1. Biosimilars are not generics because they have a different manufacturing process and excipients compared to the innovator product.
2. Hypothesis testing is not adequate for demonstrating biosimilarity because it is difficult to detect a difference with small subject numbers.
3. An "intended copy" is a biologic product that is attempting to demonstrate biosimilarity but has not fully done so yet.
QIVIVE extrapolation requires a precise correlation between exposure and the effective chemical concentration at the site where the MIE occurs.
This work demonstrates that intracellular distribution is not ruled only by physical-chemical parameters, rather it is mainly regulated by specific biological-mediated mechanisms. Substances with
apparent chemical similarity may show different distribution profile, as shown by the intra-nuclear distribution of polyphenols. While our results derive from a limited number of substances applied to
one cell line, it is plausible that using different substances and/or different cell lines would also have shown that intracellular distribution is not directly related to physical-chemical parameters.
Chemical uptake should be specifically measured and simple extrapolations based on physical-chemical properties may provide misleading decision
There are tens of thousands of man-made chemicals to which humans are exposed, but only a fraction of these have the extensive in vivo toxicity data used in most traditional risk assessments. This lack of data, coupled with concerns about testing costs, are driving the development of new methods for assessing the risk of toxicity.
This presentation by Dr. Richard Judson reviewed methods being used at the U.S. EPA to use zebrafish as an in vivo model of vertebrate developmental toxicity and build in vitro to in vivo models using human assays.
EPA is committed to sound science, and we are proud to have some of the world's best scientists, many of whom are internationally recognized as leaders in their fields. Not only are EPA's scientific experts vital to achieving our mission, but they are dedicated to sharing knowledge and contributing to their the scientific communities, which helps further advance the science that protects human health and the environment. Part of this includes giving presentations to other members of the scientific community. We have posted some of these presentations here so that more people have access.
Learn more about Dr. Richard Judson - https://www.epa.gov/sciencematters/meet-epa-researcher-richard-judson
Learn more about EPA's Chemical Safety Research - https://www.epa.gov/chemical-research
QIVIVE extrapolation requires a precise correlation between exposure and the effective chemical concentration at the site where the MIE occurs.
This work demonstrates that intracellular distribution is not ruled only by physical-chemical parameters, rather it is mainly regulated by specific biological-mediated mechanisms. Substances with
apparent chemical similarity may show different distribution profile, as shown by the intra-nuclear distribution of polyphenols. While our results derive from a limited number of substances applied to
one cell line, it is plausible that using different substances and/or different cell lines would also have shown that intracellular distribution is not directly related to physical-chemical parameters.
Chemical uptake should be specifically measured and simple extrapolations based on physical-chemical properties may provide misleading decision
There are tens of thousands of man-made chemicals to which humans are exposed, but only a fraction of these have the extensive in vivo toxicity data used in most traditional risk assessments. This lack of data, coupled with concerns about testing costs, are driving the development of new methods for assessing the risk of toxicity.
This presentation by Dr. Richard Judson reviewed methods being used at the U.S. EPA to use zebrafish as an in vivo model of vertebrate developmental toxicity and build in vitro to in vivo models using human assays.
EPA is committed to sound science, and we are proud to have some of the world's best scientists, many of whom are internationally recognized as leaders in their fields. Not only are EPA's scientific experts vital to achieving our mission, but they are dedicated to sharing knowledge and contributing to their the scientific communities, which helps further advance the science that protects human health and the environment. Part of this includes giving presentations to other members of the scientific community. We have posted some of these presentations here so that more people have access.
Learn more about Dr. Richard Judson - https://www.epa.gov/sciencematters/meet-epa-researcher-richard-judson
Learn more about EPA's Chemical Safety Research - https://www.epa.gov/chemical-research
There are tens of thousands of man-made chemicals to which humans are exposed, but only a fraction of these have the extensive in vivo toxicity data used in most traditional risk assessments. This lack of data, coupled with concerns about testing costs and animal use, are driving the development of new methods for assessing the risk of toxicity. These methods include the use of in vitro high-throughput screening assays and computational models.
This presentation by Dr. Richard Judson reviewed a variety of high-throughput, non-animal methods being used at the U.S. EPA to screen chemicals for a variety of toxicity endpoints, including methods for providing mechanistic data like the Adverse Outcome Pathway.
EPA is committed to sound science, and we are proud to have some of the world's best scientists, many of whom are internationally recognized as leaders in their fields. Not only are EPA's scientific experts vital to achieving our mission, but they are dedicated to sharing knowledge and contributing to their the scientific communities, which helps further advance the science that protects human health and the environment. Part of this includes giving presentations to other members of the scientific community. We have posted some of these presentations here so that more people have access.
Learn more about Dr. Richard Judson - https://www.epa.gov/sciencematters/meet-epa-researcher-richard-judson
Learn more about EPA's Chemical Safety Research - https://www.epa.gov/chemical-research
There are tens of thousands of man-made chemicals to which humans are exposed, but only a fraction of these have the extensive in vivo toxicity data used in most traditional risk assessments. This lack of data, coupled with concerns about testing costs and animal use, are driving the development of new methods for assessing the risk of toxicity. These methods all start with the use of in vitro assays, e.g. for activity against the estrogen and androgen receptors (ER and AR) and targets in the steroidogenesis and thyroid signaling pathways. Because all individual assays are subject to a variety of noise processes and technology-specific assay artifacts, we have developed methods to create consensus predictions from multiple assays against the same target. The goal of these models is to both robustly predict in vivo activity, and also to provide quantitative estimates of uncertainty. This presentation by Dr. Richard Judson described these models and how they are validated against both in vitro and in vivo reference chemicals.
EPA is committed to sound science, and we are proud to have some of the world's best scientists, many of whom are internationally recognized as leaders in their fields. Not only are EPA's scientific experts vital to achieving our mission, but they are dedicated to sharing knowledge and contributing to their the scientific communities, which helps further advance the science that protects human health and the environment. Part of this includes giving presentations to other members of the scientific community. We have posted some of these presentations here so that more people have access.
Learn more about Dr. Richard Judson - https://www.epa.gov/sciencematters/meet-epa-researcher-richard-judson
Learn more about EPA's Chemical Safety Research - https://www.epa.gov/chemical-research
Identification of Bioactive Compounds in the acetone extract of Daedalea eleg...AI Publications
Daedalea elegans is a Nigerian wild (non-edible) higher fungus with great potentials in the pharmaceutical, textile, cosmetics and food industry. This current study investigates the bioactive compounds that can be found in the acetone extract of D. elegans using Gas Chromatography-Mass Spectrometry (GC-MS). There were twenty-eight compounds identified to be present in the acetone extract of the fungi under study and these are Benzoic acid (0.40%), Nonanoic acid (0.14%), Oxetane, 2,2,4-trimethyl- (0.28%), n-Decanoic acid (0.09%), Phthalimide (0.44%) Dodecanoic acid (0.24%), E-2-Hexenyl benzoate (0.21%), 2,4-Difluorobenzene, 1-benzyloxy- (0.16%), Tetratetracontane (0.55%), Isopropylphosphonic acid, fluoroanhydryde (0.28%), Benzene, (1-methylundecyl)- (0.21%), Tetradecanoic acid (0.76%), Cyclohexanepropanol, .alpha.,2,2,6-tetrame (0.56%), Pentadecanoic acid (0.71%), E-2-Hexenyl benzoate (0.32%), Pentadecanoic acid (0.97%), 1-Decanol, 2-hexyl- (0.46%), 9-Tetradecenal, (Z) (1.67), n-Hexadecanoic acid (23.59%) is the second most abundant, Phthalic acid, butyl undecyl ester (1.08%), Eicosanoic acid (0.79%), 9,12-Octadecadienoic acid (Z,Z)- (44.64%) was the highest in quantity, Octadecanoic acid (6.98%), Bis(2-ethylhexyl) phthalate (2.64%), 2,2,4-Trimethyl-3-(3,8,12,16-tetramethyl-heptadeca-3,7,11,15-tetraenyl)-cyclohexanol (1.95%), 9(11)-Dehydroergosteryl benzoate (8.37%), 9(11)-Dehydroergosteroltosylate (1.28%), 4,6-Decadienal, 8-ethyl-10-[4-hydroxy-8-(2-hydroxypropyl)-3,9 (0.22%). These compounds possess activities which includes but not limited to cancer chemotherapy, antifeedant against pine weevil, antifungi agent in topical therapeutic preparation, anti-inflammatory, immunomodulatory, anti-convulsant, antioxidants, hypocholesterolemic, anti-androgenic, nematicide, analgesic, intermediate for food-grade additives, lubricants, greases, rubber, dyes and plastic, antineoplastic agent, biosynthesis of prostaglandins and cell membrane to mention a few. This study has been able to show that D. elegans is a good source of bioactive compounds with great potentials that can be harnessed in various industries.
ST8 micellar/niosomal vesicular nanoformulation for delivery of naproxen in c...Vahid Erfani-Moghadam
Naproxen (NPX) is a non-steroidal anti-inflammatory drug (NSAID) used against a variety of diseases, including autoimmune disorders and chronic inflammations. However, low water solubility limits its therapeutic efficacy and novel nanoformulations are required to bypass its poor bioavailability to reach its therapeutic effect. The purpose of the study was to investigate the role of the nanoformulation of biocompatible molecules; Squalene (S) and Tween 80 (T8) Micellar/Niosomal Vesicles (ST8MNV) prepared, by thin-film hydration method and their potential as a drug delivery system for NPX. The percentage of encapsulation efficiency was calculated to be 99.5 ± 0.2% for 5% of NPX weight in total ingredients of micellar/niosomal vesicles (w/w). The ST8MNV nanoformulation exhibited a slower rate of NPX release from the drug encapsulated over seven days, suggesting a stable complex of NPX. Finally, cell toxicity assay demonstrated that the half-maximal inhibitory concentrations (IC50) of NPX were drastically reduced by ST8MNV nanoformulation in MCF-7, A549, HeLa, and MDA-MB-231 cancer cell lines. Our data show this micellar/niosomal naproxen nanoformulation is a great candidate for the future in vitro and in vivo studies for potential clinical anti-inflammatory and anticancer applications.
The Comprehensive Guide to Genotoxicity AssessmentMilliporeSigma
Discover solutions for all phases of product development for genetox assessment from in silico analysis, screening, mode of action assessment, or GLP regulatory required assays. Our BioReliance® Genetic Toxicology Services director will share specifics and rationale for each assay category.
In this webinar you will:
- Learn the required regulatory assays
- Understand why each assay is used and how to employ different assay designs
- Learn different assays and techniques to screen potential compounds and understand mechanism and mode of action
Presented by Rohan Kulkarni, Ph.D., ERT, Director Toxicology, Study Management on February 9, 2017
Development, safety and efficacy analysis of liquid state rabiesBalaganesh Kuruba
Rabies is a highly fatal epidemic disease in the world with high mortality rate in the infected individuals. According to the survey conducted by WHO across different parts of the globe, every year 50000 people die because of Rabies. And most of the vaccines are produced as solid-state vaccines.
Before formulation the purified PV 11 derived concentrated, infected and chromatographically purified rabies antigens are checked for their efficiency, potency by invitro methods.
Four different combinations of stabilizers, additives and adjuvants are blended with rabies antigen. Those are labelled as TCARLV-A, TCARLV-B, TCARLV-C, TCARLV-D. And find estimate the constituents in single Human dose.
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3aeCPNB
Find out how we turn up the dial on quality control testing for cell and gene therapies through rapid methods for sterility, mycoplasma, and replication competent virus. We will review the current regulatory expectations as well as the benefits and limitations that come with each method.
Two of the biggest challenges with applying traditional quality control (QC) test methods to cell and gene therapies, is time to results, due to short shelf-life, and availability of sufficient sample, due to small production volumes.
So how can these challenges be overcome while still meeting regulatory expectations?
In this webinar we will discuss and review suitable methods for rapid testing of short-life cell and gene therapies that may also help conserve limited production material. We will look at benefits, limitations, and regulatory expectations for various QC needs including current and future rapid methods for sterility, mycoplasma and replication competent virus.
In this webinar, you will learn:
• Why the shelf life of a cell or gene therapy product may impact your QC testing strategy
• Current regulatory expectations surrounding rapid methods for sterility, mycoplasma and replication competent virus
• Potential impacts of pursuing a non-optimal QC testing strategy
Development of cell culture samples for drug screening with bone marrow stem ...Apollo Hospitals
Side population (SP) refers to a group of cells, which is capable to efflux Hoechst 33342, a DNA-binding dye. SP cells exist both in normal and tumor tissues. SP abundance is used as an indicator for disease prognosis and drug screening in some studies. Our study concentrates on the factors influencing SP analysis.
There are tens of thousands of man-made chemicals to which humans are exposed, but only a fraction of these have the extensive in vivo toxicity data used in most traditional risk assessments. This lack of data, coupled with concerns about testing costs and animal use, are driving the development of new methods for assessing the risk of toxicity. These methods include the use of in vitro high-throughput screening assays and computational models.
This presentation by Dr. Richard Judson reviewed a variety of high-throughput, non-animal methods being used at the U.S. EPA to screen chemicals for a variety of toxicity endpoints, including methods for providing mechanistic data like the Adverse Outcome Pathway.
EPA is committed to sound science, and we are proud to have some of the world's best scientists, many of whom are internationally recognized as leaders in their fields. Not only are EPA's scientific experts vital to achieving our mission, but they are dedicated to sharing knowledge and contributing to their the scientific communities, which helps further advance the science that protects human health and the environment. Part of this includes giving presentations to other members of the scientific community. We have posted some of these presentations here so that more people have access.
Learn more about Dr. Richard Judson - https://www.epa.gov/sciencematters/meet-epa-researcher-richard-judson
Learn more about EPA's Chemical Safety Research - https://www.epa.gov/chemical-research
There are tens of thousands of man-made chemicals to which humans are exposed, but only a fraction of these have the extensive in vivo toxicity data used in most traditional risk assessments. This lack of data, coupled with concerns about testing costs and animal use, are driving the development of new methods for assessing the risk of toxicity. These methods all start with the use of in vitro assays, e.g. for activity against the estrogen and androgen receptors (ER and AR) and targets in the steroidogenesis and thyroid signaling pathways. Because all individual assays are subject to a variety of noise processes and technology-specific assay artifacts, we have developed methods to create consensus predictions from multiple assays against the same target. The goal of these models is to both robustly predict in vivo activity, and also to provide quantitative estimates of uncertainty. This presentation by Dr. Richard Judson described these models and how they are validated against both in vitro and in vivo reference chemicals.
EPA is committed to sound science, and we are proud to have some of the world's best scientists, many of whom are internationally recognized as leaders in their fields. Not only are EPA's scientific experts vital to achieving our mission, but they are dedicated to sharing knowledge and contributing to their the scientific communities, which helps further advance the science that protects human health and the environment. Part of this includes giving presentations to other members of the scientific community. We have posted some of these presentations here so that more people have access.
Learn more about Dr. Richard Judson - https://www.epa.gov/sciencematters/meet-epa-researcher-richard-judson
Learn more about EPA's Chemical Safety Research - https://www.epa.gov/chemical-research
Identification of Bioactive Compounds in the acetone extract of Daedalea eleg...AI Publications
Daedalea elegans is a Nigerian wild (non-edible) higher fungus with great potentials in the pharmaceutical, textile, cosmetics and food industry. This current study investigates the bioactive compounds that can be found in the acetone extract of D. elegans using Gas Chromatography-Mass Spectrometry (GC-MS). There were twenty-eight compounds identified to be present in the acetone extract of the fungi under study and these are Benzoic acid (0.40%), Nonanoic acid (0.14%), Oxetane, 2,2,4-trimethyl- (0.28%), n-Decanoic acid (0.09%), Phthalimide (0.44%) Dodecanoic acid (0.24%), E-2-Hexenyl benzoate (0.21%), 2,4-Difluorobenzene, 1-benzyloxy- (0.16%), Tetratetracontane (0.55%), Isopropylphosphonic acid, fluoroanhydryde (0.28%), Benzene, (1-methylundecyl)- (0.21%), Tetradecanoic acid (0.76%), Cyclohexanepropanol, .alpha.,2,2,6-tetrame (0.56%), Pentadecanoic acid (0.71%), E-2-Hexenyl benzoate (0.32%), Pentadecanoic acid (0.97%), 1-Decanol, 2-hexyl- (0.46%), 9-Tetradecenal, (Z) (1.67), n-Hexadecanoic acid (23.59%) is the second most abundant, Phthalic acid, butyl undecyl ester (1.08%), Eicosanoic acid (0.79%), 9,12-Octadecadienoic acid (Z,Z)- (44.64%) was the highest in quantity, Octadecanoic acid (6.98%), Bis(2-ethylhexyl) phthalate (2.64%), 2,2,4-Trimethyl-3-(3,8,12,16-tetramethyl-heptadeca-3,7,11,15-tetraenyl)-cyclohexanol (1.95%), 9(11)-Dehydroergosteryl benzoate (8.37%), 9(11)-Dehydroergosteroltosylate (1.28%), 4,6-Decadienal, 8-ethyl-10-[4-hydroxy-8-(2-hydroxypropyl)-3,9 (0.22%). These compounds possess activities which includes but not limited to cancer chemotherapy, antifeedant against pine weevil, antifungi agent in topical therapeutic preparation, anti-inflammatory, immunomodulatory, anti-convulsant, antioxidants, hypocholesterolemic, anti-androgenic, nematicide, analgesic, intermediate for food-grade additives, lubricants, greases, rubber, dyes and plastic, antineoplastic agent, biosynthesis of prostaglandins and cell membrane to mention a few. This study has been able to show that D. elegans is a good source of bioactive compounds with great potentials that can be harnessed in various industries.
ST8 micellar/niosomal vesicular nanoformulation for delivery of naproxen in c...Vahid Erfani-Moghadam
Naproxen (NPX) is a non-steroidal anti-inflammatory drug (NSAID) used against a variety of diseases, including autoimmune disorders and chronic inflammations. However, low water solubility limits its therapeutic efficacy and novel nanoformulations are required to bypass its poor bioavailability to reach its therapeutic effect. The purpose of the study was to investigate the role of the nanoformulation of biocompatible molecules; Squalene (S) and Tween 80 (T8) Micellar/Niosomal Vesicles (ST8MNV) prepared, by thin-film hydration method and their potential as a drug delivery system for NPX. The percentage of encapsulation efficiency was calculated to be 99.5 ± 0.2% for 5% of NPX weight in total ingredients of micellar/niosomal vesicles (w/w). The ST8MNV nanoformulation exhibited a slower rate of NPX release from the drug encapsulated over seven days, suggesting a stable complex of NPX. Finally, cell toxicity assay demonstrated that the half-maximal inhibitory concentrations (IC50) of NPX were drastically reduced by ST8MNV nanoformulation in MCF-7, A549, HeLa, and MDA-MB-231 cancer cell lines. Our data show this micellar/niosomal naproxen nanoformulation is a great candidate for the future in vitro and in vivo studies for potential clinical anti-inflammatory and anticancer applications.
The Comprehensive Guide to Genotoxicity AssessmentMilliporeSigma
Discover solutions for all phases of product development for genetox assessment from in silico analysis, screening, mode of action assessment, or GLP regulatory required assays. Our BioReliance® Genetic Toxicology Services director will share specifics and rationale for each assay category.
In this webinar you will:
- Learn the required regulatory assays
- Understand why each assay is used and how to employ different assay designs
- Learn different assays and techniques to screen potential compounds and understand mechanism and mode of action
Presented by Rohan Kulkarni, Ph.D., ERT, Director Toxicology, Study Management on February 9, 2017
Development, safety and efficacy analysis of liquid state rabiesBalaganesh Kuruba
Rabies is a highly fatal epidemic disease in the world with high mortality rate in the infected individuals. According to the survey conducted by WHO across different parts of the globe, every year 50000 people die because of Rabies. And most of the vaccines are produced as solid-state vaccines.
Before formulation the purified PV 11 derived concentrated, infected and chromatographically purified rabies antigens are checked for their efficiency, potency by invitro methods.
Four different combinations of stabilizers, additives and adjuvants are blended with rabies antigen. Those are labelled as TCARLV-A, TCARLV-B, TCARLV-C, TCARLV-D. And find estimate the constituents in single Human dose.
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3aeCPNB
Find out how we turn up the dial on quality control testing for cell and gene therapies through rapid methods for sterility, mycoplasma, and replication competent virus. We will review the current regulatory expectations as well as the benefits and limitations that come with each method.
Two of the biggest challenges with applying traditional quality control (QC) test methods to cell and gene therapies, is time to results, due to short shelf-life, and availability of sufficient sample, due to small production volumes.
So how can these challenges be overcome while still meeting regulatory expectations?
In this webinar we will discuss and review suitable methods for rapid testing of short-life cell and gene therapies that may also help conserve limited production material. We will look at benefits, limitations, and regulatory expectations for various QC needs including current and future rapid methods for sterility, mycoplasma and replication competent virus.
In this webinar, you will learn:
• Why the shelf life of a cell or gene therapy product may impact your QC testing strategy
• Current regulatory expectations surrounding rapid methods for sterility, mycoplasma and replication competent virus
• Potential impacts of pursuing a non-optimal QC testing strategy
Development of cell culture samples for drug screening with bone marrow stem ...Apollo Hospitals
Side population (SP) refers to a group of cells, which is capable to efflux Hoechst 33342, a DNA-binding dye. SP cells exist both in normal and tumor tissues. SP abundance is used as an indicator for disease prognosis and drug screening in some studies. Our study concentrates on the factors influencing SP analysis.
On July 7, 2014, the Green Park Collaborative (GPC) of the Center for Medical Technology Policy (CMTP) and the Institute for Clinical and Economic Review (ICER) co-hosted a web conference to explore the evidence needed to demonstrate the effectiveness and value of new drugs to treat chronic hepatitis C (HCV) infection. Representatives from various stakeholder groups, including payers, patients, pharmaceutical industry, health technology assessment organizations, and regulatory bodies, presented and discussed this issue with a particular focus on:
1. The evidence generated for regulatory approval;
2. The evidence preferences of post-approval decision makers; and
3. Strategies to efficiently generate the additional evidence.
Each of the invited speakers gave a brief presentation followed by a question and answer session at the end of the presentations. Audience members had an opportunity to submit questions through a chat feature. The conference was moderated by Dr. Sean Tunis, Founder
and CEO of CMTP. More than 200 participants, including a variety of subject matter experts and stakeholder representatives, attended the web conference.
Video and webinar summary available here: http://www.cmtpnet.org/featured-projects/green-park-collaborative/gpc-usa-meetings/webinars/hepatitis-c-drugs-evidence-to-demonstrate-effectiveness-value
Newer drugs approved by US-FDA - Rxvichu!!!RxVichuZ
Hello friends...and readers...............
A moment of bliss and happiness.....................
This is my 20th ppt OVERALL!!
This ppt comprises THE NEWER DRUGS APPROVED BY US-FDA in 2016..............
CONTAINS PHARMACOLOGY OF 19 DRUGS...........................
I have included as many details as possible.................
This is PART-1 of my MEGA SEMINAR, which involves drugs APPROVED BY US-FDA in the years 2014, 2015 & 16..............
Do send ur reviews after scrutiny...............
Thanks for ur support, views, downloads, and wishes...from all around the world!!!
@rxvichu-alwz4uh! :)
Target Validation Academy Of Medical Sciences 1 Dec 2006Mike Romanos
An overview of the issues and approaches in selecting the best targets for drug discovery and validating them. Given at the Drug Discovery Forum held at the Royal Society, London and organised by the Academy of Medical Sciences
Combining Metabolite-Based Pharmacophores with Bayesian Machine Learning Mode...Sean Ekins
Slides from SERMACS 2015 meeting in Memphis 2015 describing a collaborative project with SRI International and Rutgers. The work was published in PLOS ONE http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141076
The compound characterization market is growing increasingly profitable and competitive at the same time. In order to develop a new compound product, the testing step is indispensable. Unlike drug discovery, compound testing is not as restrictive, but understanding the main workflow is still necessary to excel in the market. In order to help you improve both the efficiency and safety of compound testing, we developed the protocol to assist you in your findings.
Abstract:
The Chronopharmacotherapy the drug administration is synchronised with circadian rhythms Formulation development of Microspheres is more reliable formulation as compare to single type dosage formulation due to it avoids dose dumping, as per required drug release profile is achieved For microspheres many polymers are used such as albumin, gelatine, starch, Eudragit, Polyacrylamide (“PAM”) these material loading capacity is high. Micro sponges which are Spherical are called as micro-balloons. Due to its hollow structure it shows good floating properties. In these systems use of Carbon-dioxide (CO2) as gas generating system which are used for floating purpose. The objective of present investigation is to prepared and evaluate a floating pulsatile drug delivery system of Aceclofenac. The strategy adopted for microspheres containing Aceclofenac as a material were prepared by emulsion solvent diffusion technique. Drug and polymer were mixed in dichloromethane and ethanol at 1:1 ratio. The drug and polymer solution were poured in water 50% W/V polyvinyl alcohol maintained at 30-40 C and the solution was stir at 500rpm using mechanical stirrer, The microspheres obtain were washed repeatedly with water until free from poly vinyl alcohol. The developed formulations were evaluated yield of floating microspheres particle size and shape, drug entrapment efficiency in-vitro evolution of floating ability, in-vitro drug release study. On the basis of these evolution parameters it was found that optimised floating pulsatile release formulation F7 showed higher drug entrapment efficiency floating time 6.8 minutes and the drug and polymer 32 1:3 ratio the particle size was increased.
Key Words: Chronopharmacotherapy, Floating pulsatile drug delivery, Aceclofenac.
This 3-day event is the meeting place for international and domestic scientists to share case studies and project updates, showcase new techniques and form collaborations that pave the way towards the future of China’s biopharmaceutical industry.
How to model longevity and health effect in 3 monthsWenlan Hu
Healthspan analysis is a huge part of longevity study, which is heavily looked at by many aging labs in recent years. The older we grow, our health will be affected accordingly, and this influence what type of compound we use. To better picture what effects compounds brings to us and to extend lifespan as a goal. A three stage compound assessment is developed by IVB to solve this question.
Ya tengo un perfil LinkedIn, y ahora que hago?
El Taller: "Construyendo tu marca personal"que prepare y dicte en el IESA te podrá ayudar a evaluar tu perfil en LinkedIn.
Entender cuáles son los beneficios que podemos conseguir mediante LinkedIn.
Mas importante aun, podrás construir tu marca personal con las recomendaciones suministradas.
The Commercial Model Challenge: securing resources and management focus Giovanny Leon
Find out a methodology to map the current commercial situation and expected evolution by taking into consideration key stake holders within the process.
Alternative action evaluation (experimental): securing resources and management focus required to capitalize on the learning and developing in our current models in the face of future needs
Pensar Global, Actuar Local en la Industria Farmacéutica Giovanny Leon
Puntos principales:
-Aprovechar la fortaleza del “branding global”
-El entendimiento del mercado local permitirá reconocer las oportunidades de adaptación.
-Pensar global y actuar local (RRHH, marketing, logística, marca y reputación…)
-Escoger y construir nuestro océano azul para desarrollar nuestro producto/franquicia.
-Cuidar y desarrollar las relaciones entre la matriz (cultura corporativa) y la base operativa
Exploring the Mindfulness Understanding Its Benefits.pptxMartaLoveguard
Slide 1: Title: Exploring the Mindfulness: Understanding Its Benefits
Slide 2: Introduction to Mindfulness
Mindfulness, defined as the conscious, non-judgmental observation of the present moment, has deep roots in Buddhist meditation practice but has gained significant popularity in the Western world in recent years. In today's society, filled with distractions and constant stimuli, mindfulness offers a valuable tool for regaining inner peace and reconnecting with our true selves. By cultivating mindfulness, we can develop a heightened awareness of our thoughts, feelings, and surroundings, leading to a greater sense of clarity and presence in our daily lives.
Slide 3: Benefits of Mindfulness for Mental Well-being
Practicing mindfulness can help reduce stress and anxiety levels, improving overall quality of life.
Mindfulness increases awareness of our emotions and teaches us to manage them better, leading to improved mood.
Regular mindfulness practice can improve our ability to concentrate and focus our attention on the present moment.
Slide 4: Benefits of Mindfulness for Physical Health
Research has shown that practicing mindfulness can contribute to lowering blood pressure, which is beneficial for heart health.
Regular meditation and mindfulness practice can strengthen the immune system, aiding the body in fighting infections.
Mindfulness may help reduce the risk of chronic diseases such as type 2 diabetes and obesity by reducing stress and improving overall lifestyle habits.
Slide 5: Impact of Mindfulness on Relationships
Mindfulness can help us better understand others and improve communication, leading to healthier relationships.
By focusing on the present moment and being fully attentive, mindfulness helps build stronger and more authentic connections with others.
Mindfulness teaches us how to be present for others in difficult times, leading to increased compassion and understanding.
Slide 6: Mindfulness Techniques and Practices
Focusing on the breath and mindful breathing can be a simple way to enter a state of mindfulness.
Body scan meditation involves focusing on different parts of the body, paying attention to any sensations and feelings.
Practicing mindful walking and eating involves consciously focusing on each step or bite, with full attention to sensory experiences.
Slide 7: Incorporating Mindfulness into Daily Life
You can practice mindfulness in everyday activities such as washing dishes or taking a walk in the park.
Adding mindfulness practice to daily routines can help increase awareness and presence.
Mindfulness helps us become more aware of our needs and better manage our time, leading to balance and harmony in life.
Slide 8: Summary: Embracing Mindfulness for Full Living
Mindfulness can bring numerous benefits for physical and mental health.
Regular mindfulness practice can help achieve a fuller and more satisfying life.
Mindfulness has the power to change our perspective and way of perceiving the world, leading to deeper se
Discover various methods for clearing negative entities from your space and spirit, including energy clearing techniques, spiritual rituals, and professional assistance. Gain practical knowledge on how to implement these techniques to restore peace and harmony. For more information visit here: https://www.reikihealingdistance.com/negative-entity-removal/
Why is this So? ~ Do Seek to KNOW (English & Chinese).pptxOH TEIK BIN
A PowerPoint Presentation based on the Dhamma teaching of Kamma-Vipaka (Intentional Actions-Ripening Effects).
A Presentation for developing morality, concentration and wisdom and to spur us to practice the Dhamma diligently.
The texts are in English and Chinese.
A375 Example Taste the taste of the Lord, the taste of the Lord The taste of...franktsao4
It seems that current missionary work requires spending a lot of money, preparing a lot of materials, and traveling to far away places, so that it feels like missionary work. But what was the result they brought back? It's just a lot of photos of activities, fun eating, drinking and some playing games. And then we have to do the same thing next year, never ending. The church once mentioned that a certain missionary would go to the field where she used to work before the end of his life. It seemed that if she had not gone, no one would be willing to go. The reason why these missionary work is so difficult is that no one obeys God’s words, and the Bible is not the main content during missionary work, because in the eyes of those who do not obey God’s words, the Bible is just words and cannot be connected with life, so Reading out God's words is boring because it doesn't have any life experience, so it cannot be connected with human life. I will give a few examples in the hope that this situation can be changed. A375
In Jude 17-23 Jude shifts from piling up examples of false teachers from the Old Testament to a series of practical exhortations that flow from apostolic instruction. He preserves for us what may well have been part of the apostolic catechism for the first generation of Christ-followers. In these instructions Jude exhorts the believer to deal with 3 different groups of people: scoffers who are "devoid of the Spirit", believers who have come under the influence of scoffers and believers who are so entrenched in false teaching that they need rescue and pose some real spiritual risk for the rescuer. In all of this Jude emphasizes Jesus' call to rescue straying sheep, leaving the 99 safely behind and pursuing the 1.
2 Peter 3: Because some scriptures are hard to understand and some will force them to say things God never intended, Peter warns us to take care.
https://youtu.be/nV4kGHFsEHw
The Hope of Salvation - Jude 1:24-25 - MessageCole Hartman
Jude gives us hope at the end of a dark letter. In a dark world like today, we need the light of Christ to shine brighter and brighter. Jude shows us where to fix our focus so we can be filled with God's goodness and glory. Join us to explore this incredible passage.
1. Does Interchangeability Really Matters for
Biosimilars?
Gilberto Castañeda-Hernández
Departamento de Farmacología
Centro de Investigación y de Estudios Avanzados
del Instituto Politécnico Nacional
México, D.F.
2. Biosimilars are not generics because:
1.The innovator’s patent has not yet expired.
2.The route of administration is different.
3.The active molecule is not identical to that of the innovator.
4.The excipients are not the same with regard to the innovator.
Question 1
Correct answer: Number 3
3. Hypothesis tests, such as the Student t test, ANOVA, Chi Square,
etc. are no adequate for biosimilarity because:
1. The p value must be lower than 0.01.
2. It is not possible to detect a significant difference when few
subjects are included in the study.
3. The mathematical procedure is to complicated.
4. Non parametrical tests must be used.
Question 2
Correct answer: Number 2
4. An intended copy is:
1. A generic version of a biotherapeutic product.
2. A non-innovator biologic which has not fully demonstrated
biosimilarity.
3. A non-innovator biologic which is interchangeable with the
innovator.
4. A biologic product which being a different molecule with regard to
the innovator can be substituted.
Question 3
Correct answer: Number 2
5. An example of a interchangeability study for a biosimilar is:
1. A pharmacokinetic bioequivalence study.
2. A clinical comparative study.
3. The Framingham study.
4. The Norswitch study.
Correct answer: Number 4
Question 4
6. Statement of Possible Conflicts of Interest
• I am a Senior Investigator at the Center for Research and Advanced Studies
of the National Polytechnic Institute
in Mexico
• I have given lectures and participated in studies sponsored by: Abbott,
AbbVie, Actelion, Amgen, Astra-Zeneca, Bayer, Boehringer-Ingelheim;
Concordia, Lilly, Liomont, Medix, Merck-Serono, MSD, Novartis, Pfizer,
Roche, Sanofi, Sandoz, Senosiain, Silanes, Sophia, UCB
• I am not on the payroll or possess shares of any of these companies
7. http://www.biosimilarspipeline.com/
Humira 30
Remicade 17
Epoetin alfa 85
Neupogen 59
Neulasta 24
Enbrel 31
Rituxan 50
Herceptin 38
Lantus 10
Avastin 25
Insulin and Analogs 51
Interferons (alfa) 60
Interferons (beta) 27
Somatropins 34
Cancer indications 418
mAbs, mAb fragments 261
Some Polpular Targeted Reference Products.
No . Of biosimilars by reference product.
9. Innovator MAB/Cept DNA constructs: Genes
Design of Biosimilar MABs/Cepts by
Reverse Engineering
McCamish & Woollett. mAbs 3: 209-217, 2011
10. Transfection, Transcription, Translation
Adapted from: CHMP, Committee for Medicinal Products for Human Use Sources. Public Assessment Report. Remsima.
Procedure No. EMEA/H/C/002576/0000 http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002576/WC500151486.pdf:.
11. Protein macrostructures which could be adopted from the protein-synthesis to final 3D functional structure, L. King, J.; Protein Folding. American Association for the advancement of science. 1990. Washington pp 157-169.
Berger et al.Protein Glycosylation and its impact on Biotechnology. In Adv Biochem Engin/Biotechnol 127: 165-185, 2012.
Post-Transcription Processes:
Glycosylation, Folding and Affinity
13. Antigen Binding and ADCC
(Antibody Dependent Cellular Toxicity
Tracey D, et al. Pharmacol Ther 2008; 117:244–279; Vos ACW, et al. Inflamm Bowel Dis 2012;18:401–408; Vos ACW, et al. Gastroenterology 2011;140:221–230
14. EXPERT COMMITTEE ON BIOLOGICAL
STANDARDIZATION
Geneva, 19 to 23 October 2009
1. Introduction…………………………………………….…… 3
2. Aim…………… ……………………………………………... 4
3. Scope………………………………………………………… 5
4. Glossary……………………………………………………... 5
5. Scientific consideration………………………………….… 8
6. Key principles for the licensing of SBPs………...…… 10
7. Reference biotherapeutic product……………..………… 11
8. Quality………………………………………………………. 13
9. Non-clinical evaluation………………………………..….…22
10. Clinical evaluation………………………………………… ..26
11. Pharmacovigilance………………..……………………….. 38
12. Prescribing information and label…………..…………… 39
13. Roles and responsibilities of NRAs……………………… 39
Authors and Acknowledgements………………………...… 41
References…………………………………………………… 44
Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs)
15. Approved Biosimilars (2016)
1. CT-P13 (Remsima®). Infliximab. Celltrion, South Korea. Approvad by EMA.
2. SB4 (Benepali®). Etanercept. Samsung-Bioepis. South Korea. Approved by EMA.
3. GP2015. Etanercept. Sandoz. Austria/Germany/Switzerland. Approved by FDA.
• What was the information submitted by this products to obtain authorization?
16. Physicochemical Characterization
MAbs. 2014;6(5):1163-77. doi:10.4161/mabs.32221.
Physicochemical characterization of Remsima.
Jung SK1, Lee KH, Jeon JW. Lee JW, Kwon BO, Kim YJ, Bae JS, Kim DI, Lee SY, Chang SJ.
MAbs. 2016 Aug-Sep;8(6):1136-55. doi:10.1080/19420862.2016.1193659.Epub 2016 May 31.
Evaluation of the structural, physicochemical, and biological
characteristics of SB4, a biosimilar of etanercept.
Cho IH1, Lee N1, Song D1, Jung SY1, Bou-Assaf G2, Sosic Z2, Zhang W2, Lyubarskaya Y2
Expert Opin Biol Ther. 2016 Oct;16(10):1185-95. doi:10.1080/14712598.2016.1217329. Epub 2016 Aug 16.
Characterization and non-clinical assessment of the proposed
etanercept biosimilar GP2015 with originator etanercept (Enbrel(®)).
Hofmann HP1, Kronthaler U1, Fritsch C2, Grau R, Müller SO3, Mayer R4, Seidi A5, Da Silva A1.
20. SB4 and Enbrel®: MoA Related Bioassays
Bioassays assessed the similarity of BenepaliTM and Enbrel® by analysing the relative binding potency of
BenepaliTM or Enbrel® to TNF‐α or lymphotoxin-alpha 3 (LT‐α3), along with a TNF‐α Neutralisation Cell
Based Assay
* The similarity range was set by statistical analysis based on the tolerance interval with the given set of
available data points.
DS, drug substance; DP, drug product; LT‐α, lymphotoxin‐alpha; MoA, mechanism of action; PVR, Process
validation run. Sources: BenepaliTM EPAR;p19,Table 1.
Cho et al. mAbs, DOI: 10.1080/19420862.2016.1193659
24. Remsima®: PK in patients with
Ankylosing Spondilitis
Park et al. Ann Rheum Dis. 2013 Oct;72(10):1605-12.
25. A randomized phase l pharmacokinetic study
comparing SB4 and etanercept reference
product (Enbrel®) in healthy subjects
British Journal of Clinical Pharmacology: Volume 82: pages 64-73, 2 MAY 2016 DOI: 10.1111/bcp.12929
http://onlinelibrary.wiley.com/doi/10.1111/bcp.12929/full#bcp12929-fig-0003
26. GP2015: PK in Healthy Volunterrs
• Mean serum concentration-time profiles were comparable between GP2015 and
etanercept originator
Afonso M et al. Poster at EULAR 2016; THU0145.
Mean serum concentration-time profile
28. Clinical Study Design
One well-designed study is better than multiple
poorly-designed assays
• Choose a suitable patient population. Inter-patient variability as low as possible
• Purpose: Show biosimilarity (comparison)
• Two Groups: Innovator vs Biosimilar
• Adequate primary endpoint
• Sufficient study length to be clinically relevant
ADEQUATE STATISTICAL ANALYSIS
• No hypothesis testing (Student t test, ANOVA)
• Demonstrate equivalence or, at least, non-inferiority
Dörner T et al. Ann Rheum Dis. 2013;72:322–328; Park et al. Ann Rheum Dis. 2013;
72:1605–1612; Yoo DH et al. Ann Rheum Dis. 2013;72:1613–1620.
29. What is a sensitive population?
Castañeda-Hernández, González-Ramírez, Kay & Scheinberg. RMD Open 2015;1e:000010. doi:10.1136-2014-000010
Placebo Treatment Placebo Treatment
R
B
R
NB
B
NB
Effect R: Reference product
B: Biosimilar
NB: Non-biosimilar
Insensitive Population Sensitive Population
Can extrapolate
Cannot extrapolate
31. Sensitive Population: Oncology
Neoadjuvant breast cancer treatment
as a sensitive setting for
trastuzumab biosimilar development
and estrapolation
Christian Jackisch*,1, Frank A Scappaticci2, Dminik
Heinzmann3, Fabio Bisordi3, Thomas Schreitmüller3, Gunter
von Minckwitz4 & Javier Cortés5
Future Oncol, 2015 Jan;11(1):61-71. doi 10.2217/fon.14.187
32. Limitations of Hypothesis Testing
• Failure to achieve statistical significance (p > 0.05) in a test designed for looking for
differences is not evidence of equivalence.
Castañeda-Hernández, González-Ramírez, Kay & Scheinberg. RMD Open 2015;1e:000010. doi:10.1136-2014-000010
N small
S large
Numberofsubjects
Parameter value
33. Equivalence Testing
• A and B are the efficacy parameter values of the innovator and biosimilar.
• Ideal A=B, i.e. A/B = 1. This is almost impossible.
• Thus, an equivalence range is chosen.
• An anti-TNFα agent, A (innovator) yields an effect 30% higher than placebo. Then,
the equivalence range for A/B can be 15%. A log-transformation is performed.
• The hypothesis to demonstrate is: 0.85 < A/B < 1.18
• Results expressed as A/B ± 95% C.I. The 95% C.I. must be within equivalence
range.
Castañeda-Hernández, González-Ramírez, Kay & Scheinberg. RMD Open 2015;1e:000010. doi:10.1136-2014-000010
34. To be or not to be (equivalent)
Castañeda-Hernández, González-Ramírez, Kay & Scheinberg. RMD Open 2015;1e:000010. doi:10.1136-2014-000010
Higher equivalence
Limit (1.18)
Lower equivalence
Limit (0.85)
Non-equivalent
Equivalent
95% confidence
interval
A/B 1
35. Yoo et al. Ann Rheum Dis 2013;72:1613-1620
CT-P13 response rates at week 24
(ACR20 primary endpoint)
36. SB4 response rates at week 24
(ACR20 primary endpoint)
Emery P, et al. Ann Rheum Dis. 2015
37. GP2015 Phase III study of GP2015
vs. etanercept in PsO (EGALITY)
PASI 75 primary Endpoint
• PASI 75 at Week 12 was the primary endpoint to assess equivalence
• Primary endpoint was achieved because the 95% CI of the PASI 75 response rate
difference fell within the pre-specified margin (-18%, 18%)
Griffiths CEM, Thaci D, Gerdes S, et al. Oral presentation. PSO Congress, Paris, France, 7 July 2016.
73.4% 75.7%
-2.3% (-9.85, 5.30)
73.4% 75.7%
39. Indication extrapolation
Adapted from: 1. FDA Draft Guidances – Scientific Considerations in Demonstrating Biosimilarity to a Reference Protein Product (Feb 2012) – US Guidance;
2. EMA: CHMP Guideline On Similar Biological Medicinal Products Containing Biotechnology-derived Proteins As Active Substance: Non-clinical And Clinical Issues (22 February 2006); 3. WHO Guidelines on Similar Biotherapeutic Products.
http://www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTICS_FOR_WEB_22APRIL2010.pdf; 4. EMA: CHMP Guideline on Similar Biological Medicinal Products Containing Monoclonal Antibodies – Non-Clinical and Clinical Issues (30 May 2012)
40. REMSIMA™/INFLECTRA™ product information accessed February 24, 2014:
1. S. Korea: http://www.celltrion.com/en/BIO/bio01.asp?menu_num=1
2. EMA: http://www.ema.europa.eu/docs/en_GB document_library/EPAR_-_Summary_for_the_public/human/002576/WC500150872.pdf 3. Canadian Product Monograph; Inflextra www.hc-sc.gc.ca
4. USA: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM484859.pdf
5. www.pfizer.ca/node/7526#_ftn1
To extrapolate or not to extrapolate?
There is no unanimous criteria
Indication S Korea 2012 EU 2013 Canada 2014 FDA 2015
Rheumatoid arthritis C C C C
Ankylosing spondylitis C C C C
Psoriatic arthritis E E E E
Psoriasis E E E E
Crohn’s disease E E 2016 E
Ulcerative colitis E E 2016 E
C, approved with a complete data package including a single clinical trial; E, extrapolated indication without a Phase I or III clinical
trial;
-, not approved.
CT-P13 infliximab indications by type of approval
41. Interchangeability and substitution
in different countries
Webinar, February 15, 2012; 2. EMA, Questions and Answers on biosimilar medicines; 3. MHLW Guideline for Ensuring Quality, Safety and Efficacy of Biosimilar Products, March 2009; 4. ANVISA: Resolucao RDC N°55, de 16 de Deem bro de 2010; Diario Oficial da Uniao-Secao 1; N°
n N°7729/2011 (publicado el 21 de Noviembre de 2011); 6. Proyecto de PROY-NOM-257-SSA1-2013; 7. Norma Técnica Nº 170 Sobre Registro Sanitario de Productos Biotecnológicos Derivados de Técnicas ADN Recombinantes; Diario Oificial de la República de Chile, 6 de Septiembre
milar Guidance; 30 July 2013; 9. Health Canada Interchangeability and Substitutability of Subsequent Entry Biologics, July 2010 http://www.hc-sc.gc.ca/dhp-mps/brgtherap/applic-demande/guides/seb-pbu/01-2010-seb-pbu-qa-qr-eng.php#q15; 10. European Commission: What you need to
know about biosimilar medicinal products. Consensus Information Paper 2013
US1
FDA requirements to meet
interchangeability threshold still
unclear, automatic substitution
of interchangeable drugs to be
determined at state level
Japan3
Interchangeability and
automatic substitution
highly discouraged
EMA2
Decisions on interchangeability
and/or substitution rely on
national competent authorities
and are outside the remit of
EMA/CHMP2,10
Brazil4, Argentina5, Mexico6 Developed guidelines
for biosimilars, but have not yet addressed
interchangeability or automatic substitution
Chile7 Authorities state it is inadequate to substitute
Canada9
Health Canada does not
support automatic
substitution, but allows
provinces to determine
interchangeability
43. Substitution, interchangeability
and medical switching
stitution – Pharmacist action. Physician does not intervene. A and B must be
rchangeable.
ical switching – Treating physician decision
Drug A
Drug B
Drug A
Drug A
Drug B
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm241718.htm
44. Interchangeability Study
Norway is carrying out a large study
(US$ 3.3 million) in order to see the
mpact of substitution of innovator
nfliximab for biosimilar infliximab.
http://www.biopharma-reporter.com/Markets-Regulations/Norway-to-facilitate-switch-to-biosimilars-with-3m-Remicade-study
46. Phase III study of GP2015 vs. etanercept
in PsO (EGALITY)
cept was EU-licensed Enbrel.
s who achieved at least a PASI 50 response at Week 12 were eligible to enter Period 2.
Griffiths CEM, Thaci D, Gerdes S, et al. Oral presentation. PSO Congress, Paris, France, 7 July 2016.
https//www.clinicaltrials.gov/ct2/results?term=NCT01891864&Search=Search (Accessed June 2016) https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002011-26 (Accessed June 2016)
Study design and disposition of subjects
Period 1:
Double‐blind treatment
GP2015, N=264
(50mg twice weekly)
Etanercept, N=267
(50mg twice weekly)
BL 12Week
1:1 (N=531)R
etanercept (50mg weekly)
52
Period 2: Double‐blind
treatment
GP2015 (50mg weekly)
18 30 36 4224 48
GP2015 c
GP2015 s
Etanercept s
Etanercept c
N=150
N=100
N=96
N=151
Period 3: Double‐blind
extension
N=132N=140
N=142 N=137
N=95 N=88
N=90 N=90S1 S2 S3
Primary endpoint: Equivalence in PASI 75
at Week 12
47. How to consider switching between several
biosimilars?
1. Biologics Price Competition and Innovation Act of 2010; 2. WHO 56th Consultation on International Nonproprietary Names for Pharmaceutical Substances; Executive Summary Geneva, 15─17 April 2013
A biological product may not be evaluated against more than ONE reference product.1,2
Will interchangeability transitivity be applied in practice?
If A=B and A=C, does B=C follow?
Reference product “A” Biosimilar “B”
Biosimilar “C”
B
C
A
Indications with comparative
clinical study?
OR
Indications granted by
extrapolation?
48. Intended Copies: Licensed without biosimilar
regulation. Equivalent efficacy and safety
have not been demonstrated
Manufacturer Intended Copy Examples of countries
where it is (was)
marketed
mab Dr. Reddy Laboratories
(India)
Reditux India
Peru
Ecuador
Chile
Paraguay
Probiomed (Mexico) Kikuzubam Mexico
rcept Shanghai CP Goujian
(China)
Yisaipu
Etanar
Etart
China
Colombia
Mexico
Probiomed (Mexico) Infinitam Mexico
Castañeda-Hernández et al. Joint Bone Spine, 2014; Dörner T et al. Ann Rheum Dis. 2013; Cofepris 2012.
49. SpeB proteolysis with imaged capillary isoelectric
Focusing for the characterization of domain-specific
charge heterogeneities of reference and biosimilar Rituximab
Zichuan Zhang*, Ronel Perrault, Yun Zhao, Julia Ding*
PPD Laboratories, Biopharmaceutical Services, 8551 Research Way Suite 90, Middleton, WI 53562, USA
from India features partially cleaved Lysine residue on the protein C-terminus as well as a lower level of
on. As a demonstration, these results could be applied to the assessment of similarity during biosimilar product
ent…
Journal of Chromatography B, 1020 (2016) 148-157
Rituxan®
Mabthera®
Reditux®
50. Enbrel and Etanercept Intended Copies
M. Scheinberg , G. Castañeda-Hernández, M. Li, U.R.K. Rao, E. Singh, E. Mahgoub, J. Coindreau, J. O’Brien, S. M. Vicik, B. Fitzpatrick, B. Hassett.. Presented at PANLAR, Panama, 2016. and EULAR, London, 2016.
51. http://acrabstracts.org/abstracts/incidence-of-adverse-events-in-patients-treated-with-intended-copies-of-biologic-therapeutic-agents-in-colombia-and-mexico/
Safety of intended copies (ACR 2014)
ract Number:1506 Program: Abstract Submissions (ACR) Year: 2014
Incidence of Adverse Events in Patient Treated
with Intended Copies of Biologic Therapeutic
Agents in Colombia and Mexico
Leonor A. Barile-Fabris1, Fedra Irazoque-Plazuelos2, Ramiro Hernández Vásquez3, Sandra Carrillo Vazquez4 and R. Gúzman5, 1
Rheumatology Department, Hospital Especialidades CMN, Mexico City, Mexico,2 Centro Médico Nacional “20 de Noviembre”
ISSSTE, Mexico City, Mexico,3 Rheumatology, Hospital de Especialidades “Dr. Bernardo Sepúlveda Gutiérrez”, Mexico, Mexico,4
Rheumatology, Hospital Angeles Lindavista, Mexico Df, Mexico, 5 IDEARG, SaludCoop, Bogotá, Colombia.
52. Safety Issues with Rituximab Intended Copy
Comunicado 04/04/2012 http://www.cofepris.gob.mx/AZ/Paginas/Farmacovigilancia/Comunicados.aspx
Anaphylactic Reactions with Rituximab
There are two rituximab products in Mexico.
Analysis of the cases showed that
adverse reactions occurred after the switch
of one product for the other.
53. KIKUZUBAM A RITUXIMAB INTENDED COPY
thdrawn from the Mexican market on March 28, 2014.
ster was revoked due to absence of sound clinical data
on efficacy and to reports of adverse reactions
54. Substitution: Ethical Aspects
Any loss of response is unethical
Baquero et al. Nefrología 2011; 31: 275-285
Time
Therapeuticresponse
Innovator
Unethical
Biosimilar EPO
Substitution
Biosimilar: Ethical
Intended
Copy
55. Conclusions (1)
Biosimilars are not generics, as the active molecule is not identical to that
of the innovator. Biosimilarity is established on the basis of the totality of
evidence: analytical, non-clinical, clinical: including PK, efficacy and safety.
Equivalence clinical studies should be performed in the most sensitive
indication or, if pertinent, in a well-defined and understood population.
Criteria for interchangeability and automatic substitution of innovator and
biosimilar monoclonal antibodies are not universal. This issue is expected
to evolve rapidly in the next years, as more information is available.
56. Intended copies, despite being registered in some countries, are not
biosimilars. Information is not complete. Efficacy and safety may differ from
the innovator. Should be withdrawn.
Biosimilars, but not intended copies, are welcome, as they reduce costs
and increase access.
Conclusions (2)