SYNOPSIS ON

Quality Control Practices in Pharmaceutical Industry:

A Case Study of units Located in Haryana

QUALITY ASSURANCE IN

PHARMACEUTICAL INDUSTRIES -A CASE

STUDY OF HARYANA UNITS

I) INTRODUCTION TO TOPIC

II) TQM IN INDIAN PHARMACEUTICAL INDUSTRY

III) Indian pharmaceutical industry is fourth largest industry in its
field by volume in the world. Industry is known for providing
quality products at lower price through out the globe. Most of the
companies who were acting as domestic player now trying to
expand their business in abroad. Due to globalization trade
barriers are removed day by day to facilitate the global trade.
Most of the pharmaceutical companies are trying to tap the
emerging markets in European Union and USA due to high
profitability and more paying capacity of the customer. To cope
with other competitor from abroad Indian companies can use
TQM as a weapon. Companies have understood the importance
of TQM that is why most of the companies are trying to get ISO
certification and USFDA approvals. India has the maxim number
of US DA approved Plants after Italy.
• Good Manufacturing Practices (GMP):
GMP is that part of Quality assurance which ensures that products are consistently
produced and collected to the quality standards appropriate to their intended use and
as required by the marketing authorization or product specifications .GMP is
concerned with both production and quality control.

• Current Good Manufacturing Practices (cGMP):

They are promulgated by the commissioner of federal Food and Drug
Administration (FDA) , which specifies that the drug is deemed to be adulterated
“ if the methods used in , controls used for, its manufacture, processing ,
 packaging or holding do not conform to or are not administered in conformity
with Current Good Manufacturing Practices. The manufacture of pharmaceuticals
must be by current methods with current control as a requirement that which is
current or generally, accepted in drug industry as appropriate equipment,
methodology controls and records. The standard is not only that practices be
current .but that they also be “good”. Thus if a new practice is introduced
anywhere in the industry which is better than what is current , then all
manufacturers may seem obligated to adopt the better practices. Therefore it can
be seen that being in compliance with the GMP is not a static situation, but
requires the manufacturer to be aware of innovations which may be good. Even if
current practices were available, the FDA holds that it has special technical &
scientific experience to determine which of the current practices are also good.
A current, although not necessarily predominant, practice is considered “good” if:
1) It is feasible for manufacturer to implement.
2) It considers to ensuring or added assuring the safety, quality or purity of the drug
product.
3) The value of the contribution or added assurance exceeds the cost in money of
implementing or continuing the practice.

• Quality Assurance (QA):

QA is wide ranging concept which covers all matters which individually or
collectively influence the quality of the product. It is the sum total organized
arrangements made with the object of ensuring that medicinal products are of quality
required for their intended use. QA is related to all operations including
manufacturing, testing & records.

• Quality control (QC):

QC is a part of GMP which is concerned with sampling, specifications and testing
and with the organizations, documentation and release procedures which ensures that
the necessary tests are actually carried out and that materials are not released for use,
nor products released for sale or supply, until their quality has been judged to be
satisfactory.

• In – Process Quality Controls:

These are the checks performed during production in order to monitor & if necessary
to adjust the process to ensure that the product conforms to its specifications.
Environmental control & equipment controls are also considered as in process
control. Temperature, Humidity, Microbial count of area may be considered as
IPQC/IPC.

• Certification for the pharmaceutical industries

Following are the certificates, which are applicable for pharmaceuticals for
regulatory or commercial purposes.
1. Indian GMP (Schedule M) Statutory from June 1988 in India.
2. International Organisation for standards (ISO 9001 & 14001)
3. World Health Organisation (WHO GMP)
4. Therapeutic Goods Administration (TGA), Australia
5. Medicines Control Council (MCC), South Africa
6. cGMP Certification from US Food and Drug Administration
7. Medicines and healthcare products regulatory authority agency (MHRA), U.K
8. International Conference on Harmonization (ICH) USA, Europe & Japan
9. Certificate of Suitability (COS) – Europe
From early 20th century there has been a rapid increase in the rate of introduction of
pharmaceutical industries. Pharmaceutical is derived from Pharmacology. Pharmacology
is a branch of science about medicinal substances called pharmaceuticals. The field
encompasses drug composition, drug properties, interactions, toxicology and desirable
effects that can be used in therapy of diseases.
Pharmaceutical is referred to as formation of medicine or medicament for use in the
diagnosis, cure, mitigation, treatment or prevention of disease. Pharmaceutical industry
comprises establishments primarily engaged in one or more of the following:
(1) Manufacturing biological and medicinal products.
(2) Processing (i.e., grading, grinding and milling) botanical drugs and herbs.
(3) Isolating active medicinal principals from botanical drugs and herbs.
(4) Manufacturing pharmaceutical products intended for internal and external
consumption in such forms as tablets, capsules, vials, ointments, powders, solutions and
suspensions.
India is the forth largest manufacturer of pharmaceuticals in the global market. It clearly
depicts that the prices of medicines in India are lowest in the world. India is paying for
quality health care. India is the growth driver for global drug companies. Indian
pharmaceuticals industry has over 20,000 units. Around 246 pharmacy industries
constitute the organized sector of pharmaceuticals in Haryana, while others exist in the
small scale sector. There has been a rapid increase in the rate of introduction of new and
potent medicines. The assessment of quality of the medicines rests with the
manufacturers. Quality remains a main issue with the assurance of product to adhere
quality. A system of quality control performed at a manufacturing site is known as
Quality Assurance. It is the sum total of the organized arrangements made to ensure that
all APIs (Active Pharmaceutical Ingredients) are of the quality required for their intended
use and that quality systems are maintained. In the face of a challenging regulatory
environment pharmaceutical companies have found ways to improve quality and costs
significantly. To drive benefits from change, companies had created a culture where
quality objectives are transparent, well understood and goals can be achieved by
following certain sets of procedures called as “Standard Operating Procedures”
(SOP). A Standard Operating Procedure (SOP) governed by World Health Organization
is a set of written instructions that document a routine or repetitive activity which is
followed by employees in an organization. A Pharmaceutical Industry has an average of
1200- 1300 SOPs and these SOPs are governed by ISO: 9000 series. There are many
leading pharmaceutical industries which adopts SOPs such as: Sun pharmaceuticals,
Torrent pharmaceuticals, pfizer India, Novartis India, glaxoSmithKline, AstrZeneca etc.
In a nut shell it can be said that “Quality Assurance has undoubtedly evolve in
pharmaceutical industries stating quality from manufacturing processes, process control,
material, staff and training, organization of department to quality manuals”.

IV) SIGNIFICANCE OF THE STUDY

This study will be conducted basically to provide a new perspective to research world.
The main idea to select this topic is to have in depth knowledge in the field of Quality
Management. The study will provide knowledge how pharmaceutical companies keep
health care dimensions important by maintaining quality. This research work will
facilitate the knowledge for dimensions of quality in technical, personnel and material
terms. Pharmaceutical is the emerging field in the health care services therefore this study
is proposed to be done to touch in depth pillars of pharmacy.

TOPIC: Quality Control Practices in Pharmaceutical Industry: A Case

Study of units Located in Haryana

QUALITY ASSURANCE IN PHARMACEUTICAL INDUSTRIES-A

CASE STUDY OF HARYANA UNITS

V) EXPLANATION OF THE TERMS USED

Quality:
i) It is the totality of features and characteristics of a product or service that bear
on its ability to satisfy a given need.
ii) Quality means the degree to which a specific product satisfies a particular
class of consumers in general or the degree to which it conforms to a design
specification or the distinguishing feature of a product’s taste, color,
appearance etc.
Definition:
An asset which may be offered to the potential customer of a product or service.-
C.D.Lewis

Quality Assurance
i) It is quality control with an emphasis on quality in the design of the
products, processes and jobs in the selection of personnel and their
training.
ii) It is the system of setting the quality standards, appraising
conformance to the standards, actions taken when standards are not
met and planning changes in these standards.
Definition
All actions taken to ensure that standards and procedures are adhered to and that
delivered products or services meet performance requirements is Quality Assurance.

PHARMACEUTICAL INDUSTRIES
i) Public and private organizations involved in the manufacture of drugs and
medications.

IV. OBJECTIVES OF THE STUDY

(i) To identify & analyze the different elements of a TQM system in a
pharmaceutical entity.

(ii) To study the impact of Quality Certification, Annual Turnover and Investment in
the Manufacturing Plant on each Quality Factor.

(iii) To determine the correlation between the Quality Certification, Annual

Turnover & Investment in the Manufacturing Plant.

VI. REVIEW OF LITERATURE

Proactive pharmacovigilance should be mandatory for pharmaceutical industries
suggested by Pipasha Biswas (2007)An increase in drug safety concerns in recent years
with some high profile drug have led to raising the bar by various stakeholders more
importantly by the regulatory authorities. The number of Adverse Drug Reaction (ADRs)
reported have also resulted in a an increase in the volume of data handled and to
understand pharmacovigilance a high level of expertise is required to rapidly detect drug
risks as well to defend the product against an inappropriate removal. Proactive
pharmacovigilance throuought the product life cycle is the way forward and the future
direction for drug safety. It is a challenge to codify and standardize the act of signal
detection and risk management in the context of clinical trials and post-marketing
pharmacovigilance. While major advancements of the discipline of Pharma have taken
place in west , not much have been achieved in India, there is an immense need to
understand pharmacovigilance .for this to happen in India, the mind of people working in
regulatory agency (DCGI office) and Indian Pharmaceutical companies need to change.
various strategies are adopted for successful quality check: 1) making pharmacovigilance
mandatory and introducing pharmacovigilance inspections 2) list all drugs/ indications by
maintaining a standard database for every pharmaceutical company 3) Interaction with IT
sector in building a robust pharmacovigilance system for India.
Kishore Gnana Sam (2008) explained that readymade and informative knowledge in the
form of Standard Operating Procedures (SOPs) enhances the clinical management.
Implementing quality requires collaboration across disciplinary, functional units. Hence a
survey was carried out among thirty pharmaceutical companies to assess the need of
Standard Operating Procedures which act as a supportive management guidelines. The
lab in charge accepted that guidelines can reduce inappropriate variations and support
quality and safety initiatives. Using guidelines document as a knowledge source promote
authentic translation of domain knowledge. With these SOPs better tools are created to
facilitate the process. Majority of lab incharges supported that clinical practice guidelines
should be collaborated with laboratories so as to create collaboration among the units.

D.H.Shah(2007), has explained in his book SOPs and explained that for centuries quality
has remained a complex problem. World Health Organization (WHO) SOPs as a global
initiative for controlling variability. As per the protocol published by WHO analysis of
each SOP is necessary. This method provides rapid assessment of the quality of the
products for mass distribution and currently recommended/ adopted statutory methods. A
decision tree stating the procedure of laboratory for quality assurance and control have
the following salient features: 1) efficient identification of good quality formulations ii)
assure batch-to-batch consistency with respect to quality and performance iii) facilitate
the reduction of development time and simplify the processes.

Dr. Aniruddha (2009) has reported that by encouraging pharmaceutical companies to

put their clinics and doctors online, the Indian Health Ministry can help the Indian
pharmacy Industry to export their specialized medical devices, medicines and knowledge.
A website has become an integral part of modern medical practice. Website benefits are
not restricted to practice promotion only but also to make sales online through online
clinics. For example: doctors sell ovulation test kits and self insemination kits on the
companies’ website, allowing infertile couples in India to buy fertility tools. This is an
additional revenue stream.

While describing the status of Pharmaceutical companies in India Subodh Priolkar

(2009) analyzed that the global pharmaceutical market was around USD 735 bn in 2008.
China contributes around 2% and India’s contribution is a meagre1.8%. With such an
insignificant contribution not amounting to even double digits pressure on Indian
pharmaceutical companies has increased. There is a drastic reduction in drug approval
from USFDA. In 2007, there were only 19 approvals; the lowest in last 24 years.
Increased market of generics has lead to slow growth of pharmaceuticals. All of these
have led to tremendous escalation in the new drug development costs. galxoSmithKline
has already closed 28 plants since 2000. Novartis has reduced approximately 25, 00 jobs.
Pfizer close its in-house production and start outsourcing to china. The dream of making
India a hub of pharmaceutical requires overhauling of Indian pharma quality control
system.
A study done by Anuja. R. Shah (2008) has revealed the fact that on October 6, 2005,
the Government of India released the Gazette indicating sterile devices as drugs for
internal and external use in the diagnosis, treatment or research in human beings and
animals. In light of escalating use of medical devices, stringent regulatory standards are
made to ensure that the devices are safe, well studied and have least adverse reactions.
Drug and cosmetic act have boosted the global confidence in pharmaceutical industry in
India; pharmacy personnel can certainly play an important role in the regulation of medial
devices. Safety, risks, effectiveness and performance of the medical devices need to be
well established and regulated properly. According to WHO medical devices include
everything from highly sophisticated computerized medical equipment to simple wooden
cutter. Medical devices include medical gloves, bandages, syringes, disinfectant, surgical
lasers, machine appliances, software or other similar or related articles. The clinical
effectiveness of the devices used should be revised on parameters. Documentary of
standard devices containing technical specifications are to be recorded to ensure that
material, product, process and services are fit for their purpose and management
specifications meet their standards.
Dr. Prashant Gargava (2009) an environmental engineer in central Pollution Control
Board (CPCB) explained that QA integrates quality control, quality auditing,
measurement method validation, and sample validation in to the measurement process.
QC is intended to prevent, identify, correct, and define the consequence of difficulties,
which might affect the precision and accuracy, and or validity of the measurements. The
QC activities include: (1) modifying standard operating procedures (SOPs) to be followed
during sampling, chemical analysis & data processing by the respective organization; (2)
equipment overhaul, repair, acceptance testing & spare parts; (3) operator training,
supervision & support; (4) periodic calibrations and performance tests which include
blank (including field blanks) & replicate analysis; and (5) quality auditing. Quality
control activities begin with the design of the sampling and measurement strategy and
continue through the final validation of the database. Quality control has in fact been
identified as responsibility of the laboratory conducting the work. These activities
include:
• The development of standard operating procedures with comprehensive
measurement performance checks to ensure the quality of the measurements are
within established tolerance levels;
• Proper training and certification of operators/analysts to ensure data quality;
• The inclusion of measurements for the estimation of accuracy, precision, and
detection limits to crosscheck analytical performance needed to ensure data
quality;
• Verification of comparability with related measurements between
operators/analysts;
• Documentation of field and analytical activities; and
• Data validation

VII. RESEARCH METHDOLOGY

Contents of the Questionnaire:

The final questionnaire will include almost every aspects of Total Quality Management
relevant to a Pharmaceutical Manufacturing Plant.
The areas covered:
• Vendors control

• Control of Purchased Material

• Process Identification & Verification

• In Process Control & Measurement Assurance

• Maintenance of Production & Auxiliary Facilities

• Post Production Functions- Handling, Storage, Packaging, Preservation &

Delivery

• Quality Documentation; Records & Audits

• Commitment & Leadership for Quality

• Use of statistical tools & other tools for TQM

A) Data collection method

The plank on which the study rests is information, which will be procured of with a

judicious mix of both secondary data and primary sources of data.

1. Primary Data
Data which shall be collected specifically for this research includes: -

i) Interview and survey of pharmaceutical company personnel which will cover lab
mangers, lab technicians and scientists through a closed questionnaire with
informed ideas about the subject of the research.
ii) Observation, recognizing and recording relevant events and activities.
iii) One-to-one interview with employees.
iv) Group interviews.
 v) Observation.
2. Secondary data
i) Books
ii) Periodicals (magazines, journals)
iii) The World Wide Web for Information ‘or’ the Internet

B) Sample Design

1. Sampling Element: The basic elements which shall be studied are Plant Managers not

lab mangers, lab technicians and scientists of organized and small scale pharmaceutical

companies.

2. Population: A sample size of pharmaceutical industries of Haryana will be surveyed.

3. Sampling Methodology: The probability-based approach of stratified random

sampling will be adopted, in order to give adequate coverage to the selected area.

4. Sample Size: A sample size of 10 companies will be obtained. It should be at least 30

to 35% of the population.

D) Tools Used:

A questionnaire will be formulated to collect data for the purpose to know the level of
Quality Assurance in organized and unorganized pharmaceutical companies. For the
purpose of analysis and interpretation of the data bar charts and table formats will be used
to concise the data. To calculate and analyze the results chi-square and percentage
method shall be applied.

E) Statistics Used:
The collected data will be analyzed through following statistical tools:
(i) Frequency diagrams to analyze each attribute of TQM.
 (ii) Analysis of variance (ANOVA) between samples & within samples & carrying
out F-test at 5% level of significance for data collected across pharmaceutical
companies on each TQM attribute.

(iii) Chi-Square test to determine the correlation between attributes on

Nominal scale.

BIBLIOGRAPHY
Journals
1) Anuja.R. Shah & R.K.Goyal (2008), Current Status of the Regulations of
Medical Devices, “Indian journal ofPharmaceutical Sciences” Vol.14, pp.695-
700.

2) Kishore Gnana Sam(2008), Physician Need Assessment for Supportive Medical

Management Guidelines for Positioning in a Territory Care South Indian Hospital
“Indian Journal of Hospital Pharmacy”, Vol.7, pp.104-109.
 3) Pipasha Biswas & Arun K.Biswas (2007), Setting Standards for Proactive
Pharmacovigilance in India: The Way Forward , “Indian Journal of
Pharmacology”, Vol.39, Issue:3, pp.124-128.

4) R.D.Garg & Nupur Kaul (2008) Growth of Pharmacy in Delhi, “Indian Journal
of Hospital Pharmacy”, Vol.7 (2008), pp.119-120.

5) Subodh priolkar (2009), Can India be Pharmaceutical Superpower in 2020?

“Pharma Times”, Vol.41, No.1, pp.9-14.

6) Y.Ashokraj & Shrutidevi Aggarwal (2008) A Decision Tree for Rapid Quality
Assurance, “Indian Journal of Pharmaceutical Sciences” Vol.14, pp.1-5.

Magazines

1) Dr Aniruddha (2009), Online Doctors, “Modern Medicare Magazine” pp.52.

2) Ramesh Subrahmanian (2009), Cover Story: Pharmaceuticals, Business World,
Vol.29, pp.32-36.
Books
1) D.H.Shah (2007), Introduction to Quality Assurance, “QA Manual”, Business
Horizons, New Delhi, ISBN: 8190078828,pp.1-5,