Inger Mollerup, Vice President of Novo Nordisk A/S, testified before the Government Oversight and Reform Committee about establishing a pathway for approval of follow-on biologics. She argued that any pathway must require clinical trials to demonstrate safety because even minor differences in biologics can have major health consequences, as shown through Novo Nordisk's experience. She also stated that traceability and unique names are important for pharmacovigilance, and that interchangeability is not supported by current science given potential immunogenicity differences between products.
This document discusses biosimilars and their regulation. It begins by defining biotechnology and biopharmaceuticals. Biosimilars are described as legally approved versions of biologic drugs that are similar but not identical to the original version. The document notes challenges in developing biosimilars due to the complex nature of biologics compared to traditional small molecule drugs. It also discusses concerns regarding efficacy, safety and interchangeability of biosimilars. Finally, it provides an overview of regulatory frameworks for biosimilars in the US, EU and India.
Biosimilars are biologic medicines that are developed to be similar to existing approved biologic medicines known as reference medicines. Biosimilars must demonstrate similarity to the reference medicine in terms of quality, safety and efficacy through comprehensive testing and analysis. While biosimilars may provide reduced costs and increased access to biologic treatments, they are more complex than traditional small molecule drugs due to differences in size, structure, manufacturing processes, and potential for immunogenicity. Thorough evaluation and regulation is required to ensure biosimilars are interchangeable for the reference product without compromising patient safety.
This document discusses biosimilars, which are biologic products that are highly similar to approved biologic reference products. It provides background on biosimilars, including their development process, advantages, limitations, and future outlook. The development process involves producing a cell line containing the gene for the desired protein, growing cells to produce the protein, purifying the protein, and preparing it for patient use. Biosimilars offer cost savings over biologics but have concerns around immunogenicity and long-term effects when switching between products. The global biosimilar market is expected to grow significantly as biologic patents expire and more companies develop biosimilar versions of treatments.
This document summarizes information about biosimilars and the regulatory pathways for their approval in the United States and European Union. It discusses how biosimilars differ from traditional small-molecule generics due to biological molecules' larger size, greater complexity, and manufacturing dependence. The U.S. passed the Biologics Price Competition and Innovation Act in 2010 to create an approval pathway for follow-on biologics, requiring biosimilarity demonstration and possible interchangeability labeling. Upcoming FDA hearings will provide information to guide biosimilar approval requirements regarding analytical and clinical data needs. The E.U. has approved several biosimilars under its regulatory framework established in 2005.
This document discusses biosimilars, which are biologic drugs developed after the patents expire on innovator biologics. It provides background on biologics and biosimilars, describing their complex structures and manufacturing processes. The document outlines global guidelines for biosimilars from organizations like the WHO and regulatory frameworks in regions like Europe. It also examines trends driving biosimilar growth and challenges in developing biosimilars, such as structural variability between products and potential immunogenicity.
Biosimilars are biologic medicines that are similar to already approved biologic reference products, though due to structural complexities they are not generic equivalents. They must demonstrate similarity in terms of safety, purity and potency through comprehensive comparability studies. Biologics are large, complex molecules produced through biotechnology in living cells, whereas generics are identical small molecule chemicals. Due to minor manufacturing differences, biosimilars can have efficacy or immunogenicity issues not seen with generics. India regulates biosimilars through various agencies including the Central Drugs Standard Control Organization.
This document provides information about biosimilars. It begins by discussing the history of biotechnology and defining biosimilars as copies of commercially available biopharmaceuticals that have been rigorously tested and approved by regulatory agencies. The document then lists several biosimilar agents and conditions they can treat. It describes the complex manufacturing process for biologics, involving genetic engineering of host cells to produce the desired proteins. The challenges of manufacturing biologics at a consistent quality are also discussed. The document concludes by mentioning some biosimilars approved in India and limitations to their use.
This document provides an overview of biosimilars including their definition, categories, development principles, and regulatory approval process. Biosimilars are biological products that are highly similar to an existing approved biologic reference product. They are developed through a stepwise comparative process to demonstrate similarity in terms of safety, purity and potency. Some key points covered include:
- Biosimilars are large protein therapeutics derived from living organisms unlike traditional small molecule drugs.
- They include categories like hormones, monoclonal antibodies, and recombinant proteins.
- Their development follows principles of extensive characterization studies comparing them to the reference product.
- In India, biosimilars require approval through the regulatory pathway overseen by authorities
This document discusses biosimilars and their regulation. It begins by defining biotechnology and biopharmaceuticals. Biosimilars are described as legally approved versions of biologic drugs that are similar but not identical to the original version. The document notes challenges in developing biosimilars due to the complex nature of biologics compared to traditional small molecule drugs. It also discusses concerns regarding efficacy, safety and interchangeability of biosimilars. Finally, it provides an overview of regulatory frameworks for biosimilars in the US, EU and India.
Biosimilars are biologic medicines that are developed to be similar to existing approved biologic medicines known as reference medicines. Biosimilars must demonstrate similarity to the reference medicine in terms of quality, safety and efficacy through comprehensive testing and analysis. While biosimilars may provide reduced costs and increased access to biologic treatments, they are more complex than traditional small molecule drugs due to differences in size, structure, manufacturing processes, and potential for immunogenicity. Thorough evaluation and regulation is required to ensure biosimilars are interchangeable for the reference product without compromising patient safety.
This document discusses biosimilars, which are biologic products that are highly similar to approved biologic reference products. It provides background on biosimilars, including their development process, advantages, limitations, and future outlook. The development process involves producing a cell line containing the gene for the desired protein, growing cells to produce the protein, purifying the protein, and preparing it for patient use. Biosimilars offer cost savings over biologics but have concerns around immunogenicity and long-term effects when switching between products. The global biosimilar market is expected to grow significantly as biologic patents expire and more companies develop biosimilar versions of treatments.
This document summarizes information about biosimilars and the regulatory pathways for their approval in the United States and European Union. It discusses how biosimilars differ from traditional small-molecule generics due to biological molecules' larger size, greater complexity, and manufacturing dependence. The U.S. passed the Biologics Price Competition and Innovation Act in 2010 to create an approval pathway for follow-on biologics, requiring biosimilarity demonstration and possible interchangeability labeling. Upcoming FDA hearings will provide information to guide biosimilar approval requirements regarding analytical and clinical data needs. The E.U. has approved several biosimilars under its regulatory framework established in 2005.
This document discusses biosimilars, which are biologic drugs developed after the patents expire on innovator biologics. It provides background on biologics and biosimilars, describing their complex structures and manufacturing processes. The document outlines global guidelines for biosimilars from organizations like the WHO and regulatory frameworks in regions like Europe. It also examines trends driving biosimilar growth and challenges in developing biosimilars, such as structural variability between products and potential immunogenicity.
Biosimilars are biologic medicines that are similar to already approved biologic reference products, though due to structural complexities they are not generic equivalents. They must demonstrate similarity in terms of safety, purity and potency through comprehensive comparability studies. Biologics are large, complex molecules produced through biotechnology in living cells, whereas generics are identical small molecule chemicals. Due to minor manufacturing differences, biosimilars can have efficacy or immunogenicity issues not seen with generics. India regulates biosimilars through various agencies including the Central Drugs Standard Control Organization.
This document provides information about biosimilars. It begins by discussing the history of biotechnology and defining biosimilars as copies of commercially available biopharmaceuticals that have been rigorously tested and approved by regulatory agencies. The document then lists several biosimilar agents and conditions they can treat. It describes the complex manufacturing process for biologics, involving genetic engineering of host cells to produce the desired proteins. The challenges of manufacturing biologics at a consistent quality are also discussed. The document concludes by mentioning some biosimilars approved in India and limitations to their use.
This document provides an overview of biosimilars including their definition, categories, development principles, and regulatory approval process. Biosimilars are biological products that are highly similar to an existing approved biologic reference product. They are developed through a stepwise comparative process to demonstrate similarity in terms of safety, purity and potency. Some key points covered include:
- Biosimilars are large protein therapeutics derived from living organisms unlike traditional small molecule drugs.
- They include categories like hormones, monoclonal antibodies, and recombinant proteins.
- Their development follows principles of extensive characterization studies comparing them to the reference product.
- In India, biosimilars require approval through the regulatory pathway overseen by authorities
Drug Types: Biosimilars, generics and more. December 2017 Webinar 12122017Fight Colorectal Cancer
This document provides information about an upcoming webinar on drug types including biosimilars and generics. It outlines details like the speaker, how to ask questions during the webinar, and instructions for accessing the webinar archive and following along on Twitter. It also provides brief bios of the speaker and gives technical instructions for participating in the webinar platform. Finally, it lists some resources and includes a standard disclaimer.
The document discusses biosimilars, which are biologic medicines that are similar but not identical to an original biologic. It describes the complex multi-step process used to develop and test biosimilars. This includes characterizing the original biologic, developing a unique cell line and process, testing for similarity through analytical and non-clinical studies, and clinical trials. Regulatory agencies oversee biosimilars differently than generics due to concerns over safety, substitution, naming, and labeling of the non-identical products.
Biosimilars are biopharmaceutical drugs that are similar to an existing approved biologic drug (the reference product). Biosimilars undergo a step-wise comparability exercise to demonstrate similarity in structure, function, safety and efficacy to the reference product. Regulatory agencies such as the FDA and EMA require extensive characterization, non-clinical and clinical studies to establish biosimilarity. Guidelines for approval of biosimilars have been established in regions such as Europe, US, Korea, Singapore and India to enable a pathway for approval of biosimilar versions of biologic drugs.
This document discusses biologics and biosimilars. It begins by explaining that biologics are large protein molecules derived from living cells that are used to treat diseases. Examples include human growth hormone, insulin, and monoclonal antibodies. Biosimilars are similar but not generic versions of innovator biologic products. The document outlines key differences between biologics and small molecule drugs, challenges in developing biosimilar monoclonal antibodies, and regulatory guidelines for approving biosimilars from organizations like WHO. It also discusses benefits and concerns regarding the use of biosimilars.
Biosimilars are protein drugs that are similar but not identical to existing biologic products whose patents have expired. They offer potential cost savings compared to innovator biologics but are more complex than traditional generics. Developing biosimilars requires extensive clinical testing to demonstrate similarity due to biologics' sensitivity to manufacturing processes. Regulatory approval pathways for biosimilars are more complex than for generics and involve demonstrating similarity rather than just bioequivalence.
1) The document discusses the concept of biosimilars, including their definition as biological products that are similar but not identical to an approved biologic in terms of quality, safety and efficacy.
2) It provides an overview of the regulatory approval pathways for biosimilars in the European Union, United States, and India, which generally require demonstrating biosimilarity through comparative clinical and non-clinical studies.
3) The production of biologics is more complex than small molecule drugs due to biologics' larger size, more complex structures, instability, and potential microheterogeneity.
Presentation at the Center for Professional Advancement (CFPA) Course on Generic Drug Approval, August 2013. New Brunswick, NJ., with a focus on how biosimilars are regulated
Definition of biopharmaceuticals and biosimilars, Steps involved in manufacturing biopharmaceuticals, Points of differences between Biosimilars and Chemical Generics, Related issues with biosimilars
Biosimilars are biotherapeutic products that are similar to already approved reference biologics in terms of quality, safety and efficacy. They are developed to be highly similar but not identical to existing biologics. Regulatory agencies like EMA and FDA require extensive analytical, non-clinical and clinical studies including pharmacokinetic, immunogenicity and clinical efficacy trials to establish biosimilarity. While biosimilars could increase access and lower costs, issues related to efficacy, safety, substitution and labeling need to be addressed to ensure patient safety and appropriate use.
This document summarizes the global regulatory landscape for biosimilars. It begins by defining biosimilars and biological drugs. It then discusses the guidelines established by various regulatory bodies including the EMA, FDA, WHO, and agencies in countries like Japan, Korea, Canada, China, and India. The guidelines generally require demonstrating biosimilarity to the reference product through comparative quality, nonclinical and clinical studies. The document also discusses business opportunities for biosimilars in emerging versus established markets and strategies used by originator companies to combat biosimilar competition. It concludes by noting concerns around interchangeability between biosimilars and reference products.
The document discusses biosimilars, which are biologic medical products that are similar copies of original products manufactured by different companies. A biosimilar is a version of an already registered biologic medicine that has demonstrated similarity in physicochemical, biological and immunological characteristics, efficacy and safety based on comprehensive comparability studies. The key difference between a generic drug and a biosimilar is that a generic is a chemically derived small molecule while a biosimilar is a complex biological product subject to more heterogeneity.
The document discusses biosimilars and the regulatory pathway for biosimilar approval in India. It provides background on biosimilars and how they differ from generics in terms of manufacturing complexity and clinical development requirements. It summarizes India's draft biosimilar guidelines, including that phase III trials with 100+ patients are required for approval but phase I-II may be waived. The guidelines aim to streamline the process while aligning with global standards from the EMA and WHO. Over 20 biosimilars have been approved in India across several therapeutic classes.
This document provides an overview of biosimilars and their regulatory framework. It begins with definitions of biologics and biosimilars. Biosimilars are highly similar versions of approved biologics whose patents have expired. The development of biosimilars is unique compared to small molecule generics due to the complex nature of biologics. The document then discusses issues with biosimilars including potential efficacy, safety and substitution concerns. Finally, it provides details on the regulatory frameworks and guidelines established by organizations like WHO, EU, US and India to help facilitate the development and approval of biosimilars.
Increasing knowledge of genetics and cell processes leads to potential new biologic (and drug) targets at each step in the protein-production process. This leads to new therapies, which in turn lead to new understanding of diseases. Here is an update on relatively new drugs called biologics...
This document provides an executive summary of key information about biosimilars, biogenerics, and follow-on biologics. It discusses how biosimilars represent one of the most rapidly evolving areas in the pharmaceutical industry as patents on the first generation of biopharmaceuticals expire. The EU has legislation in place for biosimilar approval, while the US is working to pass similar legislation. The report profiles 15 companies involved in biosimilars development and forecasts that the global biosimilars market will grow from $30 million in 2006 to $3.2 billion in 2011, with Europe leading the way. It also summarizes the document's coverage of potential biosimilar targets, scientific and regulatory issues
This document discusses biologics and biosimilars. It defines biologics as biological products made from natural sources like humans, animals or microorganisms that are used to treat or prevent diseases. Biosimilars are highly similar versions of biologics that are approved because they have no clinically meaningful differences. The document outlines key differences between biologics and biosimilars like regulatory pathways and development testing. It also compares biosimilars to generics and discusses important considerations for biosimilar development like immunogenicity, bioequivalence and post-translational modification.
The document discusses key differences between biotherapeutics (large molecule medicines produced from living cells) and small molecule medicines. Biotherapeutics are much larger and more complex structures than small molecules. Their development, manufacturing, and regulatory evaluation require specialized considerations and standards due to their sensitivity, potential for immunogenicity, and structural complexity. The document outlines the complex manufacturing processes required for biotherapeutics, regulatory frameworks for evaluating manufacturing changes and ensuring comparability over the product lifecycle, and calls for dedicated legislation and guidance to appropriately regulate biotherapeutic development, approval, and post-marketing activities.
This document provides an overview of biosimilars including their advantages and disadvantages. It discusses regulatory guidelines for biosimilar approval in India, challenges in biosimilar development and production, and recently approved biosimilars. The conclusion recognizes biosimilars as an important part of the pharmaceutical ecosystem but one that faces barriers to adoption such as questions of interchangeability and not having approval for all reference product indications. It recommends overcoming challenges to biosimilar market access.
This 3-day event is the meeting place for international and domestic scientists to share case studies and project updates, showcase new techniques and form collaborations that pave the way towards the future of China’s biopharmaceutical industry.
Drug Types: Biosimilars, generics and more. December 2017 Webinar 12122017Fight Colorectal Cancer
This document provides information about an upcoming webinar on drug types including biosimilars and generics. It outlines details like the speaker, how to ask questions during the webinar, and instructions for accessing the webinar archive and following along on Twitter. It also provides brief bios of the speaker and gives technical instructions for participating in the webinar platform. Finally, it lists some resources and includes a standard disclaimer.
The document discusses biosimilars, which are biologic medicines that are similar but not identical to an original biologic. It describes the complex multi-step process used to develop and test biosimilars. This includes characterizing the original biologic, developing a unique cell line and process, testing for similarity through analytical and non-clinical studies, and clinical trials. Regulatory agencies oversee biosimilars differently than generics due to concerns over safety, substitution, naming, and labeling of the non-identical products.
Biosimilars are biopharmaceutical drugs that are similar to an existing approved biologic drug (the reference product). Biosimilars undergo a step-wise comparability exercise to demonstrate similarity in structure, function, safety and efficacy to the reference product. Regulatory agencies such as the FDA and EMA require extensive characterization, non-clinical and clinical studies to establish biosimilarity. Guidelines for approval of biosimilars have been established in regions such as Europe, US, Korea, Singapore and India to enable a pathway for approval of biosimilar versions of biologic drugs.
This document discusses biologics and biosimilars. It begins by explaining that biologics are large protein molecules derived from living cells that are used to treat diseases. Examples include human growth hormone, insulin, and monoclonal antibodies. Biosimilars are similar but not generic versions of innovator biologic products. The document outlines key differences between biologics and small molecule drugs, challenges in developing biosimilar monoclonal antibodies, and regulatory guidelines for approving biosimilars from organizations like WHO. It also discusses benefits and concerns regarding the use of biosimilars.
Biosimilars are protein drugs that are similar but not identical to existing biologic products whose patents have expired. They offer potential cost savings compared to innovator biologics but are more complex than traditional generics. Developing biosimilars requires extensive clinical testing to demonstrate similarity due to biologics' sensitivity to manufacturing processes. Regulatory approval pathways for biosimilars are more complex than for generics and involve demonstrating similarity rather than just bioequivalence.
1) The document discusses the concept of biosimilars, including their definition as biological products that are similar but not identical to an approved biologic in terms of quality, safety and efficacy.
2) It provides an overview of the regulatory approval pathways for biosimilars in the European Union, United States, and India, which generally require demonstrating biosimilarity through comparative clinical and non-clinical studies.
3) The production of biologics is more complex than small molecule drugs due to biologics' larger size, more complex structures, instability, and potential microheterogeneity.
Presentation at the Center for Professional Advancement (CFPA) Course on Generic Drug Approval, August 2013. New Brunswick, NJ., with a focus on how biosimilars are regulated
Definition of biopharmaceuticals and biosimilars, Steps involved in manufacturing biopharmaceuticals, Points of differences between Biosimilars and Chemical Generics, Related issues with biosimilars
Biosimilars are biotherapeutic products that are similar to already approved reference biologics in terms of quality, safety and efficacy. They are developed to be highly similar but not identical to existing biologics. Regulatory agencies like EMA and FDA require extensive analytical, non-clinical and clinical studies including pharmacokinetic, immunogenicity and clinical efficacy trials to establish biosimilarity. While biosimilars could increase access and lower costs, issues related to efficacy, safety, substitution and labeling need to be addressed to ensure patient safety and appropriate use.
This document summarizes the global regulatory landscape for biosimilars. It begins by defining biosimilars and biological drugs. It then discusses the guidelines established by various regulatory bodies including the EMA, FDA, WHO, and agencies in countries like Japan, Korea, Canada, China, and India. The guidelines generally require demonstrating biosimilarity to the reference product through comparative quality, nonclinical and clinical studies. The document also discusses business opportunities for biosimilars in emerging versus established markets and strategies used by originator companies to combat biosimilar competition. It concludes by noting concerns around interchangeability between biosimilars and reference products.
The document discusses biosimilars, which are biologic medical products that are similar copies of original products manufactured by different companies. A biosimilar is a version of an already registered biologic medicine that has demonstrated similarity in physicochemical, biological and immunological characteristics, efficacy and safety based on comprehensive comparability studies. The key difference between a generic drug and a biosimilar is that a generic is a chemically derived small molecule while a biosimilar is a complex biological product subject to more heterogeneity.
The document discusses biosimilars and the regulatory pathway for biosimilar approval in India. It provides background on biosimilars and how they differ from generics in terms of manufacturing complexity and clinical development requirements. It summarizes India's draft biosimilar guidelines, including that phase III trials with 100+ patients are required for approval but phase I-II may be waived. The guidelines aim to streamline the process while aligning with global standards from the EMA and WHO. Over 20 biosimilars have been approved in India across several therapeutic classes.
This document provides an overview of biosimilars and their regulatory framework. It begins with definitions of biologics and biosimilars. Biosimilars are highly similar versions of approved biologics whose patents have expired. The development of biosimilars is unique compared to small molecule generics due to the complex nature of biologics. The document then discusses issues with biosimilars including potential efficacy, safety and substitution concerns. Finally, it provides details on the regulatory frameworks and guidelines established by organizations like WHO, EU, US and India to help facilitate the development and approval of biosimilars.
Increasing knowledge of genetics and cell processes leads to potential new biologic (and drug) targets at each step in the protein-production process. This leads to new therapies, which in turn lead to new understanding of diseases. Here is an update on relatively new drugs called biologics...
This document provides an executive summary of key information about biosimilars, biogenerics, and follow-on biologics. It discusses how biosimilars represent one of the most rapidly evolving areas in the pharmaceutical industry as patents on the first generation of biopharmaceuticals expire. The EU has legislation in place for biosimilar approval, while the US is working to pass similar legislation. The report profiles 15 companies involved in biosimilars development and forecasts that the global biosimilars market will grow from $30 million in 2006 to $3.2 billion in 2011, with Europe leading the way. It also summarizes the document's coverage of potential biosimilar targets, scientific and regulatory issues
This document discusses biologics and biosimilars. It defines biologics as biological products made from natural sources like humans, animals or microorganisms that are used to treat or prevent diseases. Biosimilars are highly similar versions of biologics that are approved because they have no clinically meaningful differences. The document outlines key differences between biologics and biosimilars like regulatory pathways and development testing. It also compares biosimilars to generics and discusses important considerations for biosimilar development like immunogenicity, bioequivalence and post-translational modification.
The document discusses key differences between biotherapeutics (large molecule medicines produced from living cells) and small molecule medicines. Biotherapeutics are much larger and more complex structures than small molecules. Their development, manufacturing, and regulatory evaluation require specialized considerations and standards due to their sensitivity, potential for immunogenicity, and structural complexity. The document outlines the complex manufacturing processes required for biotherapeutics, regulatory frameworks for evaluating manufacturing changes and ensuring comparability over the product lifecycle, and calls for dedicated legislation and guidance to appropriately regulate biotherapeutic development, approval, and post-marketing activities.
This document provides an overview of biosimilars including their advantages and disadvantages. It discusses regulatory guidelines for biosimilar approval in India, challenges in biosimilar development and production, and recently approved biosimilars. The conclusion recognizes biosimilars as an important part of the pharmaceutical ecosystem but one that faces barriers to adoption such as questions of interchangeability and not having approval for all reference product indications. It recommends overcoming challenges to biosimilar market access.
This 3-day event is the meeting place for international and domestic scientists to share case studies and project updates, showcase new techniques and form collaborations that pave the way towards the future of China’s biopharmaceutical industry.
2013 ets ce course materials (stresa italy)mothersafe
This document summarizes an education course on testing strategies for biopharmaceuticals. The course included three speakers and covered the following topics:
1. Manon Beekhuijzen from WIL Research Europe gave an introduction to biopharmaceuticals and developmental and reproductive toxicity (DART) testing. She discussed the traditional segmented approach to DART testing and considerations for biopharmaceuticals from ICH S5 and S6 guidelines.
2. Paul Barrow from Roche discussed the non-clinical testing of vaccines, focusing on the FDA 2006 guidance for vaccines intended for use during pregnancy.
3. Gary Chellman from Charles River Laboratories spoke about the use of nonhuman primates for biopharmaceutical
Professor Sharon Ricardo of Monash University is researching a novel therapy using colony stimulating factor 1 (CSF-1) to promote organ growth and maturation in premature infants and those with intrauterine growth restriction. Her research was inspired by findings that CSF-1 can promote postnatal organ development. She plans to test CSF-1's effects on lung development and maturation using a newborn lamb model of intrauterine growth restriction that mimics the underdeveloped lungs seen in similarly growth-restricted human infants. If results are positive, she hopes to advance the therapy to clinical trials as CSF-1 has shown safety in previous adult trials. The research aims to develop a treatment for the health complications commonly experienced by premature infants.
Phagocytes, Natural Killer cells, Complement system
Inflammation: Localized response to infection or injury
1.1.2 Acquired immunity
Acquired immunity is the immunity that develops after exposure to an antigen either through
infection or vaccination. It provides long lasting protection against re-infection. It is a slower
acting response than innate immunity but is highly specific to the pathogen.
Includes:
Cellular immunity: Mediated by T lymphocytes
Humoral immunity: Mediated by B lymphocytes and antibodies
1.2 Monoclonal Antibodies
Monoclonal antibodies are antibodies that are made by identical immune cells that are all
clones of a unique parent
Access to Research
Date 11-08-2018
Venue Conference HAll NIAS IISc campus
Conference and workshops for clinical practitioners to introduce them to modern tools and an alternative approach to modern scientific research.
Purpose
1. Build a network of physicians across the country
2 Train physicians to analyse clinical data and restructure it to make it compatible with research standards
3. Introduce modern tools to understand the mechanism of actions of medicine
4. Introduce artificial intelligence and machine learning to clinical practitioners to support decision-making processes
Access to Science
Clinical experience and traditional knowledge are important sources of data that affect decision making processes in modern healthcare systems. This data should be made accessible for scientific evaluation and validation to improve healthcare worldwide. The Open Source Pharma Foundation believes that clinical practitioners from various disciplines should have the right to access research so that they can help identify problems, contribute their scientific knowledge, and support the discovery ecosystem.
Background
The majority of medical practitioners working on the ground level with patients do not take part in open clinical research worldwide. However, the data collected and owned by them plays an important role in establishing better discovery pathways. Through this workshop, we seek to open opportunities to enhance health care systems around the world and to overcome the following challenges faced by medical practitioners.
1. Regulatory limitations
2. Academic limitations
3. Time constraints
4. Lack of access to modern tools
2020 09-07 European Center Pharmaceutical Medicine course Biomarkers, Basel, ...Alain van Gool
Tutorial lecture on biomarkers for pharmaceutical industry R&D professionals, outlining status, potential and challenges of biomarkers in pharma, clinic and society.
- Oral insulin capsules developed by Oramed Pharmaceuticals were found to successfully lower blood sugar levels in human clinical trials. The company is now conducting a larger 90-day study to further evaluate the capsules' effects on HbA1c and their potential as a safer, more convenient alternative to injected insulin.
- Scientists at the John Innes Centre identified the last missing genes in the Madagascar periwinkle plant that allow it to produce the important cancer-fighting alkaloids vinblastine and vincristine. Understanding these genes could help increase sustainable production of these drugs through plant or synthetic biology techniques.
- Researchers at multiple institutions reported developments that could help advance cancer treatment, including
Regenerative Medicine: Impact of Convergence on Drug, Device, and Biologics D...MaRS Discovery District
Speaker Dr. Annemarie Moseley, CEO of Aggregate Therapeutics (Palo Alto) explores how drug-device combination products are altering the medical practice from development to regulation to treatment.
Part of the MaRS Emerging Technologies Event Series. More information on the series can be found here:
http://www.marsdd.com/emergingtech/
Precision medicine is an emerging strategy that considers individual variability in genes, environment, and lifestyle to diagnose, treat, forecast, and prevent disease. As regulatory health authorities begin to develop clearer regulatory pathways in precision medicine, industries must prepare to swiftly adopt to any regulatory changes. This white paper aims to provide a broad overview on the following key topics in precision medicine:
1. Genomics and Pharmacogenetics
2. Precision Medicine vs Personalized Medicine
3. Foundation of Precision Medicine as A Treatment Tool
4. Examples of Precision Medicine as A Treatment, Predictive, and Preventative Tool
5. Precision Medicine and Cancer
6. Challenges, Next Step & Opportunities in Precision Medicine
7. Regulatory insight on Precision medicine
One mans supergeneric is anothers life cycle managementMalcolm Ross
This document discusses the potential for generic pharmaceutical companies to develop "supergeneric" or value-added generic drug products. It provides examples of how simple reformulations or new delivery methods for off-patent drugs could create differentiated products with improved efficacy or compliance compared to existing generics. Developing combination products or modified release formulations are presented as opportunities requiring relatively little investment that leverage existing technical skills at generic companies.
This document discusses the use of animal models in pharmaceutical research and their limitations. It describes how animal doses are converted to human equivalent doses using allometric scaling based on body surface area. The document also discusses alternative approaches like computer-based modelling and physiologically-based pharmacokinetic/pharmacodynamic modelling to predict human responses based on data from animal and other preclinical studies in order to reduce risks in early human trials. Several companies that have implemented such modelling approaches are also mentioned.
Pharma-Nutrition: a pharma perspective. View how the pharmaceutical drug development model can and should be combined with the nutrition field to optimally implement personalized healthcare.
A study was conducted using Immunocal protein supplementation as part of a prehabilitation program for patients scheduled for colorectal surgery. The prehabilitation program, which included exercise, nutrition counseling and Immunocal, began 4 weeks before surgery. Patients who completed the prehabilitation program were able to walk significantly further in a 6-minute walking test compared to those who began rehabilitation only after surgery. The prehabilitation program helped to improve patients' functional capacity and physical strength before surgery, allowing for better recovery outcomes.
Bioanalytical Method Development and Validation of Biosimilars: Lessons LearnedSai Babitha
Biosimilars are expected to be a significant growth driver for the pharmaceutical industry over the next decade, mainly because of the current market penetration of biologics and the need to provide payers cost savings over the originator therapeutics. Legislative support and regulatory guidance have facilitated their entry into pharmacy formularies of the future. Unlike small molecule generic drugs, biosimilars are heterogeneous proteins manufactured using cell-based systems of either microbial or mammalian origin. The use of living systems to manufacture drugs raises challenges in terms of product characterization and therapeutic equivalence to the innovator protein therapeutic. In this article, we share some lessons learned from developing
and validating pharmacokinetic and immunogenicity assays that support preclinicaland clinical comparative studies for the development of biosimilars.
Dr. Adrian Stevens received his Ph.D. in computational chemistry from the University of Portsmouth. He has since worked for 9 years at a contract research organization specializing in small molecule discovery research and collaborated with pharmaceutical companies. Following a brief time at another company, he joined Accelrys in 2008 and is now a Senior Product Marketing Manager responsible for the Discovery Studio product.
Vasilios Papademetriou is a cardiologist and professor of medicine at Georgetown University who has collaborated extensively with the biomedical industry. He discusses several career pathways for medical students in the biomedical industry, including doing clinical trials sponsored by industry, serving on advisory boards, and collaborating on research. He provides examples of physicians who have successfully worked with industry to develop new drugs and devices.
“The Evolution of Pharmaceutical Biotechnology – Science, Strategies, Products, and Regulations”
Shows the latest developments in pharmaceutical biotechnology and provides a broad overview of biotherapeutic & biosimilar regulations globally and in the EU
Immuron Limited is a clinical stage biopharmaceutical company developing oral immunotherapies for inflammatory and infectious diseases. Their lead program, IMM-124E, is in Phase 2 trials for NASH, ASH, and pediatric NAFLD, with interim data expected in 3Q 2017 and full results by 4Q 2017. IMM-124E has shown positive preclinical data, demonstrating a reduction in liver fibrosis, inflammation, and metabolic markers. Immuron also has a drug candidate, IMM-529, in development for C. difficile infection, expected to begin Phase 1/2 trials in 2Q 2017.
Pacific BioLabs can assist with all stages of drug development through their scientists and testing services. The drug development process involves several stages including discovery, product characterization, formulation and delivery testing, preclinical toxicology testing and clinical trials. Pacific BioLabs' experienced staff can perform the necessary tests and studies to help drugs progress through these stages and gain FDA approval.
Similar to Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings on "Follow-On Biopharmaceuticals" (20)
Civica will manufacture and distribute biosimilar insulins at an affordable price to help the millions of Americans who struggle to afford life-saving insulin medications. They plan to produce glargine, lispro and aspart insulin and sell them for no more than $30 per vial or $55 for a box of pen cartridges. This would represent up to a 90% discount compared to current market prices and ensure no one has to ration insulin due to cost. JDRF and other organizations are partnering with Civica to help reduce healthcare disparities and make insulin universally accessible.
On March 3, 2022, the nonprofit drug company Civica Rx announced its intention to introduce 3 insulin biosimilars at list prices which promise to be below copays and cost-sharing on insulin for many insured patients, as well as much less costly for uninsured patients.
This document provides background information on Scott Strumello and his assessment of why insulin prices are so high in the US. It discusses how Strumello investigated the issue and found that while drug companies share some blame, the primary culprits are health insurance companies. Insurance companies collect large rebates on insulin but fail to pass these savings to patients, instead using the money to offer premium discounts to employers. This forces many patients to pay the full list price of insulin out of pocket due to high deductible plans. While drug companies, pharmacy benefit managers, and legislators all play a role, Strumello argues that insurance companies deserve most of the blame for the rising out-of-pocket costs that patients face.
The document contains a transcript of an online discussion between Larry Soler, Vice President of Government Relations at the Juvenile Diabetes Research Foundation (JDRF), and several participants. Soler discusses JDRF's advocacy efforts and priorities, which include expanding stem cell research policies, increasing funding for juvenile diabetes research, and increasing the availability of pancreases for islet cell transplants. He explains how JDRF utilizes volunteers and grassroots organizing to effectively lobby Congress and influence policy on issues related to diabetes research.
Spinach and Artichoke Dip (Associated Press)sstrumello
This recipe provides instructions for making a spinach and artichoke dip appetizer. It calls for Greek yogurt, cream cheese, spinach, artichoke hearts, onions, herbs, and crushed whole-grain crackers. The ingredients are combined and baked for 10-15 minutes until hot. The dip serves 8 people and each serving contains 32 calories, 2g fat, 1g protein, and 3g carbohydrates.
The document outlines the agenda for Roche's 2011 Social Media Summit, including presentations and discussions on emerging diabetes social media trends, Roche products like insulin pumps and meters, and workshops on developing ideas for engaging the diabetes community online. The summit brings together Roche representatives and guests from diabetes organizations to share insights and strategize ways to enhance digital outreach efforts.
IDF Presentation to 2011 Roche Social Media Summitsstrumello
The International Diabetes Federation (IDF) is a global organization focused on diabetes care, prevention, and treatment. It has over 220 member associations in over 160 countries. The IDF aims to stem the growing global diabetes epidemic by advocating for policies and programs, raising awareness through events like World Diabetes Day, publishing research on diabetes prevalence and costs, and convening the global diabetes community. In the lead up to the 2011 UN Summit on non-communicable diseases, the IDF is lobbying governments to commit to national diabetes plans and increased resources to fight diabetes worldwide.
This document discusses how new diabetes technologies promise easier management but many people still struggle to maintain control or avoid burnout. While technology helps, people need breaks from the constant demands of diabetes care. The document contrasts unsafe breaks like ignoring treatment with safe breaks like occasional relaxed monitoring that don't compromise long-term health but provide needed relief. It encourages planning occasional breaks to sustain motivation and enjoying life with diabetes.
Biodel, Inc. Investor Presentation January 14, 2010sstrumello
This document summarizes a presentation given at the 28th Annual Healthcare Conference in San Francisco on January 14, 2010. The presentation was given by Biodel Inc., a company focused on developing enhanced insulin therapies for diabetes. Biodel discussed their lead product candidate VIAject, an ultra rapid-acting prandial insulin, which completed two successful Phase 3 trials and is awaiting FDA approval. The presentation provided an overview of Biodel's pipeline of diabetes programs, the insulin market opportunity, and preclinical and clinical data demonstrating VIAject's superior pharmacokinetic and pharmacodynamic profile compared to existing rapid-acting insulins.
Lola, a 2-year-old Yorkshire terrier, won first place in the "Smartest Pet in Queens" contest. She knows tricks like sit, paw down, and up, and likes to pretend fly. Princess, a mixed breed dog, came in second place. She can hold a ball in her mouth with her paws and prays without a ball. Phyllis, a half Siamese cat, took third place. She alerts her owner Scott of his juvenile diabetes episodes and ensures he is okay at night.
One of the latest success stories in diabetes research has been the development of anti-CD3 monoclonal antibodies to slow the progression of type 1 diabetes, which has been in development for over a decade. Two biotechnology companies, MacroGenics and Tolerx, are currently conducting phase III clinical trials testing different anti-CD3 drugs, with the goal of preserving insulin-producing beta cell function and reducing insulin needs. If successful, the results of these trials could provide evidence for FDA approval of anti-CD3 therapy as a treatment for newly diagnosed type 1 diabetes patients.
Most commercial insulin assays fail to detect recombinant insulin analoguessstrumello
Most commercial insulin assays are unable to accurately detect recombinant insulin analogues. A study published in 2006 found that many insulin tests on the market fail to measure modern insulin formulations that are genetically engineered versions of human insulin. This can lead to incorrect results when monitoring insulin levels in patients taking analogues.
Stanford University Case Study: Novo Nordisksstrumello
Novo Nordisk was historically the second largest producer of insulin in the world in 1981, supplying 25% of global demand. While it dominated the European market, it held less than 5% share in the large and lucrative US market, which was dominated by Eli Lilly at 83% share. By 1995, the insulin industry had consolidated significantly due to changes in technology, regulation, and competition. Novo broadened its product portfolio and global presence but continued to trail Eli Lilly in the important US market. Managing this competitive challenge would be a focus for Novo Nordisk's leadership going forward.
Could Generic Insulin Soon Hit the U.S. Market?sstrumello
Diabetes blogger Scott Strumello (sstrumello.blogspot.com) investigates whether follow-on (generic) insulin formulation will soon emerge in accordance with U.S. patent law.
Publish Date: January 1, 2007
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...Donc Test
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Study Guide Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Course Hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Answers Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Course hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Study Guide Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Ebook Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Questions Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Stuvia
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings on "Follow-On Biopharmaceuticals"
1. Statement of Inger Mollerup, MSc
Vice President
Novo Nordisk A/S
Before the
Government Oversight and Reform Committee
Hearing On
“Safe and Affordable Biotech Drugs – The Need for a Generic Pathway”
March 26, 2007
2. Statement of Inger Mollerup, MSc
Vice President, Novo Nordisk A/S
Government Oversight and Reform Committee
March 26, 2007
Chairman Waxman, Ranking Member Davis, and members of the
Committee, thank you for inviting me to testify today. My name is
Inger Mollerup and I am Vice President for Regulatory Affairs at Novo
Nordisk A/S. Novo Nordisk is a healthcare company with an 80-year
history of innovation and achievement in diabetes care. In addition to
diabetes care, Novo Nordisk has a leading position within areas such
as hemostasis management, growth hormone therapy, and hormone
therapy for women. Novo Nordisk's business is driven by the Triple
Bottom Line: a commitment to economic success, environmental
soundness, and social responsibility to employees and customers. Our
global headquarters are in Denmark and our U.S. headquarters are in
Princeton, New Jersey.
For approximately 30 years, I have been involved in the design of
manufacturing processes and development programs for a number of
recombinant proteins for Novo Nordisk. With this background, in
December 2005, I presented before the European Medicines Agency
(EMEA) as part of a panel on guidelines for biosimilar insulins
(biosimilars is the term for follow-on biologics in Europe) and then
2
3. presented before the World Health Organization INN Committee in
November 2006 on the topic of naming biosimilars. Novo Nordisk
wants to work closely with Congress as it considers the best way to
establish a legal and regulatory pathway for biosimilars, or follow-on
biologics as they are called in the United States.
The creation of an entirely new approval pathway for a new class of
drug products not presently on the market is an enormous undertaking
with serious consequences for literally millions of patients. Novo
Nordisk believes any pathway for follow-on biologics should be rooted
in the best science, preserve innovation, respect proprietary
information, and most importantly be constructed to protect patient
safety. Based on my experience with all of the therapeutic proteins I
have worked with over the years, it is clear that biological medicines
are both individual and complicated. Any pathway must take into
account the fact that biological medicines are distinctly different from
chemical drugs or we will fail in our responsibility to ensure patient
safety and product efficacy.
Characterization Doesn’t Tell the Whole Story
3
4. Biological medicines are complicated – but we have a long track record
showing that they can be developed and characterized, and all the
same tools are available for the development of follow-on biologics.
However, while some of the best known peptide molecules – like
insulin – can be largely characterized with today’s technology, we do
not yet have the tools and models that enable us to predict safety and
efficacy from that characterization without undertaking human clinical
trials.
Any pathway should fully address the patient safety considerations of
medicines that are “similar to” or “comparable to” instead of “same as”
the reference product. Given that proposals currently before Congress
go far beyond the science in an effort to deem products having “minor
differences in amino acid sequence” as “highly similar,” I would like to
share with you an experience we had at Novo Nordisk with two
potential therapeutic proteins with just one amino acid difference.
Case Study: Minor Differences Can Have Major Health Consequences
Our goal was to create a fast acting insulin analogue that would enable
patients with diabetes to use the medicine in close connection with a
meal to control mealtime rise in blood glucose (and thus ease the
4
5. problem of too much or too little insulin at mealtime - a regular patient
safety issue prior to the advent of the fast acting insulins). To pursue
this goal, Novo Nordisk’s strategy was to make a change in the amino
acid sequence. We developed a number of drug candidates that were
put into an extensive chemical, preclinical and clinical program. The
candidate that we took to the market has only one change to the
amino acid sequence from its precursor: in position B28 threonine is
exchanged for aspartic acid. This change has resulted in an analogue
(NovoLog) with significantly shorter time of action than human insulin
(Novolin® R) and a unique safety profile. Significantly, an earlier
candidate, also with only one amino acid substitution, similarly showed
a positive effect on the timing of action but in full pre-clinical animal
toxicological studies, this drug candidate also created a significantly
increased tumourigenic (tumor growth response) potential in rats.
This led to a decision by Novo Nordisk to immediately discontinue this
program. As this experience shows, a seemingly “minor” difference
can have enormous consequences for important safety characteristics.
Preclinical and Laboratory Tests Not Sufficient to Determine
Immunogenicity and Other Issues
5
6. Mr. Chairman, this leads me to my next point. Based on our
experience as I’ll describe below, we believe clinical data is necessary
to ensure that a follow-on biologic is safe. We are not advocating for a
full package similar to that required of innovators, but comparable
clinical data, albeit abbreviated, should be required to ensure drug
safety.
In 2002, Novo Nordisk approached the FDA about creating a second
generation manufacturing process for our fast acting insulins. Such
upgrades are important because they ensure that our manufacturing
technology processes are up-to-date and that our production capacity
is adequate to meet demand. The changes involved in creating this
second generation process included the use of a new precursor DNA; a
new production strain and cell bank of the original host cell
(S.ccerivisiae); optimized fermentation, recovery and purification; and
a new complete production facility. Any follow-on biologic
manufacturer would have to do no less than (and most likely
significantly more) to develop their unique manufacturing process than
what was included in this undertaking for Novo Nordisk.
In order to implement these changes, the FDA required us to supply
comparability data (comprising quality data on the structure, impurity
6
7. profile, stability and in-process characteristics), and clinical data
encompassing phamcokinetics/pharmacodynamics (PK/PD) data as
well as human immunogenicity data. To clarify, immunogenicity is
how our body naturally responds to foreign substances – by
developing antibodies. In our discussions with the FDA, they
expressed confidence in our ability to detect and characterize
impurities in this newly constructed medicine. However, FDA stated
that no general safety threshold, even one as low as 0.1%, could be
applied for new impurities because proteins can be immunogenic at
very low concentrations and it is not known when “low” is “low
enough.” Because the immunogenic potential of a protein cannot be
predicted from laboratory or preclinical investigations, the FDA
required immunogenicity data from an appropriate clinical study. In
response, Novo Nordisk submitted data showing comparable
immunogenicity between the new and the older processes in a study of
several hundred patients.
FDA Authority Should Not Be Constrained
Another example that may assist the Committee in their evaluation of
how to establish a pathway that ensures that potential follow-on
therapeutic proteins are both safe and effective can be illustrated by
7
8. the challenges Novo Nordisk faces in the investigation of a second
generation process for the production of rFVIIa, a coagulation
(clotting) factor used for the treatment of hemophilia patients with
inhibitors. By moving from the current mammalian cell line derived
from baby hamster kidneys to one derived from a Chinese hamster
ovary (CHO) cell line, a more robust cell line for large scale
manufacturing will be obtained.
At an early process step we identified a low level impurity (well below
0.1% in the drug substance) from the CHO cell line, which we
proceeded to isolate and characterize. When we tested our
experimental rFVIIa material in a repeat dose animal toxicity study we
found a large number of animals developing antibodies directed
against this impurity, indicating that it was very immunogenic in
monkeys. Because this impurity is a foreign protein both to monkey
and man, it implied a significant risk that our new product could lead
to similar immunogenicity in humans with potential safety implications.
Therefore we implemented additional process steps which succeeded
in reducing this impurity to extremely low levels.
This example points out the need for the FDA to have the authority to
require any safety studies it deems necessary to protect the public
8
9. safety. The fact is that a follow-on manufacturer, even after
characterizing a product, would have a different cell line from the
innovator, different processes, different raw materials, and no matter
how well characterized, would not be able to be sure of the
immunogenic effect of its product without clinical trials. Imagine the
impact on patient safety if a follow-on manufacturer took a product to
market not realizing that there were such impurities in the product
from the host cell – and had not done clinical trials because Congress
had not allowed FDA to require it.
Indeed, when we discussed this cell change program with the FDA at a
pre-IND meeting, the FDA made it clear that rFVIIa produced in the
new host cell line would be seen as a new product, which would need
to stand on its own quality, safety and efficacy documentation
including substantial clinical work and requiring submission of a full
new BLA.
Multiple Indications Require Appropriate Data
Congress should reject proposals that would give a follow-on biologic
based on a limited comparative clinical trial in one indication all
indications of the innovator. Safety issues in different patient
9
10. populations treated with the same drug are not necessarily the same.
RFVIIa® serves as a useful example here. RFVIIa® is a coagulation
factor – meant to stop bleedings – and hence events associated with
excessive clotting or formation of thrombi (blood clots) pose potential
safety concerns. The risk of thrombus formation in a population of
hemophilia patients with inhibitors (for which the product is approved)
can be very different from the risk for patients with a normal
coagulation system (for which the product has been/is being
investigated in clinical trials). Similarly, the safety concerns for growth
hormone treatment of children with growth hormone deficiency are
different from those for adult patients with AIDS wasting for which
growth hormone is also indicated. Because of the nature of the
underlying conditions, subtle differences between a follow-on and
innovator product that may not be evident in one patient population
(i.e., may be considered a “minor” difference in that group of patients)
may express itself more dramatically and detrimentally when the
follow-on product is administered to a different patient population.
Furthermore, adequate clinical and post-marketing safety experience
in the use of a product in any indication should be established with the
innovator product before a follow-on version (with reduced amount of
safety data) can be approved.
10
11. Current Science Doesn’t Support Interchangeability
Because of the potential difference in immunogenicity and other drug-
specific adverse events, and because a follow-on biologic product
cannot be determined to be the same as the innovator product, these
products should not be allowed to be interchangeable. The European
system recognizes that “by definition similar biological medicinal
products are not generic medicinal products, since it could be expected
that there may be subtle differences between similar biological
medicinal products from different manufacturers or compared with
reference products, which may not be fully apparent until greater
experience in their use has been established.” (Guideline on Similar
Biological Medicinal Products (CHMP/437/04)) There is a further
requirement that the products are clearly identified to support post-
market monitoring. In addition, there is no evidence to support
interchangeability in existing biologics, let alone a new class of
biologics with different safety standards. For example, there are
currently three different companies who manufacture 9 different types
of insulins in 23 different presentations – and they are not
interchangeable. Indeed, the FDA expressed its concerns with
interchangeability in September, 2006: “With protein products, as of
today, the FDA has not determined how interchangeability can be
11
12. established for complex proteins. Different large protein products,
with similar molecular composition may behave differently in people
and substitution of one for another may result in serious health
outcomes, e.g., generation of a pathologic immune response.”
(http://www.fda.gov/cder/news/biosimilars.htm)
Traceability Important to Protect Safety
Congress should also carefully consider the issues involved in
traceability, as Europe has done. Because these products are similar,
but not the same, all protein drugs should be prescribed and given to
the patient based on a unique name. To reference the regulations
implemented in Europe, “in order to support pharmacovigilance
monitoring, the specific medicinal product given to the patient should
be clearly identified.” (Guideline on Similar Biological Medicinal
Products (CHMP/437/04)) Different names will underscore that the
products are, indeed, not “the same” and will help prescribers and
dispensers avoid mistakes. Even extensive pre-approval clinical
testing may be insufficient to detect rare, but potentially serious, side
effects including immunogenicity. Such effects are often specific to
one product but not another. Assurance of safety depends, even more
than for typical small molecule drugs, on pharmacovigilance and other
12
13. post-marketing surveillance measures which allow the tracing of
adverse events to a specific product – all of which are much more
difficult if products from different manufacturers bear the same name
(e.g. USAN or INN).
Conclusion
In summary, our experiences at Novo Nordisk have repeatedly shown
that even small impurities or differences in molecular structure can
lead to very important changes in properties of the product. These
changes are not always detectable by standard analytical methods or
predictable by animal tests, and therefore going beyond simple
bioequivalence studies and requiring appropriate clinical investigations
to document safety in patients is necessary.
Members of the Committee, the development of a follow-on biologics
pathway is a complicated issue because of the significant scientific and
public health issues involved. However, Novo Nordisk believes a
pathway for follow-on biologics is possible provided it is rooted in the
best science, preserves innovation of life-saving medicines for millions
of patients across the globe, respects proprietary information, and
13
14. most importantly is constructed to protect patient safety. Novo
Nordisk stands ready to assist Congress as this issue moves forward.
14