End-of-phase 2 meeting

For most drugs, one of the most important meetings with the FDA in the new drug development process is the end of Phase 2 meeting. This was initially directed at drugs of specific interest... 

Summary report/NDA - case report forms FDA contact—end of phase 2 meeting Phase 3 studies Summary report/NDA First draft of package insert Pre-NDA review Monitor summaries Review investigator summaries... 

FDA contact—end of phase 2 meeting Special statistical analysis... 

The primary focus of end-of-phase 2 meetings is to determine whether it is safe to begin phase 3 testing. This is also the time to plan protocols for phase 3 human studies and to discuss and identify any additional information that may be required to support the submission of an NDA. It is also intended to establish an agreement between the agency and the sponsor of the overall plan for phase 3 and the objectives and design of particular studies. These meetings avoid unnecessary expenditures of time and money because data requirements have been clarified. 

At the end of Phase 2, the FDA and sponsors try to come to an agreement on how the large-scale studies in Phase 3 should be done. How often the FDA meets with a sponsor varies, but this is one of two most common meeting points prior to submission of a new drug application. The other most common time is pre-NDA—right before a new drug application is submitted. 

The case-by-case approach that is needed for the effective preclinical development of biopharmaceuticals requires close collaboration and agreement between the sponsor and the regulatory agency at all stages of development. In the United States, such collaboration and scientific advice is often achieved through interaction with the FDA at pre-IND, end of phase 2, or pre-NDA meetings with the Agency. 

The BRT will review clinical data in relation to the scope of the proposed clinical studies (1) preliminary studies (Phases I and II marketed product versus not-marketed products or products marketed with safety concerns), (2) expanded studies (Phase III), end-of-phase II meeting. The BRT will provide feedback and guidance at the pre-NDA meeting, then review the data in the NDA in relationship to safety, efficacy, quality, and therapeutic consistency. 

In the past, only selected NDA candidate drug sponsors were encouraged to request an End-of-Phase 2 conference. Today, all holders of an IND for new chemical entities are entitled to this important conference. Depending on the workload of the division responsible for review of the IND, however, requests for a meeting for an end-of-phase 2 conference may be easier to arrange if the conference requested is for one of the following ... 

Type B meetings are those that usually occur for a pre-IND, an End of Phase 1 (EOP1), an End of Phase 2 (EOP2), a Pre Phase 3, or a Pre-NDA or BLA. All of these meetings will be honored by the FDA. These meetings are usually scheduled 60 days from the time the agency received the written request. If the sponsor requests a date beyond 60 days, the meeting should occur no later than 14 days after the date requested. 

End of Phase 2 Conference-Summary. When a firm has reached the end of phase 2, it should contact the appropriate division at the FDA to arrange for a conference. All clinical data should be summarized, tabulated, and statistically analyzed, as described. These data, together with any additional preclinical and manufacturing and controls data, and plans and protocols for phase 3 should be submitted at least 1 month in advance of the scheduled meeting. A copy containing only clinical data, as a rule, plus the proposed protocols for phase 3, should be provided for the FDA statistician. The submission also should include any specific questions the firm wishes to discuss. 

End of Phase I meeting After completing Phase 1, sponsor meets with FDA to discuss results of the trial and agree on plan for Phase 2 studies. 

In each hatched two-phase region, the lever rule (Section 7.3.2) can be used as usual to determine the relative amounts of the two phases at opposite ends of the tie-line. However, the quantity of precipitated solid a and/or /3 is usually of less interest than the composition of the melt, so the principal focus is on the two liquidus lines that meet at the eutectic point. These liquidus lines are also called solubility curves or freezing-point depression curves, in that they map both the saturation-solubility limits (horizontal variations) as well as the freezing-point depression of the liquid (vertical variations). 

Linkers are molecules which keep the intermediates in solid-phase synthesis bound to the support. Linkers should enable the easy attachment of the starting material to the support, be stable under a broad variety of reaction conditions, and yet enable selective cleavage at the end of a synthesis without damage to the product. Several types of linker have been developed, which meet these conflicting requirements to different extents [1]. Newer developments include linkers containing fluorine to facilitate the monitoring of solid-phase chemistry by NMR (see Section 1.3.5), and enantio-merically pure linkers that enable the synthesis on solid phase of enantiomerically enriched products [2],... 

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