CHAPTER – 6: PHARMACEUTICAL

INDUSTRY AND BASIC CONCEPTS

Points to be covered in this topic

6.1 INTRODUCTION
6.2 PHARMACEUTICAL MANUFACTURING PLANT
6.2.1 Structure of Pharmaceutical Manufacturing Plant
6.2.2 Layout of Pharmaceutical Manufacturing Plant
6.2.3 Sections of Pharmaceutical Manufacturing Plant
6.2.4 Activities of Pharmaceutical Manufacturing Plant
6.3 QUALITY CONTROL
6.3.1 Objectives of Quality Control
6.3.2 Functions of Quality Control
6.3.3 Concepts of Quality Control
6.4 QUALITY ASSURANCE
6.4.1 Function of Quality Assurance
6.4.2 Concept of Quality Assurance
6.4.3 Quality Assurance Method
6.4.4 Quality Management and Certification
6.4.5 Total Quality Management
6.4.6 Quality Audit
6.5 CURRENT GOOD MANUFACTURING PRACTICES
6.5.1 Objectives
6.5.2 Testing
6.5.3 Good Manufacturing Practices
6.6 INTRODUCTION TO CONCEPT OF CALIBRATION
6.6.1 Advantages
6.6.2 Objectives
6.6.3 Instrument Calibration
6.7 INTRODUCTION TO CONCEPT OF VALIDATION
6.7.1 Importance of Validation
6.7.2 Method of Validation
6.7.3 Guidelines of Validation
6.7.4 Types of Validation
6.7.5 Strategies of Validation
6.7.6 Department and Authorities of Validation
6.7.7 Revalidation

6.1 INTRODUCTION
Pharmaceutical manufacturing
• Pharmaceutical manufacturing is the process of

industrial-scale synthesis of pharmaceutical drugs as

part of the pharmaceutical industry.
• The process of drug manufacturing can be broken down

into a series of unit operations, such as milling,

granulation, coating, tablet pressing, and others.

6.2 PHARMACEUTICAL MANUFACTURING PLANT

• Pharmaceutical Manufacturing Plant is the place where manufacturing of the
pharmaceutical products takes place.
 • The pharmaceutical manufacturing plant is responsible for producing
pharmaceutical products in large scale that follows testing for quality and
purity of the product.
• It also includes batch integrity testing, quality assurance, calibration,

validation and facility maintenance.

6.2.1 Structure of Pharmaceutical Manufacturing Plant
• Pharmaceutical manufacturing plants are typically designed with a

cleanroom environment that prevents contamination of the products.

• The facility is divided into different areas such as production areas,

packaging areas, quality control areas, and storage areas.

• The basic structure of a pharmaceutical manufacturing plant is designed to

meet the requirements of Good Manufacturing Practices (GMP) and to

ensure that the products produced are safe and effective for human use.
• The basic structure of pharmaceutical plant in shown is fig 6.1

Pharmaceutical Company Hierarchy

1. Senior level in pharma company
• This level in pharma company is responsible for overall management and

operation of the organization and also to maintain the financial issue in the
industry.
2. Middle level in Pharma company
• The personnel in this level work under the guidance of senior executives.

• They also supervise the entry level people about the organization and make

sure that the operations continue smoothly.

3. Entry level in Pharma company
• The personnel in this level are responsible to carry day to day task and

functions.
 • These are not much experienced people.
6.2.2 Layout of Pharmaceutical Manufacturing Plant

The manufacturing plant consist of the following

Raw material storage: This area is used for the storage of raw materials that are
used in the manufacturing process.
Formulation area: This area is responsible for formulating the active pharmaceutical
ingredients (APIs) into the final product. It may include areas such as granulation,
compression, coating and packaging.
Quality control area: This area is responsible for ensuring that the products meet the
quality standards.
It may include areas such as chemical analysis, microbiology, and stability testing.
Packaging area: This area is responsible for packaging the final product into
different forms such as tablets, capsules, and injections.
Utility areas: These areas are responsible for providing the necessary utilities for
the manufacturing process, such as water, air, and electricity.
Characteristics of Pharmaceutical plant layout
• It should provide adequate space for the machines, materials, storage, and

other services needed for the production of pharmaceutical products.

• It should facilitate smooth and continuous flow of materials from one area to

another without any delays or interruptions.

• It should incorporate adequate health, safety, and security features such as

fire extinguishers, emergency exits, first aid boxes, etc.

Advantages of Pharmaceutical plant layout
• It makes the best use of the available floor space for production operations.

• It incorporates adequate health, safety, and security features such as fire

extinguishers, emergency exits, first aid boxes, etc.

• It allows effective supervision, coordination, and control of the production

processes by the staff.

6.2.3 Sections Of Pharmaceutical Manufacturing Plant
The sections of a pharmaceutical manufacturing plant are as follows:
1. Security Office: The Security Office in the pharmaceutical industry is a crucial
component responsible for safeguarding personnel, assets, information, and the
overall security of the facility. For this pharmaceutical plant employs ‘Safety
Officers’ as specified in Factory Act.
2. Vehicle Parking: Vehicle parking in the pharmaceutical industry is a significant
aspect of facility management, ensuring the organized and secure parking of
vehicles for employees, visitors, and service personnel.
3. Power Backup: Power backup is a critical aspect in the pharmaceutical industry,
where the reliability of electricity supply is essential for various processes and
operations.
4. Administrative Block: “Administrative Block” typically refers to an area or
section within a pharmaceutical facility that is dedicated to administrative functions
and activities. It consists of finance, pantry and crockery storage.
5. Production Block: In the pharmaceutical industry, a “Production Block” refers to
a specific area or building within a pharmaceutical facility dedicated to the
manufacturing and production of pharmaceutical products. This block typically
houses various units, equipment, and facilities required for the production of
pharmaceutical drugs.
6. Utility service Department: The Utility Services Department in the
pharmaceutical industry plays a pivotal role in ensuring the availability, reliability,
and efficient operation of various utility services required for pharmaceutical
manufacturing processes.
7. Scrap Yard: The concept of a scrap yard is more related to facilities that handle
the recycling and processing of various materials, often found in end-of-life
vehicles, appliances, and other consumer goods. In the pharmaceutical industry,
there are specific processes and practices related to waste management, recycling,
and disposal of materials.
6.2.4 Activities Of Pharmaceutical Manufacturing Plant
The proper activities of Pharmaceutical Manufacturing Plant are necessary to
provide the right medicine to the right patient at right time.
These includes the following:
1. Raw Material Procurement: Raw materials are procured from approved vendors
and are subjected to quality testing before use. It involves researching, selecting,
ordering, and paying for raw materials required for a business.
2. Production: The production process is carried out in accordance with standard
operating procedures (SOPs) to ensure consistency and quality.
3. Quality Assurance: Quality assurance is a process that ensures products, services,
or processes meet or exceed established quality standards.
4. Quality Control: Quality control activities are carried out throughout the
manufacturing process to ensure that the products meet the quality standards.
5. Packaging: The final product is packaged into different forms such as tablets,
capsules, and injections.
6. Storage: The raw materials, intermediates, and finished products are stored in a
controlled environment to ensure their stability.
7. Cleaning and Maintenance: Cleaning and maintenance are essential activities in
the pharmaceutical industry, as they ensure the quality, safety, and efficacy of the
products and processes. Cleaning and maintenance involve the removal of visible
and microscopic contaminants from equipment, utensils, surfaces, and personnel by
using appropriate methods, materials, and schedules.
8. Pharmaceutical Distribution: Pharmaceutical distribution is the process of
delivering pharmaceutical products from the manufacturers to the end users, such as
pharmacies, hospitals, clinics, or consumers.
9. Patient Assistance Programs; Patient assistance programs (PAPs) are initiatives
that pharmaceutical companies carry out to manage and support patients throughout
their treatment journey.

6.3 QUALITY CONTROL (QC)

• Quality Control (QC) is a procedure or set of
procedures intended to ensure that a manufactured
product adheres to a defined set of quality criteria or
meet the requirement of the customer.
• Quality control is used to verify that pre-determined quality standards are

being met through quality inspections and reviews which detect poor quality,
and identify non-conformance with those standards.
6.3.1 Objectives of Quality control
The objective of the quality control is–
 • To decide about the standard of quality of a product that is easily acceptable
to the customer and at the same time this standard should be economical to
maintain.
• To take various steps to solve any kind of deviations in the quality of the
product during manufacturing.
• To increase the operational efficiency of the organization by improving
quality of raw material, equipments etc.

6.3.2 Functions of Quality control department

The function of the quality control is–
• To suggest method and ways to prevent the manufacturing difficulties.

• To find out the points where the control is breaking down and to investigate

the causes of it.

6.3.3 Concepts of Quality control
• Quality control involves the installation of system and establishment of

quality standard to ensure and maintain the standard of the product.

Steps in Quality control
1. Establishing quality standard: Quality standards are maintained in terms of
size, design, durability, appearance etc. on the basis of customer
requirement.
2. Selecting the manufacturing process: The selection of the step determines the
specific output of the required specifications.
 3. Development of measurement techniques: This step is required to check that
whether the production conforms to the set specification or not.
4. Monitoring product quality: It helps in periodically checking of end product
to check the alteration in the set quality standard and find the location of
such alteration.
Techniques of Quality control
1. Inspection
It involves periodic checking and measuring before, during and after the production
process. It can be done in two ways:
a. Centralized inspection: Centralized inspection in the pharmaceutical industry
refers to the practice of conducting inspections and assessments of pharmaceutical
manufacturing facilities, processes, and products by a central regulatory authority
or organization.
• The aim is to ensure compliance with regulatory standards, guidelines, and

good manufacturing practices (GMP).

b. Floor inspection: Floor inspection in the pharmaceutical industry refers to the
examination and assessment of the manufacturing floor or production area where
pharmaceutical products are processed and manufactured.
➢ Advantages of Inspection
• Inspection plays a crucial role in the pharmaceutical industry, contributing to

the overall quality and compliance of pharmaceutical products.

• Inspection helps guarantee the safety of pharmaceutical products for

consumers.
2. Statistical Quality control
Statistical quality control (SQC) is the application of statistical methods for the
purpose of determining if a given component of production (input) is within
acceptable statistical limits and if there is some result of production (output) that
may be shown to be statistically acceptable to required specifications.
It is of two types
a. Process control: Process control in the pharmaceutical industry refers to the
systematic and ongoing efforts to monitor, regulate, and optimize the various stages
of pharmaceutical manufacturing to ensure the production of high-quality and safe
medicinal products.
b. Acceptance sampling: Acceptance sampling in the pharmaceutical industry is a
quality control method used to assess and make decisions about the quality of a
batch or lot of products based on the inspection of a sample.
➢ Advantages of Statistical Quality Control
• Statistical Quality Control relies on data analysis to make informed decisions

about the quality of processes and products.

• Implementing Statistical Quality Control can lead to cost savings by

reducing the need for extensive testing and inspection.

6.4 QUALITY ASSURANCE (QA)

• According to WHO, quality assurance is a wide-ranging concept
covering all matters that individually or collectively influence
the quality of a product.
• With regard to pharmaceuticals, Quality Assurance can be

divided into major areas: development, quality control,

production, distribution, and inspection.
6.4.1 Functions of Quality Assurance
• Stability testing and evaluation of shelf life of products

• Warehousing of finished products (Drug Products)

 • Complaints and product recalls
6.4.2 Concept of Quality Assurance
• QA process has a defined cycle called as PDCA cycle.

• The phases of this cycle are Plan, Do, Check and Act.

• This process ensure that the process followed in the drug’s

development and manufacturing are evaluated and improved

periodically.
(a) Plan: It deals with identification of the objectives leading to a high-quality
outcome, then determines and plans the processes that are required to deliver on
those objectives.
(b) Do: In this process necessary changes are made in the developed process,
product and services.
(c) Check: In this stage, the developed product and process are being checked either
it meets the standard requirement or not.
(d) Act: In this phase, necessary action is taken to ensure the improvements in the
product, process and service.
6.4.3 Quality Assurance Method
1. Failure Testing: Failure testing, also known as reliability testing or stress testing,
is a quality assurance practice that involves subjecting a product or system to
extreme conditions or stress levels to assess its performance under adverse
circumstances.
2. Statistical Process Control: Statistical Process Control (SPC) is a quality
assurance methodology that uses statistical methods to monitor and control
processes to ensure they operate consistently and produce products that meet
predefined quality standards.
 3. Total Quality Management: Total Quality Management (TQM) is a
comprehensive management philosophy and approach that focuses on continuously
improving the quality of products and processes throughout an organization.
6.4.4 Quality Management and Certification
A quality management system is a management technique used to communicate to
employees what is required to produce the desired quality of products and services
and to influence employee actions to complete tasks according to the quality
specifications.
Purpose of Quality Management System
1. Establishes a vision for the employees.
2. Builds motivation within the company.
6.4.5 Total Quality Management
• Total Quality Management is a management approach in which quality is

emphasized in every aspect of the business and organization.

• Its goals are aimed at long-term development of quality products and

services.
Table 6.1: Total Quality Management
TERMS DESCRIPTION
TOTAL Made up of the whole
QUALITY Degree of excellence a product or service provides

Act, art, or manner of planning, controlling and Directing. Therefore,

MANAGEMENT
TQM is the art of managing the whole to achieve excellence.
➤ Elements of TQM
1. Ethics
• Ethics is the discipline concerned with good and bad in any situation. It is a

two-faceted subject represented by organizational and individual ethics.

2. Integrity
• Integrity implies honesty, morals, values, fairness, and adherence to the facts

and sincerity. The characteristic is what customers expect and deserve to

receive.
3. Trust
• Trust is a by-product of integrity and ethical conduct. Without trust, the

framework of TQM cannot be built.

• It allows empowerment that encourages pride ownership and it encourages

commitment.
5. Training
• Training the employees require interpersonal skills, the ability to function

within teams, problem solving, decision making, job management

performance analysis and improvement, business economics and technical
skills.
5. Teamwork
• To become successful in business, teamwork is also a key element of TQM.

With the use of teams, the business will receive quicker and better solutions
to problems.
6. Leadership
• Leadership in TQM requires the manager to provide an inspiring vision,

make strategic directions that are understood by all and to instill values that
guide subordinates.
7. Communication
• It binds everything together.

• It acts as a vital link between all elements of TQM.

➤ TQM Philosophy
• TQM Focuses on identifying quality problem root causes.
• It involves the technical as well as people.

It consists of the following

1. Focus on Customer: It identifies and meet customer needs. It always stays
tuned to changing needs, e.g. fashion styles.
2. Continuous Improvement: It means continuous learning and problem
solving, incremental improvement that occurs on a regular basis.
e.g. Kaizen, 6 sigma’s
3. Employee Empowerment: It is necessary to empower all employees for
external and internal customers and involved them in quality initiatives.
4. Team Approach: Teams formed around processes of 8 to 10 people.
They should meet weekly to analyze and solve problems.
6.4.6 Quality Audit
• Quality auditing is the systematic, independent, and documented review and

evaluation of an organization’s quality management system (QMS) to

determine whether quality activities and results comply with a strategic
arrangement that is effectively implemented and appropriate to achieve the
objectives.
6.5 cGMP (CURRENT GOOD MANUFACTURING PRACTICE)
• cGMP refers to the Current Good Manufacturing Practice regulations
enforced by the FDA. cGMP provides for systems that assure proper design,
monitoring, and control of manufacturing processes and facilities.
• It’s not only required to meet current Good Manufacturing Practices (cGMP)

standards and regulatory requirements, but it’s also what sets the most
successful CDMOs and preventative.
6.5.1 Objectives
• Ensure that products are consistently manufactured and controlled to the

specified quality.
• Concerned with all aspects of production and quality control. In the

manufacture of cosmetic products, overall control and monitoring.

6.5.2 Testing
• Final testing of the product cannot ensure the Quality efficiency and safety.

• Final testing may always not detect errors.

6.5.3 GMP (Goods Manufacturing Practices)

• Good Manufacturing Practices is the aspect of quality assurance that ensures

that medicinal products are consistently produced and controlled to the

quality standards appropriate to their intended use and as required by the
product specification.
Principles of GMP:
✔ Principle 1: Defining and creating standard operating procedures (SOPs).
✔ Principle 2: This principle focuses on effectively following documents
pertaining to work procedures.
✔ Principle 3: This principle works to examine problems or complaints regarding
a product. It mandates documentation of work after completion, which also enables
regulatory compliance.
✔ Principle 4: Validation is an essential step to progress ahead in the process. This
principle involves creating documentary evidence that the techniques, processes,
and production maintain the expected level of compliance during all the stages.
✔ Principle 5: Properly defining and designing equipment and construction
facilities.
✔ Principle 6: Maintaining facilities and equipment.
✔ Principle 7: Each employee impacting the product quality should be trained.
Basic GMP theory and practice, as well as role-related training, should be included
in the training.
✔ Principle 8: Preventing contamination through cleanliness.
✔ Principle 9: This principle entails incorporating quality directly into all
production phases by putting clearly defined controls in place and preserving
accurate, timely records.
✔ Principle 10: It undertakes periodic audits to evaluate the efficacy of GMP
compliance. Therefore, audits must be performed regularly to ensure that nothing is
overlooked.
➤ Components of GMP
• GMP mainly consist of five components that is termed as 5P’s as given in fig
6.4.
6.6 INTRODUCTION TO CONCEPT OF CALIBRATION
• Calibration is the standardization process of an instrument
based on an existing standard. It helps make the instrument set
work in a required range while maintaining accuracy.
• Calibration must be performed according to approved written procedures and

the calibration records must be maintained for a certain period of time.

6.6.1 Advantages
Quality measuring system will help organization in the following ways:
• The error of an instrument is taken into account while using it and hence

correct measurements are recorded and reported.

• Wherever possible, one can adjust or repair the instrument to minimize the

error to the best extent.

6.6.2 Objectives
• Calibration brings out the nature and magnitude of error (if any) of testing

measuring instruments.
6.6.3 Instrument Calibration
• All the testing and measuring instruments calibrated at a

reputed institute or organization like RRSL, NC QC, etc.

which has a set of precise reference standard, instruments.
 • It should provide good, most accurate and reliable calibration services with
due traceability. Some of them are built to provide following facilities:

6.7 VALIDATION
• Validation is an important part of Analytical as well as
Bio-Analytical Method. The procedure involved in
checking data or programs for correctness, compliance
with standards and conformance with the requirement
specifications.
• It is establishing documented evidence, which provides high degree

assurance.
6.7.1 Importance of validation
The importance of validation is
• During the process the knowledge of process increases.

• It assures the repeatability of the process.

• It assures that the product is continuously producing according to the

marketing authorization.
6.7.2 Method of validation
1. Identification
2. Quantitative tests for content or impurities
3. Limit tests for control of impurities
6.7.3 Guidelines of validation
➤ ICH Q2A: Text on validation of analytical procedures Definitions and
Terminology (March 1995).
➤ ICH Q2B: Validation of analytical procedure: Methodology (June 1997).
➤ FDA: (Draft) Guidance for industry Analytical procedure and methods
validation.
6.7.4 Types of validation
There are various types of Validation as given below:
1. Equipment Validation
Equipment validation is established documented set up that proves any equipment
works correctly and leads to accepted and accurate results (predetermined result).
✔ Design Qualification
• It is a documented verification of design of the equipment and manufacturing

facilities.
• The main purpose of Design qualification is to make sure that all the

requirements for the systems should clearly defined at the start.

✔ Installation Qualification
• Installation qualification confirms that the precised equipment has been
received and installed as per target and agreement in exact design.
✔ Operational Qualification
• Operational qualification ensures that installed equipment/instrument will

function perfectly according to its operation specification in the mention

environmental conditions.
• It also checks that the equipment function perfectly to meet pre-assigned

performance criteria and ensure how the testing results are recorded.
2. Method Validation
Method Validation establishes documented evidence that the procedure adopted for
a test is fit for the intended purpose in terms of quality, reliability and consistency
of results.
✔ New Method Development: It established method used in a different laboratory,
analysis of instrumentation.
It demonstrates the equivalence between new and established method.
✔ Objectives: The objectives of this exercise are to consider appropriate validation
characteristics to provide a sound overall knowledge of the capabilities of the
analytical method.
✔ Scope: The scope covers analytical performance parameters.
3. Facilities Validation
Facility validation deals with establishing documented evidence that provides a
high degree of assurance that the manufacturing processes, including buildings,
systems, and equipment consistently produce the desired results according to
predetermined specifications.
4. Cleaning Validation
Cleaning validation is a procedure of establishing evidence that cleaning processes
for manufacturing equipment prevents product contamination.
5. Computer System Validation
Validation of computerized systems is a documented process to ensure that a
computerized system does exactly what it was designed to do in a consistent and
reproducible way (suitability to use), ensuring the integrity and security of data
processing.
6. Process Validation
It is establishing documented evidence, which provides high degree assurance, such
as manufacturing of pharmaceutical dosage forms will consistently produce a
product meeting its predetermined specification.
✔ Stages of Process Validation
The Process Validation has been divided into 3 different stages as given in fig 6.5
Stage 1: Process Design
This is the research and development phase and involves defining a process for
manufacturing the product.
Stage 2: Process Qualification
This stage evaluates/qualifies the process designed earlier to ensure it can
reproduce consistent and reliable levels of quality.
It involves collecting and evaluating data on all aspects and stages of the
manufacturing process.
Stage 3: Continued Process Verification
Continued Process Verification involves ongoing validation during production of
the commercial product to ensure the process designed and qualified in the previous
stages continues to deliver consistent quality.
✔ Types of Process validation
i. Prospective Validation: Validation conducted prior to the distribution of either a
new product or product made under a revised manufacturing process.
ii. Retrospective Validation: Validation of a process for a product already in
distribution based upon accumulated production and control data, or evidence, e.g.,
stability studies.
iii. Concurrent Validation: In process monitoring of critical processing steps and
end product testing of current production.
6.7.5 Strategies of Validation
This optimization consists of defining and performing the minimum number of
verification and validation actions but detecting the maximum number of
errors/faults/defects and achieving the maximum level of confidence in the system.
These includes the following:
1. Validation master plan
A Validation Master Plan, also referred to as “VMP”, outlines the principles
involved in the qualification of a facility, defining the areas and systems to be
validated, and provides a written program for achieving and maintaining a qualified
facility.
2. Validation report
The validation report summarizes all validation results, gives recommendations for
fixing errors and/or improving the overall quality of the speech corpus and gives an
executive summary.
3. Expert Evaluation
Expert evaluation is a crucial step in the validation process of a study, particularly
in fields such as research, scientific experiments, or industrial processes.
6.7.6 Department and Authority for Validation
There are different department and authority for validation as given in Table 6.2.
 Table 6.2: Department and authority for validation

DEPARTMENT / DESIGNATION RESPONSIBILITY

Responsible for manufacturing of batches and review

Manager Production
of protocol and report.
Manager QC Responsible for analysis of sample collected
Responsible for samples collection and submission to
Executive QC
QC
Manager Maintenance Providing utilities and engineering support
Responsible for preparation of protocol and
Executive Production
manufacturing of validation batches

6.7.7 Revalidation
• Analytical methods require validation whenever the conditions

for which the methods have been developed change.

Revalidation of the analytical method is required in the following
circumstances:
• An existing method is modified to meet special requirements.

• Changes to the formulation composition of an agricultural and veterinary

chemical product.
• Revalidation should be performed to ensure that the analytical method

maintains its characteristics.

• The degree of revalidation depends on the nature of the change to a new

dosage strength in a product.