In collaboration with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use – ICH, the FDA has updated the 2006 version of Q9 Quality Risk Management. The update includes various QRM principles and tools that can be used for ensuring and improving quality in the final product. 

The update is a part of the routine process where current practices and procedures are updated in response to various factors such as market complaints, feedback from various stakeholders, and, most importantly agency’s standards and operating procedures. 

Before finalizing the update, the FDA informs all the relevant stakeholders for their input or feedback and shares the draft of the proposed amendment. Upon receiving the feedback and finalizing the final regulations, the amendment becomes part of the regulations and is enforced accordingly. A copy is also made available for reference purposes through appropriate means such as websites and email. 

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use is an international body that aims to bring regulatory bodies and pharmaceutical organizations worldwide closer to each other. Its main objective is to harmonize pharma procedures, principles, and applications worldwide in different markets. 

The ICH is not an enforcing organization and does not have regulations or inspection routines. Instead, all regulation bodies collaborate with it to implement a common strategy for quality in the manufacturing process and final product. 

What is Quality Risk Management

Quality Risk Management identifies, evaluates, and removes any risks associated with the pharmaceutical industry's processes, procedures, and products. It helps to prevent defects in the product by minimizing the risk that could degrade the quality of products.

Quality Risk Management defines risk and provides guidelines to identify a risk effectively. It also provides information on controlling and communicating the adverse effect to all interested parties and reviewing risk.

Update on ICH Q9(R1) Quality Risk Management

In the updated Q9 QRM, existing section 5 “risk management methodology” has been updated, and three section called formality, risk-based decision making and subjectivity, are added. Additionally, section 6 “integration of QRM into industry and regulatory operations” has also been updated with one new sub-section “product availability risks” 

Let’s briefly discuss each of these updates

Section 5 “RISK MANAGEMENT METHODOLOGY”

In this section three additional sub-section have been added, as mentioned below

• Formality in Quality Risk Management

• Risk – Based Decision Making

• Managing and Minimizing Subjectivity

Let’s briefly discuss each of these sub-sections

Formality in Quality Risk Management

In the updated version, the structure of formality is not a binary concept (previously, it was only defined as formal and informal). Instead, it is a spectrum with various indications, from low to high. It enables personnel to adopt varying levels of formality during risk management activities. 

This section also provides guidance about the application of formality for a given risk management activity and commonly depends upon the following factors

Uncertainty: Uncertainty is related to insufficient information for identifying the hazards and indicates how much formality is required for risk aversion and management. 

Gaps related to information can be filled by various knowledge management techniques to provide all the necessary and critical information for successful risk management. 

Importance: It indicates and insists on the relevancy of quality in risk-based decisions and states that quality-based decisions require more formality and need to reduce the level of uncertainty associated with it. 

Complexity: The application of formality is directly proportional to the complexity of quality risk management for assuring product quality. 

With the above definition, it can be concluded that higher levels of uncertainty, importance, and complexity require more formal approaches toward risk assessment and mitigation. 

Higher and Lower Level of formality

This guide also describes higher and lower level formality, as described below

Higher Formality Level

• All parts of the quality risk management process must be explicitly performed and must be proceeded with standalone reports or documentation for all processes. 

•  Approved quality risk management tools must be used instead of unknown and unapproved.

• The activity must be performed by a well-trained professional, an expert in their relevant fields.

• A facilitator with relevant experience and knowledge is necessary to remain involved in the activity, ensuring higher formality.

Lower Formality Level

• Quality risk management activity is not performed as a standalone activity. Instead, it is part of other quality processes 

• Not using any quality risk management tools

• Absence of a team containing expert members

• Standalone reports and documentation are not generated or prepared

Risk Based Decision Making

The second section that is updated is “Risk based decision making”.

 It is the core mindset of quality risk management activities and provides a strong foundation during the activity. The risk-based decision starts with formality and documentation. It includes decisions such as hazards, risk control, risk acceptability, communication, and review.

Some approaches can be used to make risk-based decisions by the required level of formality and can result in higher levels for risk-based decision-making.

Some approaches defined under the updated Quality Risk Management Includes

• Formal analysis of available options before making a decision involves considering relevant factors. This approach is helpful and effective when the high uncertainty level and decisions require high priority. 

• A simple approach using existing information for assessing hazards, risks, and their control. This approach only applies when uncertainty is lower, but the priority level is high.

• Standardized approaches where a new risk assessment can be eliminated. It includes Standard Operating Procedures – SOP and policies, indicating what decision to make in what circumstances. 

The advantage of the above approaches is that they are an effective way of addressing uncertainty by using knowledge, which is, in turn, beneficial for both regulators and pharmaceutical manufacturers. 

Managing and Minimizing Subjectivity

The third section updated is “Managing and Minimizing Subjectivity”.

According to this section, subjectivity impacts the entire process and stages of risk management. Some areas critical for subjectivity include hazard identification, risk probability, severity, risk reduction, and effectiveness of decision.

Subjectivity represents how various stakeholders perceive the same hazard, harm, and risks and the subsequent activities for hazard identification and elimination.

Another scenario necessary for subjectivity is when adequate answers to risk questions are unavailable, and tools are poorly designed for risk activity.

In a real-world scenario, it is impossible to eliminate subjectivity. Still, it can be controlled to an acceptable level by addressing bias assumptions, proper use of tools, and maximizing relevant data and sources of knowledge.

Section 6 “INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY AND REGULATORY OPERATIONS”

Quality Risk Management processes and tools are important for eliminating risks and their associated consequences. However, implementing Quality Risk Management does not prevent a pharma organization from following regulatory bodies' regulations.

Quality Risk, Management, and Regulator regulations go hand in hand, and regulatory bodies can have greater confidence in a pharma organization that follows and implements Quality Risk Management as part of quality procedures.

Quality Risk Management must become part of existing operations and be documented appropriately. Additionally, both industry and regulatory body personnel must be trained for better understanding and confidence.

Some example of industry operations in which quality risk management can be integrated as follows

• Quality Management

• Development

• Facility, Equipment and Utilities

• Materials Management

• Production

• Laboratory control and stability testing

• Packaging and Labeling

• Supply chain control

• Inspection and assessment activities

Role of QRM in addressing risks associated with product availability w.r.to Quality/Manufacturing Issues

This update provides guidance on collaboration of regulatory industries w.r.to product availability risks.

One of the most important reasons for risks associated with product availability is non-compliance with Good Manufacturing Practices. It represents how drug shortage can be prevented by assessing risks and how they can be mitigated to effectively manage supply chain problems and issues.

Another area where quality risk management can effectively help supply chain issues is in cases where a pharma organization diversifies its sources. This diversification results in interdependencies that can induce risks in the supply chain.

Quality Risk Management helps a pharma organization develops an early warning system that effectively responds to quality/manufacturing risks internally and externally.

Some Quality/manufacturing factors that ensure reliability and availability include the following.

Manufacturing Process Variability and State of Control

Quality risk management can help devise monitoring practices to detect deviations in manufacturing processes for their identification and elimination. Because variable process contains quality gaps in them and impacts product availability

Manufacturing facilities and Equipment

One important variable that critically affects product availability is the present state of building and equipment. Factors such as aging facilities, maintenance issues, or a fault in operational design can severely affect the manufacturing process and the organization’s ability to fulfill demands.

Quality Risk management can be applied to the supply chain for assessing, detecting, and mitigating these factors. Using the latest technology, such as digitalization and automation, can also help manage these risks.

Oversight of Outsourced Activities and Suppliers

Outsourced activities and suppliers are an important pillar of a pharma supply chain and greatly impact quality and performance. Suppliers must be approved through risk assessments, effective knowledge management, and monitoring strategy.

Applying risk assessment in the supply chain helps to justify review and monitoring activities when a variation is identified in supplied materials and services.

About the Author

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.