DRUG RESISTANCE TESTING NEW DRUG DEVELOPMENT (ANTI RETROVIRAL HIV) Antiviral Activity in Cell Culture
Antiviral Activity in Cell Culture
The antiviral activity in cell culture of a compound indicates that it effectively inhibits replication and forms the basis for defining phenotypic resistance (detected by reductions in susceptibility to the investigational drug (see below)). The concentration of an investigational drug required to inhibit virus replication by 50 percent (EC50 for cell-based assays; IC50 for biochemical or subcellular assays) should be determined. The use of the EC50 value for determining shifts in susceptibility is preferred because it can be determined with greater precision than an EC90 or EC95 value. A well-characterized wild-type (WT) HIV laboratory strain should serve as a reference standard. Sponsors should obtain some susceptibility data with a limited number of clinical isolates grown in peripheral blood mononuclear cells (PBMCs). Theamount of susceptibility data in PBMCs needed to support an application should be discussed with the division.
The antiviral activity of drugs can vary greatly because of factors such as genetic variation in isolates, host cell type, and multiplicity of infection assay used for measurement of virus replication. Because of genetic variation, determination of antiviral activity against a broad spectrum of viruses of well-characterized HIV laboratory strains and clinical isolates sufficient to assess the breadth of antiviral activity is recommended. The antiviral activity should be assessed in multiple clade B and nonclade B isolates, T-cell tropic HIV-1 and monocyte/macrophage tropic strains, HIV-2, and well-characterized drug-resistant laboratory strains and clinical isolates
IV. NONCLINICAL STUDIES
A. Mechanism of Action
B. Antiviral Activity in Cell Culture
C. Cytotoxicity and Therapeutic Indexes
D. Protein Binding
E. Selection of Drug-Resistant HIV-1 Variants in Cell Culture
1. Genotype
2. Phenotype
F. Cross-Resistance
G. Characterization of Genotypic and Phenotypic Assays
1. Genotypic Assays
2. Phenotypic Assays
V. CLINICAL STUDIES: USE OF RESISTANCE TESTING IN CLINICAL PHASES OF DRUG DEVELOPMENT
A. General Considerations
B. Data Collection
C. Methods and Types of Analyses
1. Baseline Genotype and Virologic Response
2. Development of HIV Mutations
3. Baseline Phenotype and Virologic Response
4. Genotypic and Phenotypic Correlations: Changes in Susceptibility from Baseline
5. Cross-Resistance
6. Additional Analyses
D. Other Considerations
1. Role for Supporting Initial Activity and Dose-Finding Studies
2. Data Collection from Dose-Finding Trials
3. Use of Resistance Data to Establish an Indication
4. Use of Resistance Data for Study Enrollment Criteria, Background Regimen Selection, and Stratification Factors
5. Nonclade B Subtypes
E. Monitoring during Phase 4
REGULATORY REQUIREMENTS FOR SUBMITTING HIV RESISTANCE DATA
SUMMARY
Source:
Drug Resistance Assay and Antiretroviral drug development guidance--->
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071173.pdf
There is much more information on HIV virus new findings available on this blog.
Here are given details about symptoms of AIDS , all new symptoms of AIDS and HIV virus infection are updated.
------------------------------------------------------------------------------------------------------------
This website provideds complete information about hiv virus , hiv infection , early hiv symptoms , hiv treatment,hiv test and hiv testing centers, aids symptoms, symptoms of hiv immideately after infection.------------------------------------------------------------------------------------------------------------
Following are the most read topic on this website you should find them on blog archive of this website
Stem cell treatment for AIDS
AIDS symptoms
SYMPTOMS OF HIV
HIV infection symptoms
Latest treatment for AIDS
How anti retroviral medicines are developed
How Chemotherapeutic drugs are developed to treat HIV virus infection
New drug developments against HIV Virus AIDS
Vaccines research for HIV AIDS Why it is difficult to develop a vaccine against HIV
Mother to child prevention of HIV virus infection.
hiv virus infection prevention and education bloggers
Information about HIV Virus AIDS symptoms
Last updated :10-Oct-2010
Antiviral Activity in Cell Culture
The antiviral activity in cell culture of a compound indicates that it effectively inhibits replication and forms the basis for defining phenotypic resistance (detected by reductions in susceptibility to the investigational drug (see below)). The concentration of an investigational drug required to inhibit virus replication by 50 percent (EC50 for cell-based assays; IC50 for biochemical or subcellular assays) should be determined. The use of the EC50 value for determining shifts in susceptibility is preferred because it can be determined with greater precision than an EC90 or EC95 value. A well-characterized wild-type (WT) HIV laboratory strain should serve as a reference standard. Sponsors should obtain some susceptibility data with a limited number of clinical isolates grown in peripheral blood mononuclear cells (PBMCs). Theamount of susceptibility data in PBMCs needed to support an application should be discussed with the division.
The antiviral activity of drugs can vary greatly because of factors such as genetic variation in isolates, host cell type, and multiplicity of infection assay used for measurement of virus replication. Because of genetic variation, determination of antiviral activity against a broad spectrum of viruses of well-characterized HIV laboratory strains and clinical isolates sufficient to assess the breadth of antiviral activity is recommended. The antiviral activity should be assessed in multiple clade B and nonclade B isolates, T-cell tropic HIV-1 and monocyte/macrophage tropic strains, HIV-2, and well-characterized drug-resistant laboratory strains and clinical isolates
IV. NONCLINICAL STUDIES
A. Mechanism of Action
B. Antiviral Activity in Cell Culture
C. Cytotoxicity and Therapeutic Indexes
D. Protein Binding
E. Selection of Drug-Resistant HIV-1 Variants in Cell Culture
1. Genotype
2. Phenotype
F. Cross-Resistance
G. Characterization of Genotypic and Phenotypic Assays
1. Genotypic Assays
2. Phenotypic Assays
V. CLINICAL STUDIES: USE OF RESISTANCE TESTING IN CLINICAL PHASES OF DRUG DEVELOPMENT
A. General Considerations
B. Data Collection
C. Methods and Types of Analyses
1. Baseline Genotype and Virologic Response
2. Development of HIV Mutations
3. Baseline Phenotype and Virologic Response
4. Genotypic and Phenotypic Correlations: Changes in Susceptibility from Baseline
5. Cross-Resistance
6. Additional Analyses
D. Other Considerations
1. Role for Supporting Initial Activity and Dose-Finding Studies
2. Data Collection from Dose-Finding Trials
3. Use of Resistance Data to Establish an Indication
4. Use of Resistance Data for Study Enrollment Criteria, Background Regimen Selection, and Stratification Factors
5. Nonclade B Subtypes
E. Monitoring during Phase 4
REGULATORY REQUIREMENTS FOR SUBMITTING HIV RESISTANCE DATA
SUMMARY
Source:
Drug Resistance Assay and Antiretroviral drug development guidance--->
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071173.pdf
There is much more information on HIV virus new findings available on this blog.
Here are given details about symptoms of AIDS , all new symptoms of AIDS and HIV virus infection are updated.
------------------------------------------------------------------------------------------------------------
This website provideds complete information about hiv virus , hiv infection , early hiv symptoms , hiv treatment,hiv test and hiv testing centers, aids symptoms, symptoms of hiv immideately after infection.------------------------------------------------------------------------------------------------------------
Following are the most read topic on this website you should find them on blog archive of this website
Stem cell treatment for AIDS
AIDS symptoms
SYMPTOMS OF HIV
HIV infection symptoms
Latest treatment for AIDS
How anti retroviral medicines are developed
How Chemotherapeutic drugs are developed to treat HIV virus infection
New drug developments against HIV Virus AIDS
Vaccines research for HIV AIDS Why it is difficult to develop a vaccine against HIV
Mother to child prevention of HIV virus infection.
hiv virus infection prevention and education bloggers
Information about HIV Virus AIDS symptoms
Last updated :10-Oct-2010
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