Các nguyên tắc thẩm định vaccine chống Coronavirus SARS-CoV-2 theo tiêu chuẩn GMP Nhật Bản. Xem thêm các tài liệu khác trên kênh của Công ty Cổ phần Tư vấn Thiết kế GMP EU
More than 150 coronavirus vaccines are in development across the world—and hopes are high to bring one to market in record time to ease the global crisis.
The World Health Organization is also coordinating global efforts to develop a vaccine, with an eye toward delivering two billion doses by the end of 2021.
Hello guys , today I am discussing about various stages of vaccine development and types of vaccines already developed by various biotech companies all over the world and their current status in clinical trial till now .
Hope , Very early we can get a ideal corona virus vaccine which would be safe and effective to human and also eradicate this disease from the world .
For more information please follow these link :
https://www.nytimes.com/interactive/2...
https://www.precisionvaccinations.com...
https://www.who.int/publications/m/it...
The document discusses SARS-CoV-2, the virus that causes COVID-19. It states that SARS-CoV-2 is a positive-sense, single-stranded RNA virus surrounded by a nucleoprotein and matrix protein capsid. It has at least six open reading frames in its genome that encode for structural and accessory proteins. The two large overlapping ORFs encode for the four main structural proteins: spike, envelope, membrane, and nucleocapsid.
Presentation on ICH guidelines Q5A (R1) and Q4B Annex 2 (R1)HadiaNaz1
EXECUTIVE SUMMARY OF ICH GUIDELINES Q5A (R1) AND Q4B ANNEX 2 (R1)
VIRAL SAFETY EVALUATION OF BIOTECHNOLOGY PRODUCTS DERIVED FROM CELL LINES OF HUMAN OR ANIMAL ORIGIN – Q4B ANNEX 2 (R1):
This document is concerned with testing and evaluation of the viral safety of biotechnology products derived from characterized cell lines of human or animal origin. The scope of the document covers products derived from cell cultures initiated from characterized cell banks. It covers products derived from in vitro cell cultures, recombinant DNA – derived products and also includes products derived from hybridoma cells grown in vivo.
Three principal approaches have evolved to control the potential viral contamination of biotechnology products:
a) Selecting & testing cell lines and other raw materials, including media components, for the absence of undesirable viruses which may be infectious and/or pathogenic for humans.
b) Assessing the capacity of the production processes to clear infectious viruses.
c) Testing the product at appropriate steps of production for absence of contaminating infectious viruses.
The guideline suggests approaches for the evaluation of the risk of viral contamination and for the removal of virus from the product. Following are the recommended tests for the brief description of a general framework and philosophical background within which the manufacturer should justify the testing that was done;
1) Test for Retroviruses
2) In vitro Assay
3) In vivo Assay
4) Antibody Production Tests
TEST FOR EXTRACTABLE VOLUME OF PARENTRAL PREPARATIONS GENERAL CHAPTER – Q4B ANNEX 2 (R1):
This annex is the result of the Q4B process for the Test for Extractable Volume of Parenteral Preparations General Chapter. The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG). The acceptance criteria of this document are same in the three pharmacopoeias.
The annex contains the following considerations for the implementation;
1) General Consideration
2) FDA Consideration
3) EU Consideration
4) MHLW Consideration
Considerations for Diagnostic COVID-19 Tests in the 4 Medical Testing Centre ...semualkaira
In this study during the coronavirus disease in 2021 (COVID-19)
pandemic, design, development, validation, verification incidence
and implementation of diagnostic tests are reported by many diagnostic tests from May until December 2021 we managed to
establish clinical validation and formal approval. In this article
we summarize the crucial role of diagnostic tests during the first
global wave of COVID-19. The technical and implementation and
diagnostics during a possible resurgence of COVID-19 in future
global waves or regional outbreaks. We continued global improvement in diagnostic test that is essential for more rapid detection of
patients, possibly at the point of care, and for optimized prevention
and treatment
1. The document discusses various aspects of vaccine trials including definitions, the first documented vaccine trial conducted by Edward Jenner in 1796, historical developments in vaccine design, types of licensed vaccines, and the vaccine development process.
2. It provides details on the different phases of clinical trials for vaccines - phase I focuses on safety and immunogenicity in healthy adults, phase II assesses immunogenicity in the target population including age de-escalation studies, and phase III evaluates efficacy in the target population.
3. Accelerated vaccine development strategies are being used for COVID-19 vaccines, with some in clinical trials evaluating safety, immunogenicity, and the ability to elicit immune responses through different mechanisms of
Vaccines and their clinical phase(1,2,3)vivek singh
Vaccines work by stimulating the immune system to protect against infectious diseases. There are several types of vaccines including live-attenuated, inactivated, toxoid, and subunit/recombinant vaccines. Clinical trials for new vaccines proceed in three phases - phase 1 evaluates safety in a small group, phase 2 assesses immunogenicity and safety in a larger group, and phase 3 is a pivotal large trial to demonstrate safety and efficacy for regulatory approval. Stringent regulations and guidelines from organizations like WHO govern all stages of vaccine development from preclinical research to post-licensure monitoring to ensure vaccines are safe, effective, and manufactured properly.
This document summarizes a presentation on COVID-19 vaccines given at USC. It lists the moderators and discusses several vaccine candidates in development or approved for emergency use, including those from Oxford/AstraZeneca, Moderna, Pfizer, and others. It also covers regulatory considerations for approving vaccines, including requirements for clinical trial data to support emergency use authorization or full licensure. Community engagement efforts to promote vaccination are also summarized.
More than 150 coronavirus vaccines are in development across the world—and hopes are high to bring one to market in record time to ease the global crisis.
The World Health Organization is also coordinating global efforts to develop a vaccine, with an eye toward delivering two billion doses by the end of 2021.
Hello guys , today I am discussing about various stages of vaccine development and types of vaccines already developed by various biotech companies all over the world and their current status in clinical trial till now .
Hope , Very early we can get a ideal corona virus vaccine which would be safe and effective to human and also eradicate this disease from the world .
For more information please follow these link :
https://www.nytimes.com/interactive/2...
https://www.precisionvaccinations.com...
https://www.who.int/publications/m/it...
The document discusses SARS-CoV-2, the virus that causes COVID-19. It states that SARS-CoV-2 is a positive-sense, single-stranded RNA virus surrounded by a nucleoprotein and matrix protein capsid. It has at least six open reading frames in its genome that encode for structural and accessory proteins. The two large overlapping ORFs encode for the four main structural proteins: spike, envelope, membrane, and nucleocapsid.
Presentation on ICH guidelines Q5A (R1) and Q4B Annex 2 (R1)HadiaNaz1
EXECUTIVE SUMMARY OF ICH GUIDELINES Q5A (R1) AND Q4B ANNEX 2 (R1)
VIRAL SAFETY EVALUATION OF BIOTECHNOLOGY PRODUCTS DERIVED FROM CELL LINES OF HUMAN OR ANIMAL ORIGIN – Q4B ANNEX 2 (R1):
This document is concerned with testing and evaluation of the viral safety of biotechnology products derived from characterized cell lines of human or animal origin. The scope of the document covers products derived from cell cultures initiated from characterized cell banks. It covers products derived from in vitro cell cultures, recombinant DNA – derived products and also includes products derived from hybridoma cells grown in vivo.
Three principal approaches have evolved to control the potential viral contamination of biotechnology products:
a) Selecting & testing cell lines and other raw materials, including media components, for the absence of undesirable viruses which may be infectious and/or pathogenic for humans.
b) Assessing the capacity of the production processes to clear infectious viruses.
c) Testing the product at appropriate steps of production for absence of contaminating infectious viruses.
The guideline suggests approaches for the evaluation of the risk of viral contamination and for the removal of virus from the product. Following are the recommended tests for the brief description of a general framework and philosophical background within which the manufacturer should justify the testing that was done;
1) Test for Retroviruses
2) In vitro Assay
3) In vivo Assay
4) Antibody Production Tests
TEST FOR EXTRACTABLE VOLUME OF PARENTRAL PREPARATIONS GENERAL CHAPTER – Q4B ANNEX 2 (R1):
This annex is the result of the Q4B process for the Test for Extractable Volume of Parenteral Preparations General Chapter. The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG). The acceptance criteria of this document are same in the three pharmacopoeias.
The annex contains the following considerations for the implementation;
1) General Consideration
2) FDA Consideration
3) EU Consideration
4) MHLW Consideration
Considerations for Diagnostic COVID-19 Tests in the 4 Medical Testing Centre ...semualkaira
In this study during the coronavirus disease in 2021 (COVID-19)
pandemic, design, development, validation, verification incidence
and implementation of diagnostic tests are reported by many diagnostic tests from May until December 2021 we managed to
establish clinical validation and formal approval. In this article
we summarize the crucial role of diagnostic tests during the first
global wave of COVID-19. The technical and implementation and
diagnostics during a possible resurgence of COVID-19 in future
global waves or regional outbreaks. We continued global improvement in diagnostic test that is essential for more rapid detection of
patients, possibly at the point of care, and for optimized prevention
and treatment
1. The document discusses various aspects of vaccine trials including definitions, the first documented vaccine trial conducted by Edward Jenner in 1796, historical developments in vaccine design, types of licensed vaccines, and the vaccine development process.
2. It provides details on the different phases of clinical trials for vaccines - phase I focuses on safety and immunogenicity in healthy adults, phase II assesses immunogenicity in the target population including age de-escalation studies, and phase III evaluates efficacy in the target population.
3. Accelerated vaccine development strategies are being used for COVID-19 vaccines, with some in clinical trials evaluating safety, immunogenicity, and the ability to elicit immune responses through different mechanisms of
Vaccines and their clinical phase(1,2,3)vivek singh
Vaccines work by stimulating the immune system to protect against infectious diseases. There are several types of vaccines including live-attenuated, inactivated, toxoid, and subunit/recombinant vaccines. Clinical trials for new vaccines proceed in three phases - phase 1 evaluates safety in a small group, phase 2 assesses immunogenicity and safety in a larger group, and phase 3 is a pivotal large trial to demonstrate safety and efficacy for regulatory approval. Stringent regulations and guidelines from organizations like WHO govern all stages of vaccine development from preclinical research to post-licensure monitoring to ensure vaccines are safe, effective, and manufactured properly.
This document summarizes a presentation on COVID-19 vaccines given at USC. It lists the moderators and discusses several vaccine candidates in development or approved for emergency use, including those from Oxford/AstraZeneca, Moderna, Pfizer, and others. It also covers regulatory considerations for approving vaccines, including requirements for clinical trial data to support emergency use authorization or full licensure. Community engagement efforts to promote vaccination are also summarized.
COVID Testing and ICMR strategy and vaccinesRishikaThakur9
The document discusses COVID-19 testing strategies and vaccines in development in India. It provides details on appropriate specimen collection, storage and transport for COVID-19 testing. It outlines the types of COVID-19 tests - molecular, antigen and antibody - and provides guidance on using the different tests for various testing scenarios. It also summarizes the status of several COVID-19 vaccines in clinical trials in India, including Covishield, ZyCoV-D, Sputnik V and others.
Who 2019-n cov-sci-brief-natural-immunity-2021.1-engArvinAmores
The document summarizes current scientific evidence on immunity from natural SARS-CoV-2 infection. It finds that 90-99% of infected individuals develop detectable neutralizing antibodies within 4 weeks. Available data suggests immune responses remain robust and protective against reinfection for at least 6-8 months in most people. Some variants have reduced susceptibility to antibodies, but cellular immunity elicited by natural infection also targets other viral proteins. Studies estimate natural infection provides 80-90% protection from reinfection for up to 7 months. The emergence of variants poses challenges to immunity that require ongoing monitoring.
This document describes a computational screening study of 12 FDA-approved antiviral drugs against SARS-CoV-2 spike protein and main protease targets using molecular docking. Key findings include:
- Ganciclovir and zanamivir showed strong binding energies (below -9 kcal/mol) with both targets through hydrogen bonding interactions.
- Ribavirin and tenofovir also exhibited significant binding energies above -8 kcal/mol with multiple hydrogen bonds to the main protease and spike protein.
- The study identifies potential dual-target antiviral properties of existing drugs, providing a starting point for further pre-clinical and clinical tests against SARS-CoV-2.
This document summarizes information about vaccine clinical trials and tick-borne encephalitis (TBE). It discusses the history and development of vaccines. It then describes the phases of clinical trials and provides examples of specific vaccine trials including for TBE. Key details about the TBE virus, epidemiology, vaccines, and a recent clinical trial comparing two TBE vaccines in children are summarized. The trial evaluated safety, immunogenicity and reactions to the vaccines. The document concludes that vaccination is an effective way to prevent TBE and current vaccines have shown good safety profiles.
The document discusses various aspects of COVID vaccines in India, including their development and clinical trials. It describes the Covishield and Covaxin vaccines in detail - Covishield is developed by Oxford University and AstraZeneca, while Covaxin is an inactivated vaccine developed by Bharat Biotech. It provides statistics on vaccination rates in India and challenges like vaccine hesitancy. Other vaccines mentioned include Sputnik V, Pfizer and Moderna.
Moderna, Pfizer, and Astrazeneca have shown promising early results in Phase 1/2 clinical trials of their COVID-19 vaccine candidates. Moderna and Pfizer have both advanced their mRNA vaccines to Phase 3 trials based on robust antibody responses and good safety profiles in initial participants. Astrazeneca has also seen strong immune responses after one or two doses of its adenovirus-based vaccine. Over 200 vaccines are in development globally, progressing at unprecedented speed due to heavy research investment, with the goal of approval within 12-18 months.
This document summarizes the challenges of rapidly developing a vaccine for SARS-CoV-2 (Covid-19) during a pandemic. It discusses how previous epidemics like H1N1, Ebola, and Zika showed that vaccines often weren't available before the epidemics ended. New platforms like DNA, RNA, and recombinant protein vaccines may speed development but regulatory review and large-scale manufacturing are challenges. The pandemic requires overlapping and parallel development phases with high financial risk. Coordinated global efforts are needed to fund manufacturing at scale and establish a fair global allocation system for any successful vaccines.
Scientists develop a new sars co v-2 vaccine with the successful experience o...DoriaFang
Researchers developed a new SARS-CoV-2 vaccine based on the successful hepatitis B vaccine platform. They used yeast to express the receptor binding domain protein of the coronavirus and supplemented it with a new adjuvant. Testing in monkeys showed the vaccine reduced virus shedding and symptoms when exposed to SARS-CoV-2. The vaccine aims to help meet global vaccination needs and may be effective against emerging variants.
Most developments in biotechnology originated for their potential applications in health care.
Contributions of biotechnology are more frequent, more notable and more rewarding in health sector.
This document provides an overview of SARS-CoV-2 testing. It describes the different types of diagnostic tests used in the COVID-19 response, including molecular tests that detect the virus's genetic material, antigen tests that detect viral proteins, and antibody tests that detect antibodies produced in response to infection. Accurate and rapid diagnostic testing is essential for confirming active infections, screening suspected cases, and determining the true extent of outbreaks. The document explains key terms like antigens and antibodies and where the different types of tests can be used, such as laboratories or point-of-care settings.
In this presentation, we discuss the clinical trial process for the new Covid-19 vaccines. We discuss the different vaccine types. We also discuss the Covid-19 vaccines that the UK is currently using in the NHS, as well as vaccines likely to be used in the next year.
Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical TrialsGuy Boulianne
The document presents a critical appraisal of the reported efficacy measures for the Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines. Using epidemiological tools and data from the vaccine clinical trials, the author calculates that the absolute risk reduction for the Pfizer vaccine is 0.7% and for the Moderna vaccine is 1.1%. These measures of absolute risk reduction are much lower than the reported relative risk reduction measures of 95.1% and 94.1%, respectively. The author argues that reporting absolute risk reduction is essential to prevent outcome reporting bias and allow for informed decision making about vaccine efficacy.
Studies of vaccine safety (Pharmacoepidemiology) V PharmDDr.Sohel Memon
This document discusses selected special applications of pharmacoepidemiology, focusing on studies of vaccine safety. It describes various methods used to monitor vaccine safety, including pre-licensure clinical trials, post-licensure surveillance systems like VAERS, and epidemiological studies. It addresses some methodological challenges in vaccine safety studies like assessing causality, accounting for confounding factors, and identifying rare adverse events. Large automated databases like the Vaccine Safety Datalink are highlighted as a valuable tool for monitoring vaccine safety on a population-level.
Prospects and Problems of Development of Candidate Vaccine against COVID 19ijtsrd
There is an urgent need to develop a vaccine against coronavirus disease 2019 COVID 19 , which is caused by a new coronavirus, severe acute respiratory syndrome coronavirus type 2 SARS CoV 2 infection. Although vaccine development typically requires 3 to 5 years, there is a possibility that the vaccine developed for either severe acute respiratory syndrome SARS or the middle east respiratory syndrome MERS could be used against COVID 19 as well. Therefore, a vaccine against COVID 19 is expected to be commercialized within 1 to 2 years. If so, it will be the fastest vaccine development in human history.In this review, we have summarized the information released as of April 10, 2020. Takuma Hayashi | Yasuaki Amano | Takashi Ura | Ikuo Konishi "Prospects and Problems of Development of Candidate Vaccine against COVID-19" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38521.pdf Paper Url: https://www.ijtsrd.com/medicine/other/38521/prospects-and-problems-of-development-of-candidate-vaccine-against-covid19/takuma-hayashi
Past SARS-CoV-2 infection provides high levels of protection against re-infection and symptomatic disease from ancestral, alpha, beta, and delta variants. However, protection is substantially lower for the omicron BA.1 variant, at 45.3% effectiveness against re-infection. Protection wanes more rapidly over time for omicron BA.1 compared to previous variants. Meanwhile, protection from severe disease remains high for all variants, including omicron BA.1. The level of protection from past infection appears to be at least as high as that from two doses of mRNA vaccines.
Care start access bio antigen test covid 19 biotechh commerceHafsaWadood1
The care start covid-19 antigen test is a lateral flow immuno-chromatographic assay, for the qualitative detect of the SARS coronavirus nucleo-capsid protein (major antigen). It is a rapid, easy, diagnostic test for the qualitative detection of Covid-19 antigen. This device is intended for use at Point of Care (POC) testing services.
Die britische Regierung räumt ein, dass Impfstoffe das natürliche Immunsystem von Doppelgeimpften geschädigt haben. Die britische Regierung hat zugegeben, dass Sie nach einer Doppelimpfung nie wieder eine vollständige natürliche Immunität gegen Covid-Varianten – oder möglicherweise gegen andere Viren – erlangen können. Sehen wir also zu, wie die „echte“ Pandemie jetzt beginnt! In seinem „COVID-19 Vaccine Surveillance Report“ (Woche 42) räumt das britische Gesundheitsministerium auf Seite 23 ein, dass „die N-Antikörperspiegel bei Menschen, die sich nach zwei Impfdosen infizieren, niedriger zu sein scheinen“. Es heißt weiter, dass dieser Rückgang der Antikörper im Wesentlichen dauerhaft ist. Was bedeutet das? Wir wissen, dass Impfstoffe eine Infektion oder Übertragung des Virus nicht verhindern (tatsächlich zeigt der Bericht an anderer Stelle, dass geimpfte Erwachsene jetzt viel wahrscheinlicher infiziert werden als ungeimpfte). Die Briten stellen nun fest, dass der Impfstoff die Fähigkeit des Körpers beeinträchtigt, nach einer Infektion Antikörper zu bilden, nicht nur gegen das Spike-Protein, sondern auch gegen andere Teile des Virus. Insbesondere scheinen geimpfte Personen keine Antikörper gegen das Nukleokapsid-Protein, die Hülle des Virus, zu bilden, das ein entscheidender Teil der Reaktion bei ungeimpften Personen ist. Langfristig sind die Geimpften deutlich anfälliger für eventuelle Mutationen im Spike-Protein, auch wenn sie bereits einmal oder mehrmals infiziert und geheilt wurden. Die Ungeimpften hingegen werden eine dauerhafte, wenn nicht sogar dauerhafte Immunität gegen alle Stämme des angeblichen Virus erlangen, nachdem sie auch nur einmal auf natürliche Weise damit infiziert wurden. Quelle: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1027511/Vaccine-surveillance-report-week-42.pdf Die
This document summarizes a clinical trial of an influenza vaccine. The trial aims to compare the immunogenicity and reactogenicity of a self-administered intradermal influenza vaccine to a nurse-administered intradermal vaccine. It describes the trial design as a randomized, open-label study. The primary objective is to show non-inferior immunogenicity of the self-administered vaccine. Safety and ability of participants to self-administer will also be assessed. The trial involves vaccination, follow-up of adverse events, and measurement of antibody response to evaluate the objectives. Standard clinical trial procedures for informed consent, safety monitoring, and regulatory compliance are discussed.
This document discusses the use of case-control studies to evaluate vaccine efficacy and adverse effects after a vaccine has been introduced. Case-control studies can estimate the protective effect of a vaccine by comparing vaccination status between cases who developed the target disease and controls. They can also assess potential rare adverse effects. Key methodological issues for case-control vaccine studies include controlling for confounding, diagnosis/recall bias, and establishing temporal relationships between vaccination and disease/adverse event onset. The document reviews an example case-control study of meningococcal vaccine efficacy in Brazil and the National Childhood Encephalopathy Study which investigated adverse neurological events following pertussis vaccination in the UK.
Ομιλία – Παρουσίαση: Αχιλλέας Γραβάνης, Καθηγητής Φαρμακολογίας, Ιατρική Σχολή Πανεπιστήμιο Κρήτης, Ερευνητής, Ινστιτούτο Μοριακής Βιολογίας & Βιοτεχνολογίας του ΙΤΕ
COVID Testing and ICMR strategy and vaccinesRishikaThakur9
The document discusses COVID-19 testing strategies and vaccines in development in India. It provides details on appropriate specimen collection, storage and transport for COVID-19 testing. It outlines the types of COVID-19 tests - molecular, antigen and antibody - and provides guidance on using the different tests for various testing scenarios. It also summarizes the status of several COVID-19 vaccines in clinical trials in India, including Covishield, ZyCoV-D, Sputnik V and others.
Who 2019-n cov-sci-brief-natural-immunity-2021.1-engArvinAmores
The document summarizes current scientific evidence on immunity from natural SARS-CoV-2 infection. It finds that 90-99% of infected individuals develop detectable neutralizing antibodies within 4 weeks. Available data suggests immune responses remain robust and protective against reinfection for at least 6-8 months in most people. Some variants have reduced susceptibility to antibodies, but cellular immunity elicited by natural infection also targets other viral proteins. Studies estimate natural infection provides 80-90% protection from reinfection for up to 7 months. The emergence of variants poses challenges to immunity that require ongoing monitoring.
This document describes a computational screening study of 12 FDA-approved antiviral drugs against SARS-CoV-2 spike protein and main protease targets using molecular docking. Key findings include:
- Ganciclovir and zanamivir showed strong binding energies (below -9 kcal/mol) with both targets through hydrogen bonding interactions.
- Ribavirin and tenofovir also exhibited significant binding energies above -8 kcal/mol with multiple hydrogen bonds to the main protease and spike protein.
- The study identifies potential dual-target antiviral properties of existing drugs, providing a starting point for further pre-clinical and clinical tests against SARS-CoV-2.
This document summarizes information about vaccine clinical trials and tick-borne encephalitis (TBE). It discusses the history and development of vaccines. It then describes the phases of clinical trials and provides examples of specific vaccine trials including for TBE. Key details about the TBE virus, epidemiology, vaccines, and a recent clinical trial comparing two TBE vaccines in children are summarized. The trial evaluated safety, immunogenicity and reactions to the vaccines. The document concludes that vaccination is an effective way to prevent TBE and current vaccines have shown good safety profiles.
The document discusses various aspects of COVID vaccines in India, including their development and clinical trials. It describes the Covishield and Covaxin vaccines in detail - Covishield is developed by Oxford University and AstraZeneca, while Covaxin is an inactivated vaccine developed by Bharat Biotech. It provides statistics on vaccination rates in India and challenges like vaccine hesitancy. Other vaccines mentioned include Sputnik V, Pfizer and Moderna.
Moderna, Pfizer, and Astrazeneca have shown promising early results in Phase 1/2 clinical trials of their COVID-19 vaccine candidates. Moderna and Pfizer have both advanced their mRNA vaccines to Phase 3 trials based on robust antibody responses and good safety profiles in initial participants. Astrazeneca has also seen strong immune responses after one or two doses of its adenovirus-based vaccine. Over 200 vaccines are in development globally, progressing at unprecedented speed due to heavy research investment, with the goal of approval within 12-18 months.
This document summarizes the challenges of rapidly developing a vaccine for SARS-CoV-2 (Covid-19) during a pandemic. It discusses how previous epidemics like H1N1, Ebola, and Zika showed that vaccines often weren't available before the epidemics ended. New platforms like DNA, RNA, and recombinant protein vaccines may speed development but regulatory review and large-scale manufacturing are challenges. The pandemic requires overlapping and parallel development phases with high financial risk. Coordinated global efforts are needed to fund manufacturing at scale and establish a fair global allocation system for any successful vaccines.
Scientists develop a new sars co v-2 vaccine with the successful experience o...DoriaFang
Researchers developed a new SARS-CoV-2 vaccine based on the successful hepatitis B vaccine platform. They used yeast to express the receptor binding domain protein of the coronavirus and supplemented it with a new adjuvant. Testing in monkeys showed the vaccine reduced virus shedding and symptoms when exposed to SARS-CoV-2. The vaccine aims to help meet global vaccination needs and may be effective against emerging variants.
Most developments in biotechnology originated for their potential applications in health care.
Contributions of biotechnology are more frequent, more notable and more rewarding in health sector.
This document provides an overview of SARS-CoV-2 testing. It describes the different types of diagnostic tests used in the COVID-19 response, including molecular tests that detect the virus's genetic material, antigen tests that detect viral proteins, and antibody tests that detect antibodies produced in response to infection. Accurate and rapid diagnostic testing is essential for confirming active infections, screening suspected cases, and determining the true extent of outbreaks. The document explains key terms like antigens and antibodies and where the different types of tests can be used, such as laboratories or point-of-care settings.
In this presentation, we discuss the clinical trial process for the new Covid-19 vaccines. We discuss the different vaccine types. We also discuss the Covid-19 vaccines that the UK is currently using in the NHS, as well as vaccines likely to be used in the next year.
Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical TrialsGuy Boulianne
The document presents a critical appraisal of the reported efficacy measures for the Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines. Using epidemiological tools and data from the vaccine clinical trials, the author calculates that the absolute risk reduction for the Pfizer vaccine is 0.7% and for the Moderna vaccine is 1.1%. These measures of absolute risk reduction are much lower than the reported relative risk reduction measures of 95.1% and 94.1%, respectively. The author argues that reporting absolute risk reduction is essential to prevent outcome reporting bias and allow for informed decision making about vaccine efficacy.
Studies of vaccine safety (Pharmacoepidemiology) V PharmDDr.Sohel Memon
This document discusses selected special applications of pharmacoepidemiology, focusing on studies of vaccine safety. It describes various methods used to monitor vaccine safety, including pre-licensure clinical trials, post-licensure surveillance systems like VAERS, and epidemiological studies. It addresses some methodological challenges in vaccine safety studies like assessing causality, accounting for confounding factors, and identifying rare adverse events. Large automated databases like the Vaccine Safety Datalink are highlighted as a valuable tool for monitoring vaccine safety on a population-level.
Prospects and Problems of Development of Candidate Vaccine against COVID 19ijtsrd
There is an urgent need to develop a vaccine against coronavirus disease 2019 COVID 19 , which is caused by a new coronavirus, severe acute respiratory syndrome coronavirus type 2 SARS CoV 2 infection. Although vaccine development typically requires 3 to 5 years, there is a possibility that the vaccine developed for either severe acute respiratory syndrome SARS or the middle east respiratory syndrome MERS could be used against COVID 19 as well. Therefore, a vaccine against COVID 19 is expected to be commercialized within 1 to 2 years. If so, it will be the fastest vaccine development in human history.In this review, we have summarized the information released as of April 10, 2020. Takuma Hayashi | Yasuaki Amano | Takashi Ura | Ikuo Konishi "Prospects and Problems of Development of Candidate Vaccine against COVID-19" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38521.pdf Paper Url: https://www.ijtsrd.com/medicine/other/38521/prospects-and-problems-of-development-of-candidate-vaccine-against-covid19/takuma-hayashi
Past SARS-CoV-2 infection provides high levels of protection against re-infection and symptomatic disease from ancestral, alpha, beta, and delta variants. However, protection is substantially lower for the omicron BA.1 variant, at 45.3% effectiveness against re-infection. Protection wanes more rapidly over time for omicron BA.1 compared to previous variants. Meanwhile, protection from severe disease remains high for all variants, including omicron BA.1. The level of protection from past infection appears to be at least as high as that from two doses of mRNA vaccines.
Care start access bio antigen test covid 19 biotechh commerceHafsaWadood1
The care start covid-19 antigen test is a lateral flow immuno-chromatographic assay, for the qualitative detect of the SARS coronavirus nucleo-capsid protein (major antigen). It is a rapid, easy, diagnostic test for the qualitative detection of Covid-19 antigen. This device is intended for use at Point of Care (POC) testing services.
Die britische Regierung räumt ein, dass Impfstoffe das natürliche Immunsystem von Doppelgeimpften geschädigt haben. Die britische Regierung hat zugegeben, dass Sie nach einer Doppelimpfung nie wieder eine vollständige natürliche Immunität gegen Covid-Varianten – oder möglicherweise gegen andere Viren – erlangen können. Sehen wir also zu, wie die „echte“ Pandemie jetzt beginnt! In seinem „COVID-19 Vaccine Surveillance Report“ (Woche 42) räumt das britische Gesundheitsministerium auf Seite 23 ein, dass „die N-Antikörperspiegel bei Menschen, die sich nach zwei Impfdosen infizieren, niedriger zu sein scheinen“. Es heißt weiter, dass dieser Rückgang der Antikörper im Wesentlichen dauerhaft ist. Was bedeutet das? Wir wissen, dass Impfstoffe eine Infektion oder Übertragung des Virus nicht verhindern (tatsächlich zeigt der Bericht an anderer Stelle, dass geimpfte Erwachsene jetzt viel wahrscheinlicher infiziert werden als ungeimpfte). Die Briten stellen nun fest, dass der Impfstoff die Fähigkeit des Körpers beeinträchtigt, nach einer Infektion Antikörper zu bilden, nicht nur gegen das Spike-Protein, sondern auch gegen andere Teile des Virus. Insbesondere scheinen geimpfte Personen keine Antikörper gegen das Nukleokapsid-Protein, die Hülle des Virus, zu bilden, das ein entscheidender Teil der Reaktion bei ungeimpften Personen ist. Langfristig sind die Geimpften deutlich anfälliger für eventuelle Mutationen im Spike-Protein, auch wenn sie bereits einmal oder mehrmals infiziert und geheilt wurden. Die Ungeimpften hingegen werden eine dauerhafte, wenn nicht sogar dauerhafte Immunität gegen alle Stämme des angeblichen Virus erlangen, nachdem sie auch nur einmal auf natürliche Weise damit infiziert wurden. Quelle: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1027511/Vaccine-surveillance-report-week-42.pdf Die
This document summarizes a clinical trial of an influenza vaccine. The trial aims to compare the immunogenicity and reactogenicity of a self-administered intradermal influenza vaccine to a nurse-administered intradermal vaccine. It describes the trial design as a randomized, open-label study. The primary objective is to show non-inferior immunogenicity of the self-administered vaccine. Safety and ability of participants to self-administer will also be assessed. The trial involves vaccination, follow-up of adverse events, and measurement of antibody response to evaluate the objectives. Standard clinical trial procedures for informed consent, safety monitoring, and regulatory compliance are discussed.
This document discusses the use of case-control studies to evaluate vaccine efficacy and adverse effects after a vaccine has been introduced. Case-control studies can estimate the protective effect of a vaccine by comparing vaccination status between cases who developed the target disease and controls. They can also assess potential rare adverse effects. Key methodological issues for case-control vaccine studies include controlling for confounding, diagnosis/recall bias, and establishing temporal relationships between vaccination and disease/adverse event onset. The document reviews an example case-control study of meningococcal vaccine efficacy in Brazil and the National Childhood Encephalopathy Study which investigated adverse neurological events following pertussis vaccination in the UK.
Ομιλία – Παρουσίαση: Αχιλλέας Γραβάνης, Καθηγητής Φαρμακολογίας, Ιατρική Σχολή Πανεπιστήμιο Κρήτης, Ερευνητής, Ινστιτούτο Μοριακής Βιολογίας & Βιοτεχνολογίας του ΙΤΕ
Similar to Các nguyên tắc thẩm định vaccine chống Coronavirus SARS-CoV-2 theo tiêu chuẩn GMP Nhật Bản (20)
This document provides guidance on good manufacturing practices for medicinal products. It discusses the importance of a pharmaceutical quality system to ensure that manufactured medicines are fit for use and comply with regulatory standards. Key elements of the quality system include good manufacturing practices, quality control, product quality reviews, and quality risk management. The quality system requires participation across all departments and levels of the company to ensure product safety, quality and efficacy.
This document discusses key aspects of designing pharmaceutical manufacturing facilities according to current Good Manufacturing Practices (cGMP). It covers process design tools like block flow diagrams, process flow diagrams, and piping and instrumentation diagrams that are used to design the facility layout and process flows. The document also discusses various unit operations in solid dosage manufacturing like material handling, milling, blending, compression, and coating. Facility design must meet regulatory requirements to facilitate operations, control materials, and prevent contamination according to cGMP.
This document lists various prequalified active pharmaceutical ingredients from the WHO. It includes the product ID, INN, grade, therapeutic area, applicant, date of prequalification, and confirmation date. There are over 400 entries listed with information about different APIs that have been prequalified for treatments of conditions like HIV/AIDS, malaria, tuberculosis, hepatitis, and others.
Danh mục 37 thuốc sản xuất trong nước được cấp giấy phép lưu hành tại Việt Nam - Đợt 185.
Quyết định được Cục Quản lý Dược Việt Nam ban hành vào tháng 7 năm 2023.
Danh mục 259 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 185.
Danh mục được ban hành bới Cục Quản lý Dược Việt Nam tháng 7 năm 2023.
Ngày 21/06 vừa qua, cục Quản lý Dược vừa ban hành quyết định về việc công bố danh mục thuốc biệt dược gốc - đợt 2 năm 2023.
Ban hành kèm theo quyết định này bao gồm 83 thuốc biệt dược gốc.
Xem thêm các tài liệu khác trên trang của công ty cổ phần Tư vấn thiết kế GMP-EU.
Hướng dẫn thực hành này cung cấp thông tin cho các nhà sản xuất thức ăn có chất sát khuẩn không an toàn do thuốc chuyển sang thức ăn chăn nuôi không chứa thuốc hoặc một loại thức ăn khác. Mục đích của hướng dẫn này:
• “Sản xuất và phân phối thức ăn có chứa thuốc” đề cập đến việc sử dụng thiết bị để sản xuất, chế biến, đóng gói, giữ và phân phối thức ăn.
• “Thức ăn chăn nuôi” được sản xuất có thêm hóa chất bảo quản. Thức ăn cho động vật như vậy có thể được gọi trong hướng dẫn này là “thức ăn có tẩm thuốc” hoặc “thức ăn không có tẩm thuốc”, tùy thuộc vào việc thức ăn đó có được pha chế để chứa một loại thuốc mới dành cho động vật hay không. Để thuận tiện, chúng tôi gọi những loại thuốc mới dành cho động vật này đơn giản là “thuốc”.
• “Thuốc mang theo” đề cập đến sự hiện diện của thuốc trong lô thức ăn chăn nuôi tiếp theo.
• “Ô nhiễm không an toàn”: đề cập đến mức độ nhiễm bẩn, do một loại thuốc được phép sử dụng trong thức ăn chăn nuôi, gây ra rủi ro không thể chấp nhận được đối với sức khỏe con người hoặc động vật.
Nói chung, các tài liệu hướng dẫn của FDA không thiết lập các trách nhiệm có thể thực thi về mặt pháp lý. Thay vào đó nó mô tả Cơ quan về một chủ đề và chỉ nên được xem dưới dạng khuyến nghị, trừ khi các yêu cầu pháp lý hoặc quy định cụ thể được trích dẫn. Việc sử dụng từ nên trong hướng dẫn của Cơ quan có nghĩa là điều gì đó được gợi ý hoặc khuyến nghị, nhưng không bắt buộc.
Xem thêm các tài liệu khác trên trang của công ty cổ phần tư vấn thiết kể GMP EU.
Cục Quản lý Thực phẩm và Dược phẩm Hoa Kỳ đưa ra hướng dẫn cho các nhà sản xuất và phân phối sữa cho trẻ sơ sinh về các yêu cầu ghi nhãn nhất định đối với các sản phẩm này. Hướng dẫn này đặc biệt chú trọng đến số lượng các công thức sữa cho trẻ sơ sinh có bao bì tương tự nhưng khác nhau về thành phần hoặc mục đích sử dụng. Ngày càng nhiều các sản phẩm ghi sai nhãn về hàm lượng chất dinh dưỡng, do vậy hướng dẫn này cung cấp thông tin có thể giúp các nhà sản xuất hiểu và tuân thủ các yêu cầu ghi nhãn liên quan.
Hướng dẫn này không bao gồm đầy đủ tất cả các quy định liên quan đến việc ghi nhãn sữa công thức dành cho trẻ sơ sinh. Vì vậy bạn có thể xem thêm các hướng dẫn khác tại www.fda.gov/FoodGuidances hoặc các tài liệu trên kênh của công ty cổ phần tư vấn thiết kế GMP EU.
Ngày 25/05 vừa qua, Cục quản lý Dược vừa ban hành danh mục 69 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 184.
Theo đó, ban hành kèm theo Quyết định này danh mục 69 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 184, cụ thể:
1. Danh mục 64 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam hiệu lực 05 năm (Phụ lục I kèm theo).
2. Danh mục 05 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam hiệu lực 03 năm (Phụ lục II kèm theo).
Xem thêm các tài liệu khác trên trang của công tư cổ phần tư vấn thiết kế GMP EU.
Ngày 25/05 vừa qua, Cục quản lý Dược đã ban hành quyết định số 352/QĐ-QLD về việc ban hành danh mục 231 thuốc nước ngoài được cấp, gia hạn giấy đăng ký lưu hành tại Việt Nam - Đợt 184.
Theo đề nghị của Trưởng phòng Đăng ký thuốc, Cục Quản lý Dược quyết định:
Ban hành kèm theo Quyết định này danh mục 231 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 184, cụ thể:
1. Danh mục 172 thuốc sản xuất trong nước được gia hạn giấy đăng ký lưu hành hiệu lực 05 năm (Phụ lục I kèm theo).
2. Danh mục 52 thuốc sản xuất trong nước được gia hạn giấy đăng ký lưu hành hiệu lực 03 năm (Phụ lục II kèm theo).
3. Danh mục 07 thuốc sản xuất trong nước được gia hạn đăng ký lưu hành đến 31/12/2025 (Phụ lục III kèm theo).
Xem thêm các tài liệu khác trên trang của công ty cổ phần Tư vấn thiết kế GMP EU.
Ngày 26/05 vừa qua, Cục Quản lý Dược đã ban hành quyết định số 371/QĐ-QLD về việc công bố danh mục thuốc biệt dược gốc Đợt 1 - năm 2023.
Theo đề nghị của Trưởng phòng Đăng ký thuốc - Cục Quản lý Dược, quyết định:
Công bố Danh mục 56 thuốc Biệt dược gốc Đợt 1 - Năm 2023 tại Phụ lục kèm theo Quyết định này.
Xem thêm các tài liệu khác trên trang của công ty cổ phần Tư vấn thiết kế GMP EU.
Ngày 26/05 vừa qua, Cục Quản lý Dược vừa ra quyết định số 370/QĐ-QLD về việc ban hành danh mục 50 thuốc nước ngoài được cấp, gia hạn giấy đăng ký lưu hành tại Việt Nam - Đợt 111 bổ sung.
Theo đề nghị của Trưởng phòng Đăng ký thuốc - Cục Quản lý Dược quyết định:
Ban hành kèm theo Quyết định này danh mục 50 thuốc nước ngoài được cấp, gia hạn giấy đăng ký lưu hành tại Việt Nam - Đợt 111 bổ sung, bao gồm:
1. Danh mục 41 thuốc nước ngoài được cấp giấy đăng ký lưu hành hiệu lực 05 năm - Đợt 111 bổ sung (tại Phụ lục I kèm theo).
2. Danh mục 01 thuốc nước ngoài được cấp giấy đăng ký lưu hành hiệu lực 03 năm - Đợt 111 bổ sung (tại Phụ lục II kèm theo).
3. Danh mục 07 thuốc nước ngoài được gia hạn giấy đăng ký lưu hành hiệu lực 05 năm - Đợt 111 bổ sung (tại Phụ lục III kèm theo).
4. Danh mục 01 thuốc nước ngoài được gia hạn giấy đăng ký lưu hành đến 31/12/2025 - Đợt 111 bổ sung (tại Phụ lục IV kèm theo).
Ngày 24/05 vừa qua, Bộ Y tế vừa ban hành quyết định về việc công bố danh mục thuốc có chứng minh tương đương sinh học đợt 2 - năm 2023.
Theo đề nghị của Trưởng phòng Đăng ký thuốc - Cục quản lý Dược, quyết định:
Công bố Danh mục 28 thuốc có chứng minh tương đương sinh học Đợt 2 - Năm 2023 tại Phụ lục kèm theo Quyết định này.
Xem thêm các tài liệu khác của Công ty cổ phần Tư vấn thiết kế GMP EU.
More from Công ty Cổ phần Tư vấn Thiết kế GMP EU (20)
The biomechanics of running involves the study of the mechanical principles underlying running movements. It includes the analysis of the running gait cycle, which consists of the stance phase (foot contact to push-off) and the swing phase (foot lift-off to next contact). Key aspects include kinematics (joint angles and movements, stride length and frequency) and kinetics (forces involved in running, including ground reaction and muscle forces). Understanding these factors helps in improving running performance, optimizing technique, and preventing injuries.
- Video recording of this lecture in English language: https://youtu.be/RvdYsTzgQq8
- Video recording of this lecture in Arabic language: https://youtu.be/ECILGWtgZko
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Congestive Heart failure is caused by low cardiac output and high sympathetic discharge. Diuretics reduce preload, ACE inhibitors lower afterload, beta blockers reduce sympathetic activity, and digitalis has inotropic effects. Newer medications target vasodilation and myosin activation to improve heart efficiency while lowering energy requirements. Combination therapy, following an assessment of cardiac function and volume status, is the most effective strategy to heart failure care.
CLASSIFICATION OF H1 ANTIHISTAMINICS-
FIRST GENERATION ANTIHISTAMINICS-
1)HIGHLY SEDATIVE-DIPHENHYDRAMINE,DIMENHYDRINATE,PROMETHAZINE,HYDROXYZINE 2)MODERATELY SEDATIVE- PHENARIMINE,CYPROHEPTADINE, MECLIZINE,CINNARIZINE
3)MILD SEDATIVE-CHLORPHENIRAMINE,DEXCHLORPHENIRAMINE
TRIPROLIDINE,CLEMASTINE
SECOND GENERATION ANTIHISTAMINICS-FEXOFENADINE,
LORATADINE,DESLORATADINE,CETIRIZINE,LEVOCETIRIZINE,
AZELASTINE,MIZOLASTINE,EBASTINE,RUPATADINE. Mechanism of action of 2nd generation antihistaminics-
These drugs competitively antagonize actions of
histamine at the H1 receptors.
Pharmacological actions-
Antagonism of histamine-The H1 antagonists effectively block histamine induced bronchoconstriction, contraction of intestinal and other smooth muscle and triple response especially wheal, flare and itch. Constriction of larger blood vessel by histamine is also antagonized.
2) Antiallergic actions-Many manifestations of immediate hypersensitivity (type I reactions)are suppressed. Urticaria, itching and angioedema are well controlled.3) CNS action-The older antihistamines produce variable degree of CNS depression.But in case of 2nd gen antihistaminics there is less CNS depressant property as these cross BBB to significantly lesser extent.
4) Anticholinergic action- many H1 blockers
in addition antagonize muscarinic actions of ACh. BUT IN 2ND gen histaminics there is Higher H1 selectivitiy : no anticholinergic side effects
PGx Analysis in VarSeq: A User’s PerspectiveGolden Helix
Since our release of the PGx capabilities in VarSeq, we’ve had a few months to gather some insights from various use cases. Some users approach PGx workflows by means of array genotyping or what seems to be a growing trend of adding the star allele calling to the existing NGS pipeline for whole genome data. Luckily, both approaches are supported with the VarSeq software platform. The genotyping method being used will also dictate what the scope of the tertiary analysis will be. For example, are your PGx reports a standalone pipeline or would your lab’s goal be to handle a dual-purpose workflow and report on PGx + Diagnostic findings.
The purpose of this webcast is to:
Discuss and demonstrate the approaches with array and NGS genotyping methods for star allele calling to prep for downstream analysis.
Following genotyping, explore alternative tertiary workflow concepts in VarSeq to handle PGx reporting.
Moreover, we will include insights users will need to consider when validating their PGx workflow for all possible star alleles and options you have for automating your PGx analysis for large number of samples. Please join us for a session dedicated to the application of star allele genotyping and subsequent PGx workflows in our VarSeq software.
Storyboard on Acne-Innovative Learning-M. pharm. (2nd sem.) CosmeticsMuskanShingari
Acne is a common skin condition that occurs when hair follicles become clogged with oil and dead skin cells. It typically manifests as pimples, blackheads, or whiteheads, often on the face, chest, shoulders, or back. Acne can range from mild to severe and may cause emotional distress and scarring in some cases.
**Causes:**
1. **Excess Oil Production:** Hormonal changes during adolescence or certain times in adulthood can increase sebum (oil) production, leading to clogged pores.
2. **Clogged Pores:** When dead skin cells and oil block hair follicles, bacteria (usually Propionibacterium acnes) can thrive, causing inflammation and acne lesions.
3. **Hormonal Factors:** Fluctuations in hormone levels, such as during puberty, menstrual cycles, pregnancy, or certain medical conditions, can contribute to acne.
4. **Genetics:** A family history of acne can increase the likelihood of developing the condition.
**Types of Acne:**
- **Whiteheads:** Closed plugged pores.
- **Blackheads:** Open plugged pores with a dark surface.
- **Papules:** Small red, tender bumps.
- **Pustules:** Pimples with pus at their tips.
- **Nodules:** Large, solid, painful lumps beneath the surface.
- **Cysts:** Painful, pus-filled lumps beneath the surface that can cause scarring.
**Treatment:**
Treatment depends on the severity and type of acne but may include:
- **Topical Treatments:** Such as benzoyl peroxide, salicylic acid, or retinoids to reduce bacteria and unclog pores.
- **Oral Medications:** Antibiotics or oral contraceptives for hormonal acne.
- **Procedures:** Such as chemical peels, extraction of comedones, or light therapy for more severe cases.
**Prevention and Management:**
- **Cleanse:** Regularly wash skin with a gentle cleanser.
- **Moisturize:** Use non-comedogenic moisturizers to keep skin hydrated without clogging pores.
- **Avoid Irritants:** Such as harsh cosmetics or excessive scrubbing.
- **Sun Protection:** Use sunscreen to prevent exacerbation of acne scars and inflammation.
Acne treatment can take time, and consistency in skincare routines and treatments is crucial. Consulting a dermatologist can help tailor a treatment plan that suits individual needs and reduces the risk of scarring or long-term skin damage.
BBB and BCF
control the entry of compounds into the brain and
regulate brain homeostasis.
restricts access to brain cells of blood–borne compounds and
facilitates nutrients essential for normal metabolism to reach brain cells
This presentation gives information on the pharmacology of Prostaglandins, Thromboxanes and Leukotrienes i.e. Eicosanoids. Eicosanoids are signaling molecules derived from polyunsaturated fatty acids like arachidonic acid. They are involved in complex control over inflammation, immunity, and the central nervous system. Eicosanoids are synthesized through the enzymatic oxidation of fatty acids by cyclooxygenase and lipoxygenase enzymes. They have short half-lives and act locally through autocrine and paracrine signaling.
Storyboard on Skin- Innovative Learning (M-pharm) 2nd sem. (Cosmetics)MuskanShingari
Skin is the largest organ of the human body, serving crucial functions that include protection, sensation, regulation, and synthesis. Structurally, it consists of three main layers: the epidermis, dermis, and hypodermis (subcutaneous layer).
1. **Epidermis**: The outermost layer primarily composed of epithelial cells called keratinocytes. It provides a protective barrier against environmental factors, pathogens, and UV radiation.
2. **Dermis**: Located beneath the epidermis, the dermis contains connective tissue, blood vessels, hair follicles, and sweat glands. It plays a vital role in supporting and nourishing the epidermis, regulating body temperature, and housing sensory receptors for touch, pressure, temperature, and pain.
3. **Hypodermis**: Also known as the subcutaneous layer, it consists of fat and connective tissue that anchors the skin to underlying structures like muscles and bones. It provides insulation, cushioning, and energy storage.
Skin performs essential functions such as regulating body temperature through sweat production and blood flow control, synthesizing vitamin D when exposed to sunlight, and serving as a sensory interface with the external environment.
Maintaining skin health is crucial for overall well-being, involving proper hygiene, hydration, protection from sun exposure, and avoiding harmful substances. Skin conditions and diseases range from minor irritations to chronic disorders, emphasizing the importance of regular care and medical attention when needed.
Storyboard on Skin- Innovative Learning (M-pharm) 2nd sem. (Cosmetics)
Các nguyên tắc thẩm định vaccine chống Coronavirus SARS-CoV-2 theo tiêu chuẩn GMP Nhật Bản
1. 1
Principles for the Evaluation of Vaccines Against the Novel Coronavirus SARS-CoV-2
September 2, 2020
Office of Vaccines and Blood Products,
Pharmaceuticals and Medical Devices Agency
1. INTRODUCTION
Infectious disease preventive vaccine is a medical product to activate the immune system against specific
antigen. For general considerations regarding nonclinical and clinical evaluations of investigational
preventive vaccines for infectious diseases, Guidelines for Nonclinical Studies of Preventive Vaccines
for Infectious Diseases (PFSB/ELD Notification No. 0527-1, dated May 27, 2010)1)
and Guidelines for
Clinical Studies of Preventive Vaccines for Infectious Diseases (PFSB/ELD Notification No. 0527-5,
dated May 27, 2010)2)
can be used for reference.
As a result of the recent pandemic of SARS-CoV-2 infectious disease (COVID-19), more than 20 million
people have been affected to date worldwide. Vaccines to prevent SARS-CoV-2 infectious disease
(SARS-CoV-2 vaccines) are being developed using various modalities such as inactivated virus vaccine,
recombinant protein vaccine, mRNA vaccine that uses lipid nanoparticles (LNPs) as a carrier (LNP-
mRNA vaccine), DNA vaccine, and recombinant virus vaccine with a recombinant virus vector and so
on.
This document presents basic principles concerning the efficacy and safety evaluation to develop a
SARS-CoV-2 vaccine in Japan, based on the situation as of August 2020. It should be noted, however,
that although the principles presented in this document are based on our knowledge at present and have
been developed after discussions with experts on infectious diseases and vaccines, they may change in
accordancewithnew findings and the status of SARS-CoV-2 vaccine development in Japan and overseas.
Also this document shows one of examples concerning the benefit/risk evaluation of SARS-CoV-2
investigational vaccines and at the time of the regulatory review approval for each investigational vaccine,
its benefit/risk will be reviewed taking into account its characteristics.
For principles concerning the quality of a SARS-CoV-2 vaccine, the ICHguidelines regarding the quality
of drugs and biological medicines, and existing guidelines in Japan and overseas can be used,3)-10)
depending on the modality of the investigational SARS-CoV-2 vaccine. Investigational products used in
clinical trial must be controlled in accordance with Good Manufacturing Practice for Investigational
Drugs (GMP-ID).11)
2. NONCLINICAL STUDY
Development of SARS-CoV-2 vaccine candidates has been needed to rapidly move forward to clinical
trials. Principles for SARS-CoV-2 vaccine candidates to support proceeding to a first-in-human clinical
trials and Phase III trials are presented in the summary reports of the workshops organized by the
International Coalition of Medicines Regulatory Authorities (ICMRA), Global Regulatory Workshops
on COVID-19 Vaccine Development (March 18, 2020 and June 22, 2020).12), 13)
2. 2
2.1. Pharmacological study
The following nonclinical pharmacology assessments are generally required to support clinical trials:
Assessment of immunogenicity
To confirm production of SARS-CoV-2 antigen-specific antibodies
To confirm production of neutralizing antibodies to SARS-CoV-2
To analyze characteristics of the immune response induced by SARS-CoV-2 (e.g., SARS-
CoV-2 antigen-specific antibody titer, neutralizing antibody titer, characterization of IgG
subclass, and cytokine production)
To confirm induction of cell-mediated immunity to SARS-CoV-2
Assessment of anti-infective/disease-preventive effect
The anti-infective/disease-preventive effect against SARS-CoV-2 should be assessed in an
animal model(s) of the infection.
The correlation with immune responses such as the SARS-CoV-2 antigen-specific antibody
titer, the neutralizing antibody titer, and cell-mediated immunity should be assessed in an
animal model(s) of infection
Each assessment should be validated to ensure appropriate assessment.
Any SARS-CoV-2 vaccine candidate should be required to confirm function as an infectious disease
preventive vaccines and to assess immunogenicity of the vaccine candidate before starting clinical trials
since nonclinical safety assessment to support human safety should be conducted in relevant animals,
whichshow immune response against the vaccine candidate. In addition, in order to estimate the potential
risk of disease enhancement that can be elicited by administration of the SARS-CoV-2 vaccine (see
Section 2.4), the immune response induced by administration of the vaccine candidate must also be
characterized prior to the initiation of the clinical trials.
The assessments of anti-infective/disease-preventive effect of infectious disease in animal model(s)
should be conducted as early as possible, although they can be done in parallel with early phase of
clinical trials.
2.2. Nonclinical Safety study
For the nonclinical safety studies to support the clinical trials, Guidelines for Nonclinical Studies of
Preventive Vaccines for Infectious Diseases andthe summary reports of ICMRAWorkshops on COVID-
19 Vaccine Development can be useful as reference.
To develop the SARS-CoV-2 vaccine, the nonclinical safety should be assessed. Conducting nonclinical
safetystudies of the SARS-CoV-2 vaccine candidate in parallel with the clinical trials can be accepted if
the SARS-CoV-2 investigational vaccine is a LNP-mRNAvaccine, DNAvaccine, or recombinant virus
vaccine, andthe nonclinical safetycan be explained by using the results of nonclinical safety studies and
clinical studies of other LNP, DNAplasmid vector, or recombinant vector virus.
Nonclinical safety of a SARS-CoV-2 vaccine candidates should be conducted according to Good
Laboratory Practice (GLP) regulation.14)
To support clinical trials, assessment of safety pharmacology,
general toxicity (multiple dose toxicity), and topical irritation are usually required.
3. 3
The test substance used for nonclinical safety studies should be a formulation that properly reflects the
characteristics (composition, formulation, manufacturing process and control, etc.) of the product used
for clinical trials.
The dose in preclinical safety studies should be the maximum human dose in the clinical trials. If it is
not feasible, administrating at multiple sites should be considered, taking into account animal welfare
(3Rs principles).15)
Innonclinical safetystudies, it is preferable to use animal species susceptible to the SARS-CoV-2 vaccine
candidate. At least one animal species in which the vaccine candidate can induce immune response
should be used.
Stand-alone nonclinical studies to assess safety pharmacology and local tolerance are not recommended
if they can be assessed in repeated-dose toxicity studies.
Repeated-dose toxicity should be assessed considering the followings:
Number of doses should be equal or exceed the number of doses proposed in humans.
Systemic toxicity can be assessed even if the route of administration is different from that
intended for use in the clinical trials as long as an adequate immune response is induced, while
local tolerance should be assessed by the intended therapeutic route .
Reproductive and developmental toxicity should be assessed considering the followings:
Fertility can be assessed as part of repeated-dose toxicity studies by through standard
histopathological examination on reproductive organs.
Given that women of childbearing potential can be a recipient of the SARS-CoV-2 vaccine,
assessment of embryo-fetal development, pre-postnatal development including maternal
function should be conducted.
Generally, reproductive and developmental toxicity studies can be conducted by the time of
marketing application. If, however, there is any concern regarding the reproductive and
developmental toxicity based on the characteristics of the SARS-CoV-2 vaccine candidate,
reproductive and developmental toxicity studies should be conducted and completed prior to
the initiation of a large-scale clinical trial.
In general, study endpoints covering the period from the reproductive/developmental stage C
(implantation to closure of the hard palate) through stage E (birth to weaning) should be
assessed, in accordance with the WHO guidelines 16)
and the ICH S5 Guideline 17)
.
If a novel adjuvant is used for the SARS-CoV-2 vaccine candidate, safety assessments are required for
the adjuvant. Repeated-dose toxicity and reproductive and developmental toxicity of the adjuvant can be
assessed as part of the studies with the SARS-CoV-2 vaccine candidate. For genotoxicity, safety
evaluation of the novel adjuvant itself should be considered.
2.3. Pharmacokinetics study
Pharmacokinetic studies are usually not required for infection prophylaxis vaccines. If, however, the
vaccine contains a novel substance such as a novel adjuvant, pharmacokinetic studies of the substance
may be required.
4. 4
For an LNP-mRNA vaccine, DNA vaccine, or recombinant virus vaccine, its postdose biodistribution
needs to be assessed. This assessment must be completed prior to the initiation of the first clinical trial
in Japan for DNA vaccines and recombinant virus vaccines, or prior to the initiation of a large-scale
clinical trial in Japan for LNP-mRNAvaccines.
For an LNP-mRNA vaccine, DNA vaccine, or recombinant virus vaccine, a biodistribution study with
the SARS-CoV-2 vaccine candidate is generally needed. The need for this biodistribution study with the
SARS-CoV-2 vaccinecandidate may, however, be obviated if the biodistribution of the vaccine candidate
can be explained on the basis of the results of biodistribution and clinical studies of another vaccine with
the same LNP, DNAplasmid vector, or recombinant virus vector as the SARS-CoV-2 vaccine candidate.
2.4. Disease Enhancement Caused by Administration of SARS-CoV-2 Vaccine
The disease enhancement possibly caused byadministration of SARS-CoV-2 vaccine is referred to as an
antibody-dependent enhancement (ADE) or enhanced respiratory disease (ERD). Disease enhancement
is believed to be a phenomenonin whichantibodies (and/or other substances) produced by administration
of vaccine enhance infections or infection-induced inflammation. At present, however, its mechanism of
development has not been elucidated. In the development of coronavirus vaccines, animal studies of
vaccines against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome
(MERS) viruses suggest a possibility of these vaccines causing disease enhancement.18), 19)
As for
preventive vaccines other than coronavirus vaccines, clinical studies of vaccines against RS (respiratory
syncytial) virus and dengue virus report fatal and worsened cases to which disease enhancement may
have contributed.20), 21)
Prior to clinical trials, it is necessary to estimate the risk of disease enhancement based on the results of
the immunogenic characterization suchas the Th1/Th2 balance, SARS-CoV-2 antigen-specific antibody
titer and neutralizing antibody titer in the nonclinical pharmacology studies .
Essentially, a test system with a relevant animal infection model should be introduced to assess the risk
of disease enhancement prior to the clinical trials. Considering the current status of COVID-19, however,
conducting early phase clinical trials in parallel with the development of the animal model of infection
is unavoidable if the risk of disease enhancement has been estimated to be low in the nonclinical
pharmacology studies. Even in such a case, the results of the animal study should be reported to the
Pharmaceuticals and Medical Devices Agency (PMDA) as soon as possible.
If a relevant animal infection model becomes available, it is important to assess the risk of disease
enhancement by through histopathological examination on the target organ (e.g. lung) in challenge test.
It is recommended to assess the risk of disease enhancement using the animal infection model, prior to a
large-scale clinical trials.
If new knowledge regarding how to assess the risk of disease enhancement is obtained in the future, an
additional risk assessment by means of the new method should be considered.
2.5. Actions to the Cartagena Act
To comply with the Act on the Conservation and Sustainable Use of Biological Diversity through
5. 5
Regulations onthe Use of Living Modified Organisms (Act No. 97of 2003; CartagenaAct), some actions
are needed depending on the type or manufacturing method of the SARS-CoV-2 vaccine candidate.
To conduct a clinical study of a SARS-CoV-2 vaccine candidate that uses a recombinant virus (including
replication-incompetent virus) as an active ingredient in Japan, Cartagena type 1 use codes must be laid
down and approved in accordance with the Cartagena Act. To manufacture a protein, plasmid DNA, or
recombinant virus that is produced with a gene recombination technique in Japan, the manufacturing
facility at which a living modified organism(s) is processed must undergo a verification concerning the
Cartagena type 2 use.
When applying for approval of the type 1 use codes, not only meeting the above-mentioned conditions
concerning Sections 2.1 to 2.3 of the Cartagena Act, but submission of test results concerning
environmental assessment is also required.
Regarding the actions to the Cartagena Act, scientific advice by PMDA is recommended as early as
possible because additional studies might be required to comply with the Act and a certain length of time
is required for the reviewing process of the type 1 use codes or the verification procedure concerning the
type 2 use.
3. CLINICALTRIALS IN JAPAN
The benefit-risk judgement of any SARS-CoV-2 vaccines can differ depending on the situation of each
country/region given that the degree of the COVID-19 epidemic, that the virus may undergo mutation
according to the geographic/passageconditions, and that the percentageof severe patients with worsened
COVID-19 and thebackgroundof the worsening is being investigated in various ways. In addition, ethnic
differences might affect the efficacy and safety of the SARS-CoV-2 vaccine. There may therefore be a
high need of evaluating the efficacy and safety of the vaccine in Japanese subjects by conducting a
clinical trial(s) in Japan, even if a large-scale confirmatory trial is conducted overseas to evaluate the
disease-preventive effect.
SARS-CoV-2 vaccine candidates for which pivotal clinical trials are conducted in Japan (vaccine
candidates firstly developed in Japan) and those for which pivotal trials are conducted overseas prior to
clinical trial in Japan (vaccine candidates that are ahead of development overseas) can differ with respect
to the requirements for clinical trials in Japan. In this section, therefore, principles for the two types of
vaccine candidate are described separately.
For principles concerning theevaluation in clinical trials, the summary reports of ICMRAWorkshops on
COVID-19 Vaccine Development as well as WHO and FDA guidance documents can be used for
reference.22)-24)
3.1. Vaccine Candidates Firstly Developed in Japan
3.1.1. Selection of Dosage
Multiple dosages should be considered to conduct a clinical trial in Japan, taking into account the routes
and schedule of administration, dosages, investigated in nonclinical studies.
In the present situation in which the relationship betweenthe efficacyof vaccine against COVID-19 and
6. 6
the antibody titer has not been established, the route of administration, dose and schedule should be
determined so that a higher immune response is induced.
We must assume that in the future a situation in which limited productions of SARS-CoV-2 vaccines
must be administered widely to the public can be realized. It is therefore preferable to have a smaller
vaccination dose and a fewer administration, and if multiple doses need to be administered, it is
preferable to have a shorter dosing interval for rapid acquisition of immunity. Thus, development
considering these factors from an early stage is recommended.
3.1.2. Evaluation of Immunogenicity
Collection data on the SARS-CoV-2 antigen-specifi
c antibody titer, neutralizing antibody titer, cytokine productions, and others should be considered to
evaluate the immunogenicity of the SARS-CoV-2 vaccine candidate. The geometric mean concentration
(GMC) and geometric mean titer (GMT) of antibodies should be assessed. In late phase clinical trials, it
should beconsideredto, if possible, assess theseroconversion rate or the seroprotection rate of antibodies
after a standard value of the antibody concentration or antibody titer is established on the basis of the
immunoreactivity results (SARS-CoV-2 antigen-specific antibody titer, neutralizing antibody titer, etc.)
from completed clinical trials.
If a possible disease-preventive marker has been determined from the nonclinical data using animal
models in challenge test, it will be useful to perform assessments with the marker when conducting
clinical trials in Japan.
In clinical trials to assess the immunogenicity, information about the incidence of COVID-19 during the
observation period should also be collected in an appropriate manner by assuming symptoms possibly
related to COVID-19 beforehand, considering the possibility of being able to evaluate the efficacy and
safety of the vaccine candidate exploratorily.
For a recombinant virus vaccine, the immune response to the recombinant virus vector and its effects
should be assessed.
3.1.3. Evaluation of Efficacy
The efficacy of infectious disease preventive vaccines is in principle evaluated using the disease-
preventive effect as the primary endpoint. In the current situation in which no surrogate marker for the
disease-preventive effect against COVID-19 is known, in principle, clinical trials to assess the preventive
effect against COVID-19 must be conducted to evaluate the efficacy of the SARS-CoV-2 vaccine
candidate. Other possible key endpoints may include SARS-CoV-2 infection confirmed by a virological
or serological method, as well as endpoints concerning the severity of COVID-19 such as arterial oxygen
saturation (SpO2), requirement of oxygen therapy, management with ventilator or ECMO, and death.
If another SARS-CoV-2 vaccine of which the disease-preventive effect is demonstrated overseas
becomes available in Japan, a SARS-CoV-2 vaccine candidate clinically evaluated thereafter may be
evaluated for its efficacy in a controlled clinical trial using the efficacy-demonstrated SARS-CoV-2
vaccine as a comparator. In this case, studyendpoints should be determined on the basis of the scientific
7. 7
understanding at that point concerning the mechanism of the disease-preventive effect of SARS-CoV-2
vaccines.
If in the future the disease-preventive effect of other SARS-CoV-2 vaccines is proved in a clinical trial
and an immunogenic marker associated with the disease-preventive effect is confirmed, immunogenicity
of the vaccine may be used for reference. For example, efficacy of a SARS-CoV-2 vaccine candidate
intended to be developed might be evaluated by confirming its disease-preventive effect in nonclinical
studies and its immunogenicity in a Japanese clinical trial.
3.1.4. Evaluation of Safety
It is required to collect adverse events (AEs) of solicited local reactions (swelling, redness, induration,
pain, etc.) and solicited systemic reactions (pyrexia, headache, malaise, myalgia, etc.) observed during
the first at least 7 days after administration of the SARS-CoV-2 vaccine candidate as well as all AEs
observed during the first at least 28 days after administration; longer periods may however be required
depending on the characteristics of the vaccine candidate.
Adverse events may be collected for at least 7 days after administration of the SARS-CoV-2 vaccine
candidate using a method such as (1) calling each subject and hearing the AEs recorded in their Subject
Diary or (2) collecting the Subject Diary when the subject visits the study site. The collection of AEs
from Day 8 onward must be planned so that information is properly collected; for example, AEs may be
collected by calling each subject every week or inputted AE data by each subject on an electronic device.
Disease enhancement risk should be assessed in clinical trials based on the immunogenic characterization
such as the Th1/Th2 balance, SARS-CoV-2 antigen-specific antibody titer, neutralizing antibody titer.
When a clinical trial is conducted, it is required to implement an appropriate procedure of informed
consent inwhichsubjects have knowledge of the theoretical riskof disease enhancement, perform careful
safety follow-up of subjects, and prepare a management system for possible cases of disease
enhancement.
3.1.5. Follow-up during the Clinical Trial
To collect information about the long-term efficacy and safety after administration of the SARS-CoV-2
vaccine candidate, subjects should be followed up at least one year in a clinical trial. Afollow-up period
longer than one year may be required depending on the characteristics of the SARS-CoV-2 vaccine
candidate.
During the follow-up period, collection of information about the persistence of antibody titer as well as
incidence of COVID-19 and AEs including assessment of the disease enhancement risk are required.
It is preferable to perform the safety follow-up during the clinical trial period also for subjects
withdrawing from the trial after vaccination, considering the disease enhancement risk.
3.1.6. Procedure of Clinical Trial
Clinical trials must be properly conducted in compliance with Good Clinical Practice (GCP).25)
In a first-in-human study, appropriate measures to ensure subjects' safety must be planned and
8. 8
implemented referring the guidance document, Notification on Revision of Guidance for Safety
Assurance in First-in-Human Studies of Drug Development (PSEHB/PED Notification No. 1225-1,
dated December 25, 2019)26)
. In particular, note the following:
In a first-in-human study, for risk reduction, it is more appropriate, for example, to evaluate
the safety in one or a few subject(s) when administering the vaccine candidate for the first
time or administering each stepped-up dose for the first time and then, proceed (i.e., not
administering the vaccine candidate to the next subject or at the next dose level until the safety
evaluation in one or a few subject(s) is completed). In such a case, prior to administration to
subsequent subjects, it is necessary to assess the reactions and AEs experienced by the
previous subjects.
In the protocol, criteria for step-ups within the clinical trial (regarding, e.g., dose escalation
and extension to wider age group) and for suspension/termination of the trial, as well as the
procedures, management systems, and responsibilities for these decisions should be
predefined.
When the sponsor of a clinical study chooses study sites, it should make sure:
That each site has facilities that make it possible to respond to emergencies (such as
cardiopulmonary arrest, anaphylaxis, cytokine release syndrome, loss of consciousness,
seizure and shock) and in the site, physicians who can appropriately respond to those
emergencies are deployed, and
That in case of the occurrence of AE(s) that cannot be managed in the site, it is defined the procedure
for transferring the subject to an appropriate external emergency medical institute and for referring the
subject to another medical institute or another department in the study site that can manage the
AE(s).Actions to take when any signs or symptoms suggestive of COVID-19 is found during the study
period should be predefined in the study protocol. Subjects should be given an explanation about those
actions.
3.1.7. Necessity of Other Endpoints
If the vaccine contains novel adjuvant(s) and/or novel excipients, their pharmacokinetics may need to be
evaluated.
For a recombinant virus vaccine or live attenuated vaccine, whether the vaccine strain is shedded from
the subject and how to manage the risk of transmission to others should be determined. If the vaccine
strain is found to be shedded from the subject, the SARS-CoV-2 vaccine candidate also should be
assessed regarding the possibility of transmission to those who have contacted the subject, the genetic
stability of the vaccine strain, and the possibility of mutation to a highly virulent strain. In addition, the
possibility of shedding and the risk of transmission to others should be explained to subjects and
appropriate actions should be taken.
3.1.8. Clinical Trial Design
The sample size for a clinical trial should be determined to evaluate efficacy and safety of the SARS-
9. 9
CoV-2 vaccine candidate appropriately, considering the characteristic of the endpoints.
For a SARS-CoV-2 vaccine candidate produced using innovative technology such as an LNP-mRNA
vaccine, DNA vaccine, or recombinant virus vaccine, or for a SARS-CoV-2 vaccine candidate with a
novel adjuvant, particularly careful evaluation of its safety is required in clinical trials.
In principle, any SARS-CoV-2 vaccine candidate should be evaluated in randomized, double-blind, (e.g.,
placebo-)controlled trials to assess the effect of antibody titer increased by a natural infection of SARS-
CoV-2 on postvaccination, to evaluate the safety concerning vaccination, and to assess the incidence of
COVID-19 and the risk of disease enhancement.
3.1.9. Evaluation in the Geriatrics, Pregnant Women/Nursing Mothers, and Children
Considering the high risk of severe COVID-19 in the geriatrics,27)
it is recommended to conduct a clinical
trial in the geriatrics as early as possible after the vaccination experience in adults (except the geriatrics)
has reached a certain level. In late phase of clinical trials, it is recommended to consider inclusion of
subjects whose risk of severe COVID-19 may be high (e.g., those who have an underlying disease).
For infectious disease preventive vaccines, it is possible to initiate clinical trials enrolling women of
childbearing potential even if any developmental and reproductive toxicity study has not been conducted;
in this case, however, adequate measures to avoid pregnancy need to be implemented with an informed
consent about the embryo-fetal risk being uncertain.
Whether pregnant women/nursing mothers can be enrolled in clinical trials should be determined after
the risk of reproductive and developmental toxicity is assessed according to the type of the SARS-CoV-
2 vaccine candidate, available nonclinical and clinical study data.
For children, it is recommended to plan and conduct an appropriate clinical trial after information about
the efficacy and safety in adults is obtained.
3.2. Vaccine Candidates that are ahead of Development Overseas
Even if development precedes overseas and large-scale clinical trials are being conducted to evaluate
efficacy and safety overseas, the basic principles concerning their evaluation are the same as those for
vaccine candidates first developed in Japan, although in principle, clinical trial must be conducted also
in Japan to confirm the efficacy and safety in Japanese subjects. For the clinical trial in Japan, it is
recommended to ask scientific advice to the PMDAas early as possible.
3.2.1. Selection of Dosage
When the clinical development of a SARS-CoV-2 vaccine candidate is further along overseas than in
Japan and it can be concluded that the dosage determined overseas are appropriate for the use in clinical
trials in Japan, the dosage determined overseas can be used in Japanese clinical trials without conducting
a clinical trial in Japan for the selection of the dosage.
3.2.2. Evaluation of Immunogenicity
Measuring the SARS-CoV-2 antigen-specific antibody titer, neutralizing antibody titer, cytokine
10. 10
productions, and others should be collected. The (GMC) and (GMT) of antibodies should be also
evaluated. It should be considered to, if possible, assess theseroconversion rate or the seroprotection rate
of antibodies after a standard value of the antibody concentration or antibody titer is established on the
basis of the immunoreactive results (SARS-CoV-2 antigen-specific antibody titer, neutralizing antibody
titer, etc.) from overseas trials.
In clinical trials to assess the immunogenicity, information about the incidence of COVID-19 during the
observation period should also be collected in an appropriate manner by assuming symptoms possibly
related to COVID-19 beforehand, considering the possibility of being able to evaluate the efficacy and
safety of the vaccine candidate exploratorily.
If the SARS-CoV-2 vaccine candidate has been evaluated in clinical trials overseas, it will be useful to
examine the immunoreactive results from a Japanese clinical trial in comparison with the results from
overseas trials.
For a recombinant virus vaccine, the immune response to the recombinant virus vector and its effects
should be assessed.
3.2.3. Evaluation of Efficacy
When a large-scale confirmatory clinical trial of the vaccine candidate is conducted overseas using the
disease-preventive effect as the primary endpoint, it may be sufficient to conduct a Japanese clinical trial
to confirm the immunogenicity and safety in Japanese subjects without conducting a confirmatory
clinical trial in Japan to evaluate the disease-preventive effect in Japanese subjects. When a global
development program (multi-regional clinical trial(s)) to evaluate the disease-preventive effect is planned,
the efficacy of the vaccine candidate in the Japanese population may be evaluated by participating in the
program from Japan.
If in the future the disease-preventive effect of other SARS-CoV-2 vaccines is proved in a clinical trial
and an immunogenic marker associated with the disease-preventive effect is confirmed in multiple trial
s, immunoreactive results of the vaccine may be used for reference. For example, efficacy of a SARS-
CoV-2 vaccine candidate intended to be developed might be evaluated by confirming its disease-
preventive protective effect in nonclinical studies and its immunogenicity in a Japanese clinical trial.
3.2.4. Evaluation of Safety
See Section 3.1.4.
3.2.5. Follow-up during the Clinical Trial
See Section 3.1.5.
3.2.6. Procedure of Clinical Trial
When a vaccine candidate is clinically developed in Japan at the same time as overseas, it is necessary
to implement a system that makes it possible to obtain safety information from the overseas clinical trials
and reflect them to the Japanese clinical trial.
11. 11
See Section 3.1.6.
3.2.7. Necessity of OtherEndpoints
See Section 3.1.7.
3.2.8. Clinical Trial Design
See Section 3.1.8.
3.2.9. Evaluation in the Geriatrics, Pregnant Women/Nursing Mothers, and Children
See Section 3.1.9.
4. POST-MARKETING ACTIONS
If a SARS-CoV-2 vaccine has been given marketing approval based on the results of the clinical trials
conducted, the marketing authorization holder must take appropriate post-marketing actions for safety
based on the safety information obtained from the clinical studies. For example, for the SARS-CoV-2
vaccine candidates currently developing because certain local and systematic AEs have been reported,
safety measures at the time of administration and information provision based on these reports are
absolutely needed.
Because the safety information from the clinical studies conducted by the time of approval may be
limited, whether the vaccine can be administered widely to the public will be carefully reviewed.
Following approval, the marketing authorization holder needs to organize a system that makes it possible
to properly and rapidly collect the safety information in Japan and overseas and promptly provide it to
all medical and other institutions concerned.
Long-term follow-up results of a large-scale clinical studies can become available after approval. The
manufacturer must promptly report those results to PMDA, and publicize them and take necessary
actions.
5. ACKNOWLEDGEMENTS
This document has been prepared after hearing from the following experts, and wewould like to express
our sincere thanks to them:
IWATA Satoshi, Director, Infection Division, National Cancer Center Hospital
OUCHI Kazunobu, Professor, Department of Pediatrics, Kawasaki Medical School
OISHI Kazunori, Director General, Toyama Institute of Health
OBA Koji, Associate Professor, Interfaculty Initiative in Information Studies and Department of
Biostatistics, Graduate School of Medicine, The University of Tokyo
OKADA Kenji, Professor, Division of Basic Medical Science and Fundamental Nursing, Fukuoka
Nursing College
OKABE Nobuhiko, Director General, Kawasaki City Institute for Public Health
TAKAHASHI Yoshimasa, Director, Department of Immunology, National Institute of Infectious
12. 12
Diseases
TAKEDA Makoto, Director, Department of Virology 3, National Institute of Infectious Diseases
HAMADA Atsuo, Professor, Travellers' MedicalCenter, Tokyo Medical University Hospital
HAYASHI Kunihiko, Professor, Gunma University Graduate Schoolof Health Sciences
HIRABAYASHI Yoko, Director, Biological Safety Research Center, National Institute of Health
Sciences
YAMAGUCHI Teruhide, Visiting Professor, Department of Pharmacy, Nihon Pharmaceutical
University
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13. 13
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