# Presentation: 243822

## 10:00  A.M. – Noon
7 June 2004

- 7 June 2004

**ICH Quality **** Plenary Meeting**

## Scope of this Meeting

- Quality Topics
- Q1, Q3, Q4, Q5, Q8, Q9, QS proposal
**Focus of this meeting be limited to Q8, Q9, and the QS Scoping Document**
- Other topics be discussed separately
- Q1 – Tuesday 8:00 a.m., meeting of the group of experts
- Q3AR and Q3BR Q&A (further discussion; When? Who?)
- Q4B – “Regulatory Acceptance of Pharmacopeial Interchangeability”
- Q5E –Discussions with S&E experts (comments on statements referring to non-clinical and clinical studies)

## Meeting Agenda

- A brief perspective on Q8 and Q9
- To facilitate and structure our discussion on
- General principles and scope of Q8 & Q9
- Understanding the connection and approaches for integration between Q8 and Q9
- Q8 Progress and Next Steps
- Q9 Progress and Next Steps
- QS Scoping Document – Need, Objective, Scope, Relation to Q8 & Q9, ...?

## Pharmaceutical Development

- Multi-disciplinary complex process
- Many choices/approaches for achieving the goal
- Both industry and regulators wish to assure that
- Decisions are based on science to assure a product will perform its intended function for the required duration within a given environment
- This includes designing in the ability to maintain, test, and support the product throughout its total life cycle.
- “Building quality in” or “assuring quality is by design”
- Quality can not be tested into a product

## Opportunity

- Over the last two decades we have learned how to solve complex multi-factorial problems
- Multivariate empirical methods (e.g., Response Surface Methods)
- Systems approaches
- New measurement and information technologies
- Measurements that can predict performance
- Such information is often filtered out of regulatory submissions
- “fear” or “regulatory uncertinty”
- ICH Q8 can open the door for sharing and utilizing this information

## Within the design space only - e.g.,other variables held constant

## Predicting Dissolution

- Drug Substance

- Formulation

- Process

- Product

- NIR

- Disso
- Test

- Bio
- PK/PD

***Dissolution = f *****(*****Ex1, Ex2, P1, P2, PS...*****)**

- Real Time Release

- Stability

## Systems focus

- Provides a structured approach
- Development efficiency
- Use of prior knowledge
- Continuous learning
- Risk mitigation
- Knowledge sharing
- Knowledge communication
- Efficient and optimal decisions
- Industry - Regulators

## Drug and disease models use mathematical, statistical and pharmacological concepts to accumulate and quantify knowledge to improve decision-making.

**Traditional**

**Model-based**

**Decision-making approaches**

- Data
- Hidden Intuition
- Empirical
- Subjective

- Knowledge
- Transparent logic
- Predictive
- Objective

- Donald Stanski, FDA

## Appropriate Level of Regulatory Scrutiny 

- All regulators desire to apply an appropriate level of regulatory scrutiny to
- Risk/Benefit decisions
- Specifications, controls, change management to ensure unchanged performance
- In absence of relevant information their decisions reflect available data (unable to generalize reliably)

## Data based decisions: No Generalization 

- Data based decisions: No Generalization

## Knowledge based decisions: Improved Ability to Generalize 

- Knowledge based decisions: Improved Ability to Generalize

**Pharmaceutical Development Knowledge**

**environmental**

**raw material properties**

**process **
**conditions**

**Robust process**
**Stable and Bioavailable product**

## Ability to Generalize...

- Provides a basis for assuring appropriate regulatory oversight
- Review/assessment decisions
- Submission commitments
- Communication (Review/Inspection) for appropriate risk coverage
- Continuous improvement
- Efficiency
- Reducing variability

## An Example of our (FDA) Current Limited Ability to Generalize ..

- Change: Site of Manufacture (no other change) – Modified Release Tablet
- No IVIVC
- Bioequivalence study, up to 3 batches of accelerated stability data,... PAS
- Significant body of data (?) – 1 batch
- IVIVC
- No BE study, rest the same
- Changes in formulation – is the IVIVC still valid? [correlation may not be causal, therefore may not hold]

## Ability to Generalize ...

- Provides a “measure” of process understanding
- Provides an objective means to evaluate reliability of data/information/knowledge submitted
- Predictive ability
- Extent of coverage (design space) and data density
- Objective approach for risk coverage (regulatory oversight)
- Reliability of generalization – Post approval change management (Review – Inspection – Company QS)

## Risk

- Process
- Understanding

- Post
- approval
- change

- CMC
- regulatory
- oversight

- Company’s
- Quality system

- cGMP
- regulatory
- oversight

- ICH Q8

- ICH Q9

## ICH Q8 + Q9