Download Updates on Quality Metrics

GPhA/FDA
FALL TECHNICAL
CONFERENCE
Updates on Quality Metrics Industry Perspectives
Dan Snider
Vice President, Research and Development Mylan Inc.
Disclaimer
• This presentation contains a summary of the
opinion and perspective from GPhA member
industry representatives on the topic of
“Quality Metrics”.
• This presentation does not necessarily
represent the opinion of the presenter nor
“Mylan Inc.”.
What is Quality?
What is Quality?
Preamble to CGMP uses the word quality greater than 100 times.
The first time
Under the Federal Food, Drug, and Cosmetic Act, a drug is deemed to be
adulterated unless the methods used in its manufacture, processing,
packing, and holding, and the facilities and controls used therefor, conform
to current good manufacturing practice so that the drug meets the safety
requirements of the act and has the identity and strength and meets the
quality and purity characteristics that it is represented to have. The
regulations are being updated and made more explicit, and therefore less
subject to varying interpretations, to assure that all members of the drug
industry are made aware of the level of performance expected of them to
be in compliance with the act. EFFECTIVE DATE: March 28, 1979.
What is Quality?
Preamble to CGMP uses the word quality greater than 100 times.
The first time
Under the Federal Food, Drug, and Cosmetic Act, a drug is deemed to be
adulterated unless the methods used in its manufacture, processing,
packing, and holding, and the facilities and controls used therefor, conform
to current good manufacturing practice so that the drug meets the safety
requirements of the act and has the identity and strength and meets the
quality and purity characteristics that it is represented to have. The
regulations are being updated and made more explicit, and therefore less
subject to varying interpretations, to assure that all members of the drug
industry are made aware of the level of performance expected of them to
be in compliance with the act. EFFECTIVE DATE: March 28, 1979.
What is Quality?
FD&C Act Chapter V: Drugs and Devices
§ 351. Adulterated drugs and devices
A drug or device shall be deemed to be adulterated—
(a) Poisonous, insanitary, etc., ingredients; adequate
controls in manufacture
(1) If it consists in whole or in part of any filthy, putrid, or decomposed
substance; or (2)(A) if it has been prepared, packed, or held under insanitary
conditions whereby it may have been contaminated with filth, or whereby it
may have been rendered injurious to health; or (B) if it is a drug and the
methods used in, or the facilities or controls used for, its manufacture,
processing, packing, or holding do not conform to or are not operated or
administered in conformity with current good manufacturing practice to assure
that such drug meets the requirements
of this chapter as to safety and has the identity and strength, and meets the
quality and purity characteristics, which it purports or is represented to
possess;
What is Quality?
FD&C Act Chapter V: Drugs and Devices
§ 351. Adulterated drugs and devices
A drug or device shall be deemed to be adulterated—
(a) Poisonous, insanitary, etc., ingredients; adequate
controls in manufacture
(1) If it consists in whole or in part of any filthy, putrid, or decomposed
substance; or (2)(A) if it has been prepared, packed, or held under insanitary
conditions whereby it may have been contaminated with filth, or whereby it
may have been rendered injurious to health; or (B) if it is a drug and the
methods used in, or the facilities or controls used for, its manufacture,
processing, packing, or holding do not conform to or are not operated or
administered in conformity with current good manufacturing practice to assure
that such drug meets the requirements
of this chapter as to safety and has the identity and strength, and meets the
quality and purity characteristics, which it purports or is represented to
possess;
What is Quality?
It is not just conformance to specifications.
The words “identity and strength, and meets the quality and
purity characteristics” include:
Identity is the identification specification.
Strength is the potency specification.
Purity includes the impurity specifications.
Quality seems to be somewhat undefined.
What is Quality?
‘‘Food and Drug Administration Safety and Innovation Act’’ (FDASIA)
SEC. 711. ENHANCING THE SAFETY AND QUALITY OF THE DRUG
SUPPLY.
Section 501 (21 U.S.C. 351) is amended by adding at the end the following flush
text:
‘‘For purposes of paragraph (a)(2)(B), the term ‘current good manufacturing
practice’ includes the implementation of oversight and
controls over the manufacture of drugs to ensure quality, including
managing the risk of and establishing the safety of raw materials,
materials used in the manufacturing of drugs, and finished drug
products.’’.
This is much more clear. Quality is everything.
Where is Quality Now?
Where is Quality Now?
There is a major shift towards innovation and continuous improvement with the Pharmaceutical
cGMPs in the 21st Century.
Applicable Guidance Include:
ICH Q1 through Q11
Q8(R2) Pharmaceutical Development- How to describe the development of a product.
Q9 Quality Risk Management - Assessing risks to the Quality of a product.
Q10 Pharmaceutical Quality System - An overarching system is required.
Why is this all necessary?
Where is Quality Now?
There is a major shift towards innovation and continuous improvement with the Pharmaceutical
cGMPs in the 21st Century.
Applicable Guidance Include:
ICH Q1 through Q11
Q8(R2) Pharmaceutical Development- How to describe the development of a product.
Q9 Quality Risk Management - Assessing risks to the Quality of a product.
Q10 Pharmaceutical Quality System - An overarching system is required.
Why is this all necessary?
Quality is Everything!
Understanding Quality Today
• Quality is everything.
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Concept of modern quality system
– Robust quality system
– Quality by design and product development (lifecycle)
– Quality risk management
– CAPA
– Change control
– Idea of separate quality unit – management review of product, system, and
process quality
Essential leadership to establish company-wide commitment to quality and for the
performance of quality management system
Understanding Quality Today
In order for FDA and Industry to work to benefit the
public, Quality Metrics should be developed.
Why?
Because Quality is Everything.
“Quality Metrics”
What metrics are important to FDA and most beneficial for Industry to measure?
Examples of Potential Metrics
• Batch Failure Rate
• Right First Time
• OOS / Laboratory Failure Investigation Rates
• Definitions and foundation matters!
– Standards for Sampling/Acceptance Plans
Referenced from: Russ Wesdyk 2013 CMC Presentation – Quality Metrics
Industry Reports - Minimal
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Each FEI site reports the following (per CY) – stratify by
product and/or application number.
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# of lots attempted
# of lots rejected
# of lots reworked or reprocessed
# of lot release tests conducted
# of Out of Specification Results (# of lot release tests failed)
# of lot release results invalidated because of laboratory
error/anomaly (# of lot release test outcomes reversed due to lab
error)
Data requirements from industry are minimal
Referenced from: Russ Wesdyk 2013 CMC Presentation – Quality Metrics
Quality Metrics
•
FDA constraints: Records made available under 704, to collect under 706, to
prepare risk based inspection schedule under 705 (FDASIA)
•
Metrics need to apply across all sectors (Generic, Rx, OTC)
•
Metrics need to be Quantitative and OBJECTIVE
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Eliminate unintended consequences which incentivize the wrong behaviors.
•
Relevant to patient safety and health
•
Common ground, FDA and industry need consensus
FDA Potential Metrics
1. Batch Failure Rate
2. Right First Time
3. OOS / Laboratory Failure Investigation Rates
What can GPhA do to drive success?
The process benefits by industry providing
input both positive and negative.
Alignment on Fundamental Definitions
How exactly do we define when differences exist?
We need to all speak the same language
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How do we define?
What is a batch?
What is a lot?
What is final product disposition?
What is a rejection?
Challenging Questions
Lets do our homework, lets meet on common ground.
Pulse Check
• Is there alignment within your company on definitions?
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What metrics do you measure?
How do you calculate these metrics?
Do you stratify metrics by product or site?
How do these benefit public health?
How would these benefit the FDA?
How do these benefit the industry?
• What do we have in common?
• Where are our differences?
• Should we, the generic industry leaders, do the math and provide
the algorithms?
• What method of measurement do we use?
• What level of statistical confidence do we use?
• What can we bring to the table to help GPhA solidify these sorts of
definitions?
Food for Thought…
Who is willing to lead???
Companies
Industry
FDA
Thank You.