Understanding the Differences and Effectively Transitioning Between the US Integrated Summaries of Effectiveness and Safety (ISE/ISS) and the CTD Summaries of Clinical Efficacy and Safety (SCE/SCS)

Submitted for publication: September 10, 2009 Accepted for publication: January 5, 2010 The adoption in 2000 of the Common Technical Document (CTD) format for marketing applications notwithstanding, the US regulations requiring an integrated summary of effectiveness (ISE) and an integrated summary of safety (ISS) remain in effect. Many applicants, however, have attempted to use the CTD module 2 clinical summaries, specifically the summary of clinical efficacy (SCE) and the summary of clinical safety (SCS), alone to fulfill the regulatory requirements for an ISE and ISS, arguing that it is redundant to submit a separate ISE and ISS in addition to the SCE and SCS. Consequently, the US FDA has issued numerous guidances and made podium presentations communicating the message that, except in rare circumstances, New Drug Applications should contain the ISE and ISS documents as well as the CTD summaries of clinical efficacy and safety (SCE and SCS). The core difference between the ISE/ISS and their corresponding clinical summaries is in the depth of the analyses and the amount of information needed to support the analyses. While documenting the larger integrated analyses of efficacy and safety in the ISE and ISS, applicants should develop a strategy and process for deriving the SCE and SCS. Ultimately, submitting detailed and fully comprehensive ISE and ISS documents not only enables applicants to comply with regulations, but may also facilitate quick and efficient preparation of the SCE and the SCS. David N. Schwartz, BS Senior Regulatory Strategist and Medical Writer, Michael Umen & Co, Glenside, Pennsylvania