CLINICAL TRIAL MANUFACTURE

This story and thinking behind that statement can be traced back to war crimes. During the Second World War, the Nuremberg Code is the most influential and widely quoted code which originated in the so-called medical research carried out in the concentration camps. Part of the judgment at the “Doctors’ trial” at Nuremberg was the Nuremberg Code. It was intended to ensure that medical research should never again be abused. The first of its ten points states that:

“The voluntary consent of the human subject is absolutely essential.”

This judgment was given in 1947, the same year the World Medical Association (WMA) was formed.

Unfortunately, some doctors thought this Nuremberg Code only applied to Nazis and not to them. Therefore in 1952, the WMA began work on a statement of the ethical principles of medical research. This resulted in the 1964 Declaration of Helsinki, “Ethical principles for medical research involving human subjects”, most recently revised in Edinburgh in 2000.

The ICH Guideline for Good Clinical Practice, ICH/95/135 states that Clinical Trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki.

Both the Declaration and the ICH Guideline on GCP are referenced in the Clinical Trial Directive and its associated guidance and therefore it is recommended that persons involved in Clinical Trial work should have knowledge of both documents.

A key document for Clinical Trials work in the USA is the Belmont Report. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research published this in 1979 and it also covers Ethical Principles and Guidelines for the Protection of Human Subjects of Research.

PROTECTION CLINICAL TRIAL SUBJECTS

Covers the rights of patients, protection of subjects, etc., and the fact that informed consent is required. The interests of patients always prevail over those of science and society. The trial subject shall be provided with a contact point where further information may be obtained.

The Ethics Committee for Pediatric studies must take advice from pediatric experts or include pediatric expertise. It should be noted that EU Regulation 1901/2006 requires all new Marketing Authorization Applications from July 2008 to include results of pediatric clinical trials in the form of a Pediatric Investigation Plan (PIP). Companies can apply for a “Deferral” or “Waiver” if justified.

OPINION OF THE ETHICS COMMITTEE

Covers the function, responsibility, and opinion of an Ethics Committee. Time limits for a written opinion have been defined, generally 60 days. Gives legal underpinning to Ethics Committees.

Covers the establishment of a procedure by which one Ethics Committee opinion is adopted for each member state, i.e., national not local.

Detailed guidance will be drawn up for documentation required for an Ethical Committee opinion.

o   Ethics committees must receive a written explanation for the early termination or at the end of a trial as defined in the protocol.

o   The application form to the Ethics Committee covers the information required to identify the IMP, the formulation and strength, dose, and treatment periods. The same information is included in the Investigators Brochure.

o   Covers the information to be forwarded to the Ethics Committee in the different Member States e.g., Netherlands requires for IMO not manufactured in EU declaration of the QP that the manufacturing site works in compliance with GMP at least equivalent to EU GMP. Greece and Netherlands Ethics Committees require a copy of IMPD.