QA/QC Notes PDF

MODULE 6 PHARMCHEM 4 QUALITY ASSURANCE & QUALITY CONTROL QUALITY ASSURANCE & QUALITY CONTROL I. BASIC PRINCIPLES 4. Material Safety Data Sheet (MSDS) Contains information on the potential health effects of exposure to chemicals and on safe working procedures when handling chemical products A. DEFINI...

MODULE 6 PHARMCHEM 4 QUALITY ASSURANCE & QUALITY CONTROL QUALITY ASSURANCE & QUALITY CONTROL I. BASIC PRINCIPLES 4. Material Safety Data Sheet (MSDS) Contains information on the potential health effects of exposure to chemicals and on safe working procedures when handling chemical products A. DEFINITION OF TERMS D. SAMPLING 1. Quality The process of removal of an appropriate number of items (n) from a population (N) error:false (t) or if Sampling Plan: 1. MIL-STD-105E (Military Standard) most common batch (old); master tables size ↑ 2. ANSI/ ASQ Z1.4-2008 most common (new) 3. Square Root System easier (use in exam) Totality features or conformance to specifications of a product Ensures that products: Are fit for their intended use Safe Compliant with the requirements of the marketing authorization CTO, COOR from FDA oo - E. CONTROL CHARTS sample size 2. Total Quality Management (TQM) Graphs on which the quality of the product is plotted as manufacturing is actually proceeding Sample Statistics A combined team effort to develop, produce, market, distribute, and control products that are safe and will be effective for the time they remain in the marketplace. 3. Quality Assurance (QA) Totality of the organized arrangements made with the objective of ensuring that products are of the quality required for their intended use Wide ranging concept that covers all matters individually or collectively influence 4. Current Good Manufacturing Practice (CGMP) Part of quality assurance which ensures that products are 1: UK contamination consistently produced and controlled to the quality cross standards appropriate for their intended use risk1: Hd: 10.110s. 1974 new: 10 2012-0008 (P1c/s) mixup5. Quality Control detailed regs. Part of CGMP concerned with sampling, specifications, testing, organization, documentation and release procedures (PIC/S Guidelines QA CGMP QC) 6. Product Quality Review (PQR) Regular periodic quality reviews of all registered drug products to verify consistency of the existing process and to identify product and process improvements 7. Quality risk Management (QRM) A systematic process for the assessment, control, communication, and review of risks to the quality of the product B. QUALITY UNIT " ~ #DAI QC Unit Conducts sampling and testing of RM & FP Inspectso PM components Preforms environmental monitoring packaging material / C. DOCUMENTS 1. Monograph = Pharmacopried Specifies all the tests to be conducted on a material and the expected results ↳ Red 4 5 Zone F. VALIDATION AND QUALIFICATION 1. Validation the action of proving and documenting that any process, procedure or method actually leads to the expected results ↳ whole process for the 2. Qualification the action of proving that premises, systems or equipment work correctly and actually lead to expected results. ↳ initial steps for validation G. PRODUCT DEFECTS Non-conformance to a standard or requirement 1. According to Magnitude a. Critical Defect may endanger life of patient b. Major Defect does not endanger life of patient put affects the function of the product c. Minor Defect does not endanger life of patient and does not affect the function of the product => small issues ex.color 3. Certificate of Analysis (COA) =>by9C Shows the actual result of all tests conducted on a material to show compliance with standards discoloration 2. According to Measurability a. Variable Defect measured by an instrument b. Attributive Defect measured by inspection odor, taste, etc. 3. According to Nature a. Ocular Defect can be seen by the naked eye b. Internal Defect cannot be seen by the naked eye H. PRODUCT RECALL instruction Quality Assurance & Quality Control 3 Types: fraction 1. p-Chart proportion of defectives = whole number > 2. np-Chart non-proportion (number of defectives) * wt./ 3. X Bar Chart used for measurable characteristics tablet Thickness Gneen zone ↑Warning limit alerts the operator to closely monitor the process Action limit alerts the operator to stop the process and do corrective action Removal of product from the market because it is either defective or potentially harmful 2. Standard Operating Procedure (SOP) = written by Q Step-by-step instruction for doing a particular task or activity Module 6 2 Sample Number Classification of Product defects: An organizational unit independent of Production which fulfills both Quality Assurance and Quality Control responsibilities " lab works rfice works QA Unit Ensures the quality policies are followed Audit and monitoring Primary contact with regulatory agencies Prepares SOPs 1 Upper control line Upper warning line Target Lower warning line Lower control line Classification of Product Recall: 1. Page 1 of 8 Class I Recall may cause death or serious adverse health consequences RJAV 2022 2. A b. Accelerated Studies 140 = 20175=5% Designed to increase the rate of chemical degradation by using exaggerated storage conditions extrapolated only applicable Testing Period: 0, 3,Or 6 Class II Recall may cause temporary/ medically reversible adverse health consequences Class III Recall not likely to cause adverse health consequences ex.not FDAregistered 3. 790 I. STABILITY STUDIES 1. Stability Capacity of a drug to remain within specification Minimum Acceptable Potency: 90% amountof *P/ stan itt90 2x months years = Nocaking, => motthing, 2 = c. Stress Testing Elucidates the intrinsic stability of the drug substance and identify the likely degradation products Carried out under more severe conditions => efficacious dispension / discntegram, etc. G under double lock Warehouse Distribution Practices: Toxicologic Microbiologic 1. Eretainsterineseas Drug products are mainly decomposed by: Hydrolysis Prevented by reduction or elimination of water from the preparation preventby 0 b. Oxidation 1835a -> Prevented by antioxidants (ex: Vit. C & E) P c. Photolysis Prevented by using light-resistant containers H a. revelingone - => 2. B. IDENTIFICATION TEST To confirm the identity of a chemical substance protocific decomposition in store amber bottles 2. Shelf-life (t90) Period of time during which a product is expected to remain within specification Estimated using the Arrhenius equation => First in-First out (FIFO) In this technique, the rule is to move first the stocked products or the products that are brought first First expiry-first out (FEFO) In this technique, the products whose expiration dates are approaching are moved out of the warehouse first. Methods: 1. 2 1 Chemical Methods Color reactions -starch +12 in KIT- blue neat / Precipitation -Chloride + AgNOs TS -> white pot⑨ Evolution of gas Ammonium NGOHTS + +-pungentodorcomes - 2. NMR spectroscopy 3. Expiration Date Time or date prior to which a product is expected to remain stable and after which it must not be used Calculated using this formula after ED=> 25 Hot and dry 30 2 35 5% Hot and humid 30 2 65 5% 30 2 Types of stability Studies minimum a. Long-term Studies Conducted under normal conditions Testing period: 0, 3, 6, 9, o 12, 15, 18, 24, 36 ↑ follows zero Module 6 Humidity 45 5% Mediterranean/ Subtropical Hot and very humid 2 kinetics (30=(/75:5% RH) Quality Assurance & Quality Control 60 75 mass spectrometry To determine the amount of API or biologic activity 1. Chemical Assay To Purity Titrimetry Instrumental methods 2. Biologic Assay Animal Assay Microbial Assay canbemarketed Temperature 21 2 · Spectrometry Methods: unstable producti s Type of Climate Temperate paper. UV/ Vis. · C. ASSAY 4. Stability Studies Used to estimate the shelf-life of a drug product Evaluated over time in the same container-closure system in which the drug product is marketed Based on ASEAN Guidelines on Stability Studies Climatic I zone the or on Climatic Zone Zone I (Canada, Germany, Russia) Zone II (USA, Japan, Italy, France, Australia) Zone III (Iraq, Jordan) Zone IVA (UAE, Saudi Arabia) Zone IVB (Philippines and other Asian countries) Instrumental Methods Spectroscopy Chromatography 5% 5% - Animal Assay Drug Digitalis - Animal used Pigeon Pigeotalis Tubocurarine (t) head drop Insulin Glucagon Corticoprin Vit Cod Liver Oil A8D wasid white white Barium Chloride TS -> b. Method II: Azeotropic Distillation Based on distillation of water Toluene or Xylene (alternative) Used a toluene-moisture apparatus -> -> -> -> meigh c. Method III: Gravimetry welilh-> duy Based on loss on drying at 110-120°C for inorganic materials and 105°C for organic materials => E. PHYSICAL TESTS III. PACKAGING MATERIAL QUALITY CONTROL (PMQC) Can be used for Identification and determination of concentration of a component May also be used to determine the presence of impurities unitless plample/PH20 ⑨ 1. Specific Gravity + 1.gmL closestto 1 @ A. TESTS FOR GLASS 1. Hydrolytic Resistance (leaching) Old USP tests y'c The ratio of the density of a substance to that of a reference substance 25°C &official non-official Measured using a pycnometer or Mohr-Westphal balance Alcohol: measured using a hydrometer at 15.56°C 160F II Treat soda-lime glass III Soda-lime glass a. 3. Optical Rotation Measure of its ability to rotate an incident plane of polarized CCWCL) light CWCR) May be dextrorotatory or levorotatory Measured using a polarimeter Glass Type Type I Type III b. Parts of Solvent Required for 1 Part of Solute 10,000 Very Soluble Freely Soluble Soluble Sparingly Soluble Slightly Soluble Very Slightly Soluble Insoluble 5. Boling Point Melting Point Indicates presence of impurities (testtube, thermometer) Boiling point apparatus 6. Loss on Drying Determines the amount of volatile matter driven off after not final nt x/00 drying &Lob inial initial wif water is the volative Official Methods: only constituents a. Method I: Karl-Fischer Titrimetry Based on the reaction of water and KFR Module 6 Quality Assurance & Quality Control Powdered Glass Surface Glass aFree filtrate - ↑ eicid Water Attack Test n Sample: infer surface of Type II glass autoclave, promote Method: Acid-base titration with 0.2N H2SO4 VS using alkali reaching, methyl red as indicator to -> Filter H20 titrates Filtrates Surface Glass Test Sample: inner surface of Type I and III glass Method: Acid-base titration with 0.1N HCl VS using methyl red as indicator - c. New USP tests Type I, II, III Test Glass Grains Test I, II, III Surface Glass Test I, II Surface Etching Test - see loseanchot ⑧ will Use Distinguishes Type I from Types II and III Distinguishes Types I and II from Type III Distinguishes Type I from Type II - · Water Attack Limit (mL of 0.02N H2SO4) 1.0 preventleaching... acid consume 8.5 no protectant:↑alkalileaching, = 7. Water determination Type of Test Powdered Glass Surface Glass Powdered Glass Test autoclave Sample: crushed Type I and Type III glass &> ↓ Method: Acid-base titration with 0.2N H2SO4 VS using methyl red as indicator friturate 4. Solubility Descriptive Term Use Buffered or nonbuffered aqueous parenteral Acidic and neutral aqueous parenteral Non-aqueous or dry solid parenteral To consume a acid= sulfur T consume dioxide lavid:Boric oxide 2. Light Transmission For colored glass containers Limit: NMT 10% at any wavelength in the range of 290 to 450nm lightresistant Amber color most Page 3 of 8 RJAV 2022 leach towards ageous 3. Arsenic -can easy For Type I or Type II glass container Method: same with limit test for As -> silver Limit: NMT 0.1 per g sole. Dietwaldithiocarbamate B. TESTS FOR PLASTIC 1. Biological Reactivity Tests In Vivo Test Systemic Injection Test Intra - Intracutaneous Test dermal Eye Irritation Test Implantation Test # formation of tumors C) ↑ Sample Parenteral containers Parenteral containers Ophthalmic containers Material in direct contact with tissues death n o tsafe Animal Albino mice Albino rabbits Albino rabbits Rabbits 2. Biological Reactivity Tests In Vitro inside test Test Agar Diffusion Test Direct Contact Test Elution Test tube, Cleaning sieves: Air jet Liquid stream Gentle brushing Endpoint for Sieving: Weight difference of