"GENERAL INVESTIGATIONAL PLAN" CAN PROVIDE FOCUS FOR A PRE-IND MEETING

"GENERAL INVESTIGATIONAL PLAN" CAN PROVIDE FOCUS FOR A PRE-IND MEETING with FDA, Division of Biologic Investigational New Drugs Director Bruce Burlington, MD, maintained at a Drug Information Association (DIA) meeting in Rockville, Md. Sept. 10. Discussing the experience of the Biologics Office with the investigational plans, Burlington noted that "at the pre-IND meeting or at a meeting soon after the IND was filed, we have gone through in some substantial detail what FDA's thoughts and expectations are with the companies' thoughts and expectations, and planned together for the sort of drug development which we hope to expedite -- the overall clinical trials and getting them to the approvable state." Such review of the general investigational plans, Burlington said, "has been extremely useful." Burlington noted, however, that the experience of Biologics in interacting with companies on the plans has been mixed. "Some companies have seemed very reticent about discussing their plans with us," the FDAer said. "But I don't think that companies are particularly well served by not developing plans in conjunction with FDA, and I would hope that most of the time when they do develop plans with us that we will be able to help them get along the road that they are going more quickly." The Biologics official cautioned that "the mere possession of a plan" is not in itself a sufficient basis for seeking a pre-IND meeting with the agency. "You have to have a product in hand that you are ready to study," Burlington noted. "We run into a fair number of people who have a glimmer of an idea and want to discuss it with us and we resist those sorts of meetings." FDA divisions have shown differing interest in pursuing the pre-IND meetings. "At biologics we think pre-IND meetings are generally useful," Burlington explained; "in particular, when we are dealing with a company that is not experienced in drug development, where the product is something that is a substantial departure from previously studied products, that it is extremely useful to have such a meeting to go over the science of the product and to go over who the individuals are and what sort of regulatory scheme will be applied to the product." On the other hand, Burlington noted, "other [FDA] divisions that deal with pioneer drug manufacturers who have large staffs experienced in drug development and regulation don't feel that [the pre-IND meetings] are as valuable." FDAers emphasized the importance of the "end-of-Phase II" meetings as described in the new IND regs. Office of Biologics Research and Review Deputy Director James Bilstad, MD suggested that, as the implications of the end-of-Phase II meeting "can be fairly great" and "may effect the force of the Phase III investigations and the evidence that is going to be gathered for NDA approval," minutes of the meeting should be taken by both FDA and the sponsor and exchanged to avoid misunderstandings. "We strongly endorse that kind of cross-communication," Bilstad said. Since the end-of-Phase II and pre-NDA meetings involve time and resources on the part of both the agency and the drug sponsor, Bilstad noted, "it is important to consider how they can be conducted most efficiently." The timing of the end-of-Phase II meeting is particularly important, Bilstad said, and should be initiated by the drug sponsor. "It should be held at a time when there is sufficient information available about the clinical studies to be able to make some intelligent judgments about the Phase III plan." However, Bilstad advised, "scheduling of the meeting shouldn't delay a proceeding to Phase III," and therefore, "it may be necessary to hold the meeting before all of the Phase II studies are completed." For this reason, Bilstad noted, "some people have referred to this, perhaps more appropriately, as a pre-Phase III meeting." Bilstad maintained that ordinarily the FDA divisions will be able to schedule the meeting in six to eight weeks. He advised that background material should be submitted to the agency at least one month in advance of the meeting. "The sponsor should submit not only the summaries of Phase I and II investigations and the plan for the Phase III studies," the FDAer stated, "but also the tentative drug labeling as well."