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GOOD MANUFACTURING PRACTICES

FOR PHARMACEUTICAL PRODUCTS

Wayan Redja
Fakultas Farmasi Universitas Pancasila
Jakarta, 2018
GOOD MANUFACTURING PRACTICES
FOR PHARMACEUTICAL PRODUCTS

 Introduction
 Quality Management
 Resources and Critical Supporting
Facilities
 Processes

WR01
Introduction

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

WR02
Introduction

 Definition of GMP?
Part of Quality Assurance which ensures 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) WR03
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

WR04
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
WR05
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


WR06
Introduction
 Principles of GMP?
> Build quality into the product
> Make quality people before making quality product.
> The next process is our customer.
> The 5 NOs Principles: “ Don’t make, deliver, accept,
keep, or use defect product.”
> Accept only correct resources, activities, or product .
> 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.

WR07
The Main Principles of GMP
Processes are clearly defined and systematically reviewed to assur
e 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 pr


ocedures have been done as expected, and deviations are fully reco
rded and investigated.

Products are properly storage and distribute to minimize the risk of q


uality.

Manufacturing and distribution records are retained in a comprehens


ible and accessible form, for easy tracablility.

Product recall systems available.

Complaints are quickly handled, examined, investigated, and approp


riate measures taken to prevent recurrence.
Introduction

 Classification of Error on Violation of


GMP

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

WR08
Introduction
ISO 9001 vs GMP

ISO 9001 GMP

International Standard National, Regional Standard


Voluntary Compulsory
Any Organization Manufacturing Organization
QMS Requirements Quality Product Certification

WR09
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
WR10
Modul - 3
GMP: Introduction
MR = Marketing Request PPIC = Production Planning &
PP = Production Plan Inventory Control
GMP PROCESS FLOW PO = Purchase Order
RM = Raw Material
PR = Purchase Request
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
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


WR02
Quality Management
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, QRM
Quality Management
 Interrelation of QM, QA, GMP and QC

QM
QA
GMP
QMS R&D QC PRD

WR02
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)

WR04
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
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
Quality Risk Management
Definition
Principles
Objectives
Coverage of Application
Methodology
Process Procedure

WR22
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.
WR23
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

WR25
CONCLUSION
Do it right from the first time and every time is the key su
ccess factor in building quality into the product.

The success of Quality Management implementation dep


ends on: commitment, competency, conducive environm
ent, and consistent implementation of the
quality management principles.

GMP is QA in manufacturing

Risk management should be consider to avoid errors du


e to inconsistent implementation of GMP.

WR27
THANK YOU

WR-33-QM
The Main Principles of GMP
Processes are clearly defined and systematically reviewed to assur
e 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 pr


ocedures have been done as expected, and deviations are fully reco
rded and investigated.

Products are properly storage and distribute to minimize the risk of q


uality.

Manufacturing and distribution records are retained in a comprehens


ible and accessible form, for easy tracablility.

Product recall systems available.

Complaints are quickly handled, examined, investigated, and approp


riate measures taken to prevent recurrence.
QUALITY MANAGEMENT

QMS ISO Series 9000


QMS ISO 9000
Quality Management Principles ISO 9000
Quality Assurance Principles

WR09
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
WR13
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).

WR14
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

WR15
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

WR16
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.
WR17
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


WR18
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


WR19
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
Wgh = Weighing
Mix = Mixing
QC = Quality Control 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

WR22
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.
WR23
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

WR24
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

WR25
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 su
ccess factor in building quality into the product.

The success of Quality Management implementation dep


ends on: commitment, competency, conducive environm
ent, and consistent implementation of the
quality management principles.

GMP is QA in manufacturing

Risk management should be consider to avoid errors du


e to inconsistent implementation of GMP.

WR27

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