Good Manufacturing Practice

.in the Pharmaceutical Industry

Done by: Ali Mahmoud Jasim

Supervised: Prof. Talal A. Aburjai

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 Good Manufacturing Practices for Pharmaceuticals
What is Good Manufacturing Practices
Why GMP is important
The four most important principles of GMP
QC/QA– QM/QMS
Why is a quality management system required?
The quality manual
QC VS QA
GMP common sense
API Manufacturing Process
Secondary Manufacturing Process -Tablets
Managing Staff Training And GMP Compliance
Good documentation practice
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 ? What is GMP
 GMP is that part of Quality assurance which ensures that the
products are consistently manufactured and controlled to the
Quality standards appropriate to their intended use.
 A set of principles and procedures which, when followed by
manufacturers for therapeutic goods, helps ensure that the
products manufacture will have the required quality.

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 Good Manufacturing Practices
 A basic tenet of GMP is that quality
cannot be tested into a batch of
product but must be built into each
batch of product during all stages
of the manufacturing process.

 It is designed to minimize the risks

involved in any pharmaceutical
production that cannot be
eliminated through testing the final
product.

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 Some of the main risks
 Unexpected contamination of products,
causing damage to health or even death.
 Incorrect labels on containers, which
could mean that patients receive the wrong
medicine.
 Insufficient or too much active ingredient,
resulting in ineffective treatment or adverse
effects.

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 Why GMP is important
A poor quality medicine may
contain toxic substances that
have been unintentionally
added.
 A medicine that contains
little or none of the claimed
ingredient will not have the
intended therapeutic effect.

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 GMP

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 The four most important principles of GMP
 Every process and every task is described in detail in specification documents
(e.g. work instructions, SOPs, checklists).
 Every employee (including managers) carries out the work exactly as defined
and reports any deviation immediately.
 The employee records everything in detail while carrying out the tasks so that it
is possible at a later stage to identify the who, what, and when of something that
happened or was observed.
 At regular intervals, the results are compared and evaluated to determine if there
are trends or high occurrences of problems (review, trending).
If this is the case, the work processes and specifications must be
improved before a quality error occurs (continual improvement process, CIP).

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 ?QC/QA– QM/QMS: What is the difference
 The terms quality control (QC), quality assurance (QA), quality
management (QM) and quality management system (QMS) are
frequently not sufficiently differentiated in daily use.
Unfortunately, there are no clear differentiations or definitions in
the legislation. Therefore, it is advisable to define these terms
within a company and use them consistently.

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 Quality Control
 In Germany, quality control normally refers to the
department that is responsible for carrying out quality
testing of raw materials and products. It is also referred
to as analysis, quality testing or control laboratory.
 In the UK and USA, quality control (QC) usually
refers to more than just analysis. For this reason,
Quality Control departments in American companies
often carry out tasks that fall under quality assurance
or quality management in Germany, e.g. the approval
of specifications or the release of raw materials and
products.

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 Quality Assurance
 Quality assurance (QA) refers to all measures that are carried
out to ensure the quality of a product or service.
 This involves more than just quality testing of the product.
 It includes, for example, the approval of SOPs and specifications
for the product, deviation management, supplier qualification,
process validation, batch record review and the QA measures to
be used for the actual product or service.

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 Quality Management
 All planned measures that not only affect the quality of an individual
product, but serve to improve processes and services across the
board, are referred to as quality management.
 These measures include quality planning, the continual improvement
process (CIP), documentation and self-inspection (internal audit).
 In the regulatory requirements, the terms QM and QA are often used
synonymously.
 QM is used more frequently than QA at the present time.
 The departments responsible for quality assurance and management
can be named as quality assurance (QA), quality management (QM),
quality unit (QU) or in an other appropriate way.

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 Quality management system

 Everything that is done in a company to ensure the quality of

products or services and cross-product quality management must
be defined and documented in a quality management system.
 The terms quality assurance system and pharmaceutical
quality system (PQS) are also used.

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 ?Why is a quality management system required
 The aim of a quality management system is to control all of the processes that
could affect the quality of a product in such a way that nothing is left to chance:
from purchasing the raw materials to shipment of the finished product.
 QC and QA are an important parts of the quality system, but there are other
important elements; for example, the qualification of buildings, facilities,
personnel and suppliers, auditing and the proper way in which deviations, errors
and changes are dealt with.
 The GMP rules stipulate that manufacturers of medicinal products and active
ingredients must implement and maintain a functioning quality management
system.
 The GMP rules themselves are not a quality management system, but concrete
requirements for the manufacture and control of medicinal products that go a lot
further than the usual demands of quality assurance systems.

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 ?What does a QM system look like

 Any company that manufactures or trades in

medicinal products must specify in written form, e.g.
in a quality management manual (quality
manual), how the company ensures that only
medicinal products that comply with the high quality
standards reach the patient.
 It should cover all work processes and
responsibilities that are directly or indirectly linked
to the medicinal products.

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 The quality manual
is a collection of documents that describe the QM system. These include:
Site master file (SMF): This "company description" contains information on the buildings and
facilities belonging to the company, the number of employees and their functions, the names of the
responsible persons, the medicinal products or other products which are manufactured, the activities
which have been outsourced to contractors and a lot of other important information.
Quality policy: This document is created by the top management. It confirms that the resources
required for manufacturing, storing and shipping high-quality medicinal products (or starting
materials) will be provided by the management.
SOPs: Standard operating procedures describe in detail how certain procedures must be carried out
and who is responsible for the individual tasks. A quality manual can either contain all the SOPs or
only some top-level SOPs (policies) with cross-references to the subordinate SOPs.
Inventory of all QMS documents: There are other documents in addition to the SOPs that are
required to ensure product quality and patient safety. They include master plans, plans and reports
for qualification, validation, audit or training as well as investigation reports and action plans
related to deviations, complaints or product failures. The quality manual must contain a list of all of
these documents as a reference.
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 QC is lab based QA is company based

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 QC Responsibilities
 „Safety „
 Quality
 Labeling
 Qualification and validation reports
 Analysis reports
 Worksheets
 Good document practices
 Protocol

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 GMP
COMMON
SENSE
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 GMP
 The Quality of a formulation or a bulk drug depends on the Quality of those
producing it.
 GMP is the magic key that opens the door of the Quality
 In matter of GMP, swim with the current and in matter of Quality stand
like a rock!
 Most countries will only accept import and sale of medicines that have been
manufactured to internationally recognized GMP.

 Governments seeking to promote their countries export of pharmaceuticals

can do so by making GMP mandatory for all pharmaceutical production and
by training their inspectors in GMP requirements.

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 API Manufacturing Process

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 Secondary Manufacturing Dosage Forms

 GMP in solid dosage forms

 GMP in semisolid dosage forms
 GMP in Liquid orals
 GMP in Parenterals Production
 GMP in Bio technological products
 GMP in Nutraceuticals and
cosmeceuticals

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 Secondary Manufacturing Process -Tablets
‫ش‬ 

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 Equipment
1. Equipment design, size, and location.
2. Equipment construction.
3. Equipment cleaning and maintenance.
4. Automatic, mechanical, and electronic
equipment.
5. Filters.

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 Production and process control

1. Written procedures; deviations.

2. Charge-in of components.
3. Calculation of yield.
4. Equipment identification.
5. Sampling and testing of in-process materials and
drug products.
6. Time limitations on production.
7. Control of microbiological contamination.
8. Reprocessing.
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 Packaging labeling control

1. Materials examination and usage criteria.

2. Labeling issuance.
3. Packaging and labeling operations.
4. Tamper-evident packaging requirements for over-
the-counter (OTC) human drug products.
5. Drug product inspection.
6. Expiration dating.

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 Managing Staff Training And GMP Compliance
 What are the three most important reasons for GMP deviations? A
lack of GMP training, a lack of GMP training and a lack of GMP
training!
 The root cause for GMP deviations most frequently listed in
inspection reports is the personnel involved in API manufacture
and quality assurance.
 GMP training for manufacturing personnel is essential

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 Managing Staff Training And GMP Compliance
 Well-qualified employees are an essential part of GMP, and training
concepts and the compliance status of personnel are always within
the scope of inspections.
 Training should be planned, scheduled, conducted and documented
using a very systematic approach, particularly in large companies.
 The best way to accomplish this is through training programmes
tailored to each employee's job.
 This should not just end with an induction programme, but continue
with annual training plans and periodic retraining to ensure that an
employee's knowledge and behaviour is maintained at the required
level.

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 GOOD DOCUMENTATION PRACTICES
(GDP)

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? Why GDP

Good documentation practices (GDP) is required in order

to ensure an auditable account of work performed.

GDP is required for all documentations included in a fully

developed quality system.

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Different types of documents
Batch records Calibration Records
Specifications Standard procedure
Validation & Qualification Records Room Temperature/ %RH
Records
Stability Study Summary
Report
Machine Logs
Product and sample labels
Analytical Methods
Manufacturing Procedures

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 ISO – 9001 :2008

 Section 4: Quality Management System

 4.2.2 Control of Documents

 4.2.3 Control of Records

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 Document Vs Record

 Document An approved instruction either in paper or electronic form which guides about

how an activity shall be executed.

 Records provide evidence that activities have been performed or results have been

achieved. They always document the past.

 A document can be a procedure, specification, drawing, work instruction and the record

is also a document with the difference that it provides evidence of compliance with
established requirements and effectiveness of the operation of QMS.

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?How are mistakes corrected
Draw a single line through the error
 Make the correction next to the error
 Write an explanation for the error
 Sign and date the correction.

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Some tips on GDP

Records should be filled online.

Copy documents should be retained for a specific period

of time.

Records should be retained for at least one year after the

expiry date of the finished product.

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 Typical Retention Time
Type of Documents Minimum Retention Period
Batch related Records (Executed Documents & Analytical Report- 1 year beyond expiry date whichever is longer.
Chemical & Microbiology)

Legal Documents (Mfg. Lic.,Regulatory Approvals, Certificates) for posterity

Master Documents and Supersedes and Obsolete Copy of Master document

SOP (Standard Operating Procedures) 5 years from the Obsolete Date

Standard Test Procedures (STP), 5 years from the Obsolete Date

Site Master File For Posterity (Current version)

Master Formula Card & Quantitative Flow Ratio 5 years from the obsolete Date
,& basal metabolic rate

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 Summary and conclusions:
Principles of GMP
 Design and construct the facilities and equipments properly
 Follow written procedures and Instructions
 Document work
 Validate work
 Monitor facilities and equipment
 Write step by step operating procedures and work on
instructions
 Design ,develop and demonstrate job competence
 Protect against contamination
 Control components and product related processes
 Conduct planned and periodic audits
 TRAINNG

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 Summary and conclusions:
List of important documents in GMP
 Policies
 SOP (Standard Operating Procedure)
 Specifications
 MFR (Master Formula Record)
 BMR (Batch Manufacturing Record)
 Manuals
 Master plans/ files
 Validation protocols
 Forms and Formats
 Records

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 :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

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 References
EU Good Manufacturing Practice (GMP) Guidelines,
Volume 4 of “The rules governing medicinal products
in the European Union”
Schaufelberger, D. E., Koleck, M. P., Beutler, J. A.,
Vatakis, A. M., Alvarado, A. B., Andrews, P., ... &
Lebherz, W. B. (1991). The large-scale isolation of
bryostatin 1 from Bugula neritina following current
good manufacturing practices. Journal of natural
products, 54(5), 1265-1270.
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 References
 WHO Good Manufacturing Practices for
pharmaceutical products, Annex 4 to WHO Technical
Report Series, No. 908, 2003
 Shabir, Ghulam A. "A practical approach to
validation of HPLC methods under current good
manufacturing practices." Journal of validation
technology 10 (2004): 210-218.

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 References
• GMP as per Schedule “M”
www.cdsco.nic.in GMP
• as per WHO
www.who.int
• GMP as per MCA now
known as MHRA
• www.mca.gov.uk GMP as
per TGA www.tga.gov.au
• GMP as per US FDA
www.fda.gov
• GMP as per ICH guidelines
www.ich.org
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 References

 Schedule M of Drug And Cosmetics Act 1940

 ISO - 9001 : 2008

 US FDA CFR sections

21 CFR 11, 210 & 211

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