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Additional 505(b)(2) Benefits: Selective Safety Data Collection

Last month CDER/CBER released a short, final guidance, “Determining the Extent of Safety Data Collection Needed in Late Stage Premarket and Postapproval Clinical Investigations.” (CDER/CBER, 2016)

While brief, the guidance could provide a significant reduction in safety data collection for NDA sponsors. This could be especially true for sponsors using the 505(b)(2) regulatory pathway.

The guidance is “…intended to apply to safety data collection during late-stage premarket and postapproval clinical investigations in all disease settings except rare diseases…” FDA notes that the guidance may differ from recommendations in a specific oncology related guidance (Cancer Drug and Biological Products Clinical Data in Marketing Applications CDER/CBER 2001) and also that the guidance may well conflict with the expectations for safety data collection in other countries.

FDA also points out that: “This guidance is not intended to affect reporting (as opposed to collection) of postmarketing adverse events relevant to an approved drug as required under 21 CFR 314.80 and 600.80 or affect reporting of investigational new drug application (IND) safety information as required under § 312.32 (21 CFR 312.32). Those reporting requirements remain unchanged, and selective safety data collection may only occur in a manner that would permit all regulatory reporting requirements to be fulfilled.” The guidance describes a number of situations in late stage product development and early post-approval where it may be appropriate for the collection of safety data to be reduced in some ongoing trials. This is defined as “Selective Safety Data Collection”. Examples are:

  • No collection of certain safety data
  • Less-frequent collection of certain safety data
  • Collection of certain safety data from only a fraction of the total trial enrollment (e.g., 10 percent of patients in a large trial)

The conditions which may make selective safety data collection appropriate are listed as:

  • The number of patients and their characteristics, the duration of exposure, and the dose range used in previous clinical investigations are sufficient to adequately characterize the safety profile of the drug for common, non-serious adverse events.
  • The occurrence of common, non-serious adverse events has been generally similar across multiple clinical investigations.
  • The drug’s safety profile is established to the extent that it is reasonable to conclude that the occurrence of common, non-serious adverse events in the population to be studied will be similar to rates observed in previously conducted clinical investigations.

The types of clinical investigations that may be considered for selective safety data collection are:

  • Clinical investigations of new indications of approved drugs
  • Postapproval clinical studies and trials conducted to fulfill postmarketing requirements and postmarketing commitments
  • Late-stage premarket and postapproval outcome clinical trials
  • Premarket clinical investigations for some original applications
  • Postapproval clinical investigations in a different patient population or with different doses or other conditions of use

Next, and probably most importantly, what types of safety data are candidates for selective safety data collection?

  • Postapproval clinical investigations in a different patient population or with different doses or other conditions of use
  • Routine laboratory monitoring
  • Information on concomitant medications
  • Patient history and physical exams

The lynchpin to the possibility of selective safety data collection appears to be the existence of a robust safety database for the product in question. That is often the case with a product being developed using the 505(b)(2) regulatory pathway. By definition, an application pursuant to Section 505(b)(2) frequently relies on extensive, pre-existing safety data.

The guidance contains further details and conditions, the most important of which is the requirement to develop a plan and reach agreement on the specifics of a selective safety data collection with the relevant FDA review division or divisions at, e.g., the end-of-phase 2 meeting prior to initiation of a Phase 3 study. Premier Consulting frequently assists in these types of negotiations.