ASEPTIC PROCESSING: TWO - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 239

TABLE 10.1 A Nonexhaustive Inventory of the Locations of Bioburden
in the Aseptic Manufacturing Environment and the Respective Origin of Bioburden
Location of Bioburden

Original Source of Bioburden

Personnel gloves Human body flora
Personnel garments Human body flora
Cleanroom ceilings Cleanroom air, human body flora
Cleanroom walls, floors, doors Cleanroom air, human body flora
Tables, chairs, mobile carts Cleanroom air, human body flora, external
(uncontrolled) surfaces
Cleanroom air Supply air, human body flora
Spillages (sterile items) Cleanroom air, human body flora
Spillages (nonsterile items) Spilled material, air, human body flora
Equipment (e.g., vessels, filling lines) Cleanroom air, human body flora
Ancillary equipment and items (e.g.,
forceps)

Cleanroom air, human body flora

Paperwork and paper records Cleanroom air, human body flora

Control panels (e.g., human-machine
interfaces)

Cleanroom air, human body flora

Container closures and components
(before sterilization)

Specific material, cleanroom air, human body
flora

Packaging Specific item, cleanroom air, human body flora

Raw materials and formulated
product (before sterilization)

Sterilization and
depyrogenation
Sterilization

Wash Prepare

Container

Distribute

Wash Prepare

Closure

Store and ship

Wash Prepare Sterilization

Equipment

Formulation Lable and pack

Filtration

Inspect

Dispensing

Exterior wash and dry

Raw materials

Capping

Active control Freeze drying

Figure 10.1 Generalized schematic for the aseptic manufacture of parenteral product
presentations (vial). Reproduced with permission from Ref. [4].

The process steps and operations that actively reduce or remove bioburden and
endotoxin and are recognized as active control points are specifically identified
in Figure 10.1 [4]. In almost all manufacturing scenarios, the final mechanisms
are those steps that are the final means of actively removing or destroying any
resident microbial hazard. Generally, these are sterilization and depyrogenation