Definition of biopharmaceuticals and biosimilars, Steps involved in manufacturing biopharmaceuticals, Points of differences between Biosimilars and Chemical Generics, Related issues with biosimilars
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.
The document discusses tofacitinib, an oral JAK inhibitor drug used to treat rheumatoid arthritis. It provides background on arthritis, describing the signs and symptoms. It then discusses the mechanism of action of tofacitinib, inhibiting JAK-STAT pathways involved in inflammatory cytokine signaling. Data is presented from preclinical studies in animal models of arthritis showing tofacitinib reduced markers of inflammation and improved arthritis scores in a dose-dependent manner. Clinical trial results demonstrating the drug met efficacy endpoints at a 5 mg twice daily dose are also summarized.
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.
Biologics have revolutionized the treatment of rheumatoid arthritis. They were developed using genetic engineering principles and are highly complex protein drugs. Key biologics include TNF inhibitors like infliximab, etanercept, adalimumab; the CD-20 antibody rituximab; IL-6 inhibitors like tocilizumab; and the co-stimulation blocker abatacept. Guidelines recommend starting biologics for moderate to high disease activity that hasn't responded to DMARDs. Extensive screening for infections is required before initiating biologics due to their risks. While effective, biologics are also very expensive and can have problematic side effects.
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
Ceftazidime-Avibactam Is Superior toOther Treatment Regimens againstCarbape...Abdullatif Al-Rashed
Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia
This study compared outcomes of patients with carbapenem-resistant K. pneumoniae bacteremia treated with ceftazidime-avibactam to other regimens. It found that patients who received ceftazidime-avibactam had significantly higher clinical success and survival rates compared to those who received carbapenem plus aminoglycoside, carbapenem plus colistin, or other therapies. This provides evidence that ceftazidime-avibactam may be superior as first-line treatment for carbapenem-resistant K.
Definition of biopharmaceuticals and biosimilars, Steps involved in manufacturing biopharmaceuticals, Points of differences between Biosimilars and Chemical Generics, Related issues with biosimilars
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.
The document discusses tofacitinib, an oral JAK inhibitor drug used to treat rheumatoid arthritis. It provides background on arthritis, describing the signs and symptoms. It then discusses the mechanism of action of tofacitinib, inhibiting JAK-STAT pathways involved in inflammatory cytokine signaling. Data is presented from preclinical studies in animal models of arthritis showing tofacitinib reduced markers of inflammation and improved arthritis scores in a dose-dependent manner. Clinical trial results demonstrating the drug met efficacy endpoints at a 5 mg twice daily dose are also summarized.
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.
Biologics have revolutionized the treatment of rheumatoid arthritis. They were developed using genetic engineering principles and are highly complex protein drugs. Key biologics include TNF inhibitors like infliximab, etanercept, adalimumab; the CD-20 antibody rituximab; IL-6 inhibitors like tocilizumab; and the co-stimulation blocker abatacept. Guidelines recommend starting biologics for moderate to high disease activity that hasn't responded to DMARDs. Extensive screening for infections is required before initiating biologics due to their risks. While effective, biologics are also very expensive and can have problematic side effects.
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
Ceftazidime-Avibactam Is Superior toOther Treatment Regimens againstCarbape...Abdullatif Al-Rashed
Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia
This study compared outcomes of patients with carbapenem-resistant K. pneumoniae bacteremia treated with ceftazidime-avibactam to other regimens. It found that patients who received ceftazidime-avibactam had significantly higher clinical success and survival rates compared to those who received carbapenem plus aminoglycoside, carbapenem plus colistin, or other therapies. This provides evidence that ceftazidime-avibactam may be superior as first-line treatment for carbapenem-resistant K.
Studies of vaccine safety (Pharmacoepidemiology) V PharmDDr.Sohel Memon
This document discusses selected special applications of pharmacoepidemiology, focusing on studies of vaccine safety. It describes various methods used to monitor vaccine safety, including pre-licensure clinical trials, post-licensure surveillance systems like VAERS, and epidemiological studies. It addresses some methodological challenges in vaccine safety studies like assessing causality, accounting for confounding factors, and identifying rare adverse events. Large automated databases like the Vaccine Safety Datalink are highlighted as a valuable tool for monitoring vaccine safety on a population-level.
This document discusses several newer antiarrhythmic drugs, including ranolazine, vernakalant, ivabradine, celivarone, budiodarone, and tecadenoson. It provides details on the mechanisms of action, clinical trials, efficacy, and safety profiles of these drugs. Ranolazine, vernakalant, and budiodarone have shown efficacy in cardioversion or rate control of atrial fibrillation, while ivabradine reduces heart rate without affecting contractility. Celivarone and tecadenoson are being investigated for maintaining sinus rhythm and terminating supraventricular tachycardias, respectively.
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.
This document discusses the rational use of antibiotics. It notes that 50% of antibiotics are used inappropriately and that many infections like diarrhea and bronchitis are viral, not bacterial. It provides details on selecting antibiotics based on the infection severity, likely bacteria, patient factors, and cost. Empiric antibiotic choices are outlined for various infections. The side effects and costs of common antibiotics are also reviewed. The document emphasizes using antibiotics appropriately only for bacterial infections.
This document summarizes newer anticoagulants that are alternatives to traditional agents like heparin and warfarin. It discusses the mechanisms and properties of newer oral anticoagulants like rivaroxaban and dabigatran which directly inhibit thrombin or Factor Xa. Clinical trials showed these drugs were as effective as enoxaparin or warfarin for preventing blood clots after knee or hip surgery with lower rates of bleeding complications. The RE-LY trial found dabigatran 150mg twice daily reduced strokes by 35% compared to warfarin in atrial fibrillation patients.
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.
Pharmacogenetics involves studying genetic variations that lead to differences in individual drug responses. The goals are to optimize drug therapy and limit toxicity based on a person's genetic profile by choosing the best drug, dose, and duration for that individual. Genetic variations can occur as single nucleotide polymorphisms, which are single base pair differences between individuals. Polymorphisms in genes encoding drug-metabolizing enzymes, such as CYP2D6 and CYP2C9, are clinically significant as they can result in poor, intermediate, extensive, or ultrarapid metabolism of certain drugs. This can impact treatment outcomes and risk of adverse effects.
a brief overview about how and why to practice evidence based medicine, its clinical application, what it is and what it is not? benefits and challenges
- Bisoprolol is a highly selective beta-1 blocker used to treat heart failure, hypertension, and myocardial infarction.
- Studies show bisoprolol lowers blood pressure and heart rate more effectively than atenolol, with greater reductions throughout the day.
- The CIBIS II trial found adding bisoprolol to standard heart failure treatment reduced all-cause mortality by 34% and reduced hospitalizations compared to placebo.
This document discusses biosimilar drugs. It begins by defining biological products and biosimilars. Biosimilars are biologics that are similar but not identical to an already approved biologic reference product. They are developed to be similar in safety, purity and potency. Key differences between biosimilars and generics are discussed. For approval, biosimilars require clinical trials and other testing to show similarity rather than equivalence. Switching a patient from a reference biologic to a biosimilar requires physician approval due to unknown effects on immunogenicity. Naming of biosimilars and increasing competition in the biologics market are also covered.
The document discusses the importance of translational pharmacology in ensuring safe and effective dosing of drugs. It emphasizes using preclinical and clinical pharmacokinetic/pharmacodynamic studies and modeling throughout development to accurately translate dose levels between animal and human studies. This helps optimize dose selection for clinical trials and maximize the chances of demonstrating efficacy while avoiding toxicity. A case study illustrates how such an approach could have helped avoid failure of a Phase 2 oncology trial due to selecting a suboptimal dose.
ACELEX capsule 2mg - Tissue Selective COX-2 inhibitor CrystalGenomics Acelex NC Jan2016. Acelex® (polmacoxib) is a non-steroidal anti-inflammatory drug (NSAID), specifically a COX-2 inhibitor, for the treatment of symptoms associated with arthritis. Suffering from joints pain which might have been due to age or other reason. Acelex capsule 2 mg is one of new drug in the market for joints pain relief.
Neuroprotective drugs aim to protect neurons from damage in conditions like stroke. Currently, there are no approved neuroprotective treatments for stroke. Various targets of neuroprotection have been investigated including inflammation, oxidative stress, excitotoxicity, and apoptosis. Many agents have shown promise in animal models but failed in clinical trials. Edaravone is the only drug approved in Japan for acute ischemic stroke. Ongoing research continues to explore new targets and combinations of therapies to develop effective neuroprotective treatments for stroke.
This PPT encompasses the recent biologics overview & their uses in various rheumatological diseases according to recent guidelines. Special focus has been given to RA, SpA & SLE
The document discusses pharmacogenomics and how genetic variations can affect individual responses to drugs. It describes how pharmacogenomics examines genomic loci and biological pathways to determine drug variability. It also discusses pharmacogenetics which focuses on single gene variants. The document outlines some merits of pharmacogenomics like improving drug safety and personalized treatment. It then discusses various scenarios on how genetic polymorphisms can impact different drug metabolism pathways. Finally, it examines how specific genetic variations in drug metabolizing enzymes and transporters can influence drug pharmacokinetics and potential adverse effects.
This document discusses the increasing problem of antibiotic resistance and potential solutions. It notes the emergence of extensively drug-resistant pathogens and classifications of drug resistance. Potential solutions discussed include developing new antibiotics that target resistant bacteria, rediscovering older antibiotics, and using beta-lactamase inhibitors to enhance existing antibiotics. Several new antibiotics are summarized, including their mechanisms of action, clinical indications, and stages of clinical trials.
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.
This presentation by Gavin Giovannoni looks at the new treatment paradigm for MS. It includes: arguments for early treatment in multiple sclerosis, the effect of MS on quality of life and whether highly-effective treatments stabilise MS.
It was presented at the MS Trust Annual Conference in November 2013.
The presentation provided an overview of deprescribing, which involves reducing or stopping medications that may be unnecessary, inappropriate, ineffective, or harmful. It discussed goals of deprescribing like improving quality of life and reducing risks. Barriers and benefits of deprescribing were presented. Common drug classes that can be deprescribed included proton pump inhibitors, benzodiazepines, and others. Guidelines and tools to aid the deprescribing process were also reviewed. A case study on deprescribing a long-term PPI prescription was presented to demonstrate how to apply deprescribing principles.
This document discusses several chemotherapy drugs that were approved by the FDA between 2014-2018 for treating various cancers. It provides the drug name, generic name, mode of action, and indication for drugs approved in 2014, 2016, 2017, and 2018. Some of the drugs mentioned include Opdivo for melanoma, Lynparza for ovarian cancer, Keytruda for melanoma, Darzalex for multiple myeloma, and Lynparza for breast cancer.
This document discusses biosimilars and their manufacturing and regulation. It defines biosimilars as biological products that are similar but not identical to already approved biologics. Their manufacturing involves analyzing the reference product and replicating its structure through living cell cultures. Biosimilars undergo clinical trials to demonstrate similarity in safety and efficacy. Regulatory approval requires demonstrating comparability to the reference product. Issues include potential differences in efficacy and immunogenicity compared to the reference product.
Biological agents and it role in current era and future roleHarsh shaH
This document discusses biological agents and their role in medicine. It defines biological products and biosimilars, and describes how biosimilars differ from original biologics in their manufacturing process and ability to be replicated exactly. The document outlines regulatory guidelines for biosimilars from agencies like EMA and FDA. Biosimilars can expand access to biologic treatments for diseases like rheumatoid arthritis and have potential cost savings compared to originator biologics. Safety monitoring is important due to concerns like immunogenicity.
Studies of vaccine safety (Pharmacoepidemiology) V PharmDDr.Sohel Memon
This document discusses selected special applications of pharmacoepidemiology, focusing on studies of vaccine safety. It describes various methods used to monitor vaccine safety, including pre-licensure clinical trials, post-licensure surveillance systems like VAERS, and epidemiological studies. It addresses some methodological challenges in vaccine safety studies like assessing causality, accounting for confounding factors, and identifying rare adverse events. Large automated databases like the Vaccine Safety Datalink are highlighted as a valuable tool for monitoring vaccine safety on a population-level.
This document discusses several newer antiarrhythmic drugs, including ranolazine, vernakalant, ivabradine, celivarone, budiodarone, and tecadenoson. It provides details on the mechanisms of action, clinical trials, efficacy, and safety profiles of these drugs. Ranolazine, vernakalant, and budiodarone have shown efficacy in cardioversion or rate control of atrial fibrillation, while ivabradine reduces heart rate without affecting contractility. Celivarone and tecadenoson are being investigated for maintaining sinus rhythm and terminating supraventricular tachycardias, respectively.
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.
This document discusses the rational use of antibiotics. It notes that 50% of antibiotics are used inappropriately and that many infections like diarrhea and bronchitis are viral, not bacterial. It provides details on selecting antibiotics based on the infection severity, likely bacteria, patient factors, and cost. Empiric antibiotic choices are outlined for various infections. The side effects and costs of common antibiotics are also reviewed. The document emphasizes using antibiotics appropriately only for bacterial infections.
This document summarizes newer anticoagulants that are alternatives to traditional agents like heparin and warfarin. It discusses the mechanisms and properties of newer oral anticoagulants like rivaroxaban and dabigatran which directly inhibit thrombin or Factor Xa. Clinical trials showed these drugs were as effective as enoxaparin or warfarin for preventing blood clots after knee or hip surgery with lower rates of bleeding complications. The RE-LY trial found dabigatran 150mg twice daily reduced strokes by 35% compared to warfarin in atrial fibrillation patients.
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.
Pharmacogenetics involves studying genetic variations that lead to differences in individual drug responses. The goals are to optimize drug therapy and limit toxicity based on a person's genetic profile by choosing the best drug, dose, and duration for that individual. Genetic variations can occur as single nucleotide polymorphisms, which are single base pair differences between individuals. Polymorphisms in genes encoding drug-metabolizing enzymes, such as CYP2D6 and CYP2C9, are clinically significant as they can result in poor, intermediate, extensive, or ultrarapid metabolism of certain drugs. This can impact treatment outcomes and risk of adverse effects.
a brief overview about how and why to practice evidence based medicine, its clinical application, what it is and what it is not? benefits and challenges
- Bisoprolol is a highly selective beta-1 blocker used to treat heart failure, hypertension, and myocardial infarction.
- Studies show bisoprolol lowers blood pressure and heart rate more effectively than atenolol, with greater reductions throughout the day.
- The CIBIS II trial found adding bisoprolol to standard heart failure treatment reduced all-cause mortality by 34% and reduced hospitalizations compared to placebo.
This document discusses biosimilar drugs. It begins by defining biological products and biosimilars. Biosimilars are biologics that are similar but not identical to an already approved biologic reference product. They are developed to be similar in safety, purity and potency. Key differences between biosimilars and generics are discussed. For approval, biosimilars require clinical trials and other testing to show similarity rather than equivalence. Switching a patient from a reference biologic to a biosimilar requires physician approval due to unknown effects on immunogenicity. Naming of biosimilars and increasing competition in the biologics market are also covered.
The document discusses the importance of translational pharmacology in ensuring safe and effective dosing of drugs. It emphasizes using preclinical and clinical pharmacokinetic/pharmacodynamic studies and modeling throughout development to accurately translate dose levels between animal and human studies. This helps optimize dose selection for clinical trials and maximize the chances of demonstrating efficacy while avoiding toxicity. A case study illustrates how such an approach could have helped avoid failure of a Phase 2 oncology trial due to selecting a suboptimal dose.
ACELEX capsule 2mg - Tissue Selective COX-2 inhibitor CrystalGenomics Acelex NC Jan2016. Acelex® (polmacoxib) is a non-steroidal anti-inflammatory drug (NSAID), specifically a COX-2 inhibitor, for the treatment of symptoms associated with arthritis. Suffering from joints pain which might have been due to age or other reason. Acelex capsule 2 mg is one of new drug in the market for joints pain relief.
Neuroprotective drugs aim to protect neurons from damage in conditions like stroke. Currently, there are no approved neuroprotective treatments for stroke. Various targets of neuroprotection have been investigated including inflammation, oxidative stress, excitotoxicity, and apoptosis. Many agents have shown promise in animal models but failed in clinical trials. Edaravone is the only drug approved in Japan for acute ischemic stroke. Ongoing research continues to explore new targets and combinations of therapies to develop effective neuroprotective treatments for stroke.
This PPT encompasses the recent biologics overview & their uses in various rheumatological diseases according to recent guidelines. Special focus has been given to RA, SpA & SLE
The document discusses pharmacogenomics and how genetic variations can affect individual responses to drugs. It describes how pharmacogenomics examines genomic loci and biological pathways to determine drug variability. It also discusses pharmacogenetics which focuses on single gene variants. The document outlines some merits of pharmacogenomics like improving drug safety and personalized treatment. It then discusses various scenarios on how genetic polymorphisms can impact different drug metabolism pathways. Finally, it examines how specific genetic variations in drug metabolizing enzymes and transporters can influence drug pharmacokinetics and potential adverse effects.
This document discusses the increasing problem of antibiotic resistance and potential solutions. It notes the emergence of extensively drug-resistant pathogens and classifications of drug resistance. Potential solutions discussed include developing new antibiotics that target resistant bacteria, rediscovering older antibiotics, and using beta-lactamase inhibitors to enhance existing antibiotics. Several new antibiotics are summarized, including their mechanisms of action, clinical indications, and stages of clinical trials.
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.
This presentation by Gavin Giovannoni looks at the new treatment paradigm for MS. It includes: arguments for early treatment in multiple sclerosis, the effect of MS on quality of life and whether highly-effective treatments stabilise MS.
It was presented at the MS Trust Annual Conference in November 2013.
The presentation provided an overview of deprescribing, which involves reducing or stopping medications that may be unnecessary, inappropriate, ineffective, or harmful. It discussed goals of deprescribing like improving quality of life and reducing risks. Barriers and benefits of deprescribing were presented. Common drug classes that can be deprescribed included proton pump inhibitors, benzodiazepines, and others. Guidelines and tools to aid the deprescribing process were also reviewed. A case study on deprescribing a long-term PPI prescription was presented to demonstrate how to apply deprescribing principles.
This document discusses several chemotherapy drugs that were approved by the FDA between 2014-2018 for treating various cancers. It provides the drug name, generic name, mode of action, and indication for drugs approved in 2014, 2016, 2017, and 2018. Some of the drugs mentioned include Opdivo for melanoma, Lynparza for ovarian cancer, Keytruda for melanoma, Darzalex for multiple myeloma, and Lynparza for breast cancer.
This document discusses biosimilars and their manufacturing and regulation. It defines biosimilars as biological products that are similar but not identical to already approved biologics. Their manufacturing involves analyzing the reference product and replicating its structure through living cell cultures. Biosimilars undergo clinical trials to demonstrate similarity in safety and efficacy. Regulatory approval requires demonstrating comparability to the reference product. Issues include potential differences in efficacy and immunogenicity compared to the reference product.
Biological agents and it role in current era and future roleHarsh shaH
This document discusses biological agents and their role in medicine. It defines biological products and biosimilars, and describes how biosimilars differ from original biologics in their manufacturing process and ability to be replicated exactly. The document outlines regulatory guidelines for biosimilars from agencies like EMA and FDA. Biosimilars can expand access to biologic treatments for diseases like rheumatoid arthritis and have potential cost savings compared to originator biologics. Safety monitoring is important due to concerns like immunogenicity.
This document provides an overview of biosimilars. It defines biosimilars as subsequent versions of biologic medicines where patent protection has expired. Biosimilars are approved based on similarity to an original reference biologic in terms of quality, safety and efficacy, but are not expected to be identical due to structural complexities. The development of biosimilars involves extensive comparative studies to the reference product. Concerns with biosimilars include potential immunogenicity, efficacy issues, and uncertainty around switching between originator and biosimilar products or between biosimilars. Proper pharmacovigilance is important to monitor biosimilar safety and benefits.
Biosimilars are biological drugs that are similar to already approved biologic reference drugs. They are produced through biotechnology methods involving genetic engineering. While biosimilars hold promise to increase access to biologic treatments, they differ from traditional generics in important ways due to the complex nature of biologics. Biosimilars must undergo rigorous testing and demonstration of similarity to the reference product to ensure similar safety and efficacy profiles. Regulatory frameworks for approving biosimilars have been established by the EMA and FDA, with guidelines outlining requirements for comprehensive characterization, clinical trials, and pharmacovigilance to ensure patient safety.
Biopharmaceuticals are medical drugs derived from living cells using recombinant DNA technology. They are typically proteins, peptides, nucleic acids, or inactivated viruses/bacteria. Biopharmaceuticals structurally mimic compounds found in the body and have the potential to cure diseases rather than just treat symptoms with fewer side effects due to their specificity. Emerging biopharmaceutical technologies include monoclonal antibody production in protein-free media and genome-based technologies. Biopharmaceuticals have changed treatment for diseases like diabetes and cancer by being tailored for specific medical problems in individuals.
The present slide focuses on the applications and different uses of biosimilars along with the basic difference in between biosimilars and bioequivalence.
Pharmacovigilance Risk Management for BiosimilarsCovance
This paper focuses on pharmacovigilance (PV) and risk management for biosimilars, the issues and challenges faced in monitoring their safety and possible solutions.
Drug development and discovery in biologicsAshish sharma
This document provides an overview of drug development and discovery in biologics. It discusses key topics such as biologics and biosimilars, the integrated discovery and development process of antibodies, the market status and typical manufacturing process of biologics, their therapeutic roles and biological targets in therapy. Some of the challenges in biologics development include the complex manufacturing process, safety implications, immunogenicity, and limited shelf life. Regulations of biologics in India are outlined. Recent FDA-approved biologics are also mentioned. In conclusion, biologics and small molecules are seen as complementary approaches for drug development.
This document provides an overview of biologics and biosimilars. It defines biologics as complex medications made from living cells that treat diseases in novel ways. Biosimilars are highly similar but not identical copies of biologics that are approved through an abbreviated pathway. The FDA will determine standards for interchangeability and require rigorous testing to ensure biosimilars are safely effective for each condition and patient group. Important issues for patients include ensuring safety, transparency, and choice in biologic treatment.
Pegylation & biosimilars global scenarioMalay Singh
The document defines drugs and devices under the Drugs and Cosmetics Act of 1940 in India. It states that drugs include all medicines, substances and components for internal or external use, while devices are meant to treat, mitigate or prevent disease. Biologics and biosimilars are also included. The document then provides definitions and explanations of biotechnology, biopharmaceuticals, proteins drugs, pegylation, biologics vs biosimilars, and the FDA approach to biosimilars.
There has been a parallel advancement in the field of biosimilars with other recent biologic medications like cell line science and protein expression science. These are molecules that are chemically similar to their already approved biological medication counterparts which enable a faster and more cost-effective production as they only require one clinical trial, unlike the reference product which has to usually undergo two. Recently, various biosimilars for ophthalmic use have been developed and studied in various parts of the world.
This document summarizes guidelines for biosimilars in India. It begins by defining biosimilars as biologic compounds that are similar but not identical to reference biopharmaceuticals. It then discusses several biosimilar drugs used in cancer treatment such as G-CSF, interferons, and epoetins. While biosimilars have similar mechanisms of action, differences in manufacturing can result in differences in properties. The document concludes by outlining Indian regulatory guidelines for biosimilar approval and the importance of post-marketing safety monitoring to evaluate potential differences from reference drugs.
This document discusses biosimilars, which are biologic medications that are similar but not identical to an original biologic reference medication. It provides background on biosimilars and regulatory guidelines around them. Specifically, it notes that biosimilars take 6-9 years to develop compared to 3 years for generics, and that they require clinical trials to demonstrate safety and efficacy compared to the reference medication. The document also discusses biosimilar guidelines in India and examples of biosimilars used in cancer treatment, noting some differences between biosimilar versions of medications like G-CSF and interferons.
This document discusses biosimilars and their regulation. It begins with a brief history of biotechnology and biopharmaceuticals. It then defines biosimilars as similar but not generic versions of biologic drugs whose patents have expired. The document outlines key differences between biosimilars and generic drugs, including their larger and more complex molecular structures. It also discusses concerns regarding biosimilar efficacy, safety, interchangeability, and pharmacovigilance. Finally, it provides an overview of regulatory frameworks for biosimilars in various regions like the EU, US, India, and WHO guidelines.
Functional Overview of the Biotechnology IndustrythinkBiotech
Comprehensive introductory presentation on the business of biotechnology describing legal, commercial, scientific, and regulatory foundations; used in biotech MBA programs.
This document provides an overview of biosimilars, which are biologic drugs that are similar but not identical to an original biologic drug (the innovator product). It discusses how biosimilars present several challenges due to the complex nature of biologics, which are produced through biotechnology rather than chemical synthesis. Specifically, it notes challenges around verifying similarity between a biosimilar and innovator, determining interchangeability, developing appropriate naming, establishing regulatory frameworks, and ensuring public safety. The document also compares key differences between biologics and traditional small molecule drugs.
This document discusses biosimilar medicines. It defines biosimilars as medicines similar to existing approved biopharmaceutical medicines. Biosimilars have similar quality, safety and efficacy profiles but are not identical. Their development and approval process is more complex than for generics due to the biological nature of biopharmaceuticals which are sensitive to manufacturing changes. Guidelines from the European Medicines Agency provide recommendations on demonstrating biosimilarity in terms of quality, non-clinical and clinical testing. Ensuring biosimilars are highly similar seeks to guarantee their safe substitution for biopharmaceuticals while increasing treatment access and lowering costs.
- Biologics are large, complex molecules produced by living cells that are used to treat diseases like diabetes, cancer, and arthritis. They differ from chemically-derived drugs in their production method, structure, and potential for immune reactions.
- The production of biologics is more difficult than chemical drugs due to their sensitivity and the variability in living production systems. Their structure is heterogeneous and difficult to characterize fully.
- The targets of biologics are genes or proteins involved in disease processes. Their mechanism of action involves manipulating genetic or protein-based pathways through recombinant DNA technology or other methods.
Biosimilars, a pharmacist’s perspectiveBiosimilars
This document discusses how biosimilars may profoundly impact the role of pharmacists. Biosimilars are similar but not identical to biologic drugs, and slight manufacturing differences can impact a biosimilar's effects. This requires pharmacists to refrain from automatically substituting biosimilars and become more familiar with their potential side effects and immunogenic responses. The document also notes that future posts will explore challenges for hospital pharmacists providing biosimilars and provide additional educational resources on biosimilars.
At Apollo Hospital, Lucknow, U.P., we provide specialized care for children experiencing dehydration and other symptoms. We also offer NICU & PICU Ambulance Facility Services. Consult our expert today for the best pediatric emergency care.
For More Details:
Map: https://cutt.ly/BwCeflYo
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Address: Singar Nagar, LDA Colony, Lucknow, Uttar Pradesh 226012
Phone: 08429021957
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Can coffee help me lose weight? Yes, 25,422 users in the USA use it for that ...nirahealhty
The South Beach Coffee Java Diet is a variation of the popular South Beach Diet, which was developed by cardiologist Dr. Arthur Agatston. The original South Beach Diet focuses on consuming lean proteins, healthy fats, and low-glycemic index carbohydrates. The South Beach Coffee Java Diet adds the element of coffee, specifically caffeine, to enhance weight loss and improve energy levels.
Comprehensive Rainy Season Advisory: Safety and Preparedness Tips.pdfDr Rachana Gujar
The "Comprehensive Rainy Season Advisory: Safety and Preparedness Tips" offers essential guidance for navigating rainy weather conditions. It covers strategies for staying safe during storms, flood prevention measures, and advice on preparing for inclement weather. This advisory aims to ensure individuals are equipped with the knowledge and resources to handle the challenges of the rainy season effectively, emphasizing safety, preparedness, and resilience.
This particular slides consist of- what is hypotension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is the summary of hypotension:
Hypotension, or low blood pressure, is when the pressure of blood circulating in the body is lower than normal or expected. It's only a problem if it negatively impacts the body and causes symptoms. Normal blood pressure is usually between 90/60 mmHg and 120/80 mmHg, but pressures below 90/60 are generally considered hypotensive.
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - ...rightmanforbloodline
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - 34.
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - 34.
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - 34.
DECODING THE RISKS - ALCOHOL, TOBACCO & DRUGS.pdfDr Rachana Gujar
Introduction: Substance use education is crucial due to its prevalence and societal impact.
Alcohol Use: Immediate and long-term risks include impaired judgment, health issues, and social consequences.
Tobacco Use: Immediate effects include increased heart rate, while long-term risks encompass cancer and heart disease.
Drug Use: Risks vary depending on the drug type, including health and psychological implications.
Prevention Strategies: Education, healthy coping mechanisms, community support, and policies are vital in preventing substance use.
Harm Reduction Strategies: Safe use practices, medication-assisted treatment, and naloxone availability aim to reduce harm.
Seeking Help for Addiction: Recognizing signs, available treatments, support systems, and resources are essential for recovery.
Personal Stories: Real stories of recovery emphasize hope and resilience.
Interactive Q&A: Engage the audience and encourage discussion.
Conclusion: Recap key points and emphasize the importance of awareness, prevention, and seeking help.
Resources: Provide contact information and links for further support.
Can Allopathy and Homeopathy Be Used Together in India.pdfDharma Homoeopathy
This article explores the potential for combining allopathy and homeopathy in India, examining the benefits, challenges, and the emerging field of integrative medicine.
The facial nerve, also known as cranial nerve VII, is one of the 12 cranial nerves originating from the brain. It's a mixed nerve, meaning it contains both sensory and motor fibres, and it plays a crucial role in controlling various facial muscles, as well as conveying sensory information from the taste buds on the anterior two-thirds of the tongue.
Let's Talk About It: Breast Cancer (What is Mindset and Does it Really Matter?)bkling
Your mindset is the way you make sense of the world around you. This lens influences the way you think, the way you feel, and how you might behave in certain situations. Let's talk about mindset myths that can get us into trouble and ways to cultivate a mindset to support your cancer survivorship in authentic ways. Let’s Talk About It!
International Cancer Survivors Day is celebrated during June, placing the spotlight not only on cancer survivors, but also their caregivers.
CANSA has compiled a list of tips and guidelines of support:
https://cansa.org.za/who-cares-for-cancer-patients-caregivers/
Michigan HealthTech Market Map 2024. Includes 7 categories: Policy Makers, Academic Innovation Centers, Digital Health Providers, Healthcare Providers, Payers / Insurance, Device Companies, Life Science Companies, Innovation Accelerators. Developed by the Michigan-Israel Business Accelerator
2. Suppose a company develops a new drug
say, prednisolone
It markets it under the name “Wysolone”
it sells this drug for 20 years
And then its patent expires
4. So now another company make prednisolone
And sells it with the brand name “Omnacortil”
Because manufacturing process is very easy,
Omnacortil is IDENTICAL to Wysolone
This is a generic drug
5. Suppose a company develops etanercept
it markets it under the name “Enbrel”
It sells the drug for 20 years
then its patent expires
6. Now, etanercept has a very large and complicated structure
So it is difficult to manufacture
7. Now another company makes etanercept
and sells it with the name “etacept”
Because of the complex manufacturing process,
this is NOT IDENTICAL to enbrel
this is a biosimilar
8. What is a biological ?
• A biological is a drug produced from a cell or
living organism.
• Large, intricate proteins with unique tertiary
and quaternary structures.
9. • Companies which make biologicals do not share information
about the manufacturing process.
• So the drug which will be produced will be “similar” but not
identical.
• But their manufacturing process will not be the same.
• After the patent expires, other companies attempt to make it.
What is a biosimilar ?
10. Europe Biosimilars
USA Follow-on biological agents
Canada Subsequent entry biological
(SEB) agents
India Similar biologics
WHO Similar biotherapeutic
products
Other names
11. Even minor changes in these
manufacturing steps will lead
to variability of the biosimilar
molecule.
How is a biological/biosimilar manufactured ?
Bottling
Product goes through a series of processes
(fermentation, purification, pharmaceutical
formulation)
Large proteins undergo folding, assembly of
subunits into multimers and post-translational
modifications, such as glycosylation, oxidation
and deamidation.
genetically altered cells are then meticulously
perpetuated and stored in the form of a master
cell bank
introduce the gene for the required protein into a
living cell.
This may affect its biological
function / immunogenicity /
safety / efficacy.
12. Three major steps are
employed.
How is a biosimilar declared fit for use
13. A comprehensive physicochemical and biological
characterisation is done to prove similarity on the molecular
level (including in vivo and in vitro assays).
How is a biosimilar declared fit for use
14. A pharmacokinetic (PK) study is done to show
bioequivalence
How is a biosimilar declared fit for use
15. An efficacy study (usually a RCT) is done to demonstrate
clinical equivalence.
Also required are Phase III clinical trials, which may be of
equivalence or non-inferiority.
This is the only way to sufficiently assess the efficacy and
safety.
How is a biosimilar declared fit for use
17. What is an “intended copy” ?
If the comparison fails at any stage, the product cannot be
termed as a biosimilar.
The term intended copy is applied to such products
They do not present similar safety and efficacy to the
innovative product.
Don’t meet FDA/EMA criteria for biosimilarity.
18. Advantages
• Deliver comparable clinical, safety, and
efficacy results as the originator drug.
• Less costly to develop.
• Require less development time.
19. The argument favouring biosimilars
• Even for an innovator drug itself, two batches are not exactly
alike.
• Slight variation is possible between different commercial lots
produced using different batches of medium or at different
manufacturing sites.
20. Chemical characterization of different commercial lots of
rituximab and etanercept produced between 2007 and 2011
revealed variations in both C-terminal lysine content and
glycosylation.
The increase in unfucosylated G0 glycans in the later batches of
rituximab resulted in more potent antibody-dependent cellular
cytotoxicity.
Despite these differences each product was marketed with no
change in label throughout this time.
Case in point
Schiestl, M. et al. Acceptable changes in quality
attributes of glycosylated biopharmaceuticals. Nat.
Biotechnol. 29, 310–312 (2011).
21. The argument favouring biosimilars
The guidelines for approval set by the EMA/FDA are so
stringent that the cost of developing a biosimilar would come to
nearly as much as the innovator.
22. The argument favouring biosimilars
High prices of innovator biologics have been straining
healthcare budgets.
23. The argument favouring biosimilars
The advent of biosimilars may force innovator companies to
lower prices.
24. In UK, Merck cut the price of Remicade by 25% after biosimilars
started to eat up into its market share.
Case in point
25. In India, the price of Reditux was half that of the innovator
rituximab product, MabThera (Roche).
Roche tied up with Emcure pharma for local manufacture of
MabThera. It was marketed with the brand names Ristova and
Ikgdar.
Their prices were lowered to reflect that of Reditux.
Case in point
27. Issues with biosimilars
Developing a biosimilar with a safety profile similar to the
reference product can be challenging due to the complex
molecular structure and complicated manufacturing process
involved.
The molecular structure of biologic products is sensitive to
changes in formulation, packaging, and storage.
28. Issues with biosimilars
Safety can become compromised by process-related
impurities from:
Cell substrates (e.g. host cell DNA and proteins),
Cell culture components (e.g. antibiotics and media
components)
Downstream processing steps (e.g. reagents, residual
solvents, leachables, endotoxins, and bioburden).
29. Issues with biosimilars
There is a possibility of :
immunogenicity
hyper- sensitivity reactions
increased risk for other adverse effects.
30. Issues with biosimilars
Many adverse effects may appear only after a biosimilar drug is
used more extensively, for a longer period of time, in a greater
number of patients.
31.
32. All biological agents are immunogenic because they are
non-self; even humanised and ‘fully human’ mAbs and Cepts
can result in measurable immune responses
Immunological responses
US Food and Drug Administration. Prescribing information for
adalimumab. http://
www.accessdata.fda.gov/drugsatfda_docs/label/2011/125057s0276lbl.
pdf (accessed
10 Aug 2012).
Issues with biosimilars
33. The effects of antibiological antibodies include reduction in
serum levels, adverse events and formation of neutralising
antibodies.
Immunological responses
Strand V, Kimberly R, Isaacs JD. Biologic therapies in
rheumatology: lessons learned, future directions. Nat
Rev Drug Discov 2007;6:75–92.
Issues with biosimilars
34. Antiinfliximab antibodies have been associated with
infusion reactions in patients with Crohn’s disease
Immunological responses
Baert F, Noman M, Vermeire S, et al. Influence of
immunogenicity on the long-term efficacy of infliximab
in Crohn’s disease. N Engl J Med 2003;348:601–8.
Issues with biosimilars
35. Antiadalimumab antibodies may heighten the risk of rare
thromboembolic events in patients with RA and psoriatic
arthritis.
Immunological responses
Korswagen LA, Bartelds GM, Krieckaert CL, et al. Venous and arterial
thromboembolic events in adalimumab-treated patients with
antiadalimumab
antibodies: a case series and cohort study. Arthritis Rheum
2011;63:877–83.
Issues with biosimilars
36. Postmarketing surveillance of TNFi mAbs has identified
a potential link between antibiological antibodies and
treatment-related vasculitis, albeit very rare events.
Immunological responses
Doyle MK, Cuellar ML. Drug-induced vasculitis. Expert Opin Drug Saf
2003;2:401–9. Ramos-Casals M, Perez-Alvarez R, Perez-de-Lis M, et al.
Pulmonary disorders induced by monoclonal antibodies in patients with
rheumatologic autoimmune diseases. Am J Med 2011;124:386–94.
Issues with biosimilars
37. Biosimilar epoietins were introduced in the market without
proper attention to the possibility that they could generate
autoantibodies against the natural erythropoietin
resulting in cases of drug-derived pure red cell aplasia mainly
outside the USA.
Immunological responses
Genazzani AA, Biggio G, Caputi AP et al. Biosimilar
drugs:
concerns and opportunities. BioDrugs
2007;21:3516.
Casadevall N, Nataf J, Viron B et al. Pure red cell
aplasia and erythropoietin antibodies in patients treated
with recombinant erythropoietin. N Engl J Med
2002;346:46975.
Issues with biosimilars
38. A rituximab biosimilar has produced anaphylactic reactions
after the patients were switched to the
biosimilar in Mexico.
Immunological responses
COFEPRIS. Comunicado a los profesionales de la salud. Reacciones
anafilácticas por el
uso de Rituximab. Available from:
www.cofepris.gob.mx/AZ/Documents/Farmacovig
ilancia/Comunicado%20Rituximab.pdf
Issues with biosimilars
39. In studies with infliximab, the biosimilar [Inflectra (Hospira)],
displayed nearly identical immunological responses to the
reference drug [Remicade (Janssen)].
Immunological responses
Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-
group study to demonstrate equivalence in efficacy and safety of CT-P13
compared with innovator infliximab when coadministered with methotrexate in
patients with active rheumatoid arthritis: The PLANETRA study. Ann Rheum
Dis. 2013;72:1623-1620.
Park W, Hrycaj P, Jeka S, et al. Randomised, doubleblind, multicentre,
parallel-group, prospective study comparing the pharmacokinetics, safety, and
efficacy of CT-P13 and nnovator infliximab in patients with ankylosing
spondylitis: The PLANETAS study. Ann Rheum Dis. 2013;72(10): 1605-1612
Issues with biosimilars
40. A biosimilar called SB2 was equivalent to INF in terms of
ACR20 response at week 30.
It was well tolerated with a comparable safety profile,
immunogenicity and PK to INF.
Immunological responses
Choe, J., Prodanovic, N., Niebrzydowski, J., Staykov, I., Dokoupilova, E. and
Baranauskaite, A. et al. (2015a) A randomized, double-blind, phase III study
comparing SB2, an infliximab biosimilar, to the infliximab reference product
(Remicade®) in patients with moderate to severe rheumatoid arthritis despite
methotrexate therapy: 54-week results [abstract]. Arthritis Rheumatol 67(Suppl. 10).
Issues with biosimilars
41. Studies indicate that the development of biosimilars with lower
aggregation and/or immunogenicity than the reference products
may be possible.
Immunological responses
Barbosa MDFS. Immunogenicity of biotherapeutics in the context
of developing biosimilars and biobetters. Drug Disc Today.
2011;16(7-8):345-353.
Overview of research on safety and immunogenicity of
biosimilars in 2012. GaBIJ. http://gabi-journal.net/news/overview-
of-research-on-safety-and-immunogenicity-of-biosimilars- in-
2012. Accessed March 16, 2015.
Issues with biosimilars
42. Issues with biosimilars
Can you switch from a biological to a biosimilar and back ?
Still under much clinical and regulatory debate.
No established criteria for inter- changeability currently exist.
Substitution
British Society for Rheumatology Position statement on
biosimilar medicines (February 2015)
43. Issues with biosimilars
The acceptance of interchangeability may vary from country to
country.
In practice, replacement is not permitted in any European
country1, and it is not recommended by WHO2 or medical
societies.
1.European Generic Medicines Association (EGA) (2011)
Biosimilars
handbook, 2nd ed. EGA. Accessed 12 December 2013
2.Hodgson J (2009) WHO guidelines presage US
biosimilars
legislation? Nat Biotechnol 27:963–965.
Substitution
44. Issues with biosimilars
While writing the prescription, brand name must be used to
avoid substitution.
If a decision is made to substitute, it should be for clinical
reasons, not economic.
Substitution
British Society for Rheumatology Position statement on
biosimilar medicines (February 2015)
45. Issues with biosimilars
A biosimilar is approved for RA, can you use it for PsA ?
Again not clear.
Efficacy/safety has to be justified / demonstrated.
Extrapolation
46. Issues with biosimilars
There is no protocol of standardized procedures for
the manufacture of biosimilars.
There is lack of a sharing of know-how on new successful
processes between companies.
Manufacturing issues
47. Issues with biosimilars
Originator companies have been devising newer strategies to
combat the biosimilar competition.
Frequent process changes by the originator gives rise to
reference standards that are considerably different.
Manufacturing issues
48. Issues with biosimilars
They frequently change delivery devices (switching from vials to
prefilled syringes to autoinjectors) and media (from liquid to
lyophilized) combined with the withdrawal of older media
/device.
Manufacturing issues
49. Issues with biosimilars
The estimated costs of developing a biosimilar product for
highly-regulated markets such as Europe or the US still ranges
from $75 to $250 million.
Economic issues
51. Name Innovator
brand
Company Approval Patent
expiration
Europe
Patent
expiration
USA
Infliximab Remicade Janssen-Merck 1998 Feb 2015 Sep 2018
Etanercept Enbrel Amgen/Pfizer 1998 Feb 2015 Nov 2028
Adalimumab Humira AbbVie 2002 Apr 2018 Dec 2016
Golimumab Simponi Centocor 2009 Feb 2024
Rituximab MabThera,
Rituxan
Roche 1997 Nov 2013 Sep 2016
Abatacept Orencia BristolMyers
Squibb
2005 Dec 2017 Oct 2019
Tocilizumab Actemra Genentech Roche 2010 Jul 2010 Dec 2015
Anakinra Kineret Amgen 2001 May 2009 Feb 2022
Certolizumab
pegol
Cimzia UCB 2008 Feb 2022
52. World scenario
The first true biosimilar in rheumatology was registered in Korea in
October 2012 and is a copy of infliximab1. [Remsima (code name CT-
P13, Celltrion, Incheon, Korea)]
The trial that led to this license appears to be well done and powered to
detect differences in efficacy and safety.
It was approved by the EMA in 2013 and is currently approved in 50
countries, including South Korea , Colombia , Canada and Japan.
1. Rheumatology 2014;53:389390 doi:10.1093/
rheumatology/ ket 210 Advance Access publication 22
July 2013
EMA/CHMP. CHMP summary of positive opinion for Remsima. 2013.
http://www.
ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-
_Initial_
authorisation/human/002576/WC500144832.pdf (accessed 6 Mar
2015).
53. World scenario
The EMA (European Medicine Agency) was the first to issue
criteria for biosimilar approval in 2006.
The FDA followed suit in 2012.
Both guidelines are similar & very stringent.
FDA/EMA
54. FDA/EMA criteria :
Manufacturers must provide substantial data showing that, as compared to the
reference product, the biosimilar has :
a highly comparable chemical structure
the same mechanism of action
the same route of administration.
same dosage form.
same potency.
comparable clinical safety and efficacy outcomes
55. FDA/EMA criteria :
Human immunogenicity data are required by a phase III clinical study to
exclude an increase in immunogenicity compared to the reference product.
Only minor differences in clinically inactive components are allowable.
56. FDA/EMA criteria :
Once approved, companies must continue monitoring the safety of their
biosimilar products through pharmacovigilance programs [Postmarketing
surveillance data (ie, adverse event reporting)].
As an example of postmarketing surveillance, the EMA has required the
manufacturer of the biosimilar infliximab to maintain registries of patients
with RA and inflammatory bowel diseases for the purpose of monitoring the
risk of serious infections.
57.
58. World scenario
In the European Union, the first patents on biopharmaceuticals
expired in 2001, and the first biosimilar medicines were approved
by EMA in 2006.
These were for non-rheumatological diseases.
EU
59. World scenario
They have demonstrated similar safety and efficacy to their
reference products.
Most EU countries have developed postmarketing
pharmacovigilance programs.
EU
60. World scenario
The first biosimilar for rheumatology to be approved in EU was
Remsima, a biosimilar of Remicade (Infliximab), developed by
Celltrion healthcare.
Approved in June 2013.
EU
EMA/CHMP. CHMP summary of positive opinion for Remsima. 2013.
http://www.
ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-
_Initial_
authorisation/human/002576/WC500144832.pdf (accessed 6 Mar
2015).
61. World scenario
A biosimilar of etanercept called Benepali (Samsung Bioepis) was
approved in Jan 2016.
EU
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medic
ines/human/medicines/004007/human_med_001944.jsp&m
id=WC0b01ac058001d124
62. World scenario
The USA is reportedly biosimilar unfriendly, as it favors
everlasting and perpetual patents
USA
63. US Food and Drug Administration. Zarxio (filgrastim-sndz).
March 2015. http://www.fda.
gov/NewsEvents/Newsroom/PressAnnouncements/
ucm436648.htm. Accessed August 31, 2015.
World scenario
On March 6, 2015, the US Food and Drug Administration
approved Zarxio (filgrastim-sndz, Sandoz) as the first biosimilar
in the United States.
USA
64. World scenario
There are no biosimilars definitively approved by FDA for
treatment of rheumatic diseases in the USA.
Several randomized controlled trials (RCTs) are complete or on
going.
USA
Dorner T, Strand V, Castaneda-Hernandez G, et al. The role
of biosimilars in the treatment of rheumatic diseases.
AnnRheum Dis 2013;72:322-8.
65. World scenario
An infliximab biosimilar may be approved in April, 2016
USA
http://www.biosimilarnews.com/fda-panel-backs-
celltrion-and-pfizers-remicade-infliximab-biosimilar
66. World scenario
In regions other than USA/EU, regulations for approval of biosimilars
are less stringent.
It is felt that this might have led to approval of agents which are not
entirely proven to be safe / efficacious.
67. *Azevedo VF, Sandorff E, Siemak B, Halbert RJ (2012)
Potential regulatory and commercial environment for
biosimilars in Latin America. Value Heal Reg Issues
1:228–234
World scenario
• In Latin America many copy products have been approved
without adequate evaluation, lacking in particular, in good-
quality clinical trials.
• Two copies of etanercept already marketed in Mexico and
Columbia cannot be considered biosimilars.*
South america
68. World scenario
Like in Asia, registration of intended copies of rituximab and
etanercept are already in place without any clinical trials in
patients with RA.
Africa
69. 2.Wu B, Wilson A, Wang F et al (2012) Cost
effectiveness of
different treatment strategies in the treatment of
patients with
moderate to severe rheumatoid arthritis in china. PLoS
World scenario
In China, Shanghai CP Guojian Pharmaceutical Co. Ltd launched
a new compound in 2006 called Yisaipu, that is supposedly a
copy of etanercept.
Data are needed on its non-inferiority in relation to etanercept to
determine its biosimilarity1,2.
1.Kay J (2011) Biosimilars: a regulatory perspective
from America.
Arthritis Res Ther 13:112.
China
75. Profile of companies that are developing biosimilars or ‘intended copies’ around
76. World scenario
Biosimilars approved in India might not have been authorized
following as strict a regulatory process as is required for
approval of biosimilars in the European Union.
India
77. World scenario
India is a semi-regulated market for biosimilars and only short
trials are required to assess bioequivalence for licensing
procedures.
Rheumatology
2014;53:389390doi:10.1093/rheumatology/ket210
Advance Access publication 22 July 2013
India
78. World scenario
Required :
In vitro analytic chemical and biological characterization.
In vivo animal toxicity studies.
A Phase III clinical trial.
Post-marketing pharmacovigilance program.
Malhotra, H. Biosimilars and non-innovator
biotherapeutics in India: an overview of the current
situation. Biologicals 39, 321–324 (2011).
India
79. World scenario
However, a head-to-head clinical trial that compares the
biosimilar agent to the innovator biopharmaceutical is not
required.
Malhotra, H. Biosimilars and non-innovator
biotherapeutics in India: an overview of the current
situation. Biologicals 39, 321–324 (2011).
India
80. World scenario
Guidelines were announced in 2012.
India
The New India Guidelines on Similar Biologics. 2012. Oct, [Last accessed on
2013 Jul 16]. Available
from: http://www.biospectrumasia.com/biospectrum/analysis/3021/biosimilars-
guidelines-a-step-direction-india#.UehBf6DRiSo .
81. World scenario
The drafters of the guidelines included the drug regulator
Central Drugs Standard Control Organization, the Department
of Biotechnology, academics, and surprisingly staff of major
biotech companies, such as Biocon, Dr. Reddy’s and Roche.
India
The New India Guidelines on Similar Biologics. 2012. Oct, [Last accessed on
2013 Jul 16]. Available
from: http://www.biospectrumasia.com/biospectrum/analysis/3021/biosimilars-
guidelines-a-step-direction-india#.UehBf6DRiSo .
82. World scenario
Lax regulation ? : The Roche-Biocon lawsuit
Roche makes a biological called trastuzumab, marketed as
Herceptin.
After its patent expired, Biocon-Mylan jumped into the fray with
a version called Canmab.
It was granted approval quickly by DGCI.
India
83. World scenario
Lax regulation ? : The Roche-Biocon lawsuit
The procedure for approval is multi –step requiring a lot of time.
Approval for the drug could not have been granted legally in
such short span of time.
Roche argued that there is no public record available in the
clinical trial registry of India or elsewhere to show that these
firms actually conducted phase-I or phase-II clinical trials for
the drug.
India
84. World scenario
Lax regulation ? : The Roche-Biocon lawsuit
Delhi High Court, accordingly restrained Biocon and Mylan from
launching Canmab.
India
85. World scenario
A parliamentary standing committee had accused the Central
Drugs Standard Control Organization of acting under the
influence of the industry which it is supposed to regulate.
Parliament of India. Department-Related Parliamentary Standing
Committee on Health and Family Welfare: 66th Report on Action Taken
by the Government on the Recommendations/Observations Contained
in the Fifty-Ninth Report on the Functioning of the Central Drugs
Standards Control Organisation (CDSCO) 2013 Apr
India
86. World scenario
The health ministry plans to revamp the guidelines further.
The Economic times, Nov 18, 2015
India
87. World scenario
Reditux (Dr Reddy’s) has been produced and marketed in India
since 2007.(prior to release of guidelines)
It was licensed with data from a non-comparative open-label
study in 68 patients.
India
88. World scenario
Cipla is marketing an intended copy of etanercept, which is
produced by the Chinese company Shanghai CP Goujian
Pharmaceutical Co., the company that produces Yisaipu.
This molecule lacks data based on the international legislation
for it to be accredited as a biosimilar molecule.
Biosimilarnews (2013) Cipla launches first biosimilar
etanercept
in India. http://www.biosimilarnews.com/cipla-
launchesfirst-
biosimilar-etanercept-in-india. Accessed 26 Nov 2013
India
89. World scenario
The Indian company Avesthagen has conducted preclinical
trials on AVG01 (AVENT™).
The molecule demonstrated high structural and pre-clinical
similarity with etanercept.
However, there is a need for clinical trials to compare efficacy
and safety in humans.
Maity S, Ullanat R, Lahiri S et al (2011) A non-innovator
version
of etanercept for treatment of arthritis. Biologicals
39:384–
395.
India
90. Drug Type Brand Company Launch Cost
Infliximab Innovator Remicade Merck ₹41039/100mg
Biosimilar Infimab Ranbaxy-
Epirus
Sep 2014 ₹30476
Etanercept Innovator Enbrel Wyeth ₹7983/25mg
Biosimilar Etacept Cipla Apr 2013 ₹6150
Intacept Intas Mar 2015
Adalimumab Innovator Humira AbbVie $1000/40mg
Biosimilar Exemptia Zydus
Cadila
Sep 2014 $200
Adfrar Torrent Jan 2016
91. Drug Type Brand Company Launch Cost
Rituximab Innovator MabThera Roche ₹70870/500mg
Ristova,
Ikgdar
Roche-
Emcure
₹37500
Biosimilar Reditux RA Dr Reddy’s Apr 2007 ₹39996
Toritz RA Torrent Feb 2015 ₹39957
Maball Hetero Feb 2015
Mabtas Intas Feb 2013 ₹26995
Tocilizumab Innovator Actemra Genentech
roche
₹7392/100mg
Abatacept Innovator Orencia BristolMyers
Squibb
₹26208 /80mg
92. Take home messages
A biosimilar product can only really be classified as a biosimilar
copy with proper head-to-head trials against the innovator.
A biosimilar may have been licensed using relaxed standards
and may not be truly bioequivalent.