CLINICAL TRIAL MANUFACTURE
Clinical Trial Manufacture

This story and the thinking behind that statement can be traced back to war crimes. During the Second World War, the Nuremberg Code was 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 would never again be abused. The first of its ten points states that:  

“The voluntary consent of the human subject is 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. The 1964 Declaration of Helsinki, “Ethical principles for medical research involving human subjects,” was the outcome of this. It was last updated in Edinburgh in 2000.  

Clinical trials must follow the ethical principles outlined in the Declaration of Helsinki, according to the ICH Guideline for Good Clinical Practice ICH/95/135. Those working in the clinical trials sector must familiarize themselves with both – the “Declaration of Helsinki “ 

The reference is also established in the guidance and by reference to the EU guideline concerning Good Clinical Practice (ICH GCP). The Belmont Report is an important document for clinical trial work in the United States. This was published in 1979 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and includes guidelines for the protection of human subjects of research as well as ethical principles.  

Protection of ­­­­­­­­­­­­­­­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 Ethics Committee opinion.  

  • Ethics committees must receive a written explanation for the early termination or at the end of a trial as defined in the protocol. 
  • 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 Investigational Brochure. 
  • Covers the information to be forwarded to the Ethics Committee in the different Member States; e.g., the Netherlands requires that the IMO not be manufactured in the EU and that the QP confirms that the manufacturing site works in compliance with GMP at least equivalent to EU GMP. Greece and the Netherlands Ethics Committees require a copy of the IMPD.