# Presentation: 591932

## ICH Q9: Quality Risk Management

- H. Gregg Claycamp, Ph.D.
- Office of New Animal Drug Evaluation
- gregg.claycamp@fda.hhs.gov

***CDER ADVISORY COMMITTEE FOR PHARMACEUTICAL SCIENCE (ACPS)***
***October 5-6, 2006 Rockville, MD***

## Why was ICH Q9 needed?

- To ensure a common understanding of Quality Risk Management (QRM) by both industry and regulators
- To facilitate moving to the “Desired State”
- To facilitate communication and transparency
- To move from ‘fire fighting’ to management of risk
- ICH Q9 explains
- A common language and process
- Potential methodologies for QRM
- Where QRM can add value

## What’s in Quality Risk Management?

- Q9 has broad risk concepts and principles
- Principles for implementation
- Elements of Risk Assessment/Management Processes
- Does not discuss a single tool, but *“The Right Tool for the Job”* approach
- Risk Management Tools
- High-level  (Ideas and Concepts)
- Mid-Level  (Quantitative and Qualitative)
- Low-Level (Real numbers and real time)

## What’s not in ICH Q9 ...

- A “cookbook” for risk management
- A specific prescription for *your *risk management program
- An exhaustive treatment of theory
- An exhaustive list of methods and tools

## Q9’s Sample Process

**Risk Management Tools**

**Risk Communication**

## QRM is not a Single Process

**Start**

**End**

**Process-****step**

**Decision**

**Feedback ****procedure**

**Sub-****process**

**Sub-Sub-****process**

## Different Meanings of “Risk” 

- _Individual_: *Risk is a cognitive and emotional response to expected loss.*
- _Society_:  *Risk is a societal expression of expected harm tempered by expected benefits.*
- _Organizations_: *Risk is a combination of the probability of occurrence and severity of selected harms.*
- _Technical_: *Risk is usually based on the expected value of the conditional probability of the event occurring times the consequence of the event given that it has occurred.*

## Q9 Overarching Principles

- “The evaluation of the risk to quality should be based on scientific knowledge and ultimately link back 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.”

## Concept: Link Back to Patient Risk

- Process

- Materials

- Design

- Manufacturing

- Distribution

- Patient

- Facilities

*Opportunities to impact risk using quality risk management*

## QRM and the Design Space

*What is the chance (probability) of “falling outside” of the design space per unit time?*

- Risk analysts estimate probabilities of being outside (or inside!) of design limits, given various scenarios.

- Design parameters and their intersection in a “design space” concept

*v**1*

*v**2*

*v**3*

*design* *space*

## A systematic process for the assessment, control, communication and  review of risks to the quality of the drug product across the product lifecyle.

- QRM: Another Systems Approach

## “Risk Management” is Universal

- Company

- Strategic Risks

- Operational Risks

- Financial Risks

- Compliance Risks

- Competitor Advantage

- Company Viability

- Shareholder Harm

- Patient Harm

- ICH Q9 Impact

## Severity and Probability  Risk 

- Increasing Severity of Harm/Consequence

- Increasing Probability of Occurrence

***Low Risk***

***Medium Risk***

***High Risk***

## Tools for Risk Management 

- Tools for Risk Management

*ICH Q9 Includes an Annex of Tools*

## “High-Level” Tools 

- Often rely mixed kinds of information:
- Quantitative
- Qualitative
- Expert judgment
- Focus on systematic thinking:
- Define the risk question
_*Organize*_ information under categories, attributes
- Build decision making paths

## Examples of implementation: FDA

- CDER/ORA Site Selection process for GMP inspections
- CVM pre-approval decision support system (PAIDSS)
- Other efforts in progress

## Qualitative Risk Estimation

| Health

Severity Scale  | Probability of Occurrence |  |  |  |  |
| --- | --- | --- | --- | --- | --- |
|  | Very Low | Low | Medium | High | Very High |
| Death | Medium | Medium | High | High | High |
| Hospitalization | Low | Medium | Medium | High | High |
| Acute Illness | Low | Medium | Medium | High  | High |
| Worry | Low | Low | Low | Medium | Medium |

*SAMPLE TABLE ONLY*

## Risk Ranking –High Level 

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**Process**

**Facility**

**Product**

**(Risk Ranking) **

*SAMPLE CHART*

## Mid-Level: Combinations of Methods

- More formula-driven than High-level tools and approaches
- Expert-driven qualitative with some data
- FME(C)A
- Decision analytic methods
- Limitations
- Which experts?
- Risk-analytical methods
- Sorting value- and perception-driven assessments with quantitative variables

## FME(C)A

- 10
- 9
- 8
- 7
- 6
- 5
- 4
- 3
- 2
- 1

- Severity of Effect

- 10
- 9
- 8
- 7
- 6
- 5
- 4
- 3
- 2
- 1

- Occurrence Probability

- S

- Criticality

- S x O

- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10

- Detection*

- “SOD” or “Risk Number”

- O

- S x O x D

**Higher detection ability lowers risk score.*

## FME(C)A—Intermediate Tool

*SAMPLE CHART*

## Present Status of the Guideline

- Published as US Guidance, June 2006
- _[http://www.fda.gov/cder/guidance/7153fnl.htm](http://www.fda.gov/cder/guidance/7153fnl.htm)_
- Judging by industry and regulatory conferences, workshops, publications: *interest in Q9 remains high*
- Some members of the ICH EWG compiled presentations for information.  Now available on ICH website:
- _[http://www.ich.org/cache/compo/276-254-1.html](http://www.ich.org/cache/compo/276-254-1.html)_

## Next Steps?

- From great ideas to practice—how?
- Both industry and regulators want to know
- Which risks firsts?
- Which tools are best?
- How will I know “good” from “bad” risk management?
- Do we need dept./divisions of risk managers?

## Examples of Implementation: Industry

- Many presentations at conferences showing examples of:
- Failure modes and effects analysis (FMEAs)
- Multivariate models (QC/QA integration)
- Systems design, modeling and application are readily adaptable to QRM approaches

## Keys to Implementation

- Key to implementation:  the systems approaches in Q8-Q9-Q10 leverage the best parts of existing knowledge bases and expertise for systematic control of risks to pharmaceutical quality*.*
*Gregg’s Pareto principle for QRM:  “More than 80% of the expertise for a Quality Risk Management program exists among the domain --i.e., not risk-- experts.” *