Design of Dosage Forms & QA (PHT 4107) Lectures 1 & 2 PDF

Pharm PharmDDProgram Program (2024/2025) (2023/2024) (PHT 4107) Lectures No. (1&2) GMP By...

Pharm PharmDDProgram Program (2024/2025) (2023/2024) (PHT 4107) Lectures No. (1&2) GMP By Dr. Ibrahim Salah Ibrahim 8 October 2024 www.su.edu.eg 1  Pharm PharmDDProgram Program (2024/2025) (2023/2024) Lecture’s Aim This lecture covers the study of guidelines of GMP 8 October 2024 www.su.edu.eg 2  Pharm PharmDDProgram Program (2024/2025) (2023/2024) Lecture’s Competencies 1.C1.1 Explain the principles of GMP regulations. 1.C2.1. Apply GMP in pharmaceutical plant. 4.C1.3 Demonstrate critical thinking and problem solving in different theoretical and practical situations. 4.C2.1 Develop students’ oral and written English language skills necessary to communicate in basic social and professional interactions related to their field of specialization. 8 October 2024 www.su.edu.eg 3  Pharm PharmDDProgram Program (2024/2025) (2023/2024) Lecture’s Contents Difference between QA, QC, IPQC GMP regulations in pharmaceutical companies. 8 October 2024 www.su.edu.eg 4  Pharm D Program (2023/2024) medicines and similar products are indeed 'special', in that: 1. They are potentially very hazardous to the ultimate consumer. 2. They are usually c onsumed with unquestioning trust. 3. It is more than difficult (if not impossible) to establish their suitability for consumption by testing alone. 4. The safety and effic ac y in use c an be profoundly affected by formulation and processing changes. 5 8 October 2024 www.su.edu.eg 5  Pharm D Program (2023/2024) Two important meanings of Quality: Quality 2. "Quality" means freedom from 1. "Quality" means those features of errors that require doing work again products which satisfy the customers (rework) or that result in customer needs. dissatisfaction. this meaning is oriented to sales: The purpose of higher quality is to this meaning is oriented to costs. provide greater customer satisfaction & increase income. In this meaning: "Higher quality costs more" In this meaning: Because higher quality requires "Higher quality costs less" investment. 3 8 October 2024 www.su.edu.eg 6  Pharm D Program (2023/2024) The pharmaceutical product quality parameters are put in the form of product specifications to ensure that the product fulfills the basic requirements of identity, purity, strength and bioavailability *Identity: The product must comply with the information on the product label. *Purity: the extent to which a raw material or a drug in dosage form is free from chemical, biological, or physical adulterants. *Strength/potenc y: The produc t c ontains the quantity of eac h ingredient claimed on its label, within specified limits. -This may be determined by chemical testing (strength) or by reference to a biologic al standard (potency). *Bioavailability: It is the rate and extent of absorption of a drug from a dosage form as determined by its concentration/time curve in the systemic c irc ulation, or by its exc retion in urine. 7 8 October 2024 www.su.edu.eg 7  Pharm PharmDDProgram Program (2024/2025) (2023/2024) Quality Management(QM) Quality assurance(QA) GMP Quality control(QC) 8 8 October 2024 www.su.edu.eg 8  Pharm PharmDDProgram Program (2024/2025) (2023/2024) 9 8 October 2024 www.su.edu.eg 9  Pharm D Program (2023/2024) Quality management is the act of overseeing all activities and tasks that must be accomplished to maintain a desired level of excellence 1 0 8 October 2024 www.su.edu.eg 10  Pharm D Program (2023/2024) Quality Assurance All organized arrangements made to ensure that the products will be of the quality which meets the required specifications. 1 1 8 October 2024 www.su.edu.eg 11  Pharm D Program (2023/2024) Quality Control testing samples to check their compliance with predetermined specifications. QC must be independent from production to ensure satisfactory operation of QC. QC is not confined to laboratory operations , must be involved in all decisions concerning the quality of the product. 1 2 8 October 2024 www.su.edu.eg 12  Pharm D Program (2023/2024) IPQC The IPQC is carried out to 1-minimize error 2-detect the error 3-pinpoint the responsibility to the personnel. 10 8 October 2024 www.su.edu.eg 13  Pharm PharmDDProgram Program (2024/2025) (2023/2024) Its function is to Its function is to Prevent the error Detect the error 1 1 8 October 2024 www.su.edu.eg 14  Pharm D Program (2023/2024) GMP GMP is defined as that part of quality assurance aimed at ensuring that products are manufactured to a quality appropriate to their intended use. It is an international set of regulations needed to assure quality, effectiveness and safety of the pharmaceutical products. 8 October 2024 www.su.edu.eg 15  Pharm PharmDDProgram Program (2024/2025) (2023/2024) it has a wide concept concerned with both manufacturing and quality control procedures. GMP are generally set out as guidelines rather than rules 1 3 8 October 2024 www.su.edu.eg 16  Pharm PharmDDProgram Program (2024/2025) (2023/2024) -In many parts of the world, Europe and Arab countries GMP -In USA, the abbreviation cGMP is employed to denote current GMP( reminding manufacturers that they must employ technologies and systems which are up-to-date in order to comply with the regulation. ) -There are many different versions of GMP in use around the world -The primary source for GMP statements was taken from UK. 1 4 8 October 2024 www.su.edu.eg 17  Pharm D Program (2023/2024) Why the need for GMP? 1. Drug produc ts c ould c ause serious injury or death if produc t is defective. 2. The patient can’t judge on the quality of a drug product or its identity. 3. G MP regulations appeared after major events whic h started with: A- Elixir of Death episode in 1938 in which more than 100 children died after ingesting an ethylene glycol-based sulfanilamide "elixir". B- Thalidomide Babies tragedy in 1963 [a tranquillizer for pregnant women] babies were born without arms and/or legs (malformation). C- Death following the use of large volume parentral infusions in 1978 due to septicemia. Dr Baher A. Daihom 8 October 2024 www.su.edu.eg 18  Pharm D Program (2023/2024) Historical background: 1. c G MP regulations were 1st published in 1962. They set the minimum requirements for the pharmaceutical industry (manufacture, processing, packaging, or holding of a drug)and focused on what needed to be done rather than how it should be done. 2. In March 1979, the FDA issued revised GMP regulations. These regulations were wider and it is still in effect today, including: Manufacture, packing, storage, good laboratory practice (GLP), control of large volume parentral solutions, control of sterile product, processing, inspections of raw pharmaceutical chemicals. 3. Other guidelines were prepared by various industrial organizations as: The pharmaceutical manufacturers association [PhRMA] The parentral Drug Assoc iation (PDA), The International Society of Pharmaceutical Engineering (ISPE). -In USA, Failure to comply with cGMP regulations as set in federal regulations →subjected to regulatory action. 8 October 2024 www.su.edu.eg 19  Pharm PharmDDProgram Program (2024/2025) (2023/2024) GMP 1 7 8 October 2024 www.su.edu.eg 20  Pharm PharmDDProgram Program (2024/2025) (2023/2024) 1 8 8 October 2024 www.su.edu.eg 21  Pharm D Program (2023/2024) I-Organization and Personnel: 1 Personnel of quality control unit: -Have the responsibility and authority to approve or rejec t all components. -Have the authority to review production records to assure that no errors have occurred or, the occurred errors have been fully investigated. 2The quality control unit have the responsibility for approving or rejecting all procedures or specifications affecting the identity, strength, quality, and purity of the drug product. 3The responsibilities and procedures applicable in the quality control unit should be written. 4The training of personnel to be qualified in GMPs and in their specific responsibilities 8 October 2024 www.su.edu.eg 22  Pharm PharmDDProgram Program (2024/2025) (2023/2024) 5-Contaminants may be prevented from being introduced into the plant by making only company garments, including: a) Pants or skirts, shirts or blouses. b) Caps to cover the head. c) Plant shoes and safety glass. d) Covering for mustaches and beards should be worn within the plant at all times. 20 8 October 2024 www.su.edu.eg 23  Pharm PharmDDProgram Program (2024/2025) (2023/2024) -In changing rooms, dirty garments are segregated from clean garments: Clean garments are wrapped in plastic bags or envelopes. Soiled(dirty) garments are deposited in tightly covered containers, waiting for cleaning. there should be a procedure for sterilizing and storing clothing for use in the sterile area. 6-High standards of personal c leaning espec ially in sterile produc ts manufacturing area. a. Hand-washing facilities should be available to manufacturing personnel. but, they should not be present within sterile areas. b.avoid direct contact between the operator's hands and starting materials, intermediates and products. c. Pre-employment medical checks should be done. d. Eating, drinking, c hewing and smoking should not be permitted in manufacturing areas. Dr Baher A. Daihom 21 8 October 2024 www.su.edu.eg 24  Pharm D Program (2023/2024) II-Premises must be adequate; provide specifically defined areas for certain operations, and are designed to prevent mix-ups. design and construction features include; lighting; ventilation, air filtration, air heating and cooling, plumbing; sewage ; washing and toilet facilities; sanitation; and maintenance. 22 8 October 2024 www.su.edu.eg 25  Pharm D Program (2023/2024) III- Equipment: This include equipment design, size, location, construction, cleaning and maintenance. Provide appropriate equipment for the manufacture of the product and ensur that its material of construction is not reactive. e In the revised version of the GMPs, the requirements and the written procedures for equipment cleaning and maintenance were added. Dr Baher A. Daihom 23 8 October 2024 www.su.edu.eg 26  Pharm PharmDDProgram Program (2024/2025) (2023/2024) Radio Frequency Identification (RFID) is a technology that uses radio waves to passively identify a tagged object. 2 4 8 October 2024 www.su.edu.eg 27  Pharm D Program (2023/2024) RFID Dr Baher A. Daihom 8 October 2024 www.su.edu.eg 28  Pharm D Program (2023/2024) IV-Control of components and drug product containers and closures 1.Approval or rejection of product containers and closures and the requirements with written procedures for each. 2. Vendors (supplier) with well-controlled processes and a good record of acceptable batches are chosen. Material could be put into use based on the quality record of the supplier while testing was being performed concurrently, even if testing is only for identification and Dr Baher A. Daihom before it is released by the quality control unit. 8 October 2024 www.su.edu.eg 29  Pharm D Program (2023/2024) V-Production and process controls -This focuses on the need for written procedures and formal authorization by Q.C. for any deviation from the written procedures. -Areas covered are: addition of components; calculation of yield; equipment identification; sampling and testing of in-process materials and drug products; time limitations on production; control of microbiological contamination; and reprocessing. -Some drug companies are currently considering electronic means of: verifying component names or item codes, receiving and control numbers, weights or measure, and even the verification of component addition to a batch Dr Baher A. Daihom 8 October 2024 www.su.edu.eg 30  Pharm D Program (2023/2024) VI- Packaging A. Before packaging operation Be sure that the work area and equipment are clean and free from any product, materials or documents not required for that operation. Packaging of products of similar appearance should be avoided. 8 October 2024 www.su.edu.eg 31  Pharm PharmDDProgram Program (2024/2025) (2023/2024) At each packaging line, the name and batch of the product being handled should be displayed. 4. Risk of labeling errors should be minimized by : roll-feed labels; use of electronic code readers label counters; labels and other printed materials designed to give marked differentiation between products. 5. Containers for filling should be supplied to the packaging line in a clean condition; or be cleaned there (by washing, or by air blast). 2 9 8 October 2024 www.su.edu.eg 32  Pharm D Program (2023/2024) B. On completion the packaging operation Any unused batch-coded labels and/or materials should be destroyed. A documented procedure should be used if encoded materials are returned to stock. Packed finished product should be quarantined until released by quality control Measures should be taken to control the spread of dust during packaging of dry products. 30 8 October 2024 www.su.edu.eg 33  Pharm D Program (2023/2024) VII- Storage 1. Materials and products should be stored: a.Under special environmental conditions which minimize deterioration, contamination or breakage. b. in an orderly fashion to allow batch differentiation and rotation of stocks, and to permit easy cleaning. 2.storage arrangement should allow control agents to be effectively employed by trained personnel. 3.sampling should be done effectively, without the risk of contamination from other materials 4.Materials which have been rejected, recalled or returned should be suitably labeled and segregated to prevent confusion with other materials and products. 8 October 2024 www.su.edu.eg 34  Pharm PharmDDProgram Program (2024/2025) (2023/2024) 3 2 8 October 2024 www.su.edu.eg 35  Pharm PharmDDProgram Program (2024/2025) (2023/2024) 3 3 8 October 2024 www.su.edu.eg 36  Pharm D Program (2023/2024) VIII- Transport and distribution Materials and finished products should be transported inside and outside the factory by means which ensure that: Identification of the product is not lost. No confusion arises between a consignment which is suitable for use, and other consignments of the same product which are not. The product does not contaminate, or mixed with other products or materials. 8 October 2024 www.su.edu.eg 37  Pharm PharmDDProgram Program (2024/2025) (2023/2024) N.B. Compliance with GMPs requires that responsible employees in a firm be knowledgeable about what other firms are doing in order to comply. FDA investigators visit many firms and get a broad picture of what current practice is. Good manufacturing practices are "state of the art", and to be in compliance, a firm must regularly review procedures and policies and revise them as necessary. 3 5 8 October 2024 www.su.edu.eg 38  Pharm PharmDDProgram Program (2024/2025) (2023/2024) GLP 3 6 8 October 2024 www.su.edu.eg 39  Pharm PharmDDProgram Program (2024/2025) (2023/2024) Lecture’s References 1. Swarbrick J. Pharmaceutical process validation. Nash RA, Wachter AH, editors. New York: Marcel Dekker; 2003 May 8 October 2024 www.su.edu.eg 40