After clinical trials have been completed demonstrating safety and effectiveness, the study sponsor (or drug manufacturer) will submit a New Drug Application (NDA) to the FDA for a license to market the drug for a specified indication. NDAs contain all of the information about all of the studies, including preclinical testing, all clinical trials, dosing information, manufacturing details and proposed labeling for the new medicine. Most academic drug development efforts do not progress to this stage.
An IND is a request for FDA authorization to administer an investigational drug or biological product to humans. The application must show results of preclinical experiments, if applicable; the chemical structure of the compound; how it is thought to work in the body; any side effects found in animal studies; and how the compound is manufactured (chemistry, manufacturing and controls section). The IND must also include a detailed clinical trial plan, including how, where and by whom the studies will be conducted.
Preclinical testing begins after a potential drug has been identified in the lab. Preclinical testing involves lab and animal studies that evaluate the drug’s toxic and pharmacologic effects. Preclinical studies are also subject to the FDA regulations known as Good Laboratory Practices (GLP) for Nonclinical Laboratory Studies, 21 CFR 58. The GLP regulations specify minimum standards in such areas as personnel, facilities, equipment and operations.
FDA’s Center for Drug Evaluation and Research (CDER) is responsible for regulating manufacturing, testing and importation of pharmaceutical drugs in the US. This includes new drug approvals, abbreviated new drug approvals (generics), over-the-counter drugs, animal drugs and biologics. A drug is defined as:
Data and Safety Monitoring Boards (DSMBs) and Data and Safety Monitoring Committees (DSMCs) carry out important aspects of clinical trial monitoring. A clinical trial Data Monitoring Committee is a group of individuals with pertinent expertise that reviews on a regular basis accumulating data from one or more ongoing clinical trials. The DSMB advises the investigator regarding the continuing safety of trial subjects and those yet to be recruited to the trial, as well as the continuing validity and scientific merit of the trial.
Monitoring is the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCPs), and the applicable regulatory requirement(s). Typically, academic sites are familiar with monitors assigned by a sponsor or a contract research organization (CRO). However, GCP requires that investigator-initiated trials enrolling human subjects also provide a monitoring plan to assure that the data collected throughout the study are accurate.
The CTSI BERD (Biostatistics, Epidemiology and Research Design) Core consultations pool Penn State resources across campuses to offer training in biostatistical and epidemiological methodologies and assistance to investigators in study design, data management and analysis. BERD provides for free up to four hours of consultation per project for the development of clinical and translational science external grant proposals and consultations for institute-funded pilot projects.
College or unit administrators assist investigators submit applications and develop their non-technical sections, including the budget.
The CTSI provides provides proposal development services. Learn more and access the consultation form on the CTSI website.
This activity is required for industry-sponsored clinical studies and investigator-initiated clinical studies with funding from industry and may be needed for other research activities. In many instances a sponsor sends a Confidential Disclosure Agreement (CDA) prior to sharing a protocol or confidential documents. PIs should contact the Office of Sponsored Programs for more information and assistance.
Because it may be necessary for a researcher to obtain access to and review PHI in order to prepare a research study, HIPAA rules allow such a review upon compliance with specified criteria. An application for review of PHI preparatory to research must be submitted to the IRB for review and approval.