Published on February 19, 2014
cGMP Schedule-M Krupanidhi College of Pharmacy (Q.A) Gaurav Kumar M.Pharm (Q.A) Date:
INTRODUCTION 1) Definition. 2) Timeline of GMP. 3) Components of CGMP. 4) Areas to be covered. 5) Conclusion. Krupanidhi College of Pharmacy (Q.A)
DEFINITION: cGMP refers to the Current Good Manufacturing Practice regulations enforced by the US Food and Drug Administration (FDA). cGMP provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the cGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control 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. Definition of GMP as per WHO: GMP is that part of quality assurance, which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization. Krupanidhi College of Pharmacy (Q.A)
TRAGEDIES PREECEDING CGMP REGULATIONS 1902 - Development of the Biologic Control Act 1906 - Development of the Pure Food and Drug Act 1938 - Federal Food, Drug and Cosmetic Act 1941 - Initiation of GMP 1944 - Development of Public Health Services Act 1962 - Kefauver-Harris Drug Amendments released (It introduced a requirement for drug manufacturers to provide proof of the effectiveness and safety of their drugs before approval, required drug advertising to disclose accurate information about side effects, and stopped cheap generic drugs being marketed as expensive drugs under new trade names as new "breakthrough" medications) 1963 - Establishment of GMPs for Drugs 1975 - cGMP for Blood and Components Final Rule 1976 - Medical Device Amendments 1978 - cGMP for Drugs and Medical Devices Krupanidhi College of Pharmacy (Q.A)
1979 - GLPs Final Rule 1980 - Infant Formula Act is passed Sulfathiazole tablets contaminated with phenobarbital 1941 - 300 people died/injured FDA to enforce and revise manufacturing and quality control requirements 1941 - GMP is born Thalidomide tragedy Thousands of children born with birth defects due to adverse drug reactions of morning sickness pill taken by mothers Strengthen FDA’s regulations regarding experimentation on humans and proposed new way how drugs are approved and regulated “Proof of efficacy” law Krupanidhi College of Pharmacy (Q.A)
COMPONENTS OF cGMP a) GMP is a part of Q.A b) GMP’s main function is to produce quality products consistently. c) GMP must meet legal requirements of country. d) GMP must meet both production and Q.C. related issues. e) WHO further comments that the main function of GMP is to avoid mix-ups and contamination risks. Krupanidhi College of Pharmacy (Q.A)
cGMP COVERS a) General considerations b) Personnel c) Premises d) Equipment e) Sanitation f) SOP’s g) Raw Materials h) Self Inspection And Audit i) Master Formula Records j) Batch Manufacturing Records k) Warehousing Area l) Labels And Other Printed Materials m) QA Krupanidhi College of Pharmacy (Q.A)
GENERAL CONSIDERATIONS a) Compliance with GMP b) Consistent uniform batches c) Location And surroundings d) Water system e) Disposal Of Waste Krupanidhi College of Pharmacy (Q.A)
PERSONNEL Qualified Personnel a)Experienced b)Sufficient Number Written job description Trained Health a) Diseases. (communicable or noncommunicable). b) Open Lesions. C) Skin diseases. d) Allergic conditions. Krupanidhi College of Pharmacy (Q.A) Gowning
PREMISES Krupanidhi College of Pharmacy (Q.A)
Wyeth Pharmaceuticals, Goa Krupanidhi College of Pharmacy (Q.A)
POINTS TO BE CONSIDERED. 1) Location 2) Design 3) Construction Location Geography, climate and economic factors Neighbours a) What do they do? Premises must be located to minimize risks of cross-contamination, e.g. not located next to a malting factory with high airborne levels of yeast Pollution/effluent control (E.T.P: Effluent treatment Plant). Krupanidhi College of Pharmacy (Q.A)
Design a) b) c) d) e) f) g) h) Minimize risks of errors Permit effective cleaning Permit effective maintenance Avoid cross-contamination, build-up of dirt and dust Maximum protection against entry of insects, birds and animals Separate facilities for other products such as some antibiotics, hormones, cytotoxic substances. Maximum protection against entry of insects, birds and animals. Finishing floors, walls, and Ceilings sshould be smooth, impervious, hard-wearing, easy to clean Specific Areas 1) Production areas 2) Quality control areas 3) Weighing areas 4) Storage areas 5) Ancillary areas Hygiene Eating, Drinking, Smoking Should not be allowed in the Production area. Krupanidhi College of Pharmacy (Q.A)
1. Design and construction features: Any building used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction and location to facilitate cleaning, maintenance. The orderly placement of equipment and materials to prevent mix-ups between different components, drug product containers, closures, labeling, in-process materials, or drug products, and to prevent contamination. 2. Lighting: Adequate lighting shall be provided in all areas 3. Ventilation, air filtration, air heating and cooling. Equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product. Air filtration systems, including prefilters and particulate matter air filters, shall be used when appropriate on air supplies to production areas. there shall be adequate exhaust systems or other systems adequate to control contaminants. 4. Plumbing Potable water shall be supplied under continuous positive pressure in a plumbing system. Potable water shall meet the standards prescribed in the Environmental Protection Agency's Primary Drinking Water Regulations Drains shall be of adequate size and, where connected directly to a sewer, shall be provided with an air break to prevent back siphonage. 5. Sewage and refuse Sewage, trash, and other refuse in and from the building and immediate premises shall be disposed of in a safe and sanitary manner. Krupanidhi College of Pharmacy (Q.A)
6. Washing and toilet facilities. Adequate washing facilities shall be provided, including hot and cold water, soap or detergent, air driers or single-service towels, and clean toilet facilities easily accessible to working areas. 7. Sanitation. Building shall be free of infestation by rodents, birds, insects, and other vermin. Trash and organic waste matter shall be held and disposed of in a timely and sanitary manner. There shall be written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents. 8. Maintenance. Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a good state of repair. Krupanidhi College of Pharmacy (Q.A)
Pfizer Facility, Grange Castle site in Clondalkin, Ireland. Krupanidhi College of Pharmacy (Q.A)
EQUIPMENTS Krupanidhi College of Pharmacy (Q.A)
Equipment shall be located, designed, constructed, adapted and maintained to suit the operation to be carried out. Should be made of non reactive material, such as High grade of steel(316,302) Equipment should bea) Calibrated. b) Checked. c) Labelled. d) Sterilized. e) Accompanied with SOP. Krupanidhi College of Pharmacy (Q.A)
Krupanidhi College of Pharmacy (Q.A)
Krupanidhi College of Pharmacy (Q.A)
SANITATION Krupanidhi College of Pharmacy (Q.A)
Written procedures for: a) Gowning and de-gowning S.O.P. b) hygiene, health c) waste disposal Implementation and training of the employees in basic sanitation and toilet habits. Practices not permitted a)eating, smoking b) unhygienic practices Krupanidhi College of Pharmacy (Q.A)
Krupanidhi College of Pharmacy (Q.A)
STANDARD OPERATING PROCEDURE There shall be written Standard Operating Procedure for each operation It includea)For Equipment. b)For sampling. c)For Testing. d)For Process. f)For Packaging. Krupanidhi College of Pharmacy (Q.A)
RAW MATERIALS An Inventory should be maintained for Raw materials to be used at any stage of manufacturing: Records should be maintain as per Schedule U. Should be purchased from approved sources. Must be checked by QC department on receipt . Should be labeled. Krupanidhi College of Pharmacy (Q.A)
SELF AUDIT & INSPECTION Regular independent inspection is necessary to evaluate the manufacturer’s compliance with GMP in all aspects of manufacturing Procedure for self inspection shall be documented indicating a)Evaluation b)Conclusion c)Recommendations for Corrective action There should be a BMR ( Batch Manufacturing Record) and MFR (Master Formula Record). Krupanidhi College of Pharmacy (Q.A)
PACKAGING & LABELING CONTROL 1. Materials examination and usage criteria. Records shall be maintained for each different labeling and packaging material indicating receipt, examination or testing, and whether accepted or rejected. Labels and other labeling materials for each different drug product, strength, dosage form, or quantity of contents shall be stored separately with suitable identification. Use of visual inspection to conduct a 100-percent examination for correct labeling during or after completion of finishing operations. 2. Labeling issuance. Strict control shall be exercised over labeling issued for use in drug product labeling operations. Labeling materials issued for a batch shall be carefully examined for identity and conformity to the labeling specified in the master or batch production records. 3. Packaging and labeling operations. Prevention of mix-ups and cross-contamination by physical or spatial separation from operations on other drug products Examination of packaging and labeling materials for suitability and correctness before packaging operations, and documentation of such examination in the batch production record. Krupanidhi College of Pharmacy (Q.A)
4. Tamper-evident packaging requirements An OTC drug product for retail sale, that is not packaged in a tamper-resistant package or that is not properly labeled under this section is adulterated under section 501 of the act or misbranded under section 502 of the act, or both. Package the product in a tamper-evident package, visible evidence to consumers that tampering has occurred. 5. Drug product inspection. Packaged and labeled products shall be examined during finishing operations to provide assurance that containers and packages in the lot have the correct label. A representative sample of units shall be collected at the completion of finishing operations and shall be visually examined for correct labeling. Results of these examinations shall be recorded in the batch production or control records. 6. Expiration dating. To assure that a drug product meets applicable standards of identity, strength, quality, and purity at the time of use, it shall bear an expiration date determined by appropriate stability testing. If the drug product is to be reconstituted at the time of dispensing, its labeling shall bear expiration information for both the reconstituted and un-reconstituted drug products. Expiration dates shall appear on labeling in accordance with the requirements. Krupanidhi College of Pharmacy (Q.A)
WAREHOUSING AREA (WAREHOUSE) Krupanidhi College of Pharmacy (Q.A)
Warehousing area should be designed and adapted to ensure good storage conditions. Should be clean, dry and maintained with acceptable temperature limits. Should have appropriate house-keeping and rodents, pests and vermin control. Separate sampling area for active raw material and excipients. Every Material stored should be labeled properly. Fire Prevention Krupanidhi College of Pharmacy (Q.A)
GMP IS ACTUALLY GOOD COMMON SENSE Quality Management Quality Assurance GMP Production and Quality Control Krupanidhi College of Pharmacy (Q.A)
QUALITY ASSURANCE The main objective of the quality assurance is to ensure the products are of the quality required for their intended use Functions Adequates are made for manufacturing, supply and the use of correct starting and packing material. Adequate control on starting material, intermediate, and bulk products. Process validation in accordance with established procedures. Krupanidhi College of Pharmacy (Q.A)
CONCLUSION GMP compliance is not an option. Quality should be built into the product. 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 Krupanidhi College of Pharmacy (Q.A)
.THANK YOU. Krupanidhi College of Pharmacy (Q.A)
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