Posted: 16 May 2018 06:55 PM PDT
On May 15th, FDA published in the Federal Register a proposal to amend the product jurisdiction regulation (21 C.F.R. Part 3). This proposal seeks to update, clarify, and streamline the product classification and designation process. However, the proposal fails to address some significant flaws in the product jurisdiction and classification decision process.
FDA’s product classification and jurisdiction decisions tend to create conflict between Agency and product sponsors because the costs associated with securing marketing authorization can differ significantly based on a product’s classification. In general, device jurisdiction is favored by manufacturers.
One of the most significant changes proposed by FDA is to remove the regulatory provision requiring sponsors to seek reconsideration by the Office of Combination Products (“OCP”) (21 C.F.R. § 3.8(c)), before they can appeal a classification/designation decision to the Office of Special Medical Programs (“OSMP”) pursuant to 21 C.F.R. § 10.75. FDA correctly points out that reconsideration by OCP itself rarely (if ever) produces a different result, especially in light of the fact that a sponsor is prohibited from providing any additional data for OCP’s consideration. In its proposal, FDA effectively acknowledges that having already thoroughly reviewed the sponsor’s Request For Designation (“RFD”), nothing the sponsor says in response to OCP will change its mind. While one can question whether this close-minded approach is the right approach, it does reflect reality. The removal of this futile step is a welcome change. It does nothing, though, to address appeals to OSMP, which can languish for many months. Setting a deadline for OSMP’s decision would be a more valuable step in expediting the process than doing away with reconsideration requests.
Moreover, even with a more streamlined appeal process, the RFD process will not be as efficient as it could be if FDA permitted sponsors to provide more extensive data and reasoning in support of their product classification or designation requests in the first instance. FDA’s proposal retains the current fifteen-page limit, including attachments, for RFDs. Some of those fifteen pages are filled by other categories of information required by FDA (such as a detailed description of the product, manufacturing processes, and developmental testing), before a sponsor can get to the business of describing testing to determine the products’ mode(s) of action, comparisons to other products presenting similar issues of safety and effectiveness, etc. The limitation is also inconsistent with FDA’s views regarding the burden of proof for a classification determination. The sponsor bears the burden of proving device status, but is constrained in doing so by the fifteen-page limit. The Agency has previously indicated that a sponsor should prove the absence of chemical action contributing to a therapeutic effect to justify classification as a device. It is a difficult proposition to prove a negative in less than fifteen pages. As OCP has asked for ever more data, the fifteen-page limit has become increasingly anachronistic. FDA should seize the opportunity to drop this unnecessary and arbitrary barrier to providing all the relevant data.
FDA’s proposal also fails to address a more fundamental issue regarding combination products. FDA correctly notes that 21st Century Cures Act says that a drug/biological primary mode of action “cannot be based solely upon the product having any chemical action.” However, the Agency goes on to say that this “serve[s] to codify longstanding Agency regulatory interpretation and practices,” and thus warrants no change to the regulation. In fact, as those who followed the Prevor litigation know, FDA’s actual position has been that a component that exhibits any drug activity that contributes to its therapeutic effect could not be a device.
FDA’s new Part 3 regulation would hold firm – and indeed, further emphasize – that a single “component” of a combination product can have only one “mode of action,” (21 C.F.R. § 3.2) and that mode of action conforms to the component’s statutory definition (i.e. it must be a drug, device, or biologic mode of action). Thus, for example, if the component exhibits relatively minor chemical action contributing to its therapeutic effect, FDA may determine that it cannot meet the statutory device definition, and therefore cannot exhibit a device mode of action. Rather, the entire component is deemed to have a “drug” mode of action, even if its action is overwhelmingly physical. If the purported “drug” component is deemed to contribute most to the therapeutic effect of the combination as a product as a whole, it may then be deemed “primary,” causing the entire combination product to be regulated as a drug by the Center for Drug Evaluation and Research. FDA’s proposal seems to leave this weighted system in place.
Other proposed changes appear relatively non-controversial, such as FDA’s clarification that a request for “designation” of the Agency component with lead jurisdiction over a product, is also a request for “classification” of the product itself as a drug, device, biologic, or combination product. FDA also proposes to remove excessive verbiage in the regulations definition of a “device mode of action,” which currently reiterates the statutory definition of device, but as revised would simply reference that definition.
Interestingly, in describing the benefits of the changes, FDA alludes “to the value of the illnesses and deaths avoided,” through an improved regulation. FDA hypothesizes that the greater clarity will allow companies to eliminate unnecessary paperwork “and potentially allow sponsors and FDA personnel to divert resources,” to more productive areas. This seems to us to be something of a stretch. It is one thing for FDA to say that a clearer product jurisdiction regulation will free up resources for companies, but we would recommend that companies eschew similar speculation in their own marketing applications.
FDA is accepting comments on the new proposed rule until July 16, 2018. This proposal is modestly beneficial, but it represents a last opportunity to make significant improvements to FDA’s framework and process for product classification and designation decisions.
FDA’s product classification and jurisdiction decisions tend to create conflict between Agency and product sponsors because the costs associated with securing marketing authorization can differ significantly based on a product’s classification. In general, device jurisdiction is favored by manufacturers.
One of the most significant changes proposed by FDA is to remove the regulatory provision requiring sponsors to seek reconsideration by the Office of Combination Products (“OCP”) (21 C.F.R. § 3.8(c)), before they can appeal a classification/designation decision to the Office of Special Medical Programs (“OSMP”) pursuant to 21 C.F.R. § 10.75. FDA correctly points out that reconsideration by OCP itself rarely (if ever) produces a different result, especially in light of the fact that a sponsor is prohibited from providing any additional data for OCP’s consideration. In its proposal, FDA effectively acknowledges that having already thoroughly reviewed the sponsor’s Request For Designation (“RFD”), nothing the sponsor says in response to OCP will change its mind. While one can question whether this close-minded approach is the right approach, it does reflect reality. The removal of this futile step is a welcome change. It does nothing, though, to address appeals to OSMP, which can languish for many months. Setting a deadline for OSMP’s decision would be a more valuable step in expediting the process than doing away with reconsideration requests.
Moreover, even with a more streamlined appeal process, the RFD process will not be as efficient as it could be if FDA permitted sponsors to provide more extensive data and reasoning in support of their product classification or designation requests in the first instance. FDA’s proposal retains the current fifteen-page limit, including attachments, for RFDs. Some of those fifteen pages are filled by other categories of information required by FDA (such as a detailed description of the product, manufacturing processes, and developmental testing), before a sponsor can get to the business of describing testing to determine the products’ mode(s) of action, comparisons to other products presenting similar issues of safety and effectiveness, etc. The limitation is also inconsistent with FDA’s views regarding the burden of proof for a classification determination. The sponsor bears the burden of proving device status, but is constrained in doing so by the fifteen-page limit. The Agency has previously indicated that a sponsor should prove the absence of chemical action contributing to a therapeutic effect to justify classification as a device. It is a difficult proposition to prove a negative in less than fifteen pages. As OCP has asked for ever more data, the fifteen-page limit has become increasingly anachronistic. FDA should seize the opportunity to drop this unnecessary and arbitrary barrier to providing all the relevant data.
FDA’s proposal also fails to address a more fundamental issue regarding combination products. FDA correctly notes that 21st Century Cures Act says that a drug/biological primary mode of action “cannot be based solely upon the product having any chemical action.” However, the Agency goes on to say that this “serve[s] to codify longstanding Agency regulatory interpretation and practices,” and thus warrants no change to the regulation. In fact, as those who followed the Prevor litigation know, FDA’s actual position has been that a component that exhibits any drug activity that contributes to its therapeutic effect could not be a device.
FDA’s new Part 3 regulation would hold firm – and indeed, further emphasize – that a single “component” of a combination product can have only one “mode of action,” (21 C.F.R. § 3.2) and that mode of action conforms to the component’s statutory definition (i.e. it must be a drug, device, or biologic mode of action). Thus, for example, if the component exhibits relatively minor chemical action contributing to its therapeutic effect, FDA may determine that it cannot meet the statutory device definition, and therefore cannot exhibit a device mode of action. Rather, the entire component is deemed to have a “drug” mode of action, even if its action is overwhelmingly physical. If the purported “drug” component is deemed to contribute most to the therapeutic effect of the combination as a product as a whole, it may then be deemed “primary,” causing the entire combination product to be regulated as a drug by the Center for Drug Evaluation and Research. FDA’s proposal seems to leave this weighted system in place.
Other proposed changes appear relatively non-controversial, such as FDA’s clarification that a request for “designation” of the Agency component with lead jurisdiction over a product, is also a request for “classification” of the product itself as a drug, device, biologic, or combination product. FDA also proposes to remove excessive verbiage in the regulations definition of a “device mode of action,” which currently reiterates the statutory definition of device, but as revised would simply reference that definition.
Interestingly, in describing the benefits of the changes, FDA alludes “to the value of the illnesses and deaths avoided,” through an improved regulation. FDA hypothesizes that the greater clarity will allow companies to eliminate unnecessary paperwork “and potentially allow sponsors and FDA personnel to divert resources,” to more productive areas. This seems to us to be something of a stretch. It is one thing for FDA to say that a clearer product jurisdiction regulation will free up resources for companies, but we would recommend that companies eschew similar speculation in their own marketing applications.
FDA is accepting comments on the new proposed rule until July 16, 2018. This proposal is modestly beneficial, but it represents a last opportunity to make significant improvements to FDA’s framework and process for product classification and designation decisions.
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