Pharma QC Guide

Good Laboratory practice Good Laboratory practices in Pharmaceutical industry Document No.: GLP/00001 Table of content  WHO Good document practice Heading 1 Heading 2 Heading 3 Heading 4 Heading 5 Heading 6 INTRODUCTION HYPOTHESIS MATERIALS  WHO Good document practice The need to implement quality standards in drug research, development and testing; the situation in developing countries and the role of WHO/TDR Tropical diseases are a major public health problem in developing countries (Disease Endemic Countries – DECs). For many of these diseases no new, effective and affordable medicines have been developed, while older therapeutic agents are increasingly compromised by the emergence of resistance. Because multinational pharmaceutical companies have not traditionally focused on tropical disease research and development (R&D), WHO has initiated R&D programmes in a number of priority areas such as malaria. WHO’s Special Programme for Res...

The analytical worksheet is an internal document to be used by the analyst for recording information about the sample, the test procedure, calculations and the results of testing. It is to be complemented by the raw data obtained in the analysis. Purpose The analytical worksheet contains documentary evidence either: To confirm that the sample being examined is in accordance with the requirements. To support an OOS result. Use A separate analytical worksheet should usually be used for each numbered sample or group of samples. Analytical worksheets from different units relating to the same sample should be assembled together. Content The analytical worksheet should provide the following information:  The registration number of the sample. Page numbering, including the total number of pages (and including annexes) The date of the test request. The date on which the analysis was started and completed The name and signature of the analyst A description o...

The resolution is represented as a numeric value, such as 0.8, 1.0, or 3.0. But what is the relationship between the number representing the resolution and the actual peak separation?  At a resolution of 1.0, if the two peaks are assumed to have a Gaussian distribution and have the same peak height and peak width, then the difference in retention time from equation  become 1.0W, or 1.0 × 4σ = 4 σ.  In the case of a Gaussian distribution, 4 σ encompasses 95.4 %, such that the peaks overlap by 2.3 % ((100 % - 95.4 %)/2).  This indicates that 2.3 % of the peak intrudes into the other peak from a perpendicular line drawn in the trough.  Similarly, a resolution of 1.5 indicates a difference in retention time of 1.5× 4σ = 6σ, which corresponds to an overlap of 0.15 % ((100 % - 99.7 %)/2).

The resolution is the separation of two components in a mixture, calculated by: Resolution = 2 × (tR2 − tR1)/(W1 + W2)  where tR2 and tR1 are the retention times of the two components; and W2 and W1 are the corresponding widths at the bases of the peaks obtained by extrapolating the relatively straight sides of the peaks to the baseline.  Where electronic integrators are used, it may be convenient to determine  the resolution, by the equation:  Resolution = 1.18 × (tR2 − tR1)/(W1,h/2 + W2,h/2) What relation Resolution and Peak seperations?

Relative retention time (RRT) is the ratio of the retention time of analyte peak relative to that of another used as a reference obtained under identical conditions. RRT = (T analyte / T reference)  Wher T = Retention time As per USP Relative retention time (RRT): Also known as the “unadjusted relative retention”. Comparisons in USP–NF are normally made in terms of unadjusted relative retention, unless otherwise indicated. RRT = tR2/tR1 The symbol rG is also used to designate unadjusted relative retention values. The use of the relative retention time (RRT) reduces the effects of some of the variables that can affect the retention time. What is Retention time?

Retention time (RT) is a measure of the time taken for a solute to pass through a chromatography column. Retention time (RT) is calculated as the time from injection to detection. The RT for a compound is not fixed as many factors can influence it even if the same instrument and column are used.  These include: The flow rate Temperature differences in the oven and column Column degradation Column length What is RRT?

Chromatography Chromatography  is a  laboratory technique  for the  separation of a mixture .  The mixture is dissolved in a fluid called the  mobile phase, which carries it through a structure holding another material called the  stationary phase. The various constituents of the mixture travel at different speeds, causing them to separate.  The separation is based on differential partitioning between the mobile and stationary phases.  Subtle differences in a compound's  result in differential retention on the stationary phase and thus affect the separation. Chromatography is based on the concept of partition coefficient .  Any solute partitions between two immiscible solvents. When we make one solvent immobile (by adsorption on a solid support matrix) and another mobile it results in most common applications of chromatography. If the matrix support, or stationary phase, is polar (e.g. paper, silica etc.) it...

Laboratory “reagents, and standard solutions,” as referenced in the CGMP regulations at 211.194, includes laboratory chemicals such as solvents (including mobile phases), dry chemicals (salts, primary standards, etc.), and solutions (buffers, acids/bases, quantitative analytical preparations, etc.), whether purchased or prepared in-house. Laboratory reagents and solutions are used in analytical tests of components, in-process materials, and finished products. If the purchased laboratory reagent or solution includes a manufacturer’s suggested "use by" or expiry date, that date should be followed. For purchased laboratory reagents and solutions without a "use by" or expiry date, FDA would expect that an assessment be conducted (literature review may be acceptable) of that specific chemical's or chemical family's stability and that an appropriate "use by" or expiry date be determined. For in-house prepared solutions, such as mobi...

A nalytical error As guidance to minimise errors in the preparation of analytical solutions, Table 1, giving estimations of the relative uncertainty, is to be consulted. In order to avoid either the use of extremely low amounts or an unnecessarily large expenditure of solvents, a dilution series will often have to be prescribed for the preparation of dilute solutions used particularly for spectrophotometry measurement. In this context not all combinations of (usually 2 or 3) dilution steps will contribute equally to the random error of the dilution procedure. If critical for the purpose, the optimal dilution is prescribed in consideration of the relative errors (capacity tolerance divided by nominal volume) associated with the various sizes of volumetric pipettes and volumetric flasks commonly used for these operations (taking the usual formula: square root of the sum of the squares of individual relative errors, to estimate the relative dilution error). Tables...