INTRODUCTION TO QUALITY CONTROL

QUALITY

 Combination of attributes or characteristics of a product which, when compared to a

standard, serves as a basis for measuring the uniformity of the product and determines its
degree of acceptability

QUALITY CONTROL

 Gives the assurance that a product conforms to standards and specifications through a
system of inspection, analysis and action
 Responsible for on-line or in-process testing

QUALITY ASSURANCE

 Determines that the system and facilities are adequate, and the written procedures are
followed to assure that the finished drug product meets the applicable specifications for
quality
 Overall organizational body designed to assure product quality

POTENTIAL BENEFITS DERIVED FROM QUALITY CONTROL SYSTEM

1. Minimizes or eliminates the risk of marketing unsafe products

2. Guarantees conformance to regulatory requirements
3. Guarantees product efficacy
4. Reduces operating costs
5. Reduces operating losses
6. Produces higher employee morale
7. Motivates the pharmaceutical/medical professions to sell or prescribe the product

QUALITY CONTROL/ASSURANCE FUNCTIONS

1. Analysis Function
 Assures acceptability of a product
 Involves testing of raw materials, packaging components and bulk products during
processing and after packaging prior to its release to the market
2. Monitor function
 Assures that processes are maintained and any deviation from specified requirements
are reported
 Involves sampling and examination of materials while being processed
3. Record review and Release function
 Responsible for carefully reviewing of batch records and assuring that all necessary
records are present, complete and accurate.
4. Audit function
 Designed to detect areas where established SOP’s are not being followed and report
these findings for appropriate action
TYPES OF ERRORS

1. Indeterminate Error
 Manifest by slight variations in a series of observation by the same observer
2. Determinate Error
 Recur in a constant manner in each of a series of determination

SOURCES OF ERRORS

1. Materials
2. Machines
3. Methods
4. Men

RISKS OF ERROR

1. PRODUCER’S RISK - Probability of rejecting a good batch

2. CONSUMER’S RISK - Probability of accepting a bad batch

STANDARDS and SPECIFICATIONS

1. FORMULA
 Concise and precise statement of ingredients that comprise the product, together with the
percentage and/or weight of each
2. RAW MATERIAL SPECIFICATION
 Enumerates the characteristics of all the materials that go into the product and the
permissible range of purity of each ingredient
 Deviation beyond this range may be expected to cause failure of the product to function as
planned or may result in undesirable lack of uniformity
3. STANDARD OPERATING PROCEDURE
 Step by step method on how to go about a job
 Embrace the legal requirements set by CGMP
 Must spell out all information and instruction that assure that variations in production will be
held to within acceptable established ranges
4. FINISHED PRODUCT SPECIFICATION
 Must cover all characteristics that affect proper performance, purity, safety and stability of
the product
5. PACKAGING MATERIAL STANDARD
 Set for everything that goes around the product
 Packaging must be considered with the following:
a. Units may have to run on a high-speed line
b. May involve a complicated assembly
c. Package must be functional
d. Package must be completely compatible with the product
e. Package must protect the product and assure its stability
f. Package must ship well
6. TESTING METHODS
 Indispensable in assuring conformity to standards
 Tests must be validated to ensure precision and accuracy on application
 CLASSIFICATION OF DEFECTS

ACCORDING TO MEASURABILITY

1. VARIABLE DEFECT
 Measured directly by instruments
 Length, weight, volume, pH, concentration, thickness
2. ATTRIBUTE DEFECT
 Cannot be measured directly by instruments
 Odor, color, clarity. Taste, presence or absence of a characteristic

ACCORDING TO SERIOUSNESS OR GRAVITY

1. Critical defect - may endanger life or property and may render the product non-functional
2. Major defect – may affect the function of the object and therefore, may render the product
useless
3. Minor defect – does not endanger life or property nor will it affect the function but remains a
defect since it is outside the prescribed limits

ACCORDING TO NATURE

1. Ocular defect – defect that is visible

2. Internal defect – defect which is not seen although present
3. Performance defect – defect in function

MATERIAL CONTROL
Receiving Tally Report (RTR)

 Reception of materials, incoming cargo report, receiving report, receiving ticket

 Prepared in the warehouse by warehouse personnel
 Distributed to all groups concerned with purchase, inventory, use and control of materials
(Quality control, warehouse, purchasing and accounting departments)

Raw materials

 Ingredients intended for use in manufacturing of pharmaceutical products

 Control stages
1. Reception
1) checking of RTR by QC inspector for accuracy
2) visual examination of raw materials
3) sampling
2. Quarantine
1) Checking of RM containers with “Quarantine” or “Hold” Sticker
2) Submission of samples to the laboratory for testing
3) Testing of samples
3. Rejected
Materials not meeting monograph specifications are held at rejected materials area
 4. Approved
1) Materials that meets monograph specifications are brought to approved
materials area
2) Approved materials are tested for reassay date
3) Approved materials are audited
(FIFO – First In First Out/ FEFO – First Expiry First Out)

Stickers

 Attached on individual containers, cage or pallet of materials for identification and avoidance of
mix-ups
 No two stickers of different disposition must be present on same container
 Issued by quality control, pasted by receiving warehouse personnel
o Yellow – quarantine
o Green – approved
o Red – rejected

Printed Materials

 Labeling – all written, printed or graphic materials accompanying a product

 Minimum Criteria
o Text o Sealability
o Color o Cleanliness
o Size o Surface finish
o Thickness o Adequate paste
o Grain direction o Shape
 Bar Codes – placed to prevent mix-ups of inventories of printed labeling materials

Packaging Materials

 Should not be reactive, additive or absorptive

 2 Types
o Primary packaging components – comes in direct contact with the product itself
o Secondary packaging components – serves as accessory to primary packaging

MANUFACTURING CONTROL
IMPORTANT DOCUMENTS

1. Manufacturing monograph – basic document where master formula and batch production
records are based
2. Quality control monograph – provides specifications and methods for testing the components of
a product
3. Batch records
a. Master formula – original document used as key in production of products
b. Batch reproduction record – accurate reproduction of master formula record
 4. Standard operating procedures – explains in detail procedures and proper sequence of steps to
be done and how equipment are to be operated for maximum performance

In Process Quality Control (IPQC)

 Determines if the product meets specifications throughout the entire processing period and
particularly during critical stages of manufacturing

STABILITY
Ability of particular formulation in a specific container to remain within its physical, chemical,
therapeutic and toxilogical speification

TYPE OF STABILITY CONDITIONS TO BE MAINTAINED

CHEMICAL Retains its labelled potency

PHYSICAL Appearance, uniformity, dissolution etc…

MICROBIOLOGICAL Retain sterility, effectiveness of preservatives

THERAPEUTIC Drug action remains unchanged

TOXICOLOGIC No significant increase in toxicity

FACTORS AFFECTING DRUG STABILITY

 pH  Storage condition
 Temperature  Agitation
 Moisture  Method of manufacture
 Humidity  inversion
 Light

CAUSES OF PRODUCT DEGRADATION

Physical Chemical
 Loss of volatile constituents  Incompatibility oxidation
 Loss of water  Reduction
 Absorption of water  Hydrolysis
 Color change  Racemization
 Crystal growth  Decarboxylation
 Formation of precipitates
SHELF-LIFE

 Period of stability of a preparation

 Time from the date of manufacture of the formulation until its chemical or biological activity not
less than 90% of the labelled potency
 Calculated using Arrhenius equation or by the regression line analysis by the method of least
square
EXPIRATION DATE

 Direct application and interpretation of the knowledge gained from stability testing

STABILITY TESTING

STABILITY PRODUCT STORAGE CONDITION MINIMUM TIME

CONDITION STORAGE TEMPERATURE/HUMIDITY PERIOD
CONDITION

Accelerated Room temperature 400C +/-20 / 75% +/-5% 6 months

Refrigerator 250C +/-20 / 60% +/-5%

Long-term Room temperature 300C +/-20 / 65% +/-5% 12 Months

300C +/-20 / 35% +/-5%
250C +/-20 / 60% +/- 5%

Refrigerator 2-80C

Intermediate Room temperature 300C +/-20 / 65 +/-5%

OVERAGE

 Used to extend shelf-life

 Proposed overages
 Vitamins – 30%
 Dry dosage forms – 15%
 Fluids – 20%
 Ointment, suppositories, aerosols, creams and foams – 25%

Reassay date
 Date of retest/periodic testing to revalidate pharmaceutical materials
o 6 months – vitamins, flavors
o 12 months – active ingredient, dyes
o 24 months – active ingredients, excipients
 Retest Requirements
o Appearance o Assay
o Identification o Microbial tests
o Melting range
o Specific gravity
o Refractive index
o pH
o loss on drying, moisture/water
content
o Alkalinity/Acidity
o Alcohol content
o Degradation limit