![● The cGMP regulations for the manufacture of pharmaceutical products are
contained in Parts 210 and 211 of Title 21 of the Code of Federal
Regulations (CFR) [1].
INTRODUCTION
● Part 210 specifies the scope and applicability of the cGMP regulations and
defines terms used in the regulations.
● Part 210 also indicates that the regulations establish “minimum” cGMP
requirements and that products that are not manufactured under cGMP are
adulterated.
● Adulterated products and the persons responsible for the adulteration are
subject to regulatory action by the FDA.
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cGMP.pptx
- 2. TECH SLIDLES 01 cGMP guidelines 02 Explanation of cGMP Guidelines 03 Duties of Quality Control Unit under cGMP Regulations 04 References 05 INTRODUCTION 01 Table Of Contents 2
- 4. ● The cGMP regulations for the manufacture of pharmaceutical products are contained in Parts 210 and 211 of Title 21 of the Code of Federal Regulations (CFR) [1]. INTRODUCTION ● Part 210 specifies the scope and applicability of the cGMP regulations and defines terms used in the regulations. ● Part 210 also indicates that the regulations establish “minimum” cGMP requirements and that products that are not manufactured under cGMP are adulterated. ● Adulterated products and the persons responsible for the adulteration are subject to regulatory action by the FDA. 4
- 5. ● Part 211 contains specific good manufacturing practice requirements for finished pharmaceuticals and is divided into Subparts A-K as follows: cGMP Part 211 A. Scope B. Organization and personnel C. Buildings and Facilities D. Equipment E. Control and Component and Drug Product Containers and Closure 5
- 6. F. Production and Process Control G. Packaging and Labelling Controls H. Holding and Distribution I. Laboratory controls J. Records and Reports K. Returned and Salvaged Drug Products cGMP Part 211 6
- 7. A. The regulations in this part contain the minimum current good manufacturing practice for preparation of drug products for administration to humans or animals. B. The current good manufacturing practice regulations in this chapter as they pertain to drug products; as they pertain to drugs that are also biological products for human use; they are applicable to drugs that are also human cells, tissues, and cellular and tissue-based products (HCT/Ps) and that are drugs; supplement and do not supersede the regulations in this part unless the regulations explicitly provide otherwise. C. The requirements in this part shall not be enforced for OTC drug products if the products and all their ingredients are ordinarily marketed and consumed as human foods, and which products may also fall within the legal definition of drugs by virtue of their intended use. Scope 7
- 9. Organization and Personnel Management Responsibility • Responsible for facility, quality system, organizational structure, ensuring adequate resources • Responsible for actions of those reporting to them • Responsible for reviewing products annually, and procedures routinely • Responsible for providing adequate resources to perform operations Facilities, personnel, training, equipment, etc 9
- 10. • Quality Unit Responsible for approval or rejection of 1. all components, raw materials, containers, closures, subassemblies, packaging, labeled finished products, process validation reports, procedures and product specifications 2. Investigative reports for non-conformances and out- of- specifications (OOS’s) • Quality Unit Responsible for reviewing production records and ensuring that no errors have occurred (may include verification activities) • Responsible for releasing product for use Must be independent of manufacturing Organization and Personnel Management Responsibility 10
- 11. Building and facilities Design and construction features. Lighting. Ventilation, air filtration, air heating and cooling. Plumbing. Sewage and refuse. Washing and toilet facilities. 11
- 12. Buildings and Facilities • Buildings must be designed with adequate size and space for operations (helps to eliminate mix-ups) • Facilities must be validated • There must be a good flow pattern for personnel, materials, products and waste materials (flow from clean to dirty) • The facility must be easy to clean and sanitize (surfaces, equipment, exposed cords, floors, ceilings…) • Environmental controls must be in place (clean rooms) • Utilities must be validated (water systems, electrical, etc) 12
- 13. • Buildings and Facilities Must have engineering documents describing the layout of the clean rooms – controlled documents • Changes to the layout of the room after it has been validated must go through change control procedures and may require revalidation of the room • Any changes that potentially impact the ventilation in the room must be assessed for impact on the microbial levels in the room • Microorganisms, particulates, and hazardous materials must be controlled Buildings and Facilities 13
- 14. FOUR ILLUSTRATIONS IN ONE PLACE 14
- 15. Equipment Equipment design, size, and location. Equipment construction. Equipment cleaning and maintenance. Automatic, mechanical, and electronic equipment. Filters 15
- 16. Equipment • Equipment should be selected based on the intended use and cleanability if it is to be in a clean room • Equipment must be placed in an appropriate location (temperature, humidity, etc.) • Equipment must be properly qualified (Design, Installation, Operation, Performance) 16
- 17. FOUR ILLUSTRATIONS IN ONE PLACE 17
- 18. control of components General requirements. Receipt & storage of untested components, drug product containers and closures. Testing and approval or rejection of components, drug product containers and closures. Use of approved components, drug product containers, and closures. Retesting of approved components, drug product containers, and closures. Rejected components, drug product containers, and closures. 18
- 19. Component/Materials Control • Suppliers must be evaluated and approved and monitored for quality Incoming Materials must be tested before they can be accepted for use • Materials must be placed in stores or issued according to FIFO (stock rotation) • Materials must be stored so that they are not mixed up, damaged, or contaminated. 19
- 20. Production and process control Written procedures; deviations. Charge-in of components. Calculation of yield. Equipment identification. Sampling and testing of in- process materials and drug products. Time limitations on production. 20
- 21. Production/Process Control • Have & Follow Procedures: A good procedure is a written step- by-step procedure that provides a roadmap for Controlled and Consistent performance. • Examples: – (Manufacturing) Work Instructions – Operating Procedures – Testing Procedures – Quality Manual Deviations must be recorded and justified • Procedures should address… …verification of critical steps by a second person …line clearance …monitoring of processes to make sure they are in control …time limits and yield calculations as appropriate checks for critical processes …gowning for controlled environments (cleanrooms) 21
- 22. Packaging and labeling control Materials examination and usage criteria. Labeling issuance. Packaging and labeling operations. Tamper-evident packaging requirements for over-the-counter human drug products. Drug product inspection. Expiration dating. 22
- 23. Packaging and Labeling Control • Label is a display of a written, printed or graphic matter upon the immediate container of any article • Labeling is the label and any other packaging material or container that is printed (ex. IFU, advertising materials) • Procedures must exist that document receiving, identity, storage, handling, sampling, and testing of labels and ensure that integrity is maintained throughout production and use of product • Labeling must be separated physically in storage to avoid mix-ups • Wording of labels cannot be changed unless the FDA is notified • Labeling must be inspected prior to issuing to production • All labels must be reconciled (accounted for) if not 100% inspected. 23
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- 26. Holding and Distribution • Warehousing procedures should address… …Quarantine of drug products …storage of products under appropriate conditions • Distribution procedures should address… …FEFO (First Expiring First Out) …traceability of product lots/batches 26
- 27. Records and reports General requirements. Equipment cleaning and use log. Component, drug product container, closure, and labeling records. Master production and control records. Batch production and control records. Production record review. Laboratory records. Complaint files. 27
- 28. Records and Reports 1. Quality Records are the proof that the procedures were followed and they show traceability of product. Examples: – Lot History Records – Laboratory Notebooks – Protocols – Reports – Logbooks – Distribution Records – Complaint Files 2. Quality Records are legal documents and can be subpoenaed in a court of law as evidence 3. Signatures on documentation have the same meaning as on any kind of contract 4. Information must be recorded and signed for at the time of performance on the original record 28
- 29. Laboratory Controls • Written procedures must be established & followed • All actions must be documented at the time of performance • Calculations need to be recorded • Second person must review records • Data must be directly recorded into appropriate records • Equipment, software, and methods must be validated • An Out-of-Specification (OOS) result must be investigated and a root cause identified • Laboratory data is considered to be a quality record 29
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- 32. Duties of Quality Control Unit under cGMP Regulations The cGMP regulations assign specific duties to the quality control unit. The unit is required to have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. 32
- 33. The responsibilities of the unit extend to approving or rejecting drug products manufactured. processed, packed, or held by contract manufacturers. The organization must assure that the quality control unit has adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products. Duties of Quality Control Unit under cGMP Regulations 33
- 34. In addition to duties associated with the approval of materials and finished products, the unit is also responsible for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product. This includes review and approval of procedures for production and process control, including any changes to these procedures. These procedures, and the responsibilities and procedures applicable to the quality control unit within the organization, must be written and followed. Duties of Quality Control Unit under cGMP Regulations 34
- 35. All specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, including any changes, must be in writing and reviewed and approved by the quality control unit. Written procedures describing the handling of all written and oral complaints regarding a drug product are required. The quality control unit is responsible for reviewing any complaint involving the possible failure of a drug product to meet. Duties of Quality Control Unit under cGMP Regulations 35
- 36. References 1. cGMP guidelines; www.fda.gov 2. Shayne Cox Gad, Pharmaceutical Manufacturing Handbook, Regulations and Quality,Wiley- Interscience, A John Wiley and sons, Inc. Publications. 36
- 37. THANK YOU 37