Integrated Summary of Safety (ISS)
An ISS is pivotal for New Drug Applications (NDAs), supplemental NDAs, (sNDA) and other regulatory submissions. A well planned and executed ISS can accelerate drug approval by minimizing queries from regulatory agencies.
The sponsor’s product in this case was a groundbreaking extended-release solution, for post-operative pain relief. It received FDA approval for specified surgeries and building on its achievements, submitted a sNDA four months later, to broaden use to more surgical procedures. This was approved by FDA less than three months later, encompassing surgeries across an additional range of surgical procedures.
Precision for Medicine, a global contract research organization (CRO) and industry leader in ISS studies, managed the ISS for the product’s initial NDA. Recognizing our pivotal role in the foundational NDA, we were chosen for the sNDA’s ISS, underscoring a lasting partnership between the companies. The project details and challenges are highlighted below.
Project scope
The original ISS (ISS #1) for the NDA consolidated safety data from four clinical trials: two ongoing Phase 3 studies and two Phase 2b studies.
The ISS #2 for the sNDA amalgamated safety data from seven of the product’s trials not encompassed in the original NDA. This included a randomized, blinded Phase 4 study two open-label Phase 3b studies and four open-label Phase 2 trials evaluating the product, either standalone or with a non-opioid MMA regimen.
Timeline and Deliverables
Following the review of the sponsor’s statistical analysis plan in March, we initiated the creation of Mock Tables and Listings. Key deliverables within the compact timeline were as follows:
- 31 May: Dry Run #1
- 15 September: Dry Run #2 (Part 1)
- 19 September: Dry Run #2 (Part 2)
- 19 October & 02 November: Drafts of Final Tables and Listings
- 17 November: Final Tables and Listings
- 02 December: Draft of ISS in CDISC format
- 13 December: Final ISS in CDISC format
From Challenges to Results
One of the most daunting aspects of the ISS data pooling was the completion of two dry runs, especially since two studies were open during the ISS project. The dynamic nature of these open trials meant that timelines were in constant flux. Our team navigated this complexity by maintaining methodical communication with the sponsor and being agile in response to the changing circumstances of the trials. This agility was evident in how we adjusted deadlines and condensed milestones to meet the sponsor’s needs.
Furthermore, despite the short timelines, our programming team demonstrated exceptional flexibility and responsiveness. After both Dry Run #1 and Dry Run #2, they promptly incorporated additionally requested tables. Moreover, they managed the complexities introduced by an unlock and relock of one of the studies, ensuring that they adhered to the sponsor’s ultimate timeline of completing all work by December.
Another hurdle was accessing and aggregating data from various trials. The task of consolidating trial data was intricate due to the multiple CROs involved in the sponsor’s clinical program. Although this is a typical challenge in ISS projects, timely management is crucial to ensure seamless data integration. Recognizing and acknowledging the inherent complexities in handling data from different sources underscores the meticulous planning and execution required in such endeavors.
During the entire process, our client consistently noted the team’s remarkable adaptability, especially when handed new demands. They expressed profound satisfaction with our dedication to punctual delivery, even in the face of changing circumstances, viewing it as a clear demonstration of our unwavering commitment to the project.
The total time elapsed for this project spanned approximately nine months, which well outpaced the industry standard of a year or more.
Key takeaway
The ISS provides an in-depth view of a drug’s safety, vital for regulatory decisions. Our work on this sNDA showcases Precision’s expertise and adaptability, highlighting our focus on being a trusted collaborator.
