GOOD MANUFACTURING PRACTICE FOR BIOPROCESS ENGINEERING (ERT 421)

1. GOOD MANUFACTURING PRACTICE FOR BIOPROCESS ENGINEERING(ERT 421) Huzairy Hassan School of Bioprocess Engineering UniMAP

2. Current Good Manufacturing Practice (cGMP)

3. 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.

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

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

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

7. Quality Assurance and Quality Control ~kfk~

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

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

10. cGMP for Biopharmaceutical Industries ~kfk~ 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: Cross contamination (in particular by unexpected contaminants) Mix-ups (confusion) such as false labeling.

11. cGMP Guidelines for Biopharmaceuticals ~kfk~ • 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. • All steps of manufacturing processes and any significant changes made to the process are validated. • 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.

12. cGMP Guidelines for Biopharmaceuticals (cont) ~kfk~ Instructions and procedures are written in clear language, specifically applicable to the facilities provided. Operators are trained to carry out procedures correctly 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. Records covering manufacturing and distribution, which enable the complete history of a batch to be traced, are retained in a comprehensible form. Proper storage and distribution of the products minimized any risk to their quality A system is available to recall any batch or product from sale or supply 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.

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

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

15. The cGMP Regulations cGMP for finised Pharmaceuticals 21 CFR 210, 211 www.fda.gov/cder/dmpq ~kfk~ • First issued: June 1963 • Current = Dynamic roles (standard evolve over time)

16. Examples of cGMP codes (FDA) ~kfk~ Building, Facilities, Equipments (21 CFR 211.42-72) Equipment Identification (21 CFR 211.105) Equipment cleaning and use (21 CFR 211.182) Electronic records, electronic signature (21 CFR Part 11) Process validation (General code of FDA process validation) Rubber articles for repeated use (21 CFR 177.2600)