2018 has been notable for many reasons, not the least of which has been the flood of guidance documents FDA has issued related to medical devices. This KKB Alert highlights some of the most notable device guidances issued between January 1 and August 30, 2018, as they relate to (1) the implementation of legislative directives in the 21st Century Cures Act (“21CCA”) and the Food and Drug Administration Reauthorization Act of 2017 (“FDARA”), (2) the strategic priorities of the Center for Devices and Radiological Health (“CDRH”), (3) premarket submissions, and (4) postmarket responsibilities and activities. For ease of review, we will post our summary in four parts across four consecutive days to correspond with each of these topics.
IV. Guidances Related to Postmarket Responsibilities and Activities
On January 16, 2018, FDA announced extended unique device identifier (“UDI”) compliance dates for certain Class I and Unclassified Devices. FDA explained that it was adopting this policy so that it can focus its resources on addressing the implementation challenges associated with higher risk devices.
Postmarketing Safety Reporting for Combination Products (March 2018) (Draft Guidance)
In March 2018, FDA issued a draft guidance explaining postmarketing responsibilities for combination products and concurrently announced a compliance policy providing for delayed enforcement for certain combination product applicants. This draft guidance is intended to clarify aspects of FDA’s final rule on postmarketing safety reporting (“PMSR”) requirements for combination products issued in 2016.
In addition to reiterating the definition for a combination product found in 21 CFR 3.2(e), the guidance clarifies the definitions for “Combination Product Applicant” and “Constituent Part Applicant” found in 21 CFR 4.101 by providing useful examples of applicants who fall into each category. Both Combination Product Applicants and Constituent Part Applicants are subject to the rule, but the requirements applicable to each varies. The draft guidance also includes a detailed, though not comprehensive, analysis of the specific PMSR requirements for Combination Product Applicants, the measures designed to streamline reporting, the information sharing requirements for Constituent Part Applicants, and recordkeeping requirements. The draft guidance additionally contains an appendix entitled “Combination Product Postmarketing Safety Reporting Considerations for Entities that are not ‘Applicants’.” This section reminds manufacturers, packers, and distributors as well as importers and user facilities involved in some aspect of the manufacture or marketing of a combination product that they too have postmarketing safety reporting obligations.
Compliance Policy for Combination Product Postmarketing Safety Reporting (March 2018) (Immediately in Effect Guidance)
Recognizing that Combination Product Applicants may need time to update reporting and recordkeeping systems and procedures to facilitate compliance with the PMSR final rule, FDA announced that it was delaying enforcement of certain requirements under the rule – 21 CFR 4.102(c) and (d), 4.104(b)(1) and (b)(2), and 4.105(b). Specifically, FDA does not intend to enforce “Constituent Part”-based PMSR requirements until:
- July 31, 2019 for Combination Product Applicants using the FDA Adverse Event Reporting System and Electronic Medical Device Reporting System to report Individual Case Safety Reports (“ICSRs”)
- January 31, 2020 for Combination Product Applicants using the Vaccine Adverse Event Reporting System to report ICSRs
Finalizing its January 2018 draft guidance, FDA outlines in its June 2018 final guidance the Agency’s policy for communications from manufacturers, packers, distributers, and their representatives to payors regarding: (1) health care economic information (“HCEI”) for approved drugs and approved or cleared devices and (2) unapproved drugs and devices and unapproved uses of approved or cleared drugs and devices. First, under the scheme set forth in the guidance, FDA would not consider HCEI transmitted to payors to be false or misleading if it relates to an approved indication or use and is based on competent and reliable scientific evidence (as defined by the guidance), so long as that HCEI does not include material differences from the approved labeling. If the HCEI does include material differences from the labeling, it must also contain “a conspicuous and prominent statement describing any material differences between the health care economic information and the labeling approved for the drug.” To note, although the actuating statutory provision (FDCA section 502(a)) expressly applies to drugs, FDA takes the position that the terms of the guidance are, for the most part, applicable to the dissemination of HCEI by device firms to payors as well.
Second, when communicating to payors about unapproved drugs or devices or unapproved uses, the guidance delineates instances when FDA will not object (e.g., product information, information about indications sought, anticipated timelines, pricing information), but also recommends that firms include the following information in any such communication: (1) “[a] clear statement that the product or use is not approved/cleared/licensed, and that the safety or effectiveness of the product or use has not been established”; (2) “[i]nformation related to the stage of product development”; and (3) “a description of the material aspects of study design and methodology and disclosure of material limitations of the study design for those communications that include factual representations of results from studies.” For communications concerning unapproved uses, FDA recommends including a prominent statement disclosing the approved/cleared/licensed indications along with a copy of FDA-required labeling.
Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers (June 2018) (Final Guidance)
Released in tandem with the aforementioned Payor guidance, this guidance differs in that it addresses communications concerning medical product communications without regard to the target audience. Notably, the guidance states that FDA does not intend to rely on communicated information that is not contained in the product’s FDA-required labeling to establish a new intended use where such information is consistent with the FDA-required labeling (“CFL”). The guidance enumerates three factors on which FDA intends to rely (except with regard to devices that are 510(k)-cleared and 510(k) exempt) when making a determination of whether a given communication is CFL. These factors, in abridged form, are as follows:
- How the information in the communication compares to the conditions of use in the FDA-required labeling, looking at indication, patient population, limitations and directions for handling/use, dosing or use regimen/administration.
- Whether the representations/suggestions about the use of the product increase the potential for harm to health relative to the information reflected in the FDA-required labeling.
- Whether the directions for use in the FDA-required labeling enable the product to be safely used under the conditions represented/suggested in the communication.
The document provides examples and explanations of how FDA intends to apply these factors and how they may or may not overlap. With regard to communications regarding 510(k)-cleared devices, FDA recommends that firms look to 21 CFR 807.81(a)(3) and the previously promulgated guidance, Deciding When to Submit a 510(k) for a Change to an Existing Device. For 510(k) exempt devices, the guidance recommends that firms analyze communications in accordance with the limitations of exemptions applicable to their device at 21 CFR 862.9 through 892.9 (or the appropriate classification regulation, if applicable). According to the guidance, communications that do not trigger the need for a 510(k) are considered by FDA to be CFL, whereas communications that that do trigger the need for a new 510(k) are not CFL. Finally, when making communications that are CFL, any data, studies, or analyses relied on should be “scientifically appropriate and statistically sound.”
We will continue to monitor new device-related guidances issued by FDA during the remainder of the year.
 The authors gratefully acknowledge the contributions to this Alert by Dan Logan, KKB associate, and Celeste Wheeler, former KKB associate.
 See 81 Fed. Reg. 92603 (Dec. 20, 2016).
 This Final Guidance was issued on October 25, 2017 and replaces the 1997 Final Guidance with the same name. FDA issued at the same time a final guidance focused on software changes entitled, “Deciding When to Submit a 510(k) for a Software Change to an Existing Device.” See https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM514737.pdf.