What are the methods of cleaning and sterilizing medicinal glass bottles?

Cleaning and sterilization of pharmaceutical glass bottles is a key link to ensure the safety of medicines, and appropriate methods should be selected according to the type of bottles (e.g., injectable bottles, oral preparation bottles) and the use (whether it is in contact with sterile drugs). The following are the mainstream technologies and precautions: 
I. Cleaning Methods and Technologies 
1. Water Cleaning Technology 
Purified Water / Water for Injection Cleaning 
Applicable Scenarios: Injectable bottles, lyophilized bottles and other packages that come into direct contact with sterile medicines need to be cleaned with purified water or water for injection in compliance with pharmacopoeia standards.
Process steps: 
Rough rinsing: through high-pressure water spraying or ultrasonic vibration, to remove dust, glass debris and other impurities visible to the naked eye inside the bottle.
Fine washing: using circulating water rinsing (water flow direction from the bottom of the bottle to the bottle mouth, to avoid dead ends), with the flip-type washing machine, to ensure that there is no residue on the inner wall.
Equipment: Tunnel washing machine, ultrasonic cleaning machine (for small volume bottles).
Lye cleaning (NaOH solution) 
Scenario: Reused glass bottles (e.g. recycled infusion bottles) or containers with oily stains.
Characteristics: NaOH concentration is usually 1% ~ 3%, 60 ℃ ~ 80 ℃ warm cleaning, can dissolve proteins, oil and grease and other organic pollutants, but need to be followed up with purified water to thoroughly neutralize (pH detection to neutral).
2. Air cleaning technology 
High-pressure clean air blowing washing 
Applicable scene: bottles that have been initially cleaned, used to remove small particles (such as glass shavings, fibers).
Process: Compressed air with multi-stage filtration (subject to a 0.22μm sterilizing filter) is pulsed inside the washer to blow inside the bottles, together with mechanical turning, to ensure that the airflow covers the entire inner wall.
Ultrasonic-assisted cleaning 
Principle: the use of ultrasonic cavitation effect in the water, shocking down the bottle wall of small particles (such as 0.5μm below the impurities), often used in combination with water cleaning to improve the cleaning efficiency.
Sterilization and disinfection methods 
1. Dry heat sterilization 
Applicable scenes: injection bottles, ampoules, lyophilized bottles and other high-temperature-resistant Class Ⅰ / Class Ⅱ glass.
Process parameters: 
180℃~200℃ for more than 2 hours: kill bacterial propagules; 
250℃ for more than 30 minutes: destroy pyrogens (endotoxins), applicable to containers in direct contact with medicinal liquid.
Equipment: Tunnel dry heat sterilizer (equipped with high efficiency air filter HEPA to maintain class 100 clean area), the bottle passes through the high temperature zone on the conveyor belt and is cooled by sterile air at the same time.
2. Wet heat sterilization 
Scenario: less temperature-resistant Class II glass or packages that need to be co-sterilized with components such as stoppers (e.g. infusion bottles).
Process: 
High-temperature autoclave sterilization: 121℃, 15~30 minutes, pressure 0.1MPa, applicable to large-capacity infusion bottles, need to ensure that there is no air residue in the bottle (to avoid cold spots).
Flow steam sterilization: 100 ℃, 30 minutes, suitable for oral preparation bottle sterilization, but can not completely kill the spores. 3.
3. Chemical sterilization 
Hydrogen peroxide (H₂O₂) fumigation 
Applicable scenarios: pre-filled glass syringes, lyophilized bottles, and other high-end containers that need to be sterilized at low temperatures, or components that cannot withstand high temperatures.
Process: Vaporize 30%~35% hydrogen peroxide and pass it into the sterilization cabinet, act for 30~60 minutes under 40℃~60℃ and low humidity environment, destroy the cell structure of microorganisms through strong oxidizing, and then need to ventilate to remove the residue.
Ozone (O₃) disinfection 
Scenario: online disinfection of oral preparation bottles, or sterilization of cleaning water systems (such as purified water storage tanks).
Characteristics: Ozone dissolved in water generates hydroxyl radicals, killing bacteria and fungi, but need to control the concentration (usually 0.3~0.5ppm), to avoid corrosion of the glass surface.