A month spent at the industrial pharmacy

1. I
INPLANT TRAINING AT AADEE REMEDIES
Submitted by
Neeraj Ojha
CIST College, New Baneshwor
Affiliated to Pokhara University
To
Prashant Basnet
QA Manager
Aadee Remedies, Imadol, Lalitpur

2. II
Acknowledgement
I am extremely indebted to the technical and non-technical workers at Aadee remedies. I had
extremely good time learning from them by friendly conversations and exchanges. At
production, I am especially thankful to Sunandan Poudel and Sujan Karki who became fast
friends and helped me understand a lot about the production department in a very short time. It
would have been impossible to learn so much in such a small period of time.
At QC, fast understanding with Amit Singh helped a lot to comprehend the subtle duties of the
QC department. The QC staffs like Sujata Dahal, Kishor Chaudhary, Priyanka Bogati and Poudel
helped a lot while performing the water analysis and tests on Metronidazole. Without the help of
these assistants at QC, it would have been impossible to complete all the tests that I was assigned
to in a short duration of 7 days at QC.
Besides, I would like to express my deep and sincere gratitude at Sushant Pokharel at the Storage
Department along with the non-technical assistants over there. They helped me understand the
duties and obligations at storage department. They showed me how to do sampling and
dispensing at the production. Sushant Pokharel gave me the theoretical understanding of the
work that needs to be done at the Storage department.
Ronash Shrestha at QA and Sandesh Khatri at R&D also gave me quick run at their respective
department on the very last day of internship. I owe them a lot for their support.
Last but no least, I would like to express my deep gratitude and thanks to Prakash Bist who
referred me to this wonderful organization and Prashant Basnet who made my time at Aadee
very educative and full of learning experiences.

3. III
Abbreviations
BMR: Batch manufacturing record
BP: British Pharmacopoeia
BPR: Batch packaging record
DMW: De-mineralized water
DT: Disintegration time
FBD: Fluidized Bed Dryer
FG/FP: Finished Goods/ Finished Products
GLP: Good laboratory practice
GMP: Good manufacturing practice
HDPE: High Density Polyethylene
HEPA: High efficiency particulate air
HPLC: High performance liquid chromatography
HVAC: Heating ventilation and air conditioning
IP: Indian Pharmacopoeia
IP C: In process control
QC: Quality Control
QA: Quality Assurance
R&D: Research and Development
IPQC: In Process Quality Control
DDA: Department of Drug Administration

4. IV
CERTIFICATION
This is to certify here that Neeraj Ojha has successfully completed the in-plant
training/internship at Aadee Remedies Pvt Limited that began on Poush 4th 2078 and ended on
Magh 4th 2078. During this period, Mr. Ojha was exposed to Production department, Quality
Control, Store department, Quality Assurance and R&D.
During this period, Mr. Ojha’s conduct and behavior was found to be extremely bonafide. He
seemed to enjoy working and learning from the industry staff a lot throughout this period. We
wish him best in the future.
.........................
Prashant Basnet
Quality/Plant Manager
...........................
Amit Singh
QC In-Charge
.............................
Sunandan Poudel
Sr. Production Officer
............................
Sujan Karki
Jr. Production Officer
............................
Sandesh Khatri
R&D-In-Charge

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Contents
Acknowledgement ..........................................................................................................................II
Abbreviations.................................................................................................................................III
CERTIFICATION ........................................................................................................................ IV
1. Company Profile Information:................................................................................................. 6
1.1. Objective of internship..................................................................................................... 7
1.2. Time Frame:..................................................................................................................... 7
2. Production................................................................................................................................ 7
2.1. Weighing and dispensing: ................................................................................................ 9
2.2. Process equipment include the following: ..................................................................... 10
2.3. Tablet coating was performed the very next week but I was shifted for QC then. ........ 11
3. Quality Control ...................................................................................................................... 15
3.1. Functions of QC:................................................................................................................ 16
3.2. Raw material analysis is one of the most important functions of QC................................ 17
4. Store Department ................................................................................................................... 19
4.1. Store room/ Raw material classification ............................................................................ 20
5. Quality Assurance Department.............................................................................................. 22
5.1 Process Validation (PV)...................................................................................................... 25
5.5 Quality Risk Management................................................................................................... 26
5.6 Corrective and Preventive Action (CAPA)......................................................................... 26
5.7 Product Recall and Withdrawal........................................................................................... 27
5.8 Equipment qualification (EQ) ............................................................................................. 28
5.9 ICH guidelines..................................................................................................................... 28
5.10 Water Treatment Plant ...................................................................................................... 29
5.11 Chiller................................................................................................................................ 29
5.12 Air Compressor ................................................................................................................. 29
5.13 Generator........................................................................................................................... 29
6. Conclusion............................................................................................................................. 30
7. Suggestions:........................................................................................................................... 30
8. References: ............................................................................................................................ 31

6. 6
1. Company Profile Information:
Aadee remedies pvt. Ltd. Is a pharmaceutical company established in 23rd Ashoj 2060 B.S. and
started its operation from 11th Mangsir 2071 B.S. from Imadol, Lalitpur from an area which was
not really residential at that time. At this moment, the company is surrounded by several
residential homes. Company mostly deals with dermatological, gynecological, PPIs, dental and
urological products. Santosh Baral is the acting managing director at the head office and Prakash
Bist at Patan office. This industry has over 40 employees at the Imadol location at this moment.
Plant manager at Aadee is Prashant Basnet currently. He’s been contributing to the
pharmaceutical industry for over 7 years by working in pharmaceutical production, GMP
recommended documentation in QA department, handling of pharmaceutical machineries like
RMG, FBD, Automatic Capsule filling machine, ointment manufacturing and filling machines,
ointment manufacturing and filling machine, Dry syrup filling line, Liquid filling Line,
Autocoater, Conventional coating and much more. He has expert knowledge on handling quality
control lab equipments. Mr. Basnet observes Regulatory affairs and formulation development
closely at Aadee. He also has been supervising all the technical departments in technical matters.
He also has been individually talking to each personnel in every department towards the efficient
realization of organizational goals.
QA officers like Ronash Shrestha of Sundarijal have been preparing and maintaining documents
right from the stage of procuring raw materials. They are also involved in process monitoring at
each department. I had a lot of opportunity to learn about medicinal chemistry, quality assurance,
instrumentation, unit operations, biotechnology, pharmaceutical management, research
methodology, biopharmaceutics etc from each and every officer level technical workers at Aadee
industry within a very short period of time. These sort of moment especially at QC with Amit
Singh were very memorable and informative.
Aadee is one of the fastest growing GMP certified pharmaceutical company located in
Kumaripati-19, Lalitpur always looking for self driven, motivated, disciplined and creative team
members whether it be as intern, employees or partners.
Highly sold products of Aadee include Permethrin Lotion 5%, Halosol Gel, Halosol-G ointment,
Halosol F ointment, Oro Heal Gel, Luly 1% cream, Doxclin 100 mg tablets, Domirab tablets etc.

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1.1. Objective of internship
General Objective:
To fulfill the internship requirement of Pokhara University BPharm course graduation
Specific Objective:
 To find out which sort of work at industry might fit for my career in future;
 To practically know what I had learned for over 4 years theoretically at college;
 To know and built alliance with people who are engaged in the career I am to pursue in
the future;
 To know the work environment of an industrial pharmacy;
1.2. Time Frame:
I was at production house for a week. At QC, I was actively engaged for over a week. I was
scheduled at Storehouse for 3 days. Rest of the time, I was at QA and R/D.
2. Production
Production department in the industrial pharmacy refers to the manufacturing area where the
mass manufacturing of the product is done as per the method developed and tested by R&D in
association with the marketing department and QC. The marketing department which has a
separate establishment comes up with a product that the market is demanding and develops a
general outline of the product details. That is forwarded to the R&D department at industry.
R&D develops the product accordingly performed stability tests with the help of QC and after a
certain period of time registers for the manufacturing license at DDA. This is done online in the
present moments through http://dams.dda.gov.np/login website. The documents are submitted
by R&D online and also in paper print form in person. After approval by DDA, manufacturing
license is received by the company for the product after necessary document submission.
R&D orders necessary packaging materials and labeling from companies abroad in the case of
Nepal. After all these primary tasks are completed, the matter goes to production department for
the bulk production of the first few batches under the direction of R&D officer. This process is
repeated by production department under the direction of production officer with the same
method every time the product is needed again in bulk.

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At my time in production, wet granulation was performed for the Locet tablets under the
direction of Sunandan Poudel and assistance of Sujan Karki. I had a chance to personally assist
the non-technical workers at production during the granulation. All the process was also
supervised by Prashant Basnet of QA. After the sample granules were tested and passed by QC,
the tablet compression was performed in the same week. During this period, the hardness test,
friability test and dissolution tests were performed on the sample tablets many times. The
adjustments were also made on the tablet compression machine settings. After the sample tablets
met the necessary requirements like dissolution time (less than 15 minutes), friability (less than
1) etc., the tablet compression was performed in bulk. On the first day over 80000 tablets were
produced by the compression machine. On the next day, several lakhs of tablets were produced.
This is called IPQC, in process quality control.
Dispensing and sampling were also being done at production while I was there. This was done
under the presence of QC person, Kishor Chaudhary of Saptari in this case. The sampling of
products like permethrin and dispensing of products like menthol were done in my presence.
Sampling is the process of taking out small portion of products that are necessary to be tested at
that period in time by QC. Storage department determines which products needs to be sampled at
that period in time depending upon the several factors. “Swab pass” is a term used in this case.
This is done very frequently. Dispensing is the process of releasing the products necessary for
the bulk production according to the orders received by other departments like marketing and
R&D. For the purpose of dispensing, the machines are first calibrated with the standards. After
they are found fit and OK, the necessary products are dispensed in appropriate containers. The
containers and the ladles are properly washed first with soap and then wiped with isopropyl
alcohol (IPA).
The dispensed products are then kept in the quarantine section. Dispensing machine is used
which exchanging items between storage and the production. This machine operates with UV
radiation that kills the harmful bacteria in the containers and packaging if exposed for at least 30
secs under UV.
Room Pressure difference is maintained very well in the production department. Every person is
required to wear apron and cap before entering the production. Different slippers are assigned for
production area and mask is necessary.

9. 9
Tablets are compressed solid substances either round or cylindrical in shape containing certain
active along with several excipients meant to cure certain disease or mitigate certain medical
condition.
Creams are semisolid dosage forms containing dispersible and dispersion systems. They contain
more than 20% water or volatile components and typically less than 50% hydrocarbon or
waxes.
Ointments are also semisolid dosage forms meant especially for application on the skin. They
contain an active substance meant to act on a skin for a special purpose. They have oily or greasy
consistency and appear stiff upon application.
Granulation is a process of converting raw material particle into more spherical and uniform
structure that can be easily compressed into tablets. Granulation is generally of two types. Wet
and Dry granulations. Wetting agent or liquid is used in wet granulation while dry granulation is
performed without any liquid.
Wet granulation involves the size reduction of the particles using different kinds of mills,
sieving, shifting, mixing etc.
2.1. Weighing and dispensing:
Excipients in different containers were weighed and dispensed in a dust extraction hood. Then
the materials are sent to a cubic feet blender.
1. Pre-mixing:
Blender is used for the pre-mixing purpose. Then, it is discharged into the bins for milling.
2. Milling:
Milling is meant for size reduction. There are several methods that can be applied for the size
reduction process. Material is transferred from PK Blender to a Quadro Comil for milling. It is
used to feed other excipients and Pre-Mix. Then, the product is discharged into the drums.
3. Blending:
Blending is done with the lubricant. This is the last step at the granulation room before the
beginning of tablet compression at the different chamber.
4. Tablet Compression:
Tablet compression takes place in a very contained environment. It is a separate chamber at
Aadee Production department away from the granulation room. The blended product is
dispensed using drums and is fed through the hoppers at the top every few minutes. Following

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compression, tablets pass through the deduster and a metal detector. Rejected tablets are passed
into the reconcilator for the disposal. Acceptable tablets are collected using drums or huge plastic
bags.
Few tablets are tested in the testing room for friability, weight variation, hardness etc before the
bulk production is begun.
2.2 Process equipment include the following:
1. Quadro Comil:
It consists of mill body, infeed chute, rotor shaft assembly with impeller and screen. All the parts
are constructed of 316 stainless steel. This is a high quality rust resistant steel.
2. Blender:
All the product contact surfaces are constructed of 316L stainless steel. All other components are
constructed of 304L stainless steel. A timer can vary the blending sequence time from 0 to 20
mins.
3. Tablet Press:
The station has certain capacity. It can prove over 1 lakh tablets in no time. The press is fully
automated with PCIPLC control, recipe and data logging system. Powder is fed from the top.
The tablet press has upper and lower cam tracks, upper and lower punches, dyes, hydraulic press
force control system etc.

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Thorough mixing is done first so that active is uniformly distributed throughout the mixture. This
is then sieved through meshes of different sizes. Active is carefully handled during this process
that no loss occurs. It is then granulated in the planetary mixer. A tapping hammer is used to
prevent the granules from remaining attached to the mixer. A solution is prepared. Wetting is
done with this help of this solution. Granules are then dried in a dryer at over 40 degree Celsius
of temperature. Glidants and lubricants are then added to the mixer. Final mixing is done with
the help of turbular mixer. The sample is given to the QC for confirmation. If it is approved,
compression is done at a different section with the help of tablet compressor. Necessary tests are
performed at this section before bulk product is underway.
2.2. Tablet coating was performed the very next week but I was shifted for QC
then.
1. Tablet Coating:
Tablet coating is a process of covering up or designing of the outer covering of the
compressed tablet so as to increase its appeal or make it feasible for the consumer. Most
of the time, tablet coating may be sugar coated, enteric coated, film coated depending
upon the need or as per the timing.
Sugar coating is done in order for the tablet to be appealing in terms of taste. Most of the
time, children do not want to consume tablets despite the necessity. However, when the
same tablet is designed with sugar coating, it appeals to them as does candy.
Enteric coating is done to make the drug habitable to the intestinal environment. The
stomach ph is acidic while the intestine ph is alkaline. Enteric coating is done so that
drug is soluble in the alkaline environment. Enteric coated tablets should remain intact
in the gastric environment at least for a couple of hours.
Film coating is done for the protection from external environment or the targeted drug
release process. Thus, tablet coating has various functions depending upon the need of
the moment. Film coating is done to hide bitterness, make it smooth so that it can be
easily swallowed eg. Paracetamol. Besides the one mentioned here, there are various
other types of tablet coating.
Various advanced equipments like coating pans and other machines are used for the
purpose of tablet coating.

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2. Types of tablet coating:
 Enteric coating
 Gastric coating( Enteric coating and Gastric coating are terms very interchangeable. Dt of
the enteric and gastric coating tablets should be as such that the tablet will remain in the
gastric environment at least for 2 hrs. as mentioned earlier.) This is assured in the lab by
preparing a buffer solution out of HCL and examined whether the tablets will disintegrate in
the period of time.
 Film coating
 Sugar coating
 Compression coating
 Electrostatic coating
 Dip coating
 Vacuum film coating
 MAIC, Magnetically assisted impaction coating
 Electrostatic dry coating
 Gelatin coating: Although gelatin coating is done mostly in the case of capsules, it is
sometimes also applied in the case of tablets.
3. Critical parameters of tablet coating:
Critical parameters refer to those parameters that are set by pharmacopoeia for the
standard production of the pharmaceutical products. In the case of coated tablets, the
critical parameters are as follows:
o Spray rate: Spray rate refers to the quantity spray of the coating material per unit time.
Depending upon the thickness of coating spray rate is adjusted.
o Inlet air temperature: Air temperature determines the quality of tablet coating. Inlet air
temperature is increased or decreased as per the necessity.
o Pan speed: Pans are used for the purpose of coating of the tablets. Pan speeds are altered
according to the necessity.
o Relation between coating pan and spray gun: Distance between the coating pan and
spray gun determines the quality of tablet coating. So, it must be properly adjusted.
4. Problems in tablet coating:

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 Blistering: Blistering is a process in which the coated tablet shows a particular nature of
sweating. Or, the tablets burst out of the blister. This can be overcome by proper care during
the coating process. Mild drying is recommended in this situation.
 Mottling: This is a process of the loss of color of the tablet. This may be due to
interaction with the air particles or due to reactive oxygen species, ROS. To overcome this,
proper packaging might be done. This is a problem due to the lack of proper color mixing.
To overcome this problem, coloring agent should be made into colloid.
 Chipping: This is a process of slight breakage of the tablet due to friction during the
packaging process. This can be overcome by properly testing for the hardness, friability,
dissolution, disintegration rate etc. and adjusting the tablet coating machine accordingly. Pan
should be filled with sufficient amount of core tablets. Appropriate baffle designs should be
used. High film strength coating formula should be used. Correct pan speed should be
recommended. Tablet tooling should be replaced. Proper tablet shape should be used.
Optimum spray rate should be used. Suspension solid level should be increased. Hardness of
the film should be increased by increasing the molecular weight of the coating polymer.
 Cratering: This is a process of formation of little crater like structures on the surface of
the tablets. Cratering can be overcome by proper mixing of the raw materials during the
granulation process. Spray rate should be decreased. Optimum drying condition should be
used. Viscosity of the coating solution should be increased.
 Picking:
 Pitting:
 Blooming: Low concentration or high molecular weight plasticizer is recommended in
this situation.
 Blusing:Drying air temperature should be decreased in this circumstance. The use of
HPMC, Cellulose etc with the sorbital should be avoided in this situation.
 Bridging:
 Capping:
 Erosion:
 Twinning: Tablet shape should be changed. Less tacky coating formulas should be used.
Appropriate tablet shape should be used. Pan speed should be increased. Atomizing speed

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should be increased. Spray rate should be reduced. Optimum drying conditions should be
used.
 Peeling and frosting:
 Orange peel: Mild drying condition should be used. Viscosity suspension coating should
be used. Atomizing air pressure should be increased. The spray rate should be decreased.
Better spray guns should be used. Viscosity of the coating suspension should be decreased.
Gun should be adjusted to the bed distance.
 Color variation: Color variation can also happen in the tablet coating process. Variation
in the color can be overcome by proper temperature, proper color ratio etc.
At a time, only couple of problems listed above appears at the production house and they are
tackled by one or more methods as explained above. Experienced production managers come up
with extraordinary solutions whereas novice personnel cannot do so most of the time.
Clean Room Garments
Each and every department including the production had different aprons for the working staff,
visitors etc. These clothes were regularly washed. There were also disposable caps and gloves at
the production. Footwears also classified to be used outside and inside. Wearing the same
slippers inside and outside was not allowed. This was fully enforced by QA personnel visiting
the production.
On the other hand, QC had separate thick gloves for use at the section containing muffle furnace
and different aprons for microbiology section.
Airlocks and Change-rooms in cGMP facility

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3. Quality Control
QC is the department where the analysis is done. So, most of the time, graduates with at least
BPharm degree are required to work at QC. For over 7 days at QC, I was continuously busy in
performing analysis assigned to me by QC officer Amit Singh. First day was spent on
performing the analysis of the water quality supplied by the water system at the company. PH of
the water was tested using the pH meter. Conductivity was measured with the help of another
conductometer. Total dissolved solute TDS was determined with the help of another device.
Acidity and alkalinity of the water was compared with the help of litmus papers. Chloride test
was done. After that, nitrate test on the water was done. Two types of solutions were prepared.
Reference solution and test solution. In the reference tube, 4.5 ml of distilled water was mixed
with 0.5 ml of nitrite standard solution of 2 ppm. To this same test tube, 0.4ml of potassium
chloride was added along with 0.1 ml diphenylamine solution along with 5 ml conc sulphuric
acid. Sulphuric acid, nitric acid etc. were kept in the fume hood. Use of these acids were done
with extra care inside the fume hood. The burettes were then washed and placed in the wash after
some time.
This solution was compared with the test solution in a different test tube containing 5 ml of
water(hot solution). It was kept at 50 degree Celsius for 15 minutes. Any blue color in the test
solution was not more intense than in reference solution. This proved the absence of nitrates.
After that presence of heavy metals in the water was tested for. To the 100 ml of purified water
sample, 0.075 ml of 0.1 M nitric acid was added. Then, it was heated until the volume was
reduced to 20 ml.
Reference solution was prepared with 10 ml of lead standard solution (1 ppm) and 2 ml of
reduced solution. Blank solution was prepared with 10 ml of distilled water and 2 ml of reduced
solution. Test solution was then prepared by taking 12 ml of water. 2 ml of buffer solution was
then added along with 1.2 ml of thioacetamide reagent. They were then mixed and examined
after 2 minutes. Slight brown color was observed compared to the blank solution. Blank was then
compared with the reference solution. Any brown color in the test solution was not more intense
than in the reference solution.
After that, water was tested for the oxidizable substance. To 10 ml of sample, 1 ml of dilute
sulphuric acid was added along with 0.01 ml of 0.02 M potassium permanganate. It was then

16. 16
boiled for 5 minutes. Solution remained pink. Color remained. This proved the presence of
oxidizable substances.
Solutions were prepared as per the instructions in the volume II of Indian Pharmacopoeia. There
were two sections called general reagents and chemical reagents in the volume two of IP that
were extremely useful during my time at QC. Some of the codes like 2.30.04 brought us back to
volume I for detailed information on that matter. I found it easy to write down on my notebook
all the necessary instructions first on the copy and then continue the experiment.
Similar, tests were performed from the very next day on sample active of Metronidazole(Batch
no MTZ-0111877). It was a white/yellow crystalline powder. Sample was sparingly soluble in
water. It was sparingly soluble in ethanol. It was very soluble in acetone. It was very soluble in
dichloromethane. In conclusion, it was slightly soluble in both organic and inorganic solvents.
After that identification of metronidazole was done with the help of IR. The powder sample was
placed on the FTIR surface and the graph produced matched with the standard already present in
the computer. Similarly, when examined in the range 230 nm to 360 nm, a 0.001 % w/v solution
in 0.1 M hydrochloric acid showed an absorption maximum at about 277 nm and a minimum at
about 240 nm, absorbance at about 277 nm, between 0.365 and 0.395. On the other hand,
identification was performed by heating 10 mg in the water bath with 10 mg of Zn powder, 1 ml
of water and 0.25 ml of 2M hydrochloric acid for 5 minutes and cooled. The solution gave the
reaction of primary aromatic amines. An intense orange color was produced as mentioned in the
pharmacopoeia.
QC officer Amit Singh guided me with formulas for creating solutions of particular ppm. These
easily set formulas made my work at QC very easy.
Instruments most frequently used at QC include HPLC, FTIR, pH meter, Dissolution apparatus,
Disintegration apparatus etc. Apparatus mostly used include test tube stand, bunsen burner,
beakers of different sizes, RB flask of different sizes, test tubes, litmus paper, weighing machine
etc.
3.1. Functions of QC:
QC is one of the most important department at the pharmaceutical industry. QC performs all the
analysis after which each department proceeds with their work. QC performs the stability testing
upon the formulation produced by R&D. Only after this testing can R&D proceed with obtaining
the necessary license and registration for the new product. QC performs all the sample tests

17. 17
according to which the storage department classifies the products received or begins dispensing
for the production of bulk quantities. QC person is necessary while sampling and dispensing.
Kishor Chaudhary does this job at Aadee industry and does it well. Moreover, QC performs all
the tests on the packaging material according to the SOP developed by the company and passes
or denies the packaging material. So, QC stands as the most crucial department at the
pharmaceutical industry.
QC has to perform water analysis on the daily basis. Water is used almost everywhere in the
pharmaceutical industry and it is vital that it falls within the limit determined by the company.
QC also performs the documentation of each and every analysis that take place at the facility.
Most of these documents are preserved for at least 5 years and later shredded or destroyed
according to the decision of QA. Recently, documents were destroyed by fire at Aadee. It took a
whole day for several staffs to help them do so.
QC also manages regular pest/insect control. Most of these are done on Friday at the closing time
so that the effect of insecticide is completed on Sunday by the office time. Insects like
cockroaches and pests like rats are strictly prevented to enter pharmaceutical facilities for many
reasons.
3.2. Raw material analysis is one of the most important functions of QC.
At this moment in time, raw materials are not produced in Nepal. Most of the actives are
received from nations like India and China. In this case, the raw material analysis becomes
vitally important. Some of the time products are sent that have expiry date earlier than expected.
In this case, storage department regularly sends samples to QC to make sure that the products are
properly arranged. If QC does not approve certain product, storage department categories it
accordingly so that unapproved material does not go for production. Amit Singh led me to
multiple SOPs prepared by the company for the raw material analysis. This were to be strictly
followed by the staff's performing analysis.
Microbiology section:
There was a separate section at QC where the entrance was strictly prohibited except for the
analyst in essential cases. This was called microbiology lab. There was separate aprons and
gloves to enter into this department to avoid cross-contamination. This was the place where
organism cultures were done. There was laminar hood, autoclave, petri-dishes etc. in this
section.

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Although there was no work at this spot during my stay at QC, it has responsibilities of
performing microbial tests, antibiotic assays and microbial content of the environment. So, it was
segregated as a very sensitive area even within the QC. There was a refrigerator and incubator in
this section as well. I was instructed many times not to enter this section by the QC officer and
analysts there.
Besides, instrumentation section of the QC contained instruments like weighing balance,
potentiometer, hardness tester, friability tester, potentiometer, disintegration test apparatus, tablet
dissolution apparatus, tablet density test apparatus, digital vernier caliper, flame photometer,
polarimeter, melting point test apparatus, Karl Fischer titrator, UV visible spectrometer, FTIR,
HPLC etc.
Chemical analysis room of the QC contained water bath, fumes hood, magnetic stirrer, sonicator,
separating funnel, pH meter, centrifuge machine, vacuum pump, condenser, oven, muffle
furnace, several chemicals etc.
Stability testing chambers contained real time and accelerated stability testing machines.

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4. Store Department
This was where I learned a lot about abbreviations used at the industry like TR, RT date,
difference between PEG-400 and PEG-4000 etc. Sushant Pokharel led me to multiple SOPs that
included instructions for dispensing, documentation, operation of Bug Zapper etc.
I was sent to production department along with non-technical workers of store for sampling and
dispensing on two separate days. In this was I was able to observe in person the operations that
are conducted during these sensitive procedures.
Raw materials were classified at the store as actives, excipients and liquid/gels in separate
columns. The blister packaging was stored at a separate room. The packaging's that required
refrigeration were stored in the refrigerator.
Refrigerated packing materials at the store
There is a dispensing box using UV radiation connecting the dispensing booth of the production
department with the store department. At least 30 seconds of exposure to UV in the dispensing
box disinfects most of the microorganisms present in the packaging materials.
Depending upon the type of raw material, they come packaged in different types of jars, plastic
bags or sacks. Some of the raw materials may be borrowed or bought from the nearest
pharmaceutical company for the prompt use in case ordering raw material from abroad. One such
case was present while I was there. Florid laboratory located in Gyaneshwor had confirmed that
they had such products that Aadee needed at that moment.

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4.1. Store room/ Raw material classification
One whole section in the store room was dedicated to storing ORS raw materials that included
sodium chloride etc. ORS is highly demanded in the summer season called “Jivan Jal” in Nepali.
This is one of the most popular products for conditions such a diarrhea, dehydration etc. This
product is also popular among children in Nepal.
Store room non-technical staffs were also actively involved in helping QA officer at the final
packaging section(secondary store or finished good store) by performing checks on the final
products, their expiration date, manufacturing date on primary and secondary packaging
materials. They also helped count products in each box to assure that they do not contain less,
more or damaged products.
QA officers like Ronash Shrestha came to the final packaging room for this purpose on a daily
basis.
QC attaches green stickers in the case of approved products, they attach red stickers in the case
the test fails. In this way, the labelling with different color stickers helps store to quickly pick up
the materials when needed or segregate them at the store. This term segregation is widely used at
the store.
Different sorts of drugs were handled differently at the store:
a. Stored in the refrigerator: Actives like Mupirocin, Bacitracin Zinc, Polymixin B-
Sulphate, Halobetasol, Butenafine HCL etc. were stored in the refrigerator.
b. Protected from light: Light sensitive drugs like rabeprazole, Ilaprazole, Duloxeteine
HCL, Tretinoin, Mometasone, Hydroquinone, Ferrous Ascorbate, Lornoxicam, Leflunomide
etc. were protected from the light. While sampling or dispensing, they were kept in dark-
black colored or amber colored polybags. If necessary, they were packaged in aluminum
foils.
c. Protect from moisture: Drugs like rabeprazole sodium, Ilaprazole, Doxycycline, folic
acids etc were protected from the moisture. They were stored in a double layered polybags in
a well closed container. Often, silica gel pouches were placed between polybags and
container. Silica is a good absorber of moisture.
d. Materials with pungent odor or eye irritation: Drugs like terbinafine, salicylic acid,
miconazole nitrate, Doxycyline Hyclate, Levocetrizine HCL, Mefenamic acid, Benzoyl
peroxide etc. were handled with extra care using proper masks and safety goggles.

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e. Volatile materials: Volatile materials like Camphor and menthol were stored in double
layered polybags in tightly closed containers at room temperature.
f. Active liquids were handled with proper gowning using apron, gloves, goggles, and
mask. They were stored at room temperature in closed containers.
g. Excipient solids were stored in closed containers, stored in cool and dry places. They
were protected from moisture. Proper gowning were used during this process.
h. Moisture sensitive materials like carbomer 940, carbomer 980, HPMC 100, HPMC 15U
were stored in double layered polybags in well closed containers. Silica gel packs were
placed in between polybags and containers when necessary.
i. Materials provoking allergic reactions like Chlorocresol, BHT, BHA were handled after
proper gowning. Direct contact with eye and skin was avoided. If allergic reaction was seen,
immediately first aid treatment was performed after ablution with water.
j. Materials with pungent odor and eye irritation like sodium lauryl sulphate and sodium
metabisulfite were handled with proper gowning, gloves etc.
k. Excipient liquids were handled in air tight containers at room temperature using proper
gowning.
l. Volatile and inflammable materials like IPA were handled using aprons, gloves and
masks.
m. Liquid perfumes were handled in air tight containers protecting from the sunlight at cool
place preventing direct contact with eyes and skin.

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5. Quality Assurance Department
In this way, all the departments are highly inter-related. One cannot do without the other. So, the
better the relationship between the department heads/officers, the effective the work will be. The
internal phone networks help make the communication between departments quick and easy.
QA includes QC plus all others activities connected to it. Thus, QA is the head department as far
as the industry is concerned. They deal mostly with documenting all the activities that take place
throughout the company including the SOPs, checks payable, recruitment etc. QA has a manager
(Prashant Basnet at Aadee) and QA officers(Ronash Shrestha at Aadee). QA officers deal with
the most of the problems like ensuring the finalization of the bulk production and take the matter
to QA manager only if they doubt their decision or cannot make the final decision.
QA also executes the final shredding of most of the documents after 5 years have passed. QA is
actively engaged in supervising at every bulk production and dispensing at production
department. QA is the department that ensures the execution of GMP rules at each and every
department beginning with QA itself. Documentation, that is, do what you write and write what
you do is strictly enforced by QA throughout the industry. Documentations received from each
department are thoroughly reviewed and then sent for processing in proper file cabinet.
Some of the most important functions of the QA are as follows:
1. Batch release: After the certain batch is produced, it is kept separate from others at the
final goods store. It is the duty of QA officer to perform all the examination of the batch that
is being released. For this purpose, QA officer along with the store staffs examines each and
every product for the labelling, packaging and quantity. Market retail price, MRP, is set so
that the product is not sold in the market by anymore at price more than set by the company.
Any person or pharmacy that sells the product at price higher than MRP is liable to be
punished by law if reported. For this purpose, the QA manager regularly supervises
throughout all departments to ensure that batch release is perfectly done at all times.
2. Approval: Approval of QA is required by each and every department. Approval is the
green light from QA to go ahead with the process whether it be bulk production, packaging
or batch release. Without the QA approval, none of the departments are allowed to take on
any endeavor. In this aspect, QA is the supreme controller at the industry level and the QA
manager is the supreme.

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QA directs the creation of master formulas. The R&D developed master formula is legal at the
company level only after it is approved by the QA. Master formula are the most secret
documents at the industry level. It is an intellectual property of the company. In case it is stolen
by the competition, they will steal all the hard work, expenses, staffs and cost of materials that
were invested in creating that formulation. So, QA ensures that approved master formulas are
kept secret and not divulged to any person than those with officer level authority at the
company.
3. Self-inspection:
On the other hand, QA officer performs all the necessary entries into the DDA portal
http://dams.dda.gov.np/ with the authorized ID just like R&D first enters all the necessary
documents for product registration before submitting them in the paper form in person.
Similarly, QA officers perform all the necessary self-inspection throughout the company and
submit necessary documents online before the inspection arrives at the company in person and
demands necessary documentation. DDA does not renew the GMP certificate every two years if
the company does not pass the inspection.
4. Validation:
Aadee Remedies has a multi-products facility at Imadol, Lalitpur site here in Nepal. This
manufacturing facility is designed as per the GMP in compliance with DDA, Nepal. Validation
Master Plan includes all the matters related to maintaining GMP at the Imadol facility. These
documents and activities include Installation Qualification (IQ), Operation Qualification (OQ),
Performance Qualification (PQ), and Computer System Validation (CSV).
Validation is generally of 3 types:
 Prospective validation: It is the validation that is done prior to the production of
products.
 Retrospective validation: It is the validation done after the production of products and
execution of packaging activities.
 Concurrent validation: It refers to the validation done during the production, during the
analysis at QC, during the packaging or storing of the materials at the store. Concurrent
validation is very vital for the well being of the company on a long term.
Special Validation Plans are developed by the company as and when required as plan the
demands of the people, place and time e.g. Cleaning validation.

24. 24
Validation is a process that ensures the consistency in the all the things done at the company. It
ensures that when the same process is repeated again and again, the consistency remains in all
activities whether it be same staffs or not. In this manner, the new staffs can also follow the same
SOP after many years and produce the exact same result. This is the kind of consistency that
GMP also demands. This is a process through which QA saves time, personnel and money.
Through validation, the same documents do not have to be created again, each new staff does not
need to be trained from zero and the process or master formula does not have to be created again
and again. The same validated instructions can be followed by any personnel and produce the
same exact result. The basic idea behind systematic and scientific study in validation is
duplication. Duplication is the principle that most of the modern franchises are based on where
the same process is repeated at each establishment producing exactly the same result thus saving
time and money. Due to the principle of duplication, the product, personnel, behavior and profit
can be estimated accurately at each franchise.
This is ensured by scientific study to ensure that system, equipment or process meets or exceeds
the expectations of the design, is properly built, operated or maintained, is suitable for its
intended application, conforms to criteria set by GMP, will satisfy the regulatory bodies, and is
capable of operating consistently or produce products of consistent quality.
In order to ensure process validation, multiple observations are done and multiple repetition of
the processes are done. Three repetitions are generally standard requirement for such validations.
Testing and monitoring are also required for extended period of time in controlled environments.
In this way, validations are performed to make the duplication possible.
All the validations are documented, signed and dated. They must be endorsed by the Quality
Unit of the organization in order to put them into effect. At least three approving signatures are
required for these documents to be circulated throughout the company. These signatures include
signature of QA Manager, QC Officer, QA officer etc.
Many guidelines including ICH are studied and followed during validation process. Many
guidelines are examined and the most feasible one is chosen for the particular validation. Process
validation involves the validation of all the SOPs created for each department so that the same
SOP can be repeated again and again producing the exact result whosoever the staff may be.
Failing investigations are recommended to Quality assurance for corrective action via Deviation
Report. Utility validations are equally important. Primary utilities involve compressed air and

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purified water. Secondary utilities involve HVAC etc. These are vital components of the industry
as they are essential to be in operation on a daily basis.
5.1 Process Validation (PV)
PV is establishing documented evidence, which provides a high degree of assurance that process
to produce product A will always consistently and exactly produce the product A meeting its
product specifications and quality parameters.
Analysis of data collected from monitoring will establish the variability of process parameters
for individual runs and will establish whether or not the equipment and process control are
adequate to assure Product A specifications are met. Finished product and in process test data
can be of value in process validation, particularly in situations where quality attributes and
variability can be measured.
There are several risks that must be contained to perform perfect process validation.
Validation documents are separately indexed and classified in a special manner.
Heating Ventilation and Air Conditioning (HVAC)/Engineering and Utility
I was toured out at HVAC section on the very last day by QA officer Ronash Shrestha. HVAC is
a very important aspect at the industrial pharmacy. It ensures the heating and air conditioning at
each department as per the GMP requirements so that products produced meet the standards in
terms of quality, safety, efficacy and management.
AHU-XXX served the Blending Room #1. AHU-XXX served the QC. Similarly AHUXXX
served tablet compression room #1, #2, #3, corridor, staging , wash, and weighing rooms. As
seen in the picture, other served the warehouse area.
HVAC system is set at certain temperature and relative humidity. It is set at least 12 air changes
per hour. Air handlings units digitally adjust themselves according to the feedbacks received
from the sensors and transmitters.
Pre-cooling coil, second cooling coil, after cooling coil are some of the temperature maintaining
systems present in the HVAC. The maintain the programmed supply of right condition air to
each department. Supply air will be filtered using terminal HEPA filter. Return air and exhaust
air from the room will be filtered through terminal HEPA filter. Additional ambient air will make
up for the total predetermined air volume.

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AHU serves all other manufacturing areas like tablet compression room #1, #2, #3, corridor,
staging, wash, and weighing rooms. A main exhaust fan located in the main area of the roof will
serve areas requiring direct exhaust.
Ronash also showed me the water supply upstairs and water purification system downstairs. The
industrial area was not populated so much in the past but in the recent years, it's been populated
with several houses.
For the testing, certification and maintenance of most of the HVAC system and other heavy
equipment, engineers from the respective companies follow up at the company or are sought
out.
Each SOP is created according to the company standards and is provided to the new interns or
newly hired personnel for training purposes. Trained employees are strictly required to follow
the SOP as well.
Training programmes are often organized for new employees. Trainings are obligatory for the
new employees before they begin their task. There are various reasons to do so. Equipment used
for calibration are traced back to National Institute of Meteorology and Calibration.
Calibration is another important aspect of QA. Calibration SOPs are created for this purpose.
5.5 Quality Risk Management
Risk management is a very important aspect at QA. There are various ways of assessing risk at
different departments. Hazard identification in necessary to prevent risks or prepare for the
upcoming disaster. Industry is a very sensitive place where little carelessness might mean loss of
life property. Therefore, risks must be identified and managed. Risk management tools include
failure mode and effect analysis, fault tree analysis, fishbone diagram, CAPA etc.
5.6 Corrective and Preventive Action (CAPA)
Corrective actions are those actions performed after the problem arises. Preventive action is
already predicting the future problems and taking action to avoid them before the problem arises.
This is the major duty of QA officer at an industry. In the case of preventive action, risk is
primarily identified.
Corrective actions are reactive affairs thus they are always inferior to the preventive actions that
are proactively done.
Example can be the case of pest control. Either we can wait until the rats and mice damage our
products at final goods store and call the pest control agency. Or, we can regularly schedule

27. 27
spraying of insecticides and pesticides on a regular basis. This preventive action is taken at
Aadee every few weeks. This way the organization can take proactive stance in each and every
situation rather than wait for the problem to arise. Prevent actions in long term prove to be cost
effective and time saving than corrective actions.
Initiation of CAPA includes a list of activities strictly to be followed by the group of personnel
involved. It includes submission of source document by department head to QA, making a
decision, assigning the source document number, filling up the CAPA form, sending the CAPA
form, forwarding the form, assigning an identification code consisting of department code, serial
number and last digit of calendar year.
Similarly, closure and verification of the CAPA involves a list of procedures to be followed
strictly. They include certifying the document after completion of actions, verifying the
completion and implementation with supporting documents, maintaining the record of
documents, submitting the documents by QA person the management committee during regular
meetings, verification and review by the management and making them available upon approval
by the executive committee only.
5.7 Product Recall and Withdrawal
Product recall and withdrawal refers to the removing or pulling back of a batch or all the batches
of a certain product due to company report of quality of products or DDA notice whether it be
through DDA examination or customer complaint.
This is a very expensive and reputation harming situation for each and every pharmaceutical
company. So, everything is done by the company prior to launching product in the market to
prevent product recall and withdrawal. Aadee in last 8 years does not have more than 1 product
recalled.
For this reason, R&D places the product at accelerated stability testing machine for at least 3
months and performs real time stability after the product is produced in bulk. Any problems seen
in these stability tastings are seriously taken and might even cause company to pull down all the
related batches from the market.
Product recall may be done for various reasons like packaging issues, wrong label, toxicity
reports, ineffectiveness, tablet breakage etc.

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5.8 Equipment qualification (EQ)
Qualification and validation are synonymous terms used at the industry. It allows the trainees,
technical and non-technical workers the execution of installation, operational and performance
protocols. EQ allows proper operation of all the equipment and consistent product of quality
products.
Equipment qualification is done by assembling the validation team, determining the intended
user requirements, conducting risk assessment, conducting installation and operational
qualification, along with requalification review.
In Asia, the vendor validation is usually done on the material while in Europe, vendor
qualification is done in production. In this way, different regions might have different aspect in
which they validate.
Some of the machines that need equipment qualification include blister packaging producing
machine, semi-solid producing machine, compression machine etc. At Aadee, all of these belong
to the production house.
5.9 ICH guidelines
Although all guidelines are reviewed and studied at Aadee, ICH guidelines are primarily
followed by QA officers. ICH guidelines are primarily made by few countries like Japan, USA,
Germany etc. These guidelines are strictly followed in these nations. ICH guidelines strictly
enforce certain principles similar to GMP meant to maintain quality, safety, effectiveness and
management.
R&D(Summary of the process involved in manufacturing of a particular product)
Formulation of a product as directed by the marketing department is done by R&D by studying
research articles and looking for perfect combination in the different pharmacopoeias. After this,
at the R&D lab, the product is created in a small quantity and sent to QC for accelerated stability
testing. After some time, usually 3 months, the product is examined and if found to fulfill the
requirements, the manufacturing license application at DDA is submitted. Product license is
received if the application is approved.
Necessary packaging materials with labelling eg tubes or blisters are then ordered from the
companies in India. After the necessary packaging arrives at the firm, the product department is
commanded to start manufacturing product under the watch of R&D chief. The same process is
duplicated for bulk production in the future.

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5.10 Water Treatment Plant
EWT, Effluent water treatment is highly promoted by DDA as per the GMP requirement to
prevent the industrial water reaching the residential areas and harming the ecosystem. Thus,
water is treated inside the industry territory and is converted by the plant into non-toxic water
before leaving the industrial area.
Water received via tanker passes through these series of systems and are processed well to make
it usable for the industrial purpose as seen in the picture. Water Treatment Plant runs 24 hours at
Aadee. I had an opportunity to view the system along with the tank upstairs.
5.11 Chiller
Chiller is a machine that maintains the necessary refrigeration irrespective of the weather
conditions. During winter when HVAC cannot maintain the necessary conditions, chiller does its
work. Vapor compression chillers move the refrigerant around the system by using electricity.
Vapor absorption chillers move the refrigerant around the system by using heat energy.
Chillers at Aadee work in conjunction with HVAC system as shows in the diagram.
5.12 Air Compressor
It is a device that converts air into potential energy stored in pressurized air. It forces more and
more into storage tank thus contributing to air pressure increment.
Compressors are similar to pumps as they both can compress the fluid thus increasing its
pressure and make it flow through the pipe.
5.13 Generator
Generator is an essence at a nation like Nepal where the electricity supply is not durable and load
shedding is a regular occurrence. In this situation, if we only depend upon the electricity supplied
by Nepal Electricity Authority, Lalitpur, then the pharmaceutical industry will go in disorder.
Thus, for the constant supply of electricity irrespective of power line supply especially at HVAC
system and water treatment system, generator is of vital importance.
Generator automatically stores the electricity and supplies it to the circuit without break during
the power outage.

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6. Conclusion
My internship at Aadee was meant to fulfill the requirements of Pokhara University for
graduation. However, I had an opportunity to learn a lot on hand about the field I was going to be
involved in the future. I had a chance in person to know a lot more about industry than the
industrial tour from college to Chitwan based pharmaceutical industries.
Overall at every department, I had a chance to perform analysis individually than at college
where due to limited resources and a large group it was not feasible to do each process by
myself. I had wonderful co-operation from staff at Aadee. They poured out there knowledge to
me more than I was capable of grasping.
Overall, I had a wonderful time at Aadee.
7. Suggestions:
I think Aadee should encourage each and every personnel at its facility to take CAPA on a
regular basis. In this way, the staff will also feel a sense of ownership at the place they are
working. They might even come up with corrective and preventive actions that are far superior
than those coming from officers at higher positions. Suggestions boxes might be placed at some
place inside the company where such staffs or even the visitors can place their ideas.
Administration might save millions of rupees with a single good idea coming from an individual
that just passed by the company.
I liked how QC officer scheduled tasks for each assistant/analyst every morning and let them
enjoy spare time if they finished their task on hand. If the same process would be duplicated at
each department, the productivity of the organization would rise greatly.

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8. References:
Remington The Science and Practice of Pharmacy
ICH Guidelines
https://www.pharmaguideline.com/2010/12/qualification-of-systems-and-equipment.html
Granulation states picture reference
http://www.pharmatips.in/Articles/Production/Granulation-Particle-Bonding-Mechanism-
Process.aspx
CAPA
https://www.pharmaguideline.com/2011/07/corrective-and-preventive-actions-capa.html