Current Good Manufacturing Practices

A brief presentation on the current good manufacturing practices employed in the manufacture of pharmaceuticals in the US.
Comprises of all aspects of good manufacturing practices

1. CGMP Current Good Manufacturing Practices Department of Regulatory Affairs NGSMIPS, Nitte University Mangalore - Swapnil Dylan Fernandes 1

2. What is CGMP ? Current Good Manufacturing Practice regulations enforced by the US Food and Drug Administration (FDA). Provides for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Assures the identity, strength, quality, and purity of drug products. The "C" in CGMP stands for "current," requiring companies to use technologies and systems that are up-to-date in order to comply with the regulations. 2

3. Importance of CGMP To assure that quality is built into the design and manufacturing process at every step. 3

4. 21 CFR Part 210 CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS § 210.1 - Status of current good manufacturing practice regulations. § 210.2 - Applicability of current good manufacturing practice regulations. § 210.3 - Definitions. 4

5. 21 CFR Part 210 210.1 Status of the regulations Regulations set forth are “minimum” requirements!!!! Covers manufacturing, facilities and controls for Manufacturing, processing, packaging or holding of a drug product Failure to comply will render the drug to be adulterated The person who is responsible for the failure to comply shall be subject to regulatory action 5

6. 21 CFR Part 210 210.2 Applicability of current good manufacturing practice regulations. Applies to drug products for human use. If a person engages in only some operations subject to the regulations in this part, and not in others, that person need only comply with those regulations applicable to the operations in which he or she is engaged. 6

7. 21 CFR Part 210 210.3 Definitions Act - means the Federal Food, Drug, and Cosmetic Act. Batch - A specific quantity of drug/material intended to have uniform character and quality produced under a single manufacturing order form during the same cycle of manufacture. Component - Any ingredient intended for use INCLUDING those that may not appear in such drug product. Drug Product - Finished dosage form Fiber - Any particulate with a length at least 3 times to its width 7

8. Nonfibre releasing filter , will not release fibres into the component or drug product that is being filtered. Active ingredient , Any component intended to furnish pharmacological activity Drug is defined by the Act as any compound that has effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure or function of the body of man or animals In-process material , Any material fabricated, compounded, blended or derived for use in the drug product. Lot   means a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits Lot number, control number, or batch number   means any distinctive, from which the complete history of drug product or other material can be determined. 8

9. Acceptance criteria   Representative sample Strength Gang-printed labelling means labelling derived from a sheet of material on which more than one item of labelling is printed. 9

10. 21 CFR Part 211 CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS There are 11 subchapters Identified by letters from A through K Covers all sections of operations Designed to be all encompassing (general) – DON’T expect too many specific. 10

11. 211.1 Scope Minimum requirements Applies to drugs for human use 211.3 Definitions Those set forth in 210.3 are applicable Subpart A – General Provisions 11

12. Subpart B – Organisation & Personnel 211.22 - Responsibilities of quality control unit 211.25 - Personnel qualifications 211.28 - Personnel responsibilities 211.34 - Consultants. 12

13. Subpart C – Buildings and Facilities 211.42 - Design and construction features  211.44 - Lighting 211.46 - Ventilation, air filtration, air heating and cooling 211.48 - Plumbing  211.50 - Sewage and refuse 211.52 - Washing and toilet facilities 211.56 - Sanitation 211.58 - Maintenance 13

14. Subpart D – Equipment 211.63 - Equipment design, size, and location 211.65 - Equipment construction 211.67 - Equipment cleaning and maintenance 211.68 - Automatic, mechanical, and electronic equipment 211.72 - Filters 14

15. Subpart E – Control of components and Drug product Containers and Closures 211.80 - General requirements 211.82 - Receipt and storage of untested components, drug product containers, and closures 211.84 - Testing and approval or rejection of components, drug product containers, and closures 211.86 - Use of approved components, drug product containers, and closures 211.87 - Retesting of approved components, drug product containers, and closures 211.89 - Rejected components, drug product containers, and closures 211.94 - Drug product containers and closures. 15

16. Subpart F – Production & Process controls 211.100 - Written procedures; deviations 211.103  - Calculation of yield 211.105 - Equipment identification 211.110 - Sampling and testing of in-process materials and drug products 211.111 - Time limitations on production 211.113 - Control of microbiological contamination 211.115 - Reprocessing 16

17. Subpart G – Packaging and Labeling Control 211.122 Materials examination and usage criteria 211.125 Labeling issuance 211.130 Packaging and labeling operations 211.132 Tamper-resistant packaging requirements for OTC human drug products 211.134 Drug product inspection 211.137 Expiration dating 17

18. Subpart H – Holding and Distribution   211.142 - Warehousing procedures 211.150 - Distribution procedures 18

19. Subpart I – Laboratory controls 211.160 - General requirements 211.165 - Testing and release for distribution 211.166 - Stability testing 211.167 - Special testing requirements 211.170 - Reserve samples 211.173 - Laboratory animals 211.176 - Penicillin contamination. 19

20. Subpart J – Records and Reports 211.180 - General requirements 211.182 - Equipment cleaning and use log 211.184 - Component, drug product container, closure, and labeling records 211.186 - Master production and control records 211.188 - Batch production and control records 211.192 - Production record review 211.194 - Laboratory records 211.196 - Distribution records 211.198 - Complaint files 20

21.  211.204 - Returned drug products  211.208 - Drug product salvaging Subpart K – Returned and Salvaged Drug Products  21

22. CONCLUSION CGMP compliance is not an option. Quality should be built into the product right from the initial stage. GMP's are very similar and are really Good Common Sense. Good Practices cover all aspects of manufacturing activities prior to supply. The role and involvement of senior management is crucial. The goal is to tell you WHAT TO DO , NOT HOW TO DO it! 22

23. References https://www.fda.gov/drugs/developmentapprovalprocess/manufacturing/ucm090016.html , Current Good Manufacturing Practice (CGMP) Regulations (Accessed on 13 th September 2017) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=210 , 21 CFR Part 210 Guidelines (Accessed on 13 th September 2017) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211 , 21 CFR Part 211 Guidelines (Accessed on 13 th September 2017) P.P. Sharma, How to Practice GMPs , 7 th ed , New Delhi, Vallabh Publishers; 2015 23

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