current Good Manufacturing Practices
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The document covers the history and importance of Good Manufacturing Practices (GMP), detailing regulations from 1937 to the present that ensure drug safety, quality, and efficacy. It emphasizes the need for adherence to Current Good Manufacturing Practices (cGMP) to prevent contamination and ensure compliance with safety standards across various pharmaceutical processes. It outlines critical components of GMP, including quality management systems, personnel training, facility requirements, and regulatory compliance as mandated by agencies such as the FDA.
current Good Manufacturing Practices
- 2. Learning Outcomes What should you know after this session? • History of GMP and Various GMP Regulations. • Introduction to cGMP • Why GMP is so important? • Schedule M and 21 CFR Part 211 • Principles of Quality • Golden Rules of cGMP • How to sustain GMP compliance? SHAILENDRA SURYAWANSHI M PHARM
- 3. History of GMP 1937 Company : S.E. Massengill Formulation : Sulfanilamide elixir (Liquid) Side effects : Kidney failure, severe abdominal pain, nausea, vomiting, and convulsions. Sulfanilamide Disaster 1938 Federal Food, Drug, and Cosmetic Act was passed. It required that drug manufacturers show that a drug is safe before marketing it. Mild sleeping pill safe even for pregnant women. Side effects: Thousands of babies worldwide to be born with malformed limbs. 1962 Thalidomide Disaster 1962 The Drug Amendments of 1962 formalized Good Manufacturing Practices. SHAILENDRA SURYAWANSHI M PHARM
- 4. History of GMP Establishes good laboratory practices Manufacturing, Processing, or Holding Active Pharmaceutical Ingredients. Investigating Out-of- Specification (OOS) 1978 Establishes minimum current good manufacturing practices for manufacturing, processing, packing, or holding drug products and medical devices 1979 Company : Johnson & Johnson. Formulation : Acetaminophen- capsule poisoning by cyanide. Result: revision of GMPs to require tamper-resistant packaging for OTC products 1982 Poisoned Acetaminophen Capsules 1998 GLPs Final Rule (21 CFR 58) CGMPs Final rules for drugs and devices (21 CFR 210–211 and 820) Draft Guidances SHAILENDRA SURYAWANSHI M PHARM
- 5. Different Regulatory Agencies SHAILENDRA SURYAWANSHI M PHARM
- 6. 21 CFR Part 210 Processing, Packing, or Holding of Drugs 21 CFR Part 211 Finished Pharmaceuticals 21 CFR Part 11 Electronic Records and Signatures Introduction of cGMP Good manufacturing practices is to assure that drug is safe to use and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess. In "cGMP“,The "c" stands for "current," reminding manufacturers that they must employ technologies and systems which are up-to-date in order to comply with the regulation. Drug and Cosmetic Act 1940 (Schedule M) Good Manufacturing Practices and Requirement of Premises, Plant and Equipment for Pharmaceutical Products SHAILENDRA SURYAWANSHI M PHARM
- 7. Introduction of cGMP : cGMP refers to the Current Good Manufacturing Practice regulations enforced By the regulatory agencies. cGMPs provide systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the cGMP regulations assures the safety, identity, strength, purity and quality of drug products by requiring the manufacturers of medications to adequately control the manufacturing operations. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories. This formal system of controls at a pharmaceutical company, if adequately put into practice, helps to prevent instances of contamination, mix- ups, deviations, failures, and errors. This assures that drug products meet their quality standards. Quality built into product •Patient can not check quality of the product (through smell, Odor or sight) •Testing alone is not enough to ensure quality •Patients trust you and the company •Ensure you follow GMP and SOP for best quality product. Without/Inadequate cGMP •Product(s) may not having quality •Patient loose trust on you •Patient can be impacted •FDA may close your facility Facts about cGMP SHAILENDRA SURYAWANSHI M PHARM
- 8. Why GMP is so Important ? Quality, Safety and effectiveness must be designed and built into the product Each step of manufacturing must be controlled to maximize the chances that the finished good will be acceptable. Are safe, efficacious, and have the correct identity Deliver the same performance as described in the label Perform consistently over their shelf life Are made in a manner that ensures quality Will be available when needed Patients assume that their drugs, Who is responsible for GMP? SHAILENDRA SURYAWANSHI M PHARM
- 9. Schedule M Part Title I Good Manufacturing Practices for Pharmaceutical Products II Specific Requirements for Manufacture of Sterile Products, Parenteral Preparations (Small Volume Injectables and Large Volume Parenterals) and Sterile Opthalmic Preparations III Specific Requirements for Manufacturing of Pharmaceutical Products Containing Hazardous Substances such as Sex Hormones, Steroids (Anabolic, Androgenic) or Cytotoxic Substances IV Specific Requirements for Manufacture of Biological Products V Specific Requirements for Radiopharmaceutical Products VI Specific Requirements for Phytopharmaceuticals VIII Specific Requirements for Manufacture of Oral Solid Dosage Forms (Tablets and Capsules IX Specific Requirements for Manufacture of Oral liquids (Syrups, Elixirs, Emulsions and Suspensions X Specific Requirements for the Manufacture of Topical Products i.e. External Preparations (Creams, Ointments, Pastes, Emulsions, Lotions, Solutions, Dusting Powders and Identical Products) XI Specific Requirements for manufacture of Metered- Dose Inhalers (MDI) XII Specific requirements for Manufacture of Active Pharmaceutical Ingredient XIII Requirements of Plant and Equipment SHAILENDRA SURYAWANSHI M PHARM
- 10. Schedule – M Part – II : Specific Requirements for Manufacture of Sterile Products, Parenteral Preparations (Small Volume Injectables and Large Volume Parenterals) and Sterile Opthalmic Preparations General Consideration Quality Control Sanitation Manufacture of Sterile Preparation ProcessingSterilizationPersonnelPremises Equipment Finishing of sterile products SHAILENDRA SURYAWANSHI M PHARM
- 11. Regulations : Part 211 Current GMP for Finished Pharmaceuticals Subpart A General Provision Subpart B Organization and Personnel Subpart C Buildings and Facilities Subpart D Equipment Subpart E Control of Components and drug Product Containers and Closures Subpart F Production and Process Controls Subpart G Packaging and Labeling Subpart H Holding and Distribution Subpart I Laboratory Controls Subpart J Records and Reports Subpart K Returned and Salvaged Drug Products SHAILENDRA SURYAWANSHI M PHARM
- 12. Subpart B : Organization and Personnel 12 §211.22 Responsibilities of the Quality Control Unit Approving or rejecting drug products manufactured, processed, and packed. § 211.25 Personnel qualifications. § 211.28 Personnel responsibilities Training Education Experience Personnel shall practice good sanitation and health habits. Authorized personnel entry in facility. Person with apparent illness or open lesions are excluded from direct contact with drug product /closures. SHAILENDRA SURYAWANSHI M PHARM
- 13. Personnel & Training To perform the assigned functions and assurance of Drug product SISPQ. Each person engaged in the manufacture, processing, packing or holding of a drug product shall have combination of ; Education : Adequate number of qualified personnel to perform activity Training : On particular operation and In current good manufacturing practice Experience : To perform and supervise the manufacture, processing, packing, or holding of each drug product Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with cGMP requirements applicable to them.
- 14. § 211.42 Design and construction features. Adequate Size and Space for Operation. Construction and location to facilitate cleaning. Maintenance, and proper operations. § 211.44 Lighting. § 211.46Ventilation, air filtration, air heating and cooling. Adequate lighting & Ventilation. Adequate control over air pressure, micro-organisms, dust, humidity, and temperature. AHU system for penicillin shall be separate. . § 211.48 Plumbing Potable water shall meet 40 CFR PART 141—NATIONAL PRIMARY DRINKING WATER REGULATIONS Drains : adequate size, connected directly to a sewer, provided with an air break or other mechanical device to prevent back- siphonage. § 211.42 Design and construction features. § 211.44 Lighting. § 211.46 Ventilation, air filtration, air heating and cooling. Subpart C : Buildings and Facilities SHAILENDRA SURYAWANSHI M PHARM
- 15. § 211.50 Sewage and refuse. Sewage, trash, and other shall be disposed of in a safe and sanitary manner. § 211.52 Washing and toilet facilities. Adequate washing facilities. Hot and cold water. Soap or detergent. Air driers or single- service towels. Clean toilet facilities. § 211.56 Sanitation. § 211.58 Maintenance. Manufacturing facility shall be maintained in a clean and sanitary condition with appropriate maintenance Subpart C : Buildings and Facilities (contd) SHAILENDRA SURYAWANSHI M PHARM
- 16. § 211.63 Equipment design, size, and location. Appropriate design Adequate size Suitably located to facilitate operations for its intended use and for its cleaning and maintenance. § 211.65 Equipment construction. Surfaces that contact components, in- process materials, or drug products shall not be, Reactive Additive or absorptive so as to alter the (SISPQ) of the drug product § 211.67 Equipment cleaning and maintenance. Equipment shall be cleaned, maintained, and sanitized at appropriate intervals. § 211.68 Automatic, mechanical, and electronic equipment. Calibrated and Inspected as per written SOP. A backup file of data shall be maintained. Appropriate control over computer or electronic system Subpart D: Equipment (SISPQ) : Safety, Identity, Strength, Purity and Quality SHAILENDRA SURYAWANSHI M PHARM
- 17. Facilities & Equipment Building must be designed with adequate size and space for operations. Finish of floors, ceilings, walls etc. Floor are epoxy coated and coving at corners. Prevent Backflow. Must be with good flow pattern of, Area Classification DP Personnel Movement Utilities must be validated Water system HVAC Equipment must be properly qualified. URS Design Qualification Installation Qualification Operational Qualification Performance Qualification Equipments must be, Calibrated Cleaned Maintained to prevent contamination and Mix-ups (21 CFR 211.63, 211.67 and 211.68) SHAILENDRA SURYAWANSHI M PHARM
- 18. § 211.80 General requirements.. Written procedures for receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers /closures. § 211.82 Receipt and storage of untested components, drug product containers, and closures. Components, drug product containers, and closures shall be stored under quarantine until they have been tested or examined, as appropriate, and released. § 211.84 Testing and approval or rejection of components, drug product containers, and closures. Each lot of components, drug product containers, and closures shall be sampled tested, or examined, as appropriate, and released for use by the quality control unit. Subpart E: Control of Components and drug Product Containers and Closures SHAILENDRA SURYAWANSHI M PHARM
- 19. § 211.86 Use of approved components, drug product containers, and closures. Components, drug product containers, and closures approved for use shall be rotated so that the oldest approved stock is used first. § 211.87 Retesting of approved components, drug product containers, and closures. Components, drug product containers, and closures shall be retested or reexamined, as appropriate, for identity, strength, quality, and purity and approved or rejected by the quality control unit . § 211.89 Rejected components, drug product containers, and closures Rejected components, drug product containers, and closures shall be identified and controlled under a quarantine system. Subpart E: Control of Components and drug Product Containers and Closures SHAILENDRA SURYAWANSHI M PHARM
- 20. Subpart F: Production and Process Controls §211.100 Written procedures; deviations §211.101 Charge-in of components §211.110 Sampling & testing of in-process material & drug products continued §211.115 Reprocessing For identity, strength, quality, and purity as appropriate, and approved or rejected by the quality control unit. e.g., at commencement or completion of significant phases or after storage for long periods Weighing, measuring, or subdividing operations for components shall be adequately supervised. Each container of component dispensed to manufacturing shall be examined by a second person to assure that: (1) The component was released by the quality control unit Production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Written procedures, including any changes, shall be drafted, reviewed, and approved by the appropriate organizational units and reviewed and approved by the quality control unit. Reprocessing shall not be performed without the review and approval of the quality control unit
- 21. Deviation / Event Management Deviation is departure from, Approved Procedure/instruction Established standards / specification. Why deviation/Event occurs ? Not following the procedure /Instructions How to handle the deviation ? Any deviation from the established procedure should be documented and investigated. Why deviation to be investigated ? Deviation to be investigated to determine their impact on the SISPQ of the product. Root cause to be identified. Implement appropriate and meaningful corrective actions. SHAILENDRA SURYAWANSHI M PHARM
- 22. Subpart G: Packaging and Labelling Controls § 211.122 Materials examination and usage criteria. § 211.125 Labeling issuance. § 211.130 Packaging and labeling operations § 211.132 Tamper- resistant packaging requirements for over-the-counter (OTC) human drug products. § 211.134 Drug product inspection. § 211.137 Expiration dating Tamper-resistant packaging of OTC drug products to improve the security of OTC drug packaging to assure the safety and effectiveness of OTC drug products. Written procedures to assure correct usage of labels, labeling, and packaging materials Strict control over labeling issued for use in drug product labeling operations. Written procedures for receipt, identification, storage, handling, sampling, examination, and/or testing of labeling and packaging materials. Examination to assure that containers and packages in the lot have the correct label. Drug product shall bear an expiration date determined by appropriate stability testing SHAILENDRA SURYAWANSHI M PHARM
- 23. Subpart H : Holding and Distribution §211.142 Warehousing procedures Quarantine of drug products before release by the quality control unit. Storage of drug products under appropriate conditions of temperature, humidity and light. § 211.150 Distribution procedures A procedure whereby the oldest approved stock of a drug product is distributed first. (FIFO) A system by which the distribution of each lot of drug product can be readily determined to facilitate its recall if necessary. (traceability) SHAILENDRA SURYAWANSHI M PHARM
- 24. Subpart I: Laboratory Controls §211.160 General requirements A) Establishment of: - Specifications. -Standards -Sampling plans -Test Procedures B) Calibration of: - Instruments. - Apparatus - Gauges - Recording Devices §211.165 Testing and release for distribution A) Appropriate laboratory testing. B) Written procedure for sampling and testing plan. C) Establishment of test methods for, - Accuracy. - Sensitivity - Specificity - Reproducibility §211.166 Stability testing A) Sample size B) Storage Conditions C) Reliable and specific test methods SHAILENDRA SURYAWANSHI M PHARM
- 25. §211.180 General requirements Retention of BMR for atleast 1 year after the expiration. Availability of retained records during authorized inspection. Annual product quality review. §211.192 Production record review Review and approved by quality control unit. Investigation for unexplained discrepancy. Investigation record. . §211.198 Complaint files Establishment of complaint handling procedure. Record of complaint with, a) Name and strength b) Lot number c) Name of complainant d) Nature of complaint Investigation of complaint Subparts J : Records and Reports SHAILENDRA SURYAWANSHI M PHARM
- 26. Principles of Quality Customer Focus Leadership Engagement of People Process Approach Continuous Improvemen t Evidence Based Approach Relationship Managemen t ISO 9001:2015 defines the 7 principles of quality management. 04 Concepts of Quality Assurance Policy Process Procedure Audit A policy is a stated aim of an organization; a principle which its operations should adhere to An audit is an event where an organization or one of its parts is checked to see whether it meets certain criteria. A process is a flow within an organization whereby resources or information get transformed. SHAILENDRA SURYAWANSHI M PHARM
- 27. Quality Systems Quality : ICH Q6A: Suitability of either a Drug Substance or Drug Product for its intended use. This term includes such attributes as the, Identity Strength Purity ICH Q10 – PQS is based on International Standards Organization (ISO) quality concept. The quality subsystem at the center, Provides the foundation for the five manufacturing subsystems and helps them achieve compliance. It is a regulatory requirement
- 28. How does FDA determine if a company is complying with cGMP regulations FDA inspects pharmaceutical manufacturing facilities worldwide, including facilities that manufacture active ingredients and the finished product. Inspections follow a standard approach and are conducted by highly trained FDA staff. FDA also relies upon reports of potentially defective drug products from the public and the industry. FDA will often use these reports to identify sites for which an inspection or investigation is needed. If a manufacturer is not following cGMPs, are drug products safe for use? If a company is not complying with CGMP regulations, any drug it makes is considered “adulterated” under the law. This kind of adulteration means that the drug was not manufactured under conditions that comply with cGMP. It does not mean that there is necessarily something wrong with the drug. FDA regulatory action is intended to stop the distribution or manufacturing of violated product. For consumers currently taking medicines from a company that was not following cGMPs, FDA usually advises these consumers not to interrupt their drug therapy, which could have serious implications for their health. SHAILENDRA SURYAWANSHI M PHARM
- 29. Golden Rules of cGMP Rule- 1 Get facility design right from the start Rule- 2 Validate Processes Rule- 3 Write good procedure and follow them Rule- 4 Identify who does what Rule- 5 Keep good records Rule- 6 Train and Develop Staff Rule- 7 Practice good hygiene Rule- 8 Maintain facilities and equipment Rule- 9 Build quality into the whole product life cycle Rule- 10 Perform regular audits SHAILENDRA SURYAWANSHI M PHARM
- 30. How to Sustain GMP Compliance Providing compliance training to staff is the best way to ensure GMP compliance. All employees should receive training on recordkeeping, sanitation, proper equipment handling and labeling, and SOPs to minimize errors and maintain compliance. Compliance Training A surprise audit can help gain more accurate insight on what goes on in the facility. Identify real root causes of non- compliance and take action before it progresses into a larger issue. Surprise Audits Validation is the documented act of demonstrating instruments, processes, and activities that are regularly used or done. Validation Team of skilled workers that will focus on improving current manufacturing procedures and complying with GMP. Members will perform quality assessments on operations to identify problems and develop appropriate corrective measures. Quality team SHAILENDRA SURYAWANSHI M PHARM
- 31. Violation of cGMP results in Form 483 Warning Letter License withdrawal Shutdown of manufacturing facility Seizure of product Product Recall Injunction cases Criminal cases- Fines/Jail Front page press coverage Competitive disadvantage Response from an Organization to Agency FDA Inspection Mechanism SHAILENDRA SURYAWANSHI M PHARM
- 32. At a Glance • All activities in accordance with written SOPs • Records made at the time of action – and maintained • Deviations avoided – when occur, follow SOP • Quality unit involved for process • Checks on yields - reconciliation • One product at a time in an area • All containers, Equipment and areas labelled • Access to areas controlled • No non-GMP Product in the areas • In process controls must be performed • Prevention of mix-ups, contamination and cross-contamination SHAILENDRA SURYAWANSHI M PHARM
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