terminowPs “standards for the * of Electronic Sta pest QISERIES GUIDELINES 3.6.4 Q4 GUIDELINE Is FOR STABILITY | QIA (R2k:Stability Testing of New Drug Substances and Products: dence on how the quality of a drug ili ing i ide evi ce of stability testing is to provi h Tree or drug pr jes with time under the influence of a variety of si oduct vari environmental factors such as temperature, humidity, and light, and to establish a re-test period forthe drug substance or shelf life for the drug product. .. (Q1B:Phato stability Testing of New Drug Substances and Products: Give guidance on the basic testing protocol required to evaluate the light sensitivity and stability of new drugs and products. QIC:Stability Testing for New Dosage Forms: Gives guidelines for new formulations of already approved medicines and defines the circumstances under which reduced stability data can be accepted. + O1D:Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products. QIE:Evaluation of Stability Data: This guideline addresses the evaluation of stability data that should be submitted in registration applications for new ‘molecular entities and associated drug products. The guideline provides Recommendations on establishing shelf lives for drug substances and drug products intended for storage at or below “room temperature”. wo Stability Data Package for Registration Applications in Climatic Zones IMI and Describes harmonized global stability testing requirements in order to facilitate access to medicines by reducing the number of different storage conditions. WHO conducted ‘ survey amongst their member states to find consensus on 30°C/65% RH as the long- ferm storage conditions for hot-dry and hot-humid regions. B62 Q2 GUIDELINE IS FOR ANALYTICAL VALIDATION Q2 (Rt): Validation of Analytical Procedures {Text and Methodology! The objecti a , Paka ae of validation of an analytical procedure is to demonstrate that it is suitable meee purpose, Gives validation parameters needed for a variety of analytical 5, it also discusses the characteristics that must be considered during the validation of the analytical procedures. Procedures to be validated are: ° Identification tests ° Quanti 7 ettalte tests for impurities content ‘ests for the control of impurities46 EE 0 Lees PHARMACEUTICAW QUALITY, ASSURANCE © Quantitative tests of the active moiety in samples of drug substance or drug product or other selected components in the drug product ) Typical validation characteristics of analytical procedures Accuracy, Precision (Repeatability, Intermediate Precision), Specificity, Detection Lintt of Quantification, Linearity, Range. 3.6.3 Q3 GUIDELINE IS FOR IMPURITIES * 3A (R2): Impurities in New Drug Substances The guideline addresses the chemistry and safety aspects of impurities, including the Usting of impurities, threshold limit, identification ant quantification, Classification of Impurities: are of 3 types: 1. Organic impurities (process- and drug-related) 2. Inorganic impurities 3. Residual solvents * Q3B(R2): Impurities in New Drug Products * QSC(R4): Impurities: Guideline for Residual Solvents 1. Benzene- 2ppm 2. Carbon tetrachloride - 4 ppm 3. Dichloromethane - 5 Ppm 4. Dichloroethane - 8 ppm 5. Acetonitrile - 410 ppm 6. Chloroform -60 ppm. 7. Chlorobenzene -360 ppm 8. Formamide, Hexane -299 Ppm 9. Toulene - 890 ppm 10. Pyridine - 200 pm 11. Nitromethane - 50 ppm 12, Methanol - 3000 ppm “MMAcopoeial Texts for Use in the ICH This document descri Q4B Expert Workin cea “eweyn the evaluation and recommendation given by the it for selecti " Di Tecognition by *eBulatory authorities for use, interchanges texts to facilitate their 3.6.5 06 GupeLine IS For in the ICH regions. * ann; Vire of Human or } © viral safety ! | aN or animal origin (ie | cerned with testi i Bete deny from cell Tine fof ham, th \ avian, Ansect) nes ofoe se = The obj ive is to provide a general framework for virus testing experiments for the evaluation of virus clearance and the design of viral tests and clearance evaluation studies. « Three principal, complementary approaches have evolved to control the potential viral contamination of biotechnology products: a) Selecting and testing cell lines and other raw materials, including media components, for the absence of undesirable viruses which may be infectious and/or pathogenic for humans. b) Testing the capacity of the processes to clear infectious viruses. <) Testing the product at appropriate steps for absence of Contaminating infectious viruses. ¢ Q5B: Quality of Biotechnological Products : Analysis of the Expression Construct in Cell Used for Production of rDNA Derived Protein Products This document presents guidance regarding the characterization of the expression construct for the production of recombinant DNA protein products in eukaryotic and prokaryotic cells. Expression construct should be analyzed using nucleic acid techniques. + QS5C: Quality of Biotechnological Products: Stability Testing of Biotechnological/ Biological Products ‘+ QSD: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products « The objective of this guideline is to provide broad guidance on appropriate standards for cell substrates. * QSE: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process «The objective of this document is to provide principles for assessing the comparability of biotechnological/ biological products before and after changes are made in the manufacturing process for the drug substance or drug product. ¢ Therefore, this guideline is intended to assist in the collection of relevant technical information which serves as evidence that the manufacturing process changes will not have an adverse impact on the quality, safety and efficacy of the drug product. 3.6.6 96 GUIDELINE IS FOR SPECIFICATION FOR NEW DRUG SUBSTANCES AND PRODUCTS : 64: Specifications : Test Procedures and Acceptance Criteria for New Drug Substances lew Drug Products : Chemical Substances * The main objective of this guideline is to establish a single set of global specifications ‘Sr new drug substances and new drug products. A specification is defined as a list of tests, references to analytical procedures, and ‘PPtopriate acceptance criteria, which are numerical limits, ranges. ee 5 :Misa 48 eM c,, those tests, procedures, and acceptance «This guideline adresses specifications, ee rag substance and sriteria which play a major role in assuring t new drug product during shelf life 4+ Q6B: Specifications : Test Procedures Biological Products © This document provides guida and polypeptides which are cultures. ; © A valid biological assay to measure the biol manufacturer. 3.6.7 Q7 GUIDELINE IS FOR GOOD MANUFACTURING PRACTICE GUIDE FOR ACTIVE PHARMACEUTICAL INGREDIENTS i i is guideline i in the quality of the active Th objective of this guideline is that to maintain thé Q pharmaceutical ingredients, Personnel, Buildings and Facilities, Process equipment, Documentation and Records. 3.6.8 Q8 GUIDELINE IS FOR PHARMACEUTICAL DEVELOPMENT * This guideline is intended to provide guidance on the contents of Pharmaceutical Development of drug products. The aim of pharmaceutical development is to design a quality product and its manufacturing process to consistently deliver the intended performance of the product. The Pharmaceutical Development section also describes the type of dosage form and the formulation that are suitable for the intended use. Q8 gives information about Drug Substance, Excipients, and Container Closure System 3.6.9 Q9 GUIDELINE IS FOR QUALITY RISK MANAGEMENT "The purpose of this documentis to offer a systematic approach to quality risk management. This guideline provides principles and tools for quality risk man applied to all aspects of pharmaceutical quality including dev: distribution and the inspection and submission /review of drug substances and drug (medicinal) products Products, including the use of raw materials ‘olvents, a terials, solve © ay Is, solvents, e: and Acceptance Criteria for Biotechnological/ and setting specifications for proteins oman , ince on justifying or non-recombinant cell derived from recombinant logical activity should be provided by the agement that can be elopment, manufacturing, Processes throughout the lifecycle biological and biotechnological xcipients, packaging and labeling 3.6.10 Q10 GUIDELINE Is FoR PHARMACEUTIC This document establishes a ne n Sa new ICH tri © guideli effective quality management » Fe pha edeline deseribi fi : ; scribing el for a Pharmaceutical Quai ran 2st fF the pharmaceutical industry, reeneaeaate Comprehensive model fo : Fan effecti Intemational Standards Organization tie oemaeettical Manufacturing Practice (GMP) regulations. AL QUALITY SYSTEM Teferred to as the ality sy. quality concepts ity sy a stem is based on ” includes applicable Good