5- Manufacturing of Sterile Dosage Form

b. Clean Room

[Sterile Production Area]

Room in which concentration of airborne particles are controlled
a. Airlock
b. Clean Room
c. Quarantine Area
d. Sterile Chamber

c. Positive pressure air flow

[Sterile Production Area]

Type of air flow supplied in clean rooms
a. Negative pressure air flow
b. Neutral pressure air flow
c. Positive pressure air flow
d. Laminar air flow

c. HEPA filter

[Sterile Production Area]

Filter that removes 99.97% of particles (≥0.3 μm) from air
a. Membrane filter
b. Sintered-glass filter
c. HEPA filter
d. Cotton filter

b. Diocylphthalate Test

[Sterile Production Area]

QC test for HEPA filter
a. Bubble Point Test
b. Diocylphthalate Test
c. Sterility Test
d. Kirby-Bauer Test

b. Airlock

[Sterile Production Area]

Space with interlocked doors used for entry into clean rooms
a. Buffer Zone
b. Airlock
c. Antechamber
d. Vestibule

[Sterile Production Area]

Classification of Clean Rooms:

• Terminal Sterilization

• Aseptic Processing

[Sterile Manufacturing Operations]

Categories for Sterile Manufacturing Operations [2]

b. Terminal Sterilization

[Categories for Sterile Manufacturing Operations]

Product is prepared, filled and sterilized

a. Aseptic Processing
b. Terminal Sterilization
c. Depyrogenation
d. Membrane Filtration

b. Terminal Sterilization

[Categories for Sterile Manufacturing Operations]

Method of choice whenever possible

a. Aseptic Processing
b. Terminal Sterilization
c. Depyrogenation
d. Membrane Filtration

a. Aseptic Processing

[Categories for Sterile Manufacturing Operations]

Components are sterilized separately and assembled

a. Aseptic Processing
b. Terminal Sterilization
c. Depyrogenation
d. Membrane Filtration

• Moist Heat

• Dry Heat

• Membrane Filtration

• Gas

• Ionizing Radiation

Sterilization Methods for Sterile Manufacturing Operations [5]

c. Moist Heat

[Sterilization Methods for Sterile Manufacturing Operations]

Sterilization method using autoclave or steam under pressure (121°C, 15psi, 15-20 minutes)
a. Dry Heat
b. Membrane Filtration
c. Moist Heat
d. Ionizing Radiation

c. Protein coagulation

[Sterilization Methods for Sterile Manufacturing Operations]

MOA of moist heat sterilization
a. Oxidation
b. Alkylation
c. Protein coagulation
d. DNA mutation

b. Bacillus stearothermophilus

[Sterilization Methods for Sterile Manufacturing Operations]

Biological indicator for moist heat sterilization
a. Bacillus subtilis
b. Bacillus stearothermophilus
c. Bacillus pumilus
d. Brevudimonas diminuta

b. Dry Heat

[Sterilization Methods for Sterile Manufacturing Operations]

Sterilization method using oven (160-170°C for 2-4 hours)
a. Moist Heat
b. Dry Heat
c. Gas
d. Ionizing Radiation

c. Oxidation

[Sterilization Methods for Sterile Manufacturing Operations]

MOA of dry heat sterilization
a. Protein coagulation
b. DNA mutation
c. Oxidation
d. Alkylation

d. Bacillus subtilis

[Sterilization Methods for Sterile Manufacturing Operations]

Biological indicator for dry heat sterilization
a. Bacillus stearothermophilus
b. Bacillus pumilus
c. Brevudimonas diminuta
d. Bacillus subtilis

c. Membrane Filtration

[Sterilization Methods for Sterile Manufacturing Operations]

Sterilization method using membrane filters (0.22 μm); for heat-labile solutions
a. Moist Heat
b. Gas
c. Membrane Filtration
d. Ionizing Radiation

b. Physical separation

[Sterilization Methods for Sterile Manufacturing Operations]

MOA of membrane filtration sterilization
a. DNA mutation
b. Physical separation
c. Alkylation
d. Oxidation

c. Brevudimonas diminuta

[Sterilization Methods for Sterile Manufacturing Operations]

Biological indicator for membrane filtration sterilization
a. Bacillus subtilis
b. Bacillus stearothermophilus
c. Brevudimonas diminuta
d. Bacillus pumilus

b. Gas

[Sterilization Methods for Sterile Manufacturing Operations]

Sterilization method using ethylene oxide, formaldehyde or β-propiolactone
a. Moist Heat
b. Gas
c. Ionizing Radiation
d. Dry Heat

c. Alkylation

[Sterilization Methods for Sterile Manufacturing Operations]

MOA of gas sterilization
a. Protein coagulation
b. Oxidation
c. Alkylation
d. DNA mutation

d. Bacillus subtilis

[Sterilization Methods for Sterile Manufacturing Operations]

Biological indicator for gas sterilization
a. Bacillus stearothermophilus
b. Brevudimonas diminuta
c. Bacillus pumilus
d. Bacillus subtilis

c. Ionizing Radiation

[Sterilization Methods for Sterile Manufacturing Operations]

Sterilization method using gamma or cathode rays
a. Gas
b. Moist Heat
c. Ionizing Radiation
d. Dry Heat

d. DNA mutation

[Sterilization Methods for Sterile Manufacturing Operations]

MOA of ionizing radiation sterilization
a. Alkylation
b. Oxidation
c. Protein coagulation
d. DNA mutation

b. Bacillus pumilus

[Sterilization Methods for Sterile Manufacturing Operations]

Biological indicator for ionizing radiation sterilization
a. Bacillus subtilis
b. Bacillus pumilus
c. Bacillus stearothermophilus
d. Brevudimonas diminuta

a. Autoclave (Steam under pressure)

[Sterilization Methods for Sterile Manufacturing Operations]

121°C, 15 psi, 15-20 minutes
a. Autoclave (Steam under pressure)
b. Oven
c. Dry heat
d. Filtration

b. Oven

[Sterilization Methods for Sterile Manufacturing Operations]

160-170°C for 2-4 hours

a. Autoclave (Steam under pressure)
b. Oven
c. Dry heat
d. Filtration

• 180°C for 4 hours

• 250°C for 45 minutes

• 650°C for 1 minute

[Sterilization Methods for Sterile Manufacturing Operations]

Oven setting for Depyrogenation [3]

Cleaning

↓

Product Preparation

↓

Filtration

↓

Filling

↓

Sealing

Steps in preparing Sterile Dosage Forms [5]

b. Cleaning

[Steps in preparing Sterile Dosage Forms]

Involves:

• Manual cleaning and sterilization of equipment

• Sanitation of clean rooms

• Sterilization of components for aseptic processing

a. Product Preparation
b. Cleaning
c. Filtration
d. Filling

c. Product Preparation

[Steps in preparing Sterile Dosage Forms]

Considered the critical process, done in Class 100
a. Cleaning
b. Filtration
c. Product Preparation
d. Sealing

• Spray-drying

• Freeze-drying (lyophilization)

[Steps in preparing Sterile Dosage Forms]

Method used for DRY SOLIDS in product preparation
a. Filtration
b. Spray-drying or freeze-drying (lyophilization)
c. Sealing
d. Depyrogenation

• Dissolution

• Tonicity adjustment

• Preservation

• Filtration

[Steps in preparing Sterile Dosage Forms]

Method used for SOLUTIONS in product preparation
a. Dissolution, tonicity adjustment, preservation and filtration
b. Dissolution only
c. Tonicity adjustment only
d. Preservation only

• Clarification

• Cold Filtration

[Steps in preparing Sterile Dosage Forms]

Filtration methods for preparing Sterile Dosage forms include _______ [2]

b. Clarification

[Steps in preparing Sterile Dosage Forms]

Filtration method for 2-3 μm particles
a. Cold Filtration
b. Clarification
c. Membrane Filtration
d. Sterile Filtration

b. Cold Filtration

[Steps in preparing Sterile Dosage Forms]

Filtration method for 0.2-0.3 μm particles
a. Clarification
b. Cold Filtration
c. Terminal Filtration
d. Gravity Filtration

• Gravity Filling

• Pressure Filling

• Vacuum Filling

[Steps in preparing Sterile Dosage Forms]

Filling methods for preparing Sterile Dosage forms include _______ [3]

c. Gravity Filling

[Steps in preparing Sterile Dosage Forms]

Filling method that is hand-operated
a. Pressure Filling
b. Vacuum Filling
c. Gravity Filling
d. Automatic Filling

b. Pressure Filling

[Steps in preparing Sterile Dosage Forms]

Filling method that is semi-automatic
a. Gravity Filling
b. Pressure Filling
c. Vacuum Filling
d. Manual Filling

c. Vacuum Filling

[Steps in preparing Sterile Dosage Forms]

Filling method that is fully automated
a. Pressure Filling
b. Gravity Filling
c. Vacuum Filling
d. Semi-automatic Filling

• Tip-Seal (Bead-Seal)

• Pull-Seal

[Steps in preparing Sterile Dosage Forms]

Ampoule Sealing methods for preparing Sterile Dosage forms include _______ [2]

b. Tip-Seal (Bead-Seal)

[Steps in preparing Sterile Dosage Forms]

Ampoule sealing method made by melting the tip of the neck of an ampoule to form a bead
a. Pull-Seal
b. Tip-Seal (Bead-Seal)
c. Heat-Seal
d. Fusion-Seal

c. Pull-Seal

[Steps in preparing Sterile Dosage Forms]

Ampoule sealing method made by heating the neck of a rotating ampoule below the tip and pulling the softened glass away
a. Tip-Seal (Bead-Seal)
b. Fusion-Seal
c. Pull-Seal
d. Heat-Seal

c. Packaging

An economic way of protecting, preparing, identifying, and containing the drug products, composed of container and closure
a. Storage
b. Labeling
c. Packaging
d. Sterilization

• Primary Packaging

• Secondary Packaging

Types of Packaging [2]

[Types of Packaging]

In direct contact with product

a. Primary Packaging

b. Secondary Packaging

a. Primary Packaging

[Types of Packaging]

Considered as immediate container, affects stability

a. Primary Packaging

b. Secondary Packaging

a. Primary Packaging

[Types of Packaging]

This may provide means of administration

a. Primary Packaging

b. Secondary Packaging

• Bottles

• Caps

• Liners

• Filler

• Desiccant

[Types of Packaging]

Examples of primary packaging
a. Carton box, sticker label, inserts
b. Bottles, caps, liners, filler, desiccant
c. Conjugated box
d. Shipping container

b. Secondary Packaging

[Types of Packaging]

Outer packaging (not always present)

a. Primary Packaging

b. Secondary Packaging

b. Secondary Packaging

[Types of Packaging]

Encloses primary packaging

a. Primary Packaging

b. Secondary Packaging

• Carton box

• Sticker label

• Inserts

• Conjugated box

[Types of Packaging]

Examples of secondary packaging
a. Bottles, caps, liners
b. Filler, desiccant
c. Carton box, sticker label, inserts, conjugated box
d. Ampoules, vials

f. Well-Closed Container

[Classification of Container According to Protection Ability]

Protects content from extraneous solids

a. Tamper-Resistant Container
b. Child-Resistant Container
c. Light-Resistant Container
d. Hermetic Container
e. Tight Container
f. Well-Closed Container

e. Tight Container

[Classification of Container According to Protection Ability]

Protects contents from extraneous solids, liquids, and vapors

a. Tamper-Resistant Container
b. Child-Resistant Container
c. Light-Resistant Container
d. Hermetic Container
e. Tight Container
f. Well-Closed Container

e. Tight Container

[Classification of Container According to Protection Ability]

Protects from deliquescence, efflorescence, evaporation

a. Tamper-Resistant Container
b. Child-Resistant Container
c. Light-Resistant Container
d. Hermetic Container
e. Tight Container
f. Well-Closed Container

d. Hermetic Container

[Classification of Container According to Protection Ability]

Impervious to air or any other gas

a. Tamper-Resistant Container
b. Child-Resistant Container
c. Light-Resistant Container
d. Hermetic Container
e. Tight Container
f. Well-Closed Container

c. Light-Resistant Container

[Classification of Container According to Protection Ability]

Protects from photochemical degradation

a. Tamper-Resistant Container
b. Child-Resistant Container
c. Light-Resistant Container
d. Hermetic Container
e. Tight Container
f. Well-Closed Container

a. Amber bottle

[Classification of Container According to Protection Ability]

Example of Light-Resistant Container
a. Amber bottle
b. Clear glass bottle
c. Plastic container
d. Metal container

b. Child-Resistant Container

[Classification of Container According to Protection Ability]

Difficult for children under 5 years of age to open:

• press down and turn

• squeeze and turn

• alight the ar

• latch top

a. Tamper-Resistant Container
b. Child-Resistant Container
c. Light-Resistant Container
d. Hermetic Container
e. Tight Container
f. Well-Closed Container

• press down and turn

• squeeze and turn

• alight the ar

• latch top

[Classification of Container According to Protection Ability]

Mechanisms used in child-resistant containers include _____ [4]

a. Tamper-Resistant Container

[Classification of Container According to Protection Ability]

Uses an indicator which if breached or missing can provide evidence that tampering has occurred:

• shrink seal/ wrap

• breakable caps

• tape seal

• bottle seal

• aerosol → only true tamper-resistant packaging

a. Tamper-Resistant Container
b. Child-Resistant Container
c. Light-Resistant Container
d. Hermetic Container
e. Tight Container
f. Well-Closed Container

• shrink seal/ wrap

• breakable caps

• tape seal

• bottle seal

• aerosol

Mechanisms used in tamper-resistant containers include _____ [5]

c. Aerosol

[Classification of Container According to Protection Ability]

Only true tamper-resistant packaging
a. Shrink seal/wrap
b. Bottle seal
c. Aerosol
d. Breakable caps

[Classification of Container According to Quantity Held]

a. Single Unit Container

b. Multiple Unit Container

a. Single Unit Container

[Classification of Container According to Quantity Held]

Contains a single dose only and packaged in nonresealable containers

a. Single Unit Container

b. Multiple Unit Container

a. Single Unit Container

[Classification of Container According to Quantity Held]

No antimicrobial agent added

a. Single Unit Container

b. Multiple Unit Container

b. WFI or SWFI

[Classification of Container According to Quantity Held]

Type of water used in single unit containers

a. BWFI
b. WFI or SWFI
c. Distilled water
d. Deionized water

b. 1000 mL

[Classification of Container According to Quantity Held]

USP limit for single unit containers
a. 30 mL
b. 1000 mL
c. 500 mL
d. 100 mL

• Ampoules

• Prefilled syringes

[Classification of Container According to Quantity Held]

Examples of single unit containers
a. Vials
b. Ampoules, prefilled syringes
c. Bottles
d. Multi-dose vials

• Low cost

• Not Breakable

• Light weight

• Chemically inert

Advantages of Single Unit Container [4]

• Permeable

• Low heat resistance

• Not as clear as glass

• Poor physical stability

Disadvantages of Single Unit Container [4]

b. Multiple Unit Container

[Classification of Container According to Quantity Held]

Contains multiple doses and packaged in resealable containers

a. Single Unit Container

b. Multiple Unit Container

b. Multiple Unit Container

[Classification of Container According to Quantity Held]

With antimicrobial agent added

a. Single Unit Container

b. Multiple Unit Container

b. BWFI

[Classification of Container According to Quantity Held]

Type of water used in multiple unit containers
a. WFI or SWFI
b. BWFI
c. Distilled water
d. Purified water

c. 30 mL

[Classification of Container According to Quantity Held]

USP limit for multiple unit containers
a. 1000 mL
b. 500 mL
c. 30 mL
d. 100 mL

c. Vials

[Classification of Container According to Quantity Held]

Example of multiple unit container
a. Ampoules
b. Prefilled syringes
c. Vials
d. Single-dose syringes

b. Glass

[Classification of Container According to Material Used]

• This is the most widely used container material

• This is made up of inorganic compounds (major component: SiO₂)

a. Plastic
b. Glass
c. Rubber
d. Metal

• Rigid and transparent

• Impermeable

• Chemically resistant

• Can be easily sterilized

[Classification of Container According to Material Used]

Advantage of Glass as Container material [4]

• High cost

• Fragile

• Relatively heavy

• Prone to leaching

[Classification of Container According to Material Used]

Disadvantage of Glass as Container material [4]

a. Silica (SiO₂)

[Classification of Container According to Material Used]

Major component of glass
a. Silica (SiO₂)
b. Soda (Na₂O)
c. Lime (CaO)
d. Alumina (Al₂O₃)

c. Type I

[Type of Glass]

Highly Resistant Borosilicate Glass
a. Type II
b. Type III
c. Type I
d. Type IV/NP

b. Boron

[Type of Glass]

Component of glass that decreases coefficient of expansion
a. Silica
b. Boron
c. Sodium
d. Calcium

• Pyrex

• Borosil

[Type of Glass]

Brand names of Highly Resistant Borosilicate glass
a. Soda Lime Glass
b. Pyrex, Borosil
c. General Soda Lime Glass
d. Treated Soda Lime Glass

c. Type II

[Type of Glass]

Treated Soda Lime Glass
a. Type I
b. Type III
c. Type II
d. Type IV/NP

c. Type III

[Type of Glass]

Soda Lime Glass

a. Type I
b. Type II
c. Type III
d. Type IV/NP

c. Type III

[Type of Glass]

Type of glass used for Dry Powder Packaging

a. Type I
b. Type II
c. Type III
d. Type IV/NP

d. Type IV/NP

[Type of Glass]

General Soda Lime Glass
a. Type I
b. Type II
c. Type III
d. Type IV/NP

b. Plastic

[Classification of Container According to Material Used]

Container material composed of organic polymers of HMW
a. Glass
b. Plastic
c. Rubber
d. Metal

b. Thermoplastic

[Types of Plastic]

• Soft when heated and hard when cooled

• Flexible and squeezable

a. Thermoset
b. Thermoplastic

b. Thermoplastic

[Types of Plastic]

• Permanently hard

• Rigid

a. Thermoset
b. Thermoplastic

e. Polyethylene Terephthalate

[Types of Polymers for Plastic]

For beverages

a. Polypropylene (PP)

b. Low-density Polyethylene (LDPE)

c. Polyvinyl Chloride (PVC)

d. High-density Polyethylene (HDPE)

e. Polyethylene Terephthalate (PET)

d. High-density Polyethylene

[Types of Polymers for Plastic]

Used as hard thermoset for solid dosage forms

a. Polypropylene (PP)

b. Low-density Polyethylene (LDPE)

c. Polyvinyl Chloride (PVC)

d. High-density Polyethylene (HDPE)

e. Polyethylene Terephthalate (PET)

c. Polyvinyl Chloride (PVC)

[Types of Polymers for Plastic]

Used for blister packs

a. Polypropylene (PP)

b. Low-density Polyethylene (LDPE)

c. Polyvinyl Chloride (PVC)

d. High-density Polyethylene (HDPE)

e. Polyethylene Terephthalate (PET)

b. Low-density Polyethylene (LDPE)

[Types of Polymers for Plastic]

Used as thermoplastic for squeeze bottles and medicine droppersa. a. Polypropylene (PP)

b. Low-density Polyethylene (LDPE)

c. Polyvinyl Chloride (PVC)

d. High-density Polyethylene (HDPE)

e. Polyethylene Terephthalate (PET)

a. Polypropylene (PP)

[Types of Polymers for Plastic]

Used for autoclave containers

a. Polypropylene (PP)

b. Low-density Polyethylene (LDPE)

c. Polyvinyl Chloride (PVC)

d. High-density Polyethylene (HDPE)

e. Polyethylene Terephthalate (PET)

b. Metal

[Classification of Container According to Material Used]

Container material used in aerosol cans and collapsible tubes
a. Rubber
b. Metal
c. Paper
d. Foils

c. Foils, Films and Laminates

[Classification of Container According to Material Used]

Container material used in blister packs and strip packs
a. Rubber
b. Metal
c. Foils, Films and Laminates
d. Paper

b. Rubber

[Classification of Container According to Material Used]

Container material used in vial stoppers and syringe plugs
a. Metal
b. Rubber
c. Foils
d. Paper

d. Paper

[Classification of Container According to Material Used]

Container material used for divided powders
a. Rubber
b. Metal
c. Foils
d. Paper