GMP training session for beginners in pharmaceutical industry

1. GOOD MANUFACTURING PRACTICE
IN THE PHARMACEUTICAL INDUSTRY.
BY: AMR AHMED ALY
PHARMACEUTICAL INDUSTRIES PRODUCTION
EXPERT 4/16/2023 1

2. 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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3. 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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4. 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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5. 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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6. 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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7. GMP
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8. 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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9. 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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10. 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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11. 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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12. 4/16/2023 12
Director
Production
QC lab
Other Depts
QA

13. 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. 4/16/2023 13

14. 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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15. 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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16. 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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17. 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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18. 4/16/2023 18
QC is lab based QA is company based

19. QC RESPONSIBILITIES
Safety
Quality
Labeling
Qualification and validation reports
Analysis reports
Worksheets
 Good document practices
Protocol 4/16/2023 19

20. 4/16/2023 20

21. 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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22. API MANUFACTURING PROCESS
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23. SECONDARY MANUFACTURING DOSAGE FORMS
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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

24. SECONDARY MANUFACTURING PROCESS
-TABLETS
• ‫ش‬
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25. EQUIPMENT
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1. Equipment design, size, and location.
2. Equipment construction.
3. Equipment cleaning and maintenance.
4. Automatic, mechanical, and electronic equipment.
5. Filters.

26. PRODUCTION AND PROCESS CONTROL
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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.

27. PACKAGING LABELING CONTROL
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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.

28. 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 4/16/2023 28

29. 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 behavior is maintained at the required
level.
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30. GOOD DOCUMENTATION PRACTICES (GDP)
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31. 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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32. DIFFERENT TYPES OF DOCUMENTS
• Batch records
• Specifications
• Validation & Qualification Records
• Calibration Records
• Standard procedure
• Room Temperature/ %RH
Records
• Stability Study Summary
Report
• Machine Logs
• Product and sample labels
• Analytical Methods
• Manufacturing Procedures
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33.  Section 4: Quality Management System
 4.2.2 Control of Documents
 4.2.3 Control of Records
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ISO – 9001 :2008

34. 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.
 4/16/2023 34
Document Vs Record

35. 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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36. 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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37. TYPICAL RETENTION TIME
Type of Documents Minimum Retention Period
Batch related Records (Executed Documents & Analytical Report-
Chemical & Microbiology)
1 year beyond expiry date whichever is longer.
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
Master Formula Card & Quantitative Flow Ratio
,& basal metabolic rate
For Posterity (Current version)
5 years from the obsolete Date
Stability Study Protocol & Reports For Posterity
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38. 4/16/2023 38

39. 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 4/16/2023 39

40. 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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41. 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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42. 4/16/2023 42

43. REFERENCES
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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.

44. 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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45. REFERENCES
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•
•
•
•
•
•
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

46. 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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