Quality Control 1 Lecture Notes PDF

Dr. Nisreen Farouk Professor of Analytical Chemistry, EDA 1 Lecture 2 2 Learning outcomes By the end of the lecture, students should be able to demonstrate knowledge of: Develop analytical control lab Drug standards Monograph of pharmacopoeial drugs De...

Dr. Nisreen Farouk Professor of Analytical Chemistry, EDA 1 Lecture 2 2 Learning outcomes By the end of the lecture, students should be able to demonstrate knowledge of: Develop analytical control lab Drug standards Monograph of pharmacopoeial drugs Development of substandard drugs 3 Development of analytical control laboratory 1- Accommodation 2. Laboratory furniture and fixture 3. Chemicals and glassware 4. Books and journals 5. Staffing and manpower development 6. Ancillary staff 7. Laboratory organization and administration 4 Development of analytical control laboratory 1- Accommodation: It is desirable to have at least 500 m2 to house the chemical and physicochemical testing as follows: 1. Rooms for chief analyst and consultant 2. General office room and registry. 3. Documentation and sample room. 4. Stores (chemicals, glassware, spares and consumable of instruments) 5. Library 6. One general laboratory for routine chemical and preparative work for instrumental analysis. 7. Instrument rooms (for housing the listed instruments). 8. TLC and fume hood. 9. Distillation, washing and drying units, ovens, water baths, etc. 10. Balance room and other ancillary equipments, e.g. vacuum oven, disintegration and dissolution units, centrifuge, etc. 5 Development of analytical control laboratory 2. Laboratory furniture and fixture The indicated space of about 500 m2 will need at least 100 meters length in units of 2 meters of laboratory benches fitted with cupboards. Some of these benches should include laboratory sinks. In office, furniture will be needed for all members of staff. When ordering equipment it should be kept in mind that very often the middle range model of equipment of a company could serve the purpose. In order not to delay the establishment of a laboratory, the analytical work could start with minimum requirements, and the process of procurement could be phased for three years accordingly, the requirements for the equipment are listed in three parts: First stage: List of equipments to be obtained before analysts assures their duties. Second stage: List of equipments to be ordered in the first year. Third stage: List of equipments to be ordered in the second year. In the third year full utilization of all equipments should be achieved. By this time, two UV-VIS spectrophotometers will be in the laboratory, one of which is being used for heavy duty work. 6 Development of analytical control laboratory 3. Chemicals and glassware Immediately on assumption of duties by the consultant and/or chief analyst, a list of immediate requirements should be ordered depending on the items selected for testing. 7 Development of analytical control laboratory 4. Books and journals Required books and journals are listed and should be ordered according to the laboratory work. 8 Development of analytical control laboratory 5. Staffing and manpower development: The qualities required of a successful analyst are: 1. A good basic academic background. 2. A critical and inquiring mind. 3. A careful attitude to presentation of data 4. An interest to further develop his knowledge and technical skills A pharmaceutical qualification provides a good general academic background on which to build. All the analysts and technicians should receive in-service training during their work with consultant and chief analyst. In addition, some members of staff recruited initially could be sent abroad to gain further experience and qualifications. M.Sc. courses in analytical chemistry/pharmaceutical analysis offered by some universities will be helpful. 9 Development of analytical control laboratory 6. Ancillary staff An efficient system of documentation is essential. Competent secretarial staff is needed for maintenance of such documentation and smooth administrative functioning of the laboratory. 10 Development of analytical control laboratory 7. Laboratory organization and administration In order that the work of laboratory may proceed smoothly and efficiently it is necessary that there be instructions governing both its internal administration and its relations with external bodies. All staff members should provided with a copy of instructions. All persons working in the laboratory should have a clear job description. 11 Problems in QC lab. development The most common problems and constraints usually faced in developing a drug quality control laboratory are: 1. Maintenance and use of equipment. 2. Manpower constraints. 3. Non-availability of reference substances. 4. Unproductive use of laboratories 5. Bad reports. 12  Drug Standards Drug standards are established criteria, guidelines, and specifications set by regulatory authorities or pharmacopeial bodies used to ensure the quality, safety, efficacy, and identity of pharmaceutical products. Standards of quality for drugs may be defined in terms of chemical and physical characteristics and in some cases by microbiological and/or pharmacological characteristics. These standards serve as a reference for the development, manufacturing, testing, and regulation of drugs Standards cover various dosage forms of drugs, such as tablets, capsules, injections, creams, and more. Drug standards are not static; they are periodically updated and revised to reflect advances in science, technology, and changes in regulatory requirements. 13  Drug Standards Importance of Drug Standards Ensuring Public Safety: Drug standards protect public health by ensuring that drugs meet minimum safety requirements. Without proper standards, patients could be exposed to substandard or harmful products. Maintaining Drug Efficacy: By ensuring that the correct amount of active ingredient is present in each dosage, drug standards help maintain the intended therapeutic effect. Regulatory Compliance: Drug standards are a cornerstone of regulatory frameworks. Compliance with these standards is necessary for the approval of new drugs and the continued sale of existing ones. Quality Control: Drug standards ensure consistent quality during manufacturing, reducing variability between batches and maintaining product integrity over time. Consumer Trust: By adhering to established drug standards, pharmaceutical companies build consumer trust by delivering reliable and effective medications. 14  Drug Standards Types of Drug Standards 1. Pharmacopeial Standards These are the official standards set by national and international pharmacopeias, such as the United States Pharmacopeia (USP), British Pharmacopoeia (BP), and European Pharmacopoeia (EP). Officially recognized by regulatory authorities. 2. Manufacturer/In-House Standards These standards are developed internally by pharmaceutical companies for their products, especially during the early stages of development or when no official pharmacopeial standard exists. Must be validated against pharmacopeial or regulatory standards for later stages of development. 3. International Standards International bodies, such as the World Health Organization (WHO), set global standards to ensure the quality of essential medicines in all regions of the world. Help ensure that drugs used in different countries 15 meet similar quality criteria.  Drug Standards 4. Regulatory Standards These standards are imposed by national regulatory bodies, such as the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and Central Drugs Standard Control Organization (CDSCO) in India. They Focus on ensuring that drugs meet legal requirements for market authorization. Cover all aspects of drug development, from preclinical testing to post-marketing surveillance. 16  Drug Standards Pharmacopeia Pharmacopoeia refers to a comprehensive guide of standards, procedures, and specifications that are set by regulatory authorities to ensure the quality, safety, and efficacy of drugs. It contains information about the drug properties, formulation, analytic composition, main chemical properties used in identification, requirements and tests for strength and purity of drugs and their dosage forms and other related information. Pharmacopoeia is used as a reference book by pharmacists, and drug manufacturers to ensure the quality and consistency of drugs. Inclusion of a substance in a pharmacopoeia does not indicate that it is either safe or effective for the treatment of any disease. 17  Drug Standards Formulary : Is a list of drugs that are approved by a healthcare organization or institution for use in patient care. A formulary is usually created by a pharmacy and therapeutics committee (P&T) that includes physicians, pharmacists, and other healthcare professionals who review clinical evidence to determine which drugs should be included. The formulary includes information about the drugs, their dosage forms, and indications for use. The drugs listed in the formulary are often selected based on their safety, efficacy, and cost- effectiveness. 18  Drug Standards Physicians and pharmacists refer to the formulary when prescribing drugs to patients in hospitals or outpatient clinics. In summary, pharmacopoeia is a comprehensive guide to drug quality and standards, while the formulary is a list of approved drugs for use in patient care. 19  Drug Standards Key Differences Between Pharmacopeia and Formulary Parameter Pharmacopoeia Formulary Pharmacopoeia refers to a comprehensive guide Is a list of drugs that are approved by a healthcare of standards, procedures, and specifications that organization or institution for use in patient care Definition are set by regulatory authorities to ensure the quality, safety, and efficacy of drugs Detailed monographs on drugs, including Contains drug names, indications, dosages, chemical structure, physical properties, formulations, therapeutic alternatives, and may Content analytical methods, quality standards, and include prescribing guidelines or restrictions testing procedures. Focuses on drug identity, purity, strength, and Focuses on the clinical use, safety, and cost- Scope other quality parameters. effectiveness of drugs in a healthcare system or institution. Legally recognized by government bodies and Typically developed by hospitals, health insurance Regulatory regulatory authorities for drug manufacturing companies, or national/regional health authorities Authority and quality assurance to guide drug use in clinical practice United States Pharmacopeia (USP), European National Formulary (NF), British National Examples Pharmacopoeia (EP), British Pharmacopoeia Formulary (BNF), hospital formularies, insurance (BP). company formularies. Primarily used by pharmaceutical Used by healthcare professionals (physicians, manufacturers, regulatory authorities, and pharmacists), hospitals, and insurance providers Users analytical chemists for quality control and drug to determine which drugs to prescribe and use 20 approval  Drug Standards The United States Pharmacopeia (USP) Is a pharmacopeia (compendium of drug information) for the United States published annually by the over 200-year-old. United States Pharmacopeial Convention (usually also called the USP), a nonprofit organization that owns the trademark and owns the copyright on the pharmacopeia itself. The USP is published in a combined volume with the National Formulary (a formulary) as the USP-NF. It is recognized by the U.S. FDA for drug approval and quality control. 21  Drug Standards Drugs subject to USP standards include both human drugs (prescription, over the counter (OTC), or otherwise) and animal drugs. USP-NF standards also have a role in US federal law. USP also sets standards for dietary supplements and food ingredients (as part of the Food Chemicals Codex). 22 23  Drug Standards The British Pharmacopoeia (BP) Is the national pharmacopeia of the UK. It is an annually published collection of quality standards for medicinal substances in the UK, which is used by individuals and organizations involved in pharmaceutical research, development, manufacture and testing. Pharmacopeial standards are publicly available and legally enforceable standards of quality for medicinal products and their constituents. The British Pharmacopoeia is an important statutory component in the control of medicines, recognized by the UK regulatory authorities [UK's Medicines and Healthcare products Regulatory Agency (MHRA)]. 24 25  Drug Standards The European Pharmacopoeia (Ph. Eur.) Is a major regional Pharmacopoeia which provides common quality standards throughout the pharmaceutical industry in Europe to control the quality of medicines, and the substances used to manufacture them. It is a published collection of monographs which describe both the individual and general quality standards for ingredients, dosage forms, and methods of analysis for medicines. These standards apply to medicines for both human and veterinary use. Recognized by the European Medicines Agency (EMA). 26 27  Drug Standards Drug monograph Is a publications within pharmacopeias and other reference documents that specifies for a drug (or class of a related drugs) its identity, strength of the ingredients may contain, purity, performance, They also describe the tests to validate that a medicine and its ingredients meet the acceptance criteria. The monograph may contain important information concerning interactions with other drugs, the contraindication and limitations for which it may be offered, direction for use, warnings. Monographs articulate the quality expectations for a medicine. 28  Drug Standards Key components of drug monograph Description-Chemical name, physical characters, solubility and calarity of solution Identity - Tests to identify that a particular substance is the medicine that it claims to be. Strength - Testing methods and acceptable ranges for the potency of a medicine, as reflected in FDA's approvals. For example, this indicates the amount of API in a medicine. Purity - Information on impurities that may be present in a medicine and the amounts of these that are permitted, along with testing methods to identify and measure them. An impurity is any component in the API or finished dosage form which is not the desired product or other formulation components. Levels that exceed may present patient safety concerns. Performance - Laboratory tests to predict and demonstrate how a medicine will be released as it enters the human body. Packaging and Labeling - Standards dictate requirements for drug packaging, labeling, and storage conditions. This includes information on dosage instructions, expiration dates, and proper handling. 29  The monograph of aciclovir 30 Many drugs fail to conform to the required standards due to: 1. Inadequate product development has led to a production of a drug which although satisfactory at the time of manufacture, is unstable. 2. Properly developed drug with good stability subjected to improper storage conditions, has been exposed to excessive humidity or heat. 3. Defective packaging may result in deterioration of the drug. 4. A drug may fail to conform to required standards through careless manufacturers and neglect of a code of Good Manufactory Practices (GMP) such as that published by the Word Health Organization (WHO). 5. A drug may be produced by a licensed manufacturer, deliberately deficient in active ingredients so as to increase the profit margin. 6. A drug may contain the correct amount of active ingredient, but this may not be released on administration (not bioavailable). 7. A drug may be produced on unlicensed premises, i.e. either without or seriously deficient in the stated active ingredient. 31 32  Reference Standards A reference standard is a highly characterized material with known properties, such as purity and identity, used for comparison during analytical tests to verify the identity, strength, purity, and quality of pharmaceutical products. Importance of Reference Standards: * Assay Accuracy: Reference standards provide a basis for accurate quantification of substances in drug formulations. * Quality Control: They are essential in ensuring the consistent quality of products during manufacturing and before release. * Method Validation: Reference standards are used to validate analytical methods, ensuring they are fit for purpose. * Regulatory Compliance: Compliance with pharmacopeial standards is a legal requirement for regulatory submissions, ensuring that products meet the necessary quality standards. * Instrument Calibration: Calibration of analytical instruments such as High-Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC) requires reference standards for accurate results.. 33  Reference Standard Types of Reference Standards 1 Primary reference standards 2 Secondary reference standards 3 Working standards 4 Pharmacopeial standards 5 In- House standards 34  Reference Standard 1- Primary Reference Standard A primary reference standards are substances of the highest purity, typically ≥99.9%, that have been thoroughly characterized using precise, validated methods. Used in the initial stages of method validation. Frequently used to calibrate secondary standards. Used for calibration of instruments and to validate other standards. 2- Secondary Reference Standard Secondary reference standards are substances standardized against a primary reference standard. Lower purity than primary standards, but still accurate. Must be periodically validated against primary standards to ensure accuracy. Cost-effective for routine use. Used in routine quality control testing. Common in the pharmaceutical industry to assess the identity, potency, and purity of drug products. 35  Reference Standard 3- Working Standard Working standards are derived from secondary reference standards and used for day-to-day routine testing in quality control laboratories. Derived from secondary standards. Cost-effective for frequent, routine use. Less rigorously characterized than primary or secondary standards. Used daily in QC tests to monitor the consistency of manufacturing processes. 36  Reference Standard 4- Pharmacopeial Standard Pharmacopeial reference standards are official standards provided by recognized pharmacopeias like the United States Pharmacopeia (USP), European Pharmacopoeia (EP), or British Pharmacopoeia (BP). Legally required for pharmaceutical testing and quality control. Officially accepted in regulatory submissions. Developed according to strict guidelines and published in pharmacopeial monographs. Used for regulatory compliance in drug testing. Required in testing to ensure that the pharmaceutical product meets official standards for identity, purity, and potency. 37  Reference Standard 5- In-House standards In-house standards are reference standards prepared by a manufacturer or laboratory for internal use, especially during the early stages of drug development when official standards may not yet be available. Must be validated and traceable to recognized standards for later use. Often used in early R&D phases or when testing new formulations. Serve as a temporary standard until official standards are developed or available. substance in accordance with the ICH guidelines. 38  Reference Standard Key Differences Between the Types of Reference Standards Type Source Purity Usage Purpose Primary Standards Regulatory bodies Highest (≥99.9%) Method Calibration and (USP, EP, etc.) validation, validation instrument benchmark calibration Secondary Labs, companies, Standardized Routine QC Regular use for Standards or in-house against primary testing comparison testing Working Standards Derived from Lower than Routine daily Cost-effective secondary secondary analysis testing in QC standards standards Pharmacopeial Official Regulatory Compliance with Standards pharmacopeias Pharmacopeial submissions, official regulations (USP, BP, EP) requirement level product release Regulatory s In-House Prepared by the Varies Early-stage Temporary Standards manufacturer research and standard for R&D testing 39