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How to write a request for designation

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In the eSTAR and PreSTAR, the FDA inquires whether a request for designation (RFD) is associated with your device.

What is a request for designation (RFD)?

A request for designation is a formal request to the Office of Combination Products (OCP), where you request that OCP assign the agency division that will have jurisdiction over a combination product. In 21 CFR 3.7, the FDA outlines the information required in an RFD submission. The FDA encourages RFD submitters to review the agency’s guidance prior to submitting an RFD. It irritates the FDA when you don’t read the guidance and ask questions that are clearly answered within it. Read the guidance first (we provided links below).

What is a combination product?

Before you submit a request for designation, you need to understand what a combination product is. The term combination product includes:

  1. A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity;
  2. Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;
  3. A drug, device, or biological product packaged separately that, according to its investigational plan or proposed labeling, is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in the intended use, dosage form, strength, route of administration, 9or significant change in dose; or
  4. Any investigational drug, device, or biological product packaged separately that, according to its proposed labeling, is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.

Information regarding the drug/biologic constituent part of the combination product may be needed and accounted for throughout the various sections of your premarket submission. In addition, as described in Product Stability documentation, medicinal substance refers to the drug/biologic constituent part of the combination product as defined in 21 CFR 3.2(e).

How do you write a request for designation (RFD)?

We recommend that you always start with a pre-request for designation (pre-RFD). Once you have feedback from the FDA, then you will be ready to write your request for designation (RFD). The FDA published two guidance documents related to RFDs:

  1. How to prepare pre-request for designation
  2. How to write a request for designation

What is a pre-RFD?

A pre-RFD is a submission that you make to the Office of Combination products (OCP) to request the FDA’s preliminary, nonbinding assessment of:

  1.  the regulatory identity or classification of a product as a drug, device, biological product, or combination product, and/or
  2. whether CBER, CDER, or CDRH will regulate the product if it is a non-combination product, or
  3. which of those Agency Centers will have primary jurisdiction for a premarket submission of a combination product.

The FDA’s target review time is 60 days for providing the information requested, but a pre-RFD is not a tracked metric with budget impact. Therefore, you should set expectations with your senior management team and investors at approximately 90 days–just like the 513(g) submissions.

21 CFR §3.7 – Request for Designation (copied from eCFR)

(a) Who should file: the sponsor of:

  1. Any combination product the sponsor believes is not covered by an intercenter agreement; or
  2. Any product where the agency component with primary jurisdiction is unclear or in dispute.

(b) When to file: a sponsor should file a request for designation before filing any application for premarket review, whether an application for marketing approval or a required investigational notice. Sponsors are encouraged to file a request for designation as soon as there is sufficient information for the agency to make a determination.

(c) What to file: an original and two copies of the request for designation must be filed. The request for designation must not exceed 15 pages, including attachments, and must set forth:

  1. The identity of the sponsor, including company name and address, establishment registration number, company contact person and telephone number.
  2. A description of the product, including:
    1. Classification, name of the product and all component products, if applicable;
    2. Common, generic, or usual name of the product and all component products;
    3. Proprietary name of the product;
    4. Identification of any component of the product that already has received premarket approval, is marketed as not being subject to premarket approval, or has received an investigational exemption, the identity of the sponsors, and the status of any discussions or agreements between the sponsors regarding the use of this product as a component of a new combination product.
    5. Chemical, physical, or biological composition;
    6. Status and brief reports of the results of developmental work, including animal testing;
    7. Description of the manufacturing processes, including the sources of all components;
    8. Proposed use or indications;
    9. Description of all known modes of action, the sponsor’s identification of the single mode of action that provides the most important therapeutic action of the product, and the basis for that determination.
    10. Schedule and duration of use;
    11. Dose and route of administration of drug or biologic;
    12. Description of related products, including the regulatory status of those related products; and
    13. Any other relevant information.
  3. The sponsor’s recommendation as to which agency component should have primary jurisdiction based on the mode of action that provides the most important therapeutic action of the combination product. If the sponsor cannot determine with reasonable certainty which mode of action provides the most important therapeutic action of the combination product, the sponsor’s recommendation must be based on the assignment algorithm set forth in § 3.4(b) and an assessment of the assignment of other combination products the sponsor wishes FDA to consider during the assignment of its combination product.

(d) Where to file: all communications pursuant to this subpart shall be addressed to the attention of the product jurisdiction officer. Such a request, in its mailing cover should be plainly marked “Request for Designation.” Concurrent submissions of electronic copies of Requests for Designation may be addressed to .

[56 FR 58756, Nov. 21, 1991, as amended at 68 FR 37077, June 23, 2003; 70 FR 49861, Aug. 25, 2005]

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FDA User Fees for FY 2026 released on July 31, 2025

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The FDA User Fees for FY 2026, October 1, 2025 – September 30, 2026, were released on Thursday, July 31, 2025.

What are FDA User Fees?

At the very core of it, the FDA user fees fund the FDA Office of Device Evaluation (ODE) budget. Without these user fees, the FDA cannot begin reviewing a medical device submission. This includes 510k, PMA, and De Novo submissions. Before the FDA assigns a reviewer to your submission, you must pay the appropriate device user fee in full unless eligible for a waiver or exemption. If you pay the user fee by credit card, you must allow a few extra days for the user fee to clear. Otherwise, your submission will be placed on “User Fee Hold.” Small businesses may qualify for a reduced fee. The FDA announced the FY 2026 FDA User Fees on July 31, 2025. The FDA will announce the user fees for FY 2027 in a Federal Register notice next August 2026.

What are the FDA User Fees for FY 2026?

FY 2026 FDA User Fees with waiver 1024x547 FDA User Fees for FY 2026 released on July 31, 2025

Is there a small business discount for the establishment registration?

Certain small businesses certified through the small business designation (SBD) program may qualify for a waiver for the registration fee if the business and its affiliates:

  1. have gross receipts and sales of no more than $1 million USD,
  2. can demonstrate paying the registration fee would represent a financial hardship (for example, proof the business is in active bankruptcy), and
  3. has proof of a prior year’s payment of the registration fee.

How much did user fees increase for FY 2026?

The increase in FDA user fees from FY 2025 to FY 2026 was 7.12%, except the annual FDA Registration fee, which increased by 23.1% to $11,423. There are three components to the increase:

  1. Base Fee = a statutory base fee for each FDA user fee
  2. Standard Fee = an inflation-adjusted statutory base fee
  3. Adjusted Fee = adjusted fee to meet revenue target

The reason for each component for the user fees is described in the Federal Register.

When does the FY 2026 increase take effect?

Each year the new FDA user fees take effect on the 1st day of the FDA’s new fiscal year (i.e., October 1). You cannot pay the annual registration fee for FY 2026 until October 1, 2026, and the last day you can submit under the FY 2025 user fee pricing is Tuesday, September 30, 2025. For the submission to be accepted under the current fiscal year, the submission must be uploaded to the Customer Collaboration Portal (CCP) no later than 4:00 p.m. ET on the 30th.

What do you do if you have already paid the FY 2025 price?

If you already paid the FY 2025, and your submission is received after 4:00 p.m. ET on September 30, 2025, you must complete FDA Form 3914 for an FDA user fee payment transfer request. You will also need to pay the difference in user fees (i.e., 7.12%). If your submission is received before the FY 2025 user fee is transferred and you have paid the difference in user fees, your submission will be placed on a user fee hold. If you paid the FY 2025 user fee and are not ready to transfer your previously paid user fee to FY 2025 (and pay the difference), you can request an FDA user fee refund by filling in an online form.

What is the annual registration fee for FY 2026 due?

The annual establishment registration user fee can be paid any time between October 1 and December 31. If you pay late, there is no penalty, but your registration status will be inactive, and you cannot submit new device submissions or import products to the USA. If you are not yet distributing any devices in the USA, you are not required to have your establishment registered, and establishment registration is not required before submitting a new device submission. If you are not required to register yet, when you are paying the user fee for a new device submission on the Device Facility User Fee (DFUF) website, you will click the “Yes” button because there is no “N/A” option for the question below.

Click Yes 1024x200 FDA User Fees for FY 2026 released on July 31, 2025

Is the annual FDA registration fee prorated?

Annual registration payments are not prorated when you are paying in the middle or even near the end of the year for your initial registration. Therefore, you will need to consider if the revenues you expect to gain before the end of the current fiscal year are worth the registration cost. If you need any help with annual registration or you need a US Agent, we offer these consulting services.

FDA User Fees for FY 2026 released on July 31, 2025 Read More »

FDA eSTAR v5.5 – What’s new?

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This blog provides a deep dive into the newest version of the FDA eSTAR, version 5.5, released on February 12, 2025.

Why did the FDA release the new eSTAR version as v5.5 instead of v6.0?

A major version update consists of policy changes, regulatory changes, or major changes to the template and will be denoted by a major version number increment (e.g. 5.4 to 6.0). A minor version update will consist of other changes and will be denoted by a minor version number increment (e.g. 5.4 to 5.5). If there are policy or regulatory changes, a new major version of the eSTAR is made before the implementation date, and the previous version of the eSTAR is removed. As an example, the FDA updated v4.3 to v4.4 to enable PMA content, updates to the international pilot of the eSTAR with Health Canada, and implementation of cybersecurity documentation requirements are considered major changes that trigger the need for a major version update (i.e., 5.0) instead of a minor version update (i.e., 4.4). These changes apply to the IVD eSTAR and the non-IVD eSTAR. If you are generally unfamiliar with the FDA eSTAR, please visit our 510k course page.

What is the deadline for using v5.5?

Version 5.4 of the FDA eSTAR, both the nIVD and IVD versions, may continue to be used until v6.0 is eventually released. In fact, any v5.x may be used until v6.0 is released. Any submissions that are submitted with an expired version (v4.x) of the eSTAR will be rejected. If you have already uploaded information to an older version of the template, you will need to scroll to the bottom of the eSTAR and export the data to an HTML file. Then you import the HTML file into the newer version of the eSTAR. Any attachments you made to the older version of the template will not be exported, and you will have to attach all of the attachments to the new template.

Import Export Function in FDA eSTAR 1024x423 FDA eSTAR v5.5 Whats new?

PMA content is enabled in the new FDA eSTAR

Previous versions of the FDA eSTAR included the functionality for premarket approval (PMA) submissions, but in version 5.0 the FDA finally enabled this functionality. 510k submissions have three types: 1) Traditional, 2) Abbreviated, and 3) Special. PMA submissions also have different types. There are two types of PMA submissions for a new device: traditional and modular. Unfortunately, the FDA eSTAR is not intended for PMAs using the modular approach. For Class 3 devices, the FDA has more stringent controls over changes than Class 1 and 2 devices. Therefore, a PMA supplement is required for the following types of changes to PMA-approved devices:

  • new indications for use;
  • labeling changes;
  • facility changes for manufacturing or packaging;
  • changes in manufacturing methods;
  • changes in quality control procedures;
  • changes in sterilization procedures;
  • changes in packaging;
  • changes in the performance or design specifications, and
  • extension of the expiration date.

There are several types of PMA supplements, but only three types of supplements can use the FDA eSTAR: 1) Panel-Track, 2) 180-Day, and 3) Real Time. To determine which type of PMA supplement you should use, the FDA published guidance for modifications to devices subject to the premarket approval process.

PMA Content

The following sections in the FDA eSTAR are specific to PMA submission content requirements:

  • Quality Management System Information
  • Facility Information
  • Post-Market Study (PMS) Plans
  • Attach an exclusion statement, or an Environmental Assessment Report in accordance with 21 CFR 814.20(b)(11)

Health Canada is conducting a pilot with the FDA eSTAR

Health Canada’s FDA eSTAR pilot is now full with a total of 10 participants (originally only 9 were planned). The pilot will test the use of eSTAR for applications submitted to Health Canada. The results of the pilot should be complete soon, and then we expect an extension of the pilot to a broader number of applicants. We heard rumors that the HC eSTAR was overly complicated. Hopefully, future versions are simplified.

Were there any changes to the EMC testing section?

EMC Labeling questions were consolidated into a single question instead of four because only one citation is usually provided in this section. A copy of the older version is provided below.

Old EMC Labeling Section 1024x506 FDA eSTAR v5.5 Whats new?

The updated version 5.0 is shown below and has only one question, but the help text was changed.

Pointing to help text box 1024x250 FDA eSTAR v5.5 Whats new?

Does the FDA eSTAR now require more cybersecurity documentation?

We have updated our cybersecurity work instruction (WI-007) to address the updated FDA guidance for cybersecurity documentation. The revisions were completed earlier this month, and you can purchase the updated templates on our website. We have also been telling our subscribers to anticipate a significant revision to the FDA eSTAR cybersecurity requirements 300x71 FDA eSTAR v5.5 Whats new?template when this happens. The release of the updated eSTAR version took a little over two months, and the change resulted in a three-page section dedicated to cybersecurity documentation. The previous versions of the template included a requirement for documentation of cybersecurity risk management and a cybersecurity management plan/plan for continuing support. The following documents must be attached in this section if cybersecurity applies to your device:

  1. risk management – report (attach)
  2. risk management – threat model (attach)
  3. list of threat methodology (text box)
  4. verification that the threat model documentation includes (yes/no dropdown):
    1. global system view
    2. Multi-patient harm view
    3. Updateability/patchability view
    4. Security use case views
  5. cybersecurity risk assessment (attach)
  6. page numbers where methodology and acceptance criteria are documented (text box)
  7. verification that the risk assessment avoids using probability for the likelihood assessment and use exploitability instead (yes/no dropdown)
  8. software bill of materials or SBOM (attach)
  9. software level of support and end-of-support date for each software component (attach)
  10. operating system and version used (text box)
  11. safety and security assessment of vulnerabilities (attach)
  12. assessment of any unresolved anomalies (attach)
  13. data from monitoring cybersecurity metrics (attach)
  14. information about security controls (attach)
  15. page numbers where each security control is addressed (text box):
    1. Authentication controls
    2. Authorization controls
    3. Cryptography controls
    4. Code, data, and execution integrity controls
    5. Confidentiality controls
    6. Event detection and logging controls
    7. Resiliency and recovery controls
    8. Firmware and software update controls
  16. architecture views (attach)
  17. cybersecurity testing (attach)
  18. page numbers where cybersecurity labeling is provided (text box)

Sterility section changes include an updated question on EO residuals

In the sterility section of the FDA eSTAR there was a question about sterilant residues. Specifically, the question was “What are the maximum levels of sterilant residual that remain on the device?” The space provided for entering the information was small as well.

EO residue help text 1024x568 FDA eSTAR v5.5 Whats new?

Now the question is reworded to: “What are the maximum levels of sterilant residuals that remain on the device, and what is your explanation for why those levels are acceptable for the device type and the expected duration of patient contact?” No change was made to the help text for this question.

In addition to the changes in the sterility section regarding EO residuals, the FDA also modified the dropdown menu and the help text for pyrogenicity testing. There were options for “LAL” and “Rabbit Test” separately, but now these are combined into “LAL and Rabbit Pyrogen Test.” In addition, the following help text was added: “If you previously conducted rabbit testing on these materials, please either: 1) reference this testing according to the submission number in your attached Pyrogenicity documentation and specifically cite the attachment(s) and page number(s) where the testing is found in that submission, or 2) attach your previous test report.”

Pyrogenicity help text 1024x647 FDA eSTAR v5.5 Whats new?

What is the deadline for using v5.0?

Many clients say that they get an error message when they try to open the FDA eSTAR template. This is because they are opening the eSTAR from a PDF viewer instead of Adobe Acrobat Pro.

Please wait 1024x400 FDA eSTAR v5.5 Whats new?

Some people want to save money by using the free Adobe Acrobat Reader software instead, but this will not allow you to complete the eSTAR properly. Therefore, the FDA added a Popup message if Adobe Acrobat Reader is used.

How are devices with a breathing gas pathway evaluated for biocompatibility?

In the screen capture below, I have intentionally selected “Surface Device: Mucosal Membrane” as the type of tissue contact for a breathing gas pathway device because the device will have a mouthpiece placed in your mouth (i.e., mucosal membrane). This is a common mistake. In version 5.0 of the FDA eSTAR, the FDA clarifies that these devices should be evaluated as “externally communicating” and the tissue contact is “tissue/bone/dentin.” Specifically, the tissue contact is the lungs. For this reason, the FDA added the help text shown below in the JavaScript Window regarding the applicability of ISO 18562-1, -2, -3, and -4.

ISO 18562 references for biocompatibility 802x1024 FDA eSTAR v5.5 Whats new?

Additional questions and guidance will appear when you click on the individual blue boxes shown above. For the blue box labeled “Subacute/Subchronic,” you will find additional help text regarding the ISO 18562 standards. Similar help text is found when you click the blue box labeled “Acute Systemic & Pyrogenicity.”

Additional ISO 18562 help text 1024x395 FDA eSTAR v5.5 Whats new?

What is a cross-section change reminder?

One of the minor changes made in this FDA eSTAR version is the addition of “cross-section change reminders” to the help text in the device description section. This is not meant to help you avoid answering questions in your submission, because if you are missing a section of the submission because you answered “No” instead of “Yes” the FDA reviewer will identify this error during the Technical Review process. This will result in your submission being placed on hold and the review time clock will be reset to zero days when you resubmit with the corrections made. The screen capture below shows an example of one of these cross-section change reminders.

Cross section change reminder 1024x636 FDA eSTAR v5.5 Whats new?

What changes were made to the clinical testing section of the FDA eSTAR?

The clinical testing section will now display when using PDF-XChange Editor, but we recommend only using Adobe Acrobat Pro to edit the FDA eSTAR. This change is a bug fix, and it is specific to the nIVD eSTAR. The IVD eSTAR and the nIVD eSTAR both include a clinical testing section within the performance testing section, but the performance testing section is found in the FDA eSTAR before the electrical safety and EMC testing section, while the performance testing section is found after the electrical safety and EMC testing section. If your company is planning to submit clinical data in a future FDA submission, we have the following recommendations:

  • watch the CDRH Learn webinars on the topic of 21 CFR 812
  • conduct a pre-submission teleconference to ask questions about your clinical study protocol before IRB submission or ethics review board submission
  • before you submit the pre-sub meeting request, look at what general clinical information the FDA wants for a De Novo or PMA submission in the FDA eSTAR

FDA eSTAR clinical section 873x1024 FDA eSTAR v5.5 Whats new?

Note: The clinical section shown above is only found in the FDA eSTAR if you select a De Novo or PMA submission. If you submit a 510k submission with clinical data, the clinical section will be abbreviated as shown below.

FDA eSTAR clinical section for 510k 859x1024 FDA eSTAR v5.5 Whats new?

FDA eSTAR v5.5 – What’s new? Read More »

Secure Software Development Lifecycle

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Explanation of US FDA requirements for establishing a software development lifecycle that results in secure software.

Is cybersecurity applicable to your device?

As medical devices become more connected and threats evolve, the probability of a security breach increases. To address these growing concerns, the FDA has published 2023 guidance on “Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions” as an approach to strengthen the cybersecurity and safety of medical devices. The guidance requires manufacturers to integrate security as a fundamental aspect throughout the entire device lifecycle, from initial planning to decommissioning.

Your device is a cyber device if the following attributes apply

  • Wi-Fi or cellular
  • Network, server, or Cloud Service Provider connections.
  • Bluetooth or Bluetooth Low Energy.
  • Radiofrequency communications.
  • Inductive communications; and
  • Hardware connectors capable of connecting to the internet (e.g., USB, Ethernet, serial port)

How is secure software addressed by quality systems?

As the title of the guidance suggests, the FDA wants manufacturers to incorporate cybersecurity into their quality systems. These regulations will address both pre-market and post-market security requirements throughout the device’s life. This requirement ensures that a consistent design and labeling approach is employed throughout the industry as common practice.

  1. Premarket Quality system regulation requirements must incorporate security-related phases, such as:
    • Planning
    • Design
    • Development
    • Testing
    • Deployment
  2. Post-market Quality System requirements: To maintain robust cybersecurity, the manufacturers need to focus on the following key post-market areas for monitoring and maintenance:
    • Risk Management: Identify and mitigate risks by conducting regular vulnerability assessments.
    • Incident Response: Prepare an incident response plan for detecting, reporting, and responding to security breaches.
    • Software Updates: Regularly update and patch the software to ensure system security and integrity.
    • Reporting and Communication: Establish an effective communication strategy and policy for vulnerability disclosure.

Submission Requirements for Secure Software

The documentation requirements for regulatory submission will not be developed as a standalone.

To demonstrate that your device is secure and that it has been developed following a Secure Software Development Lifecycle (SSDLC), the manufacturers must include documents from both their pre-market and post-market security processes in their regulatory submissions to the FDA. The documents commonly include planning, secure coding, comprehensive risk assessment, and continuous security monitoring and management.

The documents for the regulatory submission include the following:

  • Threat Modeling
  • Security Architecture
  • Security risk management files
  • SBOM with EOL and LOS information
  • Safety and security risk Assessment of vulnerabilities in the OTS components identified in the SBOM.
  • Unresolved Anomalies for security impact
  • Security Metrics
  • Security controls
  • Security Testing
  • Security labeling

The flowchart below outlines a simplified process for determining pre-market and post-market requirements. It also shows what documents must be retrieved from the manufacturer’s quality systems for the regulatory submissions.

pre market and post market cybersecurity reqquirements 1024x782 Secure Software Development Lifecycle

Secure Software Development Lifecycle Read More »

FDA Human Factors Guidance

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FDA released a final FDA Human Factors Guidance that explains the requirements for human factors testing of medical devices.

Screenshot 2016 02 04 at 1.24.04 PM FDA Human Factors Guidance

FDA Human Factors Guidance

The FDA released a final guidance document on the subject of “Applying Human Factors and Usability Engineering to Medical Devices.” This is a final guidance document that replaces the previous version that was released in 2000 and the draft that was released in 2011. The diagram below is Figure 3 from this new FDA guidance, and it includes references to sections 5 through 9 of the guidance document.

What’s in the FDA human factors guidance?

The organization of the guidance is similar to an ISO standard. Section 1 is the introduction. Section 2 is the scope of the guidance. Section 3 includes definitions, and Section 4 provides an overview of the human factors process and usability engineering as these concepts apply to medical devices. Sections 5 through 9 of the guidance explain the details of the process for applying these concepts to medical devices and risk management. The guidance document includes six references to national and international standards that include human factors engineering or usability engineering, and there are 19 references to articles about human factors engineering and usability engineering at the end of the guidance document.

Incorporating human factors in your design and risk management processes

The steps in the process for human factors engineering and usability engineering mirror the risk management process as defined in ISO 14971 except this guidance does not specify developing a risk management plan or the need to create a risk management file. Although the FDA human factors guidance does not specify that a usability engineering file (UEF) is required, a UEF is required for CE Marking and electrical medical equipment. Therefore, during the design planning phase of your design and development process you should also be identifying the human factors and usability engineering tasks that are needed to complete your UEF. The essential activities to include in your usability engineering plan include:

  1. creating a use specification (your user needs) – Requirements Phase of Design
  2. identifying known use errors (design inputs) – Requirements Phase of Design
  3. performing a task analysis – Development Phase of Design
  4. creating a use-related risk analysis (URRA) – Development Phase of Design
  5. conducting formative usability testing – Development Phase of Design
  6. implementing risk controls – Design “Freeze”
  7. creating a summative usability protocol – Verification Phase of Design
  8. writing a summative usability validation report – Validation Phase of Design

Risk controls (i.e., activity #6) are implemented in order to reduce the risk of potential use errors. The unlike other types of risk controls, use-related risk controls require validation instead of verification. The use-related risk controls can be validated through simulated use studies or clinical studies. For these reasons, we recommend documenting use-related risks separately from software risks, security risks, and hardware risks. For IVD 510k submissions, the FDA specifies two different places in the eSTAR to attached your validation documentation. For non-IVD 510k submissions the validation documentation is included in the non-clinical performance testing section of the FDA eSTAR.

Creating a Summative Usability Engineering Report

Clients often ask us what they need to do with regard to human factors engineering and usability engineering for documentation in their technical file (TF) and design history file (DHF). We recommend that they create a summative usability engineering report using the outline provided in the 2016 FDA human factors guidance. We also include a template based on this guidance with our usability procedure (SYS-048) and our human factors training series. If your company makes many types of products with multiple hazard types, then you will need a somewhat generic report template. However, companies with only one or two device families should be able to pre-populate a report template with sections for specific categories of hazards that are applicable to their device family. As discussed in our summative usability report webinar, you can also pre-populate the first seven sections of the report before you conduct summative testing.

Updating Your Risk Management File to Include Usability

As suggested above, we recommend establishing a separate usability engineering file from your risk management file. However, if you already have usability included in your risk management file we recommend updating your risk management file in the following ways:

  1. update your post-market surveillance plan/risk management plan to specifically gather information about use errors related to the use environment, the user, and the device/user interface
  2. update your hazard identification report to include hazards related to use errors
  3. update your risk analysis to include risk controls that you have implemented to reduce the risk of harm related to use errors
  4. perform and document verification and validation of any new risk controls that you may implement related to use errors
  5. update your instructions for use to include warnings and precautions about use errors
  6. develop training tools, such as videos, to demonstrate possible use errors and how to avoid them

The bulk of human factors engineering and usability engineering are documented in the risk management file. Risk management documentation is only required for FDA submissions that include: 1) software, 2) De Novo Classification Requests, and 3) PMA submissions. If you have a non-software device for which you are submitting a 510(k), then you do not include a risk analysis with your submission (exceptions are identified in special controls guidance). It is still critical that design teams address usability engineering, however, because identifying use errors and implementing risk controls to eliminate use errors will prevent product complaints and adverse events. Usability engineering files (UEFs) are also required for electrical medical equipment for IEC 60601-1-6 certification. If these issues are not addressed during the design of a new product, corrective actions and possibly recalls will be needed after the product launch. FDA inspectors will also identify weaknesses in your risk management activities when they identify complaints that are not addressed in your risk analysis.

Additional Training Resources for Usability Engineering

FDA Human Factors Guidance Read More »

Use error and abnormal use training webinar

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In this use error training webinar, you will learn how to use our decision tree form to determine if you have identified a use error or an abnormal use.

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Use error training screen capture 1024x576 Use error and abnormal use training webinar

Use error and abnormal use training webinar ($79)

In this webinar, you will learn what a use error is and what abnormal use is. You will learn how to use our decision tree form to determine if you have identified a use error or an abnormal use. The webinar is a 21-minute recorded video (i.e., mp4) and includes the decision tree form with a work instruction.

Use error thumbnail Use error and abnormal use training webinar
Use error and abnormal use training webinar
In this webinar, you will learn what a use error is and what abnormal use is. You will learn how to use our decision tree form to determine if you have identified a use error or an abnormal use. The webinar is a 21-minute recorded video (i.e., mp4) and includes the decision tree form with a work instruction.
Price: $79.00

Please note: These products will be delivered to the email address provided in the shopping cart transaction. After the transaction is verified, please check your email for the download.

When is the use error and abnormal use training webinar?

This webinar is a 21-minute recording you can purchase on-demand and watch the training as often as you wish. If you need help preparing a usability engineering file (UEF) for your device, we can help you on an hourly basis. Please contact Lindsey Walker for a quote.

What you will receive in the Use error and abnormal use training webinar:

Contents of the Use Error Training 1024x221 Use error and abnormal use training webinar

Other Usability Engineering / Human Factors Training

About the Author

20190531 005146 150x150 Use error and abnormal use training webinarMatthew Walker – QMS, Risk Management, Usability Testing, Cybersecurity

Matthew brings a unique background as a former Firefighter/EMT and Rope Rescue Tech with expereince in OSHA and NFPA regulations. For the better part of a decade, he has worked as a Technical/Medical Writer and Lead Auditor. He holds degrees in Fire Science and Computer Forensics and Digital Investigations, graduating Summa Cum Laude from Champlain College. Matthew is also an active member of several academic honor societies including Omicron Sigma Sigma’s Order of the Sword and Shield. His professional focus includes Human Factors Engineering, Risk Management, and Cybersecurity with a special interest in applying Digital Forensics and Incident Response (DFIR) practices to medical technology. He combines regulatory expertise with technical insige to strengthen both product safety and oranizational resiliance.

Email: Matthew@FDAeSTAR.com

Connect on Linkedin: http://www.linkedin.com/in/matthew-walker-214718101/

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FDA US Agent – What do they do?

3 Comments / FDA, Registration / By

Medical device companies exporting devices into the USA must have a US agent to register, but what does an FDA US agent do?

What does an FDA US agent do?

Every medical device company outside the USA that distributes devices in the USA must have an FDA US agent. This includes manufacturers, contract manufacturers, and specifications developers outside the USA. The US agent assists the FDA in communication with the device company. The most common communications concern questions about devices exported to the US and scheduling FDA inspections. The role of the US agent is very similar to a European Authorized Representative, a UK Responsible Person, or a Swiss Authorised Representative. Unlike an EC Representative, you do not include US agents in your device labeling. The US agent’s name and contact information only appear on your FDA Establishment Registration record on the FDA website. 

Is there any certification or contract required for a US agent?

FDA US agents have no certification process, but you should have a formal signed agreement or contract with your agent. I have never seen the FDA request a copy of the contract or a letter from a US agent or the company that is registered. However, since the agent has a legal role and responsibility, you should ensure an agreement or contract is in place. The agreement or contract should include the following elements:

  • Scope of service
  • Commitment to perform US agent services promptly
  • Duration of service (i.e., specific start and end dates)
  • Termination provisions
  • Consulting Fees for US agent services (typically an annual fee ranging from $250-$1,500)
  • Any additional consulting fees if the FDA contacts your agent
  • Who is responsible for payment of FDA User Fees ($11,423 for FY 2026 FDA User Fee)
  • Commitment to communicating complaints, especially for potential risks to public health, serious injuries, or death, directly to your company
  • Confidentiality clause or reference to a separate confidentiality agreement (Note: The agent may be compelled to disclose information they have to the FDA, but they should notify your company first if this happens.)
  • Non-solicitation of your customers or suppliers and no solicitation of employees
  • Force Majeure clause
  • Identification of the agent’s name, address, phone, and email
  • Identification of the company name, address, phone, DUNs Number
  • Identification of the company contact’s name, title, address, phone, and email
  • Identification of who will be the “Official Correspondent” in the FDA Registration Database
  • Signature and Date

The US Agent is not required to be a legal entity, but you will need to enter a “Company Name.” There is no place to enter an EIN, and DUNS number is optional. Here’s a screen capture of the account creation form below.

FURLS Account Set up 1024x811 FDA US Agent What do they do?

You should also consider adding your agent to your Approved Supplier List (i.e., LST-003). If you do not already have a procedure for Supplier Quality Management (i.e., SYS-011), Medical Device Academy has a procedure available for purchase that includes a template for review and approval of new suppliers (i.e., FRM-005) and a template for an Approved Supplier List (i.e., LST-003). The FDA US agent doesn’t need a quality system, but they should be able to demonstrate competency in US FDA device regulations with their resume and/or training records. Specifically, competency should include 21 CFR 820, 803, 806, 830, and 807. In the future, your US agent must also be competent in ISO 13485:2016. FDA inspectors are expected to request evidence of an agreement between your company and the US agent. The inspector will also review your records for qualification, approval, and ongoing evaluation of the US agent as a supplier during FDA inspections. Ideally, your agent has been directly involved in previous FDA inspections, and they can prepare you by conducting a mock-FDA inspection.

What does the FDA do to qualify US agents?

The FDA does very little to qualify a US agent. The only thing the FDA “does” is to send an automated email to the FDA US agent when you submit your initial establishment registration or renew your FDA registration. The email subject line is “ACTION REQUIRED: U.S. Agent Assignment Notification.” The email is sent from “reglist@cdrh.fda.gov.” Your agent must ensure their email client has identified this email as a “safe sender” to prevent the email from ending up in a spam folder. For medical devices, there is no requirement for the US agent to submit any other proof to the FDA.

What is an “Action Required” email?

Below is an example of the “Action Required” email that the FDA sends to FDA US agents immediately after your registration and listing is completed by a foreign firm.

Action Required Email 1024x606 FDA US Agent What do they do?

Your FDA US agent will receive an automated email from the FDA seconds after you complete your registration for an initial FDA establishment registration or the renewal of your FDA establishment registration. The agent then has ten (10) days to log in to their FURLS account and confirm that they are willing and able to serve as your company’s US agent. The email notifying your US agent includes the following language:

“If you are the U.S. Agent for this establishment, select “Yes”, and click “Submit”. If you are not the U.S. Agent for this establishment, select “No”, and click “Submit”. You must confirm you are the U.S. Agent within 10 business days. If you do not confirm that you are the U.S. Agent within 10 days, the system will automatically cancel your Receipt Code and remove the U.S. Agent information associated with the foreign establishment.”

Suppose the agent does not confirm their role within ten business days. In that case, the FDA will automatically email your company that the agent did not confirm their role. If you select a more reliable US agent, you must resubmit the request for the same person or a new person.

If you have additional questions or need a US agent, please contact Medical Device Academy.

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Grant Writing – 5 common mistakes by medical device companies

Leave a Comment / Funding, Grant Writing / By

Would you like to learn the five most common grant writing mistakes medical device companies make when seeking funding?

Why do most medical device companies fail grant writing?

Many medical device companies will face unique challenges in grant writing that can lead to failure. One common issue is a lack of alignment between the company’s objectives and the funding agency’s priorities, as grants often emphasize societal impact or public health benefits over market potential. Companies may also struggle with presenting their proposals effectively, using overly technical language that alienates reviewers or neglecting critical aspects like societal impact and feasibility. Limited resources, such as insufficient time, staff, or grant writing expertise, exacerbate the problem, as does the absence of strong collaborations with research institutions or public health organizations. Additionally, companies frequently underestimate development timelines, submit proposals prematurely, or fail to justify their budgets convincingly.

What are the most successful grants for device companies?

In the United States, prominent grant programs such as those offered by the NIH, NSF, and CDMRP play a significant role in supporting the design and development of medical devices. These agencies release funding opportunities multiple times a year, focusing on medical device innovations. The NIH allocates $1.3 billion annually to fund cutting-edge technologies. Similarly, the NSF receives approximately $190 million each year to support technological advancements across various industries, with a significant emphasis on medical devices, particularly those involving high-risk, high-reward technologies. Meanwhile, the CDMRP, through the Department of Defense, provides funding for medical devices with dual-use applications, targeting both military and commercial markets. These programs offer valuable resources for companies seeking to innovate in the medical device sector.

How often do grant applications get rejected?

unnamed 1 1 Grant Writing 5 common mistakes by medical device companies

The path to success is highly competitive, with a substantial number of proposals facing rejection. Understanding the acceptance rates, common pitfalls, and strategies for improvement can enhance the likelihood of securing SBIR funding.

Acceptance rates for SBIR proposals vary across agencies and phases:

  • Phase I: This initial phase focuses on establishing the technical merit and feasibility of the proposed research. Acceptance rates typically range from 10% to 20%, depending on the agency and specific solicitation. For instance, the National Institutes of Health (NIH) reported a success rate of approximately 25% for SBIR Phase I proposals in recent years.
  • Phase II: Building upon Phase I results, Phase II emphasizes the development of the proposed innovation. Acceptance rates are generally higher, around 40% to 50%, as applicants have already demonstrated initial feasibility. NIH data indicates a success rate of about 44% for SBIR Phase II proposals.

Common Mistakes

The secret to successful grant writing is not just better writing. Timely preparation, ignoring program officer feedback, and matching your technology with an appropriate grant are just a few of the secrets to better grant writing.

Lack of Timely Grant Preparation

The SBIR agencies typically have a specified window every year of when the solicitation topics will be released. Common mistakes companies make is that they do not know when the announcements are made and where to find them. Many companies who miss the announcements fail to prepare in a timely manner to submit a winning grant proposal.

Not Seeking Feedback from Program Officers

During each solicitation cycle, each agency offers support from their program officers. These program officers make their contact information readily available to the public. Program officers are your best friend when you have any questions in regards to the application process and specific topics. Prior to submitting the proposal, you can meet with the program officers to ensure your project is the right fit for the topic you are seeking to apply for.

Not Matching the Technology with the Best-Suited Agency

There are 11 different agencies that partake in the SBIR program with varying focus areas. There is some overlap between these agencies and companies who want to pursue SBIR grants for the first time can miss a better suited opportunity from other agencies. It is important to take all things into consideration from funding amounts, solicitation topics, and award rates. There may be a specific topic from an agency that has a high award rate. However, if your project does not meet the needs for the topic and agency, it does not guarantee that you will be awarded. Hence why speaking to a program officer can guide you to your best-suited topic.

Not Enough Focus on the Business Side

As part of your SBIR proposal there is a heavy emphasis on commercialization, many for Phase II applications. There are lots of companies who have a great team with higher education, amazing scientific breakthroughs. However, they lack the expertise on how to bring this product to the market. A large miss on companies who do not get awarded is due to the inability to communicate in the proposal on how they will bring their product to the market. Through the process, you have to keep in mind that your business plans are just as important to your science.

Not Complying with Solicitation Requirements

At the times of when the solicitations are released, you have access to the documents on the requirements. This includes the format of the proposal, key information that is required and detailed information on the innovation the agency is seeking for the topic. The reason these documents are provided is to be of your resource. Failure to comply with these requirements is almost guaranteeing a loss. The first step to success is reading through the solicitation documents thoroughly and asking questions to experts.

What are the secrets to successful grant writing?

If your company has already won a phase 1 SBIR grant, and you are applying for a phase 2 SBIR, make sure that you obtain written feedback from the US FDA on your regulatory strategy in a pre-submission meeting request before your application deadline.

What can you do now to improve your chances of success?

Being awarded a SBIR award is never a guarantee but there are steps you can take to increase your likelihood of being awarded. 

  1. If you have never written an SBIR proposal, seek expert guidance. There are lots of intricacies and changes that happen for the SBIR program and especially within the agencies themselves. There are many experts who are paid to do the dirty work all day for you! These experts will be able to understand your science and needs for your business. Therefore, eliminating headaches for your company to spend time researching on how to best write a grant proposal, leaving time to focus on your innovative technology that will change society. 
  2. Start from Phase I. Many of the programs offer fast track programs to do a Phase I and Phase II proposal combined. As these are great opportunities to win larger grant funding amounts earlier on, your success is much lower. The fast track programs are a great opportunity if you can show you have the research completed that is needed when applying to a Phase I grant. Get your foot in the door through a Phase I award, win and then pursue a Phase II. This will increase your chances long term with the agency.
  3. Have a strong team. Your company does not need a large team but an experienced one. Those on your team must be fluent in your technology and business. Even if you are just an individual, you must have the background to prove your strong understanding of your technology and business. 
  4. Do not stop trying! Most companies obtain success upon their second submission. Almost all agencies will provide scoring and/or feedback on your proposal. Use this feedback to enhance your next submissions increasing your likelihood of success. 

Grant writing resources

https://www.sbir.gov/

https://baginskiwegner.com/

https://sbirland.com/

About the Author

Alexina Grant Writing 5 common mistakes by medical device companiesAs the Marketing Lead at BW&CO, Alexina holds a Bachelor of Business Administration in Marketing from the University of Houston. With a deep understanding of the grant funding landscape, she drives strategic marketing initiatives that elevate BW&CO’s brand and reach. Fluent in both English and French, Alexina excels at creating and executing campaigns that connect with diverse audiences. Her expertise includes developing content strategies, managing digital marketing efforts, and conducting market research to support business growth.

alexina@baginskiwegner.com

+1 (774) 257-8760

https://www.linkedin.com/in/alexinaesposito/

Baginski Webner (BW & Co)

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Inspection Results: Understanding FDA Requirements

2 Comments / Supplier Quality Management / By /

Learn three valuable tips for efficiently recording your inspection results in medical device manufacturing while remaining FDA-compliant.

What are the best ways to record inspection results?

If you are inspecting a lot of material at an incoming inspection, and the inspection plan calls for inspecting ten samples for length, what is the best way to record the inspection results?

The person who sent me this question also provided three options (read on for better suggestions):

  1. Record the maximum and minimum dimensions
  2. Record all ten measurements in a data collection table
  3. Circle “pass” or “fail” next to each sample number

6 inch caliper Inspection Results: Understanding FDA Requirements

FDA requirements for incoming inspection results

The first method fails to meet the requirement as specified in 21 CFR 820.80(b) because recording only the maximum and minimum dimensions of the ten samples does not include the inspection results for the eight samples in between the extremes. The second method meets the requirements, but this method takes the most amount of time. The third method appears to meet the requirements. However, if you read the FDA requirements more carefully, 21 CFR 802.80(e)(3) states that “[Inspection] records shall include…the results.” If the test method is pass/fail, circling pass or fail makes sense, but if the test measures a dimension, the result should be a measurement. Also, if you have to investigate a complaint or non-conforming product, this dimensional information might be critical to the analysis.

21 CFR 820.80 1024x981 Inspection Results: Understanding FDA Requirements

The FDA has provided an official interpretation of these requirements in the QSR preamble:

“Comment # 147: One comment stated that record keeping this dimensional information might be critical to the analysis if you have to investigate a complaint or non-conforming product is a significant cost factor in the operation of a total quality system and that the revised CGMP regulation should not add cost through duplication of documentation. The comment said recording all quantitative data is inappropriate and of little value.

FDA agrees that unnecessary duplication of documentation should be avoided. They also believe that the Quality System Regulation requires the minimum documentation necessary to ensure that safe and effective devices are designed and produced. FDA similarly believes that maintaining records of results of acceptance activities is imperative to ensure that non-conforming product is not inadvertently used or distributed. FDA has, however, deleted from Sec. 820.80(a) the requirement for recording the results of inspections and testing, because Sec. 820.80(e) requires that the results of acceptance activities be recorded. The requirement in Sec. 820.80(a) was, therefore, unnecessary. Further, the regulation does not specify quantitative data, but simply requires that the results be recorded.

The FDA believes that it is essential for the manufacturer to maintain records which provide evidence that required acceptance activities were completed. These records must clearly show whether the product has passed or failed the acceptance activities according to the defined acceptance criteria. If a product fails to pass acceptance activities, you must identify the product as a non-conforming product and conduct an investigation. If the acceptance records are not clear about how the product failed, then the manufacturer may end up duplicating the acceptance to perform appropriate investigations.”

Here are three other methods that can save you time and add value.

Method 1: Run Charts

If you create an inspection results form that is in the form of a “Run Chart,” then you can put an “X” on the appropriate location of the Run Chart for each sample (see Chart 1 below). It is less time-consuming to write an “X” than the actual value. However, if you need to conduct an investigation, you can convert the “X” into a quantitative number and enter the values into a spreadsheet or statistical analysis software (e.g., Minitab). Also, inspectors and supervisors can visually glance at a Run Chart and determine if the measurement is “in control” or “out of control.” This is done by marking the upper and lower specifications on the Run Chart. Over time, alert limits can be established as a preventive action, as well. You can also use this data as a rationale for eliminating certain inspections, reducing sampling, qualifying suppliers, and even converting a part from statistical sampling to a “dock-to-stock” inspection.

Chart 1 for Inspection Blog Inspection Results: Understanding FDA Requirements

One disadvantage of Method 1 is that it takes time to create inspection forms, and the forms need to be maintained as a controlled document, with the drawings for each part–as paper records or electronically. Therefore, I recommend that companies create a quality plan that calls for creating one of these charts every time an NCR is initiated for a part. That way, you only are creating this type of chart for parts that are found to be out of specification. This approach allows you to implement the work over a reasonable period of time.  You can also habitually review historical data when you have an NCR that does not already have a Run Chart created.

Method 2: Automating Inspection Results

If you have critical inspection activities and a high volume of parts to inspect, you can automate recording measurements and performing data analysis. This can be done by purchasing digital inspection devices that automatically send the values to a computer system. Devices with this capability only require pressing a button to record the value, and the computer system will often provide the inspector with the sampling plan for each lot automatically. These sophisticated software systems require validation, giving manufacturers extensive real-time data on supplier performance, in-process inspection, and final product acceptance. The primary disadvantage of this method is the cost of installation and set-up.

Method 3: Pass/Fail with Go/No-Go Gauges

If a supplier can make good parts with high certainty, you may not need routine monitoring of part dimensions. In this case, you can reduce your inspection time by using a “go/no-go” gauge for critical attributes instead of measuring the dimensions. This type of gauge would be ideal if the tolerance for a part with a tolerance of +/- 3 mm. The length of a part can be verified to be between two lines, representing the upper and lower specifications for the tolerance. This method can also be used for precise tolerance if magnification is used. Still, performing a gauge R&R study of any go. If this type of inspection is used, you can use an inspection record that only records pass/fail. However, this inspection method is not recommended for parts that are occasionally out of conformity because re-measurement of parts will be necessary to investigate non-conforming products.

Statistical Techniques

The most significant advantage of methods one and two is that they facilitate statistical data analysis. Chart one shows too much variation for the tolerance of 6.50 mm to 6.60 mm. Some companies qualify suppliers for a new part by establishing a threshold for a minimum Cpk value (i.e., process capability coefficient). A typical Cpk minimum is 1.33. Often, the company will require that suppliers provide data for 100% inspection of the initial production lot. This data is then used to create a sampling plan based on the likelihood of parts being out-of-specification. High-risk dimensions might require 99.5% confidence, medium-risk dimensions might require 99% confidence, and lower-risk dimensions might require 95% confidence. Each confidence level corresponds to a different Cpk value. It is not possible to do this type of analysis for Method 3.

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EO Sterilization – When is requalification required?

18 Comments / Process Validation / By / ,

This article discusses the need to requalify EO sterilization validation and explains what is included in our EO sterilization procedure.

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EO Sterilization Cycle EO Sterilization When is requalification required?

Do you need an EO sterilization procedure?

ISO 11135-1 is the international standard for sterilization validation for Ethylene Oxide (EO or EtO) sterilizers. The standard describes multiple methods of sterilization validation: 1) overkill approach, 2) single lot release, and 3) parametric release. The overkill approach is the most common method for validation of your EO sterilization process. The overkill approach is the method recommended by Medical Device Academy’s EO sterilization procedure. If you use a contract sterilizer, the sterilizer will already have completed an Installation Qualification (IQ) and an Operational Qualification (OQ). You must complete a Performance Qualification (PQ) for your product. A typical PQ for initial process validation consists of the following:

  1. Process Challenge Device (PCD) validation
  2. Bioburden measurement
  3. EO residual measurement (as per ISO 10993-7)
  4. Fractional Cycle (at least one)
  5. 3 Half Cycles
  6. 3 Full Cycles (or 1 Full Cycle, if performed in parallel with the three half-cycles)

Purchase the EO Sterilization Validation Procedure (SYS-031) – $299

EO Sterilization Cycle 1 150x150 EO Sterilization When is requalification required?
SYS-031 EO Sterilization Validation Procedure
This procedure was updated in 2024 to include recent versions of various standards and to incorporate changes to make the procedure consistent with other procedures in Medical Device Academy's turnkey quality system. The updated procedure defines the requirements for ethylene oxide (EO) sterilization validation and revalidation/requalification outsourced to a contract sterilizer.
Price: $299.00

What do MPQ and PPQ mean?

In the ISO 11135 standard, steps #4 and #5 listed above are referred to as the microbial performance qualification (MPQ), while #6 is the physical performance qualification (PPQ). For a successful MPQ, some PCDs must be non-sterile after a fractional cycle to demonstrate the ability to recover the BI challenge organism. After a half-cycle, however, all biological indicators should be sterile.

What are BIs, CIs, and PCDs?

To avoid destructive testing, EO sterilization processes verify sterility by using process challenge devices (PCDs) located outside the device’s primary and secondary packaging. PCDs are more challenging to sterilize than the native bioburden on your device, and the PCDs can be quickly removed from a sterilized pallet without disturbing the wrapping of the pallet. PCDs are also referred to as external biological indicators (BIs). Biological indicators are used internally and externally to your primary sterile barrier packaging during the EO sterilization validation process, but only external BIs are used during routine EO sterilization. You can create your own customized PCD for devices that are especially difficult to EO sterilize (e.g., stopcocks), but you must verify that the PCDs are more challenging to kill than an internal BI in a fractional cycle. Commercially available PCDs often incorporate a chemical indicator (CI) into the label or the cap of the PCD, and some are incorporated into sophisticated tracking software with automatic incubators that read a barcode on the PCD label and detect the results of incubating the BIs in media. These systems are rapid, self-contained BIs that provide validated results in hours, minutes, or seconds.

BIs CIs and PCDs 1024x314 EO Sterilization When is requalification required?

Outsourcing EO sterilization and requalification

Ethylene oxide sterilization is usually outsourced to a contract sterilizer due to the environmental and safety requirements of working with EO. The contract sterilizer will provide a generic protocol for full validation that is compliant with ISO 11135-1. However, the ISO 11135-1 standard requires that manufacturers perform annual process reviews to evaluate the need to requalify/re-validate the sterilization process. Assuming there have been no problems or changes to the product or EO sterilization process, re-validation is not required at the end of the first year. However, companies are required to re-validate the process after two years–even if there have been no changes.

Longer frequencies for requalification cycles

If there have been no changes to the sterilization process, the product, or the biological indicators, then the manufacturer can use this as a justification for waiting until two years have elapsed before re-validating the ethylene oxide sterilization process. Also, there should be no evidence of sterilization failures or other problems with the validated process. However, that alone is not necessarily enough to justify extending the duration between validations beyond two years. Companies that justify intervals of three or more years have multiple products that use the same EO sterilization process.

In this case, the manufacturer may alternate annually between three, four, or even five different product families that are using the same EO sterilization process. In this case, one of the product families is being re-validated each year or every two years, but the interval between validations for any one product family is longer. This approach is valid if the products are made of similar materials and use the same EO sterilization process. If you only have one product, then you need to re-validate the sterilization process once every two years to verify the process remains active.

Minimum revalidation requirements

When you determine that it is time to re-validate your ethylene oxide sterilization process, you need to perform the following tests to meet the minimum requirements of ISO 11135-1:

  1. Re-validation of PCD
  2. Bioburden measurement
  3. EO residual measurement
  4. 1 Half Cycle
  5. 1 Full cycle (to verify the EO residuals are acceptable)

The purpose of #1 is to verify that the resistance of internal BIs used in the half-cycle is more resistant than the product bioburden. The purpose of #2 is to verify that bioburden levels have not changed, and the type of organisms has not changed. In practice, most companies monitor bioburden quarterly, and therefore this step should be routine. Step 3, EO residual measurement, should be performed to verify that there have not been minor changes to the product or process that would increase the concentration of EO, Ethylene Chlorohydrin (ECH), or Ethylene Glycol (EG) beyond the Tolerable Contact Limit (TCL). The purpose of this third test is to prevent localized irritation caused by residual chemicals from the ethylene oxide sterilization process.

Step 4 of the re-validation is intended to verify that a full injection of EO is more than required to kill the bioburden present for the number of injections required for a half-cycle.

The final step is to perform a full cycle. The product from the full cycle is typically used for EO residual testing. Any product from the full cycle that is not used for testing can be sold after sterility testing is complete.

Partial loads & rework

If you occasionally sterilize loads that are less than “full loads,” then you need to ensure that you have validated a minimum load or a specific partial load (e.g., half-pallet, instead of a full pallet). In the case of a partial or minimum load, you may identify different locations in your load that is considered “worst-case.” These are the locations that had PCDs that were not sterile in a fractional cycle.

Most companies do not have concerns about the cost of the actual sterilization runs during re-validation, and biological indicators are typically less expensive than boxes of products. The primary cost concern for re-validation is any product that must be scrapped. Therefore, many companies will accumulate dunnage (i.e., empty packaging or scrap product) over time to fill a sterilizer. This dunnage may be used to ensure that every load is full, or it may only be used for re-validation.

Another alternative to using dunnage for re-validation is to validate a rework process. Any product exposed to a fractional or half-cycle can be re-sterilized in a full cycle. To justify the commercial use of that product, a company needs to validate that the product will not be damaged by exposure to two full cycles. One of the key acceptance criteria for rework is the EO residual levels in the product. However, the manufacturer also needs to determine if any product deterioration by a second exposure to EO would affect performance.

Other EO sterilization considerations

Many companies do a poor job of reviewing the potential impact of changes to a product, packaging, and biological indicators. Ideally, initial validation involves different lots of product, packaging, and biological indicators to assess lot-to-lot variability. However, the packaging and biological indicators often consist of only one lot during validation. Minor changes to the tolerances may reduce the amount of ethylene oxide that is absorbed by the product or change the resistance of the biological indicator to the sterilization process. Therefore, these minor changes should trigger a re-validation.

Changes in suppliers with the same specification can also be difficult to evaluate. If a component is made of a material that absorbs EO, then it may be recommended to re-validate sterilization for any changes to suppliers of those components. Re-validation in these cases may consist of only a fractional cycle, half cycle, or full cycle to evaluate risks associated with the change.

Who should evaluate the need for EO sterilization requalification?

Evaluating the need for re-validation should include inputting three types: 1) microbiological, 2) materials, and 3) performance. To make these assessments, typically, a cross-functional team is needed. Someone responsible for design and development can assess the performance impact of changes. A materials engineer is generally needed to assess the interaction between components and EO. Finally, a microbiologist is needed to confirm that there is no impact related to biological indicators or bioburden.

Bioburden Failure Analysis Webinar EO Sterilization When is requalification required?Additional Sterilization Training

Medical Device Academy has two webinar recordings related to sterilization validation:

If you need assistance with sterilization validation or bioburden failure analysis, please schedule a call with us by visiting our Contact Us page. 

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