Perspective on GCP Warning Letters DIA GCP and QA SIAC Perspective on GCP Warning Letters Sydney A Gilman, PhD July 27, 2010, 10:00 AM

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Regulatory Compliance Overview Regulatory Compliance IND/(A)NDA Regulations Code of Federal Regulations, Title 21, parts 50, 312 and 314 International Committee on Harmonization Good Clinical Practice (E6)

Overview - Continued Company Compliance Working within a proposed budget Challenge and resolve issues economically with focus towards a potential blockbuster Build a working regulatory strategic plan to ensure success with minimal obstacles Hire experienced staff to avoid pitfalls and delays

Overview - Continued Auditor Compliance Retain experienced auditors who have interacted successfully with companies Depend on auditors who know how FDA thinks and how FDA views sites Rely on auditors who can prepare sites for the 483s Know that auditors can prepare remediation plans to ensure corrective actions become preventative ones

Overview - Continued FDA Compliance Anticipate skilled Inspectors that follow the flow of Clinical documentation at your site Preparation of formal notice of observations (form 483) with clarification and rationale to be adequately addressed by the Sponsor/Applicant Skillfully assessing company responses that adequately and consistently fail to address critical observation(s) which contribute to the preparation of a Warning Letter

What’s on Our Minds in a Clinical Study?

Recent Warning Letter Examples Johnson & Johnson – 09-HFD-45-07-02 Ketek – Aventis – 07-HFD-45-1002 Coast IRB – 09-HFD-46-04-01 ICON CRO - 10-HFD-45-11-04

What Could be Worse? Stopping the Application process/ ban on distribution. Repeating the clinical study Consent decree

Impact of Actions After Issuance of Warning Letter Company Actions Conversion to absolute Regulatory Compliance or digging –in and challenging the system Layoffs, delays in forecasts, investment decline, credibility Company Employee Actions: Compliance to company directives; Option to look for greener pastures Starting over

Impact of Actions After Issuance of Warning Letter - Continued Auditor Actions Maintaining focus to correct and prevent Regulatory Actions Revising the development plan to ensure acceptance/approval Field Actions

What Might Help? Developing a Framework that Moves…

Embracing Change Building Company Credibility Maintaining Auditor Credibility Respecting FDA Credibility

Planning for Now and the Future Don’t be intimidated Document everything Focus on solutions Never try to hide problems

FDA Websites for Additional Information www.fda.gov/cder www.fda.gov/foi/warning.htm www.fda.gov/oc/gcp

Successful Outcomes