Source: https://www.federalregister.gov/articles/2011/08/08/2011-19957/effective-date-of-requirement-for-premarket-approval-for-cranial-electrotherapy-stimulator
Timestamp: 2016-06-25 21:15:33
Document Index: 625808057

Matched Legal Cases: ['art 812', 'art 812', '§ 812', '§ 860', '§ 860', '§ 882']

Federal Register | Effective Date of Requirement for Premarket Approval for Cranial Electrotherapy Stimulator
Dates: Submit either electronic or written comments by November 7, 2011. Submit requests for a change in classification by August 23, 2011. FDA intends that, if a final rule based on this proposed rule is issued, anyone who wishes to continue to market the device will need to submit a PMA within 90 days of the effective date of the final rule. Please see section XII of this document for the effective date of any final rule that may publish based on this proposal.
-48070 (9 pages)
Document Number: 2011-19957
Shorter URL: https://federalregister.gov/a/2011-19957 Related Topics
Effective Date of Requirement for Premarket Approval for Cranial Electrotherapy Stimulator; Closed
Table 1—Estimated Upper Bounds of Benefits and Costs
The Federal Food, Drug, and Cosmetic Act (the FD Act), as amended by the Medical Device Amendments of 1976 (the 1976 amendments) (94), the Safe Medical Devices Act of 1990 (SMDA) (101), and the Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L. 105-115), the Medical Device User Fee and Modernization Act of 2002 (MDUFMA) (Pub. L. 107-250), the Medical Devices Technical Corrections Act (Pub. L. 108-214), and the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85), among other amendments, establish a comprehensive system for the regulation of medical devices intended for human use. Section 513 of the FD Act (21 U.S.C. 360c) established three categories (classes) of devices, reflecting the regulatory controls needed to provide reasonable assurance of their safety and effectiveness. The three categories of devices are class I (general controls), class II (special controls), and class III (premarket approval).
A preamendments device that has been classified into class III may be marketed by means of premarket notification procedures (510(k) process) without submission of a PMA) until FDA issues a final regulation under section 515(b) of the FD Act (21 U.S.C. 360e(b)) requiring premarket approval. Section 515(b)(1) of the FD Act establishes the requirement that a preamendments device that FDA has classified into class III is subject to premarket approval. A preamendments class III device may be commercially distributed without an approved PMA or a notice of completion of a PDP until 90 days after FDA issues a final rule requiring premarket approval for the device, or 30 months after final classification of the device under section 513 of the FD Act, whichever is later. Also, a preamendments device subject to the rulemaking procedure under section 515(b) of the FD Act is not required to have an approved investigational device exemption (IDE) (see part 812 (21 CFR part 812)) contemporaneous with its interstate distribution until the date identified by FDA in the final rule requiring the submission of a PMA for the device. At that time, an IDE is required only if a PMA has not been submitted or a PDP completed.
When a proposed rule to require premarket approval for a preamendments device is finalized, section 501(f)(2)(B) of the FD Act (21 U.S.C. 351(f)(2)(B)) requires that a PMA or notice of completion of a PDP for any such device be filed within 90 days of the date of issuance of the final rule or 30 months after the final classification of the device under section 513 of the FD Act, whichever is later. If a PMA or notice of completion of a PDP is not filed by the later of the two dates, commercial distribution of the device is required to cease since the device would be deemed adulterated under section 501(f) of the FD Act.
The device may, however, be distributed for investigational use if the manufacturer, importer, or other sponsor of the device complies with the IDE regulations. If a PMA or notice of completion of a PDP is not filed by the later of the two dates, and the device does not comply with IDE regulations, the device is deemed to be adulterated within the meaning of section 501(f)(1)(A) of the FD Act, and subject to seizure and condemnation under section 304 of the FD Act (21 U.S.C. 334) if its distribution continues. Shipment of devices in interstate commerce will be subject to injunction under section 302 of the FD Act (21 U.S.C. 332), and the individuals responsible for such shipment will be subject to prosecution under section 303 of the FD Act (21 U.S.C. 333). In the past, FDA has requested that manufacturers take action to prevent the further use of devices for which no PMA or PDP has been filed and may determine that such a request is appropriate for the cranial electrotherapy stimulator.
The FD&C Act does not permit an extension of the 90-day period after issuance of a final rule within which an application or a notice is required to be filed. The House Report on the 1976 amendments states that: “[t]he thirty month grace period afforded after classification of a device into class III * * * is sufficient time for manufacturers and importers to develop the data and conduct the investigations necessary to support an application for premarket approval (H. Rept. 94-853, 94th Cong., 2d sess. 42 (1976)).”
If a PMA or notice of completion of a PDP for the cranial electrotherapy stimulator is not filed with FDA within 90 days after the date of issuance of any final rule requiring premarket approval for the device, commercial distribution of the device must cease. The device may be distributed for investigational use only if the requirements of the IDE regulations are met. The requirements for significant risk devices include submitting an IDE application to FDA for its review and approval. An approved IDE is required to be in effect before an investigation of the device may be initiated or continued under § 812.30. FDA, therefore, cautions that IDE applications should be submitted to FDA at least 30 days before the end of the 90-day period after the issuance of the final rule to avoid interrupting investigations.
The Bystritsky et al. study (Ref. 1) was conducted open-label, and on only 12 subjects. The study involved observational baseline versus post-treatment without a control and therefore provided insufficient evidence of safety and effectiveness. The Heffernan study (Ref. 2) concludes that a single CES treatment may have physiologic effects; however, no outcomes of anxiety, depression or insomnia were measured and the study was conducted on only 20 subjects. The Overcash study (Ref. 3) was a retrospective study design and used an anxiety rating scale that was not validated. The Voris study (Ref. 4) analyzed only a subgroup of “psychiatric subjects” which included many types of anxiety disorders as well as non-anxiety psychiatric disorders. The subgroup represents a diagnostically heterogeneous group. The subgroup analysis was not pre-specified and the number of subjects per subgroup was not specified. The Hyun study (Ref. 5) was a randomized controlled trial of 60 subjects. However, the indication under investigation was preoperative anxiety, which may not be indicative of an Axis I anxiety disorder. Moreover, the outcome measure, a 5-point Likert scale rating of anxiety, was not a standardized validated rating instrument. The Winick study (Ref. 6), which was a randomized controlled trial of 33 subjects with anxiety prior to dental procedures and utilized a 7-point Likert scale, suffers from the same limitations as the Hyun study.
A PMA must include valid scientific evidence to demonstrate reasonable assurance of the safety and effectiveness of the device for its intended use (see § 860.7(c)(2)). Valid scientific evidence is “evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. * * * Isolated case reports, random experience, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated opinions are not regarded as valid scientific evidence to show safety or effectiveness. * * *” (21 CFR 860.7(c)(2)).
A request for a change in the classification of these devices is to be in the form of a reclassification petition containing the information required by § 860.123, including new information relevant to the classification of the device.
Under the proposed rule, FDA would require producers in this industry to obtain PMA or establish a PDP before marketing new products. Currently, a CES producer receives clearance to market by submitting a 510(k). Therefore, the rule-induced cost per new product would be the difference between the cost of preparing and submitting a PMA application (which we assume to be approximately the same with PDP as with traditional PMA) and the cost of preparing and submitting a 510(k) application. Blozan and Tucker (Ref. 10) estimate the cost of an average 510(k) at $500; since the mean number of pages for the 510(k) submissions in their sample is 24, the estimated cost per page is $21, or $36 after adjusting for inflation (Ref. 11). FDA records indicate that, recently, the one or two cranial electrotherapy stimulator 510(k) submissions received per year have consisted of several hundred pages each. Assuming an average of 300 pages per submission and a cost per page of $36 yields an average cost of preparing and submitting a 510(k) of $11,000. FDA has estimated an upper bound on the cost of PMA at approximately $1,000,000 (see, for example, 73 FR 7498 at 7501, February 8, 2008); this yields a difference of $989,000 between the costs of PMA and 510(k) preparation. Multiplying this cost difference by the recent average of 1.5 new CES submissions per year yields an annual rule-induced cost equal to $1.48 million. Additionally, producers of CES products that are already on the market would need to submit PMA applications, costing approximately $1 million each. FDA believes that there are approximately 13 such products, so there would be a rule-induced upfront cost of $13 million.
Table 1—Estimated Upper Bounds of Benefits and Costs Back to Top
1Costs borne by consumers (in the form of welfare loss) are not estimated.
Better-Informed Consumer Decisions
Benefits: Ten-Year Total
Industry PMA or PDP Preparation
FDA Review, Net of User Fees
Costs: Ten-Year Total1
The supply-demand diagrams of figure 1 of this document illustrate the changes in the market for CES devices and services that would occur if the additional testing associated with class III pre-market approval were to reveal that CES devices are less safe and effective than consumers currently believe. In Panel A, the benefit of proposed requirement for PMAs or PDPs is represented by the shaded area below the current market supply curve, above the better-informed, post-call for PMA demand curve (Demand
1) and between the old and new quantities purchased (determined by the intersections of the pre- and post-call for PMAs or PDPs demand curves with the current supply curve or the vertical axis). A similar shaded benefit area appears in Panel B, but in that case, there is an offsetting loss (shown as the shaded triangle between the pre- and post-call for PMAs or PDPs supply curves) caused by CES producers passing on some costs related to PMAs and PDPs to consumers and consumers therefore purchasing even fewer CES devices or services than new information indicates they should. The overall benefit of the rule in Panel B is the difference between the areas of the Benefit and Loss triangles. In both panels of Figure 1, total CES spending by consumers, equal to the revenue collected by CES producers and shown as the rectangle LMNO, provides an upper bound on the amount of the shaded rule-induced social benefit. While total spending/revenue always provides an overestimate of the social benefit, the amount of the over-estimation may range from moderate, as in Panel A (the case in which CES products disappear from the market), to extreme, as in Panel B (the case in which there is continued use of at least some CES products).
1. Bystritsky A, L. Kerwin, J. Feusner, “A Pilot Study of Cranial Electrotherapy Stimulation for Generalized Anxiety Disorder,”Journal of Clinical Psychiatry, 69(3): 412-417, 2008.
3. Overcash, Stephen J., “Cranial Electrotherapy Stimulation in Patients Suffering From Acute Anxiety Disorders,”American Journal of Electromedicine, 16(1): 49-51, 1999.
5. Hyun J.K., Y.K. Woon, S.L. Yoon, et al.,“The Effect of Cranial Electrotherapy Stimulation on Preoperative Anxiety and Hemodynamic Responses.”Korean Journal of Anesthesiology, 55: 657-61, 2008.
6. Winick, R.L., “Cranial Electrotherapy Stimulation (CES): A Safe and Effective Low Cost Means of Anxiety Control in a Dental Practice,”General Dentistry, 47(1): 50-55, 1999.
8. Klawansky S., A. Yeung, C. Berkey, et al.,“Meta-analysis of Randomized Controlled Trials of Cranial Electrostimulation,” The Journal of Nervous and Mental Disease, 183(7): 478-485, 1995. 9. Manta: Vital Info on Small Businesses, http://www.manta.com, accessed June 11, 2010.
11. U.S. Department of Commerce, Bureau of Economic Analysis, 2010, National Income and Product Accounts Table 1.1.9., http://www.bea.gov/national/nipaweb/SelectTable.asp, accessed March 25, 2011.
12. Geiger, Dale R. FY 2003 and 2004 Unit Costs for the Process of Medical Device Review, http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/Overview/MedicalDeviceUserFeeandModernizationActMDUFMA/ucm109216.pdf, accessed September 2005.
§ 882.5800 Cranial electrotherapy stimulator.