part I- Lecture 2.pdf

Quality Control & Pharmaceutical Analysis  Lecture 2 Quality Management System Good Quality Management (GQM) It was constructed to achieve continuous good performance in all processes performing expected excellent productivity with significant perfection. Principal goals of GQM...

Quality Control & Pharmaceutical Analysis  Lecture 2 Quality Management System Good Quality Management (GQM) It was constructed to achieve continuous good performance in all processes performing expected excellent productivity with significant perfection. Principal goals of GQM were: The continuous improvement in quality through research and development (R&D), exceeding the customer needs, good personal management, and job security with understanding (know-how key) Good quality is to be built from the all beginning Realization of the Standard Operational Procedures (SOPs) Predominating the collaborative team work in all steps of the procedures understanding that “errors” are not always “mistakes” 3 Deming Cycle” or “Shewhart Cycle” or “Deming Wheel” It describes a simple method to test information before making a major decision. It is an iterative 4-step problem-solving process called PDCA “Plan – Do – Check – Act” Plan : design the experiment Do : performing the steps of experiment Check: check the results by testing information Act : act on the decisions based on those results 4 Good analytical practice (GAP)& good laboratory practice (GLP) They are concepts concerning with the building of good quality in analytical practice. In order to perform a GAP or GLP, full validated analytical methodologies and techniques in many compendia and authorities (such as the USP, BP, EP, and AOAC) must be applied. Some Standard Quality Systems for Analytical Laboratories The Organization for Economic Co-operation and Development (OECD) which has developed the Good Laboratory Practice "GLP” International Conference on Harmonization (ICH guidelines) of technical requirements for registration of pharmaceuticals for human use; validation of analytical procedures. 5 The International Organization for Standardization (ISO) has produced a range of standards and guidance relevant to lab. The European Standards (EN-series). The European Committee for Standardization (CEN) has produced its own range of standards concerning quality. The British Standards Institution (BSI) has also produced a range of standards addressing quality. 6  QUALITY CONTROL UNIT It consists of at least 2 primary units  Analytical control laboratory or unit (ACL or ACU)  Inspection control unit (ICU) Function of the analytical control unit It is responsible for testing and approving or rejecting raw material (active or not), packaging, work in-process control and finished product. It must be: 1. Staffed with well trained persons to perform complex analysis required to evaluate the acceptance of a product. 2. Well equipped with instruments which allow accurate analysis. 3. Detailed specifications of test methods including the limits for acceptance or rejection for each parameter must be available. 7  Development of Analytical Control Laboratory (ACL) Laboratory setup  Creation of pharmacy administration to provide the required framework.  Define the objectives (the drugs to be tested and the types of tests to be applied)  Sampling program Units of ACL 1. Physico-chemical investigation unit 2. Physical criteria specification unit 3. Stability indication unit 8  Physico-chemical investigation unit Function Testing of the samples through measuring the change in physico chemical nature of the drugs using different techniques such as: titrations, UV and IR absorption, different types of chromatography, gel electrophoresis, fluorescence, atomic absorption spectroscopy, and thermal analysis. These techniques are applied mainly for: Purity assessment e.g. thermal analysis is used for detn. of the purity of reference standards. Assay of materials e.g. Karl-Fischer titration method is used for the detn. of water in different compounds 9 Karl-Fischer titration 10 Physical criteria specification unit Some general tests are carried out such as: Disintegration/dissolution rates in tablets and capsules, Weight variation, Net content or declared content of tablets, capsules and injections Certain physical tests could also be applied in determining the quality of a product by visual inspection only such as: color, consistency, clarity, stability, contamination with foreign matter or fungal growth defects such as chipping of tablets, capping, cracking, moisture absorption, discoloration of the coating, decomposition, mottled appearance and various other characteristic defects. 11  Stability indication unit Some physical criteria should be taken into consideration for evaluating quality with respect to stability:  Color changes in drug substances,  Growth of microorganisms,  Hardening of tablets,  Sedimentation of suspension,  Changes in the viscosity of oils,  Crystal growth in suspension or in the surface of tablets, etc.. 12 13  BASES OF GOOD SAMPLING  Sample is a representative portion selected from the bulk. according to a defined sampling procedure.  Sampling is the process of selecting a portion of material to represent or provide information about a larger body of material.  WHO have been released guidelines for sampling of pharmaceutical products and related materials since 2005.  These guidelines are primarily intended for use by governmental organizations, quality control laboratories and police officials.  The sampling procedure should be appropriate to the purpose of sampling tests intended to be applied to the samples The material to be sampled. 14  The sampling procedure should be described in writing. Sample collection form  Written record (documentation) of the sampling operations, always kept together with the collected sample, it includes;  batch number,  sampling date/place,  reference to sampling protocol used,  description of containers and materials sampled,  possible abnormalities,  name/signature of the sampler 15  Types of samples Type of material Physical state Homogeneity  Bulk materials Gas Homogenous  Intermediates Liquid Heterogeneous  Finished products Solid Sampling plan  Representative sample  Selective sample  Composite sample  Random sample Simple random sampling Stratified random sampling Systematic random sampling 16  1- Representative sample  Sample obtained according to a sampling procedure designed to ensure that the different parts of a batch or the different properties of a non-uniform material are proportionately represented.  Is typical of the parent material for the characteristic under inspection.  Is easy to collect from homogeneous bulk but care should be taken for heterogeneous one to overcome problems of mixing variation.  It is representative if the concentration of analyte is at 5% w/w 2- Selective sample  Is chosen by using sampling plan that screens out materials with certain characteristics or with other relevant characteristics.  This may be called directed or focused sampling. 17