1
Training Program On
Good Manufacturing Practice
ICH Q 7
2
What is GMP
“Good Manufacturing Practice”
“Every product must be fit for its intended purpose’’
GMP is that part of Quality assurance which ensure that the products are
consistently manufactured and controlled to the quality standards appropriate to
their intended use.
3
Good Manufacturing Practice
ICH Q7
Introduction
Quality
Management
Personnel
Building and facility
Production and
inprocess control
Process Equipment
Documentation and
record
Material
Management
Change control
Rejection and reuse
of materials
Complaint and
recall
Contract
Manufacturers
Agents,
Brokers,Traders,Distributors,Repackers and
relabellers
Specific Guidance for APIs
manufactured by cell
APIs for use in clinical
Packaging and
identification labelling of
APIs and intermediates
GMP Chart as per ICH Q7
4
Good Manufacturing Practice
Purpose of ICH
Safe, effective and high quality medicines are developed and registered in the most
efficient and cost effective manner.
To Promote public health.
Prevent unnecessary duplication of clinical test.
Minimize the use of animal testing without compromising safety and effectiveness.
5
Good Manufacturing Practice
ICH = International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use
The European Commission (EC)
The US Food and Drug Administration (FDA)
The Ministry of Health, Labor and Welfare of Japan (MHLW) also
represented by the Pharmaceuticals and Medical Devices Agency
(PMDA)
ICH Q7 Good Manufacturing Practice Guidance for Active
Pharmaceutical Ingredients
Introduction
6
Good Manufacturing Practice
Quality Management
ICH
Q 7
A
t Coral Drugs Pvt Ltd
QA Unit
–
Review & approve all quality related documents.
Review of batch production & quality control
records.
Making sure that the premises and equipment are
maintained and records kept.
Reviewing & Approving validation protocols.
Making sure that production facilities are clean and,
when appropriate, disinfected.
Quality Assurance personnel deputed for BPR,
BCR review prior to release of the respective
batch.
Checklist filled by QA personnel after review
as per format no.CDPL/FR/QA/202.
7
Good Manufacturing Practice
Quality Management
ICH
Q 7
A
t Coral Drugs Pvt Ltd
QA Unit
–
Establishing a system to release or reject raw materials,
intermediates,
packaging and labelling materials;
Reviewing completed batch production and critical
process steps before release of the API for distribution.
Making sure that critical deviations are investigated and
resolved.
Approving all specifications and master production
instructions.
Making sure that internal audits (self-inspections) are
performed.
Quality Assurance personnel deputed for BPR,
BCR review prior to release of the respective
batch.
Checklist filled by QA personnel after review as
per format no. CDPL/FR/QA/202 and mentioned
deviation/OOS/Laboratory error with status if any.
Internal audits are performed twice in a year in
our company.
Applicable SOPs:
• Internal Audit CDPL/SOP/QA/001
• Review of BPRs, ECRs and Analytical
report CDPL/SOP/QA/017
8
Good Manufacturing Practice
Quality Management
ICH
Q 7
A
t Coral Drugs Pvt Ltd
•
Reviewing and approving validation
protocols and reports
• Making sure that effective systems are
used for maintaining and calibrating
critical equipment
Validation of production processes, cleaning
Procedures, analytical methods, in-process
control test procedures, compute- -rized
systems (software), and persons responsible
for design, review, approval and
documentation of each validation phase,
documented.
Applicable SOPs:
Review of BPR, BCR and Analytical Report
CDPL/SOP/QA/017
Validation Policy and Validation Master Plan
CDPL/SOP/QA/021
9
Good Manufacturing Practice
Quality Management
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Product Quality Review-
A review of adequacy of corrective actions.
A review of any changes carried out to the
processes or analytical methods;
A review of all batches that failed to meet
established specification(s).
Product
Quality review include
Batch wise data of in process and
intermediate data..
Qualification
Records of reprocess / rework
Deviations .
Change control.
Market complaints and return goods
for the API.
Number of batches recalled, if any.
Quality trend of purified water.
Validation if any.
10
Good Manufacturing Practice
Quality Management
Q 7
A
t Coral Drugs Pvt Ltd
A review of critical in-process control and
critical API test results
A review of all batches that failed to meet
established specification(s)
A review of all critical deviations or
A review of any changes carried out to the
processes or analytical methods;
Out of trend analysis.
Ongoing stability results.
Microbiological results.
Additional approved Vendors for
key starting material & primary
packing material
Review of previous year
recommendations.
Applicable
SOP: Product Quality Review
CDPL /SOP/QA /96
11
Good Manufacturing Practice
Quality Management
Q 7
A
t Coral Drugs Pvt Ltd
Personnel
Personnel Qualifications
Training should be regularly conducted by
qualified individuals and should cover, at a
the employee's functions.
Training is imparted to all employees
in company as given below:
1. On job training
2.In house training
a) cGMP training
b)Human Resources training
c)Safety Health and environment
3.SOP training
4.External training
Training records maintained for
personnel.
Applicable SOPs are
1)Analyst Qualification “
CDPL/SOP/QC/021”
2) Training and development “
CDPL/SOP/ADM/001”
12
Good Manufacturing Practice
Quality Management
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Personnel Hygiene-
Personnel should practice good
sanitation and health habits.
Personnel should avoid direct
contact
with intermediates or APIs.
Smoking, eating, drinking, chewing
and the storage of food should be
restricted
Persons working on the shop floor, laboratory,
stores and in material handling area wear clean
dresses appropriate for the duties they perform.
All employees shall practice good health and
sanitation habits.
Employees are not allowed to take food items in
manufacturing/process area.
Employee is not carrying any smoking/tobacco
material in the factory premises.
Applicable
SOP:
•
Personal Hygiene CDPL/SOP/ADM/016
13
Good Manufacturing Practice
Buildings & Facilities
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Design & construction
Buildings & facilities should
have adequate
space for the orderly placement of
equipment & material to prevent mix ups &
contamination.
There should be defined areas or other
control systems for the following activities:
1. Receipt, identification, sampling, and
quarantine of incoming materials, pending
release or rejection;
2. Storage of released materials.
3. Production operations
4. Packaging and labelling operations.
5. Laboratory operations.
Infrastructure fully support the cGMP
in Coral Drugs
Pvt Ltd .
We have segregated areas for sampling ,Quarantine,
rejected material, Finished goods , production
activities, and quality laboratories.
Building maintenance as
Adequate lighting, Cleaning
& sanitation, Cleaning of drains , all electrical
connection and All utility lines and maintenance,
etc performed
Applicable
Documents:
•
Site master File (Doc. No .CDPL/QA/SMF/13),
•
Procedure for Building Maintenance
CDPL/SOP/MAINT/027/03
14
Good Manufacturing Practice
Buildings & Facilities
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Utilities
All utilities that could impact on
product quality (e.g. steam, gases,
compressed air )should be maintained.
Water used in the manufacture of API
should be demonstrated to be suitable
for its intended use.
Where water used in the process is
treated by the manufacturer to achieve
a defined quality, the treatment process
should be validated and monitored with
appropriate action limits.
The main hot water pump start for circulation of hot water in
plant.
The hot water temp. maintained at 85ºC-90ºC in hot water tank.
In water system : The UV Lamps changed on running of 8000
hours.
If less than 0.40 KL Quantity of purified water is remain in water
tank, Re-generation started.
Applicable SOPs:
•
Procedure for Operation of Hot Water System
CDPL/SOP/MAINT/002
•
Procedure for Maintenance of Air compressor
CDPL/SOP/MAINT/019
•
Procedure for Operation of Purified Water Plant
CDPL/SOP/MAINT/010
15
Good Manufacturing Practice
Process Equipment
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Equipment used in the manufacture of
intermediates and APIs should be of
appropriate design and adequate size,
and suitably located for its intended
use, cleaning, sanitization (where
appropriate), and maintenance.
Production equipment should only be
used within its qualified operating
range.
Equipment Maintenance & Cleaning
Schedules and procedures (including
assignment of responsibility) should be
established for the preventative
maintenance of equipment.
We have Qualification procedure for the
equipment's and all equipment qualified
periodically as per VMP.
Cleaning of equipment’s should be done in three
levels based on the process (SOP Reference
CDPL/PROD/SOP/037).
Level 0 -for batch to batch (same stage of same
product).
Level 1 -stage to stage (different stage of same
product).
Level 2 -product change over (product to
product).
Rinse sample- by UV- for Level 1 and Level 2.
Swab sample -by UV-for Level 2.
16
Good Manufacturing Practice
Process Equipment
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Calibration
Computerized Systems
1. GMP related
computerized systems
should be validated.
2. The level and scope of
validation depends on
the diversity, complexity
and criticality of the
computerized
application.
A master calibration schedule for QC instruments
is prepared annually from January to December
as per the Format No. CDPL/FR/QC/41.
In Coral Drugs Pvt Ltd
, computer systems used in
different area is
validated with respect to DQ and
in case of software application is being used on
Computer system is validated for DQ, IQ, OQ, PQ
to
17
Good Manufacturing Practice
Process Equipment
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Calibration
Appropriate installation
qualification and operational
qualification should demonstrate
the suitability of computer
hardware and software to
perform assigned tasks.
demonstrate that the software is performed
consistently and reliably as expected, so that its
performance does not affect the product quality.
Applicable SOP:
•
SOP for calibration and maintenance of
Laboratory Instruments CDPL/SOP/QC/075
•
Validation Master Plan CDPL/VMP/18/06
18
Good Manufacturing Practice
ICH
Q 7
A
t Coral Drugs Pvt Ltd
All documents related to the manufacture
of intermediates or APIs should be
prepared, reviewed, approved and
distributed according to written
procedures. Such documents can be in
paper or electronic form.
All production, control, and distribution
records should be retained for at least 1
year after the expiry date of the batch. For
APIs with retest dates, records should be
retained for at least 3 years after the batch
is completely distributed.
We have master BPR and master
protocols for FG and Intermediate
which is approved.
BPR and Protocols are issued by QA
department and retrieved in QA after
completion of activity
(production/Analysis).
Applicable SOP:
•
Review of BPRs, BCRs and Analytical
report. CDPL/SOP/QA/017
•
Standard Operating Procedure for
Document and Data Control.
CDPL/SOP/QA/015
Documentation and Record
19
Good Manufacturing Practice
Documentation and Record
Q 7
A
t Coral Drugs Pvt Ltd
Records of major equipment use,
cleaning, sanitization and/or
sterilization and maintenance should
show the date, time (if appropriate),
product, and batch number.
Cleaning BPRs issued by QA
department and filled by
production during cleaning with
date time and batch no.
After cleaning Equipment status
board updated .
SOP
on cleaning of equipments
CDPL/ SOP/PROD/037/06
20
Good Manufacturing Practice
Documentation and Record
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Master Production Record
To ensure uniformity from batch to batch,
master production instructions for each
intermediate and API should be prepared,
dated, and signed by one person and
independently checked, dated, and signed by a
Q.A Unit.
Master production instructions should include:
1.
The name of the intermediate or API being
manufactured and an identifying document
reference code.
2.
List of raw material & it’s quality characteristics.
3.
An accurate statement of the quantity or ratio
of each raw material or intermediate to be
used.
In Coral Drugs Pvt Ltd master production
record for each intermediate and API is
prepared by production checked by
production and QC and approved by QA.
We have a specific code for each finished
product and intermediates.
Each master BPR has its number and
reference MFR number.
List of raw material code with quantity as
per requirement is mentioned in master BPR.
21
Good Manufacturing Practice
Documentation and Record
ICH
Q 7
A
t Coral Drugs Pvt Ltd
QC Documents: There should be
documented procedures describing
sampling, testing, approval, or rejection of
materials and recording and storage of
laboratory data
Testing of Intermediates and APIs
Validation of Analytical Procedures
Certificates of Analysis
Stability Monitoring of APIs
Expiry and Retest Dating
Reserve/Retention Samples
These activities performed by QC:
Preparation of SOPs related to testing.
Analysis and Approval of RM, PM, In-
process, Intermediates and FP
Validation of analytical methods
(including method for cleaning
validation)
Issue of Certificate of analysis
Conducting stability studies for APIs as
per ICH guidelines
Calibration of laboratory
instruments/equipment
Control of labels
22
Good Manufacturing Practice
Documentation and Record
ICH
Q 7
A
t Coral Drugs Pvt Ltd
A complete record of all raw data
generated during each test with graphs,
charts & spectra from laboratory
instrumentation.
Signature of the person who performed
each test & the date on which the tests
were performed
We are following cGMP and maintain all the
raw data along with approved and filled
protocol.
Entries in protocol are contemporaneous
along with sign and date.
23
Good Manufacturing Practice
Material Management
ICH
Q 7
A
t Coral Drugs Pvt Ltd
General controls: There
should be written
procedures describing the receipt,
identification, quarantine, storage,
handling, sampling, testing, and approval
or rejection of materials
Receipt and Quarantine: Upon receipt
and before acceptance, each container or
grouping of containers of materials should
be examined visually.
Sampling and Testing of Incoming
Production Materials 1.Storage -
Materials
should be handled and stored in a manner
to prevent degradation, contamination,
and cross-contamination.
We have SOPs,training policy and facility to
support all the activities involved in material
management as receipt, identification,
quarantine, storage, handling, sampling,
testing, and approval or rejection of
materials
•
Receipt of Raw Material / Packaging
Material
CDPL/SOP/STR/001
•
Sampling Procedure for Raw
Material/Packing Material and Storage of
Approved/Rejected material.
CDPL/SOP/QC/024
24
Good Manufacturing Practice
Production and In- Process Controls
ICH
Q 7
A
t Coral Drugs Pvt Ltd
A. Production Operations
B. Time Limits
C. In-process Sampling and Controls
D. Blending Batches of
Intermediates or APIs
Production operations performed as described in
batch production record.
Time limits for operations mentioned in BPR.
Production department shall be send the In-process
samples to the QC department
along with
“
Intimation slip for in process samples
”
.
QC Chemist will be registered details of the in process
sample like name/code of sample, batch No.,
Department, Stage and test to be done etc. in the
“
INVENTORY FOR INPROCESS SAMPLES
”
as per
format number CDPL/FR/QC/02 and analyse the
sample accordingly.
25
Good Manufacturing Practice
Packaging and Identification Labelling of APIs and Intermediates
ICH
Q 7
A
t Coral Drugs Pvt Ltd
There should be written procedures
describing the receipt, identification,
quarantine, sampling, examination and/or
testing and release, and handling of
packaging and labeling materials.
Packaging Materials Containers should
provide adequate protection against
deterioration or contamination of the
intermediate or API that may occur during
transportation and recommended storage.
Containers should be clean and according
to product requirement.
We have SOPs,training policy and
facility to support all the activities
involved in material management as
receipt, identification, quarantine,
storage, handling, sampling, testing,
and approval or rejection of materials
•
Receipt of Raw Material / Packaging
Material
CDPL/SOP/STR/001
•
Sampling Procedure for Raw
Material/Packing Material and Storage
of Approved/Rejected material.
CDPL/SOP/QC/024
26
Good Manufacturing Practice
Storage and Distribution
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Warehousing Procedures -
Facilities should
be available for the storage of all materials
under appropriate conditions temperature
and humidity when necessary.
Temperature and relative humidity recorded in
the the Finished Good Storage area, approved
raw material storage area and material
dispensing area of Store during all working days.
Temperature and relative humidity is monitored
through Thermo-hygrometer twice in a day and
same recorded in the format no. CDPL/FR/
STR/06.
27
Good Manufacturing Practice
Storage and Distribution
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Distribution Procedures –
1)
APIs and intermediates should
only be released for distribution
after have been released by the
quality unit.
2)
APIs and intermediates should be
transported in a manner that does
not adversely affect their quality.
In
Coral Drugs Pvt Ltd production and analytical
data reviewed and approved by QA before
dispatch.
Transportation validation is performed of
applicable product
Applicable
SOP
Temperature and Relative Humidity Recording
CDPL/SOP/STR/016/05
28
Good Manufacturing Practice
Laboratory Controls
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Testing of Intermediates and
APIs -An impurity profile
describing the identified and
unidentified impurities present in
a typical batch produced by a
specific controlled production
process should normally be
established for each API.
Validation of Analytical
Procedures
Certificates of Analysis -
Authentic Certificates of Analysis
should be issued for each batch
of intermediate or API on
request.
Testing for inprocess, intermediate and
finished product performed as per
approved protocol.
Methods of analysis are validated as per
SOP no. CDPL/SOP/QC/020.
Preparation of COA for Dispatch of Finished
goods CDPL/SOP/QA/036
Protocols are checked for results
calculations and verification of all results
and signed by QA .
29
Good Manufacturing Practice
Laboratory Controls
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Stability Monitoring of APIs –
A documented, on-going testing program
should be designed to monitor the
stability characteristics of APIs, and the
results should be used to confirm
appropriate storage conditions and retest
or expiry dates.
Expiry and Retest Dating -When an
intermediate is intended to be transferred
outside the control of the manufacturer’s
material management system and an
expiry or retest date is assigned,
supporting stability information should be
available.
There is a written testing program
designated to assess the stability Studies.
For stability testing, packing conditions of
sample is maintained equivalent to
commercial packing.
On the basis of stability data retest date
confirmed.
Stability Study & Analysis
CDPL/SOP/QC/077/02
Operating Procedure of Photo Stability
Chamber
CDPL/SOP/QC/094
30
Good Manufacturing Practice
Laboratory Controls
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Reserve/Retention Samples
-
purpose of potential future
evaluation of the quality of
batches of API.
One sample (Buffer sample)apart from the actual
number of sample is kept for charging each for
long term study and accelerated study.
The control samples of finished goods should be
prepared from each blend batch.
Control samples is prepared and stored after
approval of the material.
Control samples are packed as per commercial
packing.
Applicable SOP:
•
Preparation, storage & Issuance of control
samples CDPL/SOP/QC/016
•
Stability Study & Analysis CDPL/SOP/QC/077/02
31
Good Manufacturing Practice
Validation
Q 7
A
t Coral Drugs Pvt Ltd
A documented program, which provides a
high degree of assurance that a specific
meeting its pre- determined specifications
and quality attributes.
Validation Policy
The company's overall policy, intentions,
and approach to validation, including the
procedures, analytical methods, in-process
control test procedures, computerized
systems, and persons responsible for
design, review, approval and
documentation of each validation phase,
should be documented.
Coral overall policy, intentions, and
approach for validation, include the
Qualification of equipments, validation
of production processes, cleaning
Procedures, analytical methods, in-
process control test procedures,
Computerized systems (software), and
persons responsible for design, review,
approval and documentation of each
validation phase is documented.
Applicable SOP:
Validation Policy and Validation Master
Plan CDPL/SOP/QA/021/04
32
Good Manufacturing Practice
ICH
Q 7
A
t Coral Drugs Pvt Ltd
A formal change control system should be
established to evaluate all changes that may
affect the production and control of the
intermediate or API.
Written procedures should provide for the
identification, documentation, appropriate
review, and approval of changes in raw
materials, specification analytical methods,
facilities, support systems, equipment
(including computer hardware), processing
steps, labelling and packaging materials, and
computer software.
We follow Change control
procedure for any change regarding
facility, documents, utility etc as per
SOP no.CDPL/SOP/QA/006
User department initiate with
Change control form which is issued
by QA and evaluated by QA on the
basis of impact analysis and
duration of change
Applicable
SOP:
•
Change Control Procedure
CDPL/SOP/QA/006
Change Control
33
Good Manufacturing Practice
ICH
Q 7
A
t Coral Drugs Pvt Ltd
Intermediates and APIs failing to meet
established
specifications should be identified as such and
quarantined. These intermediates or APIs can be
reprocessed or reworked ,The final disposition of
rejected materials should be recorded.
We have OOS procedure if any material
analytical result does not fall under
specification.
Investigation performed in 3 phases-
Laboratory investigation, sampling
investigation and Production
investigation.
If required Reprocess performed as per
standard reprocess production record.
•
Standard procedure for Handling of
rejected raw material & online rejections
CDPL/SOP/STR/026
•
Reprocessing of Intermediate or API
CDPL/SOP/QA/027
•
Out of Specification CDPL/SOP/QA/013
Rejection and Reuse of Materials
34
Good Manufacturing Practice
Complaints and Recall
ICH
Q 7
A
t Coral Drugs Pvt Ltd
All quality related complaints, whether
received orally or in writing, should be
recorded and investigated according to a
written procedure.
The recall procedure should designate who
should be involved in evaluating the
information, how a recall should be initiated,
who should be informed about the recall, and
how the recalled material should be treated.
In Coral Drugs Pvt Ltd Investigation is
carried out according to “Customer
complaint Investigation form” as per
format no. CDPL/FR/QA/113. If
required supplementary appropriate
formats can be prepared to carry out
further investigation.
Applicable SOPs:
•
Handling of Customer Complaint
CDPL/SOP/QA/009
•
Recall Procedure CDPL/SOP/QA/012
35
Good Manufacturing Practice
Summary :
Good Manufacturing Practices is very important in maintaining quality of the API.
API manufacturer can improve output of the manufacturing process.
Helps to enhance productivity as well as effectiveness of the manufacturing process.
ICH Q7 ensures less batch to batch variations and less chances of recalls.
Following this guideline can also help during regulatory inspections.
36
Good Manufacturing Practice