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SITE MASTER
FILE

Compiled by Unit Quality Assurance ________________________

Mr. Darshan Trivedi

Checked by Head – Technical ________________________

Operation Mr. Kamlesh Desai
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Approved by Technical Management ________________________

Mr. Manoj Vora

INDEX

Section Table of contents Page No.

C1 General Information

C.1.1 Brief Information on Novagen Healthcare Pvt. Ltd. 5-5

Pharmaceutical manufacturing activities as

C.1.2 5–5
licensed by the national authority
Other manufacturing activities carried out on the
C.1.3 5–5
site
Name and address of the site, including
C.1.4 6–6
telephone, fax and 24-Hour telephone numbers.
Type of products manufactured on the site and
C.1.5 information about specifically toxic or hazardous 7–8
substances handled.

C.1.6 A short description of the site 8–9

Number of employees engaged in production,

quality assurance, quality control, Engineering
C.1.7 9–9
services, warehouse and Human resources and
Admin.
C.1.8 Use of outside scientific, analytical or other 9 – 10
technical assistance in relation to manufacture
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and analysis
Short description of the Quality Management
C.1.9 10 - 17
System

C2 Personnel

C2.1 Organizational chart for various departmental

17 – 17
arrangements
C2.2 Qualifications, experience and responsibilities of
17 - 19
key personnel
C2.3 Outline of arrangements for various training
19 – 21
programs and their documentations
Health requirements for personnel engaged in
C2.4 21 - 22
production

C2.5 Personal hygiene requirement including clothing 22 – 23

C3 Premises and Equipment

C3.1 Premises 23 – 23

C3.2 Nature of construction and finishes 23 - 24

C3.3 Brief description of HVAC system 25 – 27

C3.4 Brief description of water system 27 – 28

Maintenance and servicing of the air handling and

C3.5 29 – 29
water system
Major Equipments and Instruments of production
C3.6 29 – 31
and quality control laboratory

C3.7 Maintenance and servicing of equipment 31 – 31

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C3.8 Qualification, validation and calibration 32 – 35

C3.9 Sanitation 35 – 36

C4 Documentation 36 – 39

C5 Production

C5.1 Brief description of production operation 39 – 39

C5.2 Arrangement for material management 40 – 41

Arrangement for handling rejected materials and

C5.3 41 – 42
products
Brief description of the general policy for process
C5.4 42 – 42
validation

C6 Quality control

C6.1 Description of quality control system 43 – 44

C7 Contract manufacture and analysis 44 – 44

C8 Distribution, complaints and product recall

C8.1 Arrangement and recording system for distribution 44 – 45

Arrangements for handling complaint and product

C8.2 45 – 46
recall

C9 Self-Inspection 46 – 46

List of Annexures 47 - 47
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C.1 GENERAL INFORMATION:

C.1.1 Brief Information on Novagen Healthcare Pvt. Ltd.:

Novagen Healthcare Private Limited was established in the

year________ and the manufacturing plant was built in _________ and
located at Horizon Industrial Park area, village: Bamangam, NH-48,
District: Vadodara (Gujarat), India and is engaged in manufacture of
pharmaceutical formulation as per cGMP standards. This
manufacturing facility is equipped for the formulation of oral solid
dosage form (tablets, capsules), oral liquid dosage form (syrup,
suspension), dry syrups and small volume parenteral with the latest
manufacturing machines and has a team of qualified and experienced
staff to run the plant.
Novagen Healthcare Pvt. Ltd. establishes the quality of its products
with strong support from its R & D center. We are engaged with
International markets & our products are exported to almost 25
different countries all over the world.

C.1.2 Pharmaceutical Manufacturing Activities as Licensed by

the National
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Authority:
All the Pharmaceutical Manufacturing Activities are carried out as per
Schedule –M of the Indian Drugs & Cosmetics Act. The day to day
licensing and regulatory activities are controlled by Drugs & Licensing
Authority, Director of Medical & Health Services, --- --- of Vadodara &
Diu. Products are manufactured under License number GJ/ ___ and GJ/
___, valid up to ___________.

C.1.3 Other manufacturing activities carried out on the site:

No activity is carried out other than pharmaceutical manufacturing in

the site.
No any toxic or hazardous products manufactured at the site. No beta
lactams, vaccines, steroids or cephalosporin’s are manufactured at the
site.
No veterinary products are manufactured at the site.

C.1.4 Name and Address of the site, including telephone, fax and 24
hour telephone numbers:

Name, official address and contact details of the manufacturing

site:
Name : Novagen Healthcare Private Limited
Site Address : Plot 102 – 111, Horizon Industrial Park,
Bamangam,
NH-48, District Vadodara, Gujarat, India.
Pin 391243
Telephone No. :
Fax No. :
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Contact information including 24 hours telephone number as well

as email address of contact personnel for the manufacturer:
Office
Name of Personal
contact Email address
Contact Person Mobile No.
No.

Name, address and contact details for the Head office the
manufacturer
Name : Novagen Healthcare Private Limited
Head Office :
Address
Contact :
Telephone No. :
Mobile No. :
Fax :
E-Mail :
Website : www.novagenhealthcare.com
C.1.5 Types of Products Manufactured On the Site and Information
about Specifically Toxic or Hazardous Substances Handled:
Following are the brief details regarding various types of different
products manufactured as well as any toxic or hazardous substances
handled at site
A Sterile Products:
A Liquid Dosage Forms : Not
1 Applicable
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(Large Volume Parenteral Preparations)

A Liquid Dosage Forms : Not
2 (Small Volume Parenteral Preparations) Applicable
A Semi Solid Dosage Forms : Not
3 Applicable
A Solid Dosage Forms :
4 A4.1 Solid fills (Dry Powder Injectable)
A4.2 Freeze Dried
B Non Sterile Products:
B Liquid Dosage Forms : Applicable
1 (Syrup, Suspension, Solution
Preparations)
B Semi Solid Dosage Forms : Not
2 Applicable
B Solid Dosage Forms : Applicable
3 B3.1 Unit Dose Forms (Tablets and
Capsules)
B3.2 Multi Dose Forms (Dry Syrups)
C Biological Products : Not
Applicable
D Specifically Toxic & Hazardous : Not
Substances Applicable
E Packaging Only Activity : Not
Applicable
F Contract Manufacturing of any Products : Not
Applicable
G Contract Analysis activity for any third : Not
party Applicable
H Drugs for clinical trials : Not
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Applicable
C.1.5.2 The specified dosage forms are manufactured in a dedicated
manufacturing facility where air emission controls are designed to
prevent the contamination of surroundings.
C.1.5.3 Veterinary products are not manufactured at the site.
C.1.6 A SHORT DESCRIPTION OF THE SITE:
The manufacturing facility is situated in Horizon Industrial Park
established at outskirts of Vadodara city about 40 km from Vadodara
airport and about 50 km from Vadodara Railway Station. Facility will
commissioning for commercial production from _________. It is located
in a green belt and clean area away from polluting industries. The
surrounding atmosphere is free from dust & smoke.

The in-house utility facilities are operated & maintained by in-house

engineering / utility staff. Three generator sets having capacity: -
380KVA-2 Nos. +500 KVA –1No.are available to take care of power
failures.

The water system is closed with controlled storage, piping, central

water treatment and water purification facilities. The entire
manufacturing area has total build up area of 2,205 sq.mt. The
facilities provided are well maintained at all times with prompt and
adequate repairs as well as painting. The department wise details are
as shown in Annexure-I.
C.1.6.1 Site Map:
The factory is situated on the outskirts of Vadodara, which is about 25
km, south from Vadodara city and well connected with road. The site
map of facility is attached as Annexure – I.

C.1.6.2 Surrounding Area:

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The factory is located in a green belt and clean area far away from the
polluting industries. The surrounding atmosphere is free from dust &
smoke.
C.1.6.3 Nature & Use of Nearby Properties:

The factory is surrounded by green fields & non-polluting industries.

C.1.6.4 Drawings of the Site:

The detail drawing of the site with dedicated various departments with
MAN-MAT. Movement is given in Annexure – II.

C.1.6.5 Photographs of the Exterior of the Factory & It’s Surroundings:

Photographs of the exterior as well as surrounding appearance of factory
premises are attached as Annexure-III.

C.1.6.6 Age of Building:

It is a newly flagged facility with the age of 00 years.

C.1.7 Number of Employees engaged in Production, Quality

Assurance, Quality control, Engineering services, Warehouse
and Human resources and Admin.:
C.1.7.1 Production :
C.1.7.2 Quality Assurance :

C.1.7.3 Quality Control :

C.1.7.4 Warehouse :

C.1.7.5 Engineering/Utilities :

C.1.7.6 Human Resources and Admin. :

Total of above :

C.1.8 Use of outside scientific, analytical or other technical

assistance in relation to manufacture and analysis:
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Our Quality Control facilities is well equipped with all modern

sophisticated analytical equipments and instruments e.g. HPLC, FTIR,
Particle Counter, Dissolution Rate Apparatus etc.
Facilities for complete Microbiological testing are also available In-
house.

No contract manufacturing is being done currently. However, analysis

of certain materials for specific tests that cannot be carried out at the
site is done at contract laboratories. The contract laboratories are
provided with the information and specifications necessary to carry
out the tests. Written agreements have been made with the contract
laboratories. The contract laboratories are periodically inspected for
conformance with GMP.
Records of these visits are maintained.
List of Contract Laboratories is mentioned in Annexure IV.

C.1.9 Short Description of the Quality Management System:

Novagen healthcare Pvt. Ltd operates pharmaceutical manufacturing
under the control of a quality management system as per the
guidelines stated in the company quality policy & quality manual.

Quality assurance system applies to all activities of the company

(starting from vendor development and procurement of starting
material to execution and delivery of finished products) and is in line
with all applicable cGMP guidelines and regulations.

This quality system is used in the planning, designing, construction,

testing of quality systems & qualification of facilities. The Engineering,
Materials management, Vendor development, Production, Quality
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assurance, Quality control departments are all required to comply with

quality system.

Management takes a visible and leading role in creating and sustaining

core values, policies, strategies, directions and performance
expectations.

Management has the ultimate responsibility for the provision of

appropriate resources, funding and support to ensure the proper
utilization of facilities used for storage, manufacturing, packaging and
distribution or products.

C.1.9.1 Quality Policy:

The purpose of the quality policy is to ensure compliance of quality
systems and procedures so that the end product meets all the
required specifications ensuring the identity, strength, safety & purity
of the products.

Our Quality policy is based on cGMP guidelines, laws and regulations

governing the manufacture of pharmaceutical products.

Our Quality Policy is “To achieve value driven leadership in

Indian Health Care Industry and beyond. Through Quality that
is infinite Service that cares hard work that endures”.

This is achieved through the Quality principles as laid down in the

manual and relevant operating Procedures to ensure that each
product meets the customers as well as regulatory requirements for
safety, efficacy & quality. These QUALITY principles are used in the
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planning, designing, construction, testing of Quality systems &

Qualification of facilities. The Engineering/Maintenance, Materials
Management, Vendor development, Production, Quality Assurance &
Quality Control departments are all required to comply with these
Quality principles.

QUALITY is mandated and supported by top management and

coordinated by Quality Assurance, which is responsibility of everyone
in the plant. The effectiveness & applicability of Quality Assurance
system is regularly monitored.

The Quality Assurance Department is independent from manufacturing

& authorized to take appropriate decisions on quality matters of Raw
materials/ Packing materials/ Finished products or any other issues
related to quality.

C.1.9.2Responsibilities of the Quality Assurance function:

Following are the responsibilities of Quality Assurance Function;

 Process Control
 Implementation of Quality systems
 Directing and Controlling of cGMP operations.
 Providing guidance for compliance to various international cGMP
requirements.
 Approve deviations or changes in the system.
 Total Quality Management of the plant.
 Control of material specifications
 The monitoring and control of the manufacturing environment.
 Plant Hygiene
 Qualification and Validation Activities
 Training
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 The approval and monitoring of suppliers of materials

 The approval and monitoring of contract manufacturers.
 The designation and monitoring of storage conditions for materials and
products
 The retention of records
 Internal inspection, Investigation, and taking of samples, in order to
monitor factors, which may affect product quality.
 Annual Product Review
 Coordination with Regulatory department
 Investigation of non-conformances and Market Complaints
 External audit and compliance of the findings
 Authorization of manufacturing documents
 Document Control.

C.1.9.3Elements of the Quality Assurance System

Quality assurance department plays an independent and vital role in

the Organizational structure for concurrent and effective quality
practices procured at site. The organizational functional chart of
Quality assurance department is as per ANNEXURE – V,
Organization Chart

Quality assurance department is headed under the surveillance and

guidance of competent, experienced and suitable qualified personnel
to carry out the responsibilities he / she entitled.
Responsibilities of Head of Quality assurance department shall be as
follows but not limited to:
Responsibilities of Head – Quality Assurance
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Name: - Mr. / Ms.________________________

Qualifications: - _________________________

Experience: - ________ years

i. To ensure the compliance with cGMP.
ii. To develop procedures & schedules for monitoring and In-process
testing of production process & packaging processes.
iii. To develop procedures for Line clearances in production/ packaging
operations prior to product change over.
iv. To conduct process control defect analysis with production and take
corrective actions to prevent reoccurrence in future.
v. To conduct periodic cGMP audit (self audit) and initiate corrective
actions.
vi. To investigate market complaints and take necessary precautions.
vii. Responsible to approve changes/deviations as per change control
system.
viii. Responsible to approve deviations
ix. Authorized to initiation of recall of faulty product from the market
x. To approve the SOPs, formats, systems, etc.,
xi. To ensure that all the RMs /Finished product specifications are up
dated as per pharmacopoeia /addendum etc.
xii. To organize validation of existing and new products, process,
equipment & facilities.
xiii. To organize and monitor Stability Study Program and execution of
stability studies of various products and submit data to regulatory as
and when required
xiv. To ensure adequate training to employees at all levels within the
organization to achieve quality standards.
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xv. To comply with the requirements of all International /National

regulatory requirements or any other statutory rules.
xvi. To ensure periodical internal audit as per predefined schedule.

Responsibilities of Head – Quality Control

Name: - Mr. / Ms.___________________

Qualifications: - ____________________

Experience: - _____ years

i. To approve or reject raw materials, packaging materials, and finished
products and any other quality tests performed by Quality control.
ii. Develop and implement quality control procedures.
iii. To approve specifications, sampling instructions, test methods and
other Quality control procedures.
iv. To check the maintenance of the Quality Control Department,
premises and equipment.
v. To ensure that approved validated analytical methods are in practice.
vi. To ensure that the required initial and continuing training of all
department personnel is carried out and adapted according to need.
vii. Lead the team of Quality Control Executives, Officers and Chemists.
viii. Co-ordinate and provide guidance in preparation of QC SOP’s &
protocols
ix. To maintain laboratory documents & instruments as per cGLP.
x. To carryout Stability Study program by performing analytical activity
of products according to stability study protocol and approve the
product quality attributes complies throughout its assigned shelf life.
xi. Organizing the testing of Raw Materials, Packaging Materials and
Finished Products as per laid down specification.
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xii. To release the batch after reviewing the documents.

xiii. Organizing the process validation activities.
xiv. Updation of specifications as and when required.
xv. Review and approve analytical results.
xvi. Initiate and participate in lab incidence, OOS, OOT and any other
investigation to find out root cause of the incidence and generate
laboratory investigation report accordingly.
xvii. To generate CAPA report for any non-compliance finds in quality
control laboratory.

C.1.9.4 Self-Inspection and other audit Programs

Self-inspection or internal audits are conducted for cGMP / cGLP
compliance at regular intervals in accordance with the established
schedule by in-house teams, inter-unit teams, comprising of
competent persons from different departments.

Sometimes with an objective of to ensure the effective compliance,

external audit shall also be proposed for full compliance to cGMP
regulations covering quality, efficacy and safety at all steps of
processing of the products.

The self-inspection is carried out as per the SOP of self-inspection as

well as with accordance of checklist reflecting the key activities
drawn up for each areas such as warehouse, engineering services,
production, quality control, quality assurance and the reports are
made in a defined format.

Effective corrective and preventive actions are taken to ensure

compliance with the deficiencies, which may be observed.
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While carrying out audit checks, special attention is to be paid to

previous audit findings and their compliance.
Audit finding reports are made for which the concern department
makes the compliance report and the copy of it is sent to the
President Technical Operations for his review & comments.

C.1.9.5. Release procedure of finished products:

The product is undergone through analysis at various stages during

process manufacturing to comply the pre-defined product quality
specification. Quality control will perform the analysis and reporting
the results as per the relevant specification and the Analytical test
report will be handed over to quality assurance for review.

Quality assurance department check the batch manufacturing

records, batch packing records and the Analytical test report, along
with all other relevant data to comply the quality, efficacy and safety
of the product. After successfully verifying all review activities the
batch will be released by Quality Assurance.

Quality assurance head is authorized to release the finished products

and in the absence of QA head, President- Technical operation is
authorized to release the batches.

Authorized personnel for batch release are qualified and experienced.

Details on experience and qualifications are available in individual job
responsibilities.
C.1.9.6. Management of Vendor / suppliers
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All the vendors for API as well as excipients should have

manufacturing licenses as per their applicable local food and drug
administration (FDA) and vendor approval audit has to be done by
Quality Assurance and other concerned departments of the company.

C.1.9.7 Vendor Assessment /Development

Vendors of all active pharmaceutical ingredient as well as excipient

and packaging materials are assessed and qualified as per SOP of
vendor qualification. The following steps are the most important
aspects of procurement of materials:
i. Material Specifications.
ii. Vendor pre-purchase sample evaluation.
iii. Vendor audit / developments.
iv. Vendor trial order-for stability batch.
v. Vendor Approval / Certification.
vi. Periodic Vendor Audit.
Records of vendor audit / approval and subsequent vendor evaluation
shall be maintained and based on that approved vendor list shall be
prepared for raw material, packaging material and excipients. The
purchase department and the Head - Quality Control / Quality
Assurance or Head of Technical Operations are responsible for vendor
development/evaluation, which is based on their performances.

C.2 PERSONNEL

C2.1 Organizational chart for various departmental arrangements:

Organization chart showing the arrangement of Quality management,
Production, Quality control and engineering services are attached as
Annexure V (Organizational chart)
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C.2.2 Qualifications, Experience and Responsibilities of Key

Personnel:

The various activities of plant premises including process

manufacturing, quality management, engineering services is headed
under the surveillance and guidance of competent, experienced and
suitable qualified personnel to carry out the responsibilities he / she
entitled.

C.2.2.1 Responsibilities of key personnel:

Name : Mr.

Designation : Head Technical Operation

Qualificatio :
ns

Experience :

Some of the key responsibilities that President of technical operation

shall entitled are as follows but not limited to:
a) Overall responsible for production, Engineering, and warehousing
functions as per Quality Policy.
b) Monitoring and maintaining cGMP / cGEP / cGWP practices in
production Engineering, and warehousing areas.
c) Ensuring implementation of related sections of the Quality manual.
d) Ensuring achieving the standard yield batch after batch as well as
Quality.
e) Ensuring the compliance of Productivity norms in the plant.
f) Ensuring the quality of product and involvement in complaint
investigation.
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g) To issue guideline for corrective actions for non-conforming product.

h) Ensure the cost effective measure to control expenses.
i) Ensure the training & development of people.
j) Ensure the delivery / Dispatch of products as per plan.
k) Planning of routine Production activities.
l) Authorized to release the batch in absence of Quality Assurance
Head.

Name : Mr.

Designation : Manager – Engineering

services

Qualificatio : B. E
ns

Experience :

Some of the key responsibilities that Head of Engineering services

shall entitled are as follows but not limited to:
a) Responsible for Engineering dept., all Utilities and Engineering stores.
b) Facility planning of civil, electrical, instrumentation and mechanical
works.
c) Designing and layout preparation for equipment and facilities.
d) Liaison work with Govt. departments and other statutory bodies
e) Training and development program for staff members working under
engineering services department.
f) Co-ordination for Maintenance of plant and machinery.
 Planned Preventive Maintenance
 Equipment Breakdown Maintenance
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g) Contribute to improvement in systems and practices to ensure

adequate care for various machines with respect to safety, cost
saving & energy conservation
h) To monitor inventory for a required stock level of spare parts of
equipment to minimize the total breakdown time.
i) Co-ordinate with contractors in the preparation of service contracts
and GMP agreements.
j) Maintain & operate various utilities and systems in accordance with
GMP practices
k) To ensure compliance to cGMP guidelines and SOPs within the Eng.
Dept.

C.2.3 Outline of arrangements for various Training Programs and

their documentations:

Training program is established for obtaining the adequate, robust and

competent functionality at various stages with accordance of cGMP. To
comply the essentiality of training; SOP for training management
program is established at site for smoother operation.

On Job Trainings: All the personnel working in the plant and whose
job is directly or indirectly associated with product quality are given
continuous cGMP training, appropriate to their respective job activities.
The Head – QA in consultation with the Head – Plant Operation as well
as Head – HRD develop comprehensive Training Modules and
programs for employees at all levels.

Induction Training: The Human resources and Administration

Department provides induction training to all the new employees for
making them acquainted with the company’s Policies, practices and
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people, as per Induction Training schedule. Records of such

induction training and the reports are maintained by the head of the
department (Human resources and administration)

C.2.3.1Training needs for identification:

Training needs for the individuals are identified at the time of annual
performance appraisal by his / her immediate superior.

Training needs are then consolidated by the Head of Department

(Human Resources and administration) and submitted to Quality
assurance for reviews and comments. Based on comments received
from Head – QA for identified training needs of the individual, annual
training calendar shall be prepared and gets it approved by Head – QA,
Head – HRD and Authorized by President – Technical Operation.

The Head – Human Resources and Administration organizes training

program in accordance with the training schedule and maintain
appropriate training records indicating personnel performance and
need of improvements after evaluation.

C.2.3.2 cGMP Training:

Training on cGMP is targeted on the different identified groups. The
type of training given is as follows:

CORE TARGET GROUP TRAINING

All employees : Short courses on GMP.

Employees working in Packing : cGMP aspects in Packing

area operations.
Employees working in sterile : cGMP aspects in sterile area
area. operations.
Employees working in QA / QC. : Validations - a tool for cGMP / cGLP.
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Supervisory and Managerial : Advance courses in cGMP

Staff.
Employees working in : Courses on cGWP
Warehouse.
Employees working in Eng. : Courses on cGEP and outline
Dept. concepts of ISPE norms

C.2.3.3 Selection of trainer:

The training faculty is drawn from the respective area of work from the
line of managers and the senior members from Quality Assurance,
Production along with outside experts (if required). The training
program also includes practical training on working site. Following
training aids are used for effective training:

a) Reading materials – Books and notes, draft guidelines, Pharmacopeias

b) Video shows
c) Transparencies / slides with aid of projectors.
C.2.3.4 Evaluation of training:
The training evaluation is done from the identified training program as
per the training calendar. Giving questionnaires to the group of
employees attending the program does training Evaluation. Training
evaluation is recorded in prescribed training evaluation sheet standard
format prescribed as per SOP of Training management program. The
score in evaluation is taken as criteria for Re-training. Employees are
allowed 3 times more for retraining, failing which they are transferred
to non-critical operations.
C.2.3.5Training Records:
All the records pertaining to the training in prescribed formats are
available with Quality assurance department. Every department
maintains the Individual training record of the employees of their own
department, which is accessible to the level of supervisors.
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C.2.4 Health Requirements for Personnel Engaged in Production:

All personnel engaged in manufacturing should be free of any

contagious disease or severe type of reaction with specific drugs, like
Penicillin, Sulpha drugs etc.

C.2.4.1 Pre-medical check-up prior to joining the organization:

All the new employees have to undergo pre-employment medical
check-ups before joining the Organization. Company’s
Authorized Doctor, who is a registered medical practitioner, carries out
pre-employment check-ups.

C.2.4.3 Routine Medical Checkup program:

There is a well-organized program for all level of staff members and
workers, after every year to ensure the health of Personnel.
Independent professional doctor carries out medical examination. Any
unusual findings during routine check-up is found, suitable prescribed
treatment is given to recover from reported illness. Rechecking is
carried out after prescribed time period and personnel may be granted
full rest depending upon the illness. During treatment period, suitable
relocation changes are done in employee's job as advised by Medical
Consultant.
C.2.4.4 Reporting system for illness:
All the employees engaged in manufacturing activity has to report to
their immediate superior in case of any sickness or if they are in
contact with any sick person to prevent infectious contamination. In
the same line, the employees are advised to report any type of illness
observed by them.
C.2.4.5 Recovery Certificate:
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A fitness certificate from registered medical practitioner is to be

provided by the employee after recovery from the illness before
reporting to his duties.
C.2.4.6 Medical check-up for employees working in sterile area:
The employees working in sterile area are subjected for medical
check-ups after every six months. The employee’s job is rotated in
case of superficial injury or if suffering from common cold.

C.2.5 Personal Hygiene Requirement, Including Clothing:

Every person engaged in manufacturing activities has to comply with
requirements of personal cleanliness and hygiene conditions to
prevent cross-contaminations. To comply this, SOP for personnel
hygiene is in place.
C.2.5.1Change Rooms and washing facilities:
Suitable separate two changing rooms with washing facilities are
provided for both genders before entering the Manufacturing area.
The well-designed change rooms are equipped with lockers,
cupboards and all other required furniture are in place for
distinguishing and keeping cleaned and dirty clothes and foot wear
properly to prevent cross contaminations.
C.2.5.2 Clothing Pattern:
Appropriate lint free clothing is provided to the employees depending
upon nature of their work. Bouffant type caps are used for proper
covering of hair.
Clothing in non-sterile area: Workers are provided with blue
boiler suits, Caps, masks for covering mouth and nose and footwear.
Hand gloves are provided for workers coming directly contact with
products. Staff members are provided with blue aprons pants and
caps. In the core manufacturing area a procedure of secondary
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gowning is followed. Aprons are provided for secondary gowning.

Separate gown & footwear is provided for the canteen.
Clothing in sterile area: Employees working in sterile area are
provided with sterile boiler suits, headgear, booties, gloves and
goggles.
C.2.5.3 Instruction for growing procedures:
Written practice procedures is in place for gowning and de gowning
instructions in the form of SOPs are kept in each of the change rooms.
The in house laundry facility is available for washing used company
garments.

C.3 PREMISES AND EQUIPMENT:

C.3.1 Premises:
Premises have been designed, keeping cGMP, safety and
manufacturing capacity in consideration. A plan of each production
facility with indication of scale and names of the area is attached as
Annexure – II
C.3.2 Nature of Construction and Finishes:
The building is a Reinforced Cement Concrete (RCC) frame structure in
concrete with isolated RCC foundations tied to each other at plinth
level by RCC beams.
C.3.2.1 Flooring: There are mainly two types of flooring have been done in
premises. They are as follows.
a) Epoxy Flooring: All major core process area of production activities,
microbiology laboratory and other MAN-MAT movement areas have
continuous epoxy flooring. Epoxy floor gives a smooth finish, chemical
resistance and dust-free.
b) Tiles flooring: Various types of tiles like vitrified tiles, ceramic tiles
are fixed with epoxy joints in entry foyer area, change rooms, QC and
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areas utilized for storage purposes only. These Tiles are endures very
smooth surface finish, dust-free, and easy to clean.
Moreover; to avoid vertical joints between floor and wall epoxy coving
has been done which minimizes the risk of dust deposition and
microbial growth.
C.3.2.2 Paints: Various types of paints are applied on walls according to
their functional requirements.
a) All core processing area are painted with Epoxy paint which is
characterized by excellent chemical, oil, water resistant, smooth finish
and excellent Algae and Fungi growth resistance.
b) Acrylic Emulsion paint is applied in entrances, washrooms, change
rooms, passages and storage areas.
c) All external walls are painted with one coat of cement paint and two
coats of cement based water repellent paint.
C.3.2.3 Ceilings: Various types of ceilings are applied based on objectives of
that particular area.
a) Cleanroom walkable PUF ceiling panel is placed throughout the core
processing area for easy and convenient access to the utility
machineries provided for functioning of smooth operation of process
equipments.
b) The gypsum ceilings painted with washable emulsion paint as well as
grid celling is applied through all entry foyers, washrooms, storage
areas and QC laboratory.
Lightings: All the lighting in the process area is recessed or enclosed.

C.3.2.4 Door & Windows: All doors are made of anodized aluminum flushed
door having flush glazed view panels.
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C.3.3 BRIEF DESCRIPTION OF HVAC SYSTEMS:

C.3.3.1.Design Specification:
All the areas are provided with an individual air handling unit to
maintain the required room condition with respect to the
temperature, relative humidity, particulate matter count and
potential risk of airborne contamination.
Air handling units having robust filtration system comprising of 10 
fresh air filter (EU 4), 5  pre-filter (EU 5), 3  fine filter (EU 7) and 0.3
 HEPA filter (EU13) to comply the desired cleanroom classification of
air particulate matter count. The service area is provided with
openable type windows with 10  air filters for sufficient natural air
circulation.

The area for handling sterile products meets Grade - A / class 100
requirements. In addition to this the background of the Grade – A /
class 100 area meets the requirement of Grade – B / class 1000.

For oral dosage forms the class of air in core processing area meets
the requirement of Grade – D / class 100000. Pressure differentials are
maintained as per the specified guidelines for the respective dosage
forms. Temperature in all areas is 22 ± 2° C.

Relative humidity in the different sections is as mentioned below.

Relative
Section
Humidity
Tablet Area : NMT 45%
Capsule Area : 35 - 45 %
Dry Syrup Area : NMT 45 %
Sterile Product Filling : NMT 45 %
All other areas : NMT 45 %
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Co-amoxyclav products [Tablet, Dry syrup & :

NMT 30 %
Inj.]
The HVAC system design is based on re circulation of air. 80 - 85% of
the air is re-circulated and 15-20 % fresh air is taken in.

Air changes in the Grade – B / class 1000 area is not less than 60/Hour
and for Grade – D/ class 100000 area is not less than 30 /Hr.

The schematic drawings of ventilation system along with relevant

details are attached. Annexure – VI A and B.

C3.3.2.Design basis of Filtration System for cleanroom classification

of different area grade:
Following are the air filtration system for HVAC to achieve the
particulate air count as per the respective area grade of cleanroom
classification.

Particulate
Types of Filter
Air & Filter Grade of Area
Filters Efficiency
Grade
Fresh Air Grade A , Grade B , Grade C
10  (EU-4) 90%
Filter & Grade D
Return Air Grade A , Grade B , Grade C
10  (EU-4) 90%
Filter & Grade D
Grade A , Grade B , Grade C
Pre-Filter 5 (EU-5) 95%
& Grade D
Grade A , Grade B , Grade C
Fine Filter 3 (EU-7) 95%
& Grade D
HEPA Filter
Grade A , Grade B , Grade C
(Terminal or 0.3 (EU-13) 95%
& Grade D
Plenum)

C3.3.3 Filter Replacement Practices:

All ventilation filters are changed or claimed for maintenance, as soon
as the pressure drop across filters deviates from the design range.
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Such replacement of filter activity has been carried out according to in

place respective SOP.
C3.3.4 HEPA Filter Integrity Test:
All HEPA filters are checked for integrity using DOP. Such filters are
scanned for checking the leakage at filter-face of the terminally
mounted HEPA filters using a calibrated photometer.

C3.3.5 REVALIDATION:
Revalidation of the system is carried out as per given frequency
mentioned in Validation Master Plan or earlier if any changes are
incorporated in the system or in the facility.
Sr. Critical Parameters / Test Frequency
No
1. Filter Integrity Test : Six monthly
2. Air velocity (ACPH) : Six monthly
measurement
3. Recovery test : Six monthly
4. Particulate matter counts : Six monthly

C.3.4. BRIEF DESCRIPTION OF WATER SYSTEM:

Source of Water: Underground bore well (02 Nos.)
Supplied raw water from bore well shall be stored in main water storage
tanks with having total capacity of 1,50,000 Liters. It is a RCC
constructed underground tanks. Raw water from bore well pump is
pumped through appropriate pipeline to the main storage tank with
online chlorine dosing. This collected water is simultaneously pumped
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to pretreatment plant for the generation of potable water and

subsequently to generate purified water.

The sequence followed in the purified water generation is as follows;

Multi-grade filter  Softener unit  RO  RO-EDI  Storage
tank  User points

C.3.4.1 Potable Water:

Source : Reverse Osmosis Plant (01 Nos.)
Capacity : 5500 liters / hour
Recovery of Plant : 70% of feed water

Generation of Potable water:

Pretreated chlorine dose water is feed into the pretreatment plant for
sequential process steps as mentioned below to generate potable
water.
Chlorine dose water  Multi-grade filter  Softner unit  RO-
Potable water  Overhead tanks & in feed supply to PW
generation

Scope of Potable Water Supply:

Potable water is used for operation of various utility equipment, pre
wash in the process area and in feed water to purified water
generation plant.

Storage:
For RO water storage two HDPE tanks with a capacity of 10,000 Liters
each installed for utilities and for in feed of PW generation.

C.3.4.3 Purified Water Plant:

Source : Plant working on ION EXCHANGE principle.

Capacity :. Flow rate 1000 Ltrs. /Hr.
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Generation of Purified water:

Potable water is passed through RO II system for ultra-purification
purpose and then passed through EDI (Electro-deionization) system. It
consists of Cation bed, Anion bed and mixed bed. After mixed bed
water is passed through the series of filters of 10 and 5 followed by
Ultra Violet (UV) purifier and collected in storage tanks of Stainless
Steel (SS) 316 quality, located in PW generation room.
Storage & Distribution:
After passing through the UV lamp, the purified water is stored in to a
SS-316 water storage tank having capacity of 3000 Liters.

This water is then pumped through a closed loop of electro-polished

(SS-316 L) lines to the SS-316 storage tank, which is dedicated for all
user points available throughout processing area of Injection and Oral
Manufacturing areas.

Water distribution is connected with a control panel having

Programmable Logic Control (PLC) for monitoring of quality
parameters like pH, conductivity, pressure, temperature and flow.
Deviation in any of the set parameter results in a reject of water flow,
which is operated by a Flow Diverting Valve.
All the critical parameters and plant status is monitored by a
continuous monitored printer.
The schematic diagram of purified water system attached as
Annexure VII.
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C.3.5. MAINTENANCE AND SERVICING OF THE AIR HANDLING AND

WATER SYSTEMS:
All the Air Handling units (AHU) and Water treatment plants are taken
into consideration as per the established standard operating
procedure of planned preventive maintenance.

The annual plan for preventive maintenance of all AHUs and water
systems is prepared at the beginning of the calendar year. This annual
plan is prepared with the proposed date of preventive maintenance as
per defined frequency in standard operating procedures.

Preventive maintenance of all AHUs and water treatment plant is

carried out as per the respective preventive maintenance procedures.
Record of the preventive maintenance is maintained in the respective
checklist prepared as per the corresponding procedures for preventive
maintenance.

Preventive maintenance of water treatment includes servicing of Ion

exchange beds, sanitization of the plant and water distribution loop,
servicing of multiple column distillation plant, its distribution loop,
calibration of instruments and other water treatment elements.
Preventive maintenance of AHU includes filter cleaning, servicing of
AHU, integrity testing of HEPA filters, calibration of instruments and
duct cleaning. Various quality checks are identified for certain
maintenance activities.

The concerned persons responsible for maintenance are trained about

the procedures for maintenance and the relevant formats for
recording.
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C.3.6. MAJOR EQUIPMENTS & INSTRUMENTS OF PRODUCTION AND

QUALITY CONTROL LABORATORY:
List of major production and Quality control instruments and
equipment is attached as Annexure VIII.
All the product contact parts of any equipments are made up of SS
316 and non-product contact parts are made up of SS 304. All other
engineering tools like gaskets, rubbers used are made up of food
grade materials only. All equipments are designed as per GMP for ease
of cleaning and maintenance.
Cleaning of equipments having product contact surfaces are cleaned
with approved / validated cleaning procedure, applicable to the
previous product manufactured in the particular equipment.

All of the major production equipments are designed with PLC / HMI
based controlling panel. In granulation area, Powder transfer system is
installed for movement of material without intervening manual action
as this minimizes the risk of cross contamination. All the weighing
balances in the plant premises are printer enabled for recording and
printing of the weighing data at the time of activity. Encapsulation
process is fully automatic procedure as it involves empty capsule
shorter, unfilled capsule separator for robust and rapid output without
having any mix-up chance.

Quality control laboratory is highly equipped with all sophisticated

analytical instruments like HPLC, TOC analyzer, UV/VIS
spectrophotometer with their individual software based operation. All
these softwares are of license versions with an individual user’s
accounts and admin accounts with restrictive rights for access. System
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audit trial facility is also in place to adhere ALCOA principles of data

integrity and reliability.

Microbiology laboratory also equipped with all major instruments to

facilitate microbial enumeration testing, BET testing as well as sterility
testing. Storage of media and culture dedicated BOD and
bacteriological incubators are in place with various temperature
ranges to satisfy inoculation process of media and culture.

All the process controlling activities and quality systems are fully
computerized system. Computers are used for inventory management
(ERP), dispensing material issuance of raw and packing materials,
generation of QC report, QC instrument data acquisition & integration
and printing of process data sheet and other related documents.

C.3.7 MAINTENANCE AND SERVICING OF EQUIPMENT:

All the utility equipment and process related equipment are taken into
consideration as per the standard operating procedure of planned
preventive maintenance. The engineering department is responsible
for carrying out maintenance and servicing of the equipment. The
concerned department verifies the maintenance and servicing of the
equipment. The annual plan for preventive maintenance of all
equipments is prepared at the beginning of the calendar year. Such
annual plan gives the proposed date of preventive maintenance as per
defined frequency in standard operating procedures.

Preventive maintenance of all equipments is carried out as per the

respective preventive maintenance procedures. Record of such
preventive maintenance is maintained in the respective checklist
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prepared as per the corresponding procedures for preventive

maintenance.

The engineering department preserves record of maintenance and

servicing. Pre and post approval of the work done for major
modifications and changes requires the approval of the Quality
Assurance (QA) department. Various quality checks are identified for
certain maintenance activities. The concern persons responsible for
maintenance are trained about the procedures for maintenance and
the relevant formats for recording. There is a separate SOP for
handling Equipment breakdown maintenance. If any deviation is found
the engineering department informs to the concerned department and
QA on an intimation note, and categories the defect as critical, non-
critical, most critical breakdown. The QA department approves all the
corrective actions and recommendations.

C.3.8. QUALIFICATION, VALIDATION AND CALIBRATION:

C.3.8.1General policy for Qualification / Validation:

All equipments and processes are qualified and validated as per the
procedure prescribed in Validation Master Plan. There are detailed
written procedures established in Validation Master Plan to carry out
qualification / validation of equipment and processes, along with their
respective protocols.
Following is the generalize approach of the Company for
Qualification/Validation:

Design Qualification:
It is applicable to Premises, Building, Facilities, Equipment &
Machineries & used for development & verification of pre-determined
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specifications / requirements after considering the requirement of

various dosage forms, product, manufacturing conditions and annual
requirement. Design qualification (DQ) is documented verification that
the proposed design of the equipment, instrument or systems is
suitable for the intended purpose and shall be designed in accordance
with cGMP requirements.
Installation Qualification:
The IQ is carried out with an objective of to demonstrating that the
equipment and components installed are in accordance with those
specified and that they have been properly identified and installed
within the correct location in accordance with the design qualification
It is initiated along with project concept; includes equipment and
system specifications, fabrication Inspection where relevant and
completed following installation of the system/ equipment.
Operational Qualification:
Initiated following completion of the system/ equipment IQ and may be
combined with the IQ in certain circumstances (plant commissioning).
All the measuring devices are calibrated against the calibration
protocol and certified. All the parameters are checked against the
specification and protocol & certified for performance qualification.

Performance Qualification:

PQ shall be carried out following the completion of OQ and may be

combined with the OQ in certain circumstances. The PQ is the final
stage of qualification, which demonstrates how each system will
perform when challenged under simulated or actual production or
operating conditions.
Prospective Validation:
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Prospective validation is carried out on minimum three consecutive

batches for new manufacturing formula or process to demonstrate the
process capabilities as well as process capabilities for routine
manufacturing processes.
Concurrent Validation:
Concurrent validation has to be carried out to evaluate and to assure
the product quality with adhere to any changes in the process and /or
product including changes in manufacturing procedures, packing
style , equipment , vendor of raw materials.
Retrospective Validation:
Retrospective validation is based on a comprehensive review of at
least 20 batches historical data to provide the necessary documentary
evidence that the process is in well-established manner. If the product
is not manufactured routinely then minimum 10 batches of historical
data can be considered however a prior authorization is required for
this circumstance.
C.3.8.2Revalidation:
Facilities, systems, equipment and processes, including cleaning,
should be periodically evaluated to confirm that they remain valid.
Where no significant changes have been made to the validated status,
a review with evidence that facilities, systems, equipment and
processes meet the prescribed requirements fulfils the need for
revalidation.
C.3.8.3Release system for sales batches of validation batches:
Quality assurance department releases all validation batches after
completion of the validation report, provided that they meet all
specifications & have been manufactured in accordance with cGMP.
C.3.8.4Computer system Validation:
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Computerized systems should be validated at the level of appropriate

for their intended use and in accordance with quality risk management
principles. This applies to operations linked computerized systems
used in process manufacturing, utility operations and quality functions.
The objective behind validation of a computerized system is to ensure
an acceptable degree of documented evidence which establishes
confidence in the accuracy, reliability and consistency in the
performance of the system in accordance with predetermined
specifications. The validation data should meet the principles of being
attributable, legible, contemporaneous, original and accurate (ALCOA)
throughout the data life cycle.
Computer Validation including software validation is done by external
agency.
C.3.8.5 Calibration Policy:
All instruments being used for monitoring are taken into consideration
for calibration as per the Instrument calibration plan.

A plan for instrument calibration describes the identified instruments

with their technical specifications and frequency for calibration. All the
instruments are calibrated as per the respective standard operating
procedures.

Calibration status and observations are attached with the individual

instruments, showing the date of calibration and its next due date for
calibration.

Calibration certificates of the instruments and the certificates of

calibration of the reference standards used during the calibration are
preserved for the reference.
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If any deviation is found the engineering department informs to

concern department and QA on intimation note, and categories the
defect as critical, non-critical, most critical breakdown. The QA
department approves all the corrective actions with recommendations.

C.3.9. SANITATION:

Written standard operating procedures are exists for all aspects of

sanitation and cleaning of the factory and cleaning activities are done
as per the SOP on cleaning. The SOPs clearly specify the type of
detergents to be used and the sanitizing agents with their
concentration and frequency.

All the equipments are gone through with cleaning activity after their
use as per their cleaning procedure. The cleaning procedures are
validated as per their respective cleaning validation protocol.
Validation exercises are carried out with respect to cleaning of
equipment, and the effectiveness of cleaning is determined by
physical and chemical evaluation. Monitoring of effectiveness of
cleaning procedures is done regularly by chemical analysis and, where
required, by microbiology testing. The cleaning of equipment is
evaluated based on the rinse water/swab analysis.

Periodic cleaning and checking of the water lines are carried out as per
the standard operating procedure. Sanitization is carried out using
pure steam. The condensate is collected after completion of
sanitization and evaluated for chemical and microbiological
parameters.

The air handling system is cleaned as per the standard operating

procedures. Pre-filter and fine filters are cleaned with wet and dry
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cleaning method. HEPA filters are evaluated periodically and if found

damaged replaced them with new one and perform qualification of
HEPA. The ducts are cleaned with vacuum cleaner, as per the
frequency in the standard operating procedures. Dust extraction
systems are vacuum cleaned as per the standard operating
procedures.

C.4 DOCUMENTATION:
The entire documentation system of manufacturing & quality control
are very comprehensive & well controlled to avoid any ambiguity &
confusion in the plant. Standard operating procedures are available for
preparation, review, approval, distribution, storage and use of various
types of documents which contain clear instructions for carrying out
each activity.

Strict adherence to documented procedures and specifications is

ensured. Authorized Master documents such as Master batch
manufacturing record, master batch packing record and master
process data sheet are prepared and kept under control of Quality
assurance. These are issued to production as per the required usage
by quality assurance to assure uniformity of quality from batch to
batch.

All documents are reviewed periodically and revised, where necessary.

Superseded / obsolete documents are removed from use to ensure the
use of only current documents.

Standard Operating Procedure exists for all manufacturing, packaging,

storage, quality control, engineering and related activities in the
manufacture of the products. Authorized controlled copies of the
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documents and standard operating procedures are available with the

user departments issued through Quality Assurance department. There
is a centralized storage system for documents under the control of
Quality Assurance.

Separate standard operating procedure is in place for documents and

data control which describes the entire documentation system.

The level of documentation is as follows:

 Level 1 documents:
This level 1 document cover all company’s policies.
List of different policy cover in this level is as follow, but not limited to:
Quality policy
Environment policy
Safety policy
HR policy etc.
 Level 2 documents:
Level 2 documents are product registration documents, manufacturing
license documents and other related regulatory documents.
 Level 3 documents:
Level 3 documents are guidance documents for preparation of quality
management system documents.
List of guidance documents cover in this level is as follow, but not
limited to:
Quality Manual
Validation Master Plan (VMP)
Site Master File (SMF)
Product Manuals
Departmental Manuals
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Calibration / validation planner

 Level 4 documents:
Level 4 documents are master documents of quality management
system related to manufacturing, packing and testing;
List of master documents cover in quality management system are as
follow, but not limited to:
Standard Operating Procedure (SOP)
Master Batch Manufacturing Records & Master Batch Packing Records
Master Formula Records (MFR)
Standard Test Procedure and Specifications
Qualification and Validation Protocols
Technology Transfer Documents
Stability Study Protocols
Approved Vendor list
 Level 5 documents:
Level 5 documents are filled records, raw data, and calculation
datasheets.

Company Quality Policy & Quality System Manuals are available which
guides the Quality Management System to provide products &
services of highest standards with total customer satisfaction.
Company Quality Policy & Company Quality System Manual covers the
following areas:
 Premises
 Personnel Hygiene
 Cleaning & Sanitation
 Training
 Introduction parameters for Quality System
 Good Laboratory Practices & Laboratory Safety
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 Calibration
 Contamination Control
 Validation Policy
 Water for Pharmaceutical Use
 Aseptic Process Control
 Warehousing
 Laboratory Controls
 Packaging and Labeling
 Release of Semi-Finished and finished Goods
 Stability Studies
 Vendor Approval
 Out of Specification
 Change Control, Deviations
 Annual Product Review & Annual Quality Review
 Product Recall & Market Complaints
 Documentation
 Self-Inspection
Validation Master Plan is available which covers all the aspects of
Qualification and validation of facilities, equipments, process,
calibration, and- revalidation etc. and documented properly for future
reference.

Each department has it’s own departmental Manual (including Safety

& Training) which specifies the total activities related to activities of
department, role/responsibilities of personnel, different relevant SOPs,
different formats, etc.
Each department develops their respective SOPs, checked by seniors,
approved by Head of Departments / QA and authorized by President
Technical Operations after review for compliance.
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All the Master Documents are controlled by Quality Assurance

department with regulated distribution.

C.5 PRODUCTION:
C.5.1 Brief Description of Production Operation:
The Head of production is professionally qualified and has experience
of techniques and operations of production. He takes every measure
to prevent and avoid errors by means of continuous checks of the
process. As the batch manufacture progresses the related batch
manufacturing records are filled on line and completed at every stage
as and when the process is completed. The batch manufacturing is
carried out in strict accordance with batch manufacturing record only.
Only after the clearance of the packaging line the new batch is taken
for packaging. Reconciliation is done at critical Steps of manufacturing
and completion of packaging operations. Production flow sheets
indicate the departmental functioning as per Annexure – IX.

C.5.2 Arrangements for Material Management:

All materials are purchased from approved suppliers. All incoming

materials are visually checked for signs of damage to the containers.
Details of the delivery are checked against the relevant purchase
order. If any damaged goods are found labeled them as “Hold” and
kept aside for Quality Assurance’s instructions either for disposal or
return to vendor. If all found satisfactorily containers are passed
through de-dusting tunnel to de-dust the containers before entry into
the warehouse. On verification of quantity received and batch wise
segregation, the details of receipts are entered in a register called
Inward Register and the Goods receipt Note is generated with unique
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serial number. All the containers are placed in designated area labeled
as "QUARANTINE", with details of GRN No., No of containers,
manufacturer name, material code No. etc.

Prepared Goods Receipt Note (GRN) sent to Quality control to initiate

sampling. Sampling is done by QC personnel. A unique Analytical
Reference (AR) number is assigned to the lot or batch for the purpose
of identification and traceability. Samples are drawn as per sampling
plan and sampled containers are identified with sampled sticker and
tested as per the respective material specifications by Quality control
department.100% containers are sampled for identification and pooled
samples are taken for complete analysis.

After sampling “UNDER TEST” labels are affixed on each containers

having all the details like material code, quantity, total number of
containers, Manufacturer’s name, GRN No. etc.

Quality control compiles the data after analysis & decides whether the
material meets the material specification or not. Accordingly, Quality
control Approves / Rejects the material. "APPROVED / REJECTED"
labels are affixed on the material containers & the same is transferred
to designated storage area "APPROVED / REJECTED Material"
accordingly.

All packaging materials are handled as per above procedure and

approved/Rejected status labels are affixed accordingly. Printed
packaging materials are stored securely under lock and key and
reissued in requisite number only.

Status control is part of the computerized Inventory Management

System.
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The purchase, handling and control of packaging materials are done

similar to starting materials.
Typical Logic flow diagram is as follows,
Inventory Management system
Purchase order → Receipt (Stores) → Goods received Note

QC
(Sample analysis and Release / Reject)

Released stocks (stores) Reject (Stores)

Raw & packing material issuance Return / Destruction

At various places of operations separate areas are created so that the
material or product is held as 'QUARANTINE', ‘UNDER TEST’
'APPROVED', 'REJECTED, 'QUARANTINED' etc. Appropriate material
handling devices are used such as trolleys, cages, stackers for
handling of materials in warehouse. Only materials which have been
released by QC and which are within the retest period are used for
dispensing. Dispensing of material is done as per SOP on FIFO / FEFO
principle. Material dispensed for each batch are kept together and
labeled accordingly.
C.5.3. Arrangement for Handling Rejected Materials and Products:
All Rejected materials are separated from 'APPROVED' or
'QUARANTINE' and the Quality Control persons affix ‘REJECTED’ labels.
The Rejected material is transferred to a separate” Rejection" area.
Quality Assurance decides the fate of such rejected material as to
destroy or to be return. No printed packaging materials are returned
but are destroyed on the premises under supervision of Quality
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Assurance and records are maintanined. The rejected materials are

kept under lock and key and only authorized persons are allowed to
handle such materials.
C.5.4 Brief Description of the General Policy for process validation:

Process Validation studies are conducted as per the system

established in validation Master Plan and as per approved validation
protocol.
The approved validation protocol includes following parameters to
monitor:-

 Raw material Specification

 Manufacturing formula
 Manufacturing procedure
 Sampling points at various stages during manufacturing
 Critical Process Parameters and acceptance criteria
 Critical process equipments and equipment calibration data
 Process flow diagram
 Deviations if any
 Assessment of results
 Conclusions and recommendations

Prospective, Concurrent and retrospective validations for defined

processes using specified materials and equipment are periodically
carried out.
Significant amendments to manufacturing processes, including any
change in equipment or materials, are revalidated. All validations and
revalidation activities are documented and recorded.
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C.6 QUALITY CONTROL

C.6.1 Description of Quality Control System

Quality Control system has an independent role in plant as well as it is

integral part of cGMP and ensures that the necessary and relevant
quality checks are done & that neither the material nor the products
are released for use or supply, until their quality has been judged to be
satisfactory.
Quality Control laboratory is established with highly equipped
sophisticated instruments like HPLC, TOC analyzer, UV/VIS
spectrophotometer autotitrator, Karl fisher analysis, bursting strength
apparatus, leak test apparatus are available to analyze raw materials,
packing material, in-process samples and finished products.

Dedicated area and facilities is also available for microbiological

testing.

All the incoming materials are sampled in accordance with a set

sampling plan and are given a unique analytical reference number.
The analytical testing is allocated and carried out by analysts. All
analytical work is recorded in authorized controlled copies of
analytical work sheets issued by quality assurance. These raw data
are checked by supervisors for their authenticity adherence to data
integrity and data reliability. All the analysis is performed using
approved specifications and analytical methods. Finished products are
tested as per specifications using validated analytical methods.
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Retention samples are kept and maintained as per the specified

storage conditions for the specified period.
QC ensures the implementation of quality control procedures and
general analytical methods which include:
- Sampling
- Maintenance of reference and working standards.
- Analysis of Testing Procedures
- Release or rejection of materials
- Appropriate status labeling of materials
- Analysis of stability samples
- Investigation of complaints
- Validation and instrument calibration
- Analytical Method Validation
- Cleaning Validation by performing rinse/swab analysis

C.7 CONTRACT MANUFACTURE AND ANALYSIS:

No contract manufacturing is being done currently. However, analysis

of certain materials for specific tests that cannot be carried out at the
site is done at contract laboratories. The contract laboratories are
provided with the information and specifications necessary to carry
out the tests. Written agreements have been made with the contract
laboratories. The contract laboratories are periodically inspected for
conformance with GMP.
Records of these visits are maintained.
List of Contract Laboratories is mentioned in Annexure IV.

C.8 DISTRIBUTION, COMPLAINTS AND PRODUCT RECALL:

C.8.1 Arrangement and Recording System for Distribution:

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The warehouse is a segregated and secured area. It is environmentally

controlled and records are maintained. Both pallets and racking
systems are used for storage of materials as well as finished goods.
Product status is controlled by effective labeling system to identify the
status of products.
Finished goods are stored on pellets well arranged in racking system in
fully secured finished goods storage area in warehouse. Effective
stacking of the finished packs is in place on product wise and batch
number wise up to specified height.
Dispatching activities of products are carried out with principle
procedure of “First In First Expired is First Out” i.e. FIFEFO basis. Batch
traceability with respect to the batch number, quantity, date,
customer details can be obtained from the records of distribution.
The records maintained permits full batch traceability from the factory
to the customer, in terms of batch number, quantity, date of dispatch,
customer details. The importing party maintains the distribution
records. The distribution records of domestic products are maintained
in such a way that retrievability of the product marketed can be
ensured fast, in case of withdrawal or recall.

C.8.2 Arrangements for Handling Complaint and Product Recall:

Complaints:
Written procedure for handling of market complaint is in place to
provide overview idea about handling of market complains by logging
and investigation. Each complaint is acknowledged by the company
and deep investigation has been carried out by Head - Quality
Assurance with the help of concerned personnel as per standard
operating procedure.
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Based on the nature of the complaint, the same is classified and an

investigation report is prepared followed by action plan is raised and
reply to the complainant constitute documents of complaint handling
procedure. The records remain with the Head – Quality Assurance.
Complaint records are stored Minimum for three months after the
expiry of the product in question.
Product Recall:
There is a written procedure for product recall covering both voluntary
recall and recall requested by the Drug Control Authorities which
includes the following.
1. Details of distribution data for retrieval.
2. Notification to customers concerned.
3. Receipt, segregation, inspection and investigation of return goods.
4. Investigation and reporting of cause of defect.
5. Recommendation and reporting of corrective action.

Recalls are made by the action initiated by Quality Assurance, with the
support of regulatory cell / Export department and under the authority
and guidance of the President-Technical Operation. Necessary
documentation is carried out and records are maintained.
The quantity received if any, after recalling a batch is kept in secured
dedicated area till the decision about its disposal is taken. If recall of a
product is at the instance of local drug authorities, the final disposal is
done in their presence, but if it is a voluntary withdrawal, the decision
of President Technical Operations is authorized and final.

C.9 SELF INSPECTION:

Self-inspection or internal audits are conducted for cGMP / cGLP

compliance at regular intervals in accordance with the established
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schedule by in-house teams, inter-unit teams, comprising of

competent persons from different departments.
Sometimes with an objective of to ensure the effective compliance,
external audit shall also be proposed for full compliance to cGMP
regulations covering quality, efficacy and safety at all steps of
processing of the products.
The self-inspection is carried out as per the SOP of self-inspection as
well as with accordance of checklist reflecting the key activities
drawn up for each areas such as warehouse, engineering services,
production, quality control, quality assurance and the reports are
made in a defined format.
Effective corrective and preventive actions are taken to ensure
compliance with the deficiencies, which may be observed.
While carrying out audit checks, special attention is to be paid to
previous audit findings and their compliance.

Audit finding reports are made for which the concern department
makes the compliance report and the copy of it is sent to the
President Technical Operations for his review & comments.
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LIST OF ANNEXURES

ANNEXURE NO. TITLE

ANNEXURE – I SITE MAP

SITE PLAN
a) Ground Floor Plan: - Room Names with area

ANNEXURE – II classification and Differential Pressure details

b) First Floor Plan:- Room Names with area
classification and Differential Pressure details
PHOTOGRAPHS OF EXTERIORS & SURROUNDINGS OF
ANNEXURE – III
PLANT

ANNEXURE - IV LIST OF CONTRACT LABORATORIES

ANNEXURE – V ORGANIZATIONAL CHART

ANNEXURE – VI SCHEMATIC DRAWINGS OF HVAC SYSTEM

ANNEXURE – VII SCHEMATIC DRAWINGS OF WATER SYSTEM

LIST OF INSTRUMENTS AND EQUIPMENTS IN

ANNEXURE – VIII
PRODUCTION AND QUALITY CONTROL LABORATORY

ANNEXURE - IX PRODUCTION PROCESS FLOW CHART