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RegisterCalibration Curve range [Regulatives / Guidelines]
Dear All,
Kindly provide your valuable suggestion for below mentioned practice (Is it acceptable for regulatory point of view or not).
To validate “single analytical range” for “X” molecule bioequivalence study of 50mg and 100 mg strength,taking into consideration Cmax of 100 mg strength by including “additional QC” between LQC & MQC concentration. (LQC concentration: ≤ 3 times of LLOQ, MQC: average between LLOQ and ULOQ and HQC: 75-85% of ULOQ) and during study sample analysis of 50 mg Strength product “Additional QC” will be included before starting of Study sample analysis to cover at least two QC concentrations of unknown samples.
I have referred following references but not able to conclude,
As per EMEA guidelines,
"Ideally, before carrying out the validation of the analytical method it should be known what concentration range is expected. This range should be covered by the calibration curve range, defined by the LLOQ being the lowest calibration standard and the upper limit of quantification (ULOQ), being the highest calibration standard. The range should be established to allow adequate description of the pharmacokinetics of the analyte of interest".
As per USFDA guideline,
"Concentrations of standards should be chosen on the basis of the concentration range expected in a particular study".
As per, Critical Recommendations from the Third AAPS/FDA Bioanalytical Workshop
"Advice on Implementation: This reinforces the 483’s that the FDA has issued over the past several years for bioanalytical methods used to support bioequivalence studies, cited for too great an analytical range. While laboratories like to make calibration ranges as wide as linearity permits, it is clear that the FDA expects calibration ranges to be equal to the actual range of concentrations found in the study samples and that the low, medium and high QC samples represent the actual concentration range of samples analyzed within the batch. This means that labs will have to take one of two approaches: validate a series of ranges, each with three levels of QC concentrations; or validate a very wide range but with multiple QC concentrations spread over the entire range".
Thank you in advance.
Kindly provide your valuable suggestion for below mentioned practice (Is it acceptable for regulatory point of view or not).
To validate “single analytical range” for “X” molecule bioequivalence study of 50mg and 100 mg strength,taking into consideration Cmax of 100 mg strength by including “additional QC” between LQC & MQC concentration. (LQC concentration: ≤ 3 times of LLOQ, MQC: average between LLOQ and ULOQ and HQC: 75-85% of ULOQ) and during study sample analysis of 50 mg Strength product “Additional QC” will be included before starting of Study sample analysis to cover at least two QC concentrations of unknown samples.
I have referred following references but not able to conclude,
As per EMEA guidelines,
"Ideally, before carrying out the validation of the analytical method it should be known what concentration range is expected. This range should be covered by the calibration curve range, defined by the LLOQ being the lowest calibration standard and the upper limit of quantification (ULOQ), being the highest calibration standard. The range should be established to allow adequate description of the pharmacokinetics of the analyte of interest".
As per USFDA guideline,
"Concentrations of standards should be chosen on the basis of the concentration range expected in a particular study".
As per, Critical Recommendations from the Third AAPS/FDA Bioanalytical Workshop
"Advice on Implementation: This reinforces the 483’s that the FDA has issued over the past several years for bioanalytical methods used to support bioequivalence studies, cited for too great an analytical range. While laboratories like to make calibration ranges as wide as linearity permits, it is clear that the FDA expects calibration ranges to be equal to the actual range of concentrations found in the study samples and that the low, medium and high QC samples represent the actual concentration range of samples analyzed within the batch. This means that labs will have to take one of two approaches: validate a series of ranges, each with three levels of QC concentrations; or validate a very wide range but with multiple QC concentrations spread over the entire range".
Thank you in advance.
Complete thread:
- Calibration Curve rangevish14184 2013-06-18 14:05
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