A REPORT ON IN-PLANT & MARKETING TRAINING
The ACME Laboratories Ltd.
The ACME Laboratories Ltd is one of the well renowned pharmaceutical companies in Bangladesh and also in the global area. The vision of this pharmaceutical company is to be recognized as a world class pharmaceutical company by providing high standard products and services.
According to the training schedule, I visited all the departments of The ACME Laboratories Ltd. The ACME Laboratories Ltd always manufactured high quality products of various dosage forms and never compromises in the name of quality. To ensure good quality products the quality assurance and quality control departments and in process control systems have been developed.
During the in-plant training, the process of manufacturing and maintaining quality according to “Good Manufacturing Practice” (GMP) guidelines were observed and in this context, standard operations procedures were developed. As a result of visiting in such a reputed and well organized company like The ACME Laboratories Ltd, my theoretical concept regarding various issues has developed due to the practical view.
ISO (International Organization for Standardization)
Introduction:
ISO is an International Organization for Standards that was formed by technical committees. They provide user-friendly guidelines for a wide range of organizations. Examples of these organizations include manufacturing, processing, servicing, printing, forestry, and electronics. The International Standards Organization represent countries around the globe. The Organization was founded in 1947 as a non-governmental organization to promote the development of standards in quality. ISO was established in 1947, in Switzerland, with the purpose of developing intellectual, scientific, technological, and economic corporation between member countries (Bureau of Business Practice). Later in 1979 the ISO Technical Committee (ISO/TC 176) was formed to make a set of guidelines that would bring together and standardize world industries. ISO has affiliates in more than 90 countries.
Definition:
ISO comes from the Greek word “isos” which means “same as.” The words “same as” can be implied to mean the consumer gets what the consumer expects. In our quality assurance class we have learned that if the consumer gets what they expect, this is consider quality. Therefore, the root word ISO stands for quality.
The International Organization for Standardization (ISO) is an international consortium (combination of some company) of representative of bodies constituted to develop and promote uniform or harmonized international standards. Among the various ISO used in the pharmaceutical industry are those in the series ISO 9000-9004. The standards are including here pertaining to –
· Development
· Production
· Quality Assurance (QA)
· Quality Control (QC)
· Detection of defective product
· Quality Management
· Other issues as product safety and liability
Our Export Markets
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Duration of Training: Total 8 days
Quality assurance, or QA for short, is the systematic monitoring and evaluation of the various aspects of a project, service or facility to maximize the probability that minimum standards of quality are being attained by the production process. QA cannot absolutely guarantee the production of quality products.
Purpose:
GMP is that of quality assurance which ensures that, products are consistently producer and controlled to the quality stander appropriate to their intended use and as required by marketing authorization. A product specification this makes it clear that QA in the Generic, wider term.
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 always try to provide quality product to the customers and this foremost effort done by Quality Assurance Department. 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 Assurance Department of ACME monitors each step of manufacturing operation and adopted “Good Laboratory Practice (GLP)” to ensure reliability and 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:
1. Validation and Documentation.
2. In-Process Quality Assurance (IPQA).
3. Method Development and Validation.
4. Foreign Registration and export.
- Validation
Validation is defined as establishment document evidence, which provide a high degree of assurance that a specific process or system will consistently produce a result meeting its predetermined specification. Validation is normally required for processing, equipment’s service, production process and the test procedure & computer system.
The following things are validated
· Manufacturing process validation
· Critical equipment validation
· Area & facilities validation
· Cleaning & contamination validation
· Utilities validation
· HVAC system
· AHU (Air Handling Unit)
· Compressed air
· Demineralized water Plant
· Analytical method validation
· Analytical equipment validation
· HPLC
· GLC
· Computer system validation
Types of validation:
- Prospective validation: For new method, new machine, new area, new facility etc.
- Retrospective validation: If the validation is not done properly or totally then validation is done again.
- Concurrent validation: If there is any change in formulation, facilities etc then validation is done again.
- Revalidation: Same as retrospective validation but in this type full specification tests are done for validation.
Function of validation:
o IQ ( Installation qualification)
o DQ (Design qualification)
o OQ (Operation qualification)
o PQ (Performance qualification)
Process Validation:
Process Validation in the pharmaceutical and medical service industry is defined as the documented act of demonstrating that a procedure, process, and activity will consistently lead to the expected results. It often includes the qualification of systems and equipment. It is a requirement for Good Manufacturing Practice and other regulatory requirements.
Analytical tests under process validation:
– Microbiological test
– Lose on drying
– Potency test
Process Validation must have Repeatability
Reproducibility
Meet pre-determined specifications.
Critical parameters are optimized before validation. Each step of the manufacturing process should be qualified to validate the complete process.
Source Validation/Specimen Sample analysis:
Specimen sample is a small amount of sample that shows what the rest of it is like.
Various test involved in specimen sample analysis/source validation:
· Identification
· Solubility
· Appearance of the sample
· pH
· Melting point limit
· Loss on drying
· Bulk density
· Mesh size
· IR spectroscopy
· UV spectroscopy
· HPLC
· Optical rotation
· Potency determination
· Microbiological test
· Kearl fisher titration
Solubility:
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on temperature and pressure. The extent of the solubility of a substance in a specific solvent is measured as the saturation concentration where adding more solute does not increase the concentration of the solution.
The approximate solubility of a compendia substance is indicated by one of the following descriptive terms:
· Very soluble – 1gm in 1ml.
· Freely soluble – 1gm in 10 ml.
· Soluble – 1gm in 30ml.
· Sparingly soluble – 1gm in 100 ml.
· Slightly soluble – 1gm in 1000 ml.
· Very slightly soluble – 1gm in 10000 ml.
Procedure:
Sample
Fill in vol flsak
Added of water
Shake + Sonicate + Shake in water bath
Slightly soluble
As per the BP it is slightly soluble
Assay:
Assay test for compounded preparations are intended to serve as the official test in the event of a question or dispute regarding the preparations conformance to official standards.
Sample
Conical flask + water
Boiling in water bath (For 10 mins)
Added indicator (phenopthaline)
Titrated in 0.1N NaOH
Water bath:
Water bath means a bath of boiling water unless water at another temperature is indicated.
Assay =
Burette reading ×Factor ×Equivalent weight as BP×100
Sample weight
= %
Instrument used in analytical test:
| INSTRUMENTS | ORIGIN | FUNCTION | |
| HPLC
HPLC System 1 to 8 |
Waters, USA
Shimadzu, Japan Dionex,Germany. |
For separation, identification & assay | |
| GLC
(Gas Liquid Chromatogram) |
Shimadzu, Japan | Product identification, separation & assay | |
| UV Spectrophotometer | Shimadzu, Japan | Product identification | |
| Fourier Transform Infrared Spectrophotometer (FTIR) | Shimadzu, Japan | Product identification, mainly for raw materials | |
| Atomic Absorption Spectrophotometer (AAS) | Japan. | For identification/ detection of metal (elemental analysis). | |
| Dissolution Testing Apparatus
Apparatus 1 Apparatus 2 Apparatus 3 |
Erweka, Germany | Dissolution time determination. | |
| Disintegration Testing Apparatus
Apparatus 1 Apparatus 2 |
Erweka, Germany
Logan,USA |
Disintegration time determination. | |
| Melting Temperature Testing Apparatus | Gallanhamp | Melting pint determination. | |
| pH Meter | Mettler Teledo,
Suizerland |
Determination of pH. | |
| Karl Fisher Titrator | Mettler Toledo,Germany | Determination of water content. | |
| Viscometer | Brookfield,UK | Determination of viscosity. |
Method Development
Method development is a part of QC department. For analysis, methods those are described in compendium, i.e., BP, USP, are followed. But in case of non-described raw materials, the methods supplied by raw materials suppliers are followed. But, in many instances, the supplied methods don’t work. In those cases, a better & compatible method is developed. Following steps are involved in new method development:
- Development protocol, method trial, recording in the book, selection of the method, opening of a new file.
- Method writing, checking & correction.
- Method verification by analyst.
- Method approval.
After method development, it is validated. Then it is used as standard analytical procedure.
Documentation
The ACME Laboratories Ltd. record all the necessary information and documents in order to ensure the availability of all the data required for manufacturing, packaging, quality control and record 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.
Seeing BP,USP procedure for assay
PD give fix amount potency, so getting that required potency by changing procedure basis on trail and error.
After get require potency than method give procedure in master formulation that is used for assay during production time validation
IPQA (In process Quality Assurance)
In Process Operation:
1. QA Operation in Dispensing Area
A QA officer in dispensing area monitors the dispensing process &
Checks & signs the dispensing card, whether all the information’s are
Mentioned & included in dispensing card.
2. QA Operation in Solid Department
I. In Production Area
· Before compression starts, the machine & the rooms are checked for proper cleaning & few tablets checked for weight, hardness, thickness, friability, disintegration & dissolution time, organoleptic tests for chewable tablets & other relevant parameters. In case of capsule, initially, some capsules are filled to check weight variation. If tablets or capsules meet the specification, machines are started for operation.
· During compression or filling, the above parameters are checked at regular intervals (2 hrs).
· After compression or filling, the finished products are sent to QC department for analysis.
· On the basis of QC report, the tablets or capsules are approved for packing or rejected.
· Tablets that require coating are sending to QC for various tests before coating & during coating operation, all steps are monitored by a QA officer.
II. In Packaging Area
· Start up & IPC (in process control) in packaging, i.e., both primary & secondary packaging.
· Checking of product name, strength, batch no., MFG date, EXP date, license no., foil printing, pocket formation, sealing, cutting, slitting, MRP & leaflet etc.
· Leak test of blisters & strips.
· Release of finished products after checking all relevant documents & QC report.
3. QA Operation in LCO Department
I. In Manufacturing Site
- Before starting a new batch production, room cleanliness, temperature & %RH is checked.
- Random sampling for QC test & retention sample.
- During manufacturing, filling or packaging, the products are checked for proper weight, volume, filling, sealing, clarity of solution, batch printing, both inner &shipping carton are checked at regular time interval.
- At regular intervals, bottle washing & drying are checked.
II. In Packaging Site
Following parameters are checking by QA officer in case of packaging materials.
- For Bottle/ Vial
-Batch no. on Label
-MFG date on Label
-EXP. Date on Label
-MRP
-Quantity of product
-Print & color of Product
-Cap Sealing/ security overprinting
- PVC & PVDC for Blister & Strip Packaging
Color
Width
Thickness
Weight/10 cm
- Inner Carton
Product Name & Label Claim
Batch no
MFG date
EXP. Date
MRP
Print & color
Spoon/ cap/ actuator
Leaflet
- Shipping Carton
Product Name & Label Claim
Batch no
MFG date
EXP. Date
No. of packs per shipping carton
Size no. & adaptability
4. Dealing of contract manufacturing
5. Product Recall
6. Artwork Approval
Checking & finalizing all kinds of artwork (design) of packaging materials.
7. Issuing all kinds of certificates
8. Documentation
· SOPs (Standard Operating Procedures)
Prepared by relevant department, but checked, reviewed &
Approved by QA officers.
· Documents of Source Approval
· Analytical Test Report of Raw & Packaging Materials.
· Complete Batch Documents (BMR & BPR).
· Change Control Approval
Change control approval is required in case of:
– Short batch production for exports.
– Change any parameters of product, i.e., color, foil etc.
Chromatography
HPLC:
High-performance liquid chromatography (sometimes referred to as high-pressure liquid chromatography), HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.
HPLC typically utilizes different types of stationary phases, a pump that moves the mobile phase(s) and analyte through the column, and a detector to provide a characteristic retention time for the analyte. The detector may also provide additional information related to the analyte, (i.e. UV/Vis spectroscopic data for analyte if so equipped). Analyte retention time varies depending on the strength of its interactions with the stationary phase, the ratio/composition of solvent(s) used, and the flow rate of the mobile phase. It is a form of liquid chromatography that utilizes smaller column size, smaller media inside the column, and higher mobile phase pressures.
Description:
The instrument contains the following parts:
a) Pump
b) Injector
c) Guard Column
d) Column
e) Detector
f) Recorder
g) Column Oven
h) Degasser
Principle:
Sample is injected to the column. Stationary phase consists of silica gel. Compounds are flowed through the column by the liquid media (mobile phase) at a different rate. During the extraction different compounds are detected by detector. Detector detects the compound and determines the amount of compound in solution
Process:
In HPLC, a high back pressure is needed to pump the mobile phase through the column. Every reagent used in mobile phase and sample preparation should be highly purified or HPLC grade. The mobile phase and liquid sample is required to filter usually with 0.2µ filter paper. The sample (0.01ml) is injected with a syringe after each run the column must be cleaned. Generally 50% methanol is used for wash.
Uses:
· Identification
· Qualification
· separation
HPLC on QC lab:
| Instrument | Origin | Function |
| HPLC System 1 to 8 | Waters, USA
Shimadzu, Japan Dionex,Germany. |
For separation, identification & assay |
Parts of HPLC:
| Parts | Function |
| Pump | -pumping the mobile phase in the injector. |
| Injector | -inject sample. |
| Column | -separate the chemicals according to its electro negativity. |
| Detector | -detect the chemical component by using UV light. |
| Software | -identification and calculate potency. |
Spectroscopy
Atomic-Absorption Spectroscopy:
Introduction
Atomic-absorption (AA) spectroscopy uses the absorption of light to measure the concentration of gas-phase atoms. Since samples are usually liquids or solids, the analyte atoms or ions must be vaporized in a flame or graphite furnace. The atoms absorb ultraviolet or visible light and make transitions to higher electronic energy levels. The analyte concentration is determined from the amount of absorption. Applying the Beer Lambert Law directly in AA spectroscopy is difficult due to variations in the atomization efficiency from the sample matrix, and no uniformity of concentration and path length of analyte atoms (in graphite furnace AA). Concentration measurements are usually determined from a working curve after calibrating the instrument with standards of known concentration.
Fig: Schematic of an atomic-absorption experiment
Instrumentation
Light source
The light source is usually a hollow cathode lamp of the element that is being measured. Lasers are also used in research instruments. Since lasers are intense enough to excite atoms to higher energy levels, they allow AA and atomic fluorescence measurements in a single instrument. The disadvantage of these narrow-band light sources is that only one element is measurable at a time.
Atomizer
AA spectroscopy requires that the analyte atoms be in the gas phase. Ions or atoms in a sample must undergo desolvation and vaporization in a high-temperature source such as a flame or graphite furnace. Flame AA can only analyze solutions, while graphite furnace AA can accept solutions, slurries, or solid samples.
Flame AA uses a slot type burner to increase the path length, and therefore to increase the total absorbance. Sample solutions are usually aspirated with the gas flow into a nebulizing/mixing chamber to form small droplets before entering the flame.
The graphite furnace has several advantages over a flame. It is a much more efficient atomizer than a flame and it can directly accept very small absolute quantities of sample. It also provides a reducing environment for easily oxidized elements. Samples are placed directly in the graphite furnace and the furnace is electrically heated in several steps to dry the sample, ash organic matter, and vaporize the analyte atoms.
Light separation and detection
AA spectrometers use monochromators and detectors for uv and visible light. The main purpose of the monochromator is to isolate the absorption line from background light due to interferences. Simple dedicated AA instruments often replace the monochromator with a band pass interference filter. Photomultiplier are the most common detectors for AA spectroscopy.
IR Section (Infrared Spectroscopy)
What is IR?
Infrared spectroscopy (IR spectroscopy) is the spectroscopy that deals with the infrared region of the electromagnetic spectrum that is light with a longer wavelength and lower frequency than visible light. It covers a range of techniques, mostly based on absorption spectroscopy. As with all spectroscopic techniques, it can be used to identify and study chemicals.
Mechanism of IR:
Produce KBr disc of sample (raw materials),
here very minor amount of sample is used
and it must be free from moisture
placed within IR spectroscopy
allowed to pass IR through sample disc
Show absorbance
Compare with standard
Quality control is the part of good manufacturing practice, which is concerned with sampling, specification and testing as well as the organization and documentation and release procedure, which ensures that the necessary and relevant tests are, in fact, carried out and that materials are not released for use, non products released for sale or supply until their quality has been judged to be satisfactory.
GMP Requirements of the quality control department:
F Normally QC laboratories should be separated from the production areas. This is particularly important for laboratories for the control of biological, microbiological and radio isotopes, which should also be separated from each other.
F Control laboratories should be designed to suit the operations to be carried out in them. Sufficient space should be given to avoid the mix-up and cross contamination. There should be adequate suitable storage space for samples and records.
F Separate rooms may be necessary to protect the sensitive instruments from the vibration, electrical interference, humidity etc.
F Special requirements are needed in laboratories handling particular substances such as biological or radioactive samples.
Function of quality control department:
The well equipped and sophisticated QC has been working for the day by day control of quality of products. Even real time study also done to ensure the stability announced by the company. QC also checks quality of RM, packing and finished goods. QC officers and pharmacists assesses and assures that entire production process has been completed satisfactorily and satisfied all the aspects of cGMP as microbiological tests and validation ensured
Quality control is responsible for the day by day control of quality within a company. This department is stuffed with scientist and technicians who assess and assure that entire production process has been completed satisfactorily and satisfied all the aspects of GMP.
Protocol for quality control assignment
Sampling
(A quality assurance officer
does it & brings it to the Q.C department )
Supervising
(A representative from the Q.C. dept.
receives the sample & assign someone to analyze.)
Analysis
(The analyst analyses the sample according to the specification)
Checking
(After the tests, the results are checked)
Final approval
(The Q.C. manager verifies the result)
Collection
(A Q.C. officer collects the results
of the results of the sample that was assigned previously. )
Major responsibility of QC
· Sampling adequately for testing purpose.
· Issuing release, reject or quarantine advice for each batch of raw, bulk and packaging materials.
· Assessment of the finished products for their release, reject etc.
· Maintaining batch wise full quality control test records with signature of the person(s) who performs the tests.
· Batch documentation.
· Performing Environmental monitoring checks.
· Calibration and standardization of laboratory equipment.
· Control of laboratory reagents.
Packing and Packaging Section
This section deals with the checking of procure packaging and packing materials as well as monitors the proper packing of finished product for the correct label, batch number, manufacture and expiry date. The tests that are exercised by this section for packing materials are:
| Product | Test |
| PVC & PVDC | Colour, width, thickness, weight per unit area etc. |
| Cotton | Appearance, weight, moisture content sulphated. |
| Shipping cartoon | Weight, dimensions, thickness. |
| Inner cartoon | Height and level, description (text, colour, general appearance) weight etc. |
| Plastic cap | Appearance, weight, length, diameter, volume capability. |
| Dropper | Appearance, weight, length, capacity, adaptability with bottle cartoon and plastic cover |
| Mask type | Appearance, width, adhesiveness, |
| Bottles, ampules, vials | Height, neck diameter, weight, volume capacity, light transmission test, machine acceptance. |
Raw material Section
The materials, which are used to prepare a dosage form, are known as raw materials except packaging materials. Raw materials may be of two types:
1. Active ingredients
2. Excipients.
1. Active ingredients:
The substance or compounds that is intend to be used in the manufacture of pharmaceutical products, which is pharmacologically active, are called active ingredients.
2.Excipients:
Excipients are the non- drug components of a pharmaceutical formulations, which are used as a diluents, binder, adhesive, disintegrant, lubricant, glidant, color, flavor, sweetener etc.
Sampling rule:
· ?N+1 (N=no. Of container), if N>5
· If N<5,then sampled all
· For damaged containers, sampled all
When QA department confirms the raw materials as useable then they are transferred to free stock with released tag.
Tag used in warehouse:
Under test: Yellow tag
Sampled: White tag
Released: Green tag
Non-conforming: Blue tag
Urgent released: Orange tag
Rejected: Red tag
In Warehouse raw materials are stored in different environment depending on their chemical and physical nature. The store conditions are as follows:
1. Cold store (Temperature: 02-080C)
2. Cool store (Temperature: 08-150C)
3. Penicillin store (Temperature: >250C)
4. Narcotic store (Ambient temperature)
5. Control store (Temperature: >300C)
6. Empty Hard Gelatin store (Temperature: 15-250C,RH 35-65%)
The passed materials are sent to the respective production department according to their Batch Manufacturing record (BMR).
Raw Material Procurement and Analysis
Demanding of raw materials
(Demanded by production according to the needs through commercial dept.)
Raw materials received procure by store
Raw materials in quarantined area
QC sampling
Rejected QC passed (Green tag)
Documentation Stored in passed area
Dispensed
Waiting for product preparation
Various test involved in raw materials analysis:
? Identification
? Solubility
? Appearance of the solution
? PH
? Melting point limit
? Loss on drying
? Bulk destiny
? Mesh size
? IR spectroscopy
? UV spectroscopy
? HPLC
? Optical rotation
? Water content or loss on drying
? Potency determination
? Microbiological test
Product Testing Section
Oral liquid section
the section monitors all the in-process QA process as well as thefinal clearance for the finished product to be sold in the market. In-process QC exercises by the section are:
- Potency determination
- Viscosity
- pH
- taste odor & flavor
- color
Tablet section
For tablet following experiments have been done:
- Checking the cleanliness of drying and granulation area
- Determination of moisture content of granules
- Determination of harness, friability and thickness of compressed tablets
- Regular monitoring of humidity and temperature of compressed room
- Checking of weight variation, disintegration time, dissolution time and other relevant parameters
- Potency of active ingredient in tablet
- Checking the uniformity of coating coated tablets
- Finally checking the elegance of the product
Injectable section
These sections monitor all the in-process QC measures in the production of injectables. This includes:
· Monitors the cleaning procedure of compounding and filling rooms according to SOP
· Checking the integrity of membrane filter by performing bubble poin test
· Potency determination
· Volume adjustment
· Maintenance of aseptic area
· Monitoring the sterilization of products
· Monitoring the pH of a product
Ointment, Cream, Dry syrup and capsule section
Oinments and creams are checked for their microbiological contamination as well as to find the grittiness. Capsules are assayed as per the specification which includes parameters such as weight variation, potency, disintegration etc. dry syrups are regular checked by regular sampling of bottles, their qualitative and quantitative assayed are made and finally the proper sealing of the cap is monitored.
Product testing of finished products is made in the quality control laboratories. The testing of finished product for compliance with predetermined standards is a critical factor product release.
Microbiology testing section:
Microbiology department is an essential part of QC. Microbiological test perform an important role to ensure the quality of the parental and non-sterile products in various steps ranging from the raw materials to finished products. Drugs like eye drops, injections must be sterile in condition. For this purpose a varity of test have done in Microbiological laboratory.
The departments of Microbiology perform the role of immense importance to follow the GMP and to formulate as well as to implement the SOPs. Overall activity profile of the microbiology section of QC department of ACME is represent by following ways:
Sterility Test
Filter the product with 0.45µ Filter paper (Nitrocellulose Nitrate or Nitrocellulose Acetate)
Cut the filter paper into two part, one part keep in fluid (thioglycolate broth) for bacteria an another part keep in Tryptone soya broth for Fungi.
Incubate at 32.5 °C for bacteria and 22.5 °C for fungi(Both for 14 days)
Observed regularly
Bacterial Endotoxin Test
LAL test means Limulus Ameaeobocyte lysate test. Limulus amebocyte lysate (LAL) is an aqueous extract of blood cells amoebocyte from the Horseshoe crabe Limulus polyphemus. LAL reacts with bacterial endotoxin and lipopolysecharide (LPS), which is a membrane component of Gram Negative Bacteria This reaction is the basis of the LAL test, which is used for the detection and quantification of bacterial endotoxins.
Process:
Test sample add in Limulus amebocyte lysate
If any types of gel is formed, then it is consider that any type of endotoxin present in sample
Non-parenteral Product
Limit Test
· Microbiological Limit Test of raw materials & finished products.
1. Total aerobic (bacteria & fungi) count.
2. Detection of 4 pathogens, which are Escherichia coli, Pseuodomonas aeroginosa, Salmonella species & Staphylococcus aureus.
· Bioassay of raw materials & finished products
1. Bioassay is mainly performed to detect the potency of antibiotics.
· Environmental Monitoring.
1. Monitoning of Particulate Contamination And air flow in clean room
v Particle counter
2. Monitoring of settle plate exposure.
3. Monitoring Personal Hygiene
v Contact Plate Method
4. Monitoring Surfaces
v Contact Plate Method
v Swab Test
5. Monitoring of Airborne Microorganisms.
v Air Sampling by RCS Sampler
Instruments used in microbiology department:
· Sterility Testing device
· Autoclave / Steam steriliger
· Laminar air flow
· Oven
· PH meter
· Incubator
· Refrigerator
· Air supplier for air sampling
· Microscope.
· Colony counter.
· Liquid particle analyger
· Air borhe particle counter.
· Water bath
Duration of Training: One day
INTRODUCTION
Product development department is the core & heart of a pharmaceutical industry. Product development as the name implies, is responsible for the development of a new product. This department formulates new drugs & plays key role for the development & improvement of the quality of the existing drugs & for the establishment of new drugs. Moreover, this department fix ups any market complain of an existing product in the market, troubleshoots any problem arising during manufacturing the product & last, but not the least, documentation (preparation of BMR & BPR, i.e., Batch Packaging Record).
Functions of product development
· New product formulation
· Preparation of recipe or drugs
· Development of packaging materials for new product.
· Development of existing product with cost effective formulation.
· Source approval work for existing materials both active ingredients and exipients
· Preparation of master formulation and analytical procedure for new product
· Reformulation
· Reprocess
· Trouble shooting
· Handling market complain
· Preparation of BMR/BPR
NEW PRODUCT DEVELOPMENT
1. Selection new product for product development by CPM of marketing department according to the demand of the market.
2. Collection of raw material (both excipient & active ingredient) to be developed.
3. Preformulation study.
Checking of following parameters for active drug or excipients:
· Solubility.
· Water content.
· Particle size.
· Bulk / tapped density.
· Flow properties.
· Melting point.
· Crystal properties.
· Biological properties.
4. Recipe Preparation.
5. Lab scale trial batch for stability studies.
6. Analytical method development & validation.
7. Preparation of stability study protocol & stability study as per ICH (International Conference on Harmonization) guideline (30°C±2°C & 65%±5% RH, 40°C±2°C & 75%±5% RH, 25°C±2°C & 60%±5% RH ).
8. Evaluation of stability study test result after 03 months & 06 months (Accelarate) & 03 months , 06 months & 12 months (real time).
9. Preparation of master formulation an procedure.
10. Preparation of BMR (Batch Manufacturing Record) & BPR (Batch Packaging Record) for small scale commercial batch, i.e., pilot batch.
11. Pilot batch production (at least 3 consecutive successful batches).
12. Preparation of BMR & BPR for routine commercial production.
Launching a new product involves a lot of work
REPROCESS
If the chemical assay for QC for a particular batch don’t comply the standard then PD will check the batch & take necessary action accordingly.
REFROMULATION
Selection of product for reformulation to improve the product quality, product stability, manufacturing process, organoleptic properties of the product and to change elegance & packaging mode of the product.
TROUBLESHOOTING
During manufacturing of a new product in pilot commercial batch many problems may arise. In that case personnel from product development department (PDD) investigate the problems and take necessary steps and remedies to minimize those problems and carry on the manufacturing process successfully.
Such as sudden capping of tablet or denting incase of capsule or may be pH imbalance in case of liquid may occur. These types of problems are investigated by PD personnel and take necessary actions to solve these problems immediately.
DOCUMENTATION
- Preparation of product dossier for regulatory purpose.
- Preparation of export document (e.g. manufacturing process, batch formula, and stability data) as per requirement of respective countries.
AREAS
· Formulation Section.
- Tablet Compression room.
- Coating room
- Granulation, Drying & Milling Room.
· Analytical Section
1. Stability study room
2. HPLC Room.
3. DT, Dissolution analysis room.
· Documentation Room
· Official Room
Product Shelf-life determination
If meet all specifications, then the shelf-life of products is given according to the following table:
| Accelerated stability test time | Equivalent life time |
| 6 months | 2 years |
| 3 months | 1 years |
Stability Test
There are two methods by which stability is tested: Real-time stability study, and Accelerated stability study.
Products are kept in the stability chamber at three different conditions:
25°C, 60% Relative Humidity (RH)
a) Real time stability
30°C, 65% RH
b) Accelerated Stability: 40°C, 75%RH
The product stays in the stability chamber for 6 months. If the degradation of the product is less than 5% in 6 months then the shelf life is 2 years
The Analytical method development requires demonstration of suitable
· Accuracy
· Precision
· Specificity
· Sensitivity
· Ruggedness
Machineries and Materials used in PDD:
- Balance
- Oven
- Stability chamber
- PH meter
- Stirrer Propeller
- Coating machine (NEOCOTA)
- Disintegration, Dissolution tester, Refrigerator,Friability tister
- The several tester which are used for a variety of purpose in PDD are given below:
- Excipients
- Lubricating agent -e.g. providone, purified talc etc.
- Disintegrating agent –Crospovidone, Na-starch Glycolate etc.
- For flow property –Mg stearate, Colloidal SiO2 etc.
- Suspending agents
- Sweetening agents
- Flavor
- Coating materials
- Coloring agent.
Mechineries should be included:
- Granulator (singma bladed)
- Compression machine (Rimek Mini Press- 2 MT)
- Blending machine.
- Milling machine
- Silverson stirrer
- Osmo meter.
Duration of Training: One day
Product Management Department
Introduction:
Pharmaceutical industry is one of the largest sectors of business in Bangladesh. More than 300 pharmaceutical firms fight for a significant amount of market share in the pharmaceutical market. The importance of this industry in the total economy can easily be understood by the fact that pharmaceutical industry is the second highest tax payer to the Government of Ba