Vaccine Trials in the Context of Ethical and Regulatory Guidelines

Amber Bickford Cox, MPH Johns Hopkins University

Copyright 2012 Johns Hopkins University. All Rights Reserved.

Vaccine Development Process

Good Clinical Practice (GCP)

A standard for the design, conduct, performance, monitoring, auditing, recording, analysis and reporting of clinical trials Assures - Credibility and accuracy of data and reported results - Protection of the rights, integrity, and con dentiality of volunteers

ICH GCP 1.24

Good Laboratory Practice (GLP)

Embodies a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported, and archived

Good Manufacturing Practice (GMP)

The part of quality assurance which ensures that products are consistently produced and controlled to quality standards

Why

Use clinical trials to develop vaccines? Follow regulations?

Purpose of the Clinical Trial

Hallmark of the scienti c method Basic question - Is the response or outcome dierent dependent on the presence or absence of an intervention (i.e., drug, program, vaccine)? In the overall scheme, saves lives, time, and money

Why Were Research Standards Needed?

U.S. (1930s) - Tragedy in formulation of a childrens syrup Japan (1950s) - Registration of all medicinal products for sale Germany (1940s) - Doctors Trial (Nuremberg Trials) Europe (1960s) - Thalidomide tragedy

Protection of the Clinical Trial Volunteer

Entrusted with human lives Nuremberg Code (1947) Declaration of Helsinki (1964) Regulatory and Ethical Guidelines: Good Clinical Practice In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society. (Helsinki A5)

Development of U.S. Regulations

1981: U.S. adopted laws that evolved into the Code of Federal Regulations (CFR) applies to US government funded trials or trials evaluated through the US FDA Speci c titles applicable to clinical trials - 45 CFR 46: Common Rule - 21 CFR 11: Electronic records - 21 CFR 17: Financial disclosure - 21 CFR 50: Informed consent - 21 CFR 56: IRB Regulations - 21 CFR 312: Investigational new drug application - 21 CFR 314: Application for licensure

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Development of International Regulations: ICH GCP

1990: Birth of the International Conference on Harmonisation (ICH) Representatives from the US, European Union and Japan 1996: ICH GCP nalized ICH Section E6: Good Clinical Practice (GCP) - International GCP standard - Origins in the Declaration of Helsinki The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society. (ICH GCP 2.3)

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Development of International Regulations

2003: the European Union (EU) made ICH guidelines into law The World Health Organization (WHO) incorporated GLP, GCP, GMP, and promoted their use globally

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ICH GCP Strengths

Standardized clinical trials Adopted by many countries Accepted by most drug companies Faster global access to products Multi-country acceptance of products

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Limitations

Insucient representation from other regions outside of the EU, Japan, and United States Eectiveness compromised in many countries - No regulatory agencies in place to enforce - Guidelines adopted as is

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Practical Applications

How is GCP practically applied in the context of a vaccine trial?

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GCP Affects all Aspects of Clinical Trials

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