Quality Risk Management(QRM)

 

Quality Risk Management(QRM)

Quality Risk Management (QRM) is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively.

 

QRM should ensure that:

– The evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient;

– The level of effort, formality and documentation of the QRM process is commensurate with the level of risk.

      GMP (Good Manufacturing Practices)

Is the part of quality assurance that ensures that products are produced and controlled consistently and reliably.

It can only come about by having clear descriptions of the way in which the work will be done. GMP specifically addresses risks that cannot be fully controlled by testing of the final product:

• Cross-contamination
• Mix-ups

These risks can best be controlled by having a properly managed system of working that takes them into account.

 

 

       INTRODUCTION

•          Risk management is not new – we do it informally all the time
•          Risk management principles are effectively utilized in many areas of business and government.
•        Military Standard 1629 dated 1974 regarding formal risk management
•         Risk management has been used in the medical device, telecommunications, and aerospace and car industries for many years.

 

ISO 31000:2009 Principles (Clause 3) Risk management should…

1.     Create value

2.     Be an integral part of organizational processes

3.     Be part of decision making

4.     Explicitly address uncertainty

5.     Be systematic and structured

6.     Be based on the best available information

7.     Be tailored

8.     Take into account human factors

9.     Be transparent and inclusive

10.  Be dynamic, iterative and responsive to change

11.  Be capable of continual improvement and enhancement

 

• Managing risk means forward thinking
• Managing risk means responsible thinking
• Managing risk means balanced thinking
• Managing risk is all about maximizing opportunity and minimizing threats
• The risk management process provides a framework to facilitate more effective decision making

 

Quality by Design –

“Risk Management is about making value out of uncertainty”

 

       Risk Management in Pharma. Industry

 

•      From a GMP point of view, we are only concerned with risks associated with quality, safety and efficacy Quality Risk Management

•      Organizations use risk approaches in other areas, e.g. to ensure resources are utilized in the most effective way.       - Patient Safety

 

       DEFINITIONS

• Harm: Damage to health, including the damage that can occur from loss of product quality or availability.
• Hazard: The potential source of harm
• Risk (In Pharmaceutical POV): The combination of the probability of occurrence of harm and the severity of that harm.

v   Risk (In General – ISO31000): effect of uncertainty on objectives

• An effect is a deviation from the expected — positive and/or negative.
• Objectives can have different aspects (such as financial, health and safety, and environmental goals)
• Uncertainty is the state, even partial, of deficiency of information related to, understanding or knowledge of, an event, its consequence, or likelihood.
• Risk is often expressed in terms of a combination of the consequences of an event (including changes in circumstances) and the associated likelihood of occurrence.

 

       Principles

v   Two primary principles of quality risk management are:

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

 

 

       QUALITY RISK MANAGEMENT PROCESS

  Quality risk management is a systematic process for the   assessment, control,

communication and review of risks to the quality of the medicinal product across the

product lifecycle.

Risk Management Tools:

  

       Responsibilities

• Quality risk management activities are usually, undertaken by interdisciplinary teams.
• CFTs may include experts from the appropriate areas e.g., quality unit, business development, engineering, regulatory affairs, production operations, sales and marketing, legal, statistics and clinical in addition to individuals who are knowledgeable about the quality risk management process.
• A systematic process of organizing information to support a risk decision to be made within a risk management process.

F    It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards.

1.     What might go wrong (Identification)?

2.     What is the likelihood (probability) it will go wrong?

3.     What are the consequences (severity)?

 

 Risk Evaluation

• Compares identified and analyzed risk against criteria
• Considers probability, severity and detectability
• Output can be qualitative (high, medium or low)
• Output can be quantitative (probability x severity x detectability)
• Quantitative provides a relative ranking – prioritizes risk

Risk = Probability x Severity x Detectability

 

Risk definitions: Based of Quantitative or Qualitative outputs, Risks are categorized as follows:

•  Intolerable – work to eliminate the negative event or introduce detection controls is required as a priority
• Unacceptable – work to reduce the risk or control the risk to an acceptable level is required
•   Acceptable – the risk is acceptable and no risk reduction or detection controls are required.

 

Ø  Risk reduction

•  Actions taken to lessen the probability of occurrence of harm and the severity of that harm
• Typically, CAPA and change control.

 

Ø   Risk acceptance

• The decision to accept risk
• If risk reduction action taken, follows re-analysis and evaluation

  

       Risk Communication

• Risk communication is the sharing of information about risk and risk management between the decision makers and others.
• Parties can communicate at any stage of the risk management process. 

 

       Risk Review

• Risk management should be an ongoing part of the quality management process.
•  Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk.

-       Ensures nothing has changed to affect the QRM assumptions, output and conclusions

-       Consider during product review

• The frequency of any review should be based upon the level of risk.
• Risk review might include reconsideration of risk acceptance decisions

 

       RISK MANAGEMENT METHODOLOGY

• Quality risk management supports a scientific and practical approach to decision making.
• It provides documented, transparent and reproducible methods to accomplish steps of the quality risk management process.
• Traditionally, risks to quality have been assessed and managed in a variety of informal ways based on, for example, compilation of observations, trends and other information.

 

Risk Management Tools

 Pharmaceutical industry and regulators can assess and manage risk using recognized risk

management tools:

-        Basic risk management facilitation methods (flowcharts, check sheets etc.)

-        Failure Mode Effects Analysis (FMEA);

-        Failure Mode, Effects and Criticality Analysis (FMECA);

-        Fault Tree Analysis (FTA);

-        Hazard Analysis and Critical Control Points (HACCP);

-        Hazard Operability Analysis (HAZOP);

-        Preliminary Hazard Analysis (PHA);

-        Risk ranking and filtering;

-        Supporting statistical tools.

 

 

       Implementation

            PDCA or the Deming cycle is a management methodology that aims to continually improve processes. This cycle is based on four stages: plan, do, check, and act. To adapt to market changes, improve efficiency, boost productivity, and meet the needs of your customers, having a method is required. 

 

       Benefits of Risk Management Implementation:

 

• Encourages transparency – Create baseline for more science-based decisions
•  Facilitates communication

– Matrix team approach

 – An aid to convince the stakeholders with trust

• Encourages a preventive approach – Proactive control of risks and uncertainty – Benefit of knowledge transfer by team approach

1. Changes behavior

– Better understanding of risk-based decisions

– Acceptance of residual risks

 

       Conclusion

• Quality risk management is a process that supports science-based and practical decisions when integrated into quality systems.
• Effective quality risk management can facilitate better and more informed decisions, and can provide regulators with greater assurance of a company’s ability to deal with potential risks.
• In addition, quality risk management can facilitate better use of resources by all parties.
• Quality risk management should be integrated into existing operations and documented appropriately.

 

       References and Further Readings

1. ICH Q9: Quality Risk Management
2. ICH Q10: Pharmaceutical Quality System
3. ICH-Endorsed Guide for ICH Q8/Q9/Q10 Implementation
4. US FDA Guidance for Industry: Q9 Quality Risk Management
5. WHO GUIDELINE ON QUALITY RISK MANAGEMENT
6. ISO 31000:2009, Risk management – Principles and guidelines
7. ISO Guide 73:2009 Risk management – Vocabulary
8. ISO 14971:2007 Medical devices -- Application of risk management to medical devices