Scope of

QC

PMQA 311
WEEK 3: Current Good Manufacturing
Practices (cGMPs)
Unit outcome
At the end of discussion, student
should be able to:

• Explain the importance of cGMP.

Outline
● Basic Operational Roles
● Classification Used for Official Assay
● Stability of Pharmaceutical
Preparations
● Containers
● Sensitivity Test For Microorganism
● Administrative order
Basic Operational Roles
1. Control decisions must be based
solely on considerations of quality
of the product.
2. The facilities, personnel, funds,
and environment necessary to
perform their responsibility
effectively should be adequately
provided.
Basic Operational Roles
3. The operation must adhere rigidly
to the established standards or
specifications as determined
through systems inspection and
sampling and should constantly
strive for the improving the levels
of the current standards or
specifications.
Basic Operational Roles
4. The control decisions should be
independent administratively and they
must not yield or be overruled by
production or marketing under any
circumstances. The control decisions
should be subjected to review only by
the highest level of management in
time of major disagreement.
 The control decisions
involve both the health of
the consumer and
reputation of the
manufacturer.
Functions:
I. Material
A. PackagingControl
and Printed Materials
1. Drug
–Like
–The substance
materials
raw materials, or complete
to be controlled are
–
–Another
–Bar
–For
those
specs active
that
should
In general,
the
marks ingredient
appear
upon
point
label,
are be
of provided
as in
receipt aof
importance
experienced
found physical
for
the is the
specific
proof
Excipients
2.these
material,
part
areas of
practice
readers in the
of quality
materials
the final
FIFO
should
the label in control
dosage
(thickness,
raw
carefully
and and
including
materials
carton
inspectfor
inspection
Packaging
3.and performs
and appropriate
the
impact
package.
strength,
components
identification
printing.
visual and
Further
examination. light he find
. Should
purposes. precautions
the printed
packing
transmission) of materials
the raw are
against label mix-up material
also is
– Primarythen outright rejection is
defective,
essential.
– Secondary
made and no more sampling is
done.
Functions:
I. Material Control
–The materials to be controlled are
those that appear as a physical
part of the final dosage including
the package.
Functions:
I. Material Control
1. Drug substance or
active ingredient
2. Excipients
3. Packaging and
printed materials
– Primary
– Secondary
Functions:
A. Packaging and Printed Materials
–For the label, experienced proof
readers should carefully inspect
the printing. Further precautions
against label mix-up are also
essential.
Functions:
A. Packaging and Printed Materials
–Bar marks are found in specific
areas in the label and carton for
identification purposes.
Functions:
A. Packaging and Printed Materials
– In general, upon receipt of the material, the
quality control and inspection performs
appropriate visual examination. Should he
find the packing of the raw material is
defective, then outright rejection is made
and no more sampling is done.
Functions:
A. Packaging and Printed Materials
– Another point of importance is the
practice of FIFO in raw materials and
components .
Functions:
II. Control of manufacturing
practices
–The Food, Drug, and Cosmetic
Act empowered by the FDA to
inspect drug manufacturing sites
if they comply with SOPs,
practices and sanitation.
Functions:
II. Control of manufacturing
practices
–The successful application of
cGMP is complex but possible if
there is proper planning and
control.
Functions:
II. Control of manufacturing
practices
–It should be kept in mind that
GMP is an aid and not a
substitute for a good total quality
assurance program.
Classification Used
for
Official Assay
A. Titrimetric Method
• Acid-Base reaction
• Precipitation reaction
• Redox reaction
• Complexation reaction
• Anion-Cation reaction
B. Gravimetric Method
A. Weighing Drug after
Separation
B. Weighing a Derivative after
Separation
C. Weighing a Residue after
Ignition
C. Spectrometric Method
Photometric analysis depends upon:
• Spectrophotometry - the measurement
of the amount of light absorbed by a
solution,
• Turbidimetry - the measurement of the
amount of light absorbed by a suspension
• Nephelometry - the amount of light
scattered by a suspension
C. Spectrometric Method
Photometric analysis depends upon:
• Flame Photometry - the intensity of the
light emitted by an element when
subjected to high temperatures
• Colorimetry - the measurement of light in
the visible region
C. Spectrometric Method
• Visible absorption (Colorimetry)
• UV adsorption
• IR adsorption
• Plain photometric emission
• Fluorometric emissions
• Atomic Absorption
• Nuclear Magnetic Resonance Absorption
D. Electrochemical Method
• Voltammetry
• Potentiometry
E. Chromatographic
Method
The term “chromatography” is
derived from Greek, chroma = “color,”
and graphein = “to write.”
E. Chromatographic
Method
Chromatography (USP) is a procedure by
which solutes are separated by a differential
migration process in a system consisting of two or
more phases, one of which moves continuously in
a given direction and in which the individual
substances exhibit different mobilities by reason of
differences in adsorption, partition,
solubility, vapor pressure, molecular
size, or ionic charge density
E. Chromatographic
Method
• Gas Chromatography
• HPLC
• Thin Layer Chromatography
F. Miscellaneous Method
• Biological assay
• Distillation
• Functional test
• Vitamin assay
• Phase solubility
• Antibiotic assay
• Assay of fixed oil and waxes
F. Miscellaneous Method
• Gasometric acid
• Assay involving liquid volume
measure optical rotation and specific
gravity
• Enzyme assay
• Proximate assay (alkaloid)
F. Miscellaneous Method
• Gasometric Methods of analysis depend
on the measurement of the volume of a
gas liberated under the conditions that are
described in the assay
• Proximate Assay is meant the
determination of the amount of any
organic constituent that may be present in
any vegetable drug or plant to which its
value or therapeutic activity is attributed.
F. Miscellaneous Method
• Biological assay
• Distillation
• Functional test
• Vitamin assay
• Phase solubility
• Antibiotic assay
• Assay of fixed oil and waxes
 Stability of
Pharmaceutical
Preparations
Stability
Defined as the capability of
a particular formulation, in a
specific container/closure
system, to remain within its
physical, chemical,
microbiological, therapeutic, and
toxicological specifications.
Stability indicating
methods:
• Precision - agreement among
repeated means
• Accuracy - closeness of
means to the true value
Stability indicating
methods:
• Specificity - ability to
distinguish intact drug from the
composition product
• Linearity - multiples of a
concentration will elicit a
corresponding response
Criteria for Acceptable Stability

• condition maintained
throughout the shelf life of the
product
• each active ingredient retains
its chemical integrity and
labelled potency within
specified limits
Criteria for Acceptable Stability
• original physical properties
including appearance,
palatability, uniformity,
dissolution, and suspendability
are retained
• sterility or resistance to microbial
growth is retained according to
specified requirements within
specified limits
Criteria for Acceptable Stability

• therapeutics limits remains

unchanged
• no significant increase in
toxicity
Types of Stability

1. Chemical
2. Physical
3. Microbial
4. Therapeutic
5. Toxicological
Types of Stability
Chemical Stability
- Each active ingredient retains its
chemical integrity and labeled potency,
within the specified limits.
Types of Stability
Physical Stability
- The original physical properties,
including appearance, palatability,
uniformity, dissolution, and
suspendability
Types of Stability
Microbiological Stability
- Sterility or resistance to microbial
growth is retained according to the
specified requirements.
- Antimicrobial agents that are
present retain effectiveness within the
specified limits.
Types of Stability
• Therapeutic
– The therapeutic effect remains
unchanged.
• Toxicological
– No significant increase in toxicity
occurs.
Shelf Life
Refers to the duration of time
during which a drug preparation will
remain physically, chemically,
therapeutically, toxicology and
microbiology stable (possessing NLT
90% of the labeled potency)
Half Life
Time interval required for the
active ingredient to be reduced to ½
of its initial value.
Expiration Date
The time in which a drug
product in a specific packaging
configuration will remain stable
when stored under recommended
conditions.
Expiration Date
It is the sum of shelf life and the
date of manufacture.
It is expressed traditionally in terms
of month and year, denotes the last day
of the month. The expiration date should
appear on the immediate container and
the outer retail package.
Consideration in designing
stability-drug product
• Container-closure
• Extreme temperature fluctuation
• Storage temperature
• Effects of opening and closing
container
• Microbial quality
• Degradation product
• Design consideration
 Container
– a device that holds a drug and is,
or may be, in direct contact with the
drug.
• Well-closed
– it protects the
contents from
extraneous solids and
from loss of the drug
under ordinary
conditions of handling,
shipment, storage and
distribution
• Tight container
– protects the contents
from contamination by
extraneous liquids,
solids or vapors from
loss of the drug and
from efflorescence,
deliquescence or
shipment, storage and
distribution
• Light-resistant
containers
– containers that
prevent photochemical
decomposition of
substances that are
photosensitive.
• Hermetic container
– container that is
impervious to air or any
other gas under the
ordinary or customary
conditions of handling,
shipment, storage and
distribution
 TEMPERATURE
DESCRIPTION RANGE

Freezer -25°C and -10°C

(-13 and -14oF)

Cold Not exceeding 8°C

(46oF)

Refrigerator Controlled 2-8°C

(36 & 46oF)

Cool 8-15°C
(46 and 59oF)

Warm 30oC-40oC

Excessive heat Above 40oC

Protection from
Protect below 0oC
freezing:
• Controlled Cold
Temperature
–Thermostatically
controlled between 2°C
and 8°C with allowed
excursions between
0°C and 15°C as long
as the mean kinetic
temperature (MKT)
does not exceed 8°C
• If the manufacturer
labeling allows,
transient spikes up to
25°C are permitted as
long as they do not
exceed 24 hours or
manufacturer
instructions
• Room Temperature
– the ambient
temperature in the
room
• Controlled Room
Temperature
– Thermostatically
controlled between 20oC
and 25oC with allowed
excursions between 15oC
and 30oC and transient
spikes up to 40oC as long
as the MKT does not
exceed 25oC and spikes
do not exceed 24 hours
• Spikes above 40oC are
permitted if the
manufacture instructs
that this is allowed.
• An article that is to be
stored at controlled
room temperature may
be stored and
distributed in a cool
place unless otherwise
specified.
• Dry place, a place
where, at CRT, the
average relative
humidity (RH) does
not exceed 40% or
equivalent humidity at
other temperatures.
• The determination of
temperature-relative
humidity can be
based on actual
measurement in the
storage place or
reported climatic
conditions.
• It is based on not less
than 12 equally spaced
measurements during a
season, a year, or the
length of storage of the
article. RH values can
be up to 45% RH as
long as the average RH
is 40% or less.
 All drugs, chemicals,
drug products and
preparations should be
stored
and distributed under
the conditions that
meet or exceed USP-NF
or manufacturer’s
specifications
 Sensitivity Test For
Microorganism
• Filter Paper Disc
• Capillary Cup
 Bacteriological Test
• Quantitative (organism)
• Qualitative
 Stability Parameters
A. Tablet
B. Pharmaceutical capsule
C. Emulsion
D. Oral solution and
suspension
 A. Tablet
• Appearance
• Color
• Odor
• Taste
• Hardness
• Friability
 B. Capsule
• Appearance
• Color
• Shape
• Moisture

• Brittleness
 C. Emulsion
• Appearance
• Color
• Odor
• pH
 D. Oral Solution
and Suspension
• Appearance
• Color
• Odor
• Taste
• Clarity
• Dispensability
• Suspendability
• Pourability
 Initiation of Stability
1) Repair sample
⮚ Proposed commercial package
⮚ Sufficient amount for test interval
⮚ Established design
• Test interval
• Storage condition
⮚ Assigned stability # to identify
stability
 Initiation of Stability
2) Stores
3) Test
4) Right result
5) Evaluate data
6) Right conclusion
Administrative
Order
R.A. 3720 (1963)
Food, Drug and Cosmetic Act

Revenue Regulation 16-67

Narcotic Drug Regulation
A.O. 60 s. 1968
General regulations for the Enforcement of
the Food, Drug, Cosmetic Act (A-7
Operation for drug establishment, A-8
Requirements for cosmetic laboratory)
 A.O. 61 s. 1968
General regulations for the Enforcement
of the Food, Drug, and Cosmetic Act
(C-3 Misbranding: Drug and Devices)

A.O. 101 s. 1969

Regulation Part C-9:
Drugs: Registration of drugs and
pharmaceutical Specialties
 A.O. 101 s. 1969
Regulation Part C-9:
Drugs: Registration of drugs and
pharmaceutical Specialties

A.O. 109 s. 1969

Regulation Part C-1
Drug labeling:
Prescription drug
Label symbol
A.O. 126 s. 1970
Regulation Part C-10
• Statement of Lot number
• Expiration date
• Registration number
• Storage conditions of pharmaceutical
Specialties
 A.O. 150 s. 1971
Regulation Part D-4:
Cosmetic: Registration of Cosmetic
Specialties

A.O. 132 s. 1970

Regulation Part C-3.2:
Drug: Prohibition of the use of more than
one name for a given formulation
A.O. 151 s. 1971
Regulation Part C-7
Drug and Devices:
Certification of Antibiotics

A.O. 195 s. 1973

Restricted Use of Boric acid and Sodium
Borate (Borax)
A.O. 220 s. 1974
CGMP in Manufacture, Processing, Packing and
Holding

A.O. 341 s. 1978

Ban on the Use of Chloroform
(Trichloromethane)

A.O. 342 s. 1978

Banning Tetracycline for Children under 8 yrs.
Old
A.O. 34 s. 1979
The need and role for a MEDICAL
DIRECTOR in the Pharmaceutical
Industries

A.O. 38 s. 1979
Restriction on the use of several BRAND
NAMES for formulation of a drug or
pharmaceutical specialty
for listening, any questions?
Reference
• Allen, L.V. & Ansel, H.C. (2014). Ansel’s Pharmaceutical
Dosage Forms and Drug Delivery Systems 10th Ed.
Lippincott Williams and Wilkins: Baltimore, USA

• Remington’s Pharmaceutical Sciences Latest Edition

• PICs, “GUIDE TO GOOD MANUFACTURING PRACTICE FOR

MEDICINAL PRODUCTS”, PE009-13, 1 January 2017.

• Guidance and Manuals on Pharmaceutical Quality

(https://www.fda.gov>Drugs)