Special Controls Guidance Document – Content and Format

This article explains the content and format of a special controls guidance document issued for Class 2 medical devices regulated by the CDRH division of the US FDA.

There are many differences between Class 1 and Class 2 medical devices regulated by the FDA, but one of the primary differences is that many (not all) Class 2 medical devices have a special controls guidance document. Class 1 devices only have “general controls.” These “special” guidance documents can be found on the FDA website by searching the guidance document database. The title of each guidance document typically begins with “Class II Special Controls Guidance Document.” The middle of each title specifies the device type, and the end of the title states, “- Guidance for Industry and FDA Staff.” However, there are many exceptions.

Status of a Special Controls Guidance Document

A guidance document may be a final guidance or a draft guidance. Only the final guidance is considered official, however, draft guidance often indicate what the FDAs current thinking is on a topic. Draft guidance documents sometimes take years before they are approved as a final guidance. Sometimes the draft is so controversial that it will even be withdrawn. The FDA also publishes a list each year of planned guidance documents for the next fiscal year. Some of the final versions of special controls guidance documents were written in the 1990’s, but these documents remain the current final guidance until a new final guidance is approved. Often there is no urgent need to update a guidance document, because there are one or more active ISO Standards specific to the product classification and the standard(s) is recognized by the FDA.

Outline of a Recent Special Controls Guidance Document

Here is the general outline that is currently being used by the FDA for a special control guidance document for Class 2 devices:

1. Introduction
2. Topic – Background
3. Pre-Market Notification – Background
4. Scope
5. Risks to Health
6. Specific Device Description Requirements
7. Performance Studies
8. Device Specific Labeling
9. References

Each product classification has the potential for slightly different requirements due to the differences in types of devices. For example, in vitro diagnostic products do not have animal studies and typically have human clinical study requirements for the performance section of the guidance document. However, an implant is more likely to have details about the materials of construction, biocompatibility and sterilization.

Searching the Guidance Database

There are 8 fields that are searchable for the guidance database.

1. Product
2. Date Issued
3. FDA Organization
4. Document Type
5. Subject
6. Draft or Final
7. Open for Comment
8. Comment Closing Date on Draft

For a De Novo application, I sometimes need to create a proposed draft special controls guidance. For this activity, I prefer to find a representative template. In order to do this, I will typically use four of these search fields. First, I narrow the product field to “medical devices” and the FDA organization to “CDRH.” Second, I select “guidance documents” for the document type. Finally, I select “premarket” for the subject and “final.” This narrows the list to 374 documents. Not all of the 374 documents are specific to a product classification, because some of these documents cover more general premarket issues such as risks of wireless telemetry.

You can further narrow your search by adding a word or words to the keyword search field. Therefore, if you are looking for a specific guidance you can find it very quickly.

Format of Special Controls Guidance Documents

If you submit a proposed draft guidance to the FDA (anyone can do this), there is no specific required format. However, I recommend copying the most recent format used by the FDA in order to minimize the amount of work required by the FDA for modifying the guidance prior to publishing your guidance as a draft. You also do not need to include all the sections of a guidance. Some of the guidance documents only update certain sections where technological characteristics have recently changed significantly. Most importantly, if you have a strong reason for deviating from what the FDA has always done–do it. The format of guidance documents has changed since the 90’s and will continue to do so.

Additional Resources

If you are preparing a premarket notification (i.e., 510k submission), you might have more questions than just guidance document availability. You might be interested in purchasing “How to Prepare Your 510k in 100 Days” or the on-line 510k Course or one of our Live 510k Workshops.

How to create a template for 510k submission device description

This article explains how to create a template for a 510k submission device description (i.e., Section 11). The template addresses each of the requirements of a device description in the FDA refusal to accept (RTA) guidance document. The template also serves as a summary technical document (STED) for submission to a Notified Body for CE Marking.

You would think that it’s tough to screw up the device description, but the FDA screening reviewer is completing a new refusal to accept (RTA) checklist (effective October 1, 2015). That checklist has specific requirements for a device description. If you copy the device description from your draft IFU, then you will probably receive an RTA letter on Day 15 of the RTA screening process. The review “clock” is reset to zero, and you have to revise your device description and re-submit.

There are four specific requirements (questions 9-12) in section “B” of the RTA checklist, which is titled “Device Description.” In addition to this, there are similar requirements for inclusion in a device description for technical file and design dossier submissions to Notified Bodies. Rather than creating two different device description documents, I prefer to create a template that addresses each of the regulatory requirements in a single controlled document. Therefore, I created a template for the 510k submission device description with the following headings for Section 11 of the 510k submission:

1. Product or trade name
2. General description—including the intended purpose. The general description must be consistent with the device description in the labeling, and this section of the document is intended to address section 10 of the refusal to accept (RTA) checklist.
3. A list and description of each device for which a 510(k) clearance is requested in the submission. The list may refer to models, part numbers, various sizes, etc. This section of the document is intended to address section 11c of the refusal to accept (RTA) checklist. It may be helpful to combine this section with section 3 of the template, providing a table with a UDI device identifier for each product listed.
4. UDI device identifier(s)—if available.
5. Intended patient population, medical condition to be diagnosed and/or treated, and other considerations such as patient selection criteria.
6. Principles of operation of the device. This section of the document is intended to address section 11a of the refusal to accept (RTA) checklist.
7. A description of proposed conditions of use, such as a surgical technique for implants, anatomical location of use, user interface, how the device interacts with other devices, and/or how the device interacts with the patient. This section of the document is intended to address section 11b of the refusal to accept (RTA) checklist.
8. Risk class and applicable classification rule, according to Annex VII (proposed EU regulations) or Annex IX (MDD). For this section, I will cross-reference to a controlled document that includes the complete classification rationale, while this section only includes the classification and the applicable rule(s).
9. Explanation of novel features (be careful, this is a regulatory document and not a marketing document).
10. Description of components, accessories, other medical devices, and other products that are not medical devices, which are intended to be used in combination with the device. The 510k number should identify each component/accessory that was part of a previous submission. Any component(s)/accessory(s) that have not received prior clearance should also be identified. Sometimes a side-by-side table for USA and EU markets is needed for accessories where different accessories are used in different markets. This section of the document is intended to address section 12a, b, and c of the refusal to accept (RTA) checklist.
11. Description or a complete list of the various configurations/variants of the device that will be available
12. General description of the key functional elements, formulation, composition, and functionality—including labeled pictorial representations (e.g., diagrams, photographs, and drawings)
13. Raw materials incorporated into key functional elements and those making direct contact with the human body or indirect contact with the body
14. Technical Specifications of the device and any variants and accessories that would typically appear in the product specification made available to the user, e.g., in brochures, catalogues and the like.
15. Representative engineering drawing(s), schematics, illustrations, photos, and/or figures of the device. This section of the document is intended to address section 11d of the refusal to accept (RTA) checklist.
16. Reference to similar and previous generations of the device. It is important to make sure these devices are included in the clinical evaluation report. If you are submitting a 510k submission, you want to make sure that any devices are registered and listed with the US FDA in the same product category. For a device with multiple predicates, it may be necessary to create a table that organizes the “similar” devices by intended use and technological characteristics.
17. Requirements specific to the special controls guidance document. This section of the template is intended to address section 9 of the refusal to accept (RTA) checklist.

The last section of the device description STED is for any unique requirements specific to the special controls guidance document for the product classification I am working on. However, most of the requirements for a device description are met by the previous items in my outline. Therefore, I create a table that outlines each of the requirements of the special controls guidance document, and I provide a cross-reference to the section of the outline that includes this requirement. If there are requirements not covered elsewhere in the document, I address the requirement in the table itself. If there is no special controls guidance document, then I state that no special controls guidance document exists for the product.

5 Alternatives When You Can’t Find a Predicate Device

This article summarizes five alternatives that medical device manufacturers have for regulatory approval in the US when a 510k submission predicate device cannot be identified.

Choosing the best 510k submission predicate device is critical to success or failure.

The premise behind the FDA 510k regulation is that your new device is substantially equivalent to another device (i.e., predicate device) that is already on the market. Therefore, you only need to submit a premarket notification to the FDA instead of a premarket approval (PMA) submission. Most 510k submissions reference a similar device manufactured by a competitor, but what do you do when you can’t find a predicate device?

Your 5 Options if you cannot identify a 510(k) predicate device

1. Conduct a Clinical Study and Prepare a PMA Submission = $$$ + 2 years min.
2. Prepare a De Novo Submission = avg. review time was 307 days in 2019
3. Submit a 510k with Your Best, Poor Choice & Expect One of Two Responses: Refusal to Accept (RTA) or Not Substantially Equivalent (NSE)
4. Request a Pre-Sub Meeting with the FDA = 60-day Delay at the front of Project
5. Submit a 513(g) Request to the FDA = $ + 60-day Delay at Front of Project

Option 1 – Clinical Study & PMA preparation

If you cannot identify a predicate device, you may need to conduct a clinical study to demonstrate that your new device is safe and efficient. Some devices even require an investigational device exemption (IDE) approval from the FDA if the risks of the device are significant. If your device presents significant risks, likely, the De Novo process (Option #2 below) will not be an option, and the device will be considered a Class III device by the FDA. In this case, the fastest pathway to regulatory approval is a modular PMA submission. The minimum timeline for this type of submission is typically two years, and the FDA user fee for a PMA submission is very high–unless you are a start-up company and this is your first product. The following FDA webpage summarizes the process for a modular PMA.

Option 2 – De Novo Classification Request if there is no predicate device

Originally the De Novo process was created with IVD products in mind where the technological characteristics are nearly identical between the two devices. Still, the intended use is different (i.e., the device is used to diagnose a different disease). The problem with the original process is that you had to submit a 510k and have it rejected before you were allowed to submit a De Novo application. Now the De Novo process allows two pathways. A company can submit a 510k, have it rejected with a “not substantially equivalent” (NSE) letter, and then submit a De Novo application. The new option allows a company to skip the initial 510k submission and submit a De Novo application first. This extends the decision time from 90 days to 120 days, but the previous option took even longer. We recorded a webinar on the De Novo Classification Request Process in 2019. The FDA also recently updated the De Novo webpage to summarize the regulations related to the De Novo new final rule. The following FDA webpage summarizes all the De Novo Classification Requests recently granted.

Option 3 – Submit a 510k with whatever device you found

This is probably not your best approach, but sometimes it’s worth a shot to see what the FDA will say instead of waiting to schedule a pre-submission meeting, and this approach doesn’t eliminate option #2. There are two likely outcomes from this approach. First, the reviewer screening your 510k submission during the 15-day, refusal to accept (RTA) process will determine that you have not selected a suitable predicate device, and you will receive an RTA letter. In this case, you have an answer in just 15 days. You should never accept your first RTA letter. You should make the requested changes the reviewer indicates and re-submit. The FDA’s goal is to have all submissions make it through the RTA process on the second try. Therefore, you might have more success on the second try with another predicate or just by fixing other problems the reviewer identified.

The other possible outcome of this approach is that you will make it through the RTA process, but your submission will be determined to be NSE. In this case, you will receive an NSE letter from the FDA, and it will suggest options–typically a PMA or a De Novo submission. If a De Novo submission is a good option, it will be stated in the letter.

Option 4 – Request a pre-sub meeting to discuss a potential predicate device

If you are not able to identify a suitable predicate, you might consider preparing a classification rationale and selecting a potential predicate. Then this information can be summarized in a pre-submission meeting request to the FDA. The FDA will respond within 75-90 days from your submission. If you are still developing your device and you have not started any performance testing, then this option may be your best approach. I recently recorded a webinar on pre-submission meeting requests.

The webinar includes specific dos and don’ts for pre-submission meetings. There is also final guidance for the pre-submission program that was released last year on February 18, 2014. The FDA pre-submission guidance document was updated again on January 6, 2021, and we recorded a webinar on pre-submission meeting requests.

Option 5 – Submit a 513(g) application to identify the regulatory pathway

When a company has difficulty identifying a 510k submission predicate device, the FDA recommendation is to submit a 513(g) application. As I indicated in a past blog, the 513(g) process may not be your best choice for two reasons. First, the 513(g) process takes 60 days before the FDA responds. Second, the 513(g) process has a user fee that is higher than hiring a consultant to do the same research. Since the FDA 513(g) response is “non-binding,” the FDA’s opinion doesn’t necessarily hold any more weight than an experienced consultant. Therefore, paying a consultant to do the research and then requesting a pre-sub meeting is probably a better approach, but the timeline for a 513(g) submission is slightly shorter.

Do you still have questions about 510(k) predicates?

Rob Packard recorded an updated webinar on the topic of predicate selection. If you are interested in this topic, please register for the webinar. The updated webinar was recorded on March 28, 2022.

Combining a 510k Submission with CE Marking: 9 Sections that are Duplicated

This article explains how to reduce your workload by at least 35% if you integrate your two project plans for a 510k submission and CE Marking into one comprehensive regulatory plan.

My first medical device regulatory submission was for CE Marking, while my second regulatory submission was for a 510k submission of the same product. This is a very common path for medical device regulatory submissions, but it is also an inefficient path. If you know that you will be submitting both types of documents, then you should plan for this from the start and reduce your workload by at least 35%.

The reason why you can quickly reduce your workload is that there are nine key sections in both submissions that are very similar. Therefore, you can write the content for those nine sections in such a way that the material can be used for your 510k submission and CE Marking.

9 Sections are Duplicates

Here are the nine key sections that the two types of regulatory submissions have in common:

1. Device Description
2. Labeling
3. Sterilization & Shelf-Life
4. Biocompatibility
5. Software
6. EMC/Electrical Safety
7. Bench Testing
8. Animal Testing
9. Clinical Testing

There are 20 sections required by the FDA for a Traditional 510k submission, but often some of the sections are boiler plating, and other sections do not apply to the device being submitted. A few sections are unique to a 510k submission, such as:

• Substantial Equivalence
• 510(k) Summary
• User Fee Cover Sheet Form 3601 & Submission Cover Sheet Form 3514
• Declarations of Conformity on Form 3654
• Table of Contents

Technical Files for CE Marking also have a few unique sections, such as:

• Essential Requirements Checklist
• Classification Rationale
• CE Marking Application to Notified Body
• Declaration of Conformity
• Table of Contents

How to Construct Your Plan

In one of my previous blogs, I explained how I use the 510k Table of Contents as a project management tool for a 510k submission. You can do the same when you are constructing a combined plan for a 510k submission and CE Marking. The first step is to create the same kind of project management tool I use for a 510k submission (i.e., a Table of Contents) to manage your CE Marking Technical File. I recommend preparing your Technical File in accordance with the GHTF guidance document released by study group 1: N011:2008. This guidance mirrors the format that will be required in Annex III of the new European Medical Device Regulations that should be released next spring. I do not recommend using the NB-MED 2.5.1/rec 5 guidance document. Even though the content is similar to the GHTF guidance, the format is quite different. After I have two separate project plans organized in accordance with the Table of Contents, then I merge the two plans on a spreadsheet and consolidate the duplicate sections.

Scheduling Tasks & Project Management

If you are going to outsource sections of either submission, these nine sections should be written and reviewed by someone familiar with both types of submissions. The headers and footers will be unique to the type of submission, but I write the text in Google Docs without formating for ease of sharing and so I can use my Chromebook.

If you have an in-house team that prepares your 510k submissions and Technical Files, you might consider training the people responsible for each section on the requirements for each type of submission. This eliminates rewriting and reformatting later. I like to assign who is writing each section in a separate column of my Table of Contents planning tool. Then I will sort the sections by the expected date of completion. All the safety and performance testing, and any sections requiring validation, will typically be finished at the end of the project. Therefore, it is important to dedicate unique resources to those sections rather than asking one person to write several of those sections. You also will want to make sure any supporting documentation they need is completed early so that the project’s critical path doesn’t change. I typically use a Chromebook spreadsheet for all of this, because 20+ sections are just too few tasks to warrant the use of Microsoft Project or some other Gantt Chart planning tool. If you keep it simple, more of your team will read it and update it frequently.

RA Consulting Tip

I have several PCs (laptops and desktops of various vintages), but nothing is faster for writing plain text than a Chromebook. Then I export documents to Word format and work on tables and formatting of the information as needed. I can also jump on any computer with an internet connection and work on my documents. This enables me to travel very light when I need to. If you are a tablet user, there are some other solutions I prefer–such as Evernote.

Additional 510k Training

The new 510k book, “How to Prepare Your 510k in 100 Days,” ships on Monday, February 6th, 2017. There is also an on-line 510k course series consisting of 24 webinars. Please visit my webinar page to purchase individual webinars. We also have live 510k workshops.

Comparing HUD, HDE and 510k Submissions

This article compares the differences between the regulatory pathways for an HDE and 510k submission. The article also explains how the Humanitarian Use Device (HUD) designation  and Humanitarian Device Exemption (HDE) compare.

Last year the FDA released a draft guidance document explaining the regulatory process for applying for an HDE:
http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm389154.htm

HUD designation is for a product that affects less than 4,000 patients per year in the United States. There are three steps required before a HUD may be used at a user facility:

1. HUD Designation Request to Office of Orphan Products Development (OOPD)
2. HDE Application to Center for Devices and Radiological Health (CDRH)
3. Investigational Review Board (IRB) approval of using the HUD

Note: The above regulatory pathway may not apply to combination products. In the case of combination products, you should contact the Office of Combination Products (OCP).

Major Differences

• Unlike the 510k process, HDE approval is device approval rather than “clearance” for marketing and distribution.
• If another equivalent (an actual term used is “comparable”) device is already being legally marketed, then the FDA may not approve an HDE application. In contrast, the first requirement for determination of substantial equivalence of a subject device for a 510k submission is that the predicate device must be a legally marketed device that is equivalent.
• There are no user fees for an HDE application, while 510k submissions generally are subject to user fees; pediatric-only products are an exception to the requirement for 510k user fees.
• There is no requirement to demonstrate the effectiveness of devices in an HDE application. Instead, devices approved for HDE must provide an acceptable risk/benefit analysis.
• HDE approved devices are not generally eligible to make a profit. Any device that a manufacturer intends to sell for more than $250 requires a report issued by an independent public accountant.
• IRB approval for the use of a HUD-approved for marketing is required, but the IRB approval is not for a clinical study, and IRB approval is not required in the case of an emergency.

The FDA guidance document also explains how HDE approval is different from pre-market approval (PMA).

When Can I Use a Second 510k Predicate?

This article describes when you can use a second 510k predicate for demonstrating the substantial equivalence of your subject device in a 510k submission.

Recently a client questioned me about the use of a secondary predicate in a 510k submission that I was preparing. They were under the impression that only one predicate was allowed for a 510k submission because the FDA considers the two predicate devices to be a “split predicate.”  About half of the 510k submissions I helped prepare in the past year have used a secondary predicate, and all of the submissions have been cleared so far. When is a second 510k predicate allowed?

The FDA released a new guidance document that explains how to demonstrate substantial equivalence. The guidance document includes a new decision tree that summarizes each of the six questions that 510k reviewers are required to answer in the process of evaluating your 510k submission for substantial equivalence. The evidence of substantial equivalence must be summarized in Section 12 of your submission, and the guidance document reviews the content that should be provided.

Substantial equivalence is evaluated against a predicate device or multiple predicates. To be considered substantially equivalent, the subject device of your 510k submission must have the same intended use AND the same technological characteristics as the predicate device. Therefore, you cannot use two different predicates if one predicate has the same intended use (but different technological characteristics), and the second predicate has the same technological characteristics (but a different intended use). This does not prohibit you from using a secondary predicate, but you must meet the requirements of this guidance document to receive 510k clearance. The guidance document reviews five examples of multiple predicates being used correctly to demonstrate substantial equivalence.

When you are trying to use multiple predicate devices to demonstrate substantial equivalence to your subject device in a 510k submission, you have three options for the correct use of multiple predicate devices:

1. Two predicates with different technological characteristics, but the same intended use.
2. A device with more than one intended use.
3. A device with more than one indication under the same intended use.

If you use “option 1”, then your subject device must have the technological characteristics of both predicate devices. For example, your device has Bluetooth capability, and it uses infrared technology to measure temperature, while one of the two predicates has Bluetooth but uses a thermistor, and the other predicate uses infrared measurement but does not have Bluetooth.

If you use “option 2”, you are combining the features of two different devices into one device. For example, one predicate device is used to measure temperature, and the other predicate device is used to measure blood pressure. Your device, however, can perform both functions. You might have chosen another multi-parameter monitor on the market as your predicate, however, you may not be able to do that if none of the multi-parameter monitors have the same combination of intended uses and technological characteristics. This scenario is quite common when a new technology is introduced for monitoring, and none of the multi-parameter monitors are using the new technology yet.

If you use “option 3”, you need to be careful that the ability of your subject device to be used for a second indication does not compromise the performance of the device for the first indication. For example, bone fixation plates are designed for fixation of bone fractures. If the first indication is for long bones, and the second indication is for small bones in the wrist, the size and strength of the bone fixation plate may not be adequate for long bones, or the device may be too large for the wrist.

If you would like to learn more about demonstrating substantial equivalence, please join us for a live webinar during Thursday’s Learning Lunch. To register for the webinar, please visit the following webpage.