Insights & Intelligence for Regulatory Leaders

This article is an excerpt from The beginner's guide to the 510(k) ebook.

Table of Contents

• Introduction
• 510(k) basics
• Contents of a Traditional 510(k)
• 510(k) submission and timelines
• Other 510(k) forms

Congratulations! You have successfully developed a new medical device. Now you need to take it to market. In the United States, this often means submitting a 510(k). A 510(k) is a structured package of information about your device and its performance and safety that you submit to the Food and Drug Administration (FDA) for “clearance” before you can sell your device in the U.S. In order to receive clearance from the FDA, your 510(k) will need to demonstrate that your medical device is substantially equivalent to another legally marketed device (called a predicate device). The substantial equivalence approval process is a simple equation that looks something like this:

The 510(k) is generally the most efficient route to market clearance in the U.S. because you show your device is safe and effective based on this substantial equivalence standard, instead of needing to present more extensive clinical trial data.

There are three types of 510(k): Traditional, Abbreviated, and Special. This eBook will begin with a general overview of the 510(k) process, including its purpose and benefits. Next, we will explore the Traditional 510(k) and the sections and components required in depth. Finally, we will look at the Special and Abbreviated 510(k).

FDA: background and device oversight

Before we explain what a 510(k) is let’s first talk generally about the FDA and device oversight. The FDA is the U.S. governmental agency responsible for overseeing medical devices, drugs, food, and tobacco products. When it comes to medical devices, the FDA’s mission is to “protect the public health by ensuring the safety, efficacy, and security of…medical devices.” At the same time, the FDA also has an interest in “advancing public health by helping to speed innovations.” In other words, the FDA’s goal is to make sure devices are safe and effective for public use, while also ensuring that devices have a quick and efficient path to market.

In order to achieve this balance of safety and efficiency, the FDA has three different levels of oversight depending on the risk level of the device: (1) exempt from premarket submission, (2) Premarket Notification, also known as 510(k), and (3) Premarket Approval (PMA).

When is a 510(k) required?

A 510(k) is required for medium risk devices that have a predicate on the market which can be used to demonstrate the safety and effectiveness of the new device. Meanwhile, a PMA is required for high-risk or novel devices which require a higher level of scrutiny to be confirmed safe and effective.

A 510(k) is not only required for new devices, but also for devices that have been modified in a way that could impact safety or effectiveness. This could include changes to the:

• Design
• Components
• Materials
• Chemical composition
• Energy source
• Manufacturing process
• Intended use

You must submit your 510(k) at least 90 days before marketing the device.

What Exactly is Substantial Equivalence?

Now that we know what a 510(k) is, let’s talk about the substantial equivalence standard. You’ll recall from the introduction that your 510(k) must show that the new (or modified) device is substantially equivalent to at least one other legally marketed device, called a predicate device. Substantial equivalence looks at the intended use and the technological characteristics of the two devices.

More specifically, you must show:

• that the new device has the same intended use as the predicate, and
• the differences between the two devices do not raise questions about the safety and effectiveness of the new device.

Now let’s take a closer look at intended use and technological characteristics.

Intended use

Intended use means the general purpose or function of the device. The FDA will look at your proposed labelling and your Indications of Use section of the 510(k) to determine the intended use of your device (this is covered in Chapter 2). Intended use includes:

Technological characteristics

Once the FDA has determined that a predicate device exists and that the new device and the predicate device have the same intended use, it will move on to compare the technological characteristics. Technological characteristics include:

• Materials
• Design
• Energy source
• Other device features

The two devices do not have to be identical, and in fact they almost never are. The key here is to demonstrate that any differences do not have a significant impact on safety or effectiveness. Here’s what to cover when you compare your device’s technological characteristics with that of the predicate device:

Overall description of the device design

• Engineering drawings or diagrams to explain the device and component parts.
• List of component parts and explanation of how each component contributes to the overall use and function of the device.
• Physical specifications: dimensions, weight, temperature, tolerances, etc.

Materials

• Detailed chemical formulation used in all materials of constructions (especially those that come into contact with a patient).
• Any additives, coatings, paint, or surface modifications.
• How materials have been processed and what state they’re in.

Energy Sources

• Use of batteries, electricity, etc.

Other technological features

• Software/hardware
• Features
• Density
• Porosity
• Degradation characteristics
• Nature of reagents
• Principle of the assay method

In deciding whether the differences in technological characteristics impact safety or effectiveness, the FDA will typically rely on descriptive information about the technological characteristics as well as non-clinical and clinical performance data.

Let’s look at an example: A manufacturer submits a 510(k) for a new type of contact lens. Both the new device and the predicate device are indicated for daily wear for the treatment of astigmatism. The predicate device is only available in a clear lens, but the new device comes in a line of colors, including purple tinted lenses.

Who is responsible for submitting a 510(k)?

The following four types of organizations may be responsible for submitting a 510(k):

Manufacturers

• End-of-line device manufacturers who will be placing a device on the U.S. market.
• Note: Does not apply to component part manufacturers unless components will be marketed independently.

Specification developers

• Companies that develop the specifications for a finished device which has been manufactured elsewhere

Repackers or relabelers

• Required to submit a 510(k) if they significantly alter the labeling or condition of the device, including modification of manuals, changing the intended use, deleting or adding warnings, contraindications, sterilization status.
• Note: This is rare. The manufacturer, not the repackager or labeler, is typically responsible for the 510(k) submission.

Importers

• Importers that introduce a new device to the U.S. market may need to submit a 510(k), if it hasn’t already been submitted by the manufacturer.

Now that we’ve covered the basics, let’s explore what actually goes into your 510(k).

A Traditional 510(k) should contain all the following components in the list below. In some cases, a particular section may not apply to your device. When that happens, it’s a good idea to include the section anyway and just state “This section does not apply” or “N/A” under that heading.

To continue reading this eBook including a detailed walk-through of all the Traditional 510(k) components, submission requirements and timelines, and an overview of the other 510(k) forms including the Abbreviated 510(k) and the Special 510(k), please register to download the full version

This article is an excerpt from The ultimate guide to the China NMPA UDI system and database ebook.

Table of Contents

• Overview
• UDI basics and benefits
• UDI format requirements and issuing entities
• UDI database and submission requirements
• Implementation of UDI and the UDI database in China

The current Chinese medical device regulatory regime kicked-off in 2014 with the Regulation on Supervision and Administration of Medical Devices. This core set of registration requirements, modeled after the United States and European Union systems, established a set of device classifications (class I, II, and III) based on risk and procedures for obtaining market clearance for each type of device.

Medical devices in China are regulated by the National Medical Products Administration (NMPA). Class I devices, such as clinical laboratory equipment or non-invasive skin dressings, require only notification to the NMPA for marketing authorization, and that authorization does not expire. Class II and III devices such as implantable devices or devices with a measuring function require full registration and a formal review before market clearance can be obtained.

These initial regulations have been expanded since their introduction, adding accelerated pathways to market for certain products in certain regions, easing acceptance of clinical data from overseas, and more specific roles and responsibilities for local agents of international manufacturers. In addition, in 2019, the regulations added a provision that medical devices carry a unique device identification (UDI). China’s UDI requirements are similar to those in the US and European Union. They establish specific device ID and labeling requirements, as well as a central, state-administered database of devices.

This eBook walks through the basics of medical device UDIs, the specifics of China’s implementation, and how MedTech companies who market their devices in China can prepare for the full rollout of these regulations in the coming years.

A UDI is a unique alphanumeric code that is designed to identify medical devices sold in a particular country/region from manufacturing, through distribution, to use by a patient. Like other aspects of the medical device regulatory regime, the UDI system in China follows the approach taken by the United States FDA and European Commission, and is based on the guidance from the International Medical Device Regulators Forum (IMDRF). Generally, UDI systems are designed to improve patient safety and optimize care by:

• Increasing the traceability of medical devices, including field safety corrective actions
• Providing an unambiguous identification method for medical devices throughout distribution and use
• Making adverse event reports more accessible
• Reducing medical errors by providing detailed information related to the device
• Simplifying medical device documentation and making it more consistent

There are three components to the UDI system in China:

• UDI code: The actual UDI code can be assigned by one of three (3) issuing agencies and contains information about the product, it’s expiration date, and the manufacturing batch/lot it’s associated with.
• UDI labeling: Put simply, medical devices must carry the UDI code on them. The regulations stipulate how devices and their packaging must be labeled for compliance.
• UDI database: In addition to labeling, all device UDIs must be submitted to a central database that is administered by the NMPA.

The following sections explore each of these components in more detail.

The UDI code

The first element of the UDI system is the code itself. The UDI code is the alphanumeric identifier that is associated with a specific medical device. UDI codes have two (2) elements to them, the UDI device identifier (UDI-DI) or static portion, and the UDI production identifier (UDI-PI) or dynamic portion. You can see the two components in the UDI diagram below:

The UDI-DI contains information about the issuing entity—the organization that is authorized to assign UDI codes. In China, this can be one of three entities: GS1, an international barcode and electronic data interchange standards organization, and two domestic organizations: the Zhongguancun Industry & Information Research Institute (ZIIOT), and AliHealth. Additional details about the issuing agencies are covered in Chapter 2. In addition, the UDI-DI contains information about the manufacturer and the specific model or version of the device.

The UDI-PI contains information about the manufacturing and production of the device. This typically includes information about the lot or batch number in which the device was manufactured, the manufacturing date and expiration date for the device (if applicable), and the specific serial number for the device. Here you can see all of the components marked up using the same UDI example:

Note that each packaging permutation and level for a given device will need to be assigned its own UDI. So for example, let’s say that a company manufactures 5ml enteral (oral) syringes in two packaging options: 1 – packaged individually and 2 – packaged in a box of 5. Each packaging option would need its own UDI, despite the fact that the underlying product is the same.

Now looking at packaging levels, let’s assume that the manufacturer packages the single syringe offering into boxes of 6, and again into larger containers of 24. Each of those packaging options needs its own UDI as well.

Labeling

In addition to obtaining UDI code for each device as outlined in the previous section, medical device manufacturers are required to ensure that devices are appropriately labeled with the assigned UDI. This label is called the UDI Carrier. The UDI is represented in two forms on the UDI Carrier: a machine-readable form and a human-readable form.

The machine-readable form or automatic identification data capture (AIDC) is a barcode or some other technology that can be used to automatically capture UDI information. The NMPA regulations support 3 types of machine-readable formats: 1-dimensional barcode, 2-dimensional barcode, and radio-frequency identification (RFID).

The regulations note that “use of advanced automatic identification and data collection technologies is encouraged”—prompting manufacturers to use more modern 2D and RFID machine-readable carriers where possible. Note, however, that if a device uses RFID, the UDI Carrier must also include the UDI in barcode format.

The human-readable form or human-readable interpretation (HRI) is the numeric or alphanumeric code for the UDI that can be read and manually entered into systems.

The UDI Carrier should be included on the device and on all levels of packaging. The UDI Carrier must be clear and readable during the operation and use of devices. If there isn’t room on the device for both the human and machine-readable forms of the UDI, then manufacturers should prioritize the machine-readable form.

UDI database

The third component of the NMPA UDI system is the UDI database. This is a centralized database of UDI and product information, administered by the NMPA. Manufacturers are required to submit UDI information into the database within 60 days after a product is approved (for sale in China) and before it is commercialized. The database contains a more detailed product record than what is included in the UDI itself, and it is the responsibility of the manufacturer (and/or their in-country representative) to submit the information correctly, and ensure that it’s kept up to date.‍

Chapter 3 of this eBook goes into detail about the specific fields and data requirements for UDI database submissions.

To continue reading this eBook including information about UDI format requirements and issuing entities, implementation timelines, and affected device types, please register to download the full version.

This article is an excerpt from The ultimate guide to the EU MDR/IVDR UDI ebook.

Table of contents

• Overview
• UDI basics and benefits
• UDI format requirements and issuing entities
• UDI rules for specific device types
• Implementation of UDI and UDAMED in the European Union
• US vs EU UDI comparison

The EU Medical Device Regulation (2017/745) (“MDR”) and EU In Vitro Diagnosis Regulation (2017/746) (“IVDR”) introduce two new systems for information exchange: UDI (Unique Device Identifier) for device identification and EUDAMED (European Databank on Medical Devices) to centralize and disseminate information. UDI is a specific code assigned to all devices and higher levels of packaging. This will allow for devices being sold in the European market to be identified and traced through a globally harmonized approach. EUDAMED is the IT system developed by the European Commission to replace the EUDAMED2 database previously in place under the Medical Device Directives (MDD). EUDAMED is a multi-functional system that will be used to coordinate device registration, provide information about devices to industry professionals and the public, and highlight necessary safety details.

The EU MDR and IVDR UDI system is based upon the guidance of the International Medical Device Regulators Forum (IMDRF). It’s a globally harmonized system that’s designed to increase patient safety and optimize care.

UDI system goals

Increase patient safety

• Improve tracing of devices
• Reduce the presence of counterfeit devices

Ensure access to accurate information

• Unambiguous identification of devices throughout distribution and use

Improve post-market surveillance

• Improve accessibility of adverse event reports

Enhance supply chain Management

• Streamline supply chain process and inventory management
• Simplify medical device documentation processes

The UDI system has four key elements

Element 1: Assignment of UDI (UDI Components)

The first element of the UDI system is the assignment of a UDI. The UDI is a code of alphanumeric characters that acts as the access key to information about a specific medical device on the market. The EU MDR and EU IVDR requires that a UDI be assigned to all medical devices except for custom-made or investigational devices. There are three components of a UDI:

• Basic UDI-DI
• UDI (consisting of UDI-DI and UDI-PI)
• Packaging UDI (Note: This is not an official term used in the EU MDR and IVDR, but we’re using it to help explain the concept. The Packing UDI is part of the UDI itself.)

1. Basic UDI-DI

The Basic UDI-DI identifies the device group that a particular device fits into. A device group is a group of products that all share the same intended purpose, risk class, essential design, and manufacturing characteristics. A device group is generally classified by medical device manufacturers as a “Product Family” or “Product Category,” depending on the internal nomenclature used within the company. The Basic UDI-DI functions as a parent or higher-level descriptor of a device.

NOTE: There can only be one Basic UDI-DI per UDI-DI.

The Basic UDI-DI is not printed on the product itself or on the packaging of a product, but rather it must be included in the following documents and applications:

• Certificates (Including Certificate of Free Sale)
• EU Declarations of Conformity
• Techical Documentation
• Summary of Safety and Clinical Performance

2. UDI (UDI-DI and UDI-PI)

The second component is the UDI itself, which consists of two parts:

Device Identifier (DI)

Production Identifier (PI)

The UDI-DI (Device Identifier DI, also referred to as “static”) identifies specific, detailed information about a particular device. If any of the below details should change, the device will need a new UDI-DI.

• Name or trade name of the device
• Device version or model
• If labelled as a single use device
• Packaged as sterile
• Maximum number of uses
• Need for sterilization before use
• Quantity of devices provided in a package
• Critical warnings or contra-indication
• CMR/endocrine disruptors

NOTE: There can be several UDI-DIs for one Basic UDI-DI.

Meanwhile, the UDI-PI (Production Identifier PI, also referred to as "dynamic") contains manufacturing information (including serial number, lot/batch number, software identification, and manufacturing or expiry date or both types of dates.)

To better illustrate this concept of Basic UDI-DI and UDI (UDI-DI and UDI-PI), let’s use a syringe as an example. The Basic UDI-DI would identify the category of a syringe, for example, "Enteral (Oral) Syringe."

A 5ml Enteral (Oral) Syringe – Sterile (Color: Purple) would get a unique UDI-DI and a 10m Enteral (Oral) Syringe – Sterile (Color: Orange) would get a unique UDI-DI. Both products would be associated to the same Basic UDI-DI. In this case, the "Enteral (Oral) Syringe," which defines the category.

Each time that 5ml Enteral (Oral) Syringe – Sterile (Color: Purple) is manufactured at the same revision, it will get a new UDI-PI per lot. See the graphic below.

Each product is identical and therefore has the same UDI-DI. However, the UDI-PI changes to reflect the manufacturing date, lot number, expiry date, and serial number, as applicable.

The UDI will contain all device-specific information and have the same functions as the comparable database (GUDID) of the United States FDA. The main difference (in EUDAMED) is that the UDI data is divided into components of Basic UDI-DI, UDI, and Packaging UDI.

3. Packaging UDI

The third component of UDI is the Packaging UDI. (Note: This is not an official term used in the EU MDR and IVDR, but we’re using it to help explain the concept.)

Each level of packaging, except shipping containers, must receive its own unique UDI. Packaging UDI refers to the unique UDI assigned to higher levels of packaging instead of the device itself.

In the event of significant space constraints on the unit of use packaging, the UDI Carrier may be placed on the next higher packaging level.

Returning to our earlier example of syringes, if a manufacturer first packages a single sellable syringe into an individual box, this package would receive its own UDI-DI and UDI-PI.

If then the manufacturer packages those individual boxes into containers of six (6), those containers would receive their own UDI-DI and UDI-PI.

And finally, if the manufacturer packages those six (6) containers into cases of four (4), those cases would receive their own UDI-DI and UDI-PI.

Each of those levels of packaging must be assigned its own UDI-DI and UDI-PI. The initial syringe did not change, but the way it is packaged did, therefore, requiring its own UDI-DI and UDI-PI.

Element 2: Placing UDI on the device and/or packaging

The second element to the UDI system is the placing of the UDI on the device or on its packaging through what is referred to as a “UDI Carrier.” The UDI Carrier is the part of the label that contains the UDI information that is applied directly to the device or included on the device packaging. The UDI Carrier should have both a machine-readable portion (AIDC) and a human-readable portion (HRI). (Specific details about each element of the UDI will be covered in Chapter 2.)

• Machine-readable form – AIDC – (Automatic Identification and Data Capture) is a barcode or other machine-readable technology that can be accessed automatically by scanning the UDI information.
• Human-readable form – HRI – (Human Readable Interpretation) is the numeric or alphanumeric code, which can be manually entered into the system for access to the UDI information.

If there are space constraints limiting the use of both the AIDC and HRI on the label, then only the AIDC is required to appear. However, on devices that are intended to be used in home-health care or other non-medical facility settings, the HRI would be required to appear.

Single-use devices may contain the UDI Carrier on its lowest level of packaging rather than on the device itself.

Reusable devices must include the UDI Carrier on the device itself, unless any type of direct marking would interfere with the safety or performance of the device, or if it is not technologically feasible to directly mark the device. If so, this should be properly documented in your design history file.

Most importantly, the UDI Carrier must be readable for the intended lifecycle of the device.

Below is an example of a GS1 AIDC and HRI barcode label.

Element 3: Storage of UDI information by Economic Operators

Storage of UDI information by "Economic Operators" is the third element of the UDI system. 2017/745 Articles 2(35), 22(1), and 22(3) define an economic operator as:

• A manufacturer
• An authorized representative
• A distributor
• An importer
• An investigator for clinical investigations
• A person who sterilizes systems or procedure packs

Class III, implantable device:

According to EU MDR 2017/745 Annex II, the manufacturer shall keep an updated list of all UDIs that it has assigned. Economic operators and all health institutions are required to store, preferably by electronic means, the UDI of all the devices for which they have supplied or with which they have been supplied.

For Devices Other than Class III:

Member States are encouraged, and in some cases require, health institutions to store, preferably by electronic means, the UDI of the devices with which they have been supplied. The UDI must also be included in any field safety notice for reporting serious incidents and field safety corrective actions.

The EU MDR and EU IVDR also give the European Commission authority to make additional requirements regarding the submission or maintenance of UDI information. In making those decisions, the European Commission must consider six (6) areas:

• Confidentiality and data protection
• Risk-based approach
• Cost-effectiveness of the additional measures
• The need to avoid duplications in the UDI system
• The needs of the healthcare systems of the member states
• Harmonization with other medical device identification systems

To continue reading this eBook including information about the EUDAMED database, UDI format requirements and issuing entities, implementation timelines, and key differences between the EU and US UDI systems, please register to download the full version