PROCESS LIFECYCLE VALIDATION - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 208

from one product stream into another product stream. Without a touch point, the
cross-contamination process flow is interrupted and transport cannot occur.
Certain general facility risks, which are inherent to the facility and are not spe-
cific to cross-contamination risks, may be excluded from this evaluation. General
facility risks include the following:
• environmental factors inherent to biochemical manufacturing (e.g., biobur-
den);
• activities that occur outside of the facility (e.g., transport of personnel and
materials);
• receipt of raw materials; and
• QC testing of multiple products.
Step 2: Risk Analysis Following the identification of cross-contamination and
nonroutine event risks, a detailed RA is performed. The FMEA tool is used
for this analysis of all multiproduct touch points. Each identified risk is analyzed
using the severity, occurrence, and detection scoring criteria. The severity of fail-
ure, probability of occurrence, and the ability to detect a failure that could result
in cross-contamination or nonroutine event is determined for each risk identified
and scored. The severity of the cross-contamination event is determined based
on the type of cross-contamination or nonroutine event between two commercial
products.
Probability of occurrence is based on the general multiproduct controls as well
as facility-specific controls that help reduce the occurrence of the failure mode.
The detection score is based on the ability to detect the failure mode or potential
cause of the failure mode. The cross-contamination risk is estimated for each
identified risk and a RPN is calculated.
Step 3: Risk Evaluation and Risk Control Strategy The cross-contamination risk
prioritization matrix is used to determine risk acceptability and assess mitigation
controls needed on the basis of the calculated RPN value. For example, critical
risk, high risk, medium risk, and low risk. The critical risks must be mitigated
immediately and the high risks need active mitigation projects. Low and medium
risks are those considered acceptable and no further action is required.
The RA also identifies additional risks classified as acceptable with controls,
such as the following:
• transport of waste in shared corridors and common areas;
• transport of soiled equipment and parts in shared corridors and common
areas;
• cleaning supplies and equipment that are not product dedicated; and
• cross-contamination via small parts, shared equipment, and shared areas.