Quality Assurance (QA)

Definition : According to WHO, Quality Assurance (QA) is a management method that is defined as “all
those planned and systematic actions needed to provide adequate confidence that the pharmaceutical
products ,service or result will satisfy given requirements for quality and be fit for use”. According to ISO,
Quality Assurance is defined as “the sum total of the activities aimed at achieving that required standard”.

Quality Assurance = Quality Control + Good Manufacturing Practice

Figure : Objectives of Quality Assurance Department

Objectives of QA Department :

The system of QA appropriate to the manufacturer of pharmaceutical products should be ensure that :

1. Pharmaceutical products designed and developed according to GMP

2. Managerial responsibilities are clearly specified.
3. Production and control operation are clearly specified in a written form.
4. The finished product is correctly tested and Checked.
5. The quality of products are maintained throughout their shelf life.
6. Proper controls on starting materials, intermediate products, bulk products, IPC, calibration and
validation.
7. Regular evaluation of the quality of pharmaceutical products should be Conducted.
8. Deviations are reported, investigated and recorded.

Factors in Quality Assurance :

1. Raw materials
2. Manufacturing process
3. Imports & Exports control
4. QC & Analysis
5. Human resource professionals
6. Packaging
7. Storage
8. Transport & distribution
 Figure:Functions of Quality assurance Department

Functions of Quality Assurance Department:

1. Products design and development

a) Authorize Documents
b) YVendor Evaluation
c) Vendor Audit
2. Manufacturing Process
a) Environmental monitoring
b) Qualification
c) Calibration
d) Validation
e) In process control
f) Product deposition
3. Post production
a) Stability test
b) Retained sample
c) Return product
d) Product Complaint
e) Recall
4. Compliance
a) Quality management system manual
b) Change control
c) Deviation
d) CAPA
e) Self inspection
f) Documentation
g) Risk management
h) Products quality review
Quality Control(QC)
Definition :

According to the World Health Organization (WHO), the term quality control refers to the sum of all
procedures undertaken to ensure the identity and purity of a particular pharmaceutical.

Components of QC :

Objects of Quality Control:

1. Establishing quality standards

2. Smooth Production process
3. Detecting deviation in production process
4. Ascertaining reasons for low quality
5. Segregation of defective Products
6. Responsibility for quality of product manufactured be fixed
7. Maintaining proper records of quality
8. Unanimity among workers and management

Functions of Quality Control Department :

1. Determining Standards
2. Keeping records
3. Determining sampling limits
4. Development of better quality device
5. Analysis raw materials, finished products, packaging materials
6. Calibrating Laboratory instruments
7. Development of test procedure
8. Process validation
Tests for Quality Control:

The quality of a pharmaceutical products checked in different stages.These are :

Raw materials analysis

In process sample analysis
Packaging materials analysis
Finished product analysis

List of Tests Used in Quality Control Department of UCPL:

Appearance test
Dissolution Test
Disintegration Test
Friability test
Weight variation
Hardness test
Thickness Test
Leak test
LOD or Moisture content
PH Test
Spectrometric Analysis

List of Apparatus used in Quality Control department of UCPL:

Analytical balance
Disintegration Tester
Dissolution Tester
Tablet Friabilator
Hardness tester (Monsanto)
Thickness tester
Leak test apparatus
Modular circular polarimeter
Automatic refractometer
Powersonic
Karl fischer Titration
UV spectrophotometer
FT -IR
Moisture Analyzer
HPLC
PH meter
Desiccator
Different Quality Control Tests & Their Apparatus :

1.Appearance test:

The appearance of a tablet, its identity and general elegance is essential for consumer acceptance, for
maintain lot to lot uniformity and tablet to tablet uniformity. The appearance test involves size, shape,
color, presence and absence of odor, taste, surface, texture flaws. The qualities of tablet can dimensionally
monitores and controlled by size and shape.

2.Weight Variation Test:

The weight variation test is performed by weighing 20 tablets individually, calculate the avarage weight
and compare it with single tablet weight. The tablets pass USP test if no more that 2 tablets are outside the
percentage limit and if no tablets differ by more than 2 times the percentage limit.

As per USP Limit As per BP

130gm or less ± 5% 80mg or less

130mg to 324mg ± 7.5% 80mg to less than 250

More than 324 ± 10% 250 or more

Figure: Weight variation limitation

QC department of UCPL Performed their Weight variation Test by using Analytical Balance. The details
of analytical balance used in UCPL is given below:

I
Name : Analytical Balance

Model No : AE-240

Weighing Capacity : 0.1mg to 220gm

Operating Temperature : 10 to 30°C

Power Supply : 230V/60Hz

Origin:METTLER,Switzerland

Name : Analytical Balance (Sartorius)

Model No : CP- 124s

Weighing Capacity : 0.1mg to 120gm

Operating Temperature : 10 to 30°C

Power Supply : 230V/60Hz

Origin: Germany

3.Thickness Test :

Tablet thickness is determined by the diameter of the die, the amount of fill permitted to enter the die
cavity, the compaction characteristics of the fill material, and the force or pressure applied during
compression. The thickness of a tablet should be controlled within ±5% variation of a standard value
depending on the size of the tablet.

In UCPL, Thickness test performed by peacock thickness tester.

4. Hardness Test :

This measures the degree of force (in kilograms, pounds, or in arbitrary units) needed to fracture a
tablet.A force of about 4 to 10 kg is considered the minimum requirement for a satisfactory oral tablet,
3kg for chewable tablet and 10 to 20 kg for sustain release tablet. Measurement is usually carried out
using a minimum of ten tablets. The crushing strength of tablets is usually checked using Monsanto or
Stokes hardness tester in UCPL.

The details of Monsanto hardness tester is given below :

Name : Monsanto Hardness Tester

Capacity : 0 to 20 kg

Origin : Mumbai, India

5.Friability Test :

This measures the resistance of tablets or granules to abrasion or fracture. A minimum of 20 tablets are
dedusted, weighed and subjected to a uniform tumbling motion for a specified time. They are then
dedusted and reweighed. The measure of abrasion/ friability loss is usually expressed as percentage loss
in weight. The test is rejected if any tablet caps, laminates or breaks up in course of the test. As a rule of
thumb, a maximum weight loss of not more than 1% generally is considered acceptable for most
pharmaceutical products. Values of up to 2% or above have been reported in direct compression
formulations. The friability of tablets may be influenced by moisture content. Chewable tablets show a
high friability weight loss compared to conventional compressed tablets.

A number of instruments are available for friability tests. QC Department of UCPL performed their
Friability Tests by Tablet Friabilator.

The Details of Tablet Friabilator is given below :

Name: Tablet Friabilator

Speed : 25(±1) RPM

Time : 1sec to 10 hours

Powe : 220-230v/50Hz

Origin : Electrolab, India

6. Dissolution Test:

This test measures the amount of time required for a given percentage of the drug substance in a tablet to
go into solution under a specified set of conditions. It is intended to provide a step toward the evaluation
of the physiological availability of the drug substances.

The dissolution medium for each drug is available in the individual drug monograph. For basic drugs,
acidic media are used (e.g. 0.1 M hydrochloric acid) while alkaline media are used for acidic drugs (e.g.
alkaline buffers). For drugs with non-ionizing molecules, water is recommended. Dissolution rate test is
performed at 37 ± 1°C. Samples are removed from the dissolution chamber at periodic intervals and
analyzed for drug content using a spectrophotometer.

The Details of Dissolution test apparatus used in UCPL is given below:

Name : Dissolution Tester

Model : EDT-80LX

Temperature : 30-40°C ± 0.5%

RPM : 20-250 ± 0.5%

Power : 220-230V/50Hz

Origin : Electrolab, India

7.Disintegration Test:

The disintegration test is used to show how quickly the tablet breaks down into smaller particles, allowing
for a greater surface area and availability of the drug when taken by a patient. Disintegration tests are
however, useful for assessing the potential importance of formulation and process variables on the
biopharmaceutical properties of the tablet, and as a control procedure to evaluate the quality
reproducibility. To carry out a disintegration test for tablets, we use a basket which holds 1 to 6 tablets.
This is then raised and lowered into a beaker of water, which is used to simulate conditions in the stomach
at 37°C. If the tablets or capsules float, perforated plastic disks are placed on the top of the tablets to keep
them under the water level. The tablet disintegration time is taken when no residue is left in the mesh.

Disintegration time for uncoated tablet 5-10 min

Disintegration time for film coated tablet 15-30 min

Disintegration time for Enteric coated tablet 60 min

The details of Disintegration Tester used in UCPL is given below :

Name: Disintegration Tester

Model : ED-2L

Temperature : 20-30°C ± 0.55%

No of stroke : 30 ± 1 strokes / min

Stroke Height : 55mm (2mm)

Power : 220v-230V/59-60Hz

Origin : Electrolab, India.

8.Leak test :

The test which is used to check the integrity of packed strips, blisters, Bottles and small sachets
containing tablets, Capsules and Dry Powders is called leak test. Leak test Apparatus is used to test the
quality of the packaging process and to check that the seals enclosing the product are perfectly intact and
no water should go inside the pack. It is designed to find the smallest holes or Puncture and imperfections
in packed Products .

Leak test shall be performed by Production and Quality assurance during packing operation. Leak test
shall be performed Before starting of packing operation, every 3 to 4 hours interval, after Break, End of
Operation and after change in Foil roll. Take 4 litter of fresh potable water in Vacuum desiccator and add
10 to 12 drops of methylene blue solution and ensure complete mixing of methylene blue. In order to
identify the leakage in Blister or stripes methylene blue colour is used and Change the solution in the
desiccator everyday or whenever required.

The details of leak test apparatus used in UCPL is given below :

Name: Leak Test Apparatus

Model : LT-101P

Vacuum setting : less than 400mm of Hg (±10mm of Hg within 30sec)

Power : 230V/50Hz

Origin : India

9.LOD or Moisture content :

Moisture content determination is an important quality control test in pharmaceutical manufacturing, from
the checking of incoming raw materials and in-process control of tablets and capsules to undertaking
quality checks of finished drugs as part of pharmacopeial testing procedures. Moisture testing is also one
of the critical quality parameters in the stability testing of drugs. The standard method for measuring
moisture in pharmaceuticals is loss on drying using a drying oven and a laboratory balance. However, this
is a time-consuming and labor-intensive process. A halogen moisture analyzer is a viable alternative for
determining moisture content that meets regulations and provides fast, precise and reliable measurements.
The details of Moisture Analyzer used in UCPL is given below :

Name: Moisture Analyzer

Model: MA-45

Heating Element : Ceramic/Quartz-rod IR heater

Temperature range : 40-230°C

Weighing Capacity : 0.100-45 gm

Power Supply : 230V/60Hz

Origin : Sartorius, Germany.

10.PH Test :

The pH value conventionally represents the acidity or alkalinity of an aqueous solution. In the
Pharmacopoeia, standards and limits of pH have been provided for those pharmacopoeial substances in
which pH as a measure of the hydrogen-ion activity is important from the standpoint of stability or
physiological suitability. The determination is carried out at a temperature of 25°C ± 2°C, unless
otherwise specified in the individual monograph.

The pH value of a solution is determined potentiometrically by means of a glass electrode, a reference

electrode and a pH meter either of the digital or analogue type.

The details of PH meter used in UCPL is given below :

Name: PH Meter

Model : S220

Temperature : -2 to 20°C

Weighing capacity : 0.100-45 gm

Power.supply : DC9-12V

Ion: 0.000 to 10,000 ppm

Origin : Mettler Toledo, Switzerland

11.Spectrometric Analysis :

Spectrometric analysis is basically performs to determine the structure or quantity of substances by

measuring their capacity to absorb light of various wavelengths.Spectrophotometric analysis is done by
spectrophotometer. Modern spectrophotometer can interrogate wide electromagnetic spectrum including
X-ray, Ultraviolet, Visible, Infrared or microwave lengths.

The details of Spectrophotometer used in UCPL is given below :

Name : Spectrophotometer

Model : UV 1800

Photometric system : Double Beam

Wavelength range : 190-1100nm

Detector : Silicon Photidiode

Power supply : 220-230V

Origin : Shimadzu, Japan.

12. Karl Fischer Titration :

Karl Fischer reagent method of water content determination is widely used in pharmaceuticals. This is
most reliable and accurate method for moisture determination.Karl Fischer method uses the Karl Fischer
Reagents to determine the moisture content of a sample and it is a widely popular method because it
allows you to determine the water content of drug in a very fast, accurate and specific way in addition to
needing a very small amount of sample for the analysis.

The reagents consist of a solvent Alcohol (ROH), A known concentration of Iodine (I 2), a Base (RN) an<
Sulfur dioxide (SO2).

Principle of Reaction : The Bunsen reaction between iodine and sulfur dioxide in an aqueous system is
the basis for the Karl Fischer Reagents reactions.

I2 + SO2 + 2H20 = 2HI + H2SO4

The above reaction was adjusted by Fischer for the determination of water content of a substance in a
non-aqueous system.

The details of Karl Fischer Titration used in UCPL is given below :

Name: Karl Fischer Titration

Model : V20

Serial No : B210762724

Power supply : 240V/50-60Hz

Origin : Mettler Toledo, Switzerland.

13.Refractometry measurement :

It is used to determine the refractive index of a liquid sample which changes according to the moisture
content.The refractometer is a well-established instrument used for measuring the water content of liquids.

The details of Refractometer used in UCPL is given below :

Name : Automatic Refractometer

Model : Abbemet 200

Temperature : 10-30°C

Power : 220-240V/Hz

Origin : Anton paar, Germany.

14. HPLC :

HPLC is the form of liquid chromatography that is generally used in the pharmaceutical industry, as it can
provide the precise results that are required. The results can be used to analyse finished drug products and
their ingredients quantitatively and qualitatively during the manufacturing process. This is achieved
through the separation, quantification and identification of components in a mixture and can be used to
reveal the identity of a drug and monitor the progress of a therapy on a disease.One of the main benefits
of HPLC is its ability to elucidate the structure and determine the quantities of impurities in
pharmaceutical formulations.

The details of HPLC used in UCPL is given below :

Name : HPLC

Model : WATERS-1525

HPLC pump : 1500

Autosampler : 717 plus

Column : C18

Column Heater : 5-60°C

Detector : UV / Visible

Injector : Manual (Rheodyne 7725i)

Origin : Waters Co USA

15. Sonication :

Sonication is one of the processes used in sample preparation to extract an active pharmaceutical
ingredient (API) from its carrier, or excipient, prior to conducting content uniformity and potency assay
tests. Other methods of achieving desired results may be employed.

The details of Sonicator used in UCPL is given below :

Name : Powersonic 603

Temperature range : 100°C

Capacity : 1-2 litre

Power supply : 220-240V/50Hz

Origin :Hwashin Technology, South Korea.

Calibration

Calibration is a process that demonstrates a particular instrument or device produces results within
specified limits, as compared to those produced by a traceable standard over an appropriate range of
measurements. Calibration activities must be performed with qualified instruments by an accredited
laboratory.

Purpose of Calibration :

1. To maintain the accuracy and quality of measurements ptoduced by all the equipments.
2. To accurate ‘drift’ particularly when using technologies or measuring parameters such as
temperature and humidity.
3. To be confident in the results being measured to maintain the calibration of equipment
throughout its lifetime for reliable, accurate and repeatable measurements.
4. To minimise any measurement uncertainty by ensuring the accuracy of test equipment.
5. To quantifies and controls errors or uncertainties within measurement processes to an acceptable
level.

Validation

Validation is the process of establishing documentary evidence demonstrating that a procedure, process,
or activity carried out in testing and then production maintains the desired level of compliance at all
stages.
Types of Validation :

Validation is divided into following subsections which include :

1. Analytical method validation

2. Process validation
3. Cleaning validation
4. Equipment validation

Analytical method validation: The purpose of analytical validation is to verify that the selected
analytical procedure will give reliable results that are adequate for the intended purpose. There are
different parameters which come under analytical method validation. These are as follows:

Accuracy
Precision
Repeatability
Reproducibility
Specification
Linearity
Range
Detection limit
Quantitation limit

Process validation: This type of validation demonstrates documented proves. The process validation also
assures the repeatability of the process and decreases the risk of manufacturing problems which lead to an
increase in output of predetermined quality.On the bases of the stage of production under process
validation, it can be of four types which are as follow:

1. Prospective validation
2. Concurrent validation
3. Retro specific validation
4. Revalidation.

Cleaning validation: Cleaning validation provides documented set up with a high degree of surety that
particular system/equipment or part of equipment is consistently clean-up to predetermined quality and
acceptable limits. Pharmaceutical products are contaminated by variety of substances such as lubricants,
airborne materials, prepared product residues, and microbes. Hence, an adequate cleaning procedure plays
an important role to prevent contamination and cross contamination.

Equipment validation: Equipment validation is established documented set up that proves any
equipment works correctly and leads to accepted and accurate results (predetermined result). The process
of equipment validation is based on the principle that equipment must be designed, constructed,
maintained, and adapted to perform the operations which are to be carried out. Equipment’s are the basic
component of pharma industries; therefore, before performing a process in pharma industries, it becomes
primary important to issue equipment validation (documented evidences of equipment). It has different
phases which have further subsections or steps, these are as follow:

1. Design qualification (DQ)

2. Installation qualification (IQ)
3. Operational qualification (OQ)
4. Performance qualification
5. Process qualification

The process of equipment validation is mainly divided into three phases:

1. Phase – 1: Pre-validation phase.

2. Phase – 2: Process validation phase.
3. Phase – 3: Validation maintenance phase.
Importance of Validation :

1. Process parameters and controls are determined during the validation of any process or system.
2. It helps to determine the worst case and risks that may arise during the manufacturing of the
quality products.
3. Validation helps to investigate the deviations caused during the process.
4. Deep study and understanding of the system and equipment are made possible due to the
validation.
5. A validated process required less process control and the finished product testing.
6. Batch to batch variation is minimized due to the validation of processes, systems and equipment.
7. Reduces the production cost of the product.
8. Increases the production of manufacturing facility due to the minimized rework and rejection.
9. Decreases the chances of the failure of the batches.