Posted: 28 Jun 2020 04:06 PM PDT By Jeffrey K. Shapiro — In recent months, the Food and Drug Administration (FDA) has issued a record number of Emergency Use Authorizations (EUAs) under Section 564 of the Federal, Food, Drug, and Cosmetic Act (FDCA). With a large number also pending, this review pathway is becoming almost common for a wide range of products, predominantly devices, although drugs and biologics are also eligible. In this light, some questions of law and policy already settled regarding 510(k) submissions or premarket approval (PMA) applications may need to be re‑analyzed to determine if the answer is the same in the EUA context. With the COVID emergency likely to continue for some time, these questions will not soon disappear. Today, we tackle the question of whether a company may lawfully advertise a device with an EUA pending (prior to issuance of the EUA)? For more than 40 years, FDA’s policy has been that a device with a 510(k) pending may be advertised (promoted) prior to clearance. In Compliance Policy Guide (CPG) 300.600, FDA considered the question of judging when a device has entered commercial distribution (not interstate commerce). This question was central to qualifying for “preamendment” status by being “on the market” as of May 28, 1976. (The policy was issued in 1978. Obviously, this question is no longer very important.) The answer FDA gave was that a device would be considered in “commercial distribution” if it had been (i) displayed, advertised or offered for sale for a non‑research/investigational use and (ii) the manufacturer had accepted or was prepared to accept an order “that resulted, or would have resulted, in a contract of sale for the device in the United States, generally with delivery to occur immediately or at a promised future date.” So a willingness to contract or entering into actual contractual agreements was deemed an essential element of commercial distribution. In the same policy, FDA stated that, as a derivation from this analysis, devices with a 510(k) pending are not considered to enter commercial distribution if they are advertised (meeting required condition (i)) so long as no orders for sale are solicited or accepted (defeating required condition (ii)). The policy statement itself does not address orders contingent on obtaining a 510(k) clearance, but FDA historically has taken the position that such orders satisfy required condition (ii) and constitute an element of commercial distribution. At first blush, it would seem relatively straightforward to apply this policy to EUAs. An EUA authorizes the introduction of a device into interstate commerce. It is essentially a substitute legal permission in the absence of 510(k) clearance or PMA approval. Therefore, if promoting a device (without taking orders) is permissible in the 510(k) pending context, it is logical to apply the same rule in an EUA pending context. But there is a complication to consider: FDA’s policy only explicitly applies to devices with a 510(k) pending. FDA has never said that it applies to devices with a PMA pending. The EUA pathway, however, applies to all device types. A device with an EUA pending could be 510(k)‑able, but it might also be one that is ordinarily required to obtain PMA approval. The pathway depends upon the device technology and indications for use. If the device is novel, the ultimate classification may not yet be decided. It can be replied that FDA has never said the 510(k) pending policy is not applicable to PMA‑pending devices. In fact, there is not an obvious basis for excluding PMA‑pending devices from policy in CPG 300.600. This policy is based upon a determination that advertising a device is a necessary but not sufficient activity to put it into commercial distribution. That determination would logically apply to PMA‑pending devices as well. Also, the policy in CPG 300.600 was formulated in the context of a question that only implicated 510(k)‑eligible devices. Therefore, FDA did not have occasion in CPG 300.600 to address devices that require PMA approval. Nor has FDA had much occasion since that time to address whether CPG 300.600 extends to PMA‑pending devices. The reason is that a provision in the Investigational Device Exemption (IDE) regulation prohibits all promotion of an investigational device (21 C.F.R. § 812.7). Most devices requiring PMA approval require a supporting IDE study, thereby triggering this prohibition. In short, even if CPG 300.600 were to be extended to PMA‑pending devices, it is largely a moot point, because the IDE regulation flatly forbids promotion of a device while it is investigational. So what does all this mean in the EUA context? It appears that the general rule of thumb should be that a device with an EUA pending, just like a device with a 510(k) pending, may be promoted prior to issuance, provided that purchase orders are not solicited or accepted. A more difficult question is whether § 812.7 prohibits promotion of an EUA‑pending device if the same device was or is under IDE study. Take the strongest case, in which the indications for use in the IDE study (and eventual PMA application) are the same as the EUA indications. (That will not be entirely true in many cases, because an EUA must focus on fighting the pandemic.) There is no doubt that § 812.7 prohibits promotion of the investigational device. Does it apply to the same device with an EUA pending? In my view, the prohibition against promotion of the investigational device does not apply. The question really comes down to whether the IDE regulation applies simultaneously to the investigational and EUA versions of a device. One reason that the IDE regulation should be applied to the former but not the latter is that the two devices are not the same. They may have the same technology and the same or similar indications, but the EUA device will be labeled differently. Among other things, it will be labeled as an “EUA device” and not an “investigational device.” That distinction is meaningful, because the IDE regulation only applies to investigational devices. Things will get tangled up very quickly if the EUA device is subjected to the IDE regulation alongside the investigational device. For instance, the IDE regulation requires that an investigational device be labeled “Caution: Investigational Device. Limited by U.S. Law to Investigational Use” (21 C.F.R. § 812.5). If the IDE regulation were applied to an EUA device, then the EUA device would have to bear this caution as well. That result would be nonsensical. As another example, the IDE regulation requirements apply until the device receives clearance or approval. What happens when the EUA is obtained and the EUA device begins to be advertised and shipped? Does that end the investigational status of the device being studied? Arguably, it would, if the EUA and investigational versions of the device are being treated as one and the same under the IDE regulation. Therefore, it makes sense to acknowledge that the they are not the same and that the IDE regulation does not apply to the EUA version of the device. Finally, as a policy matter, there is no need to fear that the investigational devices will be deployed “off label” for an advertised EUA use. The use of the investigational devices is strictly controlled under the IDE regulation and must follow a written protocol. Therefore, if an EUA device is advertised while the EUA is pending (or after issuance of the EUA), that cannot induce off-label use of the investigational device so long as the sponsors complies with the IDE regulation. In short, under the analysis above, any device with an EUA pending may be advertised prior to issuance of the EUA. Of course, FDA has not weighed in on this issue, so there is some regulatory uncertainty. A company considering whether to advertise an EUA pending device should proceed with caution after careful consideration of all the circumstances. |
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