February 22, 2023
Real-Time or Accelerated Aging?
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EU MDR Clinical Evaluation Report (CER) Frequency
February 21, 2023
EU MDR Clinical Evaluation Report (CER) Frequency
The EU MDR doesn’t prescribe the frequency at which CERs are to be updated. Modeling this, the MDCG (2020-13) has left manufacturers the liberty to, “…Identify when updates to the clinical evaluation report shall be assessed during the surveillance and post certification monitoring activities and which frequency should be considered…”. Consequently, the frequency of updates is generally up to the manufacturer’s discretion. Yet that must be appropriate risk-based discretion.
While MEDDEV 2.7/1 revision 4 gives specific guidelines (specifically, update at least annually if the device carries significant risks or is not yet well established; or every 2 to 5 years if the device is not expected to carry significant risks and is well established), we need to remain sensitive to the fact that MEDDEV 2.7/1 isn’t generally intended for the EU MDR. Nonetheless, for now, the Notified Bodies and other Union authorities are still often generally tolerant of that MEDDEV in my experience as along as its prescription is reasonable for the subject device. Otherwise, the manufacturer is required to tailor the frequencies to its particular device scenario.
Recall Classification: EU MDR / IVDR
February 20, 2023
Recall Classification: EU MDR / IVDR
Neither the EU MDR nor IVDR contain a formal risk-classification scheme for recalls. So in general, other jurisdictions’ (e.g., U.S. FDA, Health Canada) defined recall classification tiers are not a clear paradigm of the EU MDR/IVDR (yet the future finalization of the EUDAMED database might change this). The EU MDR/IVDR are however much like the U.S. FDA and Health Canada in that a risk-based approach is still certainly required for planning and implementing a recall (e.g., to assure proper recall depth and effectiveness); for resolving the issues that caused the recall; for writing the FSN or other advisory notice, etc.
Also of note is that there are various qualitative categorizations for EU MDR/IVDR remedial actions. Specifically, the EU MDR/IVDR provide for actions such as, but not necessarily limited to, Non-FSCA Withdrawal, Non-FSCA Recall, FSCA Withdrawal, and FSCA Recall. Be sure your EU MDR/IVDR procedures clearly address these various jurisdictional permutations. This is important not only for assuring proper EU remedial action categorization, but also, for example, regarding the U.S. FDA’s comparatively differing definitions/thresholds of the same or similar terms (e.g., “Recall” and “Market Withdrawal”), which aren’t necessarily the same things as the EU’s definitions of “Recall”, “Withdrawal”, “FSCA”, etc.
Finally, when a Union Competent Authority (CA) becomes involved in an FSCA, the CA will assess the risk of the situation. Some CA’s might have their own operational risk-classification scheme for grading the FSCA. But in alignment with what I mentioned before, such classification (if any) isn’t legislatively prescribed by the EU MDR or IVDR.
Recall Classification: U.S. FDA
February 20, 2023
Recall Classification: U.S. FDA
For the U.S. FDA, a risk-based approach is required for categorizing a recall; for planning and implementing a recall (e.g., to assure proper recall depth and effectiveness); for resolving the issues that caused the recall; for writing the recall notification, etc., etc.
First, a proposed remedial action needs to be properly categorized using the following terms, as applicable:
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Correction: Repair, modification, adjustment, relabeling, destruction, or inspection (including patient monitoring) of a product without its physical removal to some other location.
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Removal: The physical removal of a device from its point of use to another location for correction.
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Recall: A manufacturer’s or distributor’s removal or correction of a product marketed in the U.S. that the Food and Drug Administration considers to be in violation of the laws it administers and against which the agency would initiate legal action, e.g., seizure. Recall does not include a market withdrawal or a stock recovery.
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Market Withdrawal: A manufacturer’s or distributor’s removal or correction of a distributed product which involves a minor violation that would not be subject to legal action by the Food and Drug Administration or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs, etc.
Again, the associated risk will have a considerable impact on which of these categories apply. Remember to characterize the risk in terms of the frequency and severity of harm associated with the issue.
For any recall queued from the aforesaid qualitative categorizations, the recall needs to be classified as either class I, II, or III:
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Class I: A situation in which there is a reasonable probability that the use of, or exposure to, a violative product will cause serious adverse health consequences or death.
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Class II: A situation in which use of, or exposure to, a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.
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Class III: A situation in which use of, or exposure to, a violative product is not likely to cause adverse health consequences.
Some will say that a firm’s classification of a recall is only voluntary since FDA will ultimately assign the recall classification for U.S. recalls (i.e., generally class I and II recalls) reported to the FDA. Nonetheless, I recommend that the recalling firm always suggest a classification to FDA, and to do so based on the outcome of the firm’s internal Health Hazard Assessment (HHA) or Health Risk Assessment (HRA) performed to mimic FDA’s own internal operating procedures. Moreover, even if a firm decides not to report a recall to the FDA (i.e., class III recalls only), then the firm is still basically obligated to, at least internally, apply and record its class III recall classification and corresponding rationale. So, in these terms, U.S. recall classification is not really voluntary for the recalling firm.
Ultimately, be sure your U.S. FDA recall procedures clearly and properly address these various aspects of recall categorization. If you need assistance with this, then ComplianceAcuity would be glad to help. This is important, not only for assuring proper remedial action categorization, but also, for example, to avoid confusion regarding other jurisdictions’ similar/identical terms (e.g., EU MDR/IVDR “Recall” and ” Withdrawal”), which nonetheless don’t have the same meanings as the U.S.’s definitions of “Recall”, “Market Withdrawal”, etc.
Marketing for Off-Label Use
February 20, 2023
Marketing for Off-Label Use
In a nutshell, ALL of a manufacturer’s advertising/promotional statements must be within the boundaries established by the FDA-cleared/approved intended use and indications. Consequently, if a manufacturer makes claims that the subject device has been tested for, or can be used for, features not directly within the boundaries established by the FDA-cleared/approved intended use and indications, then that generally misbrands the device by way of marketing for uncleared/unapproved indications.
The FDA doesn’t generally prohibit clinicians from using their clinical judgment/expertise in the use of medical devices outside of the manufacturer’s labeled intended use / indications. Clinicians are allowed to decide whether such “off-label” use is in their patient’s best interest.
Transferring Foreign 510(k) “Ownership” to Domestic Subsidiary
February 20, 2023
Transferring Foreign 510(k) “Ownership” to Domestic Subsidiary
In a nutshell, if a foreign sponsor/owner of a U.S. FDA 510(k) clearance wants to transfer/relinquish ownership and control over to its U.S. subsidiary (or any other party), then such a business/regulatory model can have regulatory merit and, if properly configured/managed, can generally work to meet FDA’s establishment registration and device listing requirements of 21 CFR Part 807. Indeed, FDA’s establishment registration and device listing obligations are primarily driven by the operations in which a firm is engaged, and only secondarily (if at all, depending on the circumstances) by who obtained the 510(k) clearance.
It is true that FDA’s standard approach is to reflexively view the 510(k) owner as the owner/controller of the device specifications (i.e., as the Part 807 “manufacturer” or “specification developer”), and thus to view that firm as being ultimately responsible for assuring proper 21 CFR Part 820 GMP compliance and ongoing Part 807 compliance for the subject device. Yet transfer of “ownership” / control of a 510(k) (and ultimate accountability for GMP) is a well-established business/regulatory scenario that FDA accepts as long as the proper notifications/adjustments are made to assure FDA knows who is the current/latest Part 807 “manufacturer”, “specification developer”, and “contract manufacturer”.
For example, a U.S. firm could, via the aforesaid FDA notifications/adjustments, take on the Part 807 role of being, as applicable, either the responsible “manufacturer” or “specification developer”, and can have the subject device fabricated outside the U.S. by a Part 807 “contract manufacturer” [such as the firm that originally sponsored/obtained the 510(k) clearance]. Moreover, if the finished devices in that scenario are imported into the U.S. by the U.S. firm and distributed from that same U.S. site into U.S. interstate commerce (whether directly to end users or to distributors), then the FDA told me that there would be no requirement for registration of an “initial importer” like there was previously when the foreign site was initially getting its products into the U.S. through a third-party importer/distributor.
Ultimately in such a scenario, don’t overlook the fact that the U.S. subsidiary site becomes the actual responsible “manufacturer” or “specification developer” who is held ultimately accountable for finished device design, fabrication, ongoing quality, etc., etc. That means, for example, that FDA’s first (and typically only) direct focus for GMP inspections will be that U.S. subsidiary. It also means that the U.S. site is ultimately responsible for critical regulatory events like recalls, 510(k) letters to file, and responding to inquiries from FDA’s adverse event monitoring group.
Recall Initiation in the U.S.
February 17, 2023
Recall Initiation in the U.S.
In most cases, FIRMS initiate recalls rather than FDA:
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If U.S. recall trigger criteria are met, then FDA generally requires that FIRMS initiate recalls. FDA’s corresponding regulation is called “Firm-initiated recall” and is located at 21 CFR §7.46.
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See also FDA’s corresponding recent guidance document, ‘Initiation of Voluntary Recalls Under 21 CFR Part 7, Subpart C, Guidance for Industry and FDA Staff‘. That guidance covers things like:
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a firm’s creation of internal procedures for initiating recalls,
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an official FDA definition of “Initiation of a Recall“, the scope of which is focused solely on the firm,
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tactics to help firms initiate recalls efficiently and properly,
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allowing firms to initiate a recall even before its investigation is finished, and even before FDA finishes its agency review (if FDA was notified) of the scenario,
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making company decisions about recall initiation independent of FDA, and
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reiterating that firms are just “requested” to notify FDA bout firm-initiated recalls unless otherwise required by other FDA regulations (see next header below in this post).
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FDA has an FAQ, “Who recalls medical devices?“. FDA’s answer: “…In most cases, a company (manufacturer, distributor, or other responsible party) recalls a medical device on its own (voluntarily)…“
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See also the attached training slides from FDA, guiding firms on firms’ recall-initiation deliberations.
Certain firm-initiated recalls (i.e., Class III recalls) of medical devices aren’t required to be reported to FDA; thus they can be initiated and happen without FDA’s involvement:
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First, 21 CFR Part 806 is not the regulation for initiation of firm-initiated recalls, nor for initiation of any other recall. Instead, FDA intends Part 806 to be for assuring proper reporting to FDA of certain recalls; specifically, class I and II recalls. FDA specifically clarified this when it promulgated Part 806 after FDA received stakeholder confusion about the relationship between Part 806 corrections and removals vs. Part 7 recalls.
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21 CFR Part 7 governs firm-initiated recalls and FDA-“requested” recalls, while Part 810 governs FDA-mandated recalls. Again, Part 806 is not for initiation of any recall.
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The issue of reporting firm-initiated Class III recalls to FDA can be tricky. But ultimately, when FDA promulgated aforesaid §7.46 (Firm-initiated recalls) after receiving stakeholder push-back, the agency conceded that notifying FDA about firm-initiated recalls is not required unless required by other FDA regulations (e.g., Part 806 regarding class I and II recalls). FDA revised proposed §7.46 accordingly during promulgation by revising it to say that firms are only “requested” to notify FDA about firm-initiated recalls. And when FDA later promulgated Part 806 (to require FDA notification about class I and II recalls), FDA emphasized that class III recalls aren’t reportable to FDA.
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That said, FDA does strongly urge firms to voluntarily report their non-reportable (i.e., class III) firm-initiated recalls. In a September 2020 FDA webpage narrative, FDA even goes so far as to state that firms are “required to immediately notify” FDA of firm-initiated recalls of violative devices. But that broad stroke doesn’t align with the aforesaid actual regulatory requirements. Accordingly, I consider that webpage narrative to be an overreach that goes beyond the regulatory requirement. Indeed, in the aforesaid attached guidance from 2022, FDA reverts to the “requested” language.
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There can be benefits of voluntary notifications of recall to FDA, but there can also be pitfalls. Each case of potential voluntary reporting needs to be pondered on its own merit.
ALL recalls are either corrections or removals. But not all corrections or removals are recalls.
FDA 21 CFR Part 7 vs. Part 806: What’s the Difference?
January 26, 2023
FDA 21 CFR Part 7 vs. Part 806: What’s the Difference?
The most succinct way I’ve seen FDA correlate 21 CFR Part 806 with 21 CFR Part 7 is by stating that Part 806 reports of corrections and removals are required for Part 7 Class I and Class II recalls, yet not for Part 7 Class III recalls. Specifically, manufacturers and importers are required to make a Part 806 report to FDA of any correction or removal of a medical device(s) if the correction or removal was initiated to reduce a risk to health posed by the device or to remedy a violation of the act caused by the device which may present a risk to health.
Having addressed when Part 806 becomes applicable, let’s now focus more on when Part 7 becomes applicable. Specifically, Part 7 has two distinct purposes:
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Regulation of FDA’s own internal practices and procedures applicable to regulatory actions (e.g., recalls) initiated by (i.e., forced by) the FDA in urgent situations as an alternative to an FDA-initiated court action.
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“Guidance” for manufacturers and distributors for their “voluntary” removal or correction (i.e., their voluntary “recall” or “market withdrawal”) of marketed products so that such voluntary actions are discharged in a way that is effective in FDA’s eyes.
In practice, if FDA detects and believes that a product needs to be recalled for protection of public health, then the agency will “suggest” to a firm that the firm should “consider” recalling the device. Let me translate this: This means the firm is essentially being ordered by FDA to recall the device, or else FDA will force the recall and will, if needed, resort to legal actions against the firm. This comes from the essence of the official definition of “recall”: A firm’s removal or correction of a marketed product that the FDA considers to be in violation of the laws it administers and against which the agency would initiate legal action, e.g., seizure (e.g., if the firm doesn’t voluntarily cooperate) [interpretive emphasis added].
So, ultimately, Part 7’s “voluntary” scope as applied to manufacturers and importers isn’t really voluntary, as those firms would alternatively be forced by the agency.
Ultimately, the most efficient and effective way for a firm to put a recall in its rear-view mirror and get back to business is by executing and documenting the recall following the recall steps outlined by Part 7 while being sure to report via Part 806 those recalls that meet the aforementioned Part 806 reporting criteria. For example, when I do a Part 806 report for a Class I or II recall, there are certain section 806.10(c) elements [e.g., subsections 7, 8, 9, 12, etc.] that are addressed via the section 7.41, 7.42, and 7.49 health hazard evaluation, recall strategy, and recall communications. Same thing, by the way, for the non-reportable 806.20 corrections or removals (e.g., Part 7 Class III recalls and market withdrawals).
For any lingering questions about the definitions, I’ll expand on the aforesaid “recall” definition by explaining that all recalls are either a correction or removal, but not all corrections or removals are recalls. The classic example of this is a “market withdrawal”, which means a correction or removal of a distributed product which involves a minor violation that would not be subject to FDA legal action or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs, etc.
Note also that Field Safety Corrective Action (FSCA) is not a concept directly recognized by the U.S. FDA. Instead, FSCA is a term of Europe’s medical device regulations. This is important to note because FSCA (and also Europe’s definition of “recall”).
EU eIFU Regulation: Broader Than Many Think
March 22, 2022
EU eIFU Regulation: Broader Than Many Think
Everyone seems to know that Europe’s Regulation (EU) 2021/2026 covers requirements for when eIFU are provided instead of paper IFU. But did you know that the Commission also demands a certain level of conformity with that Regulation also for when eIFU is provided in addition to paper IFU? Here’s an overvierw.
Specifically, the Commission’s Directorate General for Health and Food Safety told me that if ever an eIFU is provided for medical devices in the Union, whether the eIFU is provided instead of paper (for qualifying Article 3 devices) or else in addition to paper (for any devices), then the applicable provisions of Regulation (EU) 2021/2226 always apply. Plainly, eIFU may not be provided outside the scope and applicable provisions of that Regulation.
Indeed, that Regulation isn’t limited in scope only to providing electronic IFU instead of paper IFU. Rather, along with that scenario, it also contains certain provisions applicable to all medical devices (excluding EU MDR Annex XVI devices) whose IFU are provided in both electronic and paper format. Be sure not to err regarding that scope. This is in alignment with the longstanding precedent established by the sunsetting Regulation (EU) 207/2012.
Also, remember to integrate your compliance approach with measures to meet the EU MDR’s Annex I.23.1 / IVDR’s Annex I.20.1 website provision (which has overlap with the eIFU’s website-related provisions).
Remember also that EU MDR Annex I.23.1(f) reminds us that instructions for use may be provided to the user in electronic format only to the extent, and only under the conditions, set out in the eIFU Regulation.
April 24, 2023 follow-up:
For example, I definitely consider IFU placed on a website to be eIFU. And so, excluding Annex XVI devices, my interpretation of the aforesaid Commission stance is, again, that any eIFU provided in addition to paper IFU must comply with the applicable provisions of Regulation (EU) 2021/2226. But this needs to be done in remembrance that only certain aspects of 2021/2226 apply to the “in addition to” scenario. Feel free to contact us for more specific assistance regarding your particular eIFU scenario.
Standards Aren’t Required, but are Recommended, to Show European Conformity
September 28, 2021
Standards Aren’t Required, but are Recommended, to Show European Conformity
You may have heard a rumor that conformity with harmonized standards or other non-harmonized standards is mandatory when showing conformity with the IVDD, MDD, IVDR, or MDR. But that is not the intent of these European Directives and Regulations. Instead, Europe fundamentally intends that conformity with harmonized standards, and even non-harmonized standards, shall remain voluntary unless such standards happen to also represent the generally recognized state-of-the-art, or unless application of a harmonized standard is in fact mandated, such as regarding the use of symbols in the information supplied with the device.
A couple examples (of many that could be given) proving this, is where the European Commission officially [see Regulation (EU) No. 1025/2012] states that:
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“…The primary objective of standardisation is the definition of voluntary technical or quality specifications…”
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“…European standardisation…is founded on the principles recognised by the World Trade Organisation (WTO) in the field of standardisation, namely…voluntary application, independence from special interests…” [emphasis added]
If you attempt to implement a policy demanding conformity with harmonized standards, or even un-harmonized standards, then, not only would you be in contravention of European legislation, but there is also a high probability that you will fail, and/or be subject to costly nonconformities, along with delayed market entry.
The ultimate conformity assessment mandate of the IVDD, MDD, IVDR, or MDR is that the “state-of-the-art” be suitably considered, and that we keep a record of whatever conformity solution happens to be applied, be it a standard (harmonized, un-harmonized European, or international), a Common [Technical] Specification (in the context of the IVDD, IVDR and MDR), or other solution [such as internally-derived specifications, international recognized publications, historical data, best medical practice, generally acknowledged state of the art (GASOTA), etc.].
Here are a few real-world examples that can quickly be a snare for you if you get too focused on harmonized or other standards:
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There are, and have historically been, harmonized standards that no longer represent the state-of-the-art and that, consequently, are generally inappropriate for use to demonstrate conformity.
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If there are any applicable Common [Technical] Specifications (IVDD/IVDR/MDR context), then those are mandatory, and generally trump a related standard.
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There are certain conformity assessment requirements for which no standard will exist at all. For example, when demonstrating proper performance of a novel medical device whose technology is truly unprecedented.
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It is not uncommon that it is simply best medical practice that dictates what is deemed to be conformity and what is not. I’ve had instances where certain local or international clinical standards of care or medical practice governed the device’s performance criteria and/or acceptability to the user.