Critical Sites
A critical site is any location that is exposed and can allow intrusion of microorganisms and/or foreign matter. General Chapter <797> defines a critical site as, "A location that includes any component or fluid pathway surfaces (e.g., vial septa, injection ports, beakers) or openings (e.g., opened ampules, needle hubs) exposed and at risk of direct contact with air (e.g., ambient room or HEPA filtered), moisture (e.g., oral and mucosal secretions), or touch contamination."
Primary Engineering Control (PEC)
Chapter <797> defines Primary Engineering Control (PEC) as a device or room that provides an ISO Class 5 environment for the exposure of critical sites when compounding CSPs. Such devices include, but may not be limited to, laminar airflow workbenches (LAFWs), biological safety cabinets (BSCs), compounding aseptic isolators (CAIs), and compounding aseptic containment isolators (CACIs).
ISO Class Particle Count Limits
| ISO Class |
Particle Count (per m3)* |
| 3 |
35.2 |
| 4 |
352 |
| 5 |
3,520 |
| 6 |
35,200 |
| 7 |
352,000 |
| 8 |
3,520,000 |
| *The particles are 0.5 micron or larger. |
(3,520 particles per m3 is equivalent to 100 particles per ft3) |
If the PEC is a clean room, there are two general approaches and the method depends on the layout of the clean room facilities. One clean room design has a separate room for the buffer area and the ante-area with a barrier between them. The second design has the buffer area and ante-area combined. In this second design, the buffer area receives the "first air," and that air washes over the ante-area before exiting. This design is called the "displacement approach" and cannot be used for high-risk level compounding. When used for low- and medium-risk level compounding, the proper air flow must be maintained from the cleaner air downstream, with no turbulent or stagnant areas.
| Risk Level |
Equipment |
Examples |
| Low Risk |
ISO Class 5 LAFW in ISO Class 8 clean room with anteroom |
- Reconstitution of single dose vials of antibiotics or other small volume parenterals (SVP)
- Preparation of hydration solutions
- Using sterile needles and syringe to transfer sterile drugs from the manufacturer’s original packaging (vials, ampules)
- Manually measuring and mixing no more than three sterile products to compounded drug admixtures in nutritional solutions
|
| Medium Risk |
ISO Class 5 LAFW in ISO Class 8 clean room with anteroom |
- Batch preparation that do not contain bacteriostatic components
- Pooled admixtures
- Parenteral nutrition solutions using automated compounders
- TPN fluids compounding using manual or automated devices requiring multiple injections, detachments, and attachments of the nutrients’ source products to the device or machine to deliver all the nutritional complements to the final sterile container
- Filling of reservoirs of injection and infusion devices with multiple sterile drug products and evacuation of air from those reservoirs before the filled device is dispensed
- Filling of reservoirs of injection and infusion devices with volumes of sterile drug solution that will be administered over several days in ambient temperatures between 25º and 40º
- Transfer of volumes from multiple ampules or vials into a single, final sterile container or product
|
| High Risk |
ISO Class 5 LAFW in Class 8 clean room with a separate anteroom |
- Dissolving nonsterile bulk drugs and nutrient powders to make a solution which will be terminally sterilized
- Sterile ingredients, components, devices, and mixtures that are exposed to air quality inferior to ISO Class 5
- Measuring and mixing sterile ingredients in non-sterile devices before sterilization is performed
|