The 3rd edition of ISO 14971, the risk management standard for medical devices was released on December 16, 2019.
2019 Risk Management Process – 3rd edition
In October of 2018, I wrote a blog on the draft version of ISO 14971 3rd edition of the risk management standard for medical devices. That article explained the differences between the different versions of the ISO 14971 standard (i.e., 2000, 2007, 2009, and 2012). I also explained what changed between ISO 14971:2007 and ISO/DIS 14971:2018. The final 2019 version of ISO 14971 3rd edition is now available.
The changes proposed in the draft included subtle changes to the names of the processes and a minor adjustment to the numbering of the clauses. Many of the annexes were also moved to ISO/TR 24971 guidance–which was released in 2020. The draft did not, however, result in a change in the overall process of risk management.
All of the changes that were discussed in my 2018 review were maintained in the final 2019 version that was released, but the ISO/TR 24971 guidance was not released at the same time as the committee had hoped for.
There are not any surprises in the 3rd edition (i.e., 2019 version). Therefore, I plan to wait until the ISO/TR 24971 guidance is released and then prepare a new blog specific to the guidance. If you are interested in training on the ISO 14971:2019 standard, the training I recorded on October 19, 2019, provides an excellent overview of these changes and highlights some of the challenges that you will encounter when trying to harmonize your risk management procedure between the ISO 14971:2019 standard and Regulation (EU) 2017/745.
This is a lot of information to absorb. Therefore, I recommend purchasing the October 2019 webinar and your copy of the ISO 14971:2019 standard from AAMI. Anyone that has already purchased either the webinar or the procedure will receive an email offering them a discount on this new bundle that credits them for their previous purchase. If you have purchased both, you will receive credits for both purchases. Just think you can watch the video and read the new version of the standard while you are working out at the gym in January. Learn and burn!
This article explains how to write your classification recommendation for a De Novo Classification Request using a risk-based approach.
“Automatic Class III Designation” does not mean that your device is a Class III device. That phrase means that the device is new, and therefore it will be automatically classified as Class III until a company submits a De Novo Classification Request. You and your company, not the FDA, should make the classification recommendation and propose the regulatory pathway for a new device. Submitting a 513g request is an option, but a 513g request involves paying the FDA money to write a classification recommendation. The FDA will always be more conservative in their assessment than the manufacturer.
Although no FDA guidance explains how to write a classification recommendation, companies have been writing these documents for years–for Technical Files. Most countries have risk-based classification rules, while the FDA’s product classification database is centered upon precedents and adjusted over time by historical trends of adverse events and recalls. Therefore, you should write a classification recommendation for the FDA that is focused on a documented risk assessment. Your approach will also need to be modified to include classification information for similar indications for use and technological characteristics that are already established in the US market.
Most Common Mistakes in Writing a Classification Rationale
Many people mistakenly write a short classification rationale for a technical file, which simply states which classification rule applies and why. Although this approach is acceptable for a Declaration of Conformity, you must provide a comprehensive classification rationale in your technical file. First, you need to make sure that there is only one classification rule that applies. For example, classification rules fall into four general categories:
The software was haphazardly added to the active devices category until recently, and special rules were created to address emerging areas of interest and concern. Therefore, most active devices have a second rule that applies regarding the invasive nature of the device–or lack thereof. In order to write a comprehensive classification rationale, you need to review each classification rule and document your explanation for why it applies or does not apply to your device.
A Classification Recommendation Compares Indications for Use
The FDA does have classification rules, but the rules are not 13 numbered items in the Code of Federal Regulations (CFR). The FDA expects a risk assessment of comparing your device with existing devices on the US market. The basis of comparison should be: 1) the indications for use and 2) the technological characteristics. First, you should identify other devices that have similar indications for use. For example, a device intended for home use or over-the-counter (OTC) use represents a higher risk to patients and users than a device intended for prescription use only. Patients may fail to identify contraindications for a device properly, or the lack of formal medical training may result in use errors that would not occur when a physician uses the same device.
Other aspects of indications for use that impact the risk assessment are the part of the body where your device will be used and the duration of use. For example, implants are at higher risk than non-implants, because implants are in contact with the body for a much longer period of time. Implants can also expose the body to systemic risks, while a surface contacting device is likely only to have a localized effect. Degradation of implants also exposes the body to small particles, with more surface area, that can travel from one part of the body to another.
If your device is used for life support, the device will also be considered at higher risk than devices that are not required for life support. If your device is the only device used for diagnosis, this also represents a higher risk than a device that acts as an adjunct to other devices. Finally, if your device is an accessory to other devices that are high risk, your device may be considered a higher risk as well–especially if it controls the higher risk device.
In your analysis, you need to identify devices that are already on the US market that have similar indications for use. Usually, those devices will be Class II devices. However, if some of those devices are Class I or Class III, you will need to be more careful with how you differentiate your indications for use from those other devices.
A Classification Recommendation Compares Technological Characteristics
When comparing technological characteristics, the following aspects should be considered: 1) materials, 2) design, 3) energy source, and 4) other design features. For example, absorbable materials are generally considered at higher risk than devices that are not absorbable. Sterile devices are generally at higher risk than non-sterile devices because the failure of the sterilization process or the package integrity can result in serious infections and death. Devices that are electrically powered are usually considered at higher risk than devices that are not powered. Finally, software-controlled devices that provide feedback control are considered at higher risk than a device that does not have feedback control. Each technological characteristic also represents a different category of hazard. Hazard categories are listed in Table E1 of Annex E in ISO 14971:2007. These include chemical, biological, electrical, radiation, etc.
Once you have identified the Classification of other devices with similar indications for use and technological characteristics, you need to estimate the risks for each hazard identified. This involves more than just listing hazards and assigning scores for severity and probability for the occurrence of harm. Severity should consider the type of injuries, the number of injuries, and the duration of harm. Probability should consider the frequency of events (P1), and the probability of events resulting in injury (P2). These risk estimates also require clinical data.
In the end, you prepare a benefit/risk analysis for your device. This is much more than a statement that the benefits outweigh the risks. You need to identify the clinical benefits of your device when compared to alternative treatments. You also need to analyze risks relative to alternative treatments. You will need to prepare this as a summary of risks–not a list of hazards. Ultimately, your benefits should be equivalent to the benefits of existing devices on the market or better, and the risks should be equivalent to existing devices on the market or less.
Examples of Classification Recommendation
Eight different medical devices are legally marketed in the USA for weight loss or weight management:
The indications for use for these products are similar, but not identical. Plenity is indicated for patients with a BMI of 25 – 40 kg/m2. In comparison, ORBERA is indicated for patients with a BMI of 30-40 kg/m2, and AspireAssist is indicated for patients with a BMI of 35-55 kg/m2. All three of these indications have overlapping BMI ranges. However, the clinical benefits to a person with a BMI of 25 kg/m2 are not the same as the clinical benefits to a person with a BMI of 40 or 50 kg/m2. Therefore, these minor differences in BMI can have a significant impact on the benefit/risk analysis used for a De Novo approval decision and the Classification (i.e., Class II or Class III) determined by the FDA.
The only two weight management devices that received the approval of the De Novo Classification Request had very different technological characteristics from the other six devices. All six Class III, PMA devices, are implants, while the Class II devices are not implants. The risks associated with implants are much greater than with non-implants. The risk of implants breaking or leaking, and the difficulty in removing an implant, are just two of the considerations that must be evaluated in deciding whether an implantable device should be a Class II or Class III device.
This article explains what a 513g request for information is for, how to prepare a 513g request, and when to submit the request to the FDA.
What is a 513g?
A “513g” is a request for classification information from the FDA. The reference is to a section of the Food, Drug & Cosmetic Act. The purpose of the submission is to ask the FDA what product classification would be most appropriate for your device and what the appropriate regulatory pathway will be. The FDA is required by the regulation to provide a written response within 60 days of receiving the 513g request. The submission also requires payment of an FDA user fee that is eligible for a small business discount.
In a 2015 blog case study, I explained why I feel that the submission of a 513g request for information from the FDA is usually a waste of money. Since that time, our firm has prepared only a few 513g requests. There are a few good reasons for submitting a 513g request. For example, if you are developing a device that might be considered exempt under the 21st Century Cures Act as a general wellness product, your firm might submit a 513g request to verify that premarket notification is not required for your device.
When should a 513g request for information be submitted?
Usually, device companies ask me if I think they should submit a 513g or a pre-submission request to answer questions about the testing requirements. Often the device has a known product classification code requiring a 510(k) submission. Sometimes, there will even be a Special Controls Guidance document available for the product classification. In these situations, a 513g is entirely unnecessary. I can understand the difficulties that people experience when trying to navigate the FDA product classification database because the database does not use modern natural language search algorithms like Google. However, a greater concern is that most companies are asking this question after they have already started the development of their device, and just before they plan to initiate design verification testing. This is very late in the design process–even a little late to be conducting a pre-submission request. Your 513g submission should be during the beginning of your design project (i.e., during the concept or feasibility phases of design) to verify the regulatory pathway.
How to prepare a 513g
For any device submission, including a 513g, you need to prepare a detailed device description for the FDA. Many companies find this difficult. Therefore, we provide a template for the device description. For our 513g templates, we simplified the device description we use for a pre-submission request. We also identified the required sections with an asterisk. The resulting template is shorter and easier to complete.
In addition to the device description, we recommend that you include a copy of the draft labeling and instructions for use (IFU) with each device submission. A pre-submission does not require draft labeling, but a 513g classification request does require draft labeling to ensure the FDA understands your intended use for the device. Therefore, we provide templates for companies to prepare these drafts.
The last important piece of your 513g classification request is your cover letter. The most important parts of the cover letter, are the questions you ask the FDA about your device. We provide some typical questions that would be asked in a 513g submission, but you will probably have one or more unique questions you want to ask, which are specific to your device and indications for use.
If you need to submit a 513g classification request, you can learn more about FDA content requirements by watching our 513g request webinar. If you complete our subscription form for the webinar, you will also receive access to our complete set of 513g templates. The templates for the device description, draft label, and draft instructions for use (IFU) are also the three templates we provide to new clients that will be submitting a pre-submission meeting request, a 510k submission, or a De Novo Classification Request.
The article describes the most critical part of the preparation for a De Novo Classification Request, the De Novo pre IDE meeting.
There are two critical differences between a De Novo classification request and a 510k submission. First, 510k clearance is based upon a substantial equivalence comparison of a device and a predicate device that is already marketed in the USA, while a De Novo classification is based upon a benefit-risk analysis of a device’s clinical benefits compared with the risk of harm to users and patients. Second, 510k clearance usually does not require clinical data to demonstrate safety and efficacy, while a De Novo classification request usually does require clinical data to demonstrate safety and efficacy. Therefore, it makes sense that the two most common challenges for innovative medical device companies are: 1) learning how to write a benefit-risk analysis, and 2) designing a clinical study. Success with both of these tasks can be significantly improved by requesting a De Novo pre IDE meeting with the FDA.
Benefit-Risk Analysis Questions to Ask During a De Novo pre IDE Meeting
Most device companies are only familiar with substantial equivalence comparisons–not a benefit/risk analysis. The statement “the benefits outweigh the risks” is not a benefit/risk analysis. The European MDD requires a benefit/risk analysis (mentioned eight times), while Regulation (EU) 2017/745 mentions benefit/risk 69 times. Despite the obvious increased emphasis on benefit/risk analysis in the new EU Regulations, the new ISO 14971 standard that is expected to be released next month still does not require a benefit/risk analysis for all risks as required by the regulations. The international standard also does not clearly explain how to perform a benefit/risk analysis. The best explanation for how to perform a benefit/risk analysis is provided in the FDA guidance.
In addition to reading that guidance, you will need to systematically identify all of the current alternative methods of treatment, diagnosis, or monitoring for your intended use. Therefore, you should ask in a pre-submission meeting if there are any additional devices or treatments that the FDA feels should be considered. You should review each of the alternative treatments for clinical studies that may help you in the design of your clinical study. You should carefully review the available clinical data for alternative treatments to help you quantify the risks and benefits associated with those treatments too. Finally, you should consider whether one or more of these alternative treatments might be a suitable control for your clinical study. Ideally, your clinical study design will show that the benefits of your device are greater, and the risks are less, but either may be enough for approval of your classification request. If you think the risks of your device are significantly less than alternative treatments, then ask the FDA about using this factor as an endpoint in your study design.
Clinical Study Design Considerations
Ideally, there is already a well-accepted clinical model for assessing efficacy for your desired indications. This means multiple, published, peer-reviewed journal articles. You might have a better method for evaluating subjects, but don’t propose that method instead of a “gold standard.” If you feel strongly that your method is more appropriate, propose both methods of evaluation. You also need multiple evaluators who can be objective. Randomization, blinding, and monitoring of clinical studies is critical to ensure an unbiased evaluation of clinical results.
You also need to design your study with realistic expectations. Murphy’s law is always active. That means, “things will go wrong in any given situation if you give them a chance.” Therefore, you must avoid optimism and devise methods for detecting errors quickly. This is why electronic data capture systems and eSource is preferred for data collection instead of the manual collection of data on paper case study forms. Not only does it reduce errors in data collection, but it also facilitates remote monitoring of clinical sites. This includes asking questions that are open-ended or quantitative–instead of Yes/No questions or qualitative evaluations that encourage subjectivity. You can always anticipate every mistake that will be made, and open-ended questions often capture essential data that would otherwise be lost. Asking the quantitative questions also will provide you with additional data you can analyze, which may reveal unexpected relationships or help you to explain unexpected results. To help facilitate the development of these questions, try asking yourself how you could detect an error for each data point you are collecting. Then add a detection mechanism to your data collection plan wherever and whenever you can.
Goals of De Novo pre IDE Meeting
A pre-IDE meeting is not typically your first pre-submission meeting with the FDA. Usually, your first pre-submission meeting is to verify that the FDA agrees that the regulatory pathway is a De Novo classification request rather than a 510(k) submission. Hopefully, you also were able to review your overall testing plan with the FDA during your first pre-submission meeting. You may have even reviewed a clinical synopsis with the FDA during your initial pre-submission meeting. During the pre-IDE meeting, your goal is to finalize your clinical study protocol. That doesn’t mean that the FDA should agree 100% with your draft protocol. You want positive and negative feedback on all aspects of your protocol before the IDE submission. During the IDE review, changes will be made.
The most important aspects of getting right before the IDE submission are the fundamentals. Most of my De Novo clients feel that a control group is not possible, because they think that test subjects will know when a sham is used. However, trying to avoid a control group is nearly impossible. The most important factors for why a control group is needed are:
you need to minimize differences between experimental and control subjects, but you can’t do that if you are relying on data from other clinical studies
you also need to ensure that your evaluation methods are identical, which is nearly impossible when performed by different people, at different facilities, using slightly different protocols
Another area of weakness in most draft clinical protocols is the method of evaluation. Specifically:
Who is doing evaluations?
Which endpoints are important?
When are your endpoints?
What are your acceptance criteria?
The last area to consider in a pre-IDE meeting is your statistical plan. You need a statistical plan, but the statistical analysis seldom appears to be the reason for the rejection of clinical data. The reason is that changes can be made to your statistical analysis of data after the study is completed, but you can’t change the data once the study is over. The FDA is now accepting adaptive designs that allow the company to analyze data during the study to recalculate the ultimate sample size needed based upon actual data rather than initial assumptions.
This article explains the FDA regulations related to private labeled devices that are already 510k cleared and distributors want to import.
This article was initially inspired by a question asked on the Medical Devices Group website hosted by Joe Hage. Companies often ask about how to private labeled devices in the USA, because they are unable to find anywhere in the FDA regulations where private labeling of the device is described. The reason for this is because the FDA regulations for devices allow for the labeling to identify the distributor only—without any mention of the OEM manufacturer on the label. In contrast, most other countries have “own-brand labeling” regulations or regulations for private labeling devices. It is also important to remember that the FDA only approves devices through the pre-market approval (PMA) pathway. All other devices fall into one of three categories: 1) 510k exempt, 2) 510k cleared, or 3) De Novoclassification request approved. Devices that fall into the third category will subsequently fall into category 1 or 2 after the FDA approves the classification request.
Questions about the private labeled devices process for FDA
Our distribution company is interested in getting a private labeled devices agreement with an OEM to sell a Class II medical device in the USA. The OEM has 510(k) clearance, and the only product change will be the company’s name and address on the label. There will be no change to the indications for use. Please answer the following questions:
Is it legal to eliminate all mention of the OEM from the device labeling?
Who is responsible for complaint handling and medical device reporting? OEM or private-labeled distributor?
What is the process to get this private label for the Class II device?
How can our distribution company avoid paying the FDA user fee?
Answer to the first question about private labeled devices
The FDA is unique in that they allow either the distributor or the manufacturer to be identified on the label, but both are not required. Therefore, if Joe Hage were the distributor, and you were the manufacturer, there are two legal options for the private labeled device: 1) “Distributed by Joe Hage”, or 2) “Manufactured for Joe Hage.”
The manufacturer is not required to be identified on the label. However, the OEM must be registered and listed with the FDA. If the OEM is outside the USA, then the distributor must register and list with the FDA as the initial importer and reference the K number when they complete the FDA listing. There is no approval required by the FDA. You will need a quality agreement defining the roles and responsibilities of each party, but that is all.
Answer to the second question about private labeled devices
The quality agreement must specify which company is responsible for complaint handling (21 CFR 820.198) and medical device reporting (21 CFR 803). In this situation, the OEM is the specification developer, as defined by the FDA. Therefore, the OEM will be responsible for reporting and execution of recalls. Therefore, even if the distributor with a private label agreement is identified as the “complaint file establishment,” the OEM will still need to obtain copies of the complaint information from the distributor, and determine if medical device reporting and/or corrections and removals are required (i.e., recalls).
Answer to the third question about private labeled devices
There is no formal process for “getting a private label.” The entire private label process is negotiated between the distributor and the OEM with no involvement of the FDA. However, in the listing of devices within the FDA FURLS database, all brand names of the device must be identified. Therefore, the OEM will need to add the new brand name used by the distributor to their listing for the 510(k) cleared product. However, the FDA does have the option to keep this information confidential by merely checking a box in the device listing form.
Answer to the fourth question about private labeled devices
If the distribution company is the initial importer of a device into the USA, then the distributor must be registered with the US FDA as the initial importer, and the distributor will need to pay the FDA user fee for the establishment registration. That user fee is $5,236 for FY 2020, and there is no small business discount for this fee. The only way to avoid paying the user fee is to have another company import the device, who is already registered with the FDA, and to distribute the product for that company. I imagine some logistics brokers might be acting as an initial importer for multiple distributors to help them avoid paying the annual FDA user fee for establishments. That company might also be providing US Agent services for multiple OEMs. However, I have not found a company doing this.
Is private labeling of device legal in the USA?
The FDA is unique in that they allow either the distributor or the manufacturer to be identified on the label, but both are not required. Therefore, if Joe Hage were the distributor, and you were the manufacturer, there are two legal options for the private label: 1) “Distributed by Joe Hage”, or 2) “Manufactured for Joe Hage.”
Who must register, list, and pay user fees for medical devices?
This question is frequently asked, and the table with the information was not visible on my mobile browser. Therefore, I copied the table from the FDA website and posted the information in the image below. The information is copied directly from the FDA website:
Registration and Listing Requirements for Domestic Establishments
Registration and Listing Requirements for Foreign Establishments
For products that are manufactured outside the USA, and imported into the USA, the initial importer is often the company identified on the label. There are two typical private labeling situations, but other possibilities exist:
If the initial importer owns the 510(k), then the manufacturer outside the USA is identified as the “contract manufacturer,” and the initial importer is identified as the “specifications developer.” Both companies must register their establishments with the FDA, and there needs to be a quality agreement between the two companies defining roles and responsibilities. The contract manufacturer outside the USA is not automatically exempt from reporting requirements and complaint handling. The contract manufacturer outside the USA may decide to label the product as a) “Manufactured by”, b) “Manufactured for”, or c) “Distributed by.” Options “a”, “b” and “c” would list the importer’s name because they own the 510(k), and they are the distributor. This situation often occurs when companies outside the USA want to sell a product in the USA, but they do not want to take on the responsibility of obtaining 510(k) clearance. These firms often believe this will exempt them from FDA inspections, but the FDA is increasingly conducting FDA inspections of contract manufacturers due to this private label situation.
If the manufacturer owns the 510(k), then the manufacturer outside the USA is identified as the “specifications developer” and the “manufacturer,” while the initial importer will be identified as the “initial importer.” The importer may also be specified as the complaint file establishment and/or repackager/relabeler in the FDA registration database. The manufacturer outside the USA will not be able to import the device into the USA without identifying an initial importer in the USA in the FDA FURLS database. The manufacturer outside the USA may decide to label the product as a) “Manufactured by”, b) “Manufactured for”, or c) “Distributed by.” Options “b” and “c” would list the importer’s name, while option “a” would list the manufacturer’s name. This situation often occurs when US companies want to be the distributor for a product made outside the USA, and the company wants a private labeled product. This also happens when the OEM wants the option to have multiple US distributors.
In both of the above private-label situations, the non-US firm must have a US Agent identified because the company is located outside the USA. The US Agent may be the initial importer, but this is not required. It could also be a consulting service that acts as your US Agent. The US Agent will be responsible for receiving communications from the FDA and confirming their role as US agents each year when the registration is renewed. Medical Device Academy offers this service to non-US clients we help obtain 510(k) clearance.
A Korean company, with a US distribution subsidiary, would like to private label a medical device with an existing 510(k) owned by another company in their name. Does the Korean company need a contract in place before private labeling? Does the US subsidiary and/or the Korean parent company need to be registered in the USA prior distribution of the private-labeled version of the device in the USA?
Rob’s response: Initially, it was unclear from the wording of the question as to whom is the 510(k) owner, which company will be on the label, who is doing the labeling, and who is doing the importing to the USA. The person asking Joe Hage this question tried clarifying their question via email, but we quickly switched to scheduling a phone call using my calendly link. I have reworded the question above, but here are some of the important details I learned during our phone call:
The person asking was already acting as the relabeler, repackager, and they were distributing the product in the USA. This person’s company is also registered with the FDA.
The device is 510(k) cleared by another US company, and there is no need to worry about the complications of an initial importer being identified for a product manufactured in the USA.
In this situation, the relabeler/repackager can relabel the product for the Korean company’s US subsidiary as long as there is a quality agreement in place for all three parties (i.e., relabeler, distributor, and manufacturer). There is no need for the Korean parent company to register with the FDA. There is no need for a new 510(k) submission, and the US subsidiary does not need to register with the FDA—as long as the quality agreement specifies that the US subsidiary will maintain records of distribution, facilitate recalls if required, and notify the manufacturer of any potential complaints and/or adverse events immediately. The manufacturer with 510(k) clearance will be responsible for complaint handling, medical device reporting, and execution of recalls according to the agreement. The relabeler will be responsible for maintaining records of each lot of product that is relabeled for the US subsidiary, and the relabeler must maintain distribution records that link the original manufacturer’s lot to the lot marked on the relabeled product.
If you have questions about the private labeling of your device, please contact us.
This article explains how you should be integrating usability testing into your design control process–especially formative usability testing.
Why you should be integrating usability testing into the design
We recently recorded an updated usability webinar and released a usability procedure (SYS-048) with help from Research Collective–a firm specializing in human factors testing. After listening carefully to the webinar, and reading through the new usability procedure, I felt we needed to update our combined design/risk management plan to specify formative testing during phase 3 and summative (validation) testing during phase 4 of the design process. This is necessary to ensure your usability testing is interwoven with your risk management process. Integrating usability testing into all phases of your design process is critical–especially design planning (phase 1), feasibility (phase 2), and development (phase 3).
Integrating usability testing into your design plan helps identify issues earlier
During the usability training webinar, Research Collective provided a diagram showing the various steps in the usability engineering process. The first five steps should be included in Phases 1 and 2 of your design process. Phase 1 of the design process is planning. In that phase, you should identify all of the usability engineering tasks that need to be performed during the design process and estimate when each activity will be performed. The first of these usability activities is the identification of usability factors related to your device. Identifying usability factors is performed during Phase 2 of your design process before hazard identification.
Before performing hazard identification, which should include identifying potential use errors, you need to identify five key usability elements associated with your device:
prospective device users during all stages of use must be defined
use environments must be identified
user interfaces must be identified
known use errors with similar devices and previous generations of your device must be researched
critical tasks must be described in detail and analyzed for potential use errors
Defining users must include the following characteristics: physical condition, education, literacy, dexterity, experience, etc. Use environment considerations may consist of low lighting, extreme temperatures or humidity, or excessive uncontrolled motion (e.g., ambulatory devices). User interfaces may include keyboards, knobs, buttons, switches, remote controllers, or even a touch screen display.
Often the best reason for developing a new device is to address an everyday use error that is inherent to the design of your current device model or a competitor’s product. Therefore, a thorough review of adverse event databases and literature searches for potential use errors is an important task to perform before hazard identification. This review of adverse event data and literature searches of clinical literature are key elements of performing post-market surveillance, and now ISO 13485:2016 requires that post-market surveillance shall be an input to your design process.
Finally, the step-by-step process of using your device should be analyzed carefully to identify each critical user task. User tasks are defined as “critical” for “a user task which, if performed incorrectly or not performed at all, would or could cause serious harm to the patient or user, where harm is defined to include compromised medical care.” Not every task is critical, all critical tasks must be identified, and ultimately you need to verify that each critical task is performed correctly during your summative (validation) usability testing.
Evaluating Risk Control Options – Formative Usability Testing in Phase 3 (Development)
Once your design team has conducted hazard identification and identified your design inputs (i.e., design phase 2), you will begin to evaluate risks and compare various risk control options. Risk control option analysis requires testing multiple prototype versions to assess which design has the optimum benefit/risk ratio. This is an iterative process that involves screening tests. For any use risks you identify, formative usability testing should be performed. Sometimes the risk controls you implement will create new use errors or new risks of other types. In this case, you must compare the risks before implementing a risk control with risks created by the risk control.
Ideally, each design iteration will reduce the risks further until all risks have been eliminated. The international risk management standard (ISO 14971) states that risks shall be reduced as low as reasonably practicable (ALARP). However, the European medical devices regulations require risks to be reduced as far as possible, considering the state-of-the-art. For example, all small-bore connectors in the USA are now required to have unique connectors that are incompatible with IV tubing Luer lock connections to prevent potential use errors. That requirement is considered “state-of-the-art.” If your device is marketed in both the USA and Europe, you will need to reduce errors as far as possible–before writing warnings and precautions in your instructions for use.
Reaching the point where use errors cannot be reduced any further may require many design iterations, and each iteration should be subsequently evaluated with formative usability testing. Formative testing can be performed with prototypes, rather than production equivalents, but the formative testing conditions should also address factors such as the use environment and users with different levels of education and/or experience. Ultimately, if the formative testing is done well, summative (validation) testing will be a formality.
Risk Control Effectiveness During Phase 4 – Summative Usability Testing during Verification
Once your team freezes the design, you will need to conduct verification testing. This includes integrating usability testing into the verification testing process. Summative (validation) testing must be performed once your design is “frozen.” If you are developing an electrical medical device, then you will need to provide evidence of usability testing as part of your documentation for submission to an electrical safety testing lab for IEC 60601-1 testing. There is a collateral standard for usability (i.e., IEC 60601-1-6). For software as a medical device (SaMD), you will also be expected to conduct usability testing to demonstrate that the user interface does not create any user errors.
When you conduct summative (validation) testing, it is critical to make sure that you are using samples that are production equivalents rather than prototypes. Also, it is crucial to have your instructions for use (IFU) finalized. Any residual risks for use errors should be identified in the precautions section of your IFU, and the use of video is encouraged as a training aid to ensure use errors are identified, and the user understands any potential harm. When the summative testing is performed, there should be no deviations and no use errors. Inadequate identification of usability factors during Phase 2, or inadequate formative testing during Phase 3, is usually the root cause of failed summative testing. If your team prepared sufficiently in Phase 2 and 3, the Phase 4 results would be unsurprisingly successful.
Additional Training Resources for Usability Engineering
The following additional training resources for usability engineering may be helpful to you:
This article explains what a pFMEA is (i.e. Process Failure Modes and Effects Analysis) and how to use them as part of your risk management process.
I recently had someone ask for help understanding the Process Failure Mode and Effect Analysis (pFMEA) a little better. I can’t blame them, because I was lost the first time I tried to fill out a form for one. It can be confusing and overwhelming if you have never created one before.
First things first, what is a pFMEA
FMEA= Failure Modes and Effects Analysis
A lower-case letter will come before the FMEA, and that denotes the ‘what’, of what the failure is that is being analyzed. A pFMEA will often be examining process failures where a dFMEA might evaluate design failures. (dFMEA’s can be confusing as well, Robert Packard created training on how to document risk management activities without using one in his Death of the dFMEA Webinar)
Some systems capitalize all the letters. Some capitalize none. That is not what is important as long as it is consistent throughout your system. Everyone should be able to easily understand that whatever variation of pfmea is used; it means “process failure modes and effects analysis.”
What does a pFMEA do?
A pFMEA will break down your manufacturing process into its individual steps and methodically examine them for potential risks or failures. For companies that utilize ourTurn-Key Quality Management System, FRM-025 process Failure Modes, and Effects Analysis can be used as a template.
For this example, we will look at receiving inspection of injection-molded casing parts for a medical device. This receiving inspection includes a manual inspection of 10 randomly selected parts out of each delivery of 100 using an optical overlay.
This area, as the section title suggests, is the process step. When looking at the process as a whole, the pFMEA will break it down into each and every step included in that process. This area is simply that individual step that is going to be examined.
The Process Step or item function depending on what your form uses for this scenario, is going to be part of the random sampling for manual inspection of the received parts using an optical overlay. Our example is going to be the backlighting element of the optical overlay display. The backlighting element will illuminate the inspected part against the template to verify that the part is within specific dimension criteria.
Potential Failure Modes
A failure mode is a way in which that process step might fail. Since it is failure modeS, it needs to be considered that there may be more than one way for the process step to fail. Do not be fooled that because this box on the form has been filled in that the pFMEA will be complete. A thorough examination of all of the possible failures should be investigated.
Our example in this process requires the backlighting element to illuminate a visual template over the parts. The light not illuminating properly is a potential failure mode of this process.
Potential Effects of Failure
the potential effects of the failure is a look into what the ramifications would be if that failure for that process step actually happened.
In our scenario, one of the potential effects of the lighting not functioning properly is that parts outside of the designated sizing acceptance criteria may be accepted rather than rejected as non-conforming parts.
The next area is the first area that requires an estimated grading of the failure. That is ‘Severity’ which is abbreviated as S. There is a scale provided in the rating section of FRM-025 that outlines the numbering system that Medical Device Academy uses.
In this case, our example is using molded plastic pieces of the outside casing of a medical device. Pieces that are too large or too small will not fit when making the final assembly of the device. These plastic pieces do not happen to be patient contacting, and do not affect the function of the device.
The evaluation of this failure is determined to have no potential effect on patient safety or increase any potential for risk of harm, therefore the severity is assigned as a ‘business risk’ meaning that it bears no risk for the user or the patient. This makes the Severity Score 0.
Causes of Failure
This column is exactly that. What might cause this identified failure to happen? In our example might be the light bulbs in the overlay machine may slowly burn out over time with use. This burnout causes potential failure.
If the bulb is expected to only have a lifetime of 100 hours, then the more hours the bulb is used, the dimmer the light may become. A slowly dimming light decreases the sharpness of the overlay template and our parts that are supposed to have a + or – size criteria of 10% now have a fuzzy template that in reality changes the overlay to show closer to + or – 13%. Now parts that are too small or too large may be accepted.
This grading criterion is also found in the Rating section of FRM-025. This is how often the failure is expected to occur. How often will the lighting element of our optical overlay fail to function in the appropriate manner for this cause?
Hopefully not very often. In fact, regularly scheduled maintenance and calibration of the overlay machine could prevent this from ever happening in the best-case scenario. Our evaluations determine that the probability of this happening is low. However, since we cannot be certain it will never happen the potential for this risk exists and makes the Occurrence score a 4.
Current Process Controls
What is currently being done to control this risk? Our example uses regularly scheduled maintenance and calibration to prevent bulb burnout affecting the overlay.
Our current process is based on routine maintenance and visual inspection. This means that the bulb burnout is something that is visually inspected for and visual inspections for detectability on the rating scale are graded as 8. This chart is found in the Rating Section of FRM-025.
RPN (Risk Priority Number)
This is a number that is found by multiplying the Severity, by the Probability, by the Detectability. In our example, the numbers RPN is 0X4X8=32 for an RPN of 32 which is considered LOW.
Below is a short video explaining the math behind calculating the Risk Priority Number
What if anything can be done to improve this process? In our example, a recommended action may be to transfer from visual only inspections to verification of light output by the meter. This makes the Detectability of the failure measurable by meter or gage which is a detectability score of 4.
This changes the RPN now to 0X4X4=16
The pFMEA shouldn’t be a solo thing
If it can be avoided this type of analysis should be done by a multidisciplinary team. Sometimes in smaller companies, people end up having to wear more than one hat. There are many entrepreneurs that have to function as the CEO/CFO/Design Engineer/RA/QA manager.
Ideally, a team approach should be used if feasible. Have the management level staff who have ownership of the processes participating in this analysis. They should know the process more intimately than anyone else in the company and should have more insight into the possible failure modes of the processes as they have likely seen them first hand. They are also the type of employee who would know the types of recommended actions to control the risk of those failures as well.
The pFMEA should also be a living document
As new failure modes are discovered they should be added to your pFMEA. A new failure mode might be discovered through a CAPA because the process had an actual failure that was not originally analyzed. Take an instance like that as an opportunity for improvement and to update your pFMEA as part of a living breathing risk management system. Also, use this as a time to re-brainstorm potentially similar failure modes that may not have been considered previously so that they can be controlled before they happen.
If you took the time to watch the video above it is also mentioned that in some instances the very first FMEA must be based on estimates because there is no data. Managers and engineers may be forced to estimate the probability of occurrence. If that is the case the FMEA should be updated in the future to adjust the (O) score to reflect what is occurring in actuality based on real data and not the theoretical data that was used for the initial estimate.
On August 9, 2019, three generations of my family left Glastonbury, CT, on a two-week hiking expedition to complete three of the highest peaks in the USA.
Our plan for the hiking expedition was to hike four of the highest peaks. My father, Bob Packard (age 77), is trying to complete all 50 of the highest peaks in each of the United States. For this trip we planned to hike the following mountains:
Wheeler Peak – New Mexico
Kings Peak – Utah
Borah Peak – Idaho
Granite Peak – Montana
Bailey Packard (18), Noah Packard (20), Rob Packard (47), and Bob Packard (77) started on Friday, August 9, from Glastonbury, CT.
Then we drove West for a long time. On Saturday, August 10, we stopped at the Waffle House.
Then we got back in the car.
Finally, on Sunday, August 11, we arrived at the base of Wheeler Peak. We decided to hike it that day despite not acclimating to the altitude and not sleeping in two days.
Then we headed back across the ridge and down to the car. The evening we drove to Colorado and slept. The following morning, Monday, August 12, we drove through Colorado.
That evening we arrived at Henry’s Fork Trail Head in Utah several hours after dark. We pitched tents in the parking area and slept for the night. In the morning, Tuesday, August 13, we woke to ice on our tents. Then we began the long hike into the valley (see Bailey’s video above).
We were all carrying too much gear, and we needed some rest.
While we enjoyed the view of the valley.
Later we saw a couple of moose (Bailey got close enough for a selfie).
We slept the night just below Gun Sight Pass and then headed up Kings Peak in the morning of Wednesday, August 14.
Another spectacular view.
Then we headed back across the ridge (very challenging and exposed).
That afternoon Bailey got lost, but we found him back at the tents several hours later just before dark. Noah was exhausted and took a nap in the middle of the Gun Sight Pass. We all slept well and hiked back to the car in the morning of Thursday, August 15.
Then we drove to Idaho Falls, and we had all you can eat steak at Stockman’s.
We took at rest day on Friday, August 16. On Saturday, it was perfect weather, and we drove to Borah Peak in Idaho–just two hours Northwest from Idaho Falls. We arrived just after 6 am and began hiking as the sun rose.
Now I understand why Wheeler was rated a 1+ in difficulty. Kings Peak was rated a 2+ in difficulty, and Borah is 3+ in difficulty. There is a 2,000+ foot cliff on both sides of a goat path across a knife-edge. There is sharp, jagged shale everywhere and no trees. Winds are fierce, and it’s not a windy day. Temperatures were in the low 40s. I decided to “chicken out” just before we got to “Chicken Out Ridge.”
This is where Rob waited for the others.
The ice bridge was not expected, and dozens of weekend hikers with no experience were trying to crawl across the ice. Bailey used his knife for extra grip on the ice. Bob was almost knocked off the mountain by a falling boulder, and they made it to the peak waiting for Bailey’s pictures to be added later.
Then we all headed down the mountain.
The following day, Sunday, August 18, we drove home our feet were too sore to attempt Granite Peak. But along the way, we stopped on Monday, August 19 at Portillo’s for
This article describes what a gap analysis is in the context of managing your quality system when standards and regulations are updated.
What is a Gap Analysis? An introductory look.
Well, that depends on the context. The dictionary definition is “A technique that businesses use to determine what steps need to be taken in order to move from its current state to its desired, future state. Also called need-gap analysis, needs analysis, and needs assessment.” (http://www.businessdictionary.com/definition/gap-analysis.html).
For the most part, this is correct, but we need to tweak it just a little bit to fit better into our regulatory affairs niche, specifically medical device manufacturers. A Gap Analysis for financial investment or an advertising firm will be very different than one for a medical device distributor. It might even be better served to be called a Compliance Assessment/Gap Analysis, but I am sure someone else has thought of that long before me.
For our purposes, the Gap Analysis is a formal comparative review of an internal process or procedure against a standard, good practice, law, regulation, etc. This blog article will be an introductory look into that process.
What are the two BIG goals of a Gap Analysis?
It sounds like a simple exercise, but the Gap Analysis or GA for short can have two very different but complementary functions. Rather than simply hunting for areas of non-compliance, the first goal is to find and demonstrate areas of compliance.
The second more obvious goal is to find the gaps between the process and the regulatory requirements they are being compared against.
Why is demonstrating compliance important?
Because this is a formal documented review, a Gap Analysis provides documentation in a traceable manner of meeting the requirements that have been laid out. That traceability is important because it allows anyone to read the report, see the requirement, and locate the area of the procedure that demonstrates conformity with that requirement.
The report itself is an objective tool, not something that is meant to be a witch hunt. The Gap Analysis will compare document contents. If you want to verify that the entire process is fully compliant, you will need to dig deeper and observe if the activities laid out within the procedure are being performed per the procedure instructions. It is possible to draft procedures that are compliant with text requirements but non-compliant in the manner that the actions are being performed and documented.
What about gaps?
The gaps, or areas of non-compliance highlight opportunities for improvement, if there are any. A Gap Assessment may not find any gaps and present a report that clearly and neatly outlines and explains how each regulatory requirement is being met.
If there are any gaps identified, that does not mean that there is cause for concern. This should be viewed instead as an opportunity for improvement. Standards and procedures change over time, and, naturally, procedures and processes will have to change with them.
The very act of the Gap Analysis shows that there is a documented effort towards continual improvement as long as the gaps are addressed.
Addressing the Gaps
The report is ideally the first and last step, and you have a wonderful piece of paper to show that someone checked, and all of the required areas are being met. However, this is not always the case. When there are gaps, they must be filled.
Addressing a gap should happen in a traceable manner, one that shows it was identified, acknowledged, and then how it was fixed. Something that might be addressed through a CAPA process, but that is a topic for a different time.
The Compliance Assessment/Gap Analysis is a singular tool used in the overall maintenance of a quality system. Its actions and performance are similar to a simplified type of audit, but the Gap Analysis itself is not going to replace your regularly scheduled audit activities. However, it will help you monitor and keep your fingers on the overall pulse of your quality system. This is also especially helpful in situations where standards and regulations are updated, and your quality system needs to be evaluated and updated accordingly.
This article is a reminder that the new FDA User Fees FY2020 have been announced, and it is time for you to re-apply for small business qualification.
FDA User Fees FY2020 = 5.85% Increase in 510(k) User Fee
In 2016 the FDA and industry negotiated revised user fees to achieve faster decision timelines. In return for higher user fees, the FDA promised faster decision timelines. This agreement ultimately became the Medical Device User Fee Amendments of 2017 (i.e., MDUFA IV). This new higher fee structure was implemented in FY 2018 (i.e., October 2017). The MDUFA IV agreement also included plans for inflation adjustments each year. Therefore, on July 31, 2019, the FDA announced the new inflation-adjusted pricing for FDA User Fees FY2020 in the Federal Register.
This new pricing for the medical device user fees is published in Table 5 of the July 31 announcement. All of the fees increased. The 510k standard user fee, for example, increased from $10,953 to $11,594–and an increase of 5.85%. The FDA also sent out an email update about the increased user fees last week.
Before FY 2019, companies were not able to apply for small business status until October 1. However, in August 2018, the FDA changed the forms, guidance, and policies to allow companies to apply for small business status as soon as August 1. The form also now allows the applicant to fill in the applicable fiscal year. This eliminates the need for the FDA to update the application form each year.
The approval of small business status by the FDA can take up to 60 days. Therefore, every small business planning to submit a regulatory submission to the FDA in FY 2020 should apply for small business status now–instead of waiting until October or when they are planning to submit. This will reduce the possibility of a company needing to submit their submission before they have been qualified by the FDA as a small business and paying the higher standard user fee.
When you submit your application, make sure that you send an original application, because the FDA will not accept a copy–especially for international submissions. Companies located outside the USA, or companies with subsidiaries outside the USA, must obtain verification of the taxes paid by the national tax authority in each country. This extra step makes it even more critical for device companies to start the application process immediately.
In parallel with these annual user fee increases, Medical Device Academy increased our flat-fee pricing for preparing submissions on August 1. The new higher consulting fee increased from $12,000 to $14,000. This fee does not include our flat-fee for each FDA eCopy of $150/eCopy–typically averaging $600/project. However, we now include any time required to respond to RTA Hold Letters and requests for additional information. This typically ranges from 5-10 hours of consulting time at $300/hour. Therefore, the net change is from $14,250 to $14,600 (i.e., an increase of 2.46%). More importantly, it makes the total cost of hiring our firm more predictable and less time consuming for our firm to quote. Our firm’s hourly rates have not changed.
If you are interested in learning more about applying for small business status, please visit our webinar page on this topic or contact us for help. If you are interested in our new pricing, please click on the download button found on our home page.