CHAPTER 1:INTRODUCTION

COMPANY PROFILE:Indchemie Health Specialities Pvt. Ltd has been in the ethical pharma business for more than
two decades now, with leadership in few of the segments. It has a strong back up of in-house
manufacturing facility & has four Pharmaceuticals Manufacturing Units (Two at Daman, 3rd at
Baddi, Himachal Pradesh & 4th at Sikkim) in India. All four units are approved by WHO
based on current GMP Guidelines.
Out of four units, one of the manufacturing units is totally dedicated to Soft Gelatin Capsules
Formulation. In March 2006 it was audited & in June 2006 the same has been approved by TGA,
Australia. The next level of Achievement would be USFDA & MHRA, UK approvals and the
technical team has geared up for these prestigious inspections. This accreditation directly talks of
the qualitypar excellence imbibed in every brand of Indichemie.
The Beta-Lactam unit is having several commendable approvals from African Regulatory
agencies like Ethiopia, Kenya and Malawi. The technical team at Beta-Lactam facility is now
gearing up for other prestigious approvals like MCC South Africa and MHRA UK.
These approvals will further boost the confidence in our products, who today have high clinical
success.
Our comprehensive range of products covers wide therapeutic segments wherein a large number
of products are technologically backed up with Bioequivalence studies at par with brand leaders
in the segment.
In ever evolving environs of healthcare industry, keeping pace with the time is a tough task. It
requires consistent & qualitative research for which Team Indchemie is always in the forefront .
At Indchemie, we are committed to research & development with a vision to create path breaking
health solutions,both inchronicaswell as acute segments.
In an integral approach to healthcare that fuses traditional wisdom with technological
sophistication has made us what we are today, leading to become Pioneers in the Indian Pharma
Industry.

What is WHO GMP Guidelines?

The first WHO draft text on good manufacturing practices (GMP) was prepared in 1967 by a
group of consultants at the request of the Twentieth World Health Assembly (resolution
WHA20.34). It was subsequently submitted to the Twenty-first World Health Assembly under
the title Draft requirements for good manufacturing practice in the manufacture and quality
control of medicines and pharmaceutical specialities and was accepted.
The revised text was discussed by the WHO Expert Committee on Specifications
for Pharmaceutical Preparations in 1968 and published as an annex to its twentysecond report. The text was then reproduced (with some revisions) in 1971 in the
Supplement to the second edition of The International Pharmacopoeia.

 In 1969, when the World Health Assembly recommended the fi rst version of the
WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in
International Commerce in resolution WHA22.50, it accepte the same time the
GMP text as an integral part of the Scheme. Revised versions of both the
Certification Scheme and the GMP text were adoptedin 1975 by resolution
WHA28.65. Since then, the Certification Scheme has been extended to include
the certification of:
veterinary products administered to food-producing animals;
information on safety and efficacy (resolution WHA41.18, 1988).
Good practices in production and quality control, provides guidance on
actions to be taken separately by production and by quality control personnel for
the implementation of the general principles of QA.
Considerable developments in GMP have taken place in the intervening years,
and important national and international documents, including newrevisions,
have appeared (2,3,4,5). Thus the necessity to revise the mainprinciples and
incorporate the concept of validation.
Among other feedback which was discussed during the consultation onWHO
guidelines for medicines quality assurance, quality control (QC)laboratories and
transfer of technology on 2731 July 2009, the need was identified to
incorporate a new section (1.6) on Product quality reviewunder Chapter 1:
Quality assurance.In addition, several updates were suggested to further
enhance the guidelines and include the concept of risk management, replacing
drugs by the termmedicines and newly introduce the concept of a quality
unit.

General considerations
Licensed pharmaceutical products (marketing authorization) should be manufactured
only by licensed manufacturers (holders of a manufacturingauthorization) whose
activities are regularly inspected by competent nationalauthorities. This guide to GMP
shall be used as a standard to justify GMP status, which constitutes one of the elements of
the WHO CertificationScheme on the quality of pharmaceutical products moving in
internationalcommerce,

through

the

assessment

of

applications

for

manufacturingauthorizations and as a basis for the inspection of manufacturing facilities.

It may also be used as training material for government medicines inspectors,as well as
for production, QC and QA personnel in the industry.
The good practices outlined below are to be considered general guides15,and they may be
adapted to meet individual needs.

Al though there are a number of them, all guidelines

follow a few basic principles:
Hygiene: Pharmaceutical manufacturing facility must maintain a clean and hygienic
manufacturing area.
Manufacturing processes are clearly defined and controlled. All critical processes
are validated to ensure consistency and compliance with specifications.
Manufacturing processes are controlled, and any changes to the process are evaluated.

Changes that have an impact on the quality of the drug are validated as necessary.
Instructions and procedures are written in clear and unambiguous language. ( Good
Documentation Practices)

Operators are trained to carry out and document procedures.

Records are made, manually or by instruments, during manufacture that demonstrate that
all the steps required by the defined procedures and instructions were in fact taken and
that the quantity and quality of the drug was as expected. Deviations are investigated and
documented.
Records of manufacture (including distribution) that enable the complete history of a
batch to be traced are retained in a comprehensible and accessible form.
The distribution of the drugs minimizes any risk to their quality.
A system is available for recalling any batch of drug from sale or supply.
Complaints about marketed drugs are examined, the causes of quality defects are
investigated, and appropriate measures are taken with respect to the defective drugs and
to prevent recurrence.

INDIAN GMP

INDIAN GMPs
Quality, efficacy and safety of drug have always been a matter of concern for people. Drugs
being a very important component of health care systems need special attention in regard to their
quality, efficacy and safety. A brief review over half a century of drugs scenario in India will
shows us how we have come a long way in controlling of quality of product. The first GMP was
published in june1963.
Thus major contribution of this amendment was introduction of preventive approach to the
control of the drug products. These regulation were first revised in January 1971. A major
revision approached in late 1978.

The current regulation GMP appeared in part 210 of title 21 of code of federal regulations
published by the Food and Drug Administration, Department of Health and Human Services of
USA.
The following are the main objects of GMPs
To produce products confirming to the predetermined specification.
To produce product of consistent quality.
To minimise contamination.
To eliminate error.
Generally text of GMPs provide guidelines on important aspects of manufacture of drugs
like premises, personnel, equipments, sanitation, starting material, manufacturing
operation, validation, quality control system, documentation etc
Many Indian Drug Manufactures are exporting pharmaceutical preparation to developing
countries which are participant to WHO certification scheme.
These countries require a certificate from regulatory agency that the plant in which it
have been manufactured is subjected to inspection at regular intervals and the plant
confirms to requirements for good practices in the manufacture and quality control of
drug as recommended by WHO.
Therefore, Indian drug manufacturers as well as their technical personnel should be
aware of the GMPs prepared by WHO. For convenience, these GMPs have been referred
to as the WHO GMPs.

WHO GMP:
INTRODUCTION AND SIGNIFICANCE

WHO GMP
The World Health Organisation (WHO) is an agency of United Nation. It is a specialized
agency and its primary responsibilities include international health matter so that the goal
(health) of all can be achieved.
WHO expert committee on specification for pharmaceutical preparation discussed the
text in1968 and the revised text was published as an annexure to its 22 nd report. Text on
GMP was accepted as an integral part of WHO certification scheme on the quality of
pharmaceutical product moving in international commerce by WHA in1969 when it
recommended the first version of scheme. There have been many development since
then. Several nation and international GMPs document have appeared. GMPs text
applicable to the revised text contain three parts:
Part 1 outlines general concepts of quality assurance and salient components of GMPs.
These component of GMPs which includes hygiene, validation, self-inspection,

personnel, premises, equipments, materials and documentation are joint responsibilities

of the top management.
Part 2 provides guidelines on the action to be taken by production and quality control
personnel separately implementing in the general principles quality assurance.
Part 3 is an open ended section and has two supplementary guidelines at present. It is
anticipated that guidelines for special product will be develop in future.

WHO CERTIFICATION SCHEME

The Good Practices in the manufactured control of the drugs (knows as GMPs) form an
integral part of WHO certification scheme.
This scheme envisages that.
1) A comprehensive system of quality assurance should be established on a reliable
system of licensing/registration.
2) An independent analysis of finished product should be carried out.
3) An assurance should obtained through independent inspection that all manufacturing
are carried out in conformity with GMP as laid down by WHO.

Note-:The General Requirements as given in Part I of this Schedule relating to Requirements

of Good Manufacturing Practices for Premises and Materials for pharmaceutical products shall
be complied with,mutatis mutandis, for the manufacture of Sterile products, Parenteral
preparations (Small Volume Injectables and Large Volume Parenterals) and Sterile Ophthalmic
Preparations. In addition to these requirements, the following Specific Requirements shall also
be followed, namely: -

General
Sterile products, being very critical and sensitivein nature, a very high degree of
precautions, prevention and preparations are needed. Dampness, dirt and darkness are to
be avoided to ensure aseptic conditions in all areas.
There shall be strict compliance in the prescribed standards especially in the matter of
supply of water, air, active materials and in the maintenance of hygienic environment.

Quality Assurance: Adequate arrangement are made for manufacture,supply,and use of the correct starting
and packaging materials.
Adequate controls on starting materials,intermediateproducts,and bulk products and other
in-process controls,calibrations,and validations are carried out.
The finished product is correctly processed and checked in accordance with establish the
product.
Quality assurance=GCPs + GMPs + GLPs + any other measures to achieve intended
quality

Good

manufacturing

practices

for

pharmaceutical

products: GMP is that part of QA which ensures that products are consistently produced and
controlled to the quality standards appropriate to their intended use and as required by the
marketing authorization.

 Such risks are essentially of two types: cross-contamination (in particular of unexpected
contaminants) and mix ups (confusion) caused by, for example false labels being put on
containers;
Under GMP:
All manufacturing processes are clearly defined, systematically reviewed in the light of
experience, and shown to be capable of consistently manufacturing pharmaceutical
products of the required quality thatcomply with their specification;
All necessary resources are provided, including:
Appropriately qualified
Trained personnel;
Adequate premises and space;
Suitable equipment and services;
Appropriate materials, containers and labels;
Approved procedures and instructions;
Suitable storage and transport;

Sanitation in the manufacturing premises: The manufacturing premises shall be cleaned and maintained in an orderly manner so that
it is free from accumulated waste,dust,debris and other similar material.A validated
cleaning procedure shall be maintained.
The manufacturing areas shall not be used for storage of materials,except for the material
being processed.It shall not be used as a general through fare.

Qualification and Validation: In accordance with GMP, each pharmaceutical company should identify what
qualification and validation work is required to prove that thecritical aspects of their
particular operation are controlled.
The key elements of a qualification and validation programme of a company should be
clearly defined and documented in a validation master plan.

Complaints and adverse reactions: Reports of serious adverse drug reactions resulting from the use of a drug along with
comments and documents shall be forth with reported to the concerned licencing
authority.
A person responsible for handling the complaints and deciding the measures to be taken
should be designated, together with sufficient supporting staff to assist him or her. If this
person is different from the authorized person, the latter should be made aware of any
complaint and investigation or recall.

Product recalls: The authorized person should be responsible for the execution and coordination of
recalls. He/she should have sufficient staff to handle all aspects of the recalls with the
appropriate degree of urgency.
There should be established written procedures, which are regularly reviewed and
updated, for the organization of any recall activity. Recall operations should be capable of
being initiated promptly down to the required level in the distribution chain.

Contract production and analysis: Contract production and analysis must be correctly defined and agreed and controlled in
order to avoid misunderstandings that could result in a product or work or analysis of
unsatisfactory quality.

(a)General: All arrangements for contract production and analysis, including any proposed changes in
technical or other arrangements, should be inaccordance with the marketing authorization
for the product concerned.
The contract should permit the contract giver to audit the facilities of the contract
acceptor. (b)Contract giver: The contract giver is responsible for assessing the competence of the contract acceptor in
successfully carrying out the work or tests required, for approval for contract activities,

And for ensuring by means of the contractthat the principles of GMP described in this
guide are followed.

(C)The contract: The contract must clearly state the way in which the authorized person, in releasing each
batch of product for sale or issuing the certificate of analysis, exercises his or her full
responsibility and ensures that each batch has been manufactured in, and checked for,
compliance with the requirements of the marketing authorization.

Self-inspection, quality audits and suppliers audits and

approval: The purpose of self-inspection is to evaluate the manufacturers compliance with GMP in
all aspects of production and QC. The self-inspection programme should be designed to
detect any shortcomings in the implementation of GMP and to recommend the necessary
corrective actions.
Items for self-inspection: Premises including personnel facilities;
Maintenance of buildings and equipment;
Storage of starting materials and finished products;
Equipment;
Production and in-process controls;
QC;
Documentation;
Sanitation and hygiene;
Validation and revalidation programmes;
Calibration of instruments or measurement systems;
Recall procedures;
Complaints management;
Labels control;

Personnel:-

Number of personnel employed shall be adequate and in direct proportion to the workload.
These may include, depending on national regulations:
Authorization of written procedures and other documents, including amendments;

Monitoring and control of the manufacturing environment;

Plant hygiene;

Process validation and calibration of analytical apparatus;

Training, including the application and principles of QA;

Approval and monitoring of suppliers of materials;

Approval and monitoring of contract manufacturers;

Training: The manufacturer should provide training in accordance with a written programme for all
personnel whose duties take them into manufacturing areas or into control laboratories
(including the technical, maintenance and cleaning personnel) and for other personnel as
required.
Besides basic training on the theory and practice of GMP, newly recruited personnel
should receive training appropriate to the duties assigned to them. Continuing training
should also be given, and its practical effectiveness periodically assessed. Approved
training programmes should be available.

Personal hygiene: All personnel, prior to and during employment, as appropriate, should undergo health
examinations. Personnel conducting visual inspections should also undergo periodic eye
examinations.
All personnel should be trained in the practices of personal hygiene.
A high level of personal hygiene should be observed by all those concerned with
manufacturing processes. In particular, personnel should be instructed to wash their hands

before entering production areas. Signs to this effect should be posted and instructions
observed.

Ancillary areas: Rest and refreshment rooms shall be separate from other areas.These areas shall not lead
directly to the manufacturing and storage areas.
Facilities for changing and storing clothes and for washing and toilet purposes shall not
lead directally to the manufacturing and storage areas.

Storage areas: Storage areas should be of sufficient capacity to allow orderly storage of the various
categories of materials and products with proper separation and segregation: starting and
packaging materials, intermediates and bulk and finished products, products in
quarantine, and released, rejected and returned or recalled products.

Weighing areas: The weighing of starting materials and the estimation of yield byweighing should be
carried out in separate weighing areas designed for that use, for example, with provisions
for dust control. Such areas may be part of either storage or production areas.

Production areas: The production area shall be designed to allow the production preferably in uni-flow and
with logical sequence of operations.
In order to avoid the risk of cross-contaminations and separate dedicated and self
contained facilities shall be made available for the production of sensitive pharmaceutical
products like peniciline or biological preparation with live microorganism.

Quality control areas:-

 Quality Control Laboratories shall be independent of the production areas.Separate areas

shall be provided each for physic-chemical and biological and microbiological or radioisotope analysis.
Quality Control Laboratories shall be designed appropriately for the operations to be
carried out in them.Adequate space shall be provided to avoid mix-up and crosscontamination.

Equipment: Equipment shall be located,designed,constructed,adapted and maintained to suit the

operations to be carried out.Each equipment shall be provided with a log book ,wherever
necessary.
The parts of the production equipment that come into contact with the product shall not
be reactive additive or adsorptive to an extent that would affect the quality of the product.

 Equipment should be installed in such a way as to minimize any risk of error or of

contamination.

Materials: The main objective of a pharmaceutical plant is to produce finished products for patients
use from a combination of materials (starting and packaging).
Materials include starting materials, packaging materials, gases,solvents, process aids,
reagents and labelling materials.

(a)General: No materials used for operations such as cleaning, lubrication of equipment and pest
control, should come into direct contact with the product. Where possible, such materials
should be of a suitable grade (e.g.food grade) to minimize health risks.

(b)Starting materials: The purchase of starting materials is an important operation that should involve staff who
have a particular and thorough knowledge of the products and suppliers.

(c)Packaging materials: The purchase, handling and control of primary and printed packaging materials should be
as for starting materials.
Particular attention should be paid to printed packaging materials.

(d)Intermediate and bulk products: Intermediate and bulk products should be kept under appropriate conditions.

 Intermediate and bulk products purchased as such should be handled on receipt as though
they were starting materials.

(e)Finished products: Finished products should be held in quarantine until their final release, after which they
should be stored as usable stock under conditions established by the manufacturer.
The evaluation of finished products and the documentation necessary for release of a
product for sale are described in section 17,Good practices in quality control.

(f)Rejected, recovered, reprocessed and reworked materials: Rejected materials and products should be clearly marked as such and stored separately
in restricted areas. They should either be returned to the suppliers or, where appropriate,
reprocessed or destroyed in a timely manner. Whatever action is taken should be
approved by authorized personnel and recorded.

Documentation: Good documentation is an essential part of the qualityassurance system and, as such,
should exist for all aspects of GMP. Its aim to define the specification and procedures for
all materials and methodsof manufacture and control; to ensure that all personnel
concerned with manufacture know what to do and when to do it; to ensure that authorized
persons have all the information necessary to decide whether or not to release a batch of a
medicine for sale, to ensure the existence of documented evidence, traceability, and to
provide records and an audit trail that will permit investigation. It ensures the availability
they will usually be separate.

(a))General:Documents should be designed, prepared, reviewed and distributed with care. They should
comply with the relevant parts of the manufacturing and marketing authorizations.

(b)Documents required:-

Labels: Labels applied to containers, equipment or premises should be clear, unambiguous and in
the companys agreed format. It is often helpful in addition to the wording on the labels
to use colours to indicate status (e.g.quarantined, accepted, rejected, clean).

Specification and testing procedures: Each specification should be approved, signed and dated, and maintained by the QC, QA
units or documentation centre. Specifications for starting materials, intermediates, and
bulk, finished products and packaging materials are referred to in sections 15.1815.21.

Specifications for finished products:The designated name of the product and the code reference, where applicable;
The designated name(s) of the active ingredient(s) (if applicable, with the INN(s)
The formula or a reference to the formula;
A description of the dosage form and package details;

Master formulae: A formally authorized master formula should exist for each product and batch size to be
manufactured.
The name of the product, with a product reference code relating to its specification;

Batch processing records: A batch processing record should be kept for each batch processed. It should be based on
the relevant parts of the currently approved specifications on the record. The method of
preparation of such records should be designed to avoid errors. (Copying or validated
computer programmes are recommended. Transcribing from approved documents should
be avoided.)

Batch packaging records: A batch packaging record should be kept for each batch or part batch processed. It should
be based on the relevant parts of the approved packaging instructions, and the method of
preparing such records should be designed to avoid errors. (Copying or validated
computer programmes are recommended. Transcribing from approved documents should
be avoided.)

Standard operating procedures and records: SOPs and associated records of actions taken or, where appropriate and conclusions
reached should be available for: Equipment assembly and validation;
Analytical apparatus and calibration;
Maintenance, cleaning and sanitization
Personnel matters including qualification, training, clothing and hygiene;
Environmental monitoring;
Pest control;
Complaints;
Recalls;

Good practices in production: Production operations must follow clearly defined procedures in accordance with
manufacturing and marketing authorizations,with the objective of obtaining products of
the requisite quality.

General All handling of materials and products, such as receipt and cleaning,quarantine,
sampling, storage, labelling, dispensing, processing, packaging and distribution should be
done in accordance with written procedures or instructions and, where necessary,
recorded.

Prevention of cross-contamination and bacterial contamination

during production When dry materials and products are used in production, special precautions should be
taken to prevent the generation and dissemination of dust. Provision should be made for
proper air control (e.g. supply and extraction of air of suitable quality).

Contamination of a starting material or of a product by another material or product must

be avoided.

Packaging operations
When the programme for packaging operations is being set up, particular attention should
be given to minimizing the risk of crosscontamination, mix-ups or substitutions. Different
products should not be packaged in close proximity unless there is physical segregation
or an alternative system that will provide equal assurance.
Before packaging operations are begun, steps should be taken to ensure that the work
area, packaging lines, printing machines and other equipment are clean and free from any
products, materials or documents used previously and which are not required for the
current operation.

Good practices in quality control

QC is the part of GMP concerned with sampling, specifications and testing, and with the
organization and documentation which ensure that the necessary and relevant 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. QC is not confined to
laboratory operations, but may be involved in many decisions concerning the quality of
the product.
The independence of QC from production is considered fundamental.
Each sample container should bear a label indicating:
The name of the sampled material;
The batch or lot number;

 The number of the container from which the sample has been taken;
The number of the sample;
The signature of the person who has taken the sample;
The date of sampling.

Test requirements
Starting and packaging materials: Before releasing a starting or packaging material for use, the QC manager should ensure
that the materials have been tested for conformity with specifications for identity,
strength, purity and other quality parameters.

An identity test should be conducted on a sample from eachcontainer of starting material.

Batch record review: QC records should be reviewed as part of the approval process of batch release before
transfer to the authorized person. Any divergence or failure of a batch to meet its
specifications should be thoroughly investigated.
The investigation should, if necessary, extend to other batches of the same product and
other products that may have been associated with the specific failure or discrepancy. A
written record of the investigation should be made and should include the conclusion and
follow-up action.

Stability studies: QC should evaluate the quality and stability of finished pharmaceutical products and,
when necessary, of starting materials and intermediate products.
QC should establish expiry dates and shelf-life specifications on the basis of stability
tests related to storage conditions.

On site verification:

From receiving to store

Sampling and weighing
Manufacturing areas
Utilities
Documentation review

R&D Policy:Indchemie has strong support and focus on R&D which substantially scaled up on its
investments to build its capabilities in all the areas of generic research as a short to medium term
strategy. Generic drug development encompasses both small and large molecules. Indchemie
strongly believes that there are attractive opportunities in the highly competitive global generic
space. Indchemie believes in strategic alliance for R&D and offers its R&D and scale-up
facilities to major players for development activities in the Indian Pharma Industry.
The business focus is backed with the building up of captive manufacturing operations and of
complying with the regulatory standards of the advanced markets.
Indchemie's generic drug development meets the speed and quality attributes, as all the elements
of research have been conducted within the same campus, situated at Taloja, Navi Mumbai.
Indchemie committed a substantial amount of its resources to the development of Novel Drug
Delivery Systems and this shall be the key element in providing momentum to consolidate its
objective of value addition
Indchemie is also collaborating with several Indian companies for their development of difficultto-make products and the development of other unique technologies. Indchemie is progressing
with leaps and bounds in the Nutraceutical segment of healthcare and wellness. Nutraceutical
R&D efforts are mainly directed towards providing vitamins and nutritional products for the
better management of health in the todays busy life. Commendable success has been achieved in
this area of research and development

3.4 DATA COLLECTION PROCESS

Data collection is done through primary and secondary data. All the people from different
professions were personally visited and interviewed. They were the main source of Primary data.
The method of collection of primary data was direct personal interview through a structured
questionnaire. The secondary data was collected from internal sources such as various
management books, documents, official records, newspapers, magazines, articles.
RESEARCH INSTRUMENT
The research instrument was the structured questionnaire formulated for the respondent. The
questionnaire includes open, closed ended questions and likert scale. This was done, so that the
consumers can understand the questions easily and to maximize the response.

3.6TOOLS USED

Data analysis and interpretation tools and techniques are decided keeping in view the nature and
type of data collected. Sample from the above these questions will be compiled in the SPSS
software data and further will be analyzed with the help of Cross tabulations, and frequency
table. SPSS software will be used for overall analysis.
Limitations

Due to the financial and time constraints the study wasnt able to include more
respondents.

The respondents may be biased or influenced by other factors.

As majority of the respondents have done their shopping from retail websites, so this
report is made considering only the retail websites.

Another limitation could be lack of knowledge. Being student I undertake this project
as a learning experience. I have made many mistakes and then learned from them. Have
tried my best to be as authentic and as accurate as possible in the research analysis taking
the help of my project guide on relevant primary and secondary data.

Respondents below 18 year of age were not included in the present study, as it was
assumed that respondents of 18 years and above can answer questions related to internet
advertising.