In order to strengthen the regulatory monitoring of new drug applications (NDAs) and biologics license applications (BLA), US FDA has now issued a standardised format for all major pivotal studies used to support safety and efficacy claims in NDA and BLAs. The regulatory authority expects the comments on the same before April 2018.
 
It also applies when the data is submitted in certain investigational new drug applications (INDs) in advance of a planned NDA and BLA.
 
The Center for Drug Evaluation and Research (CDER) uses the data to plan bio-research monitoring (BIMO) inspections to facilitate the timely identification of sites for inspection. This is to ensure that field investigators from the FDA Office of Regulatory Affairs (ORA), responsible for the inspections, have the information needed to conduct the audits. The data in NDAs and BLAs must be submitted electronically in the format specified in this guidance.
 
To comply with GGP (good guidance practices) highlights that data from NDAs and BLAs are used to facilitate the timely planning and conduct of inspections. These are identification of all entities to which sponsors have transferred regulatory obligations for 164 clinical trial-related activities. Locations of clinical study-related documentation which includes the Applicant/Sponsor/Contract Research Organization records. There is also a need to specify the locations of clinical investigator sites. In addition, case report tabulations of data for each patient in each study that are needed to conduct a proper review of the application.
 
In addition, in an effort to provide a more timely approach to site selection, CDER has developed a risk-based model to select clinical investigator sites for inspection. The model uses an array of risk parameters across clinical investigator sites associated with marketing applications. To facilitate site selection, the model uses a summary-level clinical site dataset that highlights and summarizes the characteristics and outcomes of clinical investigations, both at the study level and at the level of the individual study site. CDER anticipates that the risk-based model will provide for earlier identification of clinical investigator sites for inspection and, therefore, that these inspections will be conducted earlier in the review cycle.
 
Using the risk-based site selection model is advantageous because it facilitates good review management practices. The completion of inspections earlier in the review cycle also provides applicants the opportunity to address significant inspection observations earlier in the process.
 
Study-specific data both clinical study-level information and clinical site data submitted to FDA as part of NDA and BLA packages are also provided. The required electronic format for these submissions is said to accompany Bioresearch Monitoring Technical Conformance Guidance.
 
To verify key study data during inspections, subject-level data line listings by clinical site are provided to ORA investigators. By-site listings for major pivotal studies, including those with different treatment indications, include listings for each clinical site that consented subjects and contain primary data points in addition to derived data. For instance in a pain trial in which subjects recorded pain scores in a diary, the actual diary scores are the primary data points that are used to calculate the derived primary endpoint and any other derived protocol elements, as per the guidance.