Sterile manufacturing
Amjad Hussain PhD (Pharm Tech.)
Sterile products
• Those product which are free from viable microbes
• These include parenterals, ophthalmics and
irrigation solutions
• Formulations are
– Ophthalmics
– Freeze dried products
– Long acting formulas
– Suspensions
– Emulsions
Composition
• API
• Vehicle
– Aqueous (Water for injection)
– Non-aqueous (PEG, fixed oils)
• Added substances
– Preservatives,
– antioxidants,
– solubilizer,
– suspending, agents,
– buffers,
– stabilizers etc.
– Bulking agents/tonicity modifier
Get their detail from Lachman
Sterile state & Sterilization
methods
• Sterile is “free from viable microbes” it is an absolute term
• Microbial death kinetics terms
– D-value
– Bioburden & Microbial load
– Resistance time
– F-Value
• Methods
– Dry heat sterilization
– Moist heat sterilization
– Chemical sterilization
– Filtration
– Radiation
For Detail description of these methods see class presentaions
Production
(include all operations from accumulation of ingredients to packing)
1. Facilities
• Clean area/room (Class A, B ,C and D)
for their specification/particle limit consult class presentation
• Supplies and basic design (GMP/cGMP), Layout, HVAC system
• Uni-directional flow of materials (see Figure 23.3 of Lachman)
2. Environment Control
• Traffic control (no direct entry, uni-directional flow)
• Minimum entry/only trained personnel (follow SOPs)
• Air control (HEPA filters, its design, types and working)
• Airlocks
• Positive and negative pressure
for their detail consult Lachman
Conti….
3. Housekeeping
• Separate tool/equipment for sterile area
4. Surface disinfection
• Use disinfectant in rotation
5. Air control
• Laminar Flow Hood (LFH), Horizontal and vertical
• Environment monitoring (Table 23.6 in Lachman)
6. Personnel
• Their Training
• Follow SOPs
• Clothing
Processing
1. Water for Injection
– Water supply& its Pre-filtration (Sand filter, Carbon filter, UV)
– Reverse osmosis/De-ionization
– Distillation
– Filtration & storage
2. Cleaning the Equipment and containers
– Decartoning & Dedusting of containers
– Hand scrub
– High pressure rinsing
– Hot air drying
– Oven sterilization of containers
3. Compounding the product
4. Filtration (i.e. Bulk Sterilization)
5. Filling (for liquids or solids)
6. Sealing
– Ampoules (melting, hermetically sealed)
– Vials (snugly close rubber closure)
Conti…..
8. Sterilization (Terminal sterilization i.e. after packing use
radiation or autoclaving).
9. Quality Control testing
• Clarity Go/No go tests
• leakage,
• Pyrogens
– In-vitro (LAL test)
– In-vivo (Rabbit test)
• Sterility
– Media and its testing
– Incubation
– Interpretation of results
Containers for sterile products
(consider for autoclavibility and permeation/leaching of additive)
• Glass (Type I, Borosilicate glass)
– Quality of glass is tested by
– Alkalinity testing/Powdered glass test
• Plastic
– Additive of plastic may leach in the product therefore,
always check
• Toxicity of plastic containers (BP method)
• Drug plastic interaction (see under Packaging chapter)
• Rubber
– For closure due its elastic and resealable nature
