Page 223 - Assurance of Sterility for Sensitive Combination Products and Materials

202 Assurance of sterility for sensitive combination products and materials

7.4.2 Other factors influencing the assurance of sterility
Other factors influencing the SAL or PNSU* should also be considered.
These include:

7.4.2.1 Patient’s immuno-compromised status and ability to treat the
infection
The patient’s condition may vary significantly. Elderly patients or patients
with multiple comorbidities are more likely to exhibit a more compromised
status and a decreased ability to fight off an infection. Some patients are
given a prophylactic dose of antibiotics prior to treatment with the health-
care product which improves their ability to resist infection. Many microor-
ganisms are resistant to the medications that have traditionally been used to
treat the infections caused by the organism. Multi-drug resistant organisms
(MDRO) may be present impacting the ability of patients to be treated.
It has been estimated up to 50% of antibiotics are ineffective in treating
MDROs. The ability to treat patients is also influenced by the patient’s fail-
ure to take antibiotics as prescribed.

7.4.2.2 Bioburden control in the manufacturing environment
As per nonquantifiable aspects of standards, manufacturers have imple-
mented numerous controls for bioburden to help ensure adequate steriliza-
tion. These controls include:
• Environmental Monitoring to support controlled manufacturing en-
vironments. Typical monitoring includes viable air testing and viable
surface testing. It should be noted that the level of controls for asep-
tic processing is significantly higher than that required for terminal
sterilization.
• Utility systems are routinely monitored to ensure control of contami-
nation in the controlled manufacturing environment. The manufacture
of aseptically processed finished goods often takes place in controlled
environments such as isolators.
• Typical engineering controls in these areas include the following. It
should be noted again that the level of controls for aseptic processing is
significantly higher than that required for terminal sterilization.
• high-efficiency particulate air (HEPA) filtering of the incoming air,
• differential pressure to direct airflow from the manufacturing area
out to the ancillary spaces and beyond,
• temperature and humidity control to ensure manufacturing area is
not conducive to microorganism growth and for the comfort of the
manufacturing operators,