FDA, Global Expectations, and Validation · PDF fileFDA, Global Expectations, and Validation Statistics ... include appropriate statistical quality control criteria as a condition

FDA, Global Expectations, and

Validation Statistics

Marlène García Swider, Ph.D., CQM

Institute of Validation Technology

June 23 – 24, 2015

Philadelphia, PA

Personal Claim

This presentation is based on

journal articles written by the author and

does not reflect a position, official or

unofficial, of the FDA. Any reference to FDA information is based on public information.

6/19/2015 3

Past

Previously, one or two firms were

responsible for the entire manufacturing

of a product or they outsourced others to

help with some of the manufacture.

6/19/2015 4

Currently,

Today, the increasing demand for the

products along with the pressure to

reduce cost and increase productivity

calls for globalization.

No matter what part of the world

All imported products to U.S. are required

to meet the same standards as domestic

goods – must be pure, produced under

sanitary conditions, and contain

informative and truthful labeling in English.

6/19/2015 5

6/19/2015 6

Statistics are no exception

“Where appropriate, each manufacturer

shall establish and maintain procedures

for identifying valid statistical

techniques…” – FDA Quality System Regulation (1996)

6/19/2015 7

What is Process Validation?

According to FDA, process validation is

the collection and validation of data, from

the process design stage throughout

production…

6/19/2015 8

What FDA wants?

Evidence that a process is capable of

consistently delivering quality product.

FDA depends on statistics…

to assure that batches of products meet

each appropriate specification and

appropriate statistical quality control

criteria as a condition for their approval

and release.

6/19/2015 9

FDA requires…

that statistical quality control criterial shall

include appropriate statistical quality

control criteria as a condition for their

approval and release.

6/19/2015 10

What are Statistical methods?

“Statistical methods are tools to be utilized

for better risk-based decision making in the

face of variation and uncertainty.”-

Paul L. Pluta, Ph.D.

6/19/2015 11

6/19/2015 12

FDA Globalizes

6/19/2015 13

No matter where you are…

The same FDA guidance apply to all

the inspections done by the Agency

(in U.S. or any other country.)

6/19/2015 14

Globalization Influence Diagram

Outsourcing Globalization

State-of-the-art Science, Innovation and

Harmonization

6/19/2015 15

FDA Guidelines

Through experience accumulated

through the years, FDA revised the

Process Validation Guidance in 2011.

6/19/2015 16

Process Validation – 3 Stages

Process Design

Process Qualification

Continuous Process Verification

6/19/2015 17

How it is done - Example 1

Process Design

DOE

Risk Analysis (screening potential

variables)

Models of the commercial process

6/19/2015 18

How it is done - Example 2

Process Qualification

Design of facility and equipment/utilities

qualification

Process Performance Qualification (PPQ)

Intra-batch and inter-batch metrics

Comparison and Evaluation of process

measures, in-process, and final product

attributes

How it is done - More Examples

Bayesian Statistics:

Learning from evidence as it accumulates.

6/19/2015 19

How it is done - More Examples

Process Control Techniques

SPC Techniques (probability, multivariate

statistics, and statistical control charts)

Process Analytical Techniques (PAT)

Process Capability Studies

Control Charts

Comparison of CPK and CQA

6/19/2015 20

6/19/2015 21

New Trends

What are others talking about…

Customized medication

Customers speak different languages

Introduction of new products while increasing

quality of care and reducing costs

6/19/2015 22

In Conclusion

Study and familiarize yourself with FDA

policies and regulation in order to comply

Network and participate on forums like this

one to keep in top of changes and trends

Inform yourself through researching

literature

Advice No. 1

Ensure that a statistician or person with

adequate training develops statistical

process control techniques.

6/19/2015 23

Advice No. 2

Develop data collection plans and

statistical methods and procedures for

measuring and evaluating process stability

and process capability

6/19/2015 24

Advice No. 3

Describe how trending and calculations

are performed and detect unintended

process variability

6/19/2015 25

Advice No. 4

Collect production data to evaluate

process stability and capability

6/19/2015 26

Advice No. 5

Understand the role of the quality unit and

review process

6/19/2015 27

Advice No. 6

Identify variability in the process and/or

signal potential process improvements

6/19/2015 28

References

FDA 2011 Process Validation Guidance

FDA, Quality Systems Approach to

Pharmaceutical CGMP Regulations, Guidance

for Industry, 2006

Case Study: Use of Statistical Process Control

to Detect Process Drift (Torbeck, 2011)

Guidance for the Use of Bayesian Statistics in

Medical Device Clinical Trials

www.fda.gov

6/19/2015 29

6/19/2015 30

Contacts

Globalization issues at

[email protected] or at

(301) 796-4600