3-Hour FDA Audit Preparation Virtual Seminar

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FDA Audit, Preparation, Inspection, ConductDos
and Donts
By Speaker
Charles H. Paul, President C. H. Paul Consulting,
Inc.
2024 C. H. Paul Consulting Inc. All rights
reserved
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Topics

• Inspection basics
• Types of inspections
• Consequences of non-compliance
• Why does the FDA inspect?
• Who does the FDA inspect?
• Good Manufacturing Practices
• Who are the inspectors and how do they work.
• Investigation reference documents

• How to prepare for an FDA inspection
• Quality System Inspection Readiness
• Records and documents
• CAPA and the FDA inspection
• Inspection prep for CAPA
• Data integrity
• The inspection process
• Personal behaviors during the inspection

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FDA Inspections Introduction

• The Food and Drug Administration (FDA) plays a
  pivotal role in safeguarding public health by
  regulating various sectors within the life
  sciences industries.
• Central to its regulatory framework is the
  practice of conducting inspections.
• Inspections serve as a crucial mechanism for
  ensuring compliance with regulatory standards and
  Good Manufacturing Practices (GMP).
• FDA inspections are unannounced and encompass a
  comprehensive review of all aspects of
  production.
• During inspections, FDA investigators
  meticulously evaluate facilities' adherence to
  regulations.
• By scrutinizing critical components, the FDA aims
  to identify any deviations or deficiencies.

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Types of Inspections

• Pre-Approval Inspections (PAIs)
• Post Approval Inspections
• Routine Surveillance Inspections
• For-Cause or Compliance Follow-Up Inspections
• Post-Market Inspections
• Import Inspections

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Difference between Post Approval, Post Market,
and Surveillance Inspections

• Post-Approval FDA Inspection Occurs after a
  product has received regulatory approval or
  clearance
• Post-Market Inspection Conducted after a product
  has been approved or cleared for marketing
  Routine
• Surveillance Inspection Conducted periodically
  or as needed to assess compliance with regulatory
  requirements.

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Inspection Overview

• Initiated without prior notice,
• FDA inspections are conducted by trained
  investigators
• Manufacturing facilities, laboratories, and
  processes are examined.
• These inspections may be routine or conducted in
  response to complaints, adverse events, or
  emerging safety concerns.
• Investigators employ a systematic approach to
  evaluate facilities' adherence to Good
  Manufacturing Practices (GMP) and other
  regulations.
• Reviewing critical documentation such as standard
  operating procedures.
• Investigators assess the physical infrastructure
  of facilities.

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What Is The Difference Between Inspections?

• Pharmaceutical inspections
• Biotechnology inspections
• Medical device inspections
• Combination product inspections

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What is a Warning Letter?

• The issuance of a warning letter represents a
  formal notice from the FDA to the recipient that
  corrective actions are required.
• Warning letters are considered public documents
  and are typically posted on the FDA's website for
  public access.
• The issuance of a warning letter may have
  significant implications for the recipient,
  including reputational damage, increased
  regulatory scrutiny, and potential legal
  liabilities.

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Why Is Sound Inspection Preparation Important?

• Regulatory Compliance standards during
  inspections.
• Risk Mitigation
• Reputation Management
• Product Quality and Safety
• Business Continuity
• Continuous Improvement

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Critical Inspection Mistakes

• Inadequate Documentation
• Poor Record-Keeping Practices
• Non-Compliance with GMPs/QSRs
• Lack of Adequate Training
• Insufficient Risk Management
• Ineffective CAPA Processes
• Poor Communication with FDA Inspectors
• Failure to Implement Lessons Learned

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Best Practices Do the right Things Right

• Preparation
• Have adequately trained staff with relevant
  expertise and accountability.
• Obtain upper management support
• Utilize and value independent regulatory
  compliance and quality assurance teams
• Ensure the commitments made from previous
  inspections have been implemented
• Understand your potential quality data sources so
  information can be quickly and easily sourced as
  required
• Implement and assess an effective quality system
• Ensure there is a designated company Inspection
  Team
• Ensure all proper documentation and records are
  up-to-date
• Maintain effective Management Review and CAPA
  systems.
• Identify true root causes of issues using
  appropriate problem-solving tools.
• Understand when a product, or quality issue is
  significant.
• Have defined metric systems to monitor your
  quality system in order to identify trends, gaps,
  and opportunities

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What is the Regulatory Expectation?

• What is the implied documentation expectation?
• That documents are complete provide all
  necessary information
• Clear easily understood
• Visual
• Flawlessly written
• Accurate - timely
• Provide sufficient information for users to
  exactly perform the task in the case of WIs or
  exhibit the behavior in the case of other
  general/policy SOPs
• Are consistently followed management element
• Controlled and secure
• Easily revised as requirements change
• Training element

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What is CAPA?

• Corrective and Preventive Actions. It is a
  systematic approach used by organizations to
  identify, investigate, and address
  non-conformities, quality issues, and potential
  risks.
• The purpose of CAPA is
• Corrective actions focus on addressing an
  existing issue or non-conformance, aiming to
  eliminate the root cause, mitigate immediate
  risks, and restore compliance.
• Preventive actions are proactive measures
  implemented to prevent the recurrence of similar
  issues or potential problems in the future.

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Preparation Steps

• Understand Regulatory Requirements
• Review and Update CAPA Procedures
• Conduct Internal Audits
• Train Personnel
• Perform Mock Inspections
• Document and Organize CAPA Records
• Conduct CAPA System Review
• Stay Updated on Regulatory Changes
• Maintain a Culture of Compliance

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What is Data Integrity?

• Data integrity refers to the accuracy,
  reliability, and consistency of data
• It is a fundamental aspect of regulatory
  compliance
• Data integrity encompasses various principles,
  practices, and controls

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Elements of Data Integrity

• Accuracy
• Completeness
• Consistency
• Validity
• Timeliness
• Security
• Traceability

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Common Data Integrity Violations

• Failure to maintain complete data derived from
  all laboratory tests conducted to ensure
  compliance with established API specifications
  and standards
• Failure to prevent unauthorized access or changes
  to data, and failure to provide adequate controls
  to prevent omission of data
• Failure to record activities at the time they are
  performed and destruction of original records.
• Failure to train employees on their particular
  operations and related GMP practices.

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Common Data Integrity Errors

• Incomplete Data
• Data Falsification
• Data Entry Errors
• Data Overwriting
• Data Duplication
• Data Loss or Corruption
• Lack of Data Traceability
• Non-Compliant Electronic Records
• Poor Data Management Practices
• Insufficient Training and Oversight

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Documents that Cannot be Reviewed

• Audit reports
• Financial records and documents
• Research data/protocols
• Personnel records
• Management meeting minutes

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Exit Process

• Inspector will present a written FDA form (FDA
  483) if necessary
• Company should take extensive notes and make sure
  everyone understands the issues
• Any response to a 483 observation by the company
  should be brief
• If issue remains unresolved, request that the
  inspector annotate the FDA 483
• Note any corrective actions

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Post Inspection

• Date of inspection
• Inspection team members
• Reasons for response
• Response to each cited deficiency
• Description of preventive and corrective action
• Items still in dispute

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The Psychology Of Behavior And Communications

• Trust and Rapport Building
• Perception and Interpretation
• Active Listening
• Emotional Intelligence
• Assertiveness and Advocacy
• Conflict Resolution
• Cultural Sensitivity and Diversity
• Posture and Nonverbal Communication

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Behaviors That Must Be Exhibited

• Professionalism
• Cooperation
• Transparency
• Documentation
• Attention to Detail
• Compliance Mindset
• Timeliness
• Positive Attitude

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Doing The Right Thing

• Always be professional
• Be dressed properly neat and clean
• Follow all company cleanliness, movement, and
  dressing requirements
• Be courteous and polite at all times
• Correct all errors and miscommunications when
  discovered as soon as possible

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Doing The Right Things

• When providing documents do so in a timely manner
• Have documents available
• Limit the inspectors access
• Always review the requested record before
  providing
• Check that the record is the one asked for
• Send only the record

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Dealing With Difficult Inspections and Inspectors

• Remain Calm and Composed
• Listen Attentively
• Clarify Misunderstandings
• Redirect to Procedure
• Seek Resolution
• Invoke Chain of Command
• Document Interactions
• Follow Up Appropriately

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Questions
2024 C. H. Paul Consulting Inc. All rights
reserved