QC Lecture 1.pdf

# Quality Control of Pharmaceuticals ## Zagazig University - Faculty of pharmacy - Analytical Chemistry Department ## Departments in Pharmaceutical Factory | Department | Description | |...

# Quality Control of Pharmaceuticals ## Zagazig University - Faculty of pharmacy - Analytical Chemistry Department ## Departments in Pharmaceutical Factory | Department | Description | | ------------------------ | ----------------------------------------------------------------------------------------------------------- | | Production | Responsible for producing the drug product. | | Supply Chain (Warehouse) | Responsible for procuring raw materials and storing finished goods. | | Regulatory Affairs (RA) | Responsible for ensuring that the drug product meets all regulatory requirements. | | Development (R&D) | Responsible for researching and developing new drug products. | | Quality Control (QC) | Responsible for ensuring that the drug product meets quality standards. Includes Chemical and Microbiological Labs | | Quality assurance(QA) | Responsible for ensuring that the quality management system is effective. | ## Chapter 1: Introduction to Quality Control - The International Organization for Standardization (ISO) is an international standard-setting organization composed of representatives from various **national standards bodies**. There is only one member per country that represents ISO in its country. - Founded in 1947, ISO has published more than 19,500 **international standards** covering all aspects of technology and business. ## Why adopt ISO standards? - To eliminate country to country differences (international marketing) - To eliminate terminology confusion - To increase quality awareness - To give customers the assurance of the quality of products provided by any organization. ## ISO Standards - **ISO 9000 series:** provide a framework for quality management and quality assurance. - **ISO 14000 series:** provide a similar framework for environmental management. ## What does ISO 9001 certification mean? - **ISO 9001** is the most popular standard in the ISO 9000 series and commonly used standard in any organization. - It sets out the criteria for an organization’s **Quality Management System**. - Certification means that the quality management system has met the requirements designated under ISO 9001. This means that the **quality of products and services** are maintained and meet the customer requirements. ## Quality ### Definitions - Quality is a measure of excellence or a state of being free from defects, deficiencies, and significant variations. - The quality of pharmaceutical products is essential to assure the maximum level of **customer’s (patient)** satisfaction. ### According to ISO: - Quality is the degree to which a set of **inherent characteristics** fulfils requirements. - **Degree:** a level which a product or service satisfies, i.e., excellent, good, or poor quality. - **Inherent characteristics:** Features that are a part of the product and are responsible for achieving satisfaction. - **Requirements:** needs of the **customer, organization, and regulatory bodies**. ### Quality Components | Area | Quality Components | | --------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Airlines | On-time, comfortable, low-cost service. | | Healthcare | Correct diagnosis, minimum wait time, low cost. | | Food services | Good taste, free from contamination, fast delivery, good environment. | | Pharmaceutical Quality | **Safety, potency, efficacy, stability, and patient acceptability.** | ## Quality Control in Pharmaceutical Industry - **What to achieve?** The most important criteria for the qualities of any pharmaceutical dosage form are **safety, potency, efficacy, stability, and patient acceptability.** - **When to achieve?** The total qualities are ensured by the success of two vital processes termed: **in-process quality control and finished product quality control tests.** - **Why to achieve?** To manufacture and deliver **zero-defect** products to the patients. ### Poor quality medicines: - Waste money, cause health hazards, and contain toxic substances. - Cause harm to **patients, health care workers, policy makers, regulators, and manufacturers.** ## Concepts of Drug Quality Control ### Old concept - **Inspection:** Separating good products from bad ones with no feedback to the production process. - **Revealing Control:** Some examples of poor quality products include: - **1935:** Elixir Sulfanilamide made with poisonous solvent (Contamination of Glycerine contaminated with Di ethylene glycol) caused 107 deaths. - **1941:** Nearly 300 people were killed or injured by sulfathiazole tablets tainted with the sedative, phenobarbital. ### Modern Concept - **Building in Quality:** Concerns about building in quality into the product during the production process. ### Preventive Control - Quality becomes the collective responsibility of every individual in an organization from top management to lower levels of management. ## After the Nineties - The pharmaceutical industry adopted a **broad concept of quality management** that emphasizes: - **Building in Quality** - **Maintaining Quality** - **Continuously Improving Quality** - This is being approached through the concept of **Total Quality Management (TQM)**. ## Total Quality Management (TQM) - We will study the following items: - Definitions - Principles of TQM implementation - Goals - Steps - Inspection - QA - GMP - QC ### Definitions of TQM - **Total:** The involvement and the input of everyone. - **Quality:** Fully meeting customers' needs and requirements all the time. - **Management:** The way we act, operate, control, and handle it. ### According to ISO - TQM is a **management approach** for an organization. - It is based on the **participation of all its members**. - It is centered on **quality** and aiming at long-term success through **customer satisfaction**, which benefits **all members of the organization and the society.** ### Six Cs of TQM - Commitment from employees - Control effective - Customer Focus - Cooperation among employees - Culture - Continuous Improvement ### Principles of TQM Implementation - TQM implementation should become a normal part of everyone's job. - **Control effective:** For monitoring and measuring the real performance. - **Customer Focus:** Requirement satisfaction. - **Cooperation among employees:** Application of Total Employee Involvement (TEI) principles. - **Commitment from employees:** - **Culture:** Follow a modern culture through training on a regular basis to foster positive change in culture and attitudes. - **Continuous improvement:** All policies, procedures, and activities. ## How to Implement Total Quality Management? 1. Commitment from employees 2. Quality Improvement Culture 3. Continuous Improvement in Process 4. Co-operation from employees 5. Focus on Customer Requirements 6. Effective Control shall be laid down ## The Goals of TQM The ultimate goals of TQM in the pharmaceutical industry are to assure that the **finished drug product:** - Contains the labeled amount of the active ingredients within the **accepted tolerance limits**. - Should be of the highest possible **purity (no contamination)**. - Is stable within the specified time **(shelf time)**. - Is therapeutically efficacious, i.e., **bioavailability and bioequivalence studies** have been carried out in the research and development phase. - The variation of drug levels between dosage units is **minimized**. ## Steps of TQM - **Deming Wheel or Deming Cycle or Shewhart Cycle** - **PDCA:** The continuous quality improvement cycle is an iterative 4-step problem-solving process called PDCA. - **Plan:** Establish the objectives and processes necessary to deliver results in accordance with the specifications. - **Do:** Implement the processes. - **Check (Study):** Monitor and evaluate the processes and results again to objectives and specifications and report the outcome. - **Act:** Take actions to the outcome for necessary improvement. ## Inspection of TQM - **Self inspection:** Should be carried out to ensure that TQM concepts and practices are followed. - **Governmental regulatory authorities:** Should periodically inspect the drug industry. - In Egypt, **NODCAR**(The National Organization for Drug Control and Research). - In USA, **FDA**(Food and Drug Administration). ## Quality Assurance (QA) - **Prevention of defects** - QA is the sum total of **planned and systematic actions** necessary to obtain confidence that the required quality of medical products is satisfactory for their intended use. - QA is a way of - **Preventing mistakes and defects** in manufactured products. - **Avoiding problems** when delivering products or services to customers. ### Key aspects of QA - **Process Development:** Designing processes that consistently yield products meeting quality standards. - **Documentation:** Creating and maintaining comprehensive records of procedures, specifications, and standards. - **Training:** Ensuring that all personnel are properly trained to adhere to quality standards. - **Audits and Reviews:** Regularly auditing processes and reviewing performance to identify areas for improvement. ## G(X)P - **Good…Practices:** The term of GxP is a generalization of quality guidelines for specific practice. | G(X)P | Description | | --------- | ----------------------------------------------------------------------------------------- | | GMP | Good manufacturing Practices | | GLP | Good Laboratory Practices | | GAP | Good Analytical Practices | | GSP | Good storage Practices | | GDP | Good documentation Practices | | GCP | Good clinical Practices | | GRP | Good review Practices | ## Good Manufacturing Practices (GMP) - GMP regulations is the part of QA that ensures that products are **consistently produced and controlled** to the quality standards. - It is also sometimes referred to as “**cGMP**", where C stands for "**current**" to remind manufacturers that they must employ technologies and systems which are **up-to-date** to comply with the regulation. ### The basic principle of GMP - **Quality must be built into a product** during all stages of the manufacturing process, **not just tested into the finished product.** - **All manufacturing processes are clearly defined and systematically reviewed.** ### Examples - GMP in solid dosage forms. - GMP in semisolid dosage forms. - GMP in liquid orals. - GMP in Parenterals Production. - GMP in Biotechnological products. - GMP in Nutraceuticals & cosmeceuticals. ### GMP guidelines for pharmaceutical industry - Each country has a particular agency or organization that enforces GMP regulations. | Regulatory Authority | Description | | -------------------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------- | | TGA | Therapeutic Goods Administration - Australia | | EMA | European Medicines Agency - EU | | FDA | U.S. Food and Drug Administration - USA | | WHO | World Health Organization | | PICS | Pharmaceutical Inspection Co-operation Scheme - International | ### The GMP are: - A set of regulations that contain **minimum requirements for the methods, facilities, and controls used** in manufacturing, processing, and packing of drug product, medical devices, certain types of food, and blood. - **Proactive Steps:** These regulations are required to take proactive steps to ensure that their products are safe, pure and effective. ### The basic requirements (key aspects) of GMP: | Aspect | Description | | ------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Premises | Suitable premises with sufficient space, suitable location, suitable equipment and services. | | People | Well-trained operators, system for complaints and recalls. | | Processes | Clear, written, and approved instructions and procedures. | | Products | Correct handling of starting/packaging materials, correct materials, containers, and labels. | ## Standard Operating Procedure (SOP) - **Authorized documents in GMP:** One of the important documents in GMP is an authorized written procedure that describes the step-by-step instructions for performing operations not necessarily specific to a given product or material. - **Detailed procedure information:** Provides information on equipment operation, maintenance, and cleaning, validation of processes, equipment, and systems, cleaning of premises, environmental control, sampling, and inspection. ## What Would Happen If a Pharmaceutical Product Is Produced Without Following GMP Guidelines? - Production without GMP guidelines would result in a **high risk of producing defective and unsafe** pharmaceutical products. ## Why GMP Is Important - **Minimize risks:** GMP is designed to minimize risks involved in the production of pharmaceutical products that cannot be eliminated through testing of the final product alone. - **Decreases the risks of:** - Poor quality raw materials. - Contamination of products (microbial, particulate or other) or cross contamination. - Poor formulation practices. - Insufficient or excess active ingredient. - Incorrect labels on containers. ## Quality Control (QC) - **Detection of defects:** QC is that part of GMP which is concerned with: - **Sampling:** Starting & packaging materials, finished, intermediates, and bulk products. - **Testing:** - **Specification:** Obtaining products or used materials - **Documentation:** Specifying sampling & testing procedures, analytical reports. - **Release procedures:** Outlining the responsibility and protocols for the release of the product to the market. ### QC Importance - **Manufacturer should have a QC department.** - **Headed by a qualified professional:** QC should be headed by an appropriately qualified and experienced person. - **Independent from production:** QC should be independent from production and other departments. - **Adherence to GLP:** All the quality control activities are performed in adherence to the GLP (Good Laboratory Practices). ## QC Role - **Analytical tests and assessment of operations:** QC is not only the analytical tests of the finished products, but also the assessment of all operations beginning from the receipt of raw materials and continuing through the production and packaging operations. - **Production and quality control functions should be independent of each other.** ## Responsibilities of QC in Pharmaceutical Industry ### What to analyze? - Raw, intermediate and packaging materials analysis (Ch. 4 & 8) - Finished product analysis (Ch. 4 & 8) - Environment monitoring. (Ch. 6) - Conducting stability studies. (Ch. 6) ### How to analyze? - Carrying out sampling and testing of materials or products (Ch. 2) - Analytical method development and validation. (Ch. 5) ### What relation to consumer? - **Evaluation of complaint samples:** Evaluation of complaint samples related to the quality of the product. - **Sufficient samples:** Sufficient samples of starting materials and products must be retained to permit future examination. - **To ensure quality:** To ensure that no materials or products will be released for sale or supply, until their quality have been evaluated and judged to be satisfactory. ## Quality Relationship - QC is a part of GMP, and GMP is a part of QA. ## Relation Between GMP, QC, QA | Aspect | GMP | QC | QA | | ---------- | ---------------- | ------------------ | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Definition | That part of QA. | That part of GMP. | The sum total of planned and systematic actions necessary to obtain confidence that the required quality of medicinal products is satisfactory for their intended use. | | Aim | Ensuring products are manufactured to a quality appropriate to their intended use. | Ensuring that the necessary & relevant tests are performed and the product is released only after ascertaining its quality. | | Focus | Quality assurance | Quality control | Ensuring that products will be of the quality required for their intended use. | | Processes | Managing and planning for quality | Verifying the quality of the output | | ### TQM - Total Quality Management - **Management approach:** TQM is a management approach for an organization that focuses on quality through ongoing refinements in response to continuous feedback.