The current QSR expressly addresses risk management activities primarily in the context of the risk analysis associated with design validation. See 21 CFR § 820.30(g).Although Part 820 contemplates that manufacturers should address risk in various processes, such as corrective and preventive actions (CAPAs), through the incorporation of ISO 13485, FDA clarifies its intent to expressly address risk management and risk-based decision-making throughout the lifecycle of device manufacturing.

As an example, this would apply to a manufacturer of a new medical air purifier that has not been approved or cleared by the FDA and that is effective in filtering out dust particles and bacteria, and the manufacturer would like to modify the filter mesh size to filter out viruses, including the SARS-CoV-2 virus. This could also apply to a manufacturer of a new sterilizer that is effective in killing the SARS-CoV-2 virus but has not otherwise been approved or cleared by the FDA.To ensure devices do not create an “undue risk,” the FDA has outlined specific performance and labeling requirements that must be met. Importantly, manufacturers must document any changes made to the device in the manufacturer’s device master record and change control records “and make this information available to FDA, if requested, consistent with 21 CFR 820.30 and 21 CFR 820.180.” Manufacturers of all Class II, Class III, and specific Class I devices listed under 21 CFR 820.30(a)(2) must establish and maintain procedures to control the design of the device ensuring that specified design requirements are met. Under 21 CFR 820.30, manufacturers must establish and maintain a design history file containing or referencing the records that demonstrate that the design was developed in accordance with the approved design plan and the requirements under that section.

FDA noted that its response was inadequate because the manufacturer failed to commit to perform appropriate validation for each of its products and to fully remediate its systems for investigations of deviations. 2020 warning letter citations for medical device manufactures include: Failure to establish adequate design controls (21 CFR 820.30(a)): Medical device manufacturer was cited for failing to establish and maintain procedures to control the design of the device in order to ensure that design requirements are met. The warning letter explains that the manufacturer had distributed a medical device since September of 2018, prior to establishing a Design History File (DHF) that complies with FDA’s design control requirements. Failure to establish and maintain procedures for validating the device design that includes risk analysis, where appropriate (21 CFR 820.30(g)): FDA noted that the manufacturer’s 483 response was inadequate, in part, because while the manufacturer provide a CAPA to address the deficiency and represented that it was in the process of implementing the corrective actions, the manufacturer failed to provide confirmation that the proposed corrective actions were appropriate and effective.

on Scientific asserted counterclaims, including for rescission of the Agreement based on Channel’s alleged breaches of representations and warranties in the Agreement. The action was tried in April 2019, with post-trial argument and supplemental briefing occurring thereafter.Relevant Merger Agreement Provisions Channel asserted that Boston Scientific breached Section 6.3(b) of the Agreement, which required Boston Scientific to “take all further action that is necessary or desirable to carry out the purposes of this Agreement” and to “use its commercially reasonable efforts to take all such action and refrain from taking any actions which would be reasonably expected to frustrate the essential purposes of the transactions contemplated by the Agreement.”12Boston Scientific asserted that Channel breached three categories of representations in the Agreement, which representations related to (i) Channel’s compliance with healthcare laws, including a provision entitled “Design Controls,” at 21 CFR § 820.30, which required Channel to “establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met,” (ii) the adequacy of the quality assurance procedures followed in connection with the clinical trials and (iii) the accuracy of Channel’s submissions to the FDA with respect to Cerene. Each such representation contained an express materiality qualifier.13 Boston Scientific alleged that each of these representations were breached as of the date of the Agreement as a result of Shankar’s misconduct.Based on these alleged inaccuracies in Channel’s representations, Boston Scientific asserted that it had the right to terminate the Agreement pursuant to Section 8.1(f), which permitted Boston Scientific to terminate “at any time prior to the Effective Time” if “any representation or warranty of [Channel] contained in this Agreement shall be inaccurate or shall have been breached as of the Agreement Date . . . such that the condition

and blood components in 21 CFR Part 606.The QMSR uses the definition of “top management” set forth in ISO 9000 rather than the term “management with executive responsibility” or its definition from the QSR. FDA clarified, however, that this change in terminology does not change FDA’s expectation that manufacturers, led by individuals with executive responsibilities, embrace a culture of quality as a key component in ensuring the manufacture of safe and effective medical devices that otherwise comply with the FDCA.3DifferencesThe QMSR places more emphasis than the QSR on risk management throughout the life cycle of medical devices to ensure their safety and effectiveness. The QMSR, unlike the QSR, includes a specific requirement that device manufacturers “shall document one or more processes for risk management in product realization” and shall maintain records of risk management.4 Currently, risk management in the QSR is captured primarily in requirements concerning design controls in 21 CFR § 820.30. According to FDA, “the more explicit integration of risk management throughout ISO 13485 and incorporated into the QMSR will help best meet the needs of patients and users and facilitate access to quality devices along with the progress of science and technology.”5The QMSR will no longer use certain terms that are in the QSR. These terms include “design history file,” “device manufacturing record” and “device history record.” Moreover, the terms “safety and performance” in ISO 13485 will be used in lieu of, and be deemed to have the same meaning as, “safety and effectiveness” in the FDCA. Although it is debatable whether “performance” has the same meaning as “effectiveness” – and FDA acknowledged in the preamble to the QMSR that these terms are not interchangeable – FDA was satisfied that the provisions of the QMSR collectively are intended to assure that finished devices will be manufactured to meet the statutory requirement for safety and effectiveness under the FDCA.6 Thus, “safet

he American National Standards Institute (ANSI) Incorporated by Reference (IBR) Portal.Additionally, FDA stated it would not immediately update the QMSR when future revisions of ISO 13485 are published. Instead, the Agency will review the ISO revision and consider whether to revise the QMSR accordingly using the rulemaking process, as appropriate.d. Section 820.10 (Requirements for a Quality Management System)This section of the QMSR final rule incorporates the Quality System requirements of ISO 13485, while ensuring that additional FDA medical device-related regulatory requirements are maintained, including:Unique Device Identification, 21 C.F.R. Part 830;Medical Device Tracking, 21 C.F.R. Part 821;Medical Device Reporting, 21 CFR Part 803; andCorrections and Removals, 21 CFR Part 806.This section clarifies that the scope of devices that are subject to the design and development requirements of ISO 13485 (clause 7.3), which replaces the QSR’s design control requirements (as set forth 21 C.F.R. § 820.30), includes Class II and Class III devices, as well as certain, limited class I devices. This scope is unchanged from the scope outlined in the QSR.ISO 13485 (clause 7.5.9.2) provides traceability requirements for implantable devices. This QMSR section specifies that those traceability requirements extend to devices that support or sustain life. Finally, this section states that failure to comply with the requirements of the new QMSR found in the amended 21 C.F.R. Part 820 (and, by extension, ISO 13485) renders a device adulterated.e. Section 820.35 (Control of Records)In the proposed rule, this section stated that in “addition to the requirements of Clause 4.2.5 in ISO 13485 . . . , Control of Records, the manufacturer must obtain the signature for each individual who approved or re-approved the record, and the date of such approval, on that record and include the below information in certain records.” This statement resulted in some anxiety on the part of several commenters who argue

) and meets the regulatory requirements under CLIA to perform high-complexity testing” 88 FR at 68009.Id. at 68009-68012.Id.Id.Id.Id.Id. at 68009.Id.Id.Id.Id. at 68009-68010.Id.Id.Id.With the proposed amendment, the regulation would read: “These products are devices as defined in section 201(h) of the [FDCA], and may also be biological products subject to section 351 of the Public Health Service Act, including when the manufacturer of these products is a laboratory” 88 FR at 68031 (emphasis added).In other words, in this stage, requirements that would begin to apply include: (1) establishment registration and device listing requirements (21 USC § 360 and 21 CFR Part 807); (2) labeling requirements (21 USC § 352 and 21 CFR Parts 801 and 809); and (3) investigational use requirements (21 USC § 360j(g) and 21 CFR Part 812).For LDTs designed, manufactured and used in the same laboratory that is CLIA-certified for high-complexity testing, the QS requirements are limited to design controls (21 CFR § 820.30), purchasing controls (21 CFR § 820.50), acceptance activities (21 CFR § 820.80 and 820.86), corrective and preventive actions (21 CFR § 820.100) and records requirements (21 CFR Part 820, Subpart M).LDTs may continue to be offered after this date while a PMA is under review by FDA.LDTs may continue to be offered after this date while a 510(k) or De Novo is under review by FDA.See 21 CFR Part 812.See, e.g., 21 CFR § 807.3(d) and § 820.3(o).See 21 CFR § 820.3(o) and § 820.3(w).See a statement from Jeffrey Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, and Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, on the agency’s warning to consumers about genetic tests that claim to predict patients’ responses to specific medications.See the FDA’s April 4, 2019, warning letter related to the Inova Genomics Laboratory.See FDA’s April 2018 final guidance, Use of Public Human Genetic Variant Databases to Support Clinical Validity

ere are no waivers or reductions for small establishments, businesses, or groups for this fee. The annual registration user fee for fiscal years 2023 and 2024 is $7,653.Best practices for advertising and promotion should be implemented; however, many medical device principles of advertising and promotion will become applicable in later stages of the phaseout policy once FDA clearance or approval has been obtained.Stage 3: Three years later New regulatory requirements enforced: Quality system (QS) requirementsFDA’s rationale: FDA believes that compliance with QS requirements is essential to ensure the quality and validity of IVDs offered as LDTs, and that three years is “adequate time for laboratories to come into compliance with QS requirements.”Key considerations: For IVDs offered as LDTs for which all manufacturing activities occur within a single high-complexity CLIA-certified laboratory, FDA would expect compliance with solely a subset of QS requirements – Design controls (21 C.F.R. § 820.30)Purchasing controls, including supplier controls (21 C.F.R. § 820.50)Acceptance activities (receiving, in-process, and finished device acceptance (21 C.F.R. §§ 820.80 & 820.86)Corrective and preventative actions (21 C.F.R. § 820.100)Records requirements (21 C.F.R. Part 820, Subpart M)For all other IVDs offered as LDTs that are subject to the phaseout policy, FDA would expect compliance with all QS requirements three years after finalizing the phaseout policy.FDA has proposed to amend its device QS regulation (21 C.F.R. Part 820) to more closely align with international consensus standards (87 Fed. Reg. 10119 (February 23, 2022)). FDA indicates that it intends to finalize the amendment to the QS regulation expeditiously such that the amended QS requirements would be in effect before the beginning of Stage 3 of the proposed phaseout policy.Stage 4: 3.5 years later (but not before October 1, 2027)New regulatory requirements enforced: For high-risk IVDs offered as LDTs – Premarket Appro

f steps to help support a grandfathering approach, including ideas to help address FDA’s concerns about grandfathered test performance.FDA also requests information on how it might leverage the New York State CLEP and Veterans Administration programs, respectively. In particular, FDA requests comments on whether it should continue to exercise enforcement discretion with respect to tests that successfully participate in those programs.FDA also requests comments on whether it should continue enforcement discretion for tests offered at AMCs.Tests offered in a single CLIA-certified laboratory would be subject to a subset of the usual “device” quality systems requirements. For tests where all manufacturing activities occur within a single CLIA-certified clinical laboratory and for which distribution does not occur outside that single laboratory, FDA expects compliance with some, but not all, quality systems requirements. Specifically, labs must comply with the following: Design controls (21 CFR 820.30)Purchasing controls (21 CFR 820.50)Acceptance activities (21 CFR 820.80 and 820.86)Corrective and preventive actions (820.100)Records requirements (21 CFR 820, Subpart M).For all other IVDs offered as LDTs, FDA proposes to end enforcement discretion for all quality systems requirements three years after finalization.The proposed rule is open for comment until December 2, 2023.AnalysisIf finalized as proposed, the rule would impose significant new regulatory requirements on clinical laboratories offering LDTs.The agency’s proposal also raises several critical (and unanswered) questions:Does the agency have legal authority to regulate LDTs? Notwithstanding the agency’s contention, this issue has not been conclusively addressed by the courts. Any final rule will almost certainly be subject to legal challenge(s) by interested laboratory stakeholders.How will FDA address the practical issues associated with regulating LDTs as medical devices? Unlike an IVD test kit, an LDT is not a physica

ld be a standalone section within the marketing submission, should include the following:A range of FDA-authorized specifications for the characteristics and performance of the planned modifications (i.e., description of modifications)Associated verification and validation testing and acceptance criteria to ensure the device remains safe and effective when modified in accordance with the PCCP based on identified test methods, data and statistical analyses (i.e., the modification protocol)Documentation of the assessment of the benefits and risks of implementing a proposed PCCP (i.e., the impact assessment).FDA notes that the PCCP should be described in sufficient detail and in the public-facing portions of the submission (e.g., 510(k) summary, de novo decision summary, premarket approval summary of safety and effectiveness or approval order) in order to support transparency. The PCCP should also comply with the quality system regulation at 21 CFR Part 820, particularly design controls (21 CFR § 820.30), nonconforming products (21 CFR § 820.90), and corrective and preventive action (21 CFR § 820.100).As discussed below, the draft guidance includes additional information on what applicants should include within their description of modifications, modification protocol and impact assessment sections.Description of ModificationsFDA expects a PCCP’s description of modification to identify the modifications to the ML-DSF that the manufacturer intends to implement. FDA recommends that a PCCP include only a limited number of modifications that are specific, can be verified and validated, and are described in sufficient detail to permit understanding of such modifications. This recommendation is consistent with the NIST AI Risk Management Framework’s emphasis on explainable and interpretable AI. The description of modifications should also clearly state the following:If the manufacturer intends to implement the proposed modification automatically (i.e., the modification will be implemented