Table of Contents

Overview

Effective risk analysis is a progression that starts with risks to patient safety and efficacy. Product attributes that may impact patient requirements are evaluated next. Finally, process risks to product quality attributes are evaluated and mitigated with a proper definition of acceptance criteria. In this way, risk-based development arrives at a well-controlled process. Understanding the risks associated with your product is fundamental.

Key Concepts

QbDVision uses a Risk Assessment model that seeks to rationalize the various definitions of risk into a consistent set that can be applied to any type of product development scenario (drug, medical device, diagnostic, etc.) while staying consistent with international standards such as ISO 14971.

The presence of risk is associated with a hazardous situation that has the potential to cause harm. The first layer of risk assessment starts with Criticality, which is the product of the Impact (severity) of the harm and the Uncertainty of the harm. In our Risk Assessment model, Impact is conceptually the same as the severity of harm. Similarly, Uncertainty is conceptually the same as the Likelihood of harm. So, in the context of ISO 14971, Criticality is the product of the severity of harm and the Likelihood of harm, even though this definition is not immediately apparent in the standard.

The second layer of risk folds in the Capability Risk conceptually the same as the Occurrence of measured data outside the acceptable range. If measured data are frequently outside of the acceptable range, the Occurrence is high. Put another way, the risk related to the process capability is high. The product of Criticality and Occurrence provides a measure of Process Risk, which matches the definition of risk in ISO 14971. In other words, the product of Impact (severity) and probability of occurrence (Likelihood of harm * Occurrence) is equal to the product of Criticality and Occurrence. Even though the ISO 14971 standard does not include Detectability in its discussion of risk, this final layer of risk has also been included in the comparison to yield the Risk Priority Number (RPN), which is a measure of overall risk.

It is important to note that Criticality is driven by Impact (severity) and Uncertainty (Likelihood) and is not improved by a reduction in Capability Risk (Occurrence) or Detectability Risk. Better process capability, which reduces the probability of an attribute or parameter being outside of the acceptable range as demonstrated by manufacturing data, will reduce Process Risk. Similarly, earlier or more sensitive detection capability will reduce Detectability Risk and drive lower overall risk. With this structure, an attribute or parameter can be Critical but have low overall risk with robust process capability and control. This is the methodology used to define your design space, where these attributes and parameters can vary within predefined limits without impacting critical quality attributes (CQAs).

Risk Linking Records

Before setting up risk relationships in a process, users must have all Unit Operations and Final Attributes added. Users may then add Process Parameters, Material Attributes, and Intermediate Attributes for each unit operation.

Users will set up risk links between records in the “Criticality Assessment” section of a record (see screenshot below). This section captures risk information based on a valuable science-based process used in quality risk management (ICH Q9) that can aid in identifying which material attributes and process parameters potentially have an effect on product CQAs (see screenshot below). The Criticality Assessment is typically performed early in the pharmaceutical development process and is repeated as more information becomes available and greater knowledge is obtained.

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Risk Linking Video Tutorial

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Reports & Visualizations

Risk Map

The Risk Map is a graphical visualization that shows color-coded risk links from inputs to outputs for the entire manufacturing process. Users can select to create a map that displays the Impact, Uncertainty, Criticality, Capability Risk, Process Risk, Detectability Risk, or RPN risk information by Risk Label or Score Label. Additional filters can be used to customize the elements and relationships displayed on the map.

It is important to note that the Risk Label/Score Labels filters only apply to the elements selected, not the elements related via relationships. Additionally, if selected, the Filter Override options will display all of the Upstream and/or Downstream relationships and elements connected to the elements filtered for, regardless of their label. The Filter Override overrides other filter selections (ex. criticality).

Frequently Asked Questions

When creating a project, you can choose between a PHA or Risk Ranking.  There are 3 default RMPs in the system and they all appear to be a scored risk ranking.  Is one of them supposed to represent the PHA?  Is there a default PHA template? 

• The Risk Management Plans (RMPs) provided as defaults provide comprehensive risk management definitions by data type (FQA, IQA, PP, etc.) for you to use or modify for your product and process risk assessments.  

• When it is time to deploy the RMP for a particular project, you have to make two choices: 

  • The RMP and The Product Risk Assessment type.

• The Product Risk Assessment type will use the selected RMP regardless of selection.

• Product Risk Assessment types:

  • The Preliminary Hazards Analysis (PHA) is a more straightforward risk where you only assess the overall impact/severity and the uncertainty/likelihood relative to that impact/severity.  PHAs don’t allow you to assess a Final Quality Attribute against multiple risks.

  • You will select a Risk Ranking assessment if you want to assess a Final Quality Attribute against multiple risks.  For example, if you wanted to individually assess Final Quality Attributes against Safety and Efficacy or PK/PD and Immunogenicity, you would define these elements as General Attributes. Then you would be able to assess the risk of each FQA against each of these General Attributes.