Clinical Trials Directive

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Clinical Trials Directive

• Directive 2001/20/EC
• The Medicines for Human Use (Clinical Trials)
  Regulations (2003 ?)

VIain Fenton-May QC WALES
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• The Directive (SI)
• Implications
• Guidance
• Next steps

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Purpose of the Directive

• To protect human rights
• Requires legal consent
• Pharmacovigilance
• Simplify and harmonise admin
• Assure results of the trials
• Introduce GMP into IMP production
• Introduce GCP

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UK Statutory Instrument

• Ethics Committees
• Authorisation for CTs and Ethics Committee
  opinion
• Good Clinical Practice
• Pharmacovigilance
• Manufacture and Importation
• Labelling
• Enforcement, Fees

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Implications

• Ethics Committee(s)
• Sponsors
• QPs
• Commercial and Non commercial trials

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Guidance
EU database EUDRACT
MHRA
Ethics
Sponsor
Prin Investigator
MREC
Investigators
Pharmacy
LREC
Production
IMP
QP
Patient
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Roles

• Adviser to Ethics Comm (Clinical Pharmacist)
• Organiser and keeper (CT coordinator)
• Manufacturer (Production Pharmacist)
• QP (Quality Control Pharmacist)

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QP

• Each batch to be certified as
• Compliant with GMP
• Compliant with CTA
• Traceability for recalls etc

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QP accountability

• Legal and ethical responsibility to MHRA, patient
  and employer
• Personally and professionally liable for
  decisions
• Assessed by inspection by MHRA
• Must only act within level of competence

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QP duties

• Responsible for ALL quality aspects of
  manufacture
• Must be aware of any deviations
• Can delegate tasks but not responsibility

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Annex 13

• 4. The QP should in particular be responsible for
  ensuring that there are systems in place that
  meet the requirements of this annex and should
  therefore have a broad knowledge of
  pharmaceutical development and clinical trial
  processes

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Annex 13

• Any person engaged in activities as the QP at
  the time when the Directive is applied shall
  be authorised to continue those activities in the
  Member State concerned

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Annex 13

• Product Specification File Art 9
• The information should form the basis for
  assessment of the suitability for certification
  and release of a particular batch by the QP and
  should therefore be assessable to him/her
• NB this included comparators

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Annex 13

• The QP is responsible for
• In the case of the IMP manufactured in a third
  country that each batch is in accordance with
• GMP
• The product spec file
• The information notified to the Reg Authorities

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CTA application

• Guidance notes published April 2003
• Submission to the CA
• Submission to EC
• EUDRACT Database
• Eudravigilance
• ADR reporting

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Core information for CTA

• EUDRACT number
• Covering letter
• Application form
• Protocol with all amendments
• Investigators brochure

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Core information cont..

• IMP dossier
• Simplified IPMD
• SmPC (for products with MAs)
• List of CAs to whom applications have been made

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Core info UK specifics

• Summary of protocol
• Outline of all active with same IMP
• Copy of manufactures MA or QP declaration of GMP
  compliance
• Copy of importers authorisation
• Copy of C of A where impurities are not justified
  by specifications
• Viral safety studies

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Core info UK specifics

• Samples of labels
• TSE certificates
• Declaration of of GMP status of active biological
  substances

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Next steps

• Licences
• Training
• DDX applications