Risk Management for Aseptic Processing - Pharmaceutical Technology

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Risk Management for Aseptic Processing
The author discusses the risks involved with aseptic processing, methods and tools used to identify and control risk, and regulatory guidelines relevant to the risk-management process.

Pharmaceutical Technology

The uses for quality-risk-management tools are nearly limitless. A few examples of the uses of these tools in aseptic processing include:

  • Equipment and facility design. QRM tools such as 3-D risk assessment can be used to identify high-risk equipment and facilities, as well as low-risk equipment and facilities; this will allow risk-control efforts to focus on eliminating the highest risks (4). Design of high-risk equipment and facilities can be enhanced using input from tools such as failure mode and effects analysis (FMEA) and fault tree analysis to identify potential failure modes. This input allows the equipment designer to add preventive measures to the equipment design to reduce the occurrence of, or even eliminate, potential failure modes.
  • Equipment and facility qualification. QRM tools can be used to identify the critical aspects of the aseptic processing equipment or facility that need to be intensively qualified, and the low-risk aspects of the equipment or facility. QRM tools can also be used to determine the extent and frequency of requalification efforts.
  • Change control. QRM tools can be used to identify high-risk equipment and facilities that need to be maintained under strict change control, as well as the equipment and facilities that can be placed under a simpler engineering change management program.
  • Process validation. QRM tools can be used to identify the key inputs, key process parameters, and key outputs that need to be monitored and controlled. This allows for focused process validation that ensures that process parameters that are critical to product quality are appropriately validated.

What is quality risk management?

Risk is the combination of the probability of harm and the severity of harm. For the purposes of QRM, it is the risk to the patient that is important, not the risk to other stakeholders such as government, industry, medical practitioners, etc.

According to ICH Q9, quality risk management is defined as "a systematic process for the assessment, control, communication, and review of risks to the quality of the drug product across the product lifecycle" (2).

Some key concepts in this definition are that QRM is a systematic process, and that it is designed to manage the risks to product quality across the product lifecycle. The introduction of a systematic process for managing product quality is crucial to consistently providing a high-quality product to the customer.

ICH Q9 defines the two primary principles of quality risk management as follows:

  • The evaluation of risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient
  • The level of effort, formality, and documentation of the quality-risk-management process should be commensurate with the level of risk (2).

These principles lead to a need for a formal risk-management program for manufacturers of parenteral products. Because these products, which include most biotechnology-derived drugs, bypass many of the body's defense systems, the level of risk to the patient is significantly higher than in oral or topical products.

The quality-risk-management process

Figure 1: Risk-management process (2). (FIGURE 1 IS COURTESY OF ICH)
ICH Q9 describes the quality risk-management process. Figure 1 illustrates the components of the quality risk-management process across the product lifecycle.

Risk assessment. Risk assessment is the first portion of the quality-risk-management process. It consists of identifying potential hazards, analyzing hazards, and risks associated with exposure to those hazards. A few key points about the risk assessment process include:

  • Risk assessments should be performed by a team of qualified experts from disciplines such as engineering, quality assurance, validation, and manufacturing, preferably facilitated by someone familiar with the risk assessment process. This team should clearly define the risk question. A poorly defined risk question can lead to lack of focus in the risk assessment.
  • Three fundamental questions should be answered in the risk assessment: What can go wrong, how likely is it to go wrong, and how severe are the consequences?
  • A few of the more popular methods for risk assessment are given in the "Risk assessment tools" section. These tools share some of the key characteristics of a risk assessment process:
  • Systematic identification of hazards referring to the risk question (risk identification)
  • Estimation of the risk associated with the identified hazard (risk analysis)
  • Comparison of the identified and analyzed risk against pre-determined criteria (risk evaluation).


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