in-plant tarining report on acme

8/11/2019 In-Plant Tarining Report on ACME

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The ACME Laboratories Ltd

Submitted To:

The ACME Laboratories Ltd.

Submitted By:

Md. Hasif SinhaFarjana Yasmin

Taslema Khandaker

Stamford University Bangladesh



In-plant training program p age no . 1

We are the students of Stamford University Bangladesh, have the privilege to

express our cordial thanks to the following authority of the ACME-

1) Md. Dabir Uddin (Executive Director, Factory)

2) Md. Rafiqul Islam (Director, Marketing & Sales)

3) Asif Ainul Haque (Head of HR Division)

4) Md. Moklesur Rahman Bhuiyan (GM, Plant)

5) Md. Mahfijur Rahman (Product Development Manager)

6) Khandoker Mahbubul Haque (QO, Manager)…………& all the employees of the ACME……for their nice co -operations.

A ACCK K NN OO WW LLEEDDGGEEMMEENNTTSS




CHAPTER 1: INTRODUCTION

TOPICS PAGE NO.

INTRODUCTION

COMPANY HISTORY

THE PLANT

ACME‟s GLOBAL OPERATION

FOUNDERS

THE OVER ALL FUNCTION OF A PHARMACEUTICAL

COMPANY

CHAPTER 2: P RODUCTION DEVISION

TOPICS PAGE NO.

QUALITY OPERATION

PRODUCT DEVELOPMENT DEPERTMNT

TABLET SECTION

ORAL LIQUID SECTION

DRY SYRUP SECTION

CREAM AND OINTMENT

INJECTABLE SECTION

INHALER AND SUPPOSITORIES

CAPSULE SECTION

WARE HOUSE

CCOO NN TT EE NN TT SS




CHAPTER 3: MARKETING DEVISION

PRODUCT MANAGEMENT DIVISION

S UGGESTION C ONCLUSION




Subject like Pharmacy demands practical knowledge in the own field. Thus industrial

training program is one of the most important parts of a students studying in a dynamic

subject like Pharmacy.

As per the course outline of Bachelor of Pharmacy (Hons.) degree of Pharmacy

Department of Stamford University Bangladesh every graduation student must carry on

in-plant training in any industry. I am very lucky to get the opportunity of training in a

burgeon drug producer of Bangladesh- The ACME Laboratories Ltd . which is also

internationally renowned. My training period taught me that only theoretical knowledge is

not enough for proper understanding. I got my training in the Dhamrai plant of The

ACME Laboratories Ltd . This plant is really well equipped with state-of-art

technologies, which not only ensure the highest quality of medicine but also contribute to

the future development of medicine in Bangladesh.

I have gone through the books about the machinery of drug manufacturing. I heard

about the quality control, quality assurance etc. but when I were in the plant I realized

that only academic knowledge is not enough to be a good pharmacist. After the

completion of 4 weeks in-plant training in The ACME Laboratories Ltd . I found myself

as the pharmacist with practical experiences, because in the plant I have seen more

than what I had learnt.

II NNTTR R OO DDUUCCTTII OONN




The history of ACME Laboratories Limited dates back to 1954 when a proprietorship

firm was conceived to manufacture ethical drugs. It started with the modest introductionof a few oral liquid products. Late Hamidur Rahman Sinha was the founder of the firm

and had been the main visionary of the organization since its inception until his sad

demise in 25 th February, 1994.

After its initial years of trials and tribulations, the firm was converted into a Private

Limited Company in the year 1976 and the Balancing Modernization, Replacement and

Expansion (BMR&E) work on the small old unit started in 1976 at a large new premise

at Dhamrai, Dhaka.

Commercial Operation of the new modernized plant equipped with sophisticated and

advanced facilities began toward the end of 1983. Many challenges were faced and

overcome successfully to transform the company from a very small unit to what it is

today a giant in its field.

ACME‟s modernized plant is located at Dhamrai, about 40 km N. W. of Dhaka, the

capital of Bangladesh. While designing & constructing the plant, proper attention was

paid to the latest concepts of cross contamination, air circulation & air handling, particle

free finishes, equipment layout, process flow, hygiene & safety. Special care has been

also given in selecting machineries & laboratory instruments. The plant has the mostsophisticated equipments & machines. As a whole, ACME‟s plant is a testimony to its

basic commitment for manufacturing the highest obtainable standard of ethical drugs.

CCOO MMPP A A NN Y Y HHII SS TTOO R R Y Y

TTHHEE PP LL A A NNTT




ACME‟s success in the domestic market promoted it to explore the international market.

With the philosophy of ensuring health, vigour & happiness for the whole mankind, ACME started its international business operations in 1995 by exporting medicines to

Bhutan. Since then, ACME made a strong presence in the international market. At

present, ACME is successfully exporting its quality medicines to Nepal, Bhutan,

Myanmar, Afghanistan, Pakistan, Sri Lanka, Philippines, Vietnam, Hong Kong, East

Timor, Papua New Guinea & Kenya.

ACME now dictates a very good share of pharmaceutical business in the international

arena by stepping into the markets in Asia, Africa, CIS, Middle East & Latin America.

Born in the year of 1914 and educated in Calcutta University, Late Late Hamidur

Rahman Sinha passed through several fields of activities of profession and business to

ultimately become on industrialist. In 1954, he took interest in the manufacture of

pharmaceutical items and established a propietorship concern under the name and style

of ''The ACME Laboratories'' . In 1976 the firm was converted into a private limited

company. Since then he had been acting as a Managing Director and in 1987 became

the Chairman of the company. Our beloved founder - Chairman expired on 25 February

1994.

Late Nurjahan Sinha, beloved wife of the Founder, was the inspiring figure for

intablishing the company. ACME's today's success would never have been possible

without her devotion, dedication, sacrifice and above all mental support in all hr lifetime.

FFOOUUNNDDEER R SS

A A CCMMEE'' SS GGLLOOBB A A LL OO PP EER R A ATTII OONN




METHOD DEVLOPEMENT

Injectables

TTHHEE OO V V EER R A A LLLL FFUUNNCCTTII OO NN OO FF A A PP HH A A R R MM A A CCEEUUTTII CC A ALL CCOOMMPP A A NN Y Y

Drug AdministrationManagement

PMD

PDD

Ware houseDry syrup

Inhaler &su ositories

Liquid

Capsule

Tablet

Cream & Ointment




Duration of Training : Five Days

Introduction :

Once upon a time when only ultimate goal of any business company was to be beneficial

but at this modern age this idea is changed. Now the vision of any company is to provide

quality products to the customers and beneficial simultaneously. As The ACME

Laboratories Company is the leading ethical drug producer of Bangladesh, they alwaystry to provide quality product to the customers and this foremost effort done by Quality

Operation Department. Quality Operation Department has two sectors. These are

Quality Assurance and Quality Control.

QA may be defined as the responsibilities of an organization to determine that the

system, facilities and written procedures are adequate and followed in order to assure

that the products are controlled and will meat, in the final dosage form, all the applicable

specifications. Thus QA is a preventive development process.

The Quality Control Department of ACME monitors each step of manufacturing

operation and adopted “Good Laboratory Practice (GLP)” to ensure reliability a nd

accuracy of the Pharmaceutical product. The department is subdivided into different

section so as to ease and facilitate documentation and proper operations. The sections

are:

Raw materials section

Oral liquid section Tablet section

MDI and DPI & HPLC section

Capsules, Ointment, Cream section

IR section

Microbiology section

Packaging section

PP R R OO DDUUCCTTII OONN DD II V V II SS II OONN

QQ UU A ALLII TT Y Y OO PP EER R A ATTII OO NN DDEEPP A A R R TTMMEENNTT [[ QQ OO]]




Activities of Quality Assurance(QA) Department:

Raw Material Section:

Raw Material Procurement and Analysis

Demanding of raw materials (Demanded by production according to the needs through

commercial dept.)

Source approval

Raw materials received

Raw materials in quarantined area

QC sampling

Rejected Under test

Destroyed QC passed (Green tag)

Documentation Stored in passed area

Retest

Dispensed

Documentation

Quality Assurance (QA)

Chemical Test Physical Test Microbiological Test

Microbiological limit test Antibiotic assay




Various test involved in raw materials analysis :

● Identification ● Solubility ● Appearance of the solution ● p H

● Melting point limit ● Loss on drying ● Bulk destiny ● Mesh size

● IR spectroscopy ● UV spectroscopy ● HPLC ● Optica l rotation

● Water content ● Potency determination ● Microbiological test

Oral Tablet Section:

Observed Material: Paracetamol

Use: Antipyretic

Appearance: Almost white

Test:

1. Identification:

Small amount of sample was taken in a test-tube & dissolve in conc. HCI Add K 2Cr 2O 7 (8-10ml)

Greenish color

2. Moisture content: 4.37%

3. Assay: Assay of Paracetamol by UV spectroscopy

0.1500gm sample + 5 ml 1M NaOH solution

Shake for 20min

Volume it 200 ml with water

10 ml

100 ml with water

10 ml solution + 1 ml 1M NaOH + 80 ml water

4. Data for calculation:

Wave length : 257 nm

A (1%, 1cm) : 715

Abs. Of sample (Au) : 0.533

% of paracetamol:

Abs of sample ×200×100×100×10 A(1%, 1cm) ×0.533×100×10×10

0.533×200×100×100×100=

715×0.533×100×100

= 99.33%

So potency of Paracetamol was found to 99.33% (Limit 98-102%).




Oral Liquid Section:

This section monitors all the in process quality control process as well as gives the final

clearance for the finished product to be sold in the market. In process quality control

exercises by this section are:

● Appearance Potency determination ● Viscosity ● p H

● Taste, odor and flavor ● color

The QA in liquid section involves-

I. Before starting compounding or filling, the machines and rooms are checked forproper cleaning.

II. During manufacturing/filling/packaging the products are checked for properweight, volume, scaling etc. at regular intervals

III. At regular intervals bottle washing and drying are checked.

Assay of Leo-500 (Levofloxacin):

1. Sample preparation: 1ml

0.0250g sample + 200ml 0.1N HCl Volume it 100 ml with 0.1N HCl

2. Data for calculation: Wavelength: 292 nm

Abs of Sample: 0.460 Abs of Standard: 0.430

Potency: 95.78%% of Levofloxacine:

Abs of sample×200×100×w std ×2×Potency

Abs of Std.×W sam ×1×100×100

0.460×2×0.0253×2×95.78=

0.431×0.1346

= 76.86%

Content of Levofloxacin:

76.86×Average Weight=

100

76.86×670=

100=514.96 mg

Limit: 490.00-537.00




Microbiology Section: Among all other sections of QA this section is the most sensitive one. This section plays

a vital role in producing a quality product as it cheeks all the parameter related with

manufacturing a quality product in a clean and healthy atmosphere.

There are two categories of test is done by microbiology section are

1) Sterility test for injectable items, eye drops and such types of products.

2) Limit test for other products

The equipments used by microbiology department are:

• Incubator • Microcope • Deluxe Colony counter

• Laminar air • Liquid particle analyzer • Turbo meter • flow station

Injection Section is closely monitored by microbial section .This section monitors

all the in process quality control measures in the production of Injection. This includes:

Monitoring the clearing procedure of compounding and filling rooms according to

SOP

Checking the integrity of the membrane filter by performing bubble point test.

Potency determination

Volume adjustment

Maintenance of aseptic area

Monitoring the sterilization of products

Monitoring the p H of a product etc.

Packaging and Packing Section:

This section deals with the checking of procured packaging and packing materials as

well monitors the proper packing of finished products for their correct label, batch

number, manufactured and expiry date. The tests that are exercised by this section for

packing materials are:

Product Test

PVC and PVDC Color, width, thickness, weight per unit area etc.

Cotton Appearance, weight, moisture content sulfated

Shipping cartoon Weight, dimensions and thickness

Inner cartoon Height and level, description (text, color, general appearance)

weight etc.

Plastic cap Appearance, weight, length, diameter, volume capability

Dropper Appearance, weight, length, capacity, adaptability, with bottle

cartoon and Plastic cover




Product Test

Bottles, ampoules

and vials

Height, neck diameter, weight, volume capacity, light

transmission test, machine acceptance etc.

Ointment, Creams, Dry Syrup and Capsules Section:

Ointment and creams are checked for their microbiological contamination as will as to

find the grittiness; capsules are assayed as per the specification which includes

parameters such as weight variations, size, potency, disintegration etc. Dry syrup are

checked by regular sampling of the bottles, their qualitative and quantitative assay are

checked and finally that proper sealing the cap is monitored.

Equipments observed in QA department:

1. Analytical balance (METTLER)

2. Dissolution tester (ERWEKA)

3. Disintegration tester (ERWEKA)

4. Hardness tester (ERWEKA)

5. Friabilator (ERWEKA)

6. Microprocessor p H meter

7. 0.5µ particle counter

8. Polarimeter

9. UV visible Spectrophotometer (SIMADZU)

10. Carl Fischer titrator (METTLER)

11. Analytical balance (SARTORIUS)

12. Moisture analyzer

13. Sonicator

14. Leakage test apparatus

15. Water bath

16. Shaker

17. Drier

18. HPLC (WATERS and SHIMADZU)

19. Destiny measurement apparatus

20. IR machine

Documentation:

The ACME Laboratories Ltd . records all the necessary information and documents in

order to ensure the availability of all the date required for manufacturing packaging,

quality control and the records the history of the batch. Such as raw materials analytical




sheet, packaging material analytical sheet, certificate of analysis of raw materials,

finished products analytical sheet, material requisition sheet.

During of training: One day

Introduction:

For a pharmaceutical company, Research and Development (R&D) is the indispensable

component needed to ensure steady growth and improvement. If anyone want to know

about production process of any product, then PDD able to give a to z idea about that

product. Product development department virtually is the department, which is liable for

the development of a product. This department is regarded as the mini production floor.

This department formulates new drugs and plays the vital role for the development and

the improvement of the quality of the existing drugs and for the establishment of new

drugs. Moreover, any problems during manufacturing, PDD moves forward and solve it.

PDD handles the following functions as mandatory:

1. New products formulation

2. Reformulation

3. Reprocess

4.Trouble shooting

5.Preparation of B.P.R for new prod.

6.Developements of exiting product.

1. Development of new products:

Step-1: Product information from marketing along with the necessary attributes such as

Source→Sample→Q.C test (Potency), LOD etc.

Step-2:

→Pre -formulation study of the active drug and exicipent.→The active drug and exicipent.

→Chemical activity

→Function

→Moisture conte nt etc.

→Interaction

→Boiling point

→Contraindication

Step-3: Collection of raw material of active drug and exicipent.

PP R R OODDUUCCTT DDEE V V EELLPP OOMMEENNTT DDEEPP A A R R TTMMEENNTT [[ PP DDDD]]




Step-4: Different trials for development of a stable, effective and active formulation.

Step-5: Drug administration formalities include:

a. Submission of recipe of drug administration which contains

1. Strength

2. Dosage form3. Dissolution

4. Precaution

5. Slide effect

6. Indication

7. M.R.P

b. Sample submission for INN products.

c. Approval of sample from drug administration and inclusion of D.A.R and

d. Submission of inclusion dossier.f. Final approval of commercial production.

Step -6 : Pilot trial and accelerated stability.

Step -7: Readjustment if necessary.

Step-8: BPR preparation if every aspect is satisfied which contains

→Product name →Theoretical yield

→Code →Batch size

→Size →Annexure etc.

Step-9: Transfer to the commercial product.

2. Reformulation: It is done for three reasons-

i. For further improvement of product quality

ii. To increase productivity

iii. For more cost effective formulation maintaining quality

3. Rerocessing:

If the chemical assay by QA for a particular batch don‟t comply the standard, then PDD

will check the batch and take necessary action following approved SOP and discussion

with QA.

4. Trouble Shooting (Problem solving related to formulation &

manufacturing, when obligatory):




During production PDD, QA, production department investigate the cause of formulation

defects and take necessary steps accordingly.

5. Preparation of Master Formula for a new product:

Among many important functions, preparation of master formula is very important duty of

the PD department. This document contains all the records regarding raw materials,

procedure, packaging and quality assurance profile of product.

6. Development of Existing products:

Product development department also deals with the development of the

existing product formulation.

Increasing the quality of a product.

Prevention of any type of problem existing in the product.

To minimize process time and cost maintaining quality.

Increasing the patient acceptance.

Machineries used in PDD:

o Balanceo Oveno Accelerated stability testero P H metero Stirrer Propellero Coating machine (NEOCOTA)o Disintegration test, Dissolution tester, Refrigerator

The several chemicals which are used for a variety of purpose in PDD are given below:

Active materials,

Lubricating agent -e.g. providone, purified talc etc.

Disintegrating agent – Crospovidone, Na-starch Glycolate etc.

For flow property – Mg stearate, Colloidal SiO 2 etc.

Suspending agents

Sweetening agents

Flavor

Coating materials

Without active materials all other listed in above are known as excipients which are used

by considering a plenty of parameters. For a drug its dosages form is especially a most

important issue fixed by PDD.




Experimental formulation of FAST suspension is given below:

1. Ingredients:

1. Paracetamol 2. Sweetening agent 3. Suspending agent 4.Preservatives

5. Coloring agent

2. Steps Involved for manufacturing:

Step-1: Mixing of Paracetamol, sucrose dried powder, Arosil-200, sodium benzoate,

pineapple flavor for 40 min.

Step-2: Accelerated stability testing.

Accelerated Stability Testing For Pharmaceutical Products:Temperature Relative Humidity

(%)

Time Equivalent

Duration

60 oC 75 3 weeks 1 years

40 oC 75 6 months 2 years

60 oC 0 21 days 2 years

But initially during the product development this industry runs stability study for a certain

period, which is called initial period “Ambient”.

The Project File:

It contains project related every papers such as→

(1) Product attributes.

(2) Lab tried process.

(3) Lab tried process records.

(4) Approved product data sheet.

(5) Sales forecast.

(6) Standard packaging material samples.

(7) Process validation protocol record.

(8) Relative correspondence.




Duration of training: Two days

Introduction:

Tablets are solid pharmaceutical dosage forms containing drugs substance, with of

without suitable diluents, disintegrates, binders, coloring or flavoring agents and

prepared either by compression or molding methods. The tablets in The ACME

Laboratories Ltd . are produced only by compression method.

All Ingredients Mixing

Granulation

Wet Granulation Dry Granulation

Drying Lubrication

Compression into Tablets

Coating

Blister-Strip sealing/Bottle/Container filling

Packing

Fig: Flow chart of Tablet production

Operation:

The preparation of tablet dosage forms is done in following steps:

1. Requisition and collection and collection of Raw materials:

According to the quantitative estimate a requisition is made following SOP. At the time of

collection from ware house, raw materials are again checked and reweighed.

2. Granulation: Granulation is done;

TT A A BBLLEETT SS EECCTTII OONN




To improve the flow properties of powder materials.

To get better the compression characteristics of the mix (blend).

To prevent segregation of the constitution of the powder mix.

Two types of granulation processes are performed.

a) Dry Granulation:

Substances, which are heat and moisture sensitive and do not compress well after wet

granulation are formulated by Dry granulation.

b) Wet Granulation:

The substances, which are not water sensitive and can not be made by direct

compression and dry granulation, are formulated by wet granulation.

3. Drying of Wet Granules:

After sieving of wet mass, half drying is done at temperature above 60 o C most

ingredients are dried at 70 o C at 10 min. when it is semi dried contents again sieved to

get granules. Again dry the granules at the same temperance until the loss on drying

(LOD) come down to acceptable limit. Intensity of temperature number of mesh, time of

drying and loss on drying are not fixed for all ingredients. It may differ from product to

product.

4. Machine used for granulation:

Name of machine Manufacture PurposePlanetary mixture Ganson - India To mix the ingredients.High speed mixture Sainath & Saizoner mixture- India To mix the ingredients.Multi mill Ganson - India To reduce the size of

granules.Drum blender Bangladesh To blend.Roller compactor CLIT- India For slugging.Fluid bed dryer Alliance and Ganson - India To dry the granules.Fray dryers Bangladesh To dry the exicipent.

5. Compression:

After obtaining the approval from Quality Assurance department, the granules are

compressed to form tablets of specified weight, hardness and thickness, the process of

compression is preformed in eight (8) separate rooms, each room equipped with

compression machine, weighing machine, batch production record sheet, wet bulb and

dry bulb thermometer, a de-duster and de-humidifier.

During and after compression, following tests are preformed:




▪ Hardness ▪ Thickness and diameter▪Moisture content of tablet ▪ Friability Temperature

▪ Disintegration time▪ Relative humidity

6. Coating:

Coating is the process in which a core material is coated in order.

To increase the elegance of the product

To mask unpleasant test

To save the drug from the attack of gastric HCL acid.

To get delayed action from the product

To save the drug from moisture

Two types of coating were observed in The ACME Laboratories Ltd . These are:

Film coating

Enteric coating

Coating agents:

For enteric coating :

1. Cellulose acetate phthalate.

2. Hydroxy propyl methyl cellulose phthalate

3. Diethyl phthalate

For film coating:

a. Hydroxy propyl methyl cellulose

b. Polyethylene glycol

c. Methylene chloride

Solvent: Acetone, Ethanol, Methylene chloride recently H 2O is used as solvent coating

of Ecosprin tablet.

Sugar coating is not used in Acme Laboratories.

Problems of coating:

1. Logo bridging.

2. Edge chipping or erosion. .

3. Picking or sticking.

4. Cracking.

5. Blocking.

6. Poor erosion.

7. Loss of logo definition

8. Orange peel roughness.




9. Twining.

10. Mottling.

Packaging Zone:

After compression of tablets and coating (if required) the tablets are packed either in

blister pack or in the strip pack.

Blister package:

Blistering materials:

1. PVC (Polyvinyl chloride)2. Polyethylene laminated aluminum foil.3. PVDC4. Alu-Alu foil.

Strip package: A strip package is a form of unit dose packaging which is commonly

used for the packing of tablets and capsules.

Striping materials: Polyethylene laminated aluminum foil.

Observed product:

Baby Zink Tablet:

Active Ingredients- Mono zinc sulphate

Exicipent- Vanilla powder, Aspirin A-Cal tablet:

The following materials are mixed accurately:

(1) Dry mixing : CaCO 3 , Sodium starch Glycollate (Primajole), Lactose, Poridone.

Then it was sieved through 20 mesh on to H.S.M.

(2) Paste preparation & kneading: It was made slurry of starch, boil and add slurry

with boil water and then cool.

(3) Drying: It was drying. Wet Granules→ Fluid Bed dryer (70 o C) →16 mesh sieve→

granules→ dry (Until LOD 1.5% -2%) →Q.C

(4) Lubrication: Dried granulation→Mg -stearate + purified talc. (5min) →

Discharge granules.

(5) Compression: Then it was compressed in a compression machine.

(6) Coating: Then the compressed tablets are coated with Insta Moinst shield aqua.

(7) Blister sealing → packaging→ Marketing.




Duration of Training: Two days

Introduction:

By this department ACME started their production. Oral liquid represents syrup,suspension and drops. The oral liquid section of ACME Laboratories Ltd. consists ofcompounding area, filling & sealing area and packaging & packing area. The area isfurther subdivided as per antacid and non antacid preparations. Oral liquid in The ACME

Laboratories Ltd . can be classified as follows

Manufacturing Flow Chart of Syrup:

Preparation of syrup (hot water+sucrose)

Addition of preservatives

Cooling and addition of co-solvent, buffers etc.

Addition of active ingredient

Addition of color/flavor

Volume adjustment

Filling

Bottle washing and dryingSealing

OO R R A A LL LLII QQUUII DD SS EECCTTII OONN

Oral Liquid

Syrup Suspension

Non-sugar Antacid Other liquids Sugar




CheckingLabeling

Packing

Observed Product:

1. OXYCONE suspension

2. OXYCON-S suspension

3. Fast suspension

4. V- Plex syrup

5. Nutrum junior syrup

Description of OXICONE suspension:

Compounded in a separated room because it is a microorganism sensitive

preparation.

Room Condition: Double door system, positive pressure in the room, temp 280

C,

UV treated DI water, microorganism controlled range.

Fumigation: (1) Na-Nitrite 100mL(6.9%W/V). It is given to the pipe line.

(2) 250 mL formalin sprayed in the whole room for whole night.

N.B: Hydration of dried Al and Mg hydroxide was carried out fir minimum 16 hours. The ingredients used for this suspension:

Hydrated AL-hydroxide gel Active ingredientsHydrated Mg-hydroxide gel Active ingredients

AL-hydroxide paste Active ingredientsSorbitol solution (70%) Sweetening agentPotassium citrate BufferMethyl Parabin /Butyl parabin PreservativeSaccharin Sweetening agentMonochloramine water Preservative

Peppermint oil Flavoring agentCarboxy methyl cellulose Suspending, thickening and viscosity

agent.

Machine used for Compounding (For Syrup and ForAntacid):

The machineries and utensils that are used for compounding are listed below:

1. Compounding vessels (capacity: 500L, 250L, 100L and 210L)

2. Silverson stirrer 3. Homogenizer 4. Filter press pump

5. Colloid mill 6. Transfer pump and 7. Storage vessels




Bottle washing and drying:

The bottle that are bought are washed both internally and externally with clean water.

The washed bottles are dried at 130 oC. For antacid preparation, bottles are first passed

through NaOH solution, then passed through CL-water and finally dried at 130 oC.

Filling and Sealing:

The machineries used for this purpose are;

Automatic filling, sealing and labeling

Semi-automatic filling and sealing machine

Packaging and packing:

It involves the scrubbing outside of the bottles with clean cloth, visual inspection on

bright Light, placing the bottle in suitable container and packing in dozen boxes and

sealing the boxes with a sealing tape.

Duration of training: One day

Introduction: Those active materials from which we are virtually unable to produce drugs in liquid form

directly due to stability are converted into dry powder and finally administered orally as

liquid dosage form. They are to be reformulated by mixing with certain amount of cooled

boiled water and should be used up within certain periods (generally 5 to 7 days at

normal temperature).

Types:

The ACME Laboratories Ltd . produces three diferent formulations for Dry syrup-

Powders for suspension

Powders for syrup

Powders for pediatric

Physical Plant Design:

It is divided into two areas-

1) Manufacturing area (blending or mixing area)

2) Filling and Sealing area

DDR R Y Y SS Y Y R R UUPP DDR R Y Y SS Y Y R R UUPP




Manufacturing Flow Chart:

Weighing of all ingredients

Sieving of ingredients

With different sieve size

All ingredients Blending/mixing

Bottle washing andDrying at 130 oC

Filling of dry syrup in bottle

Sealing of Bottles

Checking

Packing

In process control:

Manufacturing: Relative Humidity should not exceed 50% and temperature

should be in between 25-28 oC.

Filling/Sealing: Weight variation, relative humidity, temperature and sealing

check.

Observed product: Sefril (Cefradine) powder for suspension 100 ml

Ingredients Used:

Ingredients Justification

Cefradine (micronized powder) Active ingredient

Dried sucrose powder Sweetening agent

Raspberry red color Coloring agent

Aerosil-200 Absorbs moisture Increase flow properly




Suspending agent

Sodium benzoate Preservative

Banana/Raspberry trusil flavors Flavoring agent

Manufacturing Procedure:

Step-1: Dried sucrose powder + Dried Cefradine (micronized) powder. Seieve with 20

mesh screen. Transfer into cone blender.

Step-2: Sodium benzoate + Banana trusil flavors + Raspberry trusil flavors + Aerosit-

200. Seieve with 20 mesh and transfer into cone blender.

Step-3: Finally, Raspberry red color (40 meshes) is transferred into cone blender. All

ingredients are blending for one hour.Step-4: Bottle filling and sealing. Average fills wt. 60.29 gm. Then checking and final

packaging.

Precaution:

1. Manufacturing area, utensils, sieve must be cleaned according to SOPs.

2. Room temp. is about to 28 oC and RH not exceeds 50%.

3. Workers must healthy and must wearing clean dressing, head cover, and face

cover.

Duration of Training: One day

Introduction:

Creams are the viscous liquids or semi-solid emulsions either O/W or W/O for topical

applications contains both oil and water phase. Ointment is semisolid solution or

suspension contains only oil phase. It is used for external application to the skin and the

mucous membrane..

In The ACME Laboratories Ltd . there are two adjacent rooms for the manufacture of

ointments and creams.

• Eye ointment (aseptic) • skin ointment and cream (non -aseptic)

Manufacturing of Cream:

All Ingredients Blending

Homogenizing

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All collapsible Filling and sealing

Tubes Checking Packing

Manufacturing of Ointment: ALL ingredients blending

Homogenizing

Aluminum-tubes Filling and sealing

Checking

Packing

Special care for eye-ointment:

Tubes for eye ointment are sterilized.

The room is sterilized with UV radiation and fumigation is performed withformalin.

Ointments must free from gritty particles.

pH viscosity and consistency is strictly maintained (Monitored by Q.C).

Machineries Observed:

Name of the machine Manufacturer Purpose

Jacketed S.S Planetary

mixer/vat “MONITA”

Italy To mix the active ingredients with

excipientsHomogenizer/colloid mill

„GANSONS”

India To prepare homogenize mixture.

Semi auto tube filling and

sealing machine

India For filling and sealing purpose.

Observed Product:

NEOBET (Neomycin Sulfate, Betamethason Valerate) Cream.




Preparation of NEOBET Cream 10gm:

Active Ingredient: Neomycin Sulfate

Oil phase: Liquid paraffin, white soft paraffin, cetomacrogol, ceostearyl alcohol,

polyethylene glycol.

Water phase: Tween 80, Butylated hydroxyl toluene, Formalin.

Room condition: Relative humidity -Not exceed 50%.

Temperature - Not more than 25 oC.

Manufacturing process:

Step-1: All oil phase ingredients in 5.5 jacketed planetary mixer using high temperature.

Keep for one hr. at that temp. Cool down to about 40 oC with slow stirring.

Step-2: All water phase ingredients in 5.5 jacketed planetary mixer. Heating at temp.

90o

C and then cool down with slow stirring.Step-3: in a S.S bowl Neomycin Sulfate, Betamethason valerate and oil phase and

water phase solution mix manually until homogenous.

Step-4: Pass the product through homogenizer for two times to get smooth mass. Then

transfer to the storage vat.

Cleaning of ointment room, vat, utensils etc:

The remained ointment to the vat and floor is cleaned with clean cloth.

Isopropyl alcohol is taken in clean cloth and then charge vat, utensils,

homogenizer, storage vat etc.

200 ppm chlorine water is used to clean up the whole room, wall etc.

Durating of Training: Two day

Introduction:

Injectables are sterile and pyrogens free products that intended to be

administered in the body with the help syringe and needles through various routes such

as intravenous (IV), intramuscular (IM), intrathecal (IT), intraperitoneal (IP) etc. The

ACME Laboratories Ltd . produces 39 categories injectables in vials and ampoules

meant for administration in the body through IV or IM routes and The ACME

Laboratories Ltd . has separate for Injectables which consists of several sub units:

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• Compounding area • Aseptic rooms for filling and sealing

• Sterilization room (auto claving and terminal sterilization)

• Vials and ampoules washing and sterilizing room • Packaging and packing room.

The ACME Laboratories Ltd . produced three types of Injectables, they are:

• Aseptic products • Terminally sterilized products • Powder for i njection

Manufacturing of Liquid Injection:

Solution preparation

Empty ampouleswashing, sterilizationand cooling

Filtration

Filling and sealing (class 100)

Terminal sterilization (if

necessary)

Visual inspection

Blister sealing

Packing

Room condition:

Room temperature: 20-25 oC • Room humidity: >50%

Pressure difference: 10-15pascle Clothes, utensils and removable parts of the machine: autoclave at 121 oC for

15mm.

Depending on particle count aseptic rooms are classified as

follows:

1. Class-100: Not more than 100 particles (0.5 p)/ft air

2. Class-10,000: Not more than 10,000 particle (0.5 p)/ft air

3. Class- 100,000: Not more than 100,000 particles (0.5 p)/ft air




The Laminar air flow chamber is a class-100. Ampoule and vial filling is done under the

laminar airflow system.

Observed product: Rhinozole Drop

Durating of training: Two day

INHALER:

Among three MDI & DPI producer of Bangladesh ACME is of them.Inhaler may be

defined as pressurized packaging system that depends on the power of a compressed

or liquefied gas or any other mechanical stress to expel the contents from the container.

The ACME Laboratories Ltd . produces two different types of Inhaler system:

1. Metered Dose Inhaler (MDI)

2. Dry Powder Inhaler (DPI)

SUPPOSITORIES:

This dosages form especially designed for those patient who unable to take solid, liquid

and parental drug forms. This form also suggested for those patient who are in serious

condition and need immediate action. Suppository is as medicated solid dosage from

generally intended for use in the rectum, vagina and to a laser extended, the urethra.

Rectal and suppositories usually employ vehicle that melt or softened at body

temperature, whereas the vaginal suppo sitories, sometime called „pessaries‟, are alsomade as compress tablets that disintegrate in the body fluid.

In The ACME Laboratories Ltd . we observed only the manufacturing of rectal

suppositories. We observed the manufacturing fast (paracetamol).

Manufacture of suppositories:

In The ACME Laboratories Ltd . an automatic machine is used for the manufacture of

rectal suppositories. By this machine, mixing, pouring, cooling and ejection is performed

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in a single preparation. The machine contains a rotary cooling chamber to cool and

solidify the suppository.

Machine observed: Automatic suppository machine “SARONG” (Italy)

Function: Suppository compounding, filling and sealing.

Operators must be used hand gloves.

Duration of Training: Two days

Introduction:

Capsule may be defined as solid pharmaceutical dosage form in which medicinal and/or

non-medicinal inert substances are enclosed within a tasteless, hard or soft soluble

small shell or container made up of a suitable gelatin.

The ACME Laboratories Ltd . Produces almost 32 types of capsules, most of them areantibiotics, and others are hematinic vitamins, antidiarrheal etc. The ACME

Laboratories Ltd . use only hard gelatin capsule for their production.

Capsule Shell Size:

Capsule shells are supplied as a number of sizes. The number varies from 000 to 5, the

former being largest and later the smallest. The exact amount of medicament which can

be filled in a particular size of capsule shell depends upon the density of the materials to

be filled in. Generally capacity varies from 600mg to 30mg.

We know that,

Capsule filled weight=Tapped bulk density × capsule volume.

Capsule volume=Tapped bulk density/weight of capsule.

Most widely used capsule sizes are 1 and 2. The largest capsule shell 000 is used for

veterinary purpose.

Capsule Filling Areas:

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There are three distinct areas for encapsulation in The ACME Laboratories Ltd .

Penicillin area

Cephalosporin area

Non-penicillin non-Cephalosporin area

Filling room condition:

Temperature: must kept at 20 to 25 oC

Relative Humidity: not exceed 50%

Filling the capsule shell:

At first, the weighed amount of active ingredients and additives filling operation. Now the

empty capsule shell are taken to separate them into cap and body. The body is taken

filled with the prepared powder mixer or granules. Now the cap is pressed in the body to

close it. Finally the filled capsule shells are ejected for cleaning and polishing.

Manufacturing Flow Chart:

Weight of raw materials

Sieving of all raw materials

All Ingredients blending (Drum mixing)

Empty capsule Filling

Checking

Polishing

Blister/Strip Sealing Checking

Packing

Machineries Observed:

Name of the machine Manufacturer Purpose

Drum mixer Bombay To mix the active

ingredients with excipients




Semi-automatic capsule filling

machine “SCORPIO”

India To fill capsule shell with

medicaments

Strip sealing machine “GANSONS” India To seal

Blister sealing machine “HORN

NOACK”

Germany To seal

Observed product:

In our training period we observed various capsule productions. These are:

Moxcilin-500 (Amoxicillin), Maxima-40 (Dsomiprazole), Sefril (Cefradine)


Introduction:

Warehouse section can be considered as an input and output section simultaneously .As

a vast drug producer company ACME has a spacious well arranged ware house. The

warehouse is an essential part of pharmaceutical industry. Here raw materials, packing

and packing materials as well as finished products are stored in specified condition and

then are distributed. The storage department of The ACME Laboratories Ltd . includesthe following sections:

Raw materials store

Packing and packing material store and

Finished product store.

Areas of warehouse:

1) Quarantine area: Purpose of Quarantine area:

To receive the raw materials

To store the material before it passed the QA test

To store the material before the decision is taken whether it is passed or rejected.

To manage the materials properly and systemically.

2) Released area: Purpose of released area:

To store the approval materials

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To store the approved materials in different conditions as specified by the

manufacture.

3) Dispensing area:

The area from where raw materials, packing and packing materials are dispensedaccording to the requisition sheet for the production. Raw materials, packing and

packing materials and finished products kept in different places should be labeled

properly. Only the approval (green tagged) materials are brought to the dispensing area.

Materials that come first are dispensed first according to the FIFO (first in first out) rule.




4) Finished product area:

This is the area where the finished products are stored after the total manufacturing

process.

5) Special area:

It includes cold room, freeze room and room for flammable materials.

The ACME Laboratories Ltd. maintains the following storage conditions:

Area Temperature ( oC) Relative Humidity

Sterile product / Cool store 4 -15 42%

Empty Gelatin shell store Below 30 60%

Covered store Below 30 Not necessary A/C store 25 60%

Antibiotic store 25 60%

Flavor store 25 60%

COMMENTS:

1. All materials are properly labeled.

2. Documentation system is excellent.

3. Here “first in f irst out” principle is strictly followed.

4. If Q.A. department releases any materials, release Label should be attached with

the container and it is followed here properly.





Introduction :

If we imagine a pharmaceutical company like a human body then PMD will be the heart

of that body. The function of this department is to design new products, monitoring the

existing products, mutation of existing products, find out the new market, and stop the

production of any product if necessary. This department does all of the aforementionedtasks by discussing with the higher management. If all the above criteria are seemingly

positive then this department discuss with higher management and PDD for launching a

new product. The PMD department of ACME is very exclusively dynamic, e.g. the

demand of herbal products has increased successively across the globe, and they

launched herbal products for first time in Bangladesh. This department justifies the

market demand of any product, market size, customer category etc.

Now ACME is marketing about 335 products for human and 120 products of veterinary

and 6 herbal products both in Bangladesh and in foreign countries with turn over of more

than covered store about Tk. 380 cores annually.

Among a lot of works of this department marketing system present here somewhat

elaborately.

At first PMD gives training to marketing officers about a new product in details.

In pharmaceutical field, customers can be categorized as-

1. Doctors

2. Chemist shop

Selected Marketing Strategy:

Discuss why the strategy was selected, then the marketing mix decisions (4 P‟s) of

product, price, place (distribution) and promotion.

Product:

The product decisions should consider the product‟s advantages and how they will be

leveraged. Product decisions should be included:

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• Brand name • Quality • Scope of production line • Warranty • Packing • price

Distribution (Place): Decision variables include:

Distribution channels, such as direct, retail, distributors & intermediates

Motivating the channel – for example, distributor margins

Criteria for evaluating distributors

Location

Logistics, including transportation, warehousing and order fulfillment.

Promotion:

Advertising, including how much and which media

Public relations

Promotional programs

Budget etc. Product Positioning:

Positioning is used as a communication toot to reach target customers in a crowded

market place. Positioning has become a key aspect of marketing communications.

PMD of ACME has a strong International Marketing section, which can be

understood from following data:

Regular Export Market Market Development

Myanmar Nepal Ethiopia TaiwanSri Lanka Pakistan Myanmar Yemen

Afghanistan Philippines Cambodia KenyaHong Kong Vietna Nigeria (Vet) KSA

Internationl Market of ACME

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10

20

30

40

50

60

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The monthly observations of ACME operate us to think in a practical way for the proper

running of a plant with maintaining all the standards related to cGMP.Though it is a super class plant, we may impart some suggestions to solve some of its

observable problems to ensure the product safety as well as human safety in the plant.

The suggestions are-

1) The warehouse department may arrange the items in an alphabetical order,

manage proper place to separate different raw materials & finished products.

2) In the solid package centre, storage of the finished products done is the passage

of the station, which should be avoided for proper following of the GMP.3) In the solid department, laminar air flow should install & single line operation

should be practiced.

4) It would be better if it is possible to feed the hopper for compression

automatically instead of manually.

5) A central library enriched with all the modern information‟s should be established.

6) There should be more enriched lab facilities in the product department & more

manpower is needed in this department.

By the overall performance of all the departments, we really feel lucky to beintroduced with the world class modern pharmaceutical technology.

Thus ACME is serving the nations. We hope ACME will continue to fight against the

diseases of the world & bring glory to the country by ensuring quality products.

SS UUGGGGEESS TTII OONN

in-plant tarining report on acme

Documents