Sponsors ansvar ved outsourcing af en klinisk afprøvning. Dansk Selskab for GCP. Medlemsmøde 23 November 2010

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1 Sponsors ansvar ved outsourcing af en klinisk afprøvning Dansk Selskab for GCP Medlemsmøde 23 November 2010 Agenda Introduktion v/jane Arce, Formand for Dansk Selskab for GCP Lovgivning Hvorfor kontrol samt hvilken trend ses Sponsors erfaring v/irene Rasmussen, LEO Pharma Hvordan håndterer LEO Phama oversight af deres CRO er? Hvilke tiltag er der gjort og hvilke erfaringer har man indhentet sig? CRO s erfaring v/ Susanne Fugmann, Norma Er der over de seneste år sket en ændring i sponsors kontrol af det arbejde, der outsources til et CRO? Hvad gør et CRO for at imødegå kravene? Myndighedernes erfaring v/lene Bjerring Bork, LMS Hvilke observationer har myndighederne gjort ved inspektioner af Sponsor/CRO? Hvad kigger myndighederne efter, når en klinisk afprøvning er outsourcet i forhold til en ikke-outsourcet klinisk afprøvning? 1

2 Regulatory Framework FDA 21 CFR (a) A sponsor may transfer responsibility for any or all of the obligations set forth in this part to a CRO. Any such transfer shall be described in writing. If not all obligations are transferred, the writing is required to describe each of the obligations being assumed by the CRO. If all obligations are transferred, a general statement that all obligations have been transferred is acceptable. Any obligations not covered by the written description shall be deemed not to have been transferred. (b) A CRO that assumes any obligations of a sponsor shall comply with the specific regulations in this chapter applicable to this obligation and shall be subject of the same regulatory action as a sponsor for the failure to comply with any obligation assumed under these regulations. Thus, all references to sponsor in this part apply to a CRO to the extent that it assumes one or more obligations of the sponsor. Regulatory framework EU Commission Directive 2005/28/EC Chapter 2: Sponsor A sponsor may delegate any or all trial-related functions to an individual, a company, an institution or an organisation. However, in such cases, the sponsor shall remain responsible for ensuring that the conduct of the trials and the final data generated by those trials comply with Directive 2001/20/EC as well as this Directive 2

3 Regulatory Framework ICH ICH Guidelines for GCP Chapter 5: SPONSOR The sponsor may transfer any or all of the sponsor s trial related duties and functions to a CRO, but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. The CRO should implement Quality Assurance and Quality Control (5.2.1) Any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing (5.2.2) Any trial related duties and functions not specifically transferred to a CRO are retained by the sponsor (5.2.3) All references to a sponsor in this guideline also apply to a CRO to the extent that a CRO has assumed the trial related duties and functions of a sponsor (5.2.4) Why performing Oversight? In a true quality system, sponsors are responsible for setting and maintaining requirements that must be met by suppliers, contractors, and consultants for services that go into their regulatory authority regulated medical product development If the sponsor outsources regulatory authority regulated activities, then the sponsor ultimately bears responsibility for the performance of their outsourcing partners All activities outsourced must be overseen by the sponsor, but in a manner that does not duplicate the expensive effort that has been outsourced 3

4 Trend. Increasing focus from authorities FDA are increasing their enforcement efforts Sponsors and CROs can expect more scrutiny of their outsourcing relationships, particularly when sponsors engages a CRO to complete the full range of services needed Number of FDA inspections increased with 20% in 6 years Warning letters increased with 50% over 3 years Source The CenterWatch Monthly, August 2010 Trend.CROs to be held responsible FDA warnings letters SPONSOR August April 2010 CRO 27 November 2009 Observations Study was not conducted according to GCP and not properly monitored Failure to identify that drug infusions were given at the identical time to multiple subjects Failure to recognize or report the overdosing of 13 subjects Failure to ensure proper monitoring of the clinical investigations [21 CFR Message: and (a)] For the first time in 2009 a CRO received a warning letter for clinical trial responsibilities delegated from a Sponsor 4

5 Trend. Warnings for lack of Oversight -A US sponsor company has received an FDA warning letter following the discovery of serious violations at a study site -The sponsor was cited for the selection of an inappropriate investigator and inadequate study oversight Message: Sponsor was aware of the violations but did not take any actions when given the information Oversight expectations It is not enough for sponsors to hand off monitoring to CROs and then forget about it The sponsor has to stay actively involved and continue to ensure that the CRO is effectively monitoring the trial sites and If a CRO identifies any problems, the CRO needs to escalate those right away to the sponsor and the sponsor has then to take immediately actions Source The CenterWatch Monthly, August