QUALITY VARIATION AND CONTROL

1. SORCES OF QUALITY VARIATIONS
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 occurdue to any mistake
during the whole process i.e. from the reception of raw material up to the final
productin the packaged form. The risk of error increases as the material increases
and the method become very complicated.
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.

2. CONTROL OF QUALITY VARIATIONS
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.
CONTROLPROCEDURE:
Controlling each and every step of process can controlvariations. Control can be
divided into:
1.MATERIALCONTROL
2. MANUFACTURING PRACTICESCONTROL
3.PACKING CONTROL
4.DISTRIBUTIONCONTROL
1.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.
2.MANUFACTURING PRACTICES CONTROL:-
SuccessfulGMP 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:
A. Personnel.
B. Equipment and building.
C. Control of record.

3. D. Production procedure control.
(A). PERSONNEL:
Usually properly educated and well-trained persons should be in the industry.
1.There should be properselection and training in all departments i.e.
production, packaging, labeling, etc, etc.
2. There should be general lectures for less educated persons who work in the
labeling or packaging section in an understandable language.
3.They should be made aware of the fact that what is the importance of life
saving.
4. They should be warned about all the dangers of their mistakes and errors.
5. There should be properly educated supervisors working above the workers.
6. The supervisors should always be there so that in case of any trouble or
question, they must be available.
(B). EQUIPMENT AND BUILDING:
1.The equipments and building used in storage, processing, checking and
packaging should be of a suitable design, size, construction and location.
2.In case of equipments, these should be constructed in a propersize and proper
way. The size should be such that complete batch can be processed all at once.
3.The surfaces of equipments should be non-reactive, non-absorptive and
nonadditive.
(C) CONTROLOF RECORD:
The records suchas 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 personand must be countersigned.
f. Master formula record include the following information:
i. Name of the product, dosageform 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.

4. 2. BATCH PRODUCTIONRECORD:
a. Batch productionrecord must be prepared, maintained and controlled for
each batch of a product.
b. It must be retained for about 5-years after productdistribution.
c. Batch productionrecord should have following information in addition to
master formula record.
i. Batch number.
ii. Codenumber.
iii. Manufacturing date.
iv. Expiry date.
(D). PRODUCTION PROCEDURE CONTROL:
The processesofmanufacturing are operated according to the established rules
from the reception of material up to delivery of final product.
1. In the production procedurecontrol, some tests are done during the process,
which is called “In Process Quality Control(IPQC)”
2.The IPQC is under Quality ControlDepartment.
3.Both Quality Control and ProductionDepartments are responsible for the
production procedurecontrol.
� 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.

5. 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.
3.PACKAGING CONTROL:
The packaging control is usually completed before manufacturing of product.
1. When the productcome 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.
2. The packaging material is used according to the nature and distribution of
product.
4.DISTRIBUTIONCONTROL:
The responsibilities of Quality Control Department are not finished even after
the distribution of finished dosage form in the market.
1. 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.
2.These are kept for years in order to examine or test the material for any
purposeor necessary demand.