Stability Analysis for the Pharmaceutical Industry

Introduction to Stability Testing:

• Why is it necessary
• Who uses it
• What do the Regulatory Authorities require

What is the True Mean
:

• Highlighting vagaries within data using diagrams.
• Summarising data using an average – mean or median and a measure of variability – standard deviation or range.
• Obtaining a confidence interval for the true mean based on the sample mean and standard deviation. Estimating the sample size necessary to obtain a required width of confidence interval.

Samples and Populations:
Conclusions are generally drawn about a population from data obtained from a sample.

• What is a population
• What is a sample
• How should the sample be selected

Introduction to Significance Testing:
The significance testing procedure using the one sample t-test for the mean and the F-test for comparison of standard deviations.

• Formulation of hypotheses and the use of statistical tables.
• When to choose significance tests or confidence intervals.
• Choice of sample size and the need for a relevant design if valid conclusions are to be drawn from a significance test.

Significance Tests for Comparing Two Means:

• The importance of designs involving two groups (e.g. control and treatment).
• Analysis using the twosample t-test for independent samples and the one-sample t-test for paired samples.
• Sample size required to detect a difference.

The Normal Distribution:

• The use of the Normal Distribution.
• Obtaining probability values and percentage limits from statistical tables.
• The circumstances for which the distribution of data is likely to be Normal.
• Problem solving using normal probability plots.

Outliers:

• The assumptions behind outlier tests.
• The importance of the Normal distribution.
• Applying Grubbs’ test.
• The circumstances in which Grubbs’ test is unsuitable.

Regression Analysis:

• Fitting a straight line to data by least-squares regression.
• Assessing the variability about the line using the residual standard deviation.
• Determining the goodness of fit of the line using the correlation coefficient and percent fit.
• Confirming that a relationship exists between two variables using the correlation coefficient.
• Trending and extrapolation of data – obtaining predicted values and confidence intervals.
• Assumptions behind regression analysis.
• Regression in calibration and process improvement.
• The importance of residual values.

Calibration:

• Estimating the uncertainty in the response factor and the concentration of an unknown sample. Improving the precision of a calibration by changing the design.
• Checking on validity of assumptions using residuals.
• The effect of fixed and relative biases on error structures.

Combining Standard Deviations:

The need to improve the accuracy of an estimate of precision (standard deviation) by combining standard deviations from relevant sets of data.

Analysis of Variance and Pooling:

• A statisticians view of the guidance as written.
• What are its limitations and consequences”
• Examining overall variability within a batch.
• Understanding an Analysis of Variance table.
• Comparing Estimating within-batch SD and batch-to-batch SD from an investigation.
• Determining whether several groups are significantly different

Review of ICH Q1A and Q1E:

A detailed review of the technical requirements of ICH Q1A and Q1E.

Stability Testing – How to Apply the Standard:

How to implement statistical analysis as given in the WHO Technical Report No. 953 “Stability Testing of pharmaceutical ingredients and finished pharmaceutical products”.

Interactive Case Exercise:
Interactive case exercises, based on real industrial problems, are a feature of the course.

Tutorials:
Tutorials follow each lecture. Course members, under the guidance of experienced tutors, learn how to apply newly-found knowledge by solving realistic problems from industry.

Problem Seminars:
Problem Seminars and additional tutorials are held in the evenings, when extra help and guidance are available.

Free Consultancy Service:
A free consultancy service is available to course members which allows for practical problems to be presented for advice and help.