1. ICH GCP, the MHRA and PATHOLOGY PATHOLOGY QUALITY ASSURANCE Rob Wosley MRQA rob.wosley@phnt.swest.nhs.uk 01752 763008 SEPTEMBER 2009

2. PURPOSE The purpose of this presentation is to provide a top level awareness of Good Clinical Practice, why it exists, and how the MHRA will apply it to NHS Pathology departments. This should prove useful when facing MHRA Inspectors….. The purpose of this presentation is to provide a top level awareness of Good Clinical Practice, why it exists, and how the MHRA will apply it to NHS Pathology departments. This should prove useful when facing MHRA Inspectors…..

3. WHAT IS GOOD CLINICAL PRACTICE? A set of guidelines followed in Europe, Japan and the United States which harmonise the conduct of clinical trials. A set of guidelines followed in Europe, Japan and the United States which harmonise the conduct of clinical trials. The basis of the EU Clinical Trials Directive, which resulted in the Statutory Instrument 2004:1031 and its subsequent amendments. The basis of the EU Clinical Trials Directive, which resulted in the Statutory Instrument 2004:1031 and its subsequent amendments. Common Sense! Common Sense!

4. WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI Ethical Principles for Medical Research Involving Human Subjects Ethical Principles for Medical Research Involving Human Subjects Adopted in 1964, amended six times since. Adopted in 1964, amended six times since. 1996 Amendment referenced in British Law (SI 2004:1031) 1996 Amendment referenced in British Law (SI 2004:1031) 2008 Amendment now published 2008 Amendment now published

5. DECLARATION OF HELSINKI It is the duty of the physician in medical research to protect the life, health, privacy and dignity of the human subject. It is the duty of the physician in medical research to protect the life, health, privacy and dignity of the human subject. Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research. Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research. The subjects must be volunteers and informed participants in the research project. The subjects must be volunteers and informed participants in the research project.

6. GOOD CLINICAL PRACTICE HISTORY US tragedy in 1930s with children’s syrup led to Product Authorisation System under the Food and Drug Administration (FDA). US tragedy in 1930s with children’s syrup led to Product Authorisation System under the Food and Drug Administration (FDA). Japanese government required all medicines to be registered for sale from the 1950s. Japanese government required all medicines to be registered for sale from the 1950s. Thalidomide tragedy in Europe in the 1960s led to an increase in regulation and law for medicines. Thalidomide tragedy in Europe in the 1960s led to an increase in regulation and law for medicines. ICH formed in 1990 after pioneering legal framework within the European Community. ICH formed in 1990 after pioneering legal framework within the European Community.

7. FLAWED RESEARCH THALIDOMIDE THALIDOMIDE NAZI WAR CRIMES IN DEATH CAMPS NAZI WAR CRIMES IN DEATH CAMPS TUSKEGEE (ALABAMA) SYPHILIS STUDY 1932 – 1972 TUSKEGEE (ALABAMA) SYPHILIS STUDY 1932 – 1972

8. FLAWED RESEARCH 2 NY JEWISH CHRONIC DISEASES HOSPITAL INJECTION OF CANCER CELLS INTO TRANSPLANT PATIENTS 1963 NY JEWISH CHRONIC DISEASES HOSPITAL INJECTION OF CANCER CELLS INTO TRANSPLANT PATIENTS 1963 NY WILLOWBROOK SCHOOL HEPATITIS INJECTIONS IN ‘RETARDED’ CHILDREN 1964 NY WILLOWBROOK SCHOOL HEPATITIS INJECTIONS IN ‘RETARDED’ CHILDREN 1964

9. GOOD CLINICAL PRACTICE PRINCIPLES 1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirements. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

10. GOOD CLINICAL PRACTICE PRINCIPLES 2 The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society. The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial. Clinical trials should be scientifically sound, and described in a clear, detailed protocol. A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.

11. GOOD CLINICAL PRACTICE PRINCIPLES 3 The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective tasks. Freely given informed consent should be obtained from every subject prior to clinical trial participation. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.

12. GOOD CLINICAL PRACTICE PRINCIPLES 4 The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol. Systems with procedures that assure the quality of every aspect of the trial should be implemented.

13. GCP AND THE LAW European Medicines Agency (EMEA) published the ICH GCP Guidelines in 1997. European Medicines Agency (EMEA) published the ICH GCP Guidelines in 1997. European Parliament published the European Directive on Good Clinical Practice in the conduct of clinical trials on medicinal products for human use in 2001 (2001/20/EC). This was revised in 2005. (2005/28/EC). European Parliament published the European Directive on Good Clinical Practice in the conduct of clinical trials on medicinal products for human use in 2001 (2001/20/EC). This was revised in 2005. (2005/28/EC). UK law implemented in 2004; SI 2004:1031 The Medicines for Human Use (Clinical Trials) Regulations. This was amended twice in 2006 and again in 2008 and 2009. UK law implemented in 2004; SI 2004:1031 The Medicines for Human Use (Clinical Trials) Regulations. This was amended twice in 2006 and again in 2008 and 2009.

14. GCP AND YOU Pathology laboratories handle samples from Clinical Trials on a regular basis. It’s important that you know and understand that you have a duty of care to the patients involved in that study as much as any other patient’s samples. Pathology laboratories handle samples from Clinical Trials on a regular basis. It’s important that you know and understand that you have a duty of care to the patients involved in that study as much as any other patient’s samples. That duty of care is laid down in GCP, and you are delegated authority to process those samples by the Principal Investigator (Doctor) managing the study on behalf of your Trust. That duty of care is laid down in GCP, and you are delegated authority to process those samples by the Principal Investigator (Doctor) managing the study on behalf of your Trust. You need to be aware of the Principles of GCP and the Core Principles of the Declaration of Helsinki. You need to be aware of the Principles of GCP and the Core Principles of the Declaration of Helsinki.

15. How the MHRA might use GCP GOOD CLINICAL PRACTICE Guidance on the maintenance of regulatory compliance in laboratories that perform the analysis or evaluation of clinical trial samples. Organisation & Personnel Organisation & Personnel Serious Breaches Serious Breaches Contracts & Agreements Contracts & Agreements Study Conduct Study Conduct Additional Work & Sub-Contracting Additional Work & Sub-Contracting Patient Safety and Informed Consent Patient Safety and Informed Consent

16. How the MHRA might use GCP 2 Sample Receipt and Chain of Custody Sample Receipt and Chain of Custody Method Validation Method Validation Repeat Analysis Repeat Analysis Data Recording & Reporting Data Recording & Reporting Facilities and Equipment Maintenance Facilities and Equipment Maintenance Computerised Systems Computerised Systems QA & QC, SOPs & Policies QA & QC, SOPs & Policies (Un)Blinding (Un)Blinding Retention of Data Retention of Data Preparation and Distribution of Clinical Kits Preparation and Distribution of Clinical Kits

17. HELPFUL STUFF http://www.mhra.gov.uk/index.htm - the MHRA’s homepage. Sign up for email alerts on a host of GCP and Pathology related issues. http://www.mhra.gov.uk/index.htm - the MHRA’s homepage. Sign up for email alerts on a host of GCP and Pathology related issues. http://www.mhra.gov.uk/index.htm http://www.ich.org/ - the ICH homepage, where GCP was born. http://www.ich.org/ - the ICH homepage, where GCP was born. http://www.ich.org/ http://www.wma.net/e/ethicsunit/helsinki.htm - the Declaration of Helsinki site, keeping you abreast of developments. http://www.wma.net/e/ethicsunit/helsinki.htm - the Declaration of Helsinki site, keeping you abreast of developments. http://www.wma.net/e/ethicsunit/helsinki.htm www.canarybooks.com – publishers of GCP, Helsinki and Regulatory handbooks. www.canarybooks.com – publishers of GCP, Helsinki and Regulatory handbooks. www.canarybooks.com