GOOD MANUFACTURING PRACTICES

FOR PHARMACEUTICAL PRODUCTS (CPOB)

Wayan Redja
Fakultas Farmasi Universitas Pancasila
Jakarta, 2019
 GOOD MANUFACTURING PRACTICES
FOR PHARMACEUTICAL PRODUCTS (CPOB)

A. INTRODUCTION
B. QUALITY MANAGEMENT IN GMP
C. GMP RESOURCES
D. GMP PROCESSES

E. ANNEX OF GMP
 A. INTRODUCTION

1. WHAT, WHY AND HOW GMP?

2. COVERAGE OF GMP
3. PRINCIPLES OF GMP / QA / QM
4. ERROR CLASSIFICATION OF GMP
5. GMP PROCESS FLOW
6. PDCA CYCLE OF GMP PROCESS IN ACCORDANCE
WITH QMS ISO 9001:2015
 1. WHAT, WHY AND HOW GMP
 WHAT? GMP (CPOB) = Good QM (QA) for Pharmaceutical Product

Definition of GMP?
Regulation issued by BPOM on CPOB as part of QA which
ensure that products are consistently produced and controlled
to the quality standards appropriate to their intended use and
as required by the marketing authorization.

(WHO, Technical Report Series, No.961, 2011)

# quality standards = specified quality = specification
GMP : GMP for Pharmaceutical Products (CPOB)
GMP for Active Pharmaceutical Ingredients (CPBBOB)
GMP for Traditional Medicine (CPOTB)
GMP for Cosmetic (CPKB), etc
Regulation of Food & Drug Control Agency. (BPOM)
 1. WHAT, WHY AND HOW GMP?
 WHY?
Why GMP must be implemented?
- To assure product quality
- Substandard medicine may risk life
- CPOB is government regulation.
- Punishment
- Bad image > bankrupt

 HOW
How to implement GMP?
- Do it right from the first timeand every time!
- Follow the GMP regulation
- Follow all GMP principles
- Do what is written, and write what is done. SOP > Record
- Follow the PDCA cycle consistently.
 2. COVERAGE OF GMP/CPOB
A. Management C. Processes
1. Quality System 6. Qualification and
in Pharmaceutical Validation
Industry 7. Production
8. Quality Control
B. Resources and Critical 9. Self Inspection,
Supporting Facilities 10. Outsourcing Activities
11. Handling of Product
2. Personnel Complaint and Product
3. Premises and Recall
Facilities 12. Good Storage and
4. Equipment Distribution Practice
5. Documentation
D. Annex: 13 Topics
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 3. PRINCIPLES OF GMP/QA/QM

 Principles
> Do it right from the first time and every time
> Do what is written and write what is done
> Build quality into the product
> Only correct resources, activities, product can be passed.
> Activities shall be made in an air controlled room if
there is possibility of air contact with material or product,
> Wash your hands before and after work
> Use appropriate protective clothes whenever you enter
production room.
 4. ERROS CLASSIFICATION OF GMP

 Classification of Error on Violation of GMP

1. Cross Contamination
2. Degradation of Quality
3. Mix-up
4. Other Errors
5. Health Hazard
 5. GMP PROCESS FLOW
MR = Marketing Request PPIC = Production Planning &
PP = Production Plan Inventory Control
PO = Purchase Order PR = Purchase Request
RM = Raw Material Pcs = Purchasing
IP = Intermediate Product Rcv = Receiving
BP = Bulk Product Qrt = Quarantine
FP = Finished Product Wgh = Weighing
MR/ST IPC = In Process Control Mix = Mixing
QC = Quality Control Fill = Filling Tab =Tabletting
ST = Stock Pkg = Packaging
PPIC
PP/PR QA

Pcs I PC / QC

PO RM RM IP IP BP BP FP FP
Pcs Rcv, Qrt Wgh > Mix Qrt Fill,Tab Qrt Pkg Qrt

PROCESSING PACKAGING

PRODUCTION

MANUFACTURING: GMP
 6. PDCA CYCLE OF GMP (CPOB) PROCESS FLOW

C. Processes
12. Qualification and Validation
a. Principle
b. Planning
c. Documentation
d. Qualification
e. Process Validation
f. Cleaning Validation
g. Change Control
h. Revalidation
i. Analytical Method Validation.
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 B. QUALITY MANAGEMENT IN GMP

1. Quality Management
a. Organization
b. Organization Structure and Skill
c. Management
d. Quality Management
1). Principle
2). Quality Assurance
3). CPOB
4). Quality Control
5). Product Quality Review
6). Quality Risk Management WR10
 B. QUALITY MANAGEMENT IN GMP

1. Quality Management
a. Organization
People or group of people in a system with adequate
resources to achieve their goal in accordance with their
mission and vision.

- Institution, company, foundation (government, private,

profit, non-profit)
- Good Quality Management (Quality Assurance)
forgoal achievement

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 B. QUALITY MANAGEMENT IN GMP
1. Management
a. Organization Structure and Skill

TOP

MIDDLE

LOWER M GT

WORKER / DOER

ORGANIZATION STRUCTURE SKILL

 B. QUALITY MANAGEMENT IN GMP

1. Quality Management
a. Organization
b. Organization Structure and Skill
c. Management
Coordinated activities to direct and control an
organization.
- POAC
- PDCA
- QA > Do it right from the first time, and every time!
 C. GMP RESOURCES

Resources
2. Personnel
a. Principle
b. General (Qualification, Quantity,
Organization Structure, Job Description.)
C. Key Personnel
d. Organization, Qualification and
Responsibility
e. Training

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 C. GMP RESOURCES

Resources
3. Premises and Facilities
a. Principle
b. General
c. Weighing Area
d. Production Area
e. Cleanliness Room Qualification
f. Storage Area
g. QC Area
h. Supporting Facilities
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 C. GMP RESOURCES

Resources
3. Premises and Facilities
i. Critical Supporting Facilities
1). AHU
- Principle
- Type
- Component Function
- Operational Principle
- Room Classis
2) Water Treatment

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 C. GMP RESOURCES

B. Resources
3. Premises and Facilities
i. Critical Supporting Facilities
2) Water Treatment
- Principle
- Water Purification Methods
- Types of Purified Water
- Quality Control

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 C. GMP RESOURCES

Resources
4. Equipment
a. Principle
b. Design and Construction
c. Installation
d. Maintenance

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 C. GMP RESOURCES

Resources
5. Documentation
a. Principle
b. General
c. Type of Documents
- Specifications
- Master Production Document
- Master Processing Procedure
- Master Packaging Procedure
- Batch Processing Record
- Batch Pakaging Record
- SOP
- Records and Reports
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 D. GMP PROCESSES

Processes
6. Sanitation and Hygiene
a. Principle
b. Personnel Hygiene
c. Premises and Facilities
d. Equipment
e. Cleaning and Sanitation Validation

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 D. GMP PROCESSES

Processes
7. Production
a. Principle
b. General
c. Raw Material
d. Process Validation
e. Prevention of Cross Contamination
f. Batch / Lot Numbering System
g. Weighing and Dispensing
h. Processing
i. Solid Material and Product
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 D. GMP PROCESSES

Processes
8. Quality Control
a. Principle
b. General
c. GLP
d. Documentation
e. Sampling
f. Testing
g. Testing Requirement
h. On-going Stability Program
i. Solid Material and Product
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 D. GMP PROCESSES

Processes
9. Self Inspection,Quality Audit, Supplier
Audit & Approval
a. Principle
b. Quality Audit
c. Supplir Audit & Approval

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 D. GMP PROCESS

Processes
10. Handling of Product Complaint and
Recall
a. Principle
b. Poduct Complaint
c. Product Recall

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 D. GMP PROCESS

Processes
11. Contract Manufacture and Analysis
a. Principle
b. General
c. Contract Giver
d. Contract Receiver
e. Contract

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 D. GMP PROCESSES

Processes
12. Qualification and Validation
a. Principle
b. Planning
c Documentation
d. Qualification
e. Process Validation
f. Cleaning Validation
g. Change Control
h. Revalidation
i. Analytical Method Validation
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 E. ANNEX OF GMP (CPOB)
 Annex
1. GMP for Active Pharmaceutical Ingredient
2. GMP of Sterile Peoduct
3. GMP of BiologicalMaterial and Product for
Human Use
4. GMP of Blood Product
5. GMP of Investigational Product
6. GMP of Presurized Measured Dose Inhalation
7. GMP of Medicinal Gas
8. GMP of Radiofarmaca
9. The Use of Ionizer Iradiarion in Drug Manufacturing
10, Quality Risk Manajemen
11. Real Time and Parametric Release
12. Reference Sample and Retained Sample
13. Real Time and Parametric Release Test.
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 COMPREHENSIVE GMP PROCESS

PROVISION OF INFRASTRUCTURE
- License - Critical Supporting Facilities
- Access - Approval of BPOM
- Premises

PROVISION OF OTHER RESOURCES

- Specification & SOP - Equipment
- Personnel - Qualification and Validation
- Material

OPERATION
- PPIC > Purchasing > Receiving > QC >
> Processing / IPC / QC > Packaging / IPC / QC > QA
WR-29-QM
THANK YOU

WR-30-QM
WR-31-QM
GOOD MANUFACTURING PRACTICES
FOR PHARMACEUTICAL PRODUCTS

 Introduction
 Quality Management
 Resources and Facilities
 Processes

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Quality Management in CPOB
Quality Management
> Management with regard to quality.
> One aspect of management function to
establish Quality Policy and commit on it.

Basic Elements
> Quality Management System
> Quality Assurance
> GMP: Production , QC, etc.
> Quality Risk Management
> Product Quality Review
> Quality Management Review:
QMS, QA (GMP, QC, PQR, QRM)
 Introduction

 Definition
 Purpose
 Why and How to implement GMP?
 Principles of GMP
 Classification of Errors in GMP
 GMP vs ISO 9001
 Coverage of GMP

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 Introduction

 Definition of GMP?
Regulation issued by BPOM as part of QA which
ensure that products are consistently produced
and controlled to the quality standards appropriate
to their intended use and as required by the
marketing authorization.
(WHO, Technical Report Series, No.961, 2011)
# quality standards = specified quality = specification

GMP : GMP for Pharmaceutical Products (CPOB)

GMP for Active Pharmaceutical Ingredients (CPBBOB)
GMP for Traditional Medicine (CPOTB)
WR03
GMP for Cosmetic (CPKB), etc
 Introduction

 Purpose of GMP?
To ensure the quality of products by
eliminating the nonconformance in the
implementation of GMP such as:

Cross-contamination,
Mix-ups (confusion),
Degradation,
Errors,
Health hazards
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 Introduction
Goal
> Good Quality Medicine

Three criteria of Quality Medicine ?

QES
Quality Efficacy Safety
To assure the quality medicine appropriate to their
intended use until the medicine appropriately used by
the patient, Total QA (GMP, GSP, GDP, GPP)* shoulld
be undertaken by the person in charge)
*Person in Charge: Medical Doctor, Pharmacist, Patient
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 Introduction

 Why GMP?
- Government regulation
- QA of drug

 How to Implement GMP?

Practice the principles of Quality Management
> Do it right from the first time and every time.
> Do what’s written and write what is done.
> Implement Quality Management Principles
(ISO 9000 : 2015).

Practice the principles of GMP

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 Introduction

 Principles of GMP?
> Build quality into the product
> Make quality people before making quality product.
> The next process is our customer.
> Only correct resources, activities, product can be passed.
> Activities shall be made in an air controlled room if
there is possibility of air contact with material or product,
> Wash your hands before and after work
> Use appropriate protective clothes whenever you enter
production room.

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 Introduction
 Classification of Error on Violation of
GMP

1. Cross Contamination
2. Degradation of Quality
3. Mix-up
4. Other Errors
5. Health Hazard

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 Introduction
ISO 9001 vs GMP

ISO 9001 GMP

International Standard National, Regional Standard

Voluntary Compulsory
Any Organization Manufacturing Organization
QMS Requirements Quality Product Certification

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 Introduction
 Coverage of C. Processes
GMP 6. Sanitation and Hygiene
7. Production
A. Management 8. Quality Control
9. Self Inspection, Quality
1. Quality Management
Audit, Audit and Vendor
Approval
B. Resources 10. Handling of Product
2. Personnel Complaint and Product
3. Premises and Recall
Facilities 11. Contract Manufacture and
4. Equipment Analysis
5. Documentation 12. Qualification and Validation
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 Process
Activity to transform input into output using resources

Efficiency Effectiveness

INPUT PROCESS
OUTPUT
RESOURCES, 5M
Value
adding
low
Customer Customer
Requirements Satisfaction
Infor-
Feedback mation
flow

Productivity = output / input = effectiveness / efficiency

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 Quality Management
 Interrelation of QM, QA, GMP and QC

QM/QA GMP GMP

QMS R&D QC PRD

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 GMP Quality Management
Quality Management System
> Organization Structure
> Processes
QA, QC, Production, Qualification & Validation,
Sanitation & Higiene, Audit, Contract Manufacture &
Analysis, Handling of: complaint, product recall,
returned products.
> Procedures
> Resources (5M)
 Quality Management

 Quality Assurance (QA)

> QA is a wide-ranging concept covering all matters that
individually or collectively influence the quality of a
product.
>The totality of arrangements made with the object of
ensuring that pharmaceutical products are of the
quality required for their intended use.
(WHO, Quality Assurance of Pharmaceuticals, Vol.2, 2007, p.309)

> Part of quality management focused on providing

confidence that quality requirements will be fulfilled.
(ISO 9000:2015)

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 Quality Management
Quality Assurance
Coverage: All matters of PDCA cycle in R&D, Production,
Quality Control.
Authority and Responsibility in GMP
> Qualification and Validation > Change control
> Production & QC > Quality Risk Management
> Product Release > Product Quality Review
> Audit (internal & external) > Quality Management Review
> Nonconformance handling

Pinciple: “ Do it right from the first time, and every time.”

Conduct the PDCA cycle in accordance with the principles of:religion,
regulation, science & technology.
 Quality Management
GMP (Production and QC)
POAC
> Resources
> Processes

Pinciple
Build quality into the product
 Quality Management
Production
Part on GMP focus on producing the
right quantity of quality product at the
right time as planned.

Quality Control
Part of GMP or QA focus on testing of
materials, products and environment
to fulfill quality requirements.

Basic Principle
Do what is written and write what is done!
 Quality Management
Product Release
Chek
> Bach Production Record (Processing & Packaging)
> COA
> Marketing authorization document
> Retained Sample

Report
> Product Release & Reject Chek List
> Release or Reject Label
> File: Original (Head of QA), Copy ( QA staff)
Report of Nonconformance

General
Nonconformance Test Results
(HULS)
Production
Contamination
Equipment
Critical
Nonconformance Handling

Purpose
Coverage
Responsible Person
Forms
Procedure
Documentation Distribution
 Change Control

Purpose
Coverage
Responsible Person
Forms
Procedure
Documentation Distribution
 Product Quality Review

Purpose
Coverage
Responsible Person
Procedure
Documentation Distribution
THANK YOU

WR-55-QM
 Coverage of GMP

Quality Management
Personnel
Premises
Equipment
Sanitation and Hygiene
Production
Quality Control
Self Inspection and Quality Audits
Handling of product Complaint, Product Recall, and
Returned Product
Documentation
Contract Manufacture and Analysis
Qualification and Validation
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 The Main Principles of GMP
Processes are clearly defined and systematically reviewed to
assure consistent performance.

All necessary resources are provided:

- qualified trained personnel,
- adequate premises and space,
- suitable equipment and services,
- appropriate materials, containers and labels,
- approved procedures and instructions,
- suitable storage and transport,
- adequate personnel, laboratories, and equipment for IPC.

Qualification and validation are performed

Instructions and procedures are written in clear and unambiguous

language, applicable to the facilities provided.
 The Main Principles of GMP
Operators trained to carry out procedures correctly.

Records are made during manufacture to assure instructions and

procedures have been done as expected, and deviations are fully
recorded and investigated.

Products are properly storage and distribute to minimize the risk of

quality.

Manufacturing and distribution records are retained in a

comprehensible and accessible form, for easy tracablility.

Product recall systems available.

Complaints are quickly handled, examined, investigated, and

appropriate measures taken to prevent recurrence.
 QUALITY MANAGEMENT

QMS ISO Series 9000

QMS ISO 9000
Quality Management Principles ISO 9000
Quality Assurance Principles

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 Definition of
Introduction
Management, and Quality Management

Management (ISO 9000)

Coordinated activities to direct and control an organization.
Those activities consist of interrelated activities are known as
Management Functions, i.e. POAC (Planning, Organizing, Actuating,
and Controlling ) or PDCA (Plan, Do, Check, Act).

Quality Management
Management with regard to quality
Quality Management = QMS + QA
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 ISO 9001

ISO 9001
International standard of Quality Management System –
Requirements, published by ISO.
● It specifies requirements for a quality management
system.
● To provide products that fulfill customer and
regulatory requirements.
● To enhance customer satisfaction

# ISO The International Organization for Standardization, Geneva, Switzerland.

The members are the Standard Institutions of more than 160 countries including
Indonesia (BSN).

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 ISO 9001 vs GMP

ISO 9001 GMP

International Standard National, Regional Standard

Voluntary Compulsory
Any Organization Manufacturing Organization
Quality Management Quality Management &
Requirements Technical Requirements

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 ISO 9000
Introduction
Quality Management Principles

Customer focus
Leadership
Involvement of people
System approach to management
Process approach
Factual approach to decision making
Mutually beneficial supplier relationship
Continual improvement

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 Quality Assurance Principles

• Make quality people, before making quality product.

Quality People
Good attitude, Knowledgeable, Skillful

• Quality must be build into the product.

•: Do it right from the first time and every time
(POAC / PDCA)
• Do what was written and write what is done.
• The next process is our customer
• 5 NOs: Don’t make, deliver, accept, keep, or use
bad quality product.
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 Quality Assurance Principles
POAC / PDCA
POAC (Management) PDCA (worker)
Plan Plan
- activities and resources. - the activity and the resources
Organize Do
- what are planed - what is planned
Actuate Check
- what are organized. - what is done
Control Act
- what are actuated and - correct or report
solve the problems the problem
 Process-based QMS of ISO 9000

CUSTOMER Management CONTINUAL

REQUIREMENTS Responsibility IMPROVEMENT

1 Measurement
Resource CUSTOMER
Analysis
Management SATISFACTION
Improvement
5
Product
Realization
INPUT OUTPUT
2 PROCESSES
3 4

Value-adding activities Information flow

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 Process
Activity to transform input into output using resources

PDCA CYCLES Continual Improvement

Effectiveness
PROCESS
INPUT OUTPUT
RESOURCES, 5M
Value
Efficiency adding
low
Customer Customer
Requirements Satisfaction
Infor-
Feedback mation
flow

Productivity = output/input = effectiveness / efficiency

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 PRODUCT REALIZATION IN GMP

Quality Management
Sanitation & Hygiene
Customer Production Customer
Requirements Quality Control Satisfaction
Self Inspection & Quality Audits
Claim Handling & Recall
Contract Manufacture & Analysis
Qualification & Validation

INPUT PROCESSES OUTPUT

RESOUCES
Personnel, Premises, Equipment,
Material, Documentation,

QA & QRM
 MR = Marketing Request PPIC = Production Planning &
PP = Production Plan Inventory Control
PO = Purchase Order PR = Purchase Request

PROCESS FLOW RM = Raw Material

IP = Intermediate Product
BP = Bulk Product
Pcs = Purchasing
Rcv = Receiving
Qrt = Quarantine

IN GMP FP = Finished Product

IPC = In Process Control
QC = Quality Control
Wgh = Weighing
Mix = Mixing
Fill = Filling Tab =Tabletting
ST = Stock Pkg = Packaging

MR/ST

PPIC
PP/PR
I PC / QC
Pcs

PO RM RM IP IP BP BP FP FP
Pcs Rcv, Qrt Wgh > Mix Qrt Fill,Tab Qrt Pkg Qrt

PROCESSING PACKAGING

PRODUCTION

MANUFACTURING: GMP
MODERN CHAIR
 Quality Risk Management
Definition
Principles
Objectives
Coverage of Application
Methodology
Process Procedure

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Quality Risk Management (QRM)

Definition
Systematic process on evaluation, control, and review of
product quality risk

Principles
- Evaluation of product quality is based on scientific
knowledge and process experiences in: R&D, GMP,
and product life-cycle focused on patient safety.

- The extent of effort, formality and the documentation of

the QRM should be equal to the potential opportunities
of the risk.
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Quality Risk Management (QRM)

Objectives
- Establish more understanding on the process and
product
- Establish and maintain a state of control
- Support better quality assurance of product quality
- Achieve product realization
- Effective and consistent decision making on CAPA
- Provide higher confident to achieve patient safety
- Facilitate continual improvement of quality

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 Quality Risk Management
Coverage of Application
- R&D
- Commercial manufacturing (Resources, processing,
QC, packaging, label, stability test, storage, distribution)
- Product discontinuation ( Effective management of the
terminal stage of the product lifecycle).
Methodology
- HACCP (Hazard Analysis of Critical Control Point)
- SOP on evaluation and risk handling
- Quality audit
- Annual product review
- Trend analysis

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 Quality Risk Management
General Process

Risk
Identification
Risk
Elimination
Risk
Input
Analysis
Risk Risk
Output
Acceptance Review
Risk
Evaluation
RISK
REVIEW
RISK RISK
EVALUATION CONTROL WR26
 CONCLUSION
Do it right from the first time and every time is the key
success factor in building quality into the product.

The success of Quality Management implementation

depends on: commitment, competency, conducive
environment, and consistent implementation of the
quality management principles.

GMP is QA in manufacturing

Risk management should be consider to avoid errors

due to inconsistent implementation of GMP.

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