1. Quality System
QC & Validation, BioT 006

2. Quality Systems in Manufacturing
What is a Quality System?
An infrastructure involving:
the organizational structure,
procedures,
processes &
Resources
THAT ARE necessary to
Ensure Adequate Confidence that a product
will satisfy given requirements for quality.

3. Quality Systems Where is it found? What does it do?
Commitment to Quality by the Organization
Commitment to and by the management to a WRITTEN quality program
Commitment to an appropriate organizational structure to insure product quality and safety
Commitment to manufacturing for proper resources, facility, equipment, the organization’s structure, staff, and training to do things right the first time
Commitment to manage a program of continuous improvement including internal assessments and initiation of necessary corrective action
Where is it found?
What does it do?
Who does it affect?
When does it start?

4. Obejectives To understand key concepts of: Quality management
Quality assurance
GMP
Quality control
To understand level of quality documentation.
To understand specific requirements on quality manual.
To develop quality manual based on GMP requirements

5. BASIC PRINCIPLE OF QUALITY MANAGEMENT
Manufacturer should ensure the products comply with the requirements of FDA
They should also comply with any other applicable regulations:
ICH, state and/or local
The attainment of this quality objective should be led by:
the senior management and requires the participation and commitment by:
staff, suppliers and distributors.

6. BASIC PRINCIPLE OF QUALITY MANAGEMENT 2
To achieve the reliable quality objective, there should be a comprehensive QA system incorporating GMP.
The QA system should be fully documented and its effectiveness should be monitored.
All parts of QA system should be adequately resourced with:
competent personnel
suitable and sufficient:
premises
equipment
facilities

7. BASIC PRINCIPLE OF QUALITY ASSURANCE
QA covers all matters which:
Individually or collectively influence the quality of a product.
QA refers to a sum total of activities organized with an aim to:
Ensure the products are of the required quality.
QA incorporates:
GMP and
Factors that fall outside the scope of the GMP Guide.

8. BASIC REQUIREMENTS OF QUALITY ASSURANCE
Ensure that products are designed and developed based on:
sound scientific rationale
Taking GMP or GLP (Good Laboratory Practice) principles into consideration.
Ensure that managerial responsibilities are clearly specified.
Ensure that production and control operations are clearly specified and GMP is adopted.
Organize supply and use of correct raw materials/starting and packaging materials.
Ensure that finished products are:
correctly processed and checked before release.

9. BASIC PRINCIPLES OF GOOD MANUFACURING PRACTICES
Part of QA which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use.
Minimize risks :
cross contamination
mix up
Ensure products/materials are traceable to the original source.
Product testing is a not reliable way to assure product quality.
Should BUILD quality into the product!
Production and quality control functions should be independent of each other.

10. BASIC PRINCIPLES OF GOOD MANUFACURING PRACTICES II
All necessary facilities/resources for GMP should be provided :
clearly defined manufacturing processes using unambiguous language
Good documentation system
Appropriate storage and transport
Systematic internal quality audit
Proper product recall system
Correct handing of complaints
Comprehensive CAPA

11. BASIC PRINCIPLES OF GOOD MANUFACURING PRACTICES II
QC is part of GMP.
QC is concerned with:
sampling
specification
testing
Manufacturer should have a QC department.
QC should be headed by an appropriately qualified and experienced person.
QC should be independent from production and other departments.
Ensure that the necessary and relevant tests are actually carried out.
Ensure that no materials or products will be released for sale or supply until their quality has been:
Evaluated &
Is judged to be satisfactory

12. SCOPE OF QC Items concerned : Starting materials Packaging materials
Bulk products
Intermediate/in-process materials
Finished products
Environmental conditions

13. BASIC REQUIREMENTS OF QUALITY CONTROL
Adequate facilities, trained personnel and approved procedures should be available for:
Sampling
inspecting and testing
environment monitoring
Sampling by QC personnel
Testing by approved test methods
Maintenance of QC records
Any failure investigation records.

14. BASIC REQUIREMENTS OF QUALITY CONTROL II
Ingredients comply with regulatory specification (grade, composition, strength)
Review and evaluation of production documentation
Assessment of process deviations
Release of batches by authorized person
Sufficient reference samples of starting materials and finished products

15. OTHER DUTIES OF QC Establish QC procedures Manage reference standards
Ensure correct labeling
Stability testing
Complaint investigation
Environmental monitoring

16. QUALITY CONTROL ASSESSMENT OF MANUFACTURING ACTIVITY
Must include the following:
Production conditions
In-process quality control activity
Manufacturing documentation
Compliance with finished product specification
Examination of the finished products
QC Access
QC personnel MUST have access to production area for sampling and investigation
Access to QC lab is strictly for QC personnel

17. QUALITY CONTROL ACTIVITIES
QC covers the following:
Sampling
Specification
Testing
Release procedures
Recalls and complaints
Decision making in all quality matters
Laboratory operations
Release authorization
Investigation and reporting

18. Quality Relationship Quality Management Quality Assurance GMP
Quality Control

19. OBJECTIVE OF DOCUMENTATION
A reliable evidence for GMP compliance.
To establish, monitor, and record “quality” for all aspects of the production, quality control and quality assurance.

20. PURPOSE OF DOCUMENTATION
Clearly written documentation prevents errors
Provides assurance that quality related activities are carried out exactly the way they have been planned and approved
Employees know what to do
Responsibilities and authorities are identified
Forms the basis for continuous improvement

21. QUALITY SYSTEM DOCUMENTATION
Documentation is the key to operating a manufacturing company in compliance with GMP requirements.
All the elements, requirements and provisions adopted by manufacturing company for its quality system should be documented in a systematic, orderly and understandable manner in the form of policies and procedures.
Documents should be developed, prepared, approved, reviewed and distributed in a controlled manner.
It should be written in detail and in simple language that can be understood by the user.

22. TIERS OF DOCUMENTATION
Quality Manual
Quality Procedures
Supporting Documents or work instruction
Quality Records
Broadly,
all documents relating to QUALITY
fall into these categories & should be controlled
All levels are integrated to form a comprehensive and cohesive documentation network via a system of cross referencing

23. Controlled Documents
A controlled document must meet the following conditions: 1. It must be numbered or coded according to the defined numbering scheme.
It must be reviewed and approved before issue.
3. Changes to these documents must be authorized and controlled.

24. Supporting Documents or work instruction
Quality Manual
Quality Manual
Quality Procedures
Supporting Documents or work instruction
Quality Records
The strategic document that outlines the company’s system of providing Quality Assurance to achieve customer satisfaction.
The Quality Manual could be in one document supported by several tiers of document, each becoming progressively more detailed.
The Quality Manual defines
the policy of the company,
the organisational structure, functions,
responsibilities,
procedures,
instructions,
processes and resources
for implementing the quality management.

25. Supporting Documents or work instruction
Quality Procedures
Quality Manual
Quality Procedures
Supporting Documents or work instruction
Quality Records
The tactical document that outlines the activities or operations of the organization in implementing the stated quality policies.
The Quality Procedures ensure that if necessary, samples of starting materials, intermediate, and finished products are taken, tested to determine their release or rejection on the basis of test results and other available evidence related to quality.
The quality procedures enable every employee:
to work individually and collectively to achieve the organization’s quality objectives.

26. Supporting Documentation
Quality Manual
Quality Procedures
Supporting Documents or work instruction
Quality Records
The operational document containing instructions specifying how the activities are performed or products are accepted.
The Working Instruction should describe step by step instruction specific to a process and machine, specifying the tools, workmanship criteria, tolerance, and direction for the process.
The working instructions is the easy guide for the operator to confirm each step in executing a task.
The working instructions are needed to guide the staff in performing a specific function or task.

27. Supporting Documents or work instruction
Quality records
Quality Manual
Quality Procedures
Supporting Documents or work instruction
Quality Records
Quality Records refer to results as well as charts and data pertaining to activities performed such inspection, testing, survey, audit, review, etc. They should be maintained as important evidence to demonstrate :
conformance to specific requirements;
the effective operation of the quality system
All Quality Records should be :
Legible and clear
Dated
Readily identifiable and retrievable
Carry authorization status
Retained for a designated period
Protected from damage, light and deterioration while storage

28. ESTABLISHMENT OF QUALITY MANUAL
Quality Procedures
Supporting Documents or work instruction
Quality Records
Main points of consideration

29. QUALITY MANUAL DESCRIPTION
This Quality Manual should state the company’s commitment to quality and describe the quality system of an organization .
Quality System refers to the appropriate infrastructure encompassing Procedures, Processes and Resources.
Included in the Quality Manual shall be a clearly defined and documented quality policy statement that states the company’s commitment to produce safe and quality products and its responsibility to its customers.
The company’s senior management shall demonstrate commitment to the implementation of the Company Quality Policy by signing off the policy.
All supervisory staff and key personnel shall understand and implement the policy.
The quality policy shall be communicated to all staff of the company and regularly reviewed.

30. QUALITY MANUAL DESCRIPTION II
Top management shall establish its quality policy and ensure that it :
is appropriate for the needs of the organization and its customers;
includes commitment to meeting requirements and continual improvement;
provide a framework for establishing and reviewing quality objectives;
is communicated, understood and implemented throughout the organization;
is reviewed for continuing suitability.

31. QUALITY MANUAL DESCRIPTION III
It is a formal declaration by the company of how it conducts its business with respect to the achievement and assurance of quality.
It is a documented set of managerial instruction on quality matters.
It should describe the organization structure and define clear job description of key employees.
The Quality Manual should be readily available to relevant staff.
The company’s management shall regularly review its quality system to ensure continued effectiveness and suitability.

32. PREPARATION OF A QUALITY MANUAL
Quality manual can be prepared according to ISO prescribed format if it does incorporate the GMP principles or it should contain the following features :
Title and Scope – which company sites and operations are covered?
Example:
This manual describes the quality arrangements for manufacturing process starting from receiving of starting materials to delivery of finished products which are manufactured at :
11111 California Avenue
Los Angeles, CA 91234
This manual describes the policies and summaries of the quality management system established.

33. PREPARATION OF A QUALITY MANUAL II
Management Organization
There should be a person named as management representative for ensuring the implementation of QM.
This person should be appointed by senior management to represent the management authority and to monitor the system
Company’s
organizational structure,
authority,
responsibilities and functions
Control of Manual
Review and revision to ensure:
relevancy and accuracy
Distribution

34. PREPARATION OF A QUALITY MANUAL III
Contents
Describe how the quality management system works relating to
Personnel  Internal Audit
Premises  Storage
Equipment  Contract Manufacturing
Sanitation & Hygiene & Analysis
Production  Product Complaint
Quality control  Product Recall
Documentation
Draw attention to the specific use of formally written and established procedures.
Reference may be in the form of table appended to the manual
Contain only the management policies which govern the application of procedures.
Technical procedures are not included

35. PREPARATION OF A QUALITY MANUAL IV
Checklist for a Quality Manual
Does it define the scope of the Quality Management System that it operates?
Is it a controlled document?
Is there an authorized management representative?
Are the organization structure and control system described and documented?

36. PREPARATION OF A QUALITY MANUAL V
Specify the company’s policies on:
Criteria of staff involved in the manufacturing activities
Assuring staff’s competency in their work
Assuring staff’s understanding of procedures, work instruction, GMP etc.
Assuring that there is no ambiguity of staff’s roles and responsibilities
Staff resources allocation
Authority of QC and Production

37. QUALITY MANUAL CONTENT PREMISES
Specify the requirements of location, design , constructions and maintenance of manufacturing premises with respect to the following:
prevention of contamination from surrounding environment and pests
prevention of mix up of materials and products
facilities such as toilet, changing rooms, sampling areas and QC lab
defined areas for certain activities
wall, ceiling, drains, air intake and exhaust, lighting and ventilation, pipe work and light fitting
storage areas

38. QUALITY MANUAL CONTENT EQUIPMENT
Describe the requirements of the:
design
installation and maintenance of the equipment and its support system such as ventilation system.

39. QUALITY MANUAL CONTENT SANITATION & HYGIENE
Describe the sanitation and hygiene practices to avoid contamination of the manufacturing of products with respect to :
health condition of the staff
good personal hygiene
avoid direct physical contact with product
restricted activities within controlled areas
measures to prevent contamination by staff

40. QUALITY MANUAL CONTENT PRODUCTION
Describe the control of manufacturing process with respect to the following :
Checking and verification of starting materials (raw materials and water)
Traceability of starting materials to the
product
Handling of rejected materials
Batch numbering system
Weighing and measurement
Production process of dry and wet products
Labeling and packaging
Finished product: Quarantine and Delivery

41. QUALITY MANUAL CONTENT QUALITY CONTROL
Describes how QC ensures products contain the correct materials of specified quality and quantity and are manufactured under proper conditions.
Describes the QC requirement on the following:
Sampling
Inspecting
Testing
Environmental monitoring program
Review of batch documentation
Sample retention program
Stability studies
Maintenance of material or product specification
Reprocessing
Returned products

42. QUALITY MANUAL CONTENT DOCUMENTATION
Describe the documentation control system
with respect to the following:
Documentation structure (e.g. Quality Manual, Quality Procedures, Instructions and Records)
Format requirement for different types of documents
Numbering and reference system
Handling of controlled and uncontrolled documents
Handling of obsolete versions
Preparation, approval, distribution of documents
Review and change control
Documentation controller
Storage of master documents
Retention period for records
List of controlled documents

43. QUALITY MANUAL CONTENT INTERNAL AUDIT
Describe the policies related to Internal Audits
Audit team
Frequency of audit
Follow up actions
Overall responsible person for organizing the internal audit (Who)

44. QUALITY MANUAL CONTENT STORAGE
Specifies the requirements concerning storage of materials/ products with respect to the following:
Space, design, security and cleanliness
Storage of quarantine stocks
Storage of hazardous substances
Conditions of storage area
e.g. temperature & relative humidity
Receiving of incoming materials
Stock control
e.g. FIFO principle, proper labeling on the container

45. QUALITY MANUAL CONTENT PRODUCT COMPLAINT
Describes the systems for handling product complaints with respect to the following:
The designated person responsible for handling complaints
Authorized person who will decide on the measures to be taken
Investigation
Corrective and Preventive Actions
Review of report
Notification to Authority

46. QUALITY MANUAL CONTENT When Something Goes Wrong
CAPA:
Corrective action means fix the problems that
have already occurred and may happen again
Preventive action means looking for problems
that have not yet occurred and to prevent them
RCA:
Root cause analysis
OOS:
Out-of-specifications
It is a result in which product fails to
meet its requirements

47. QUALITY MANUAL CONTENT PRODUCT RECALL
Describe the systems for recalling from the market of products known or suspected
to be defective:
The designated person responsible for coordination
Classification of product recall
Provision of sufficient resources
Maintenance of Distribution records
Progress report and final report with reconciliation