MODULE NO.

:TM/001-01
Effective Date : 06/01/14
Prepared By:

Approved By:

Why GMP?
Provides a high level assurance that medicines
are manufactured in a way that ensures their
safety, efficacy and quality
Medicines are manufactured to comply with their
marketing authorization
Quality is built in
Testing is part of GMP, but alone does not provide a
good level of quality assurance

Why inspections?
Verify compliance with GMP
Verify compliance with marketing authorization
Dossier: "Dedicated equipment is used"
Inspection: Observation that this means "dedicated while used
for the product or not being used for another product"
Dossier: "The vials are removed from the lyophilliser and
crimped in a grade A environment"
Inspection: Correct, but before crimping they are stored in an
uncontrolled corridor

Good Manufacturing Practices

1. Quality assurance
2. Good manufacturing practices for pharmaceutical products
3. Sanitation and hygiene
4. Qualification and validation
5. Complaints
6. Product recalls
7. Contract production and analysis

General
The contract giver
The contract accepter
The contract

Good Manufacturing Practices (cont'd)

8. Self-inspection and quality audits
Items for self-inspection

Self-inspection team
Frequency of self-inspection
Self-inspection report
Follow-up action
Quality audit
Suppliers audits and approval

9. Personnel
General
Key personnel

10. Training

Good Manufacturing Practices (cont'd)

11. Personal hygiene
12. Premises
General

Ancillary areas
Storage areas
Weighing areas
Production areas
Quality control area

13. Equipment

Good Manufacturing Practices (cont'd)

14. Materials
General

Starting materials
Packaging materials
Intermediate and bulk products
Finished products
Rejected, recovered, reprocessed and reworked materials
Recalled products
Returned goods
Reagents and culture media
Reference standards
Waste materials
Miscellaneous

Good Manufacturing Practices (cont'd)

15. Documentation
General
Documents required:
Labels
Testing procedures
Specifications for starting and packaging materials, for
intermediate and bulk products and for finished products
Master formulae and Batch Processing Records
Packaging instructions and Batch Packaging Records
Standard Operating procedures (SOP's) and records
Logbooks

Good Manufacturing Practices (cont'd)

16. Good practices in production
General
Prevention of cross-contamination and bacterial
contamination during production
Processing operations
Packaging operations

17. Good practices in quality control

Control of starting materials and intermediate, bulk and
finished products
Test requirements
Batch record review
Stability studies

GMP is actually Good Common Sense

Quality Management

Quality Assurance

GMP

Production and Quality Control

Quality management in the drug industry

Philosophy and essential elements:
"The concepts of quality assurance, GMP, quality
control and quality risk management are
interrelated aspects of quality management, and
should be the responsibility of all personnel.
their relationship and their fundamental
importance to the production and control of
pharmaceutical products."

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
The totality of these actions is referred to as Quality
Assurance

The five P's

Premises
Primary materials
People

Processes defined and recorded

Quality Assurance
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 Assurance
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 continuously of the right
quality for the intended use
Quality Assurance incorporates GMP
and also includes product design and
development, with special focus on process design

The position of QA
Director
Director

QA
QA

Production
Production

QC lab
lab
QC

Other Depts
Depts
Other

Quality Assurance means to assure:

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 means to assure:

(cont'd)
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 means to assure:

(cont'd)
Procedures for self-inspection and quality audits
are applied
Deviations are reported, investigated and
recorded
System for change control is applied
Regular evaluation of product quality to verify
consistency and continued improvement

Quality Assurance includes:

Responsibility of the Manufacturer for the quality of the product
Fit for intended use
Comply with marketing authorization
Safety, efficacy and quality
Commitment of senior management and involvement of all staff
Comprehensively designed and well implemented quality
system
Full documentation and monitoring of effectiveness
Competent personnel, sufficient premises, equipment and
facilities

Good Manufacturing Practices

That part of QA that ensures that products are
consistently produced and controlled
Quality standards
Marketing authorization
Aim: Diminishing risks that cannot be controlled
by testing of product
Contamination and cross-contamination
Mix-ups (confusion)

Basic requirements for GMP:

Clearly defined and systematically reviewed
processes
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

Basic requirements for GMP:

(cont'd)

Clear, written instructions and procedures

Trained operators
Records of actions, deviations and
investigations
Records for manufacture and distribution
Proper storage and distribution
Systems for complaints and recalls

GMP = continuous urge for improvement

Involvement of the management
Annual Product Quality Review
Quality risk management
Complaints handling
Self-inspection

Involvement of the management

The senior management is responsible to attain the company's
quality objectives
All different departments and all levels within departments
should be involved; and it's the senior management who
should facilitate this
Also suppliers and distributors should be involved
The senior management should make available the required
resources
The basis of the quality system is the quality statement and
quality policy, by the senior management

Product Quality Review

Objectives of Product Quality Review:
To review and verify the consistency and
appropriateness of the existing process
To identify and highlight any trends in the
process, e.g. in analytical results, yields etc.
To identify any possible product or process
improvements

Product Quality Review (cont'd)

Review of starting materials/ packaging
materials, especially from new sources
Review of in-process control results and finished
product analytical control results
Amount of batches and packaging units
produced and their yields
Reviews of:
Out-of-spec situations, rejections, deviations, changes
Plus investigations and analysis of causes

Annual Product Quality Review (cont'd)

Review of Marketing Authorization variations submitted,
granted or refused (incl. third countries)
Review of stability programme and trends
Review of adequacy of previous decisions on changes
or improvements or corrective actions
For new Marketing Authorizations (plus new variations)
a review of post marketing commitment
The qualification status of all relevant equipment and
utilities (like water, HVAC, gases, etc.)
Review of Technical Agreements (if applicable)

Complaints handling
Complaints: Principle
All complaints and other information concerning
potentially defective products must be carefully
reviewed according to written procedures and
corrective action should be taken.

Complaints Procedure
Designated responsible person:
To handle complaint
Decide on measure to be taken
May be authorized person - if not, must advise authorized
person of results
Sufficient support staff
Access to records
Written procedure (SOP):
Describes action to be taken
Includes need to consider a recall (e.g. possible product
defect)

Complaints Procedure cont'd

Thorough investigation:
QC involved
With special attention to establish whether "counterfeiting"
may have been the cause
Fully recorded investigation reflect all the details
Due to product defect (discovered or suspected):
Consider checking other batches
Batches containing reprocessed product

Complaints Procedure cont'd

Investigation and evaluation should result in
appropriate follow-up actions
May include a "recall"
All decisions and measures taken should be
recorded
Referenced in batch records
Records reviewed - trends and recurring problems

Complaints - other actions

Inform competent authorities in case of serious
quality problems such as:
Faulty manufacture
Product deterioration
Counterfeiting
Have a thorough recall procedure that is consistent
with the complaints handling procedure
Trend complaints, their investigations and results

Self-Inspection
Purpose is to evaluate whether a companys operations
remain compliant with GMP
The programme should
cover all aspects of production and quality control
be designed to detect shortcomings in the implementation of
GMP
recommend corrective actions
set a timetable for corrective action to be completed

Should be performed routinely

Also on special occasions such as
Recalls
Repeated rejections

Self-Inspection (cont'd)
Performed by team appointed by management, with:
authority
sufficient experience, expertise in their own field.
knowledge of GMP
may be from inside or outside the company
Frequency should normally be at least once a year
May depend on company requirements
Size of the company and activities

Self-Inspection (cont'd)
Report prepared at completion of inspection,
including:

results
evaluation
conclusions
recommended corrective measures

Follow-up action
Effective follow-up programme
Company management to evaluate both
the report and corrective actions

Summary and conclusions:

GMP compliance is not an option
Quality should be built into the product
GMP's are very similar and are really
Good Common Sense
Good Practices cover all aspects of
manufacturing activities prior to supply
The role and involvement of senior
management is crucial

THANK YOU
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