AADEE REMEDIES PVT. LTD, IMADOL, LALITPUR
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Feb 26, 2022
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Slide Content
INPLANT TRAINING AT AADEE
Submitted by
Neeraj Ojha
CIST College, New Baneshwor
Affiliated to Pokhara University
To
Prashant Basnet
QA Manager
Aadee Remedies, Imadol, Lalitpur
Submitted by
Neeraj Ojha
CIST College, New Baneshwor
Affiliated to Pokhara University
To
Prashant Basnet
QA Manager
Aadee Remedies, Imadol, Lalitpur
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 QC 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.
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 QC 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.
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
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
CERTIFICAFTION
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 4
th
2078 and ended on Magh 4
th
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 Officer
.............................
Sunandan Poudel
Sr. Production Officer
............................
Sujan Karki
Jr. Production Officer
............................
Sandesh Khatri
R&D Officer
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 4
th
2078 and ended on Magh 4
th
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 Officer
.............................
Sunandan Poudel
Sr. Production Officer
............................
Sujan Karki
Jr. Production Officer
............................
Sandesh Khatri
R&D Officer
Table of Contents:
Company Profile Information
Objective of internship
Abbreviations
•Production
•Quality Control
•Store & Generator
•QA-R&D
•Summary of process involved in manufacturing of a particular product
•Water Treatment Plant
Engineering and Utility
Air Compressor
Generator
•Conclusion
Suggestion
References
Company Profile Information
Objective of internship
Abbreviations
•Production
•Quality Control
•Store & Generator
•QA-R&D
•Summary of process involved in manufacturing of a particular product
•Water Treatment Plant
Engineering and Utility
Air Compressor
Generator
•Conclusion
Suggestion
References
1. Company Profile Information:
Aadee remedies pvt. Ltd. Is a pharmaceutical company established in 23
rd
Ashoj 2060 B.S. and started its
operation from 11
th
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
Aadee remedies pvt. Ltd. Is a pharmaceutical company established in 23
rd
Ashoj 2060 B.S. and started its
operation from 11
th
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.
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;
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.
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.
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.
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.
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.
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.
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.
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.
After sieving
Mixing before sampling the granules
Mixing before sampling the granules
Granulation room and equipments
Fig. Granulation flow diagram
2.1 Weighing and dispensing:
Fig. Granulation flow diagram
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 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.
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
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 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.
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 turbula 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.
2.3 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.
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
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 turbula 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.
2.3 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.
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 some times
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:
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:
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 some times
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:
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
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 can not do so most of the time.
Equipment available at Production:
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
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 can not do so most of the time.
Equipment available at Production:
Tablet Compression machine (Upper punch, lower punch, Lower and Upper Cam track)
Digital weighing machine
Computer/Internet
Sieves used during granulation
Quarantine jars and plastic bags
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
No table of contents entries found.
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
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
No table of contents entries found.
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 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.
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 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 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.
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 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.
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.
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.
5. 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.
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.
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.
5. 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.
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.
5.1 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.
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.
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.
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.
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.
6. 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
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.
6. 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.
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.
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
supreme controller at the industry level and the QA manager is the supreme.
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.
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 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.
6.1 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
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 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.
6.1 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
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.
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.
6.2 VALIDATION MASTER PLAN Template
PRODUCT X MANUFACTURING FACILITY
Table of Content Page
I. Introduction
II. Scope
III. Validation
IV. Facility Description
V. Process Description
VI. Utility Systems
VII. Process Equipment
VIII. Control System
IX. Responsibilities
X. Project Schedule
XI. Other GMP Programs
volume.
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.
6.2 VALIDATION MASTER PLAN Template
PRODUCT X MANUFACTURING FACILITY
Table of Content Page
I. Introduction
II. Scope
III. Validation
IV. Facility Description
V. Process Description
VI. Utility Systems
VII. Process Equipment
VIII. Control System
IX. Responsibilities
X. Project Schedule
XI. Other GMP Programs
XII. Reference Documents
XIII. Terms & Definitions
XIV. Appendices
6.3 Management Review
Approved by Signature Date
VALIDATION MANAGER
FACILITY, UTILITY AND
EQUIPMENT QUALIFICATION
MANAGER
COMPUTER VALIDATION
MANAGER
PRODUCT TRANSFER,
PROCESS AND CLEANING
VALIDATION MANAGER
MANUFACTURING MANAGER
PROJECT MANAGER
PLANT ENGINEER
QUALITY ASSURANCE
MANAGER
XIII. Terms & Definitions
XIV. Appendices
6.3 Management Review
Approved by Signature Date
VALIDATION MANAGER
FACILITY, UTILITY AND
EQUIPMENT QUALIFICATION
MANAGER
COMPUTER VALIDATION
MANAGER
PRODUCT TRANSFER,
PROCESS AND CLEANING
VALIDATION MANAGER
MANUFACTURING MANAGER
PROJECT MANAGER
PLANT ENGINEER
QUALITY ASSURANCE
MANAGER
6.4 GENERAL VALIDATION SCHEDULE & RESPONSIBILITIES
Programme Responsibili
ty
Week
1 2 3 4 5 6 7 8 9 10
1 Establish
Scope
Plant
manager
2 Consult FDC Plant
manager
3 Establish
validation
master
plan(VMP)
Plant
manager
4 Calibrate
laboratory
instruments
QC
5 Validate
analytical
methods
QC
6 Appoint
external
contractor for
IQ & OQ
Plant
manager
7 Collect
document (on
facility,
utility,
systems etc.)
Engineering
8 Establish IQ
protocol
Engineering
*Concept
*Review &
approval
9 Establish OQ
protocol
Engineering
10 Establish PQ
protocol
Production
*Concept
*Review &
approval
11 Establish
validation
performance
QA
12 Training on
GMP, SOPs
& protocols
QA
13 Preparation of
list of
equipment &
instrument for
calibration
QC &
Production
Programme Responsibili
ty
Week
1 2 3 4 5 6 7 8 9 10
1 Establish
Scope
Plant
manager
2 Consult FDC Plant
manager
3 Establish
validation
master
plan(VMP)
Plant
manager
4 Calibrate
laboratory
instruments
QC
5 Validate
analytical
methods
QC
6 Appoint
external
contractor for
IQ & OQ
Plant
manager
7 Collect
document (on
facility,
utility,
systems etc.)
Engineering
8 Establish IQ
protocol
Engineering
*Concept
*Review &
approval
9 Establish OQ
protocol
Engineering
10 Establish PQ
protocol
Production
*Concept
*Review &
approval
11 Establish
validation
performance
QA
12 Training on
GMP, SOPs
& protocols
QA
13 Preparation of
list of
equipment &
instrument for
calibration
QC &
Production
14 Perform
calibration
QA
Lab.
instruments
QC
Production
equipment
Production
15 Establish
SOP, Change
control
QA
16 Performance
of IQ
Engineering
Facility
Utility
Equipment
17 Revise IQ QA/Engineeri
ng
18 Performance
of OQ
Engineering
*Utility
*Equipment
19 Revise OQ Engineering
20 Performance
of PQ/Process
validation
Production
*Equipment/S
ystem-
placebo
21 Revise
PQ/Process
validation
Production
22 Prepare
validation
report
QA
23 Approval/Cer
tification
QA & plant
manag.
Prepare by:
Date:
Checked by:
Date
Authorized by:
Date
No:
Date:
Supersedes No:
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.
calibration
QA
Lab.
instruments
QC
Production
equipment
Production
15 Establish
SOP, Change
control
QA
16 Performance
of IQ
Engineering
Facility
Utility
Equipment
17 Revise IQ QA/Engineeri
ng
18 Performance
of OQ
Engineering
*Utility
*Equipment
19 Revise OQ Engineering
20 Performance
of PQ/Process
validation
Production
*Equipment/S
ystem-
placebo
21 Revise
PQ/Process
validation
Production
22 Prepare
validation
report
QA
23 Approval/Cer
tification
QA & plant
manag.
Prepare by:
Date:
Checked by:
Date
Authorized by:
Date
No:
Date:
Supersedes No:
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.
6.5 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.
6.7 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 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.
6.8 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.
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.
6.5 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.
6.7 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 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.
6.8 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.
6.9 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.
6.10 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.
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.
6.9 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.
6.10 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.
6.11 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.
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.
6.11 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.
6.12 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.
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.
6.12 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.
6.13 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.
6.14 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.
7. 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.
At QC, 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.
8. Suggestions:
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.
6.14 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.
7. 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.
At QC, 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.
8. 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.
Similarly, during my stay at the company, it was Sujata Dahal’s birthday and Amit Singh’s first
anniversary at Aadee. If there was a department or a person assigned to celebrate each staff’s important
day, they would feel a belonging to the organization and work harder on their tasks. This sort of culture
was not seen at Aadee where each person was treated like a person. Employee's loyalty could be earned
in this sort of behavior.
9. 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
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.
Similarly, during my stay at the company, it was Sujata Dahal’s birthday and Amit Singh’s first
anniversary at Aadee. If there was a department or a person assigned to celebrate each staff’s important
day, they would feel a belonging to the organization and work harder on their tasks. This sort of culture
was not seen at Aadee where each person was treated like a person. Employee's loyalty could be earned
in this sort of behavior.
9. 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
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