Principles of Good Clinical Practices

Principles of Good Clinical Practices – Role of the FDA

In this post we will discuss about the basic principles of Good Clinical Practices and how they apply to clinical trials.

Before discussing the Good Clinical Practice regulations and guidelines, here is a brief look at the Food and Drug Administration (FDA).

Today, in the United States, the FDA is responsible for ensuring that, among others, new drugs are safe and effective. The FDA is primarily one of the country’s oldest and largest consumer protection agencies. It is a federal agency within the Department of Health and Human Services (DHHS). The FDA is headed by the Commissioner of the FDA who is appointed by the President of the United States.

FDA uses regulations and product standards as the “yardsticks” that define specific requirements manufacturers must follow to assure product safety and to provide accurate information to health professionals and consumers. Among the laws enforced by the FDA is the Federal Food, Drug, and Cosmetic Act (FDC Act). In the next few paragraphs you will see how the GCP regulations and guidelines, and the role of the FDA evolved to their present status.

Let us start with the question “What is Good Clinical Practice, or GCP?”

GCP refers to regulations and guidelines established to ensure that clinical research is consistently performed to high ethical and scientific standards. The question that logically follows is

“What events have prompted the development of GCP guidelines?”

Principles of Good Clinical Practices – Historical Developments of GCP

A case in point is the sulfanilamide tragedy in 1937. This drug was promoted to the public as an all-purpose anti-infective. To make the drug more palatable to consumers, the manufacturer converted the drug to an elixir containing diethylene glycol, which is a component of anti freeze. Use of the elixir resulted in the deaths of 107 people, including many children.

Despite the manufacturer’s failure to list diethylene glycol as an ingredient in the elixir, they were only indicted for misbranding, as the FDA lacked authority to press more significant charges.

In response to the sulfanilamide tragedy, in 1938 the Federal Food, Drug and Cosmetic Act was passed. For the first time, manufacturers were required to test for drug safety and to present safety testing results to the FDA prior to marketing a drug.This act also prompted implementation of the New Drug Application, or NDA, process, which defined a regulatory role for the US government in the approval of drugs prior to marketing.

Despite the expanding role of the government in overseeing the manufacture, testing and approval of drugs, public health tragedies continued to surface. In 1941, nearly 300 deaths occurred as a result of a drug manufacturing error in which sulfathiazole was accidentally tainted with Phenobarbital.

This prompted the beginning of Good Manufacturing Practice, or GMP, guidelines. In 1961, birth defects occurred in thousands of babies across 20 countries as a result of expectant mothers’ use of a medication called thalidomide, which was promoted to treat morning sickness. The FDA’s requirement for safety testing delayed release of the drug in the US and several other countries, thus preventing further cases of birth defects as a result of thalidomide treatment.

Principles of Good Clinical Practices – The Declaration of Helsinki

The basic principles stressed in The Declaration of Helsinki include justice, respect for persons, beneficence-that is, to maximize benefits and to minimize harm-and non-maleficence-that is, to do no harm. The Declaration of Helsinki was the first worldwide GCP document to call for a written protocol and the need for its independent approval prior to the conduct of clinical research. Present day global standards or guidelines on clinical research are based on The Declaration of Helsinki.

International Conference on Harmonisation

We will start by addressing the question “What is the International Conference on Harmonization, or ICH?

It is a joint initiative involving both regulators and industry as equal partners in the scientific and technical discussions of the testing procedures required to ensure and assess the safety, quality and efficacy of medicines.

The European Community (now the European Union) pioneered in the 1980s, a move towards the harmonization of regulatory requirements for the development of pharmaceuticals. At the same time there were discussions between Europe, Japan and the US on possibilities for harmonization. At the WHO Conference of Drug Regulatory Authorities (ICDRA) in Paris, in 1989, specific plans for action began to materialize. Soon afterwards, the authorities approached the International Federation of Pharmaceutical Manufacturers Associations (IFPMA) to discuss a joint regulatory-industry initiative on international harmonization.

The birth of ICH took place at a meeting in April 1990, hosted by the European Federation of Pharmaceutical Industries and Associations (EFPIA) in Brussels. Representatives of the regulatory agencies and industry associations of Europe, Japan and the USA met, primarily, to plan an International Conference but the meeting also discussed the wider implications and terms of reference of ICH.

Thirteen Key Principles of ICH GCP

The current ICH GCP guidelines address thirteen key principles, including

  1. Research on human subjects should be consistent with the ethical principles of The Declaration of Helsinki, good clinical practice standards, and regulatory requirements;
  2. The benefit or benefits of conducting clinical research should justify the potential risk or risks to human subjects;
  3. The rights, safety, and well-being of individuals participating in clinical research should prevail over interests of science and the greater good of society:
  4. Available background data on the study drug should support the design of the proposed clinical trial;
  5. The study design should be scientifically sound, and described in a clear, detailed written protocol;
  6. Investigational sites must maintain compliance with the Institutional Review Board- or Independent Ethics Committee-approved protocol;
  7. Subjects participating in a clinical study should be under a qualified physician’s care;
  8. Clinical study staff are to be adequately trained for their tasks;
  9. Informed consent must be given freely prior to a study subject’s participation in a clinical trial;
  10. Data are to be correctly recorded for accurate reporting, interpretation, and verification of study results;
  11. The confidentiality of trial subject records should be protected;
  12. Manufacturing standards for the investigational product, or study drug, should comply with Good Manufacturing Practice and used as described in the protocol; and
  13. Quality systems should be implemented for every aspect of the trial.

This completes our discussion on Principles of Good Clinical Practices. We hope this gives you insight into the Principles of Good Clinical Practices.

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