In the pharmaceutical industry, ensuring the sterility and safety of products is of utmost importance. That's why aseptic processing, the manufacturing of sterile pharmaceutical products under controlled sterile conditions, is critical for heat-sensitive drugs like biologics, vaccines, and injectable therapies that can't survive terminal sterilisation.
What is aseptic processing: a detailed overview
Aseptic processing involves maintaining sterile conditions throughout the entire manufacturing process – from individual component sterilisation to final product assembly. Unlike terminal sterilisation, which sterilises a completely sealed product, aseptic processing requires each component to be sterilised separately before being assembled in a controlled sterile environment.
Critical steps in aseptic processing
The aseptic process involves five critical steps.
1. Component sterilisation
All individual components undergo separate sterilisation – containers and closures through dry heat or steam, equipment via autoclaving, and drug substances through 0.2-micron sterilising-grade filtration.
2. Environmental preparation
Establishing Grade A critical zones with unidirectional HEPA-filtered air flowing at 0.45 m/s (±20%) creates a sterile manufacturing environment.
3. Aseptic assembly
Sterile components move into the aseptic core where formulation and final filtration occur under strictly controlled conditions.
4. Filling operations
Automated equipment in Grade A environments ensures sterile product filling into pre-sterilised containers.
5. Quality control
Comprehensive monitoring, including continuous environmental surveillance and sterility testing, validates process effectiveness.
Common applications of aseptic processing
Aseptic processing is essential for the manufacturing of:
What are the differences between aseptic processing and terminal sterilisation?
The fundamental difference lies in when sterilisation occurs and what products can be processed.
With aseptic processing, you sterilise each component separately, then assemble everything in a sterile environment. This approach works for heat-sensitive products, like biologics and vaccines, but requires sophisticated cleanrooms, highly trained operators, and extensive environmental controls. The complexity means higher costs and greater reliance on perfect execution throughout the process.
Terminal sterilisation takes the opposite approach: you fill and seal the product first, then sterilise the entire finished unit using heat, steam, or radiation. This method achieves a quantifiable Sterility Assurance Level (SAL) of 10⁻⁶ – meaning less than one in a million units could potentially be non-sterile. It's simpler, more cost-effective, and provides robust sterility assurance. However, it only works for products that can withstand sterilisation conditions.
When to use aseptic processing
Choose aseptic processing when products can't withstand terminal sterilisation conditions, particularly for biologics, vaccines, and other heat-sensitive therapeutics.
The role of filtration in aseptic processing
Filtration is your last line of defence against contamination. Sterilising-grade membrane filters remove bacteria and microorganisms before they can contaminate your final product, making them a critical component of your overall contamination control strategy.
Sterile filtration removes microorganisms
0.2 µm sterilising-grade filters are the industry standard for removing bacteria from heat-sensitive drug substances.
The process works for both liquids and gases. Liquid drug products get filtered to remove bacteria while maintaining product quality, and sterile air filters keep tanks, compressed air lines, and process gases contamination-free.
Filter types used in aseptic processing
- Membrane filters: remove bacteria and microorganisms from your product
- Particulate pre-filters: remove large debris and particulates
- Gas filters: provide sterile air for tank venting and compressed air systems
Best practices for aseptic processing
Validate your process with media fills
Media fill studies prove your process works by using sterile growth medium instead of actual product. Requirements are strict:
- Minimum 3,000 units per study
- Zero contaminated units to pass
- Run studies every six months
- Investigate any contamination immediately
Test filter integrity (PUPSIT)
EU GMP Annex 1 now requires Pre-Use Post-Sterilisation integrity testing, though alternatives exist for technically difficult cases.
The three common testing methods are:
- Bubble point test: measures pressure needed to force bubbles through wetted filter (30-50 psi for 0.2 µm filters)
- Diffusion test: measures gas flow through wetted membrane – more sensitive to small defects
- Pressure hold test: monitors pressure drop over time – cost-effective for large systems
Meet regulatory requirements
The 2022 EU GMP Annex 1 revision tightened requirements significantly:
- Mandatory contamination control strategies
- Zero tolerance for microbial growth in Grade A areas
- RABS or isolators now expected as minimum standard
- Grade A areas must maintain ≤3,520 particles ≥0.5 μm/m³ with <1 CFU
Getting aseptic processing right
The pharmaceutical industry is shifting toward biologics, cell therapies, and personalised medicines that can't survive heat sterilisation. These advanced treatments require even more sophisticated aseptic processing and tighter contamination control.
Get it right, and you can manufacture life-saving treatments safely. Get it wrong, and you may face recalls, regulatory action, and potential harm to patients.
