars-intellectual-property-creation-and-protection-by-pioneer-and-by-biosimilar-manufacturers/

For Financial Aspects of Biosimilars, go to:

Biosimilars: Financials 2012 vs. 2008

http://pharmaceuticalintelligence.com/2012/07/30/biosimilars-financials-2012-vs-2008/

Tr e n d s i n B i o / P h a r m a c e u t i c a l I n d u s t r y , 1 9 -26

Special Report on Biosimilars

About the Author: Dr. Bao-Lu has over 18 years of experience in product development, CMC regulatory, manufacturing management and quality oversight. He is currently the Director of Manufacturing and Process Development at Sangamo BioSciences. In this role, he oversees outsourced GMP production and testing of Sangamo’s gene therapy products and is responsible for the release and disposition of final drug product. He also provides CMC regulatory support and manages the in-house quality system by maintaining GMP database and implementing quality SOPs. Previously, Bao-Lu served as an Associate Director of Formulation at Xencor and Chiron and a Formulation Scientist at Amgen. Bao-Lu graduated with a BS degree from Fudan University and was selected as one of the forty chemistry students in the first year CGP Doering program. Bao-Lu earned his Ph.D. in Chemistry from University of Oregon and performed postdoctoral research in Biology at Massachusetts Institute of Technology.

http://www.tbiweb.org/tbi/file_dir/TBI2009/Bao-lu%20Chen.pdf

CMC Issues and Regulatory Requirements for Biosimilars

Abstract

Chemistry, Manufacturing and Controls (CMC), preclinical and clinical are three critical pieces in biosimilars development. Unlike a small-molecule generic drug, which is approved based on “sameness” to the innovator’s drug; a biosimilar is approved based on high similarity to the original approved biologic drug. This is because biologics are large and complex molecules. Many functional-, safety- and efficacy-related characteristics of a biologic depend on its manufacturing process. A biosimilars manufacturer won’t be able to exactly replicate the innovator’s process. The traditional abbreviated pathway for generic drug approval through the Hatch- Waxman Act of 1984 doesn’t apply for biosimilars as drugs and biologics are regulated under different laws. New laws and regulations are needed for biosimilars approval in the US. The EU has issued biosimilars guidelines based on comparative testing against the reference biologic drug (the original approved biologic). A full scale CMC development is required including expression system, culture, purification, formulation, analytics and packaging. The manufacturing process needs to be developed and optimized using state-of-the-art technologies. Minor differences in structure and impurity profiles are acceptable but should be justified. Abbreviated clinical testing is required to evaluate surrogate markers for efficacy and demonstrate no immunogenic response to the product.

We anticipate the package for a biosimilars approval in the US will be similar to that in the EU and contain a full quality dossier with a comparability program including detailed product characterization comparison and reduced preclinical and clinical requirements.

Biosimilars Become Inevitable

Biologics developed through biotechnology constitute an essential part of the pipeline for medicines available to patients today. Biologic drugs are quite expensive and many of them are top-selling medicines (see Table 1). Since they come at extremely high prices to consumers, some patients may not be able to afford the use of biologics as the best-available treatments to their conditions. The patent protection on a large number of biologics has expired since 2001. These off-patent biologics include Neupogen, Novolin, Protropin, Activase, Epogen or Procrit, Nutropin, Humatrope, Avonex, Intron A, and Humulin. Traditionally, when a drug patent expires, a generic drug will be quickly developed and marketed. Similarly, generic version of off-patent biologic drugs (also referred to biosimilars or follow-on biologics or biogenerics) represents an extraordinary opportunity to companies that want to seize the potentially great commercial rewards in this unexploited territory. Biosimilars not only benefit the biosimilar manufacturers but also can save patients, and insurance companies, substantial cost and allow patients to gain access to more affordable biologics resulting in market expansion. The government can use biosimilars to reduce healthcare costs. Therefore, development and marketing of bosimilars are supported by both manufacturers and consumers.

Differences between Generic Drugs and Biosimilars

Enacted in 1984, the US Drug Price Competition and Patent Term Restoration Act, informally known as the “Hatch-Waxman Act of 1984” standardized US procedures for an abbreviated pathway for the approval of small-molecule generic drugs. The generic drug approval

is based on “sameness”. In comparison to the innovator’s drug, a generic drug is a product that has the same active ingredient, identical in dose, strength, route of administration, safety, efficacy, and intended use. For approval, the generic companies can go through the Abbreviated

New Drug Application (ANDA) process with reduced requirement in comparison to approval for a new drug entity. The generic drugs need to show bioequivalence to the innovator drugs typically based on pharmacokinetic parameters such as the rate of absorption or bioavailability in 24 to 36 healthy volunteers. No large clinical trials for safety and efficacy are required. The generic companies can rely on the FDA’s previous findings of safety and effectiveness of the innovator’s drugs.

However, the abbreviated pathway for generic drugs legally doesn’t apply to biologics as small-molecule drugs and biologics are regulated under different laws and approved through different pathways in the US (Table 2). Small-molecule drugs are regulated under the Food, Drug and Cosmetic Act (FD&C) and require submission of a New Drug Application (NDA) to FDA for drug review and approval. Biologics are regulated under the Public Health Service Act (PHS) and require submission of a Biologic License Application (BLA) to FDA for review and approval. The Hatch-Waxman Act of 1984 doesn’t apply for biosimilars. New laws are needed to establish a pathway for biosimilar approval.

There are some crucial differences between biologics and small-molecule drugs (Table 3). Small-molecule drugs are made from chemical synthesis. They are not sensitive to process changes. The final product of a small-molecule drug can be fully characterized. The developmentand production of generic drugs are relatively straightforward. Biologics are made from living organisms so that its functional-, efficacy- and safety-related properties depend on its manufacturing and processing conditions. They are sensitive to process changes. Even minor modifications of the manufacturing process can cause variations in important properties of a biological product. Thus it is believed that a biologic product is defined by its manufacturing process. Biologics are 100- or 1,000-fold larger than small-molecule drugs, possess sophisticated three-dimensional structures, and contain mixtures of protein isoforms. A biological product is a heterogeneous mixture and the current analytical methods cannot characterize these complex molecules sufficiently to confirm structural equivalence with the reference biologics.

Laws and Regulatory Pathways for Drug Approval in the US

Law/Application Small-molecule Drug Biologics

Law Food, Drug and Cosmetic Act (FD&C) Public Health Service Act (PHS)

Drug application New Drug Application (NDA) Biologic License Application (BLA)

Generic application Abbreviated New Drug Application(ANDA) No pathway yet

Immunogenicity Poses a Concern

One of the major complications that biologics can produce is immunogenicity as therapeutic proteins are inherently immunogenic [2]. Immunogenicity is related to biologics structure and formulation and is dependent on dose, route of administration and frequency of administration.

Clinical implications of immunogenicity are not always predictable. Formation of antibodies can result in harmless clinical effect or produce significant adverse events or severe disease. Examples are provided below. The Eprex (Erythropoietin, EPO) has been marketed by Johnson & Johnson (J&J) in the European Union (EU) countries for 10 years with no noticeable

Differences between small-molecule drugs and biologics

Product characteristics

Small-molecule generics Small, simple molecule

(Molecular weight: 100-1,000 Da)

Biosimilars Large, complex molecules, Higher order structures, Post-translational, modifications

(Molecular weight: 15,000-150,000 Da)

Production

Small-molecule generics Produced by chemical synthesis

Biosimilars Produced in living organisms

Analytical testing

Small-molecule Well-defined chemical structure, all its various components in the finished drug can be determined

Biosimilars Heterogeneous mixture, difficult to characterize, some of the components of a finished biologic may be unknown

Process dependence

Small-molecule Not sensitive to manufacturing process changes. The finished product can be analyzed to establish the sameness.

Biosimilars Sensitive to minor changes in manufacturing process. The product is defined by the process

Identity and purity

Small-molecule Often meeting pharmacopeia or other standards of identity (e.g., minimums for purity and potency)

Biosimilars Most have no pharmacopeia monographs

immunogenicity issues prior to 1998. When J&J made a change in the Eprex formulation by replacing human serum albumin (HAS) with polysobate 80 and glycine in response to the

request from European health authorities, some patients developed pure red-cell aplasia (PRCA), a severe form of anemia. Eprex induced antibodies neutralize all the exogenous rHuEPO and cross-react with endogenous erythropoietic proteins. As a result, serum EPO is undetectable

and erythropoiesis becomes ineffective. Upon investigation, J&J found that polysorbate 80 might have caused uncoated rubber stoppers in single-use Eprex syringes to leach plasticizers, which stimulated an immune response that resulted in PRCA. Replacing with Teflon coated stoppers resulted in 90% decrease in PRCA by 2003 [3,4]. The effect of neutralizing antibodies has not always resulted in serious clinical consequences. Three interferon beta products, Betaseron, Rebif and Avonex, are marketed by three different companies. These products induce neutralizing antibodies in multiple sclerosis patients from 5 to 50% after one year treatment. Although these antibodies might be associated with loss of efficacy of treatment resulting in some patients to withdraw from the treatment, it seems no other severe adverse effects were detected [5,6].

Regulatory Landscape

The US, the EU and Japan are the three cornerstonemembers of the International Conference on Harmonization (ICH), which intends to harmonize the regulatory requirements for drug or biologic approval in these three regions. With the other two members, the EU and Japan, already have established biosimilar approval procedures (see below), the US lags behind in the biosimilar race. There are no formal approval pathways for biosimilars in the US. Congress needs to establish a legal framework in order for FDA to develop guidelines. Legislation has been under discussion in Congress since 2007. The legislative debate is centered on patient safety and preserving incentives to innovate with introduction of biosimilars. Two bills introduced in March 2009 deserve attentions [7,8]. The Waxman bill (H.R. 1427) proposes 5 years of market exclusivity to the innovator companies and requires no clinical trials for biosimilar development. The Eshoo bill (H.R. 1548) proposes 12 years of market exclusivity to the innovator companies and requires clinical trials for biosimilar development. Obama administration appears to favor a 7-year market exclusivity [9]. Once a legal framework is established for biosimilars, the FDA will likely take a conservative approach using the comparability as an approval principle. Clinical proof of efficacy and safety will be required, probably in reduced scale.

In the EU, the European Medicines Agency (EMEA) issued regulatory guidelines for approving biosimilars in 2005 (Figure 1) [10-16]. These include two general guidelines for quality issues [11] and non-clinical and clinical issues [12] and four class-specific annexes for specific data requirements for Granulocyte-Colony Stimulating factor (G-CSF) [13], Insulin [14], Growth hormone [15] and Erythropoietin [16]. In addition, a concept paper on interferon alpha [17] is also available. So far, there are eleven biosimilar products which received market authorization in the EU and they are biosimilar versions of human growth hormone, Epoetin and filgrastim. It is estimated six to eight years on average for a biosimilar to be developed [18].

The EMEA treats a biosimilar medicine as a medicine which is similar to a biological medicine that has already been authorized (the “biological reference medicine”) in the EU, The active substance of a biosimilar medicine is similar to the one of the biological reference medicine.

A biosimilar and the biological reference medicine are used in general at the same dose to treat the same disease. A biosimilar and the biological reference medicine are not automatically interchangeable because biosimilar and biological reference medicine are only similar but not identical. A physician or a qualified healthcare professional should make the decision to treat a patient with a reference or a biosimilar medicine. Since the biosimilar may contain different inactive ingredients, the name, appearance and packaging of a biosimilar medicine differ to those of the biological reference medicine. In addition, a pharmacovigilance plan must be in place for post-marketing safety monitoring.

Japan’s Ministry of Health, Labor and Welfare (MHLW) issued guidelines for follow-on proteins or biosimilars approval in March 2009. The first biosimilar, Sandoz’ growth hormone Somatropin, was approved in June 2009. The MHLW’s guidelines consider biosimilars drugs which are equivalent and homogeneous to the original biopharmaceuticals in terms of quality, efficacy and safety. Biosimilars are also requested to be developed with updated technologies and knowledge. Biosimilars need to demonstrate enough similarity to guarantee the safety and efficacy instead of absolute identity to the original biologics. Biosimilars’ regulatory approval applications will be categorized separately from conventional generic drugs. In general, the applications should be submitted, as the new drug applications, with data from clinical trials, manufacturing methods, long-term stability and information on overseas use. The MHLW will assess the data on absorption, distribution, metabolism and excretion (ADME) on a case-by-case basis. The applications do not need to provide data on accessory pharmacology, safety pharmacology and genotoxicity.

Biosmilars are already thriving in Eastern Europe and Asia, where regulatory and intellectual property (IP) standards for biosimilars are more liberal. Biosimilars developed in these regions are primarily sold domestically. These markets are considered less controlled. The quality of the biosimilars may not be in full compliance with ICH guidelines although they are often developed through comparative quality testing and clinical trials against the biologics which are already approved in Western countries

CMC Development

The CMC requirements for biosimilars in the EU are those described in the ICH Common Technical Document (CTD) Quality Module 3 with supplemental information demonstrating comparability or similarity on quality attributes to the reference medicine product.

Since the US is a member of ICH and encourages submission using CTD format, once the legal framework for approving biosimilars is established in the US, the CMC development will be similar to those in the EU.

Biosimilar manufacturers will have no access to the manufacturing process and product specifications of the innovator’s products because these are proprietary knowledges. To develop a biosimilar, a biosimilar manufacturer will need to first identify a marketed biologic product to serve as the reference biologic product. Then a detailed characterization of the reference biologic product will be performed. The information obtained from the characterization of the reference biologic product will be utilized to direct the process development of the biosimilar product and comparative testing to demonstrate bioequivalence between the biosimilar product and the reference biologic product. A biosimilar will be manufactured from a completely new process, which may be based on different host/vector system with different process steps, facilities and equipment.

A flow chart for a typical work flow from production to drug use is shown in Figure 2. The CMC development starts with establishment of the expression system. A cell-line will be selected among bacterial, yeast and mammalian host strains and then the correct DNA sequence will be inserted. Elaborate cell-screening and selection methods are then used to establish a master cell bank. Extensive characterization on the master cell bank needs to be carried out to provide microbiological purity or sterility and identity [19].

Bulk protein production involves developing robust and scalable fermentation and purification processes. The goals for fermentation are to increase the expression level and efficiency without compromising the correct amino acid sequence and post translational modification. Achieving high expression requires optimizing culture medium and growth conditions, and efficient extraction and recovery procedures. Correct amino acid sequence and post translati0nal modification will need to be verified.

Cell Bank

↓

Fermentation

↓

Purification

↓

Drug Substance

↓

Formulation

↓

Fill/finish

↓

Drug Product

↓

Shipment

↓

Administration

Typical flow chart for a biologics from production to drug use, above

Solubilization and refolding of insoluble proteins are sometimes necessary for proteins which have tendency to aggregate under the processing condition. Differences in the cell bank and production processes may create impurities that are different from the innovator’s product. The purification process needs to remove impurities such as host-cell proteins, DNA, medium constituents, viruses and metabolic by-products as much as possible. It is important for biosimilar manufacturers to accept appropriate yield losses to achieve high purity, because any increase in yield at the expense of purity is unacceptable and can have clinical consequences.

The final product is produced by going through formulation, sterile filtration and fill/finish into the final containers. Selection of formulation components starts from basic buffer species for proper pH control and salt for isotonicity adjustment. Surfactants may be needed to prevent proteins from being absorbed onto container surface or water-air interface or other hydrophobic surfaces. Stabilizers are required to inhibit aggregation, oxidation, deamidation and other degradations. The container and closure system can be glass vials, rubber stoppers and aluminum seals or pre-filled syringes or IV bags. The container and closure integrity needs to be verified by sterility or dyeleak test.

Biologics are not pure substances. They are heterogeneous mixtures. Each batch of a biologic product for clinical or commercial use needs to be produced in compliance with current Good Manufacturing Practice (cGMP) and is typically tested by a panel of assays to ensure the product meets pre-defined specifications for quality, purity, potency, strength, identity and safety. The product purity is often measured by multiple assays, which measure different product related variants (biologically active) or product related impurities (biologically inactive). Biologics are parenteral drugs and filled into the final containers through the aseptic process so that microbiological control is critical. It is advisable to set up product specifications for a biosimilar within the variation of the reference biologic product. Product characterization can be performed on selected batches for primary sequence, high order structures, isoform profiles, heterogeneity, product variants and impurities and process impurity profiles. Physicochemical characterization tests include IEF, CE, HIC, LCMS, carbohydrate analysis, N & C terminal sequencing, amino acid analysis, analytical ultracentrifugation, CD and DSC [20,21]. Biologics are highly sensitive to environmental influences during storage, shipment and handling. Temperature excursion, movement, and exposure to UV light can lead to protein degradation. Product expiry needs to be based on the real time stability data. Stability program should also include accelerated or stress studies to gain insight of the degradation profiles. In-use stability studies are carried out to verify shipping conditions or handling procedures cause no detrimental effect to the drug product.

Comparability Demonstration

A comparability exercise based on the ICH guideline [22] needs to be performed to demonstrate that the biosimilar product and the reference biologic product have similar profiles with respect to product quality, safety, and efficacy. This is accomplished by comparative testing of the biosimilar product and the reference biologic product to demonstrate they have comparable molecular structure, in vitro and in vivo biological activities, pre-clinical safety and pharmacokinetics, and safety and efficacy in human patients. Comparison of quality attributes between the biosimilar and the reference biologic product employs physicochemical

Product release assays for biologics

Type Assays

Quality Appearance, particulates, pH, osmolality

Purity SDS-PAGE, SEC-HPLC, IEX-HPLC, RP-HPLC

Potency In vitro or in vivo bioactivity assays

Strength Protein concentration by A280

Identity Western blot, peptide mapping, isoelectric focusing

Safety Endotoxin, sterility, residual DNA, host cell proteins

and biological characterization. Comparability on physical properties, amino acid sequence, high order structures, post-translationally modified forms are evaluated by physicochemical tests. In vitro receptor-binding or cell-based (binding) assays or even the in vivo potency studies in animals need to be performed to demonstrate comparable activity despite they are often imprecise. Levels of product related impurities (aggregates, oxidized forms, deamidated forms) and process related impurities and contaminants (host cell proteins, residual genomic DNA, reagents, downstream impurities) need to be assessed and quantified. Stability profiles of the biosimilar product and the reference biologic product also need to be studies by placing the products under stressed conditions. The rate of degradation and degradation profiles (oxidation, deamidation, aggregation and other degradation reactions) will be compared. If unknown degradation species are detected, they need to be studied to determine if they affect safety and efficacy. If differences on product purities and stability profiles are present between the biosimilar product and the reference biologic product, these differences need to be justified using scientific knowledge or preclinical or clinical studies. Changes in the impurity profile should be justified as well.

The demonstration of comparability in quality attributes does not necessarily mean that the biosimilars and the reference biologics are identical, but that they are highly similar. In many cases, the relationship between specific quality attributes and safety and efficacy has not been fully established. For example, physicochemical characterization cannot easily predict immunogenicity and slight changes in manufacturing processes or product composition can give rise to unpredicted changes in safety and efficacy. Changes in bioavailability, pharmacokinetics, bioactivity bioactivity, and immunogenicity are the main risks associated with the manufacturing of biosimilars. In vivo studies should be designed to measure the pharmacokinetics and pharmacodynamics relevant to clinical studies. Such in vivo studies should be designed to detect response differences between the biosimilar and the reference biologic not just responses per se. In vivo studies of the biosimilar’s safety in animals may be used to research any concerns into the safety of the biosimilar in human patients. Although extensive clinical testing is not necessary for biosimilars, some degree of clinical testing is needed to establish therapeutic comparability on efficacy and safety between the biosimilar and the reference biologic product [23,24]. This includes using surrogate markers of specific biologic activity as endpoints for demonstrating efficacy, and showing that patients didn’t develop immunogenic responses to the product. In general, the approval of biosimilars will be based on the demonstration of comparable efficacy and safety to an innovator reference product in a relevant patient population. Clinical data requirement for each individual product will be different and will be determined on a case-by-case basis.

Small-molecule Generics versus Biosimilars

Small-molecule

Approval based on “sameness”

Biosimilars

Approval based on “high similarity”

Small-molecule

Replicate the innovator’s process and product and perform a bioavailability study demonstrating similar pharmacokinetic properties

Biosimilars

Full CMC development with comparative testing, conduct substantial clinical trials for efficacy and safety including immunogenicity

Small-molecule

Abbreviated registration procedures in Europe and US

Biosimilars

Regulatory pathway is defined in EU on “Comparability” status, no pathway yet in US under BLA

Small-molecule

Therapeutically equivalent, thus interchangeable

Biosimilars

Lack of automatic substitutability

Small-molecule

$1 to $5 million to develop

Biosimilars

$100-$200 million to develop

Small-molecule

Brand-to-generic competition

Biosimilars

Brand-to-Brand competition

Conclusion

REFERENCES

1. Federal Trade Commission Report, June 2009.

2. Schellekens, H.; Nat. Rev. Drug Discov. 2002, 1: 457-462.

3. Van Regenmortel, M.H.V.; Boven, K. and F. Bader, BioPharm International, August 1, 2005, Vol 18, Issue 8.

4. Locatelli, F.; Del Vecchio, L. and P. Pozzoni, Peritoneal Dialysis International, 2007, 27(Supplement 2): S303-S307.

5. Hartung, H.P.; Munschauer, F. And Schellekens, H., Eur J. Neurol., 2005, 12, 588-601.

6. Malucchi, S. et al., Neurol. Sci., 2005, 26, suppl, 4:S213-S214.

7. Greb, E., Pharmaceutical technology, June 2009, pp. 36-42.

8. Del Buono, B.J., BioPharm International, July 2009, pp 46-53.

9. Usdin, S., Biocentury, July 20, 2009, 17(32): A1-A6.

10. “Guideline on Similar Biological Medicinal Products”, (Doc. Ref.: EMEA/CHMP/437/04, London, 30 October 2005).

11. “Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Quality Issues”, (Doc. Ref.: EMEA/ CHMP/BWP/49348/2005, London, 22 February 2006).

12. “Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-Clinical and Clinical Issues”, (Doc. Ref.: EMEA/CHMP/BMWP/42832/2005, London, 22 February 2006).

13. “Annex to Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-Clinical and Clinical Issues – Guidance on Similar Medicinal Products Containing Recombinant Granulocyte-Colony Stimulating Factor”, (Doc. Ref.: EMEA/CHMP/ BMWP/31329/2005, London, 22 February 2006).

14. “Annex to Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-Clinical and Clinical Issues – Guidance on Similar Medicinal Products Containing Recombinant Human Soluble Insulin”,(Doc. Ref.: EMEA/CHMP/BMWP/32775/2005, London, 22 February 2006).

15. “Annex to Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-Clinical and Clinical Issues – Guidance on Similar Medicinal Products Containing Somatropin”, (Doc. Ref.: EMEA/ CHMP/BMWP/94528/2005, London, 22 February 2006).

16. “Annex to Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: Non-Clinical and Clinical Issues – Guidance on Similar Medicinal Products Containing Recombinant Erythropoietins”, (Doc. Ref.: EMEA/CHMP/BMWP/94526/2005 Corr., London, 22 February 2006).

17. “Annex to Guideline on Similar Biological Medicinal Products Containing Biotechnology-derived Proteins as Active Substance: (Non) Clinical Issues – Concept paper on similar biological medicinal products containing recombinant alpha-interfero (Doc. Ref.: CHMP/BMWP/7241/2006, London, 26 April 2006).

18. “EGA Handbook on Biosimilar Medicines”, European Generic Medicines Association, Received August 2009).

19. “Points to Consider in the Characterization of Cell Lines to Produce Biologicals”, FDA CBER, 1993.

20. Chirino, A.J. and A. Mire-Sluis, Nature Biotechnology, 2004, 22(11): 1383-1391.

21. Kendrick, B.S. et al., BioPharm International, 2009, August, pp 32-44.

22. “Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process”, ICH Harmonized Tripartite Guideline Q5E, 18 November 2004.

23. Mellstedt, H.; Niederwieser, D. and H. Ludwig, Annals of Oncology, September 14, 2007, pp. 1-9.

24 Schellekens, H., NDT Plus, 2009, 2 [suppl 1]: i27- i36.

http://www.wolfgreenfield.com/files/2426_biosimilars_2_final_pdf.pdf

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A Possible Boon to Diligent Innovators in US

Posted in Uncategorized, tagged Grants, House of Representatives, Kirsten Gillibrand, New York, Senate, United States, United States House of Representatives, Venture capital on July 29, 2012| Leave a Comment »

Reported by: Dr. Venkat S. Karra

Two bills collectively called the America Innovates Act of 2012 were introduced in Congress, one in the Senate and the other in the House of Representatives, in April that have the potential to help universities that need funding to create spinout companies, says Patent Docs’ Kevin Noonan. “The bill provides for the US to establish an American Innovation Bank as an ‘independent agency,’ that will ‘promote the commercialization of science and engineering discoveries’ by ‘provid[ing] grants, loans, and other assistance to eligible entities and individuals to enable the entities and individuals to perform the necessary research and development to make research discoveries attractive for private investment that will lead to the development of new companies, products, and jobs,'” Noonan says.

The grants would be available to institutes of higher learning and non-profit research institutions, and would be awarded on a competitive basis. Further, Noonan adds, the bill also provides for grants to be awarded directly to individuals. “The Bank is intended, among other things, to help companies navigate the ‘valley of death’ where university-related start-up companies go through initial funding monies before having sufficient experimental results to attract venture capital or large company investment or commercialize their products,” he says.

However, though the bills have been referred to the respective committees in the House and Senate that would need to approve them, it is unlikely they will receive any attention until after the election, Noonan says.

But one of the bill’s sponsors, Senator Kirsten Gillibrand (D-NY), is working hard to promote it. “That kind of promotion … could be the ticket for accelerating consideration of the bills before November,” Noonan adds.

source

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Future of Calcitonin…?

Posted in Bone Disease and Musculoskeletal Disease, CANCER BIOLOGY & Innovations in Cancer Therapy, tagged Committee for Medicinal Products for Human Use, EMA, European Medicines Agency, European Union, Food and Drug Administration, osteoporosis, United States, Upsher-Smith Laboratories on July 20, 2012| 16 Comments »

Reported by: Dr. V.S. Karra, Ph.D.

The European equivalent of the US Food and Drug Administration (FDA) yesterday recommended withdrawing calcitonin nasal spray — indicated for treating osteoporosis in the European Union — because of an increased risk for cancer.
The European Medicines Agency (EMA) also said that the long-term use of calcitonin-containing medicines delivered by injection or infusion increases the risk for cancer. Calcitonin in any formulation should not be used to treat osteoporosis at all, the agency said.

In the United States, 2 nasal-spray versions of calcitonin are FDA-approved for treating postmenopausal osteoporosis in women: Fortical (Upsher-Smith Laboratories) and Miacalcin (Novartis). Neither of the labels for the 2 drugs contains restrictions on how they should be used or a warning about the risk for cancer.

Calcitonin, also called calcitonin-salmon, is a synthetic copy of a polypeptide hormone secreted by the ultimobranchial gland of salmon.

The EMA said it based its recommendations on a review of the benefits and risks of calcitonin-containing medicines. Conducted by the agency’s Committee for Medicinal Products for Human Use (CHMP), the review encompassed available data from the companies that market these drugs, postmarketing safety data, randomized controlled studies, 2 studies of unlicensed oral calcitonin drugs, and experimental cancer studies, among other sources.

CHMP found that “a higher proportion of patients treated with calcitonin for long periods of time develop cancer of various types, compared with patients taking placebo.” The increase in cancer rates ranged from 0.7% for oral formulations to 2.4% for the nasal formulation. CHMP concluded that the benefits of calcitonin for osteoporosis did not exceed the risks. The nasal spray’s only indication is for osteoporosis, thus justifying the drug’s removal from the market.

As a solution for injection or infusion, calcitonin should be administered for no more than 4 weeks to prevent acute bone loss resulting from sudden immobilization, and normally for no more than 3 months to treat Paget’s disease, the EMA said. The agency did not specify a time frame for the short-term use of calcitonin for treating hypercalcemia caused by cancer.

For further details go to their website

Source

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Great Hearts Serving the ‘Little Ones’

Posted in Cardiovascular Pharmacogenomics, Health Economics and Outcomes Research, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, tagged Artificial heart, Bambino Gesù Hospital, Cardiac muscle, heart muscle disease, Infant, Reuters, Robert Jarvik, Rome, United States on May 25, 2012| Leave a Comment »

Title: The Jarvik-7 Artificial Heart Image ID: 3559 Photographer: Unknown Restrictions: Public Domain http://fmp.cit.nih.gov/hi/ (Photo credit: Wikipedia)

The doctors at Rome’s Bambino Gesu hospital said the operation was carried out last month and made public this week. The baby, whose identity has not been disclosed, was kept alive for 13 days before the transplant and is now doing well.

The baby was suffering from dilated myocardiopathy, a heart muscle disease which normally causes stretched or enlarged fibers of the heart. The disease gradually makes the heart weaker, stopping its ability to pump blood effectively.

“This is a milestone,” surgeon Antonio Amodeo told Reuters television, adding that while the device was now used as bridge leading to a transplant, in the future it could be permanent.

Before the implant, the child also had a serious infection around a mechanical pump that had been fitted earlier to support the function of his natural heart.

“From a surgical point of view, this was not really difficult. The only difficulty that we met is that the child was operated on several times before,” he said.

The tiny titanium pump weighs only 11 grams and can handle a blood flow of 1.5 liters a minute. An artificial heart for adults weighs 900 grams.

Amodeo said the baby had become family and his team wanted to do everything to help him.

“The patient was in our intensive care unit since one month of age. So he was a mascot for us, he was one of us,” the doctor said.

“Every day, every hour, for more than one year he was with us. So when we had a problem we couldn’t do anything more than our best,” he said.

Doctors said the device, invented by American Doctor Robert Jarvik, had been previously tested only on animals.

The hospital needed special permission from Jarvik and the Italian health ministry before going ahead with the procedure.

source

Reported by: Dr. V.S.Karra, Ph.D.

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Posts Tagged ‘United States’

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Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes

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“A Synergistic Approach towards Biowaivers & Biosimilars”. Biosimilars-2012 is scheduled on September 10-12, 2012 at Hilton San Antonio Airport, USA.

Click here to view the downloadable Preliminary Program

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The matter has been address by the NIH and was reported in my post on June 27, 2012

Picturing US-Trained PhDs’ Paths and Pharmaceutical Industry’s Crisis of Productivity: Partnerships between Industry and Academia

Related matters on that subject are addressed in the following Posts by Dr. Jonathan Thon

Dr. Thon holds joint appointments within the hematology division at Brigham and Women’s Hospital, and Harvard Medical School in Boston, and is an American Society of Hematology Scholar.

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Biosimilars: Financials 2012 vs. 2008

Biosimilar Drugs by US Sales – not included in the Top 100 Drug List

U.S. Pharmacuetical Sales – 2012: Top 100 Drugs for Q1 2012 by Sales – Small Molecule Drugs (in green) and Biosimilars (in red)

Biosimilars Drugs by US Sales – not included in the Top 100 Drug List

2011 US Sales vs. 2008 US Sales (in Billions) for Top Selling Biologics

[i.e. Drug Name Enbrel, 2008 Sales $8.0B, Year approved 1998 , Indication RA]

Enbrel $8.0 1998 — RA, psoriatic arthritis, or ankylosing spondylitis indication

Remicade $7.9 1998 — RA & Chron’s Disease

Humira $7.3 2002 — treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis

Rituxan $7.3 1997 — cancer medicines to treat non-Hodgkin’s lymphoma or chronic lymphocytic leukemia.

Herceptin $5.7 1998 — treat metastatic breast cancer that has progressed after treatment with other chemotherapy

Lantus $5.1 2000 — long-acting form of the hormone insulin.

Epogen/Procrit $5.1 1989 — Anemia, low RBC

Latest study shows anemia drugs Epogen, Aranesp and Procrit cause strokes, says FDA

Epogen / Procrit / Aranesp: The July 2012 News Report Which Tells Story Of Big Pharma Profits Over Patient Safety And Drug Efficacy

Procrit — (epoetin alfa) is a man-made form of a protein that helps your body produce red blood cells

Epogen — (epoetin alfa) is a man-made form of a protein that helps your body produce red blood cells

Neulasta $4.2 2002 — used to prevent neutropenia, a lack of certain white blood cells caused by receiving chemotherapy. stimulates the bone marrow and promotes the growth of white blood cells called neutrophils

Novolog $3.7 2000 — Insulin aspart is a fast-acting form of insulin. NovoLog is used to treat type 1 (insulin-dependent) diabetes in adults and children who are at least 2 years old. It is usually given together with a long-acting insulin.

Erbitux $3.6 2004 — used to treat cancers of the colon and rectum. It is also used to treat head and neck cancer.

Aranesp $3.2 2001 — Anemia, low RBC, (darbepoetin alfa) is a man-made form of a protein that helps your body produce red blood cells.

1/24/2011, Amgen boosts prices to offset Aranesp sales

Recombinate $2.9 1998 — Antihemophilic Factor VIII (Recombinant)

Lucentis $2.7 2006 intraocular injection. (ranibizumab injection) is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A).

Novolin $2.5 1991 — Novolin R (insulin regular) is a short-acting form of human insulin, Diabetes, Type 1 Type 2

Novo Nordisk launches iPhone app Posted 17th September 2010, 15:11:54

Pegasys $2.0 2002 — (peginterferon alfa-2a) is made from human proteins that help the body fight viral infections. Pegasys is used to treat chronic hepatitis B or C. It is often used together with another medication called ribavirin (Copegus, Rebetol, RibaPak, Ribasphere, RibaTab).

Cerezyme $1.5 1994 — Gaucher disease and Fabrazyme for Fabry disease.

Tysabri $1.4 2004 — Multiple Sclerosis by Elan and Biogen

NovoSeven $1.4 1999 — Anti-fibrinolytics by Novo Nordisk —

Synagis $1.3 1998 — Generic Name: palivizumab Anti-virals by AstraZeneca

Betaseron $1.2 1993 — (interferon) is made from human proteins. Interferons help the body fight viral infections. Betaseron is used to treat relapsing multiple sclerosis (MS). Betaseron will not cure MS, it will only decrease the frequency of relapse symptoms.

Humulin $1.1 1992 Insulin Human by Eli Lilly

Conclusion

REFERENCES

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Biosimilars: CMC Issues and Regulatory Requirements

Biosimilars in the US: How much can we learn from Europe?

Comparability: The Final Frontier of Protein Therapies

Special Report on Biosimilars

CMC Issues and Regulatory Requirements for Biosimilars

Biosimilars Become Inevitable

Differences between Generic Drugs and Biosimilars

Laws and Regulatory Pathways for Drug Approval in the US

Law/Application Small-molecule Drug Biologics

Immunogenicity Poses a Concern

Differences between small-molecule drugs and biologics

Regulatory Landscape

CMC Development

Comparability Demonstration

Product release assays for biologics

Small-molecule Generics versus Biosimilars

Conclusion

REFERENCES

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