Regulatory Update
Ellen Leinfuss
SVP, Life Sciences
Topics Covered Today
• US FDA Update
- 6 Steps Outlined by New FDA Administrator
• European Medicines Agency (EMA) Update
• Medical Device Directives Update
• Trends in Warning Letters
US FDA Update
• Set Post-Inspection Deadlines
- Once issue found, company to have 15 days to respond
- Goal is to issue warning letters on a timely basis and facilitate
prompt corrective action
• Take Responsible Steps to Speed the Warning Letter
Process
- New policy limiting the review of warning letters by the FDA’s
Office of Chief Counsel to “significant” or “novel” legal issues
- Goal to streamline process
• Work More Closely with FDA’s Regulatory Partners
- To develop effective risk controls and enforcement strategies
US FDA Update
• Prioritize Follow-up on Warning Letters and Other Enforcement
Actions
- A Warning Letter or recall will trigger enforcement follow up
- Cases will no longer be allowed to languish or remain open with uncertain
resolution. Firms will get a knock on the door and an inspection
• Be Prepared to Take Immediate Action in Response to Public
Health Risks
- No multiple warning letters. The second warning letter to a firm will trigger
increased scrutiny and follow up actions
• Develop and Implement a Formal Warning Letter “Close-out”
Process
- For firms that have taken the necessary corrective actions
- It could play “an important motivating role” in spurring corrective actions
European Medicines Agency Update
• Changed acronym from EMEA to EMA
• Priority areas for 2010
-
Improve safety monitoring (pharmacovigilance)
Focus on counterfeit medicines legislation and supply chain integrity
Work closely with international partners and activities
Provide more information to patients
• Incorporation of ICH Q9 and Q10
- ICH Q9 (Quality Risk Management) is a systematic process for the
assessment, control and review of risk to the quality of a drug across its life
cycle
- ICH Q10 (Pharmaceutical Quality System) ccis a model for a
pharmaceutical quality system that can be implemented throughout the
different stages of a product lifecycle.
Medical Device Directive Update
• Directive 2007/47/EC comes into effect 21 March 2010
• Key impact: Device Classification
- Software now considered active medical device, whether integral to device
or stand-alone product. Software validation required
- Clarification on borderline products; active implantables; products that
incorporate human tissue, blood or plasma; reusable surgical instruments;
combination products
• Key impact: Clinical Evaluation
- Clinical investigation of devices seen as continuous process to identify,
generate, document and evaluate clinical data
- All devices, including Class I now require clinical data
- All side effects must now be reported
- Clinical investigation requirements now extend to include post-market
surveillance
Medical Device Directive Update
• Key Impact: Technical Knowledge
- Level of technical knowledge, experience, education or training of intended
user is now explicitly a relevant factor in the evaluation of the safety of a
device
- Manufacturers must now provide a summary of characteristics for Class II
and III products
- Goals are safety of device usage
• Key Impact: Increased Transparency
- More information on product information and clinical data will be publicly
available
• Key Impact: European Database
- Clinical data to be collected in common database and shared among
Competent Authorities
Most Frequent FDA 483 Observations
Deficiency
Number of
Observations
Quality Control Unit responsibilities
887
Adherence to production procedures
709
Production procedures (validation)
618
Laboratory controls
553
Written procedures for production
518
Investigations
506
Testing and release
478
Personnel qualification and testing
456
Batch record preparation and review
449
Equipment cleaning and maintenance
397
Compliance v.3.0 – Driving Behavior Change
483 Observations Can Escalate
 Product Seizure
 Legal Injunctions
 Not able to Execute Govt. Contracts
 Failure to Issue Export Certifications
 Holds on Pending New Drug Applications
 Refusals for Export
 Increased Regulatory Intervention
Most Warning Letters Issued because Company Responses
Failed to Adequately Address FDA Concerns
Compliance v.3.0 – Driving Behavior Change
Summary
The Cornerstone for the Quality
Organization is the Site Compliance
Program. Companies should take a
risk-based approach and employ
internal audits and established audit
management practices to remain
“inspection-ready” at all times. If issues
are found, the company should respond
promptly with a detail corrective action
program.