Prepared & Presented BY :Abhishek Mishra

Semester-VB.E (Pharmaceutical Technology)

INDUSTRIAL TRAINING AT

ZYDUS CADILA HEALTHCARE LTD. ANKLESHWAR

Content

Introduction .

History.

QC Dept

Sections of QC Dept.

Raw material and Storage

In process( kf , FTIR, UV MP, )

GC and HPLC

Microbiology and Stability Section.

Conclusion n doubts ???

Vision statement

Zydus shall be leading healthcare provider with robust product

pipeline;

Stepping beyond the billion, we shall achieve of over USD 3

billion in 2015and be a research based Pharma company by

2020.

API shall contribute to this by being reliable service provider to

our customer, maintaining cost competitiveness through

Continuous improvement in process, offering quality product

keeping prime focus on environment, health safety…

Product Manufacturing in Ankleshwar (API

Division)

Amlodipine

Famotidine

Fluxetine

Hydrochloride

Tramadol

Loratidine

Meloxicam

Losartan

Glibenclamide

Fluconazole

Omeprazole

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API DIVISION

(Active Pharmaceutical Ingredient)

In API Division the production of API’s was carried out

through process from raw material to finished product

“An API starting material can be material purchased from

one more suppliers under the contract or commercial

agreement, or produced In-house. API starting materials

normally have defined chemical properties and structure.

QA (Quality Assurance)

It is the way of preventing mistakes and defects in manufactured

products and avoiding problems when service is delivered to

Customers.

The basic two principle of QA are ….

1. Fit for Purpose – “the product should be suitable for intended purpose”

2. Right first time - “mistake should be eliminated”

It includes management of quality of raw material, assemblies,

products, components, service related to production and

management along with regular inspection processes.

Now in pharmaceutical industries GMP and cGMP are

very important aspects in an organization

cGMPs now generally recognize( QA- Compliance, QC-

Testing)

cGMP

QA Quality

Assurance

QCQuality Control

QC- Quality Control

QC is a process by which entities review the quality of all factors involved in production

QC emphasis on three aspects

Elements such as controls, job management, defined and well managed process, performance and integrity criteria, and identification of record.

Competence such as knowledge, skill, experience and qualification.

Soft elements such as personnel, integrity, confidence, organization culture, motivation, team spirit and quality relationship.

Responsibility

Responsibilities of QC unit

To Check and test the incoming material( raw material,

intermediates, in process samples) and declared the

result as per controlled specification whether it is pass

or fail and informed to QA Dept.

Sections….

Documentation Room

In documentation section all the data and records are kept and stored by electronic software system.

Various kind of form that to be filled during analysis or testing of product.

SAP Form

SOP Form

COA Form

GTP Form

Specification Form

SAP formation: It is networking software having different modules for human resources controlling, finance, plant, maintenance, production planning, quality management, sales & distribution, etc.

Cont.

Quality management module of SAP:

Inspection lot processing.

Release of inspection lot physical sample drawing.

Result recording against inspection lot.

Usage decision against inspected lot.

COA printing.

Creation of physical sample

Storage and Ware House

Raw material Section :

All material that to be used in manufacturing of

finished bulk (even though it is not present in

finished API e.g. certain solvents (Me-OH,

alcohols, acetone)) and material that to be used

in production of API called as raw material (it

can be KSM or non KSM). It can be either active

drug or inactive substance.

In this section the testing of raw materials & packing materials is

carried out and complete analysis of raw materials out using GC &

HPLC.

The following parameter is to be analyzed in this section as follows:

Description by physical appearance & odour.

Identification & purity testing by HPLC.

Detection sulfated ash & ignited residues by using muffle furnace.

Assay by titrimetry.

Water or moisture content by Karl Fischer apparatus etc.

Sampling Procedure

In Process Section

In this section two types of analysis are carried out wet analysis and

instrument analysis.

In wet analysis the description solubility, clarity alkalinity and titration

test of compound are carried out.

Sample & intermediate from plant or production are analyzed in this

section and finished API sampling done by QA department and samples

are then analyzed in process section, samples can be from SRP (solvent

recovery plant) for analysis in process section.

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They register sample inward register data are to be

filled in register like batch no, inspected no, mfg qty;

batch qty; and sample qty.

Then they distribute sample for analysis to HPLC or GC

according specifications of material or intermediate.

Process Flow

Instruments in process section

Karl Fischer titrator.

Melting point apparatus.

FTIR (Fourier Transform Infrared Spectroscopy)

pH meter

HPLC

Gas Chromatography

Karl Fischer titrator.

The Karl Fischer titrator designed forfast volumetric moisture titration,providing the perfect solution toroutine measurements.

The advantages of Karl Fischertitrator are follows:

Fast titration results

Ultimate analytical performance accuracy

Push-button operation

Minimal training required

Compact setup

POlarimeter

A polarimeter is a scientificinstrument used to measure the angleof rotation caused by passingpolarized light through an opticallyactive substance.

Because many optically activechemicals such as sucrose, arestereoisomer.

Application

Steroids

Diuretics

Antibiotics

Narcotics

Vitamins

Analgesics

Amino Acids

Essential Oils

Polymers

Starches

Sugars

Melting point apparartus

The automatic melting point uses the latest technology in digital image processing to accurately identify the melt of up to three samples simultaneously.

It is used to determine M.P of product(API) , intermediate raw material during analysis.

Uv Spectrophotometer

To check the

absorbance/transmittance

of solution.

Absorbance , A of a

solution is defined as the

logarithm to base 10 of

the reciprocal of the

transmittance T for

monochromatic light.

FTIR

IR spectrum mainly used to measure the vibration spectrum or to detect the functional group under the examined by passing IR radiation through it.

Procedure of Sample preperation

Triturate 1 to 2 mg of the test sample under examination to fine in agate mortar with pestle to obtain a uniform sample in kBr.

Carefully grid the mix, spread it uniformly in die and press to obtain transparent disc about 0.1mm thick and 10-15mm diameter.

Put disc in holder and record the spectrum between 400cm-1 to 650cm-1 and compared with standard reference spectra.

Gas Chromatography

Gas Chromatography (GC or GLC) is a commonly used analytic technique in many research and industrial laboratories for quality control as well as identification and quantitation of compounds in a mixture.

GC is also a frequently used technique in many environmental and laboratories because it allows for the detection of very small quantities.

In this section testing of related substance present in volatile compound are carried out.

There are three models of GC:

PERKIN ELMER

SHIMADZU

AGILENT TECHNOLOGY

The GC having two types

Head Space-only vapor is used.

Head on- only liquid is used

Nitrogen Gas used as source and oxygen and hydrogen is used as flame.

Various Detectors used in GC

FID –Flame Ionization Detector.

TCD- Thermal Conductive Detector

ECD-Electronic Conductive Detector.

Process Flow of GC analysis

HPLC

Cont.

HPLC is chromatography technique used to separate compounds that are dissolved in solution.

HPLC consist of a reservoir of mobile phase, a pump, an injector, a separation column, and a detector.

Normal Phase.- Polar stationary phase and non-polar solvent(moving).

Reverse Phase.- Non-polar stationary phase and a polar solvent(moving).

In this section testing has related to substance present in compound and their assay carried out. There are four models of HPLC

DIONEX

AGILENT

SHIMADZU

PERKIN ELMER

Software for HPLC Comparison:

Chromolion

HPLC DIAGRAM

Process Flow

Microbiology LAb

Microbiology Section

In this section environmental monitoring of plant,process water testing & testing of finished API arecarried out.

There are mainly following types of testing is carriedout...

Growth Promotion test: check the growth promotingproperty of microbiological media used in microbiology lab.

Environmental monitoring of plant: check the microbialstatus of environment in clean areas of processing &packaging areas. It is done by sedimentation method & airsample methods.

Pathogen Testing : Check the Pathogen present in API

Microbial limit test : It is carried out for total viable count (bacteria &f fungi ) & and specified microbial species( coli, salmonella, staphylococcus)

Water Testing : following testing is carried out

1. Hardness test of pre-process and potable water

2. Free chlorine test for pre-process water

3. TDS (total dissolved solid) test of potable water.

Instrumental Analysis

Quantification of Total organic carbon in process water by

TOC analysis.

Quantification of microbial colony by colony counter.

Sections of Microbiology Lab

1. Documentation Room

2. Testing Section

3. Incubation Section

4. Changing Section

5. Storage section

6. Disposal Autoclave section

Instruments in Microbiology Lab

1. Incubator

2. Hot air oven

3. Autoclave

a). Vertical (for disposal of culture)

b). Horizontal (for sterilization purpose)

4. Referigator

5. Colony counter

6. Total organic carbon analyzer

Stability Section

In this section they store sample in

humidity chamber according to

respective pharmacopeia for specific

humidity limit & temperature to

determine shelf life of API or

intermediate.

Stability Storage condition

In stability rooms provide a stable, temperature and/or

humidity-conditioned environment for worry-free operation with

a control system that is easy to use and saves you time. These

chambers are designed for stability studies and testing large

batches of product.

In this section they determine the shelf life of product and ensure

that product in market are within the stability period.

There are various stability study duration

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Conclusion

• It was an amazing experience for us to seeactual QC process and documentation work .

• We also got an oppourtunity to learn GoodManufacturing Practice & cGMP GLP, SOP to befollowed in industry

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Thank you...