By James Hamilton
The issuance of guidance from the Food & Drug Administration is a wake-up call for the biopharma industry and is a strong indication that the agency’s attention might be turning to a particular concern. In October of 2009, the Guidance for Industry, Investigator Responsibilities was published after more than 25 warning letters were issued between Jan. 1, 2009 and Sept. 30, 2009. Aimed at investigators, sponsors, and institutional review boards (IRBs), the guidance clearly spells out the FDA’s expectations for protecting the rights, safety, and welfare of study subjects.
The guidance was a collaborative effort of the FDA’s Office of the Commissioner, the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), and the Center for Devices and Radiological Health (CDRH). The offices’ representatives came together as the Investigator Responsibilities Working Group and were charged with the task of formalizing the FDA’s current thinking and recommendations on the topic.
For anyone who is conducting a clinical investigation of a drug, biological product, or medical device, the guidance spells out their duties and aims to help them meet their responsibilities to protect the human subjects and ensure the integrity of the data. Investigators and sponsors are able to clearly ascertain the FDA’s expectations for their responsibility:
THE TRIGGER POINT: FDA WARNING LETTERS
Whether it was the number of warning letters issued in a short period of time or whether it was the number and scope of violations that were found, the FDA’s Investigator Responsibilities Working Group released the guidance to the industry. A review of the warning letters indicates that the violations were given investigational priority.
INVESTIGATOR RESPONSIBILITIES: GUIDANCE HIGHLIGHTS
Although, in drugs and biologics, the investigator responsibilities are different from the responsibilities of an investigator in medical device clinical trials, the general duties are fundamentally similar. The guidance is clear in stating the overall responsibilities and focus of the investigator and the review board:
The guidance outlines the investigator’s role in supervising the conduct of the clinical investigation and protecting the rights, safety, and welfare of participants in drug and medical device clinical trials. Tasks can be delegated, but the investigator is responsible for providing supervision of the third party to whom they have assigned the task and is accountable for any regulatory violations.
A. Supervision Of The Conduct Of A Clinical Investigation: Guidance Highlights
B. Protecting The Rights, Safety, And Welfare Of Study Subjects: Guidance Highlights
While this specific guidance, as with other FDA guidance documents, does not describe legally enforceable regulations, it does accurately describe the agency’s current position on the topic. The guidance does explain recommendations that the agency deems important and that relate back to the regulations and statutes cited in the document.
NOW IS THE TIME FOR THE INDUSTRY TO FOCUS
It is evident that the FDA considered the types of violations found as major risks to study participants. The investigators’, sponsors’, and IRBs’ violations were found across the drugs, biologics, and medical device trials. The industrywide problems needed to be addressed in light of the possible consequences to the human subjects. Serious injury or even death must always be considered if protocol and regulations are not followed.
The industry must also consider that if violations by investigators, sponsors, and IRBs are found and are not properly addressed, and that while the data generated might be scientifically valid, it may not be acceptable for review by the FDA. If the study cannot be used, it may have to be repeated, costing additional monies, but more importantly, the loss of development time.
The main emphasis of the Guidance For Industry, Investigator Responsibilities was on investigators and sponsors, while the IRBs’ responsibilities were not as clearly defined. It is inferred that the IRBs must have complete information from the investigator or sponsor in order to complete their responsibilities of protecting human subjects. Although warning letters were sent to the IRBs, the guidelines do not address their responsibilities directly, in regards to having a quorum, having enough data, and assuring that the investigators have attained informed consent.
The guidance document also does not fully discuss deficiencies found with nonclinical laboratories. These deficiencies must be addressed by the sponsors utilizing these labs.
The FDA has addressed these issues with the guidance document, and they will be high priority in upcoming inspections this year. It is now up to the industry to update and revise their operational procedures to handle the anticipation of increased FDA scrutiny.
About The Author
A veteran of the FDA’s Compliance Office and of senior level positions in private industry, James Hamilton brings a deep and diverse expertise of industry, regulatory compliance, team building, technical, and leadership resources to his company’s (J.E. Hamilton & Associates) clients.