1. MANUFACTURING AND PRODUCTION OF BIOLOGICAL PRODUCTS (ERT 455)
GOOD MANUFACTURING PRACTICES (GMP) FOR BIOLOGICAL PRODUCTS
Munira Mohamed Nazari
School of Bioprocess Engineering
UniMAP

2. Course Outcome (CO3)
Ability to FORMULATE and PROPOSE primary/secondary processing, and up- scaling facilities for bio products manufacturing in accordance with Good Manufacturing Practices (GMP)

3. TOPIC OUTLINE Quality Management
Quality assurance & Quality control
Heating Ventilation and air-conditioning systems
Validation – biological products
Application of hazard analysis and critical control point (HACCP)

4. introduction

6. QUALITY CONTROL
Goal
GMP
&
SAFETY

7. Pre-requisite program
Assist manufacturers of food products and food related products to provide assurance to their customers that their products are manufactured in a hygienic manner and in accordance to best practices in manufacturing.
Required to be established before Hazard Analysis and Critical Control Points (HACCP) can be implemented, having GMP certification would definitely pave the way to an easier HACCP implementation and certification.
Certificate scheme
GMP
Pre-requisite program
Aspect
MS 1514
ASPECT - In short, it comprises the basic requirements of a manufacturing facility covering establishment, infrastructure, equipment design, construction, maintenance, process controls and personnel hygiene and awareness.
Standard for prescribing the requirements of pre-requisite programs which is required to be established before the implementation of HACCP. Applicable to all food manufacturers, primary and secondary processors, food catering and service operators, food retailers and food related industries
Design and facilities in the establishment, control of operations by equipment, temperature, time, pH or water activity control, maintenance and sanitation, personal hygiene, personnel training, transportation, conveyors, product information and consumer awareness

8. GMP Certification Scheme For Food Processing
GMP is a sanitary and processing requirement applicable to all food processing establishments. Many food industry companies have implemented the GMP certification scheme for food processing as the foundation upon which they have developed and implemented other food quality assurance systems and food safety management systems, such as HACCP, SQF 2000, ISO 9001 and ISO Certifying your food management system against the GMP standard will bring the following benefits:
Enhancement of your food safety management system;
Demonstration of your commitment to producing and trading safe food;
Prepare you for HACCP certification;
Increase in consumer confidence in your products; and
Prepare you for inspection by regulatory authorities and other stakeholders (food processing regulation compliant)

9. GMP Basic Requirement What is GMP ?
Part of Quality Assurance (QA) which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by marketing authorization or product specification.

10. GMP Basic Requirement Engineering for cGMP: Project Life-Cycle
those activities performed throughout the project life-cycle, which ensures that it will be easy and natural to operate the completed facility in accordance with current Good Manufacturing Practice.
Project Life-Cycle
means from project inception through feasibility studies/ conceptual design, engineering, construction, installation, start-up, operation, maintenance to final plant decommissioning or modification.

11. GMP Design requirements
1) Process issues
- closed or open (piping and equipment, expose to environment- measure to prevent contamination)
- level of batch to batch integrity required (simultaneous filling self-emptying vessels, or cleaning, or drying, sterilization between batches?)
2) Layout issues
- site location and layout – existing site, brown and green field, and overall site layout
- facility layout – cored vs. linear layout, segregation of areas, environment, containment strategy, security etc.

12. GMP Design requirements
3) Automation Strategy issues
- level of technology, use of design tools and models
- availability / redundancy, modularization / expansion
- instrumentation / cabling / field devices
- paperless batch records, electronic signatures.
4) Flow issues
- people (security, access, occupancy level)
- equipment (mobile or fixed, use of hard piping, cross-
contamination)
- components / materials (materials handling systems, cross-
contamination / mix-ups)

13. GMP Design requirements
5) Regulatory issues
- stage of development and production, category of the product (sterile medical, biological medical, herbal medicinal, medical gases, liquid, creams, tablets etc) and production process employed, facility location etc.
6) Validation Strategy issues
- validation required, validation team(s), validation plan(s).

14. Categories suggested for guidance
Facilities and environment
Services and utilities
Personnel flows
Material flows
Equipment flows
Equipment design
Computerized systems
Maintenance and services
Waste management
Procedure and documentation
Where to Apply

15. Quality management

16. Objectives QUALITY MANAGEMENT
To understand key issues in quality assurance/ good manufacturing practices/quality control.
To understand specific requirements on quality management and quality assurance including:
Organization
Procedures, processes and resources.
Objectives

17. Production and Quality Control
QUALITY MANAGEMENT
Quality relationships
Defining the overall policy of the organization towards quality, is over everything else.
Quality Management
Production and Quality Control
GMP
Quality Assurance
Concept that ensures the policy is achieved.
Part of quality assurance. It deals with the risks that cannot be tested. It builds quality into the product.
It is that part of GMP that is focused on testing of the environment and facilities, as well as the testing of the materials, components and product in accordance with the standard.

18. Philosophy and essential elements
QUALITY MANAGEMENT
What is Quality Management?
Is defined as the aspect of management function that determines and implements the quality policy.
The quality policy is a statement by the top management of the company of its overall intentions and direction relating to quality, formally expressed as a corporate policy. The top management of a company usually includes the board of directors or general manager of the company, the plant or factory managers together with the senior managers.
Philosophy and essential elements

19. QUALITY MANAGEMENT The basic elements are:
An appropriate infrastructure or “quality system” encompassing the organization structure, procedures, processes and resources.
The systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for “Quality”
Philosophy and essential elements
The totality of these actions is termed “Quality Assurance”

20. QUALITY MANAGEMENT Quality Management
Quality assurance is a management tool.
In contractual situations, it also serves to generate confidence in a supplier.
QA, GMP and Quality Control are interrelated aspects of Quality Management.
They are described on the following slides in order to emphasize their relationship and their fundamental importance to the production and control of pharmaceutical products.
Quality Management

21. Principles of Quality Assurance (QA)
QUALITY MANAGEMENT
Wide-ranging concept
covers all matters that individually or collectively influence the quality of a product.
Totality of the arrangements
to ensure that the drug is of the right quality for the intended use.
Quality Assurance incorporates GMP
and also product design and development which is outside the scope of this module
Principles of Quality Assurance (QA)
Therefore QA is not the duty of one organizational unit in the company alone, but is the responsibility of all staff members QA is a wide-ranging concept that covers all matters that individually or collectively influence the quality of a product. who in any way can influence product quality

22. Quality Assurance (QA)
QUALITY MANAGEMENT
QA System should ensure:
Products are designed and developed correctly.
Complying with, e.g. GMP, GCP, GLP
Production and control operations are defined.
Managerial responsibilities are defined
In job descriptions
The manufacture, supply and use of correct starting and packaging materials.
Quality Assurance (QA)
1. It must ensure that products are formulated and developed in accordance with quality assurance principles. Product quality begins with the development process. All of the development work should be undertaken with a commitment to quality assurance. This will enable easier adherence to quality assurance principles in the other areas of manufacturing.
2. It must ensure that all production and control operations are defined
3. It must identify all management responsibilities, with written job descriptions and organization diagrams. This will assist in ensuring that there are sufficient qualified and experienced people available who have the correct training to carry out their responsibilities.
It must ensure the manufacture, supply and use of correct starting and packaging materials
GMP – Good Manufacturing Practice
GCP – Good Clinical Practice
GLP – Good Laboratory Practice

23. Quality Assurance (QA)
QUALITY MANAGEMENT
QA System should ensure (cont...):
Controls are performed, including intermediates, bulk, calibration and validation
Correct processing and checking of the finished product
Products are sold/supplied only after review by the authorized person
Complying with marketing authorization, production and QC requirements
Proper storage, distribution and handling
Quality Assurance (QA)

24. Quality Assurance (QA)
QUALITY MANAGEMENT
QA System should ensure (cont...):
Procedures for self-inspection and/or quality audits
Reporting, investigation and recording of deviations
System for change control/approval
Regular evaluation of product quality to verify consistency and continued improvement
Quality Assurance (QA)

25. Quality Assurance (QA)
QUALITY MANAGEMENT
Manufacturer is responsible for the quality of the product.
Fit for intended use
Comply with marketing authorization
Safety, efficacy and quality
Senior management and commitment of all staff.
Requires a comprehensively designed and well implemented QA system.
Fully documented, and effectiveness monitored.
Competent personnel, sufficient premises, equipment and facilities.
Quality Assurance (QA)

26. Good Manufacturing Practices (GMP)
QUALITY MANAGEMENT
Is the part of QA that ensures that products are consistently produced and controlled.
Quality standards
Marketing authorization
Aim: Diminishing risks that cannot be fully controlled by testing of the final product.
Cross-contamination
Good Manufacturing Practices (GMP)
EXAMPLE
This risk can best be controlled by having a properly managed system of working that takes them into account. This means that there must be good design, and planned maintenance of facilities. The quality checking system also must be designed with this risk in mind and set out to find whether any errors have occurred. If we do not know what sort of cross contamination we have, then the work of the analyst is very difficult. The analyst should ideally know what to test for before commencing testing. In other words, if we do not know what the likely cross-contaminant is, then we cannot analyse for it.
Good Manufacturing Practice (GMP) is the part of quality assurance that ensures that products are produced and controlled consistently and reliably. This consistency of production and control is essential. It can only come about by having clear descriptions of the way in which the work will be done.
GMP specifically addresses risks that cannot be fully controlled by testing of the final product:
Cross-contamination
Mix-ups
These risks can best be controlled by having a properly managed system of working that takes them into account. This means that there must be good design, sound operation, and planned maintenance of facilities. It also means that the quality checking system must be designed with these risks in mind and set out to find whether any errors have occurred. Let us look at this problem in another way. If we do not know what sort of cross contamination we have, then the work of the analyst is very difficult. The analyst should ideally know what to test for before commencing testing. In other words, if we do not know what the likely cross-contaminant is then we cannot analyse for it.
There are a number of basic requirements for GMP, which we shall look at next

27. Good Manufacturing Practices (GMP)
QUALITY MANAGEMENT
Basic Requirements for GMP.
Clearly defined and systematically reviewed processes.
Batch documentation
Quality specification
Standard of Procedures (SOP)
Qualification and validation is performed.
Appropriate resources are provided:
Qualified and trained personnel
Premises, space, equipment and services
Materials, containers, labels
Procedures, storage, transport
Laboratories and in-process control
Good Manufacturing Practices (GMP)
Basic requirements for GMP are as follows:
1. Clearly defined and systematically reviewed manufacturing processes. This means that all batch documentation, all quality specifications and all relevant SOPs must be prepared in harmony with one another. It also means that all departments involved must be aware of the work of the other departments in order to eliminate discrepancies. Finally, the quality control staff acting as the overall coordinator of all these activities should be involved in all decisions related to the quality of the production. It is their responsibility to ensure that the activities are aimed at producing products that meet the required specifications. The specifications are approved by the drug regulatory authority.
2. Critical steps of production processes are validated. Since there is variability in the quality of materials and in the performance of the equipment, we need to check whether the process works with all the variability that can arise. This process of checking and documenting variability is known as validation. It means that the company must have sufficient knowledge of its materials, equipment and processes that it knows what variables are likely to arise. It can then carry out controlled experiments to ensure that whatever variables do occur, they can still produce products meeting specifications. Validation is also required if there is a change in any part of the process, materials or equipment used in the manufacturing.
3. Appropriate resources: personnel, buildings, equipment and materials are available to produce a quality product. This means that the company has evaluated all of the elements it needs to produce a product and has sufficient resources of the right quality for its production.
4. Manufacturing is based on clearly written procedures. The procedures referred to here include the batch manufacturing and testing instructions and the SOPs needed for every department. Preparing these procedures and documents is a very important task that needs careful thought. The module on documentation goes into this in more detail.
5. Operators are trained. A company can have "all the documentation in the world" but if its operators are not properly trained to carry out the tasks that they are supposed to perform then the company will not be successful. We will talk more about this in the session on personnel. Operators not only need initial training but also follow-up training

28. Good Manufacturing Practices (GMP)
QUALITY MANAGEMENT
Basic Requirements for GMP. (cont..)
Clear, written instructions and procedures
Trained operators to carry out the procedures correctly.
Records of actions, deviations and investigations
Records for manufacture and distribution
Proper storage and distribution of the products minimizes any risk to their quality.
Systems for complaints and recalls from sale or supply.
Good Manufacturing Practices (GMP)

29. QUALITY MANAGEMENT
Focused on testing of the environment and facilities, as well as the testing of the materials, components and product in accordance with the standard.
Quality Control (QC)

30. QUALITY MANAGEMENT

31. References QUALITY MANAGEMENT
World Health Organization, Basic Principles of GMP, Module 2, January 2006
Quality Assurance of Pharmaceuticals, Volume 2, Good Manufacturing Practices and Inspection. World Health Organization
References

33. heating ventilation and air-conditioning systems