Risk Management: FDA and Industry Experience

Dan Snider, Ph.D Vice President Morgantown RD

Mylan Pharmaceuticals Inc.

Disclaimer

• This presentation contains a summary of the opinion and perspective from GPhA member industry representatives on the topic of “Risk Management: FDA and Industry Experience”.

• This presentation does not necessarily

represent the opinion of the presenter nor “Mylan Pharmaceuticals Inc.”.

Risk Management and ANDA Review

• Under GDUFA review goals are mandated. • Risk Ranking is being used by the agency

to rate applications prior to review. • The goal for risk ranking would be to save

time on simple applications and apply the time to more complex applications. In aggregate this should speed up the review process.

Why Are We Talking About Risk Management Today

• GDUFA Goals 1. Enhanced SAFETY through risk based

inspection parity for all participants 2. Improve ACCESS to generics through more

timely and predicable approvals 3. Better TRANSPARENCY through improved

feedback and communication with industry

Why Are We Talking About Risk Management Today

• GDUFA Goals 1. Enhanced SAFETY through risk based

inspection parity for all participants 2. Improve ACCESS to generics through more

timely and predicable approvals 3. Better TRANSPARENCY through improved

feedback and communication with industry

Why Are We Talking About Risk Management Today

• GDUFA Goals 1. Enhanced SAFETY through risk based

inspection parity for all participants 2. Improve ACCESS to generics through more

timely and predicable approvals 3. Better TRANSPARENCY through improved

feedback and communication with industry

Current OGD Workload

According to Activities Report of the Generic Drug Program

• A change in the review philosophy seems necessary. • FDA has indicated that Risk Management of ANDAs is

a mechanism for that change.

ICH Q9 Guidance for Industry

Quality Risk Management • ICH Q9 was finalized in June of 2006. • From ICH Q9 Principles of Quality Risk

Management. – 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.

What is risk? • Manufacturing Risk

– Based on prior knowledge, what is the quality risk of the chosen manufacturing process?

– Do the critical quality attributes of the drug product address these risks?

• Drug risk – What is the inherent risk based upon the drug

product and its potential affect on the patient? – Do the critical quality attributes of the drug

product address these risks?

Manufacturing Risk

• The more complicated the process, the greater the risk? – Looks like we have already weighed in on this question.

• QbD IR example product development report is 107 pages. • QbD MR example product development report is 161 pages.

• How do we account for the experience of the firm

on similar processes to mitigate those risks. – Can Quality Metrics for the firm/site be used to

decrease the risk ranking? – Does familiarity with the process decrease the risk

ranking?

Drug Risk? • Risk from the drug product itself must be

considered. – What categories will require additional level of

effort, formality, and documentation of the quality risk?

• FDA and Industry should work together and transparently to achieve a common understanding of which drugs and or drug categories will require this effort.

Tools for Risk Assessment • ICH Q9 suggests several methodologies. • All methodologies share three basic

elements. – Risk Identification

• What might go wrong? – Risk Analysis

• What is the likelihood of the occurance? – Risk Evaluation

• How does the risk compare to the risk criteria?

Tools for Risk Assessment • ICH Q9 suggests several methodologies.

– 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.

FDA Risk Management and Industry Perspective

• Call for collaboration and transparency. – Similar to efforts on QbD, the Agency should work with

industry to assure that the details of the algorithm used are clear

– Work with Industry to provide guidance on any risk ranking that is based on the molecule and independent of the manufacturing process.

• Assure that resources are balanced so that complex drugs are approved in a timely and predictable fashion despite the increased Risk Ranking. – Complex products with more risk should have adequate

resources applied to their review. – Complex products and their associated risk should not

delay access to affordable generic drug products.