SAFETY IN API OF PHARMACEUTICAL

INDUSTRY

INTERNSHIP REPORT

Submitted by

ARULPRASAAD A M
(611219423001)

In partial fulfillment for the award of the degree of

MASTER OF ENGINEERING
IN INDUSTRIAL SAFETY
ENGINEERING

KNOWLEDGE INSTITUTE OF TECHNOLOGY,

SALEM

DEPARTMENT OF MECHANICAL

ENGINEERING ANNA UNIVERSITY::CHENNAI

AUGUST2020

1
 ACKNOWLEDGEMENT

At this pleasing moment of having successfully completed my Internship at

BIOCON LIMITED., I wish to convey my sincere thanks and gratitude to our beloved
President Thiru.R.KUMARASAMY, Secretary Thiru.V.SURESH KUMAR, B.E.,
and all the members of Knowledge Institute of Technology Trust for providing all the
facilities to me.

I take privilege to express my profound thanks to my beloved Principal

Dr.PSS.SRINIVASAN, M.Tech (IIT-B), Ph.D., who has been a bastion of moral
strength and a source of incessant encouragement to me for carrying out this Internship.

I express my sincere thanks to Dr.K.VISAGAVEL, M.E., Ph.D., Vice Principal

and Head of the Department, Mechanical Engineering who offers his continuous advice
and encouragement to me.

I express my sincere thanks to Dr.N.PANNEERSELVAM, M.E., Ph.D., PG

Incharge for his valuable guidance and suggestions.

With deep sense of gratitude, I extend my earnest and sincere thanks to my class
advisor Mr.G.THANGARAJ M.E., Assistant professor, Department of Mechanical
Engineering for the kind guidance and encouragement.

I also thank to my family members and the teaching, non-teaching faculty

members of Mechanical Engineering Department and all my classmates who stood with
me to complete the Internship successfully.
CHAPTER
TOPICS PAGE NO
NO

ABSTRACT 6

1 INTRODUCTION 7

1.1 COMPANY PROFILE 7

1.2 MANUFACTURING PROCESS 12

1.2.1 STEP BY STEP OPERATIONS IN API 13

EHS (ENVIRONMENT HEALTH AND

1.2.2 13
SAFETY)

1.2.3 HEALTH AND SAFETY AT WORKPLACE 14

EMERGENCY PREPAREDNESS & RESPONSE

1.2.4 15

1.2.5 EHS TRAINING AND EMPLOYEE ENGAGEMENT 15

1.2.6 16

1.3 17

4
2.1 HAZARD AND CONTROL MEASURES 18

WEEKLY OVERVIEW OF INTERNSHIP

3.1 22
ACTIVITIES

4.1 WORK RESPONSIBILITY 29

5.1 SKILLS LEARNED / KEY LEARNING’S 31

6.1 OUTCOME OF INTERNSHIP 36

7.1 SUGGESTIONS FOR IMPROVEMENT 38

8.1 CONCLUSION 39
 ABSTRACT

I carried out my internship in Biocon Limited. Internship is an opportunity

to relate what has been covered in class and what is applicable in the field in an
operational environment. The purpose of the program is to fulfil the core
equipment for the award of a Master’s Degree in Industrial Safety Engineering to
get a practical aspect of the theoretical work studied at the university, to
understand the operations in the pharmaceutical API manufacturing industries
and to gain experience in different tasks.

During my internship period a number of approaches and exposure

methods were used which included: Hazard Identification and Risk Assessment,
Accident and Near miss investigation, ISO 14001:2015, OHSAS
18001:2007etc., I was assigned to different departments which include safety,
quality, engineering, production, and maintenance which helped me to acquire
information and gain the benefits related to Environment, Health and Safety. I
gained knowledge on conduct safety inspections, investigations, documents, 5S,
kaizen, and other legal requirements related to health and safety.

In conclusion, this was an opportunity to develop and enhance

skills and competencies in our career field which I actually achieved.

KEYWORDS: Safety, Hazards, Pharmaceutical, Manufacturing,

Risk.
 CHAPTER I
INTRODUCTION

1.1 COMPANY PROFILE

Biocon Limited  is an Indian  biopharmaceutical  company based in
Bangalore, India by Kiran Mazumdar-Shaw, the founder. The Company
manufactures generic active pharmaceutical ingredients (APIs) that are sold in over 120
countries across the globe, including the developed markets of the United States and
Europe. It also manufactures novel biologics, as well as, biosimilar insulins and
antibodies, which are sold in India as branded formulations. Biocon's biosimilar
products are also sold in both bulk and formulation forms in several emerging markets.
In research services, Syngene International Limited (Syngene), a publicly listed
subsidiary of Biocon.

Fig. No. 1.1 Company Founder

Biocon's formulations for the Indian market include Metabolics, Oncology,
Immunotherapy, Nephrology and Specialty. Some of Biocon's key brands in India
include INSUGEN (rh-insulin), BASALOG (Glargine), BIOMAb EGFR
(Nimotuzumab), BLISTO (Glimepiride + Metformin), CANMAb (Trastuzumab),
Evertor (Everolimus), TACROGRAF (Tacrolimus), ALZUMAb (Itolizumab) and
KRABEVA (Bevacizumab).

Biocon and Syngene together employ about 9200 personnel.

Biocon was founded in 1978 with ₹10,000 (US$140) as the initial capital. Now the total
assets of this company is ₹14,443.80 crore (US$2.0 billion)

Biocon's first product to go to market was papain, an enzyme found in papaya which is used to

prevent beer from turning hazy. Until 1983, the company blended enzymes and supplied them to
brewing, textiles, biofuels, animal feed and other such industries across the world.

In 1989, the Irish Biocon was acquired by Unilever.

Biocon's milestone events in each year are as follows:

· 29 November 1978 - Biocon India is incorporated as a joint venture between Biocon

Biochemicals Ltd. of Ireland and Kiran Mazumdar-Shaw.

· 1979 - Becomes the first Indian company to manufacture and export enzymes to USA and
Europe.

· 1989 - Unilever acquires Biocon Biochemicals Ltd. in Ireland and merges it with its
subsidiary, Quest International; Biocon receives US funding for proprietary technologies.

· 1994 - Establishes Syngene International Pvt. Ltd. as a Custom Research Company (CRC).

· 1998 - Unilever agrees to sell its shareholding in Biocon to the Indian promoters. Biocon
becomes an independent entity.

· 2001 - Becomes the first Indian company to be approved by USFDA for the manufacture
of lovastatin; Pla Fractor is granted a US 2001 and worldwide patent.

· 2003 - Biocon becomes the first company worldwide to develop human insulin on
a Pichia expression system.

· 2006 - BIOMAb EGFR, first indigenously developed humanised monoclonal antibody for
head-and-neck cancer is launched and Dr. APJ Abdul Kalam inaugurates India's Largest
Biotech-Hub "Biocon Park".

· 2008 - Biocon acquires a 70% stake in German pharmaceutical company, AxiCorp GmbH.
· 2009 - Syngene -Bristol Myers Squibb research facility is established in Bengaluru.

· 2009 - Mylan announces strategic collaboration with Biocon to Enter the Global Generic
Biologics Market.

· 2010 - Biocon expands to Malaysia, biopharmaceutical manufacturing and R&D facility

established in Iskandar Malaysia, Johor.

· 2011 - Biocon launches INSUPen®, a convenient and affordable reusable insulin delivery
device.

· 2012 - Abbott announces collaboration with Syngene to Open First Nutrition R&D Center
in India.

· 2013 - Biocon launches biologic drug ALZUMAb to treat psoriasis.

· 2014 - Biocon launches world's first biosimilar drug CANMAb to treat breast cancer.

· 2015 - Biocon launches hepatitis-C drug in India under brand name CIMIVIR-L.

· 2016 - Becomes the first Indian company to launch a biosimilar  Insulin Glargine pen in
Japan.

· 2016 - Syngene sets up Amgen R&D center in Bangalore.

· 2017 - Biocon's Insugen is the first locally manufactured biosimilar product to be approved
for sale by the Malaysian drug regulator.

· 2017 - USFDA approves Mylan-Biocon's biosimilar for cancer drug Herceptin.

· 2018 - Biocon, Mylan get European Commission approval to market biosimilar insulin
glargine.
Fig. No. 1.2 Company view
S.No Details Description

1 Name of the Company : Biocon Limited

Plot No. 1,2,3,4 and 5, Bommasandra Jigani

2 Address : Link Road, Bommasandra Industrial Area,

Bengaluru, Karnataka 560099

3 Total Area coverage : 90 acres

4 Type of Company : Biopharmaceutical

5 Category : Orange

6 Name of the Occupier : Kiran Mazumdar-Shaw

7 Designation of the Occupier : Chairperson & Managing Director (M.D)

8 CEO & Joint Managing : Siddharth Mittal

Director

9 Scale of Industry : Large

10 Total Employees : 11000+ members

11 Improving Lives : 120+ countries

12 Major Manufacturing : Cardiology, Oncology, Diabetology and

Medicines Nephrology

Shift-A (06:00 ~ 14:00 hrs),

Shift –B (14:00 ~ 22:00 hrs),

13 Shifts & its Timings :
Shift-C (22:00 ~ 06:00 hrs),

General (08:15~16:15 hrs)

Table 1.1 Company details
 1.2 MANUFACTURING PROCESS

Fig. No. 1.6 Basic API process layout

STEP BY STEP OPERATIONS

RAW MATERIAL

API SYNTHESIS

CHEMICAL /
BIOLOGICAL PROCESS

PRELIMINARY
PURIFICATION

CENTRIFUGATION

FILTRATION

CRYSTALLISATION

DRYING

TAP MILL

MICRONISATION

BLENDING

PACKING

DISPATCH
 Active Pharmaceutical Ingredient (API) is defined by U.S. Food & Drug
Administration as: any substance or mixture of substances intended to be used as
the active ingredient in the manufacture of a drug (medicinal) product. Such
substances are intended to furnish pharmacological activity or other direct effect
in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect
the structure or function of the body. API may exist in the form of liquids,
powders, crystals and extracts that obtained by chemical synthesis, plant
extraction, or biotechnology and is not taken by patients directly. Only when API
is processed into a pharmaceutical preparation, can the product be used for
clinical use. The synthesis of APIs is usually a complicated and multi-step
process involving numerous chemical transformations and operations on a range
of raw materials with different physical and chemical properties. Specialized
expertise is needed to achieve the synthesis of these molecules. 
1.3 EHS (ENVIRONMENT HEALTH AND SAFETY)

Our EHS Management System and the Occupational Health and Safety
Management Systems are established in compliance with ISO 14001:2015 and
OHSAS 18001:2007, respectively.
The comprehensive EHS Management System encompasses all operations in
manufacturing, research & development, supply chain network, as well as,
administration.

In our constant endeavour to raise the bar, we are transitioning to the new
ISO 45001:2018 standard, the first global standard and a single benchmark for
management of Occupational Health and Safety. Continuous self-evaluation,
correction and improvement of operations and processes based on findings of
annual internal and external audits continue to lead us to the next orbit in EHS.

HEALTH AND SAFETY AT WORKPLACE:

Safety and health of employees is of paramount importance for any
organization, therefore, we have built a strong culture of occupational health
and safety at Biocon over the years.
Several safety-related initiatives, awareness campaigns and drives were
conducted to promote a “zero incidents” mindset among employees. These
efforts resulted in behavioural change, making FY19 a zero-reportable-incidents
year.

By applying scientific risk assessment technologies at work on chemicals

and biologicals, we ensured that highest workplace safety standards were
implemented across R&D and the manufacturing value chain. We accorded
additional focus on road safety by initiating a comprehensive logistics and road
safety assessment of our facilities and designed a traffic management blueprint
for enhanced man-material segregation in Biocon facilities.
EMERGENCY PREPAREDNESS & RESPONSE:
Risk engineering and emergency response planning are critical components
of our EHS management system. We have a well-trained emergency response
team (ERT) and advanced fire protection systems to respond quickly to
emergencies. During the year, several EHS training workshops were held to
augment the ERT’s efficiency to ensure swift response during any emergency.

We further strengthened our fire protection system and emergency

preparedness by introducing an advanced firefighting vehicle with a 42-meter
aerial ladder platform and hydraulic rescue tools.

Periodic Mutual Aid meetings were organised with representatives from nearby
industrial units for enabling collaboration and swift response during any
emergency.
EHS TRAINING AND EMPLOYEE ENGAGEMENT:
We organized close to 22,000 man hours of training for our employees
across 346 sessions covering chemical safety, lab safety, fire safety, emergency
preparedness, first aid and advanced process safety.
As a part of our commitment to enhance employee awareness on EHS-
related matters, several awareness campaigns were held around World
Environment Day, National Safety Week, Fire Services Week, World Water
Day, and World Ozone Day.
 CHAPTER 2

2.1 HAZARDS AND CONTROL MEASURES

Sl.No. Hazard Hazard Control measures

Type
1 Chemical Shifting of Solid,  Blower is provided at
Hazard
Liquid major locations.
Chemicals and  Scrubber is provided in
Solvent Drums. every Charging and
During the Unloading Area of
operation of the equipment
centrifuge  Organic Vapour mask
provided to the employee
as Personal Protective
Equipment

2 Electrical Working in the  Only Competent person is

electrical panels located allowed to perform
in the shop floor. electrical activity.

 Warning signage is placed

on each and every panel.
 Fire Extinguishers are
placed at easily accessible
locations.
 Conductive metal or
jewellery (bracelets, chains,
rings, etc.) is not allowed
when working on
electricity
3 Work at Working on Tap mill  Ladders are locked
Height  Non-routine works are
managed using the Work
Permit.

4 Mechanical Working on equipment  Machine guards are used to

like Reactor, Vessel, avoid direct contact with
Centrifuge,etc.. rotating or moving parts.
  Unauthorized entries are
prohibited.
 Personal Protective
Equipment is used by all
the workers.
 Adequate lighting is
provided in the shop floor.
 Designated walkways are
provided.
5 Dust Working on Powder  Laminar Air flow hoods
Packing Machines Area. and blower are provided
near the Packing Area.
 Proper Scrubbing System is
provided.
 Dust mask or Organic
Vapour mask is used by the
workers.
6 Ergonomics Lifting and placing the  Platform or conveyor is
material. provided wherever
possible.
 Trolley, fork lift and pallet
is provided for the workers
for moving heavy
load material.
 CHAPTER 3

3.1 WEEKLY OVERVIEW OF INTERNSHIP ACTIVITIES

DATE DAY ACTIVITY

WEEK 1 19-10-2020 MONDAY 1. Guidelines
2. Explain about Fire Triangle
3. Explain about Fire
Extinguisher
4. Various classes of Fire
extinguisher
5. Fire Extinguisher in our
Working area

20-10-2020 TUESDAY 1. Practical demo of Fire &

Safety Training
2. Demo of Handling Fire
Extinguisher
 3. Accident
Investigation
5. Machine lifting work at
height (net process)

 Work at height (forklift)

 Work at height (cutting
work, without goggles,
near electrical switch box)
 Electric wire (without
socket)
6. Liquid Nitrogen filling
observation (driver PPE, 2
fire extinguisher, earthing,
wheel breaker)
7. HIRA and JSA
8. Act, Rules, Procedures.

21-10-2020 WEDNESDAY 1. Process Observation and

Safety Measures in
Intermediate Area of API
2. Explain the Various Machine
Guards in the Equipment
3. Explain the safety Valves
4. Means of escape in case of
Fire

5. Road safety training

program
 8. Onsite training
9. Work permit system

22-10-2020 THURSDAY 1. Explain about fire alarm and

Hooter
2. Report of Karnataka Pollution
of Control Board about Air, noise
and Meteorological efffects
Report
3. Under explained their Range
limit and Control Measures

23-10-2020 FRIDAY 1. Material Safety Data Sheet

2. Various types of Hazards And
Control Measures
3. Explained About Personal
protective Equipment
4. Explained about Hierarchy of
controls
5. Explained various Cartridge
Mask and Dust mask
24-10-2020 SATURDAY 1. Safety pictogram symbols in
Work Area
2. Unsafe act and unsafe conditions
identifications
WEEK 2 27-10-2020 TUESDAY
1. Disaster management
plan training
2. Disaster Management using
PHAST software

3. Emergency shutdown procedure

4. Electrical Power Failure, Key

Utility failures & Fire protection
system
5. Emergency Control
Room - is the focal
point in case of an
emergency from where
the operations to handle
the emergency are
directed and
coordinated. It will be
equipped with Internal
and P & T telephones,
Paging system and
Emergency siren.
6. Emergency safety equipment &
Reporting and response to
emergency

7. Emergency Help from nearby

industries and tie up with nearby
industries
8. Fire hydrant inspection

28-10-2020 WEDNESDAY 1. Safety measures in production

Area
2. Pressure safety valves for
storage tanks & Pipelines

3. Level transmitter, Level gauge

 and Temperature indicators
for the storage tanks
4. Fire protection
arrangements in
the form of Fire
Hydrants and
Monitors for the
storage tanks.

5. Emergency
Handling checklist
and procedure
6. Pressure alarm High and
Pressure alarm low for
Storage Tanks
7. Level indicators with
monitoring from control for
storage tanks
29-10-2020 THURSDAY
1. Risk assessment
2. Emergency response plan.

30-10-2020 FRIDAY 1. Process observation and

Safety measures in Clean
room area
2. Equipment Cleaning with
Various Safety Measures
Discuss about OHSAS
18001:2007
Document Preparation and SOP
preparation
 4.

WEEK 3 2-11-2020 MONDAY

1. Hazardous waste disposal
2. Vehicle fuel consumption
inspection
3. Medical record
4. Safety board updating
5. Food waste inspection
6. Foam Fire trolley provided
to paint shop
7. ISO 14001:2015 and OHSAS
18001:2007 discussion
8. Fire hydrant inspection
3-11-2020 TUESDAY 1. Patrol (Morning & Evening)
2. ISO 14001:2015 discussion
and review
3. Flow meter updating
4. Preparing SOP for forklift
activities.

4-11-2020 WEDNESDAY 1s. ISO 14001:2015 EMS

review
3. Document preparation
4. ISO 14001:2015 session
5. Visual audit of EMS

5-11-2020 THURSDAY 1. Patrol (Morning & Evening)

2. Induction training to new
contract workers
3. Maintenance work for EMS
audit
4. EMS document updating.

6-11-2020 FRIDAY 1. Patrol (Morning and

Evening)
2. ISO Internal Audit report
preparation on PC
3. Incident report (from
production and engineering
department for the incident
 that happened on
30.10.2020)
4. Fire extinguisher Checklist
preparation.
5. Electrical panel maintenance
requirements for STP, ETP
and WWTP.
6. Site visit for Tank cleaning
process.

7-11-2020 SATURDAY 1. Patrol (Morning and

Evening).
2. Incident report verification
and preparation.
3. All safety related documents
filed.
4. Implementation of 4s in IT
store room.
5. ISO 14001:2015
Environment
Audit.
10-11-20 TUESDAY 1. Patrol (Morning and
Evening)
2. Unsafe act and Unsafe
conditions identification
3. Fire safety audit
4. Document verification
5. 4s audit.
 CHAPTER 4
4.1 WORK RESPONSIBILITY

Sl.No. RESPONSIBILITY PURPOSE / DUTY

ASSIGNED
1. Safety Rounds 1. To identify and report the
abnormalities in the shop floor.
2. To review the daily documents like
work permit, status boards, medical
register, etc.,

2.

3. API production Area To inspect and monitor the activities

inspection
related to Various Hazards and Risk ,
Safety Pictogram symbols and
Equipment Guards

7 5S Workplace To supervise the 5S activity in the

Production Area.
8 Identify the Hazards To inspect the shop floor related to
environmental issues and correct or report
them to the concerned
department.
 CHAPTER 5
5.1 SKILLS LEARNED / KEY LEARNING’S:

1. Daily Inspection of Workplace areas:

The workplace is inspected at least twice a day to ensure:
 The workers are working in a safe manner with adequate PPE.
 Site is free from abnormalities and if present, the abnormalities are
notified to the concerned department.
 To report issues related to spillage, poor work procedure, etc., if any.
2. Work Permit Systems:
 To ensure that the non-routine works comply with the work permit
requirements and to review the previous work permits related to high
risk activities like working at height, welding, Liquid nitrogen
dispensing, etc.,
3. Fire Audit:
 To conduct the fire audit in the work area and to ensure that the
previous control measure as mentioned in the previous audit report
are in place.
 To inform the concerned department in case of any non-conformance
and report the same to the EHS department.
4. Inspection of Fire Extinguishers:
To ensure that the fire extinguisher are in good condition based on the
following checkpoints:
 Hose is in good condition with block or damage.
 Appropriate pressure is maintained.
 Fire Extinguisher is free from physical damages.
 Fire Extinguisher signage is in proper condition.
 Fire Extinguisher is not kept on floor but hanged at 0.750 m height.
 Fire Extinguisher sticker having details of service and refilling.
 Access to the Fire extinguisher is not blocked.
 5. Inspection of Fire Hydrant System:
To ensure that the fire hydrant system are in good condition based on the
following checkpoints:
 Fire Hydrant System is free from physical damages.
 Have sufficient Nozzles and in proper condition.
 Box is not rusty.
 Glass is in good condition and have the key and hammer.
 Access to the Fire hydrants systems are not blocked with materials or
grass.

6. Practical investigation of Accident Investigation Reporting for Incident:

 Investigating the accidents or incidents to identify the root cause,
providing control measures and coordinate with the concerned
department to prepare the Accident investigation report.
7. 5W-1H Analysis:
 To create a Standard Operating Procedure (SOP) related to welding
activities and forklift activities based on the 5W-1H Analysis.
 5W-1H analysis refers to:
o Who?
o What?
o Where?
o When?
o Why?
o How?

8. Emergency Response & Preparedness Plan:

 Emergency Preparedness plan during uncertain situations like fire,
medical emergency, etc., are learnt and the following arrangements
are made in the company to tackle such situations.
o Ambulance is available all the time to manage the medical
emergencies.
o Fire Hydrant and Fire Extinguishers are placed at regular
intervals and at high risk areas to manage fire emergencies.
o Assembly point is placed at the safest place to conduct the
headcounts during emergency situations.
o Emergency lightings, Emergency exits, Manual call points are
kept at regular intervals to alert and direct the workers towards
the safe assembly point during emergency situations.
9. Implementation of 5S in Productions department:
 5S is a system for organizing spaces so work can be performed
efficiently, effectively, and safely. This system focuses on putting
everything where it belongs and keeping the workplace clean, which
makes it easier for people to do their jobs without wasting time or
risking injury. A list of five Japanese words: “Seiri”, “Seiton”,
“Seisō”, “Seiketsu”, and “Shitsuke” is used as a base which means
"Sort", "Set In order", "Shine", "Standardize" and "Sustain".
Supervision was done at the Production department to ensure that the
5S system are followed.
 CHAPTER 6
6.1 OUTCOME OF INTERNSHIP:

This internship is helpful to get a opportunity to apply my knowledge and

skills acquired in the classroom to a professional context. Helps to understand what
skills are transferrable to new contexts. The exact nature, activities and emphasis
can be able to understand in the safety field. It helps to identify and understand the
practices and protocols of the pharmaceutical industry and their work nature.
 CHAPTER 7
7.1 SUGGESTIONS FOR IMPROVEMENT:
1. Standard Operating Procedure for handling the Tap milling should be
reviewed again and appropriate changes to be made for avoiding spillages
2. Mock Drill should be conducted on monthly basis to ensure that the
employees or the workers are aware of the emergency preparedness
procedures.
3. MSDS should be displayed on the locations where the chemicals are
handled especially in the working area so that the workers are aware of the
physical and chemical properties of the chemical being used.

CHAPTER 8
8.1 CONCLUSION:
Our humble thanks and regards to our Biocon Limited., Bangalore
for giving this great opportunity, it’s very useful for us to learn technical
knowledge and skills on safety in the period of internship. This Internship helps us
to develop our career in future and guide us to implement safety at workplace.