BIOPHARMACEUTICAL MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 356

TABLE A.2 Example of Risk Analysis Scales
Risk Factor

Rank Severity Likelihood

High Failure has a severe impact on product

safety and efficacy

Frequently occurs

Medium Failure has a medium impact on product

safety and efficacy

May occur if not controlled

Low Failure has a severe low on product

safety and efficacy

Rarely occurs

Risk evaluation: Risk evaluation is the act of assessing the risks and determining their acceptability
in terms of potential impact to product safety and efficacy. Risks are frequently rated as broadly
acceptable, as low as reasonably practical, and intolerable. The terms may be defined as indicated
in Table 12.5.

contamination (prion, e.g., TSE), contamination (particle), FBS out of specifi-
cation, and FBS degraded. These hazards are caused by a variety of factors as
shown in the “Cause” column of the hazard analysis table. The predominate cause
is a potential lack of compliance by the vendor with established health authority
regulations as noted in the following:

• Serum collection does not comply with applicable protocols.
• Serum collection by untrained personnel.
• Serum collected in contaminated vessels.
• FBS processing does not comply with cGMPs.
• Testing does not comply with European Pharmacopeia requirements.

Risk analysis : A hazard analysis is a tool that facilitates a high level assessment
of risk. It typically looks at the classic risk parameters of severity and likelihood
of occurrence of the harm. Detectability, often included in more extensive risk
assessments, is not a factor in a hazard analysis. Both severity and likelihood
were examined for the hazards identified and are shown in the hazard table. Both
severity and likelihood were ranked on a three-level—high, medium, low—basis.
If desired, a more detailed scale, for example, a 5-point or 10-point scale, may
be utilized. An example of a three-point scale is shown in Table A.2.
The hazard analysis shows that all risks were assessed as either broadly accept-
able or as low as reasonably practical given the current level of mitigation.

A.4 Risk Control
Risk reduction : Risk reduction involves identifying and implementing measures to
minimize and controls the risks that have been identified. An underlying assump-
tion is that mitigations will be reasonable and practical. A point of diminishing