Huzairy Hassan School of Bioprocess Engineering UniMAP

Current Good Manufacturing Practice (cGMP)

Definition - cGMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. - Assure the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations.

Quality Management System QMS PROCESS Input Output Management Responsibility, Resource Management, Product Realization, Measurement, Analysis and Improvement Raw Materials Energy Customer Requirement

Plan-Do-Check-Act PLAN -Define the systems -- Assess current situation - Analyze causes DO -- Try out system or improve theory CHECK - Study the system or results ACT - Standardize improvements -Plan continuous improvement

QMS and cGMP in Biopharmaceutical Co. Senior Management Responsibility To achieve the quality objectives, a well- establish and documented system of Quality assurance (QA) incorporating Good Manufacturing Practice (GMP) should be followed) - Quality- Safety- Efficacy

Quality Assurance and Quality Control Is defined as the sum total of organized arrangements made with the objective of ensuring that the products are of quality required for their intended use. QA It is the part of GMP which is concerned with sampling, specifications, testing, documentation and release which ensures that necessary and relevant tests are carried out and that materials/products are released For use/ sale only after their quality is judged to be satisfactory. QC 7 ~kfk~

What QA systems should includes? 1. GMP and GLP are taken into account during designing and developing products. 2. All production and control operations are clearly specified and documented. 3. Key personnel responsibilities are clearly defined. 4. All arrangements for procurement and use of correct starting materials and packaging materials are made. 5. In process checks and validations are carried out in a defined manner. 6. The final product is manufactured, packed and checked as per defined procedures. 7. Regulatory aspects and internal requirements for the final product are fulfilled. 8. Storage, handling and distribution procedures for the final product are followed to ensure maintenance of quality throughout shelf life. 9. Self-inspection procedures are defined to regularly monitor the effectiveness of the quality assurance system. 10. Corrective actions 11. Statistical process control 8 ~kfk~

What QC systems should includes? 1. Appropriate procedures, training personnel and adequate facilities for sampling, inspection and testing of starting materials, intermediate, bulk and finished products. 2. Validated test methods 3. Maintenance of records to demonstrate that all procedures have been carried out. 4. Certification of starting materials to be of specified quality and purity, and their storage and adequate labeling before use in final product. 5. Release of batch of product ONLY after certification by qualified person that it meet required criteria or specifications. 6. Maintain sufficient samples of starting materials and final product for future examination, if necessary. 7. Recording and investigation of out of specification results, changes, incidents and deviations. 9 ~kfk~

cGMP for Biopharmaceutical Industries Is it part of QA or QC? GMP is that part of quality assurance which ensures that products are consistently produced and controlled to be quality standards appropriate to their intended use and as required by the marketing authorization. GMP rules are directed primarily to diminishing the risks, inherent in any biopharmaceutical production, that cannot be prevented completely through testing the final products. Risk are: 1. Cross contamination (in particular by unexpected contaminants) 2. Mix-ups (confusion) such as false labeling. 10 ~kfk~

cGMP Guidelines for Biopharmaceuticals 1. All manufacturing process are clearly defined, systematically reviewed in the light of experience, and shown to be capable of consistently manufacturing biopharmaceutical products of the required quality and specifications. 2. All steps of manufacturing processes and any significant changes made to the process are validated. 3. All necessary facilities are provided, including: ◦ Appropriate qualified and trained personnel ◦ Adequate premises and space ◦ Suitable equipment and services ◦ Correct materials, containers and labels ◦ Approved procedures and instructions ◦ Suitable storage and transport ◦ Adequate personnel, laboratories and equipment for in- process control under the responsibility of the production management. 11 ~kfk~

cGMP Guidelines for Biopharmaceuticals (cont) 4. Instructions and procedures are written in clear language, specifically applicable to the facilities provided. 5. Operators are trained to carry out procedures correctly 6. Records are made (Manually, with signature or recording instruments) during manufacturing to show that all steps required by the defined procedures have been taken and the expected quantity and quality were reached. Any significant deviations are fully recorded and investigated. 7. Records covering manufacturing and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible form. 8. Proper storage and distribution of the products minimized any risk to their quality 9. A system is available to recall any batch or product from sale or supply 10. Complains about marketed products are examined, the causes of quality defects investigated, and appropriate measurements taken in respect of the defective product(s) and to prevent recurrence. 12 ~kfk~

Information and material flow in pharmaceutical/ biopharmaceutical production process 13 ~kfk~

cGMP premises maintenance In-process control QC Sanitation & Hygiene Validation & Re-validation Self inspection team Complain management Recall procedures Calibration system Documentation equipment Label control personnel storage 14 ~kfk~

The cGMP Regulations  First issued: June 1963  Current = Dynamic roles (standard evolve over time) cGMP for finised Pharmaceuticals 21 CFR 210, ~kfk~

Examples of cGMP codes (FDA) Building, Facilities, Equipments (21 CFR ) Equipment Identification (21 CFR ) Equipment cleaning and use (21 CFR ) Electronic records, electronic signature (21 CFR Part 11) Process validation (General code of FDA process validation) Rubber articles for repeated use (21 CFR ) 16 ~kfk~