This document provides guidelines for conducting nonclinical and clinical studies to register recombinant human alpha-interferon as a biological product using comparability development. It outlines requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies along with immunogenicity assessment and pharmacovigilance plans. Nonclinical studies should include comparative toxicity, local tolerance and pharmacodynamic studies in animals. Clinical studies should evaluate pharmacokinetics, pharmacodynamics, efficacy and safety compared to an approved reference product. Overall immunogenicity and long-term safety through pharmacovigilance are also important considerations.
1. A randomized, double-blind study compared the pharmacokinetic and pharmacodynamic profiles of two recombinant human interferon alpha-2b formulations, INTRON A and HEBERON ALFA R, after a single intramuscular injection in 24 healthy male volunteers.
2. Both formulations induced similar increases in serum beta-2-microglobulin levels and fever profiles. Pharmacokinetic parameters like AUC, Cmax, and Tmax were similar between the groups, though INTRON A showed slightly smaller AUC and distribution values.
3. Overall, the study concluded that despite some differences in pharmacokinetic parameters, both formulations exhibited similar pharmacodynamic effects and safety profiles.
1) The document discusses various methods for extrapolating data from in vitro and preclinical animal studies to humans, including the NOAEL and MABEL methods.
2) It explains that the NOAEL method involves determining the No Observed Adverse Effect Level from animal studies, converting it to a Human Equivalent Dose using scaling factors, and applying a safety factor.
3) Two common methods for interspecies scaling are linear extrapolation, which assumes dosage is directly proportional to weight, and allometric scaling, which accounts for nonlinear relationships between pharmacokinetics and weight.
This document provides an overview of biopharmaceuticals. It discusses how biopharmaceuticals are medical drugs produced using biotechnology, especially genetic engineering. Some key points made in the document include:
- Biopharmaceuticals include cytokines, enzymes, hormones, monoclonal antibodies, and other protein or nucleic acid based therapies.
- Emerging biopharmaceutical technologies include monoclonal antibody production, vaccine manufacturing improvements, and non-ribosomal peptide synthesis.
- Biopharmaceuticals have changed treatment for diseases like diabetes and cancer by being tailored to specific medical problems in individuals with fewer side effects than traditional drugs.
The document discusses the importance of pharmacovigilance for biotherapeutic medicines. It notes that biotherapeutics are more complex and difficult to characterize than traditional small molecule drugs due to their large size and biological production processes. This underscores the importance of specific traceability for biotherapeutics in pharmacovigilance activities. The document recommends that the WHO work to develop global naming recommendations for biotherapeutics to facilitate accurate tracking and tracing of products and linkage of adverse events to the appropriate product. It also discusses new EU legislation requiring identification of biotherapeutics by brand name and batch number in adverse event reporting.
This document discusses the challenges of pharmacovigilance for biotherapeutic medicines. It notes that pharmacovigilance systems are developing at different rates globally, with inconsistent naming approaches for biotherapeutics. This can weaken signal detection. The document outlines five key challenges for biotherapeutics: 1) They are more complex and sensitive than small molecule drugs. 2) They can potentially elicit an immune response. 3) They can have complex pharmacology through multiple mechanisms. 4) Their properties are not fully predictable through preclinical studies. 5) They may follow different regulatory pathways than originator biologics like biosimilars. Comprehensive pharmacovigilance is needed due to potential safety differences between
Topic explained as a M.Sc. Microbiology Student point of you. It contains general Properties of drug, its discovery process and Rational Drug Design Process using Bioinformatic Tools.
1. A randomized, double-blind study compared the pharmacokinetic and pharmacodynamic profiles of two recombinant human interferon alpha-2b formulations, INTRON A and HEBERON ALFA R, after a single intramuscular injection in 24 healthy male volunteers.
2. Both formulations induced similar increases in serum beta-2-microglobulin levels and fever profiles. Pharmacokinetic parameters like AUC, Cmax, and Tmax were similar between the groups, though INTRON A showed slightly smaller AUC and distribution values.
3. Overall, the study concluded that despite some differences in pharmacokinetic parameters, both formulations exhibited similar pharmacodynamic effects and safety profiles.
1) The document discusses various methods for extrapolating data from in vitro and preclinical animal studies to humans, including the NOAEL and MABEL methods.
2) It explains that the NOAEL method involves determining the No Observed Adverse Effect Level from animal studies, converting it to a Human Equivalent Dose using scaling factors, and applying a safety factor.
3) Two common methods for interspecies scaling are linear extrapolation, which assumes dosage is directly proportional to weight, and allometric scaling, which accounts for nonlinear relationships between pharmacokinetics and weight.
This document provides an overview of biopharmaceuticals. It discusses how biopharmaceuticals are medical drugs produced using biotechnology, especially genetic engineering. Some key points made in the document include:
- Biopharmaceuticals include cytokines, enzymes, hormones, monoclonal antibodies, and other protein or nucleic acid based therapies.
- Emerging biopharmaceutical technologies include monoclonal antibody production, vaccine manufacturing improvements, and non-ribosomal peptide synthesis.
- Biopharmaceuticals have changed treatment for diseases like diabetes and cancer by being tailored to specific medical problems in individuals with fewer side effects than traditional drugs.
The document discusses the importance of pharmacovigilance for biotherapeutic medicines. It notes that biotherapeutics are more complex and difficult to characterize than traditional small molecule drugs due to their large size and biological production processes. This underscores the importance of specific traceability for biotherapeutics in pharmacovigilance activities. The document recommends that the WHO work to develop global naming recommendations for biotherapeutics to facilitate accurate tracking and tracing of products and linkage of adverse events to the appropriate product. It also discusses new EU legislation requiring identification of biotherapeutics by brand name and batch number in adverse event reporting.
This document discusses the challenges of pharmacovigilance for biotherapeutic medicines. It notes that pharmacovigilance systems are developing at different rates globally, with inconsistent naming approaches for biotherapeutics. This can weaken signal detection. The document outlines five key challenges for biotherapeutics: 1) They are more complex and sensitive than small molecule drugs. 2) They can potentially elicit an immune response. 3) They can have complex pharmacology through multiple mechanisms. 4) Their properties are not fully predictable through preclinical studies. 5) They may follow different regulatory pathways than originator biologics like biosimilars. Comprehensive pharmacovigilance is needed due to potential safety differences between
Topic explained as a M.Sc. Microbiology Student point of you. It contains general Properties of drug, its discovery process and Rational Drug Design Process using Bioinformatic Tools.
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.
Hepatoprotective and Antioxidant Effects of the Flavonoid-rich Fraction of th...IOSRJPBS
The leaves of Jatropha tanjorensis are edible and used in herbal medicine in the treatment of diseases associated with oxidative stress. The present study demonstrates the antioxidative effect of the flavonoid-rich fraction of the methanol extract of Jatropha tanjorensis leaves (FRJT) against CCl4-induced hepatotoxicity in rats. Hepatoprotective and antioxidant properties of FRJT were determined by serum biochemical enzymes; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), antioxidant enzymes (SOD, CAT and GPx), heamatological pararmeters (PCV, Hb and WBC) and histology study. The results obtained showed a significant reduction (p < 0.05) in the activities of liver marker enzymes across the pre-treated groups compared with the untreated rats. Assay of antioxidant enzymes showed that the extract significantly (p < 0.05) enhanced SOD and GPx activities whereas CAT activity was non-significantly (p ˃ 0.05) increased when compared with the untreated animals. PCV, Hb and WBC levels were significantly (p < 0.05) lower in the untreated group. However, supplementation with FRJT and Silymarin ameliorated the induced depletion of blood in the pre-treated animals. Histological examination of the liver tissue showed marked reduction in fatty degeneration across the pre-treated groups when compared with the untreated group. The results in this study indicate that FRJT exhibited varying levels of protection against CCl4-induced oxidative stress in rat models. These results also indicate that the flavonoid-rich fraction contains antioxidants, which mop up free radicals in the system and support its use in the treatment of diseases resulting from oxidative damage.
The drug development process takes an average of 10-12 years and costs $500 million to $2 billion. Only one in 10,000 to 30,000 potential drug candidates makes it to market. The process involves drug discovery, preclinical testing in animals, and clinical trials in three phases with humans. Phase I tests safety in small groups, Phase II explores efficacy in larger groups, and Phase III tests effectiveness in large patient populations. If successful, the drug sponsor submits a New Drug Application to the FDA for review and potential approval. Post-marketing studies monitor long-term safety and efficacy. Thalidomide caused birth defects when tested inadequately in the late 1950s, highlighting the importance of rigorous preclinical and
Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings o...sstrumello
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.
Genotoxicity studies can be defined as various in-vitro and in-vivo tests designed to identify any substance or compounds which may induce damage to genetic material either directly or indirectly by various mechanisms. These tests should enable the identification of hazard with respect to DNA damage and fixation.
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.
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.
Potential role of bioactive peptides in prevention and treatment of chronic d...NxFxProducerDJ
This review analyzes studies and clinical trials on bioactive peptides and their potential roles in preventing and treating chronic diseases. The review focuses on cardiovascular diseases, immunity, cancer, and other areas. Bioactive peptides from various food sources like fish, milk, meat, and plants have shown effects like lowering blood pressure and lipids in clinical trials. Some peptides also demonstrate anticancer activity in vitro and in vivo as well as immunomodulatory and antimicrobial effects. However, more clinical evidence and standardized extraction procedures are still needed to confirm these effects and enable use of bioactive peptides as preventive or therapeutic treatments.
This document discusses new biological targets for drug development. It begins by defining biological targets and describing common targets such as G protein-coupled receptors, enzymes, and ligand-gated ion channels. Specific examples of new targets discussed include macrophages for HIV drugs, proteins involved in insulin signaling for diabetes therapies, and the cytokine IL-23 for inflammatory bowel disease. The document also mentions research into new targets for skin cancer, cardiovascular disease, and general efforts to identify novel drug targets from biological systems.
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.
Biosimilar a biological drug evaluation includes the biopharmaceutical families, the difference between small molecules and bio-pharmaceutical products, the regulatory requirements for biosimilars and the fact about biosimilars and biologic / bio pharmaceuticals the competent authorities and the key component of successful pharmacovigilane programs
Definition of biopharmaceuticals and biosimilars, Steps involved in manufacturing biopharmaceuticals, Points of differences between Biosimilars and Chemical Generics, Related issues with biosimilars
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.
The document discusses the importance of biotechnology in drug discovery. It notes that biotechnology has produced over 200 new therapies targeting various diseases. Biotechnology companies are more entrepreneurial and nimble compared to traditional pharmaceutical companies. The document also provides details on the large and growing biotech market in India and worldwide. It describes several applications of biotechnology across various stages of the drug discovery process, including target identification and validation, assay development, high-throughput screening, biomarker analysis, and protein engineering.
This document provides an overview of immunotoxicity testing procedures. It discusses the framework for immunotoxicity risk assessment, including hazard identification, characterization, exposure assessment, and risk characterization. General terminology related to immunotoxicity is defined. Test procedures are outlined, including animal selection, dosing, observation, and functional tests like the plaque forming cell assay and immunoglobulin quantification. The document also discusses additional tests that may be conducted depending on evidence, such as host resistance assays, hematology, and histopathology examinations. Test data is to be treated and reported according to good laboratory practice standards.
The document discusses the process of developing a molecule into a drug. It begins with choosing a disease and identifying a drug target. Lead compounds are found through screening existing drugs, natural products, combinatorial synthesis or computer-aided design. Lead compounds are then optimized in pre-clinical development through studies of toxicity, pharmacokinetics, and absorption, distribution, metabolism, and excretion. This involves testing in animal and computer models to improve the compound's activity and safety profile before human clinical trials.
The document discusses the process of drug discovery, including target selection, lead discovery, medicinal chemistry, in vitro and in vivo studies, and clinical trials. Target selection involves identifying cellular or genetic targets involved in disease through techniques like genomics, proteomics, and bioinformatics. Lead discovery focuses on identifying small molecule modulators of protein function through methods like synthesis, combinatorial chemistry, assay development, and high-throughput screening. Medicinal chemistry then works to optimize these leads. [/SUMMARY]
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.
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.
Intellectual Property Considerations During Nonclinical Drug DevelopmentMaryBreenSmith
Presentation provides a brief overview of regulatory and patent market exclusivities for new drugs. Presentation also covers the types of intellectual property typically arising out of preclinical studies.
Zipcar is a global car sharing service that provides vehicles by the hour or day to both personal and business members. It has over 650,000 members and 9,000 vehicles worldwide. Zipcar allows businesses to save time, money, and hassle compared to owning vehicles or using taxis/rental cars. Employees can reserve vehicles online or via app for meetings, errands, client meetings, and other occasions. Zipcar is also environmentally friendly by taking personally owned vehicles off the road. Business memberships provide discounted hourly rates and other benefits.
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.
Hepatoprotective and Antioxidant Effects of the Flavonoid-rich Fraction of th...IOSRJPBS
The leaves of Jatropha tanjorensis are edible and used in herbal medicine in the treatment of diseases associated with oxidative stress. The present study demonstrates the antioxidative effect of the flavonoid-rich fraction of the methanol extract of Jatropha tanjorensis leaves (FRJT) against CCl4-induced hepatotoxicity in rats. Hepatoprotective and antioxidant properties of FRJT were determined by serum biochemical enzymes; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), antioxidant enzymes (SOD, CAT and GPx), heamatological pararmeters (PCV, Hb and WBC) and histology study. The results obtained showed a significant reduction (p < 0.05) in the activities of liver marker enzymes across the pre-treated groups compared with the untreated rats. Assay of antioxidant enzymes showed that the extract significantly (p < 0.05) enhanced SOD and GPx activities whereas CAT activity was non-significantly (p ˃ 0.05) increased when compared with the untreated animals. PCV, Hb and WBC levels were significantly (p < 0.05) lower in the untreated group. However, supplementation with FRJT and Silymarin ameliorated the induced depletion of blood in the pre-treated animals. Histological examination of the liver tissue showed marked reduction in fatty degeneration across the pre-treated groups when compared with the untreated group. The results in this study indicate that FRJT exhibited varying levels of protection against CCl4-induced oxidative stress in rat models. These results also indicate that the flavonoid-rich fraction contains antioxidants, which mop up free radicals in the system and support its use in the treatment of diseases resulting from oxidative damage.
The drug development process takes an average of 10-12 years and costs $500 million to $2 billion. Only one in 10,000 to 30,000 potential drug candidates makes it to market. The process involves drug discovery, preclinical testing in animals, and clinical trials in three phases with humans. Phase I tests safety in small groups, Phase II explores efficacy in larger groups, and Phase III tests effectiveness in large patient populations. If successful, the drug sponsor submits a New Drug Application to the FDA for review and potential approval. Post-marketing studies monitor long-term safety and efficacy. Thalidomide caused birth defects when tested inadequately in the late 1950s, highlighting the importance of rigorous preclinical and
Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings o...sstrumello
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.
Genotoxicity studies can be defined as various in-vitro and in-vivo tests designed to identify any substance or compounds which may induce damage to genetic material either directly or indirectly by various mechanisms. These tests should enable the identification of hazard with respect to DNA damage and fixation.
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.
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.
Potential role of bioactive peptides in prevention and treatment of chronic d...NxFxProducerDJ
This review analyzes studies and clinical trials on bioactive peptides and their potential roles in preventing and treating chronic diseases. The review focuses on cardiovascular diseases, immunity, cancer, and other areas. Bioactive peptides from various food sources like fish, milk, meat, and plants have shown effects like lowering blood pressure and lipids in clinical trials. Some peptides also demonstrate anticancer activity in vitro and in vivo as well as immunomodulatory and antimicrobial effects. However, more clinical evidence and standardized extraction procedures are still needed to confirm these effects and enable use of bioactive peptides as preventive or therapeutic treatments.
This document discusses new biological targets for drug development. It begins by defining biological targets and describing common targets such as G protein-coupled receptors, enzymes, and ligand-gated ion channels. Specific examples of new targets discussed include macrophages for HIV drugs, proteins involved in insulin signaling for diabetes therapies, and the cytokine IL-23 for inflammatory bowel disease. The document also mentions research into new targets for skin cancer, cardiovascular disease, and general efforts to identify novel drug targets from biological systems.
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.
Biosimilar a biological drug evaluation includes the biopharmaceutical families, the difference between small molecules and bio-pharmaceutical products, the regulatory requirements for biosimilars and the fact about biosimilars and biologic / bio pharmaceuticals the competent authorities and the key component of successful pharmacovigilane programs
Definition of biopharmaceuticals and biosimilars, Steps involved in manufacturing biopharmaceuticals, Points of differences between Biosimilars and Chemical Generics, Related issues with biosimilars
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.
The document discusses the importance of biotechnology in drug discovery. It notes that biotechnology has produced over 200 new therapies targeting various diseases. Biotechnology companies are more entrepreneurial and nimble compared to traditional pharmaceutical companies. The document also provides details on the large and growing biotech market in India and worldwide. It describes several applications of biotechnology across various stages of the drug discovery process, including target identification and validation, assay development, high-throughput screening, biomarker analysis, and protein engineering.
This document provides an overview of immunotoxicity testing procedures. It discusses the framework for immunotoxicity risk assessment, including hazard identification, characterization, exposure assessment, and risk characterization. General terminology related to immunotoxicity is defined. Test procedures are outlined, including animal selection, dosing, observation, and functional tests like the plaque forming cell assay and immunoglobulin quantification. The document also discusses additional tests that may be conducted depending on evidence, such as host resistance assays, hematology, and histopathology examinations. Test data is to be treated and reported according to good laboratory practice standards.
The document discusses the process of developing a molecule into a drug. It begins with choosing a disease and identifying a drug target. Lead compounds are found through screening existing drugs, natural products, combinatorial synthesis or computer-aided design. Lead compounds are then optimized in pre-clinical development through studies of toxicity, pharmacokinetics, and absorption, distribution, metabolism, and excretion. This involves testing in animal and computer models to improve the compound's activity and safety profile before human clinical trials.
The document discusses the process of drug discovery, including target selection, lead discovery, medicinal chemistry, in vitro and in vivo studies, and clinical trials. Target selection involves identifying cellular or genetic targets involved in disease through techniques like genomics, proteomics, and bioinformatics. Lead discovery focuses on identifying small molecule modulators of protein function through methods like synthesis, combinatorial chemistry, assay development, and high-throughput screening. Medicinal chemistry then works to optimize these leads. [/SUMMARY]
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.
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.
Intellectual Property Considerations During Nonclinical Drug DevelopmentMaryBreenSmith
Presentation provides a brief overview of regulatory and patent market exclusivities for new drugs. Presentation also covers the types of intellectual property typically arising out of preclinical studies.
Zipcar is a global car sharing service that provides vehicles by the hour or day to both personal and business members. It has over 650,000 members and 9,000 vehicles worldwide. Zipcar allows businesses to save time, money, and hassle compared to owning vehicles or using taxis/rental cars. Employees can reserve vehicles online or via app for meetings, errands, client meetings, and other occasions. Zipcar is also environmentally friendly by taking personally owned vehicles off the road. Business memberships provide discounted hourly rates and other benefits.
Este documento resume los conceptos básicos de la cría de Pokémon, incluyendo la selección de padres, el uso de ítems de cría para heredar ciertos IVs, y la importancia de la naturaleza para maximizar los stats de un Pokémon. Explica que la cría comienza con la elección del Pokémon y sus movimientos Egg, además de los IVs y padres importantes, y que los ítems como Everstone ayudan a heredar ciertos stats de los padres a los huevos.
Este documento resume los conceptos básicos de la cría de Pokémon, incluyendo la selección de padres, el uso de ítems de cría para heredar ciertos IVs, y la importancia de la naturaleza para maximizar los stats de un Pokémon. Explica que la cría comienza con la elección del Pokémon y sus movimientos Egg, además de los IVs y padres importantes, y que los ítems como Everstone ayudan a heredar ciertos stats de los padres a los huevos.
16 12 11_-_sdm_project[1] [modo de compatibilidade]Clapbio
This document outlines a research project on using shared decision making (SDM) to guide discussions about biosimilars and biological agents in Latin America. The project will involve two stages: 1) an international survey to understand stakeholders' perspectives on SDM and its applicability to biosimilars, and 2) development and testing of a decision aid tool to facilitate SDM discussions on biosimilars while accounting for cultural factors. The goal is to explore barriers to SDM implementation and develop a validated decision aid to guide discussions and priority setting around biosimilar treatment options in Latin America.
La lista presenta los estudiantes con excelencia académica en el primer trimestre. Algunos de los estudiantes destacados son María Gómez, quien obtuvo las mejores calificaciones en matemáticas, y Juan Pérez, que se destacó en ciencias.
El documento presenta las instrucciones para un juego de mesa sobre el Camino de Santiago. Los jugadores deben avanzar por un tablero contestando preguntas sobre la ruta y la ciudad de Santiago. El juego se puede jugar de forma individual o por equipos. El objetivo es ser el primero en llegar a la Catedral de Santiago respondiendo correctamente a las preguntas.
Este documento presenta las normas y las instrucciones de un juego de mesa sobre la ciudad de Santiago. Los jugadores avanzan por casillas tirando un dado y respondiendo preguntas sobre lugares y hechos de la ciudad. El juego contiene 23 casillas con sitios emblemáticos de Santiago y 20 preguntas sobre su historia, cultura y símbolos.
The document outlines the history and current state of childcare in Japan. It traces the origins of kindergartens back to 1871 and daycare centers to 1890. Today, the formal childcare system includes kindergartens overseen by the Ministry of Education for children ages 3-5, and daycare centers overseen by the Ministry of Health and Welfare for children ages 0-5. Attendance in preschool education has increased over time and there is a trend toward more free public options. The underlying philosophy focuses on teaching children etiquette, independence, and confidence. Childcare workers require specific training and certificates.
This document lists the names of several architectural projects including PREPKITCHEN Little Italy, DIGITARIA, Solace & the Mooonlight Lounge, GoPro, Davanti, UCSD International Center, and Indian Wells Tennis Garden—Shade Structure.
Este documento contiene las respuestas de un estudiante a varias preguntas sobre una lectura. En resumen, el estudiante opina que la actitud de dependencia de los pájaros no es buena, ya que no tienen un rumbo definido. También dice que es importante definir metas y no depender de los demás. Finalmente, el estudiante explica que su rumbo es terminar sus estudios y cumplir sus sueños a través del trabajo duro.
Guide for conducting comparability exercise for biological product registrationClapbio
This document provides guidance for conducting a comparability exercise between a proposed biological product (BP) and an authorized comparator biological product (CBP) for the purpose of biological product registration. It outlines the quality, stability, manufacturing process, and data requirements that must be evaluated and presented in a comparability study to demonstrate that the BP is similar to the CBP, upon which reduced nonclinical and clinical data can be relied. Key aspects that must be compared include quality attributes, samples from manufacturing process stages, stability under stress conditions, and data from multiple batches. Significant unjustified differences found would indicate the products are not similar.
This document outlines regulations for controlling human pharmaceutical products in a national system. It establishes the Ministry of Health and the Institute of Public Health as the competent authorities responsible for regulating pharmaceutical activities including registration, manufacturing, distribution, and advertising. It also assigns responsibilities to Regional Health Departments for authorizing product admission and enforcing compliance. Finally, it provides definitions for 29 key terms related to pharmaceutical quality, safety, and regulation.
The document provides guidelines for the evaluation of similar biotherapeutic products (SBPs). It outlines key principles for licensing SBPs, which include:
1) Development of a SBP involves stepwise comparability exercises starting with quality comparisons to a reference biotherapeutic product (RBP), with demonstration of similarity a prerequisite for reduced non-clinical and clinical data requirements.
2) Licensing of a SBP is based on its demonstrated similarity to a suitable RBP in quality, non-clinical, and clinical parameters.
3) Comparability exercises include integrated quality, non-clinical and clinical studies to provide comparative data between the SBP and RBP. Differences require investigation and may necessitate additional data.
The document summarizes the history and development of kindergarten and daycare centers in Japan. It notes that the first kindergarten was established in 1876, and kindergarten became part of the basic school education system in 1947 under the Ministry of Education. The first daycare center opened in 1890, and they were set up in factories starting in 1894, receiving subsidies beginning in 1908 and becoming classified as child welfare facilities in 1947 under the Ministry of Health and Welfare. Attendance rates for preschool education increased over time, reaching 100% for 4-5 year olds by 1981. Public and private kindergartens and daycares receive different levels of financial support. A basic plan from 2008 aimed to increase
Guide for elaboration of clinical study reports for biological product regist...Clapbio
This document provides guidance on the minimum content and format required for clinical study reports submitted for biological product registration or post-registration changes. It outlines 20 sections that should be included, such as background on the study design, objectives, treatments, endpoints, results analyses, and conclusions. Adherence to this standard format will help ensure clinical reports contain all necessary information to support regulatory reviews.
This executive decree modifies regulations regarding the health registration of biological and biotech products in Panama. It establishes new requirements for registering biotech products, including presenting clinical trial data, quality and manufacturing information, risk management programs, and certificates of analysis for each imported batch. Biotech products already registered must now present clinical trials within 60 days to maintain their registration. The decree aims to ensure the efficacy, safety and quality of biopharmaceuticals marketed in Panama.
La Fundación Junior Achievement Colombia, mejor conocida como Colombia Emprendedora se complace en
presentar a ustedes el programa Mujeres Emprendedoras, que se ejecutará gracias al patrocinio de Accenture
Ltda. y con la colaboración de la Fundación Ana Restrepo del Corral.
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This document provides information about biological assays. It begins by defining an assay and describing different types including chemical, immuno, and biological assays. It then focuses on biological assays, explaining that they measure the effect of a substance on a living organism or tissue. The key advantages of biological assays are that they determine actual biological activity rather than just concentration, and can assess compounds when chemical structure is unknown. However, biological assays are generally less precise and more time-consuming than chemical assays. The document provides details about how biological assays are performed and standardized, including the use of standard preparations and units of activity. It also discusses quantitative, graded, and characterized bioassays as well as the principles, techniques, applications, and limitations of biological assays
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This document discusses key concepts in pharmaceutics and drug development. It covers:
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Guide for conduction of nonclinical and clinical studies for registration of alphainterferon as biological product by comparability development
1. Guide for conduction of nonclinical and
clinical studies for registration of alpha-
interferon as biological product by
comparability development
2. National Health Surveillance Agency | Anvisa
Guide for Conduction of Nonclinical and
Clinical Studies for Registration of
Alpha-Interferon as Biological Product
by Comparability Development
Brasilia 2011
4. Table of contents
1 Introduction.................................................................................................................................................... 4
2 General Considerations ...................................................................................................................................4
3 Nonclinical studies.....................................................................................................................................5
4 Clinical studies ...........................................................................................................................................6
5 Immunogenicity ..........................................................................................................................................7
6 Indication Extrapolation..........................................................................................................................7
7 Pharmacovigilance Plan ..........................................................................................................................7
8 References .................................................................................................................................................8
Guide for conduction of nonclinical and clinical studies for registration of heparins as biological product in development by comparability 3
5. 1
Introduction
This guide outlines the clinical and nonclinical requirements for registration of recombinant human alpha-interferon in Anvisa
[National Health Surveillance Agency] as biological product, using the route of individual development. The nonclinical section
deals with the pharmaco-toxicological requirements, and the clinical section addresses the requirements for pharmacokinetic,
pharmacodynamics, efficacy and safety studies, as well as pharmacovigilance aspects. Suggestions of nonclinical and clinical
protocols are also presented.
In this guide, we will bring general directions for the conduction of nonclinical and clinical studies for registration of recombinant
human alpha-interferon by comparability. However, if the researcher/institution is able to evidence the efficacy and safety of these drugs
through other scientific and technically more feasible studies, the data presented will be evaluated by ANVISA and the deviation
from the guide’s directions must always be justified.
This Guide will address only the requirements for nonclinical and clinical studies applicable for registration of recombinant human
alpha-interferon by comparability, being that the other items of the specific standards must be complied with for health registration
of the product.
2 General
considerations
Recombinant human alpha-interferon (2a a n d 2 b ) i s a known and well characterized protein made up of 165 amino acids.
The non-glycosylated protein has a molecular weight of approximately 19.240 Da. The protein contains two disulfide
bridges, one between the cysteine residues 1 and 98 and another between the cysteine residues 29 and 138. The sequence
contains potential O-glycosylation sites. Physical, chemical and biological methods are available for protein
characterization.
Recombinant human alpha-interferon is approved for different indications like hepatitis virus B and C, leukemia, lymphoma, renal
cell carcinoma and multiple myeloma and can be used separately or in combination with other drugs. Alpha-interferon can have
different pharmacodynamics effects. The importance of these pharmacodynamics effects in each one of the clinical applications is still
unknown. Generally, the use of alpha-interferon in oncology has reduced considerably and is being replaced by other treatments.
The dose and therapeutic scheme required to obtain the desired response vary greatly according to the different indications.
Alpha-interferon is normally used subcutaneously, although it can also be used intramuscularly or intravenously. Treatment with
alpha-interferon 2a and 2b is associated with different adverse reactions like fever, discomfort, fatigue, myalgia and can also be
associated with psychiatric, hematological and renal adverse events.
Therapy with alpha-interferon can lead to development of auto-antibodies. A variety of autoimmune disorders like problems in the
thyroid, rheumatoid arthritis, systemic erythematous lupus, neuropathies and vasculitis have been observed with the use of alpha-
interferon.
Both neutralizing and non-neutralizing antibodies were observed during use of alpha-interferon.
This guide does not address the quality requirements. For aspects related to quality, the principles are applied as set forth in the Guide
for conduction of the comparability exercise for registration of biological products by comparability and Resolution RDC No. 55/10
and its updates.
According to RDC 55/10, the comparer biological product (CBP) cited in this guide is recombinant human alpha-interferon
registered at Anvisa through presentation of a complete dossier.
6. 4 Guide for conduction of nonclinical and clinical studies for registration of heparins as biological product in development by comparability
7. 3 Nonclinical studies
Before starting the clinical development, nonclinical studies must be conducted. The nonclinical studies must be comparative and
designed to detect differences in the pharmaco-toxicological response between the alpha-interferon to be registered and the CBP, and
not just to evaluate the response per se. The approach adopted must be fully justified in the nonclinical summary.
Pharmacodynamic studies
In vitro studies:
In order to compare the changes in the activity between the alpha-interferon to be registered and the CBP, one must provide data on a
series of comparative bioassays (bond with receptor, antiviral effect in cell culture, anti-proliferative effects in tumor cell lineages),
being that several of these assays will already be part of the quality dossier in the comparability exercise.
In vivo studies:
One must compare the in vivo pharmacodynamics activity of the alpha-interferon to be registered and of the CBP in:
• a suitable animal pharmacodynamics model (e.g. evaluation of the effects on pharmacodynamics markers, like 2’-5’-
oligoadenylate synthetase activity in the serum). If possible, these evaluations must be conducted as part of a toxicity
study.
and/
or
• suitable tumor animal model and/or
• suitable antiviral animal model
Toxicology Studies
Data on at least one repeated dose toxicity study in relevant species must be provided. The study must have duration of at least 4
weeks.
Toxicokinetic studies must be conducted as part of the repeated dose toxicity study and must include evaluation of the antibody
formation potential.
Data on the local tolerance in at least one species must be provided. If possible, these local tolerance tests can be conducted as part of
a repeated-dose toxicity study.
E Pharmacological studies on safety, reproductive toxicology, mutagenicity and carcinogenicity are not routine requirements for the
nonclinical tests of a biological drug product containing recombinant human alpha-interferon.
For the case of nonclinical development, comparative studies must be conducted using the alpha-interferon elected as comparer product
(alpha-interferon registered at Anvisa through presentation of a complete dossier) and the alpha-interferon to be registered. At least
two relevant species should be used if available and local tolerance, acute toxicity and repeated dose toxicity studies must be
conducted. Comparative evaluation of pharmacokinetic, pharmacodynamics and immunogenicity (whenever possible) parameters are
also required.
Guide for conduction of nonclinical and clinical studies for registration of heparins as biological product in development by comparability 5
8. 4 Clinical studies
Pharmacokinetic/Pharmacodynamic Studies
The pharmacokinetic/pharmacodynamics properties of the alpha-interferon to be registered and of the CBP must be compared in a
randomized, single-dose study in health volunteers. The primary pharmacokinetic parameters recommended are area under the curve
(AUC) and the secondary parameters are Cmax, T1/2 and CL/F.
The equivalence margins must be pre-specified and appropriately justified.
Pharmacodynamic Studies:
Different pharmacodynamics markers are available, like β2 microglobulin, neopterin and 2’-5’- oligoadenylate synthetase activity
in the serum, which are relevant to measure the interaction between alpha-interferon and the immune system. The doses selected must
be in the ascending linear region of the dose response curve. Even though the importance of these pharmacodynamics effects is still
unknown in the different indications, a complete comparative evaluation after administration of epoetin alpha to be registered and the
CBP can provide useful data.
After conducting the necessary nonclinical studies with satisfactory results, the conduction of a Phase I, comparative, double-blind
study is recommended with health volunteers and a wash-out period of 4 weeks. The aim of this study is comparison of the
pharmacokinetic and pharmacodynamics parameters and gathering of preliminary safety data.
Clinical Efficacy
Study population
The action mechanism of alpha-interferon includes a series of different unrelated effects.
Demonstration of effect similarity between the product to be registered and the CBP is required. This can be done in a virgin
population of treatment with hepatitis C (HCV), as outlined by the indication of the CBP. Other populations must be studied
according to the indications desired.
Study outlining and duration
A parallel, randomized group study for comparison of the products for at least 48 weeks is recommended. The study must be double-
blind at least up to the point in which the data from the primary analyses is generated. If this is not possible, a justification must be
presented and all actions to eliminate possible biases must be clearly identified in the protocol.
The posology (dose, administration route and administration methodology) must be the same as for the CBP. The alpha-interferon
must be administered together with the standard treatment for hepatitis C used together with the CBP.
The study must be outlined so as to allow conduction of the primary efficacy analysis in the twelfth week for all recruited patients. A
homogeneous population is preferably recommended, for example, a single viral genotype. If a heterogeneous population is selected,
stratification must be conducted according to the viral genotype.
Outcomes
Primary: virological response evaluated by the number of patients with absence of HCV RNA detection by quantitative PCR in the
twelfth week. The methodology used and the cutoff applied must be justified. A decrease of 2 log in the viral growth must have a co-
primary outcome.
Secondary: virological response in the fourth week and at the end of treatment; sustained virological response (24 weeks after the end
of treatment); changes in the hepatic biochemical parameters including levels of transaminase and morbidity.
6 Guide for conduction of nonclinical and clinical studies for registration of heparins as biological product in development by comparability
9. Clinical safety
The safety data must be collected from the patients after repeated doses in a comparative study during the treatment period and
another period of 24 weeks of follow-up. The number of patients must be enough for comparison of the adverse effect profiles.
Evaluation of lab changes of immune-mediated disorders must be included. The safety profile between the alpha-interferon to be
registered and the CBP must be similar for the most common adverse events (fever, discomfort, alopecia, myalgia, leukopenia,
anemia and thrombocytopenia).
If the results of the Phase I Study are satisfactory, a Phase II/III study can be conducted to evaluate the efficacy and safety of the
alpha-interferon to be registered in relation to the comparer biological product. It must be a double-blind study to compare
non-inferiority or equivalence in patients with Hepatitis C and have minimum duration of 48 weeks. The primary outcome of
the study must be viral remission (evaluated through quantitative PCR) in the 24th week and the secondary outcomes will be
virological response in the 4th, 12th and 48th weeks (evaluated through quantitative PCR); biochemical parameters must also be
evaluated (including transaminases) and morbidity levels. Evaluation of safety (type, severity and incidence of adverse events)
and of immunogenicity must be done for the period of the study duration (48 weeks). In case of any significant finding in
relation to the safety and immunogenicity parameters, additional studies may be requested.
5 Immunogenicity
Comparative data on immunogenicity (levels of antibodies) must be collected during the study period and also during the 24-week
follow-up period. The antibodies, when present, must be evaluated for neutralizing capacity and potential impact on product efficacy.
Furthermore, any potential for neutralization of the alpha-interferon’s endogenous effect (development of autoimmunity) must be
evaluated. Any immunogenicity impact must be evaluated in patients who do not respond to the treatment, patients who present loss
of response in the primary treatment and patients who present unexpected adverse reactions or immune-mediated events.
6 Indication Extrapolation
At first, the extrapolation of therapeutic indications is possible when the action mechanism and/or receptors are the same for which the
clinical similarity was established, through comparative clinical study.
7 Pharmacovigilance Plan
Within the authorization procedure, the applicant must always present a pharmacovigilance plan and a risk reduction plan whenever
required according to the legislation in effect and pharmacovigilance guidelines.
Special attention must be paid to issues related to immunogenicity and later serious adverse effects in patients under chronic
administration of the product. Safety data must be gathered from patients covering all approved indications.
The Pharmacovigilance Plan must include follow-up of the patients included in the Phase II/III study for evaluation of relapses.
Guide for conduction of nonclinical and clinical studies for registration of heparins as biological product in development by comparability 7
10. 8 References
Guideline on similar biological medicinal products (CHMP/437/04/draft).
Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical
and clinical issues (EMEA/CPMP/42832/05/draft).
Note for guidance on repeated dose toxicity (CPMP/SWP/1042/99).
Note for guidance on toxicokinetics: A Guidance for assessing systemic exposure in toxicological studies (CPMP/ICH/384/95).
Note for guidance on non-clinical locale tolerance testing of medicinal products (CPMP/SWP/2145/00).
Guideline on risk management systems for medicinal products for human use (EMEA/CHMP 96286/2005).
Note for Guidance on Good Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (CPMP/
ICH/377/95).
ICH Note for Guidance on Planning Pharmacovigilance Activities (CPMP/ICH/5716/03 - Final approval by CHMP on PHV).
Guidance on Planning Pharmacovigilance Activities (CPMP/
8 Guide for conduction of nonclinical and clinical studies for registration of heparins as biological product in development by comparability