Transcript FDA Compliance and Audit Preparation

Compliance:
U.S. Healthcare Industry Overview
&
Basic U.S. FDA Inspection Preparation
William Sellers
Director, J&J Regulatory Compliance
ASQ – Reading, PA
10 June 2013
Agenda

Brief History of the U.S. FDA

The U.S. Compliance Environment

The Systems Approach to Compliance

Preparing for the Inspection
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Brief History of the U.S. FDA
1862
Bureau of Chemistry
Established by President Lincoln; predecessor of FDA
1906
Food & Drugs Act
Meat Inspection Act
Both passed on same day
Prohibit interstate commerce of misbranded and
adulterated foods and drugs
Upton Sinclair’s, The Jungle
1927
Food, Drug & Insecticide
Administration
Bureau of Chemistry reorganized into two entities:
FD&I (regulatory) and Bureau of Chemistry & Soils
(research)
1930
Food & Drug Administration
1933
FDA Recommends
Complete Revision of
1906 Food & Drug Act
Bill introduced to U.S. Senate
5 year battle
1937
Elixir of Sulfanilamide
Made with diethylene glycol – kills 107, many children
Highlights need to establish safety before marketing
1938
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Food, Drug & SUBGROUP
Cosmetics
New drugs to be proven
0000 safe before sale (NDA)
Safe levels for unavoidable poisons/toxic additives
Authorized factory inspections
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Brief History of the U.S. FDA (continued)
1951
Durham-Humphrey
Amendment
Defines drugs that cannot be used safely without
medical supervision and restricts their free sale - Rx
1958
Food Additives
Amendment
Color Additives
Amendment
Manufacturers must establish safety in foods, drugs
and cosmetics – “specifically to induce cancers”
GRAS – Generally Regarded As Safe
Kefauver-Harris Drug
Amendments
Thalidomide Babies – Western Europe
Increased drug safety and proof of effectiveness
cGMP
Enforced by the FDA under the 1938 Act
Manufacturing principles that must be observed
1972
OTC Drug Review
Regulation of Biologics
Enhance safety, effectiveness and labeling
Serums, vaccines and blood products from NIH
1976
1980
1982
1983
1992
2002
Medical Device Amendments
Infant Formula Act
Tamper-resistant Packaging Regulations
Orphan Drug Act
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Generic Drug Enforcement Act
Public Health Security and Bioterrorism Preparedness and Response Act
1960
1962
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The U.S. Compliance Environment
Worldwide Economics & Globalization
• The Great Recession = Tight Budgets …. Everywhere
• No longer a cloistered industry of a small number of highly-specialized companies,
protected by high capital, technology, and skilled labor barriers to competitive entry
• High profit margins, increased demand, and a pharmaceutical industry focused on cost
reduction and containment have stimulated a surge in the number of new manufacturers
and suppliers globally
• Increase in sourcing from emerging market countries to exploit lower operating costs
and government incentives
• Exploding new technologies
FDA’s 21st Century Initiative – 1997 FDA Modernization Act
• Integrate system (QSIT) and risk management approaches
• Focus on greatest risk to public safety
Workload
Resources
• Encourage industry to adopt modern and innovative technologies
and approaches (science-based policies & standards)
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• Support harmonization efforts within FDA and with other global
agencies
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The U.S. Compliance Environment
High Profile Public Health and Safety Events
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Vioxx Recall – Thoroughness of FDA clinical data review process questioned
Contaminated Pet Foods – melamine contamination (China supply of wheat glutens)
Blood Thinner Heparin – unknown contaminant (China supply of active API)
Toys – lead paint and tiny magnets (Multiple Far East manufacturers)
Peanuts, Spinach, and Cookie Dough – micro. contamination
New Sheriff In Town
On August 6, 2009, new FDA Commissioner Margaret Hamburg issued a major policy address
in Washington, D.C., in which she discussed the Agency’s "use of enforcement to promote
public health." She stated her intent to "pump up enforcement" at FDA. Under her
leadership, the FDA has changed its “enforcement posture to one that is more aggressive
and forward leaning."
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Hire investigators
Streamline warning letter process and implement a warning letter “close-out” step
Work more closely with
itsNAME:
regulatory
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REGION AND/OR partners
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Prioritize follow-up on warning letters and other enforcement
actions
Be prepared to take immediate action in response to public health risks
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The U.S. Compliance Environment
Increased FDA …
 Expectations
 Inspections
 Enforcement
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Concepts of Systems-based Control
Quality System Inspection Technique (QSIT)
Quality must be built into the product.
Testing for Quality is no substitute.
• Quality by design
• Transfer of product and process knowledge - design through
commercial manufacturing
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• Set specifications,
monitor/control processes,
investigate
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discrepancies, and mitigate risks
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6 Systems
2002 Abbreviated
Routine Drug
Inspections
Facility &
Equipment
•2 or more systems
•Quality system mandatory
Materials
Production
Quality
Packaging
& Labeling
Laboratory
Controls
Company “out of control”
if any one system is
found to be out of control
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A Closer Look at the Quality System
Management Responsibilities
 Provide Leadership Expectation and Direction for:
 Product and process quality
 Customer value and satisfaction
 Continuous improvement
 Design and Resource the Organization to Achieve Success
 Quality unit on equal standing with other units
 Structure - decisions of quality and compliance made
independent of conflicting operational priorities
 Qualified personnel
 Design Process for On-going System Reviews
 Suitable
 Adequate and effective
 Correction
and
SUBGROUP
NAME:improvement
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A Closer Look at the Quality System
Resources
 Appropriate Allocation = Robust Quality System
 Design and maintain suitable facilities and equipment
 Acquire materials and services suitable for intended purpose
 Provide for the development and implementation of suitable systems,
processes and controls
 Identify and develop qualified personnel
 Education and experience
 On-going training and education – includes GMP and work duties
 Transfer of knowledge
 Culture of SUBGROUP
improvement,
encouragement, and engagement
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A Closer Look at the Quality System
Manufacturing
 Design, implement, maintain, and document products and processes
 Qualifications and validations
 Procedures and work instructions
 Critical process parameters and specifications
 Change Control
 Examine inputs, materials, and products
 Perform and monitor operations
 Robust in-process controls
 Process capability
 SPC/PAT
 Address non-conformities
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A Closer Look at the Quality System
Product & Process Evaluation
 Trends
 Rejections
 Annual Product Reviews
 Consumer complaints
 Deviations and CAPA
 Change Control
 Internal Audits and Assessments
 External manufacturers and Suppliers
 Risk Management
 Aid in development of critical process parameters and
specifications
 Mitigate risk = proactive approach to Quality
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Preparing for the Inspection
The Federal Food Drug and Cosmetic Act (FDC Act) gives the
FDA the authorization to inspect establishments (at reasonable
times, within reasonable limits and in a reasonable manner)
Why An Inspection ?
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New Facility
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Routine: Every 2 years
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For Cause
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Follow-up to warning letter
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Complaints from customers, industry, etc.
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Recall Effectiveness Check
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Pre-approval Inspection (PAI)
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Preparing for the Inspection
FDA
Office of Regulatory Affairs
Regional & District Offices
District Offices
• Chicago
• Philadelphia
• New Jersey
• Baltimore
• Minneapolis
• Detroit
• Cincinnati
District Offices
• New York
• New England
District Offices
• San Francisco
• Los Angeles
• Seattle
District Offices
• Atlanta
• Florida
• New Orleans
• San Juan
District Offices
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• Dallas
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Denotes Regional Office
• Kansas City
• Denver
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Preparing for the Inspection
Culture
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Quality and Compliance is the way business is done … every single day.
The Inspection is your opportunity to communicate and demonstrate this
commitment.
Know your gaps and your plans to mitigate.
Preparing for an inspection is an every day event.
20 Minute Rule
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You are never more than 20 Minutes away from being fully ready for
inspection.
Good Housekeeping and 5S Techniques
Correct, complete, and organized documents
Procedures Perfected & Systems Challenged
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Inspection Readiness
Inspection Conduct
Internal Audits
Routine Management Reviews
Personnel
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SUBGROUP
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Educated, trained,
andNAME:
engaged
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Subject Matter Experts (SMEs)
Be confident and factual
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Preparing for the Inspection
Investigator Interview Techniques for Gathering Information & Data
FDA Investigators are Trained to “Maximize” Disclosure
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Five Questions
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Silence (after question answered)
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Rapid-fire Questioning
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Restate Answer as Question
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Same Question Several Different Ways
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Same Question of Different Employees
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Questions About Another Area or Job
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Broad, Open-ended Questions
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Hypothetical Questions
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Preparing for the Inspection
What If the Investigator Talks to Me?
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Be friendly, polite, and cooperative
Project confidence (Don’t Brag) – you’re the expert
Show by attitude and actions - inspection is important and
serious
Understand each question and its context before answering
Answer clearly and concisely - make references to site
procedures or official documents
Answer only the question asked – stop talking when the
question is answered
It’s OK to say you don’t know
Don’t get defensive, confrontational, or feel threatened
Don’t answer for someone else or about other areas
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Preparing for the Inspection
What Can Cause Investigator Suspicion ?
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Any attempt to delay or stall
Unavailable records
Refusals to provide records or information
Evasive answers
Suspicious body language – No eye contact or excessive
glancing to others
Indication of record falsification
Changing answers
Data that is “too good”
Significant amounts of training completed on the same date
Sudden halts in production
Obvious worker confusion or erratic behaviors
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Thank You
Questions & Comments ?
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