QUALITY CONTROL PROCEDURE IN PHARMACEUTICAL INDUSTRY

The word ”Quality“ refers to the characteristics of a product from both qualitative and quantitative point of view. It refers to the quality of process as well as the
product itself. The word “Control“ implies a procedure by which decisions may be made regarding whether production is proceeding according to the plan and
meeting the standards established previously. The quality of a pharmaceutical product is standard, which is designed after a long research and development. Here
quality does not concern with active substance but the quality depends upon many other factors such as excipients and product development procedures.
The pharmaceutical industry is responsible to design, test and produce dosage form, which provides quality, purity, stability, safety, uniformity of contents and
physiological availability to the consumer.

THE AUTHORITY OF PROCESS CONTROL

The maintenance of quality of a drug depends upon each and every person and setup in industry. To provide Quality Assurance; Quality Function and Quality
Control must be maintained. Quality Assurance:
Quality Assurance means that it can be said with confidence that Quality Function is being performed adequately the Quality Assurance group of company
provides a strict supervision in all parts of each step. Its function is to inspect various phases of production so that the final product should be of highest quality.
The monitoring of records, procedures, systems, facilities, labeling personnel and performing tests is the responsibility of Quality Assurance Group. The Quality
Assurance may be the part of Quality Control Department or it may work independently under its own manager.
Quality Variation:
When the quality of any drug is given by industry, then it is responsible for any variation from the standard. Quality Variation may occur due to any mistake
during the whole process i.e. from the reception of raw material up to the final product in the packaged form.
The risk of error increases as the material increases and the method become very complicated. The general sources causing product Quality Variation during
manufacturing are as follows:

SOURCES OF VARIATIONS:
1. MATERIALS:
a. Variations among suppliers of same substances.
b. Variations among batches from same suppliers.
c. Variations within a batch.
2. MACHINES:
a. Variation of equipment of same process.
b. Difference in adjustments of equipment.
c. Aging of machines and improper care.
3. METHODS:
a. Wrong procedure.
b. Inadequate procedure.
c. Negligence in procedure by chance.
4. MEN:
a. Improper working conditions.
b. Inadequate training and understanding.
c. Lack of interest and emotional upheavals*.
d. Dishonesty fatigue and carelessness.

QUALITY VARIATION CONTROL:

The mistakes can be controlled, minimized or eliminated by material control; packaging control and GMP variations can be controlled when Quality Control,
Quality Function, and Quality Assurance work side by side.

* Upheavals: a violent or sudden change or disruption.

• Material control.
CONTROL PROCEDURE:
Controlling each and every step of process can control variations.
Control can be divided into:
• Manufacturing practice control.
• Packaging control.
• Distribution control.

MATERIAL CONTROL: It starts just after the reception of materials. Most of the materials that are active substances, excipients, packaging and printed materials
are received by the industry from suppliers. Thus there should be adequate established system for the receipt, testing and storage of all these supplies. There
should be a complete record of all the procedures and tests. In the material following things are included:
• Drug substances.
• Excipients.
• Packaging and printed materials.

After the reception of material, it is kept in a definite area. Thus before laboratory testing, proper containers, labels, lot number, expiry dates etc all are checked.
The material is stored in a proper way either they are arranged alphabetically or they are differentiated depending upon physical nature. Then samples are taken
for laboratory testing and a label (Sampled) is fixed on material.
In case of active constituents, percentage purity, adulteration, expiry date, lot number, exact packing etc is checked.
In case of printing and packaging material especially the color of label, weight of label and cartons and grammage etc is checked.
If the material is up to the mark, then a label (Passed) is pasted on it and it is placed at its proper place.
On the other hand, if it is substandard, then it is kept in “Rejected Area” and sent back to the supplier.

MANUFACTURING PRACTICES CONTROL:

Successful GMP is difficult to attain but to some extent, it can be modified and controlled. Specific procedures can be applied to attain the best quality.
In case of manufacturing, following controls are important:
 Personnel.
 Equipment and building.
 Control of record.
 Production procedure control.

(A). PERSONNEL:
Usually properly educated and well-trained persons should be in the industry.
 There should be proper selection and training in all departments i.e. production, packaging, labeling, etc, etc.
 There should be general lectures for less educated persons who work in the labeling or packaging section in an understandable language.
 They should be made aware of the fact that what is the importance of life saving.
 They should be warned about all the dangers of their mistakes and errors.
 There should be properly educated supervisors working above the workers.
 The supervisors should always be there so that in case of any trouble or question, they must be available.
 All the workers should be properly checked and all the processes at different steps should also be monitored by highly educated and experience persons who
may not only be well qualified but experienced as well.

(B). EQUIPMENT AND BUILDING:

 The equipments and building used in storage, processing, checking and packaging should be of a suitable design, size, construction and location.
 In case of equipments, these should be constructed in a proper size and proper way. The size should be such that complete batch can be processed all at once.
 The surfaces of equipments should be non-reactive, non-absorptive and non-additive.
 The equipment should be constructed and fitted in such a way that it is easy to replace, easy to wash easy to operate and easy to empty.
 In case of building, there should not be any contamination i.e. the tablet and liquid section should be separated completely and even there should be complete
separation in tablet machines. It means that machines should have separate cabinet.

(C) CONTROL OF RECORD:

The records such as master formula record and batch production record must be maintained.

1. MASTER FORMULA RECORD:

a. The master formula record must be prepared for each product.
b. It must be signed by a competent and responsible person.
c. The language must be so that it may not be miss-interpreted.
d. It should be checked by another competent person and must be countersigned.
e. The master formula varies from production to production and from batch to batch.
f. Master formula record include the following information:
i. Name of the product, dosage form and strength.
ii. Complete list of ingredients including excipients.
iii. Quality by weight or volume of each and every ingredient.
iv. Standards or specifications of each ingredient.
v. Any calculated excess of an ingredient.
vi. Theoretical yield and termination of process.
vii. Manufacturing and control instructions, specifications and precautions.
viii. Complete description of closures, containers, labeling, packaging and other finishing material.

2. BATCH PRODUCTION RECORD:

a. Batch production record must be prepared, maintained and controlled for each batch of a product.
b. It must be retained for about 5-years after product distribution.
c. Batch production record should have following information in addition to master formula record.
i. Batch number.
ii. Code number.
iii. Manufacturing date.
iv. Expiry date.

(D). PRODUCTION PROCEDURE CONTROL:

The processes of manufacturing are operated according to the established rules from the reception of material up to delivery of final product.
 A complete list of ingredients along with their quantities is delivered to the Production Department. It is called Master Formula of that batch. It contains all the
information of that batch i.e. procedures and equipments to be used and precautions to be taken, etc, etc.
 This master formula is taken into the store and all the materials for the batch are weighed and delivered to Production Department. All ingredients are rechecked
and tested in laboratory.
 In the production procedure control, some tests are done during the process, which is called “In Process Quality Control (IPQC)”
 The IPQC is under Quality Control Department.
 Both Quality Control and Production Departments are responsible for the production procedure control.
 IPQC tests for different dosage forms are as under:

1. IPQC TESTS FOR TABLETS:

a) Drug contents determination.
b) Moisture contents of granules.
c) Assay of active ingredients.
d) Weight variation of uncoated tablets.
e) Hardness test.
f) Disintegration test.

2. IPQC TESTS FOR SYRUPS AND SUSPENSIONS:

a) Drug contents determination.
b) Assay of active ingredients.
c) pH.
d) Weight per ml.
e) particle size

3. IPQC TESTS FOR SEMI-SOLIDS:

a) Drug contents determination.
b) Assay of active ingredients.
c) Uniformity and homogeneity test.
d) Viscosity and specific gravity test.
e) Filling test.
f) Leakage test.
4. IPQC TESTS FOR INJECTABLES:
a) Drug contents determination.
b) Assay of active ingredients.
c) pH.
d) Pyrogen test.
e) Stability test.
f) Leakage test.
g) Check up of particulate matters.

PACKAGING CONTROL:

The packaging control is usually completed before manufacturing of product.

 When the product come in packaging section, it should be packed in recommended containers and there should not be any mistake in case of labeling and
writing of batch number, etc, etc.
 The packaging material is used according to the nature and distribution of product.

DISTRIBUTION CONTROL:

The responsibilities of Quality Control Department are not finished even after the distribution of finished dosage form in the market.
 The samples of each batch are kept in record and these samples are selected during packaging and are in the same packs as they are marketed.
 These are kept for years in order to examine or test the material for any purpose or necessary demand.

QUALITY CONTROL AND ITS ORGANIZATION

What is quality?
QUALITY:
It is a combination of all the characteristics of a product that determine the degree of acceptability of the product.
The PMA (Pharmaceutical Manufacturing Association) says that the quality of a product is its degree of possession of those characteristics designed and
manufactured with and which contribute to the performance of extended functions when the product is used as directed.
The central idea of Quality Control is that quality must be built into the product during research and development and production.
Central control as it applies to pharmaceutical industry is the organized effort within an entire establishment to design product and assure the specified quality in
each unit of product distributed.
It the responsibility of pharmaceutical company to design tests and procedures to produce dosage form that contains exact quantity and quality of drugs, which is
acceptable, reproducible, convenient and elegant.

PRODUCTION CHARACTERISTICS:
The most important pharmaceutical characteristics are:
Identity. Purity.
Potency. Uniformity.
Stability. Safety and efficacy.
Physiological availability. Therapeutic activity.

ORGANIZATION OF QUALITY CONTROL:

The individual responsible for the quality of drug product in a pharmaceutical company is generally the director of Quality Control. He should report to the
president or vice-president and should be on the same organizational level as that of Production Manager. Only the highest level of management should review
his decisions about quality.

A. ORGANIZATIONAL CHART OF QUALITY CONTROL:

President
Vice-President
Director/Manager

Analyst Supervisor Quality Control & Quality Assurance

B. FUNCTIONAL CHART OF QUALITY CONTROL:

President

Director

Specification & Analytical Department

Biological
Testing
Laboratory
Central
Release
Office
Inspection
&
Checking
Chemical Testing
Laboratory

There are five departments of functional Quality Control chart. These are discussed one by one.
1. SPECIFICATION AND ANALYTICAL DEPARTMENT:
Quality of the finished product depends upon quality of the raw material used in the manufacturing operation.
This department is responsible to analyze raw material and the product according to the specifications.
Following are the specifications, which must be considered to maintain quality of the product.
Solubility. Identification.
Particle size. Surface tension.
Loss on drying. Residue on ignition.
Crystal shape. Viscosity, etc, etc.
These are the specifications originated by the efforts of Quality Control research during product development.
All specifications include those requirements, which are applicable to federal and state Government’s official compendia.
The major cost of Quality Control lies in the testing of product throughout manufacturing operations.

2. CHEMICAL TESTING LABORATORY:

Every lot of every shipment of raw material and every lot of finished product, which can be controlled by physical and chemical tests, is tested in the ”Chemical
Testing Lab”.
This requires a well-equipped chemical lab properly staffed for better performance of great number of chemical analysis.
It should be located in an accessible area and protected from noise and vibrations common in manufacturing operations.
3. BIOLOGICAL TESTING LABORATORY:
A number of finished products require biological assay. Biological tests are not confined to a group of products recognized as biologicals in drug industry; since a
number of pharmaceutical products such as parenterals require sterility and pyrogen testing before release to market.
Biological lab should have essential animals.
The staff in the biological testing lab should be well trained.
4. CENTRAL RELEASE OFFICE:
The record resulting from the exercise of Quality Control functions throughout all the steps of manufacturing and packaging operations are voluminous. Quality
Control organization is responsible to check these records.
The record provides complete history of each lot of each product manufactured and therefore makes it possible to construct the relevant features of any package
distribution into the market.
The assay and access of central release office to records together with its liaison** with all manufacturing and packaging operations makes it possible for the group
to investigate customers’ complaints about product quality.
5. INSPECTION AND CHECKING:
The responsibility for inspection and sampling of every shipment of raw material received and every lot of finished goods turned over for distribution falls within
the province of Quality Control Inspectors.
The selection of samples of raw material and finished goods is an important aspect of Quality Control function.

** Liaison: communication and co-operation.

SPECIFICATIONS FOR PACKAGING MATERIALS:

BOTTLE:
Capacity.
Material (Glass, Plastic, Aluminum).
Weight of bottle.
Thread of bottle.
Cap material (Rubber, Plastic coated).
Thickness.

COTTON:
Type.
Moisture contents.

SILICA BAG:
Weight.
Capacity.

CARTON:
Dimensions (Notches, Locking system).
Quality of Board (Grammage).
Printings.
Color (lovibond, Tinctometer is used; the local industries have an album of colors).
LABEL:
Dimensions.
Printing.
Weight.
Striations (Lines on Paper).
Summary
FLOW CHART-1

QUALITY CONTROL PROCEDURE

1) AUTHORITY OF PROCESS CONTROL.

2) QUALITY ASSURANCE.
3) QUALITY VARIATION.
a. SOURCE OF VARIATION
i. Material
ii. Machine
iii. Method
iv. Men
4) QUALITY CONTROL OF VARIATION.
a. MATERIAL CONTROL
b. MANUFACTURING PRACTICES CONTROL
a. Personnel
b. Equipment & Building
c. Control of Record
i. Master formula record
ii. Batch production record
c. PRODUCTION PROCEDURE CONTROL
a. IPQC for Tablets
b. IPQC for Syrups and Suspensions
c. IPQC for Semisolids
d. IPQC for Injectables
d. PACKAGING CONTROL
e. DISTRIBUTION CONTROL

FLOW CHART-2
QUALITY CONTROL AND ITS ORGANIZATION

1) ORGANIZATION OF QUALITY CONTROL

2) ORGANIZATIONAL CHART OF QUALITY CONTROL

PRESIDENT
VICE-PRESIDENT
DIRECTOR/MANAGER
QUALITY CONTROL AND QUALITY ASSURANCE
SUPERVISOR
ANALYST
3) FUNCTIONAL CHART OF QUALITY CONTROL
a) PRESIDENT
a. DIRECTOR
i. SPECIFICATION AND ANALYTICAL DEPARTMENT
ii. CHEMICAL TESTING LABORATORY
iii. BIOLOGICAL TESTING LABORATORY
iv. CENTRAL RELEASE OFFICE
v. INSPECTION AND CHECKING

DETERMINATION OF EMULSION TYPES

There are many methods available for the determination of emulsion type but the most commonly used are:
1. Drop dilution method.
2. Dye solubility method.
3. Fluorescent test.
4. Electrical conductivity test.
5. Direction of creaming test.
6. Filter paper test.
These methods determine whether the emulsion is oil in water (o/w) type or water in oil (w/o) type.

1. DROP DILUTION METHOD:

This method is based on the principle that emulsion is always miscible with the external phase. If water is added to water in oil w/o type emulsion, it will not be
mixed. On the other hand, oil mixes well.
Same is the case with o/w type emulsion. If oil is added to oil in water o/w type emulsion, it will not be mixed. On the other hand, water mixes well.
2. DYE SOLUBILITY METHOD:
It is based on the solubility of any dye in the external phase. Amaranth, a water soluble dye gives color to oil in water o/w type emulsion, but not to water in oil
w/o type emulsion. Same is the case with oil soluble dyes.
3. FLUORESCENT TEST:
Based on the fluorescence of oils under ultraviolet light, the emulsion is examined under the light in the microscope. If the whole fluid is fluorescent, it is water in
oil w/o but in case of oil in water o/w spotty fluorescence will appear.
4. ELECTRICAL CONDUCTIVITY TEST:
Based on the electrical conductivity of aqueous solutions, the electric current is supplied and electrodes are placed in the emulsion. If the current is passed, it is oil
in water o/w and if is not passed, it is water in oil w/o.
5. DIRECTION OF CREAMING TEST:
Creaming is the sedimentation of the dispersed phase which is either upwards or downwards, upon which this test is based. The density of oil is mostly less than
water. Thus if creaming is at the upper side, it is oil in water o/w and if it is downwards, it is water in oil w/o type of emulsion.
6. FILTER PAPER TEST:
Take a filter paper, put a drop of emulsion on the filter paper. Evaporate it; if there is a spot on the filter paper, the emulsion will be water in oil w/o. On the other
hand, if there is no spot, the emulsion will be of oil in water o/w type.