Good Manufacturing Practice

in the Pharmaceutical Industry.

Done by: Ali Mahmoud Jasim
Supervised: Prof. Talal A. Aburjai

1 10/10/2022
 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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 Director

QA

QC lab

Production Other Depts

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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 [Link] 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
❑ 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
[Link] 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

37 Stability Study Protocol & Reports For Posterity 10/10/2022

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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”
[Link] GMP
• as per WHO
[Link]
• GMP as per MCA now known as MHRA
[Link] GMP as
• per TGA [Link]
GMP as per US FDA
• [Link]
GMP as per ICH guidelines
• [Link]

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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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