How to Respond to a Notified Body Deficiency on Your Biological Evaluation

Receiving a deficiency letter from a notified body on your biological evaluation documentation is not unusual. Notified bodies have repeatedly indicated that biological evaluations are among the most frequent sources of nonconformities during EU MDR technical documentation review, alongside clinical evaluations and risk management.¹ How you respond to the deficiency matters as much as what you fix, because a poorly structured response that addresses the literal question but misses the underlying concern will often generate a follow-up deficiency on the same topic.

This article covers how to structure a deficiency response, the mistakes that turn one deficiency into two, and how to verify that your revised documentation does not introduce new gaps while closing existing ones.

Understand what the reviewer is actually asking

Deficiency findings on biological evaluations are often written in formal language that can be difficult to interpret. The first step in responding is to identify what the reviewer is actually asking for, which is not always the same as what the finding literally says.

For example, a finding that states "the BER (Section 5.3) excludes sensitization testing based on the device's material history, but no reference to chemical characterization data or specific material constituents is provided to support this exclusion; please provide a device-specific justification in accordance with ISO 10993-1:2025 Clause 6.4" is telling you exactly what is missing: the justification lacks traceability to the chemical characterization data. The response needs to provide that specific link, not rewrite the entire sensitization section.

Other findings are broader. A finding that states "the biological evaluation does not provide justification for each biological effect listed in the evaluation plan" could mean that several biological effects were evaluated without explaining why they were selected, or that some effects were excluded without documented rationale. In these cases, reading the finding against your submitted documentation reveals which biological effects lack justification and what form the justification needs to take.

Before drafting a response, read the finding in the context of your submitted documentation. Look at which section of your BER or BEP the reviewer was evaluating when they raised the finding. If the finding references a specific clause of ISO 10993-1 or a specific GSPR from Annex I of the EU MDR, go back to that clause and compare what it requires against what your documentation actually says. The gap between the two is what the reviewer identified, even if the finding's language does not describe it precisely.

If the finding is genuinely ambiguous and you cannot determine what the reviewer needs, most notified bodies allow a request for clarification before the formal response deadline. TUV SUD, BSI, and other major notified bodies have client managers or reviewer contact channels for this purpose. Asking for clarification is not a sign of weakness. Submitting a response that misinterprets the finding wastes more time than a brief clarification request.²

Structure the response for traceability

A deficiency response should be structured so that the reviewer can verify the fix without re-reading the entire biological evaluation package. The reviewer who reads your response is often handling dozens of submissions simultaneously. If they have to search through your revised BER to find where you addressed their concern, the review takes longer and the risk of a follow-up finding increases.

For each deficiency finding, the response should include:

The finding restated. Quote or summarize the deficiency exactly as it was written. This confirms to the reviewer that you understood the finding and are responding to the correct issue.

Your interpretation of the finding. In one or two sentences, state what you understand the reviewer to be asking for. This is especially important when the finding is broad or could be interpreted multiple ways. If your interpretation is wrong, the reviewer will tell you immediately rather than after you have drafted an entire revised BER based on a misunderstanding.

What was changed. Describe the specific changes made to the documentation, referencing the exact section, page, and paragraph numbers in the revised BER or BEP. If new test data was generated, summarize it and reference the full report. If a justification was rewritten, include the revised text in the response document so the reviewer can read it without opening the BER.

Where to find the evidence. Point the reviewer to the specific documents and sections that contain the supporting evidence. BSI has noted that as far as is practical, submissions should be standalone and not require the reviewer to search through previously submitted files to find evidence of compliance.³ The same principle applies to deficiency responses: make the evidence easy to find.

Common deficiency categories and how to approach them

Insufficient justification for excluded biological effects

This is one of the most frequent biological evaluation deficiencies. The BER excluded one or more biological effects from evaluation but the justification was too generic to support the exclusion. For example, "hemocompatibility testing was not performed because the device does not contact blood" without any supporting analysis of whether indirect blood contact could occur through the device's clinical use.

The response should include a revised justification that is device-specific, references the device's actual contact conditions, and cites the relevant data (chemical characterization, clinical use description, anatomical placement) that supports the exclusion. If the exclusion cannot be adequately justified, the response should acknowledge this and include a plan for conducting the evaluation, with a timeline.

Missing or inadequate chemical characterization

Deficiencies on chemical characterization typically fall into specific sub-categories: incomplete solvent justification, AET stated without calculation methodology, extractable compounds not carried through to the TRA, or testing performed on materials rather than the final finished device. An IQVIA MedTech case study documented a situation where an orthopedic implant manufacturer received a BSI nonconformity requesting full evidence of evaluations or justification for each biological effect per ISO 10993-1, after the manufacturer had initially submitted only a brief paper-based biocompatibility rationale based on raw materials and manufacturing processes.⁴

The response should address the specific sub-category identified in the finding rather than revising the entire chemical characterization section. If the finding is about solvent selection rationale, provide the rationale. If it is about AET methodology, provide the calculation. Wholesale revision of sections that were not cited in the deficiency creates unnecessary review burden and risks introducing new inconsistencies.

Risk management integration not demonstrated

The 2025 revision of ISO 10993-1 explicitly aligns biological evaluation with ISO 14971 risk management. Deficiencies in this category typically ask for evidence that biological hazards were identified, traced to hazardous situations, and assessed with severity and probability estimation. A BER that presents biological test results without connecting them to identified biological hazards will draw this finding.

The response should demonstrate the traceability chain from identified biological hazards through hazardous situations to potential harms, with risk estimation for each. If this analysis was performed but not visible in the BER, the response should reference where the analysis exists (typically in the risk management file) and either include the relevant sections by reference or, preferably, add the traceability to the revised BER directly.

Biological equivalence not adequately substantiated

If your BER uses a biological equivalence argument to reduce testing requirements, the deficiency will ask for evidence that the comparison addressed all required dimensions. Under MDCG 2020-5, equivalence claims must address chemical, physical, and clinical characteristics, and any differences must be assessed for their impact on biological safety. A response that provides additional information on one dimension but does not address the others will generate a follow-up finding.

Testing history with initial failures

When biocompatibility testing produced initial failures followed by passing rechallenges, the deficiency will ask about the testing history and the basis for considering the passing results representative. The response must present the complete testing history (both failures and passes), a root cause investigation (even if inconclusive), and a justification for why the rechallenge results are considered more representative than the initial results.

For example, if initial sensitization and pyrogenicity testing failed at a specific reprocessing timepoint using a specific cleaning agent but passed at all other timepoints and with alternative cleaning agents, the response should document this pattern, identify the cleaning agent interaction as the probable contributing factor, describe any process changes implemented (such as revising the reprocessing protocol), and present the rechallenge results in the context of those changes. Omitting the initial failures from the response is not an option, because the test laboratory records exist and the reviewer can request them.

The biggest mistake: fixing one finding and creating another

Deficiency responses are written under time pressure, and the focused effort on addressing specific findings sometimes introduces new problems elsewhere in the biological evaluation package. This is one of the most common patterns in deficiency cycles: the fix for Finding 1 creates a new gap that becomes Finding 2 in the next review cycle.

This happens because deficiency responses tend to focus narrowly on the cited sections without checking whether the changes are consistent with the rest of the document. For example, revising the device contact categorization in response to a finding may mean that the biological effects evaluation table in a different section of the BER is now inconsistent with the revised categorization. Updating the TRA with a new compound identified in revised chemical characterization data may mean that the BER's summary of biological risks is now incomplete because it does not reference the new compound.

After drafting the response and revising the documentation, review the entire package for internal consistency. Check that the BEP's scope still matches the BER's content. Check that every compound in the E&L study still appears in the TRA. Check that the risk management file's biological hazard list is consistent with the BER's hazard identification. This cross-document consistency check is the most effective way to prevent a deficiency response from generating a new deficiency.

Timeline and process expectations

Notified bodies typically allow 15 to 30 days for responding to major nonconformities, though this varies by notified body and by the severity of the finding.⁵ For biological evaluation deficiencies that require new testing (such as a finding that a biological effect was excluded without adequate justification and evaluation is now required), the timeline for generating new data may extend well beyond the standard response window. In these cases, communicate with the notified body early to negotiate an extended timeline and submit an interim response that acknowledges the finding, describes the plan for generating the required data, and provides a realistic timeline for the complete response.

Under the EU MDR, notified body capacity constraints have made review cycles longer across the board. A 2026 survey of notified body operations found that incomplete technical documentation is the most frequently cited reason for submission delays, and that clarification requests from notified bodies add weeks or months to the review timeline.⁶ A complete, well-structured deficiency response submitted on the first attempt is the most effective way to avoid extending an already long review cycle.

Using a gap analysis before resubmission

Running your revised documentation through a structured pre-submission gap analysis before resubmitting is one of the highest-value steps in the deficiency response process. The gap analysis checks whether the revisions addressed the cited findings, whether the changes are internally consistent with the rest of the package, and whether any new gaps were introduced during the revision process.

This is especially important when the deficiency response involved substantive changes to the BER (such as revising the device categorization, adding new chemical characterization data, or restructuring the risk assessment). These types of changes ripple through multiple sections of the biological evaluation package, and a structured check catches the cross-document inconsistencies that manual review under time pressure tends to miss.

If you have received a deficiency on your biological evaluation and want to verify that your response addresses the findings without introducing new gaps, request a gap analysis or get in touch to discuss your package.