Insights & Intelligence for Regulatory Leaders

This article is an excerpt from The ultimate guide to the medical device single audit program (MDSAP) ebook.

Table of contents

• What is MDSAP?
• History of MDSAP
• Who is responsible for the MDSAP?
• How does an MDSAP audit work?
• Audit sequence
• You got a nonconformity – now what?
• What does an MDSAP audit cost?
• Why choose the MDSAP certification process?
• Potential disadvantages of the MDSAP
• Ready to participate? – Here’s how to get started
• Completing a successful MDSAP audit

The Medical Device Single Audit Program (MDSAP) was designed and developed to allow a single audit of a medical device manufacturer to be applied to all country markets whose regulatory authorities are members of the program. The MDSAP provides efficient and thorough coverage of the standard requirements for medical device manufacturer quality management systems, and requirements for regulatory purposes (ISO 13485:2016). In addition, there are specific requirements of each medical device regulatory authority participating in the MDSAP that must be met:

• Conformity Assessment Procedures of the Australian Therapeutic Goods (Medical Devices) Regulations (TG(MD)R Sch3)
• Brazilian Good Manufacturing Practices (RDC ANVISA 16)
• Medical Device Regulations of Health Canada (ISO 13485:2003)
• Japan Ordinance on Standards for Manufacturing Control and Quality Control of Medical Devices and In Vitro Diagnostic Reagents (MHLW Ministerial Ordinance No 169)
• Quality System Regulation (21 CFR Part 820), and specific requirements of medical device regulatory authorities participating in the MDSAP program.

This means that a report from a single MDSAP audit of a medical device manufacturer would be accepted as a substitute for routine inspections by all the member Regulatory Authorities (RAs) across the world. There are currently five participating Regulatory Authorities (RA) representing the following countries: Australia, Brazil, Canada, Japan and the USA.

In April, 2021, the RAs released an “Audit Approach” document (MDSAP AU P0002.006) that combines the formerly separate MDSAP Audit Model and Process Companion documents into a single guidance document. It includes guidance for assessing the conformity of each process and includes an audit sequence, instructions for auditing each specific process, and identifies links that highlight the interactions between the processes.

In March 2012 the US FDA announced that they had approved a final pilot guidance document “Guidance for Industry, Third Parties and Food and Drug Administration Staff: Medical Device ISO 13485:2003 Voluntary Audit Report Submission Pilot Program.” This allowed the owner or operator of a medical device manufacturing facility to be removed from FDA’s routine inspection work plan for 1 year upon completing a ISO 13485:2003 audit. This guidance document went into effect in June 2012, and was intended as an interim measure while a single audit program was being developed.

This pilot program was not very successful and few companies signed up because they did not see any advantage in participating. The manufacturer had to pay for a third party to inspect their facilities, generate a report, and share the inspection results back to the FDA. Many companies were reluctant to contract “someone else” to perform their inspection when they could easily wait for the FDA to conduct an inspection for free.

During its inaugural meeting in Singapore in 2012, the International Medical Device Regulators Forum (IMDRF) appointed a working group to develop a set of documents for a harmonized third-party auditor system. Hence, the “Medical Device Single Audit Program” (MDSAP) was formed. The concept was similar to the FDA’s original idea of creating a third-party auditor to help reduce their workload of performing regulatory audits of medical device manufacturers’ quality management systems. This new approach would consist of a single audit that would review regulatory QMS compliance, conducted by a third-party, who would later be called an Auditing Organization (AO).

From January 2014 to December 2016, five countries participated in a Medical Device Single Audit Program Pilot. In June 2017, a report was generated summarizing the outcomes of prospective “proof- of-concept” criteria established to confirm the success of the program. The outcomes are documented in the final MDSAP Pilot Report and recommended that the program become fully active and open to any manufacturer who requested this type of audit.

The governing body of the MDSAP is the Regulatory Authority Council (RAC), which is composed of two senior managers (and a few other staff members) from each participating RA. They are responsible for executive planning, strategic priorities, setting policy, and making decisions on behalf of the MDSAP International Consortium. The RAC also reviews and approves documents, procedures, work instructions, and more. The mission of the MDSAP International Consortium is to jointly leverage regulatory resources to manage an efficient, effective, and sustainable single audit program focused on the oversight of medical device manufacturers on a global scale.

Other international partners that are involved in the MDSAP include:

MDSAP Observers:

• European Union (EU)
• United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA)
• The World Health Organization (WHO) Prequalification of In Vitro Diagnostics (IVDs) Program

MDSAP Affiliate Members:

• Argentina’s National Administration of Drugs, Foods and Medical Devices (ANMAT)
• Republic of Korea’s Ministry of Food and Drug Safety
• Singapore’s Health Sciences Authority (HSA)

The observers and affiliate members are not the same as the participating member RA’s. The observers simply observe and/or contribute to RAC activities. Affiliate members, on the other hand, are interested in engaging in the MDSAP program and are subject to certain rules. They are only given access to a certain level of information about the manufacturers, audit dates, and information in audit reports.

They are also invited to attend sessions that are open to members, observers, and affiliates only.

Audits can also be conducted by MDSAP participating RAs at any time and for various reasons including:

• "For Cause" due to information obtained by the regulatory authority
• as a follow up to findings from a previous audit
• to confirm the effective implementation of the MDSAP requirements

The purpose of audits conducted by the RAs is to ensure appropriate oversight of the AOs MDSAP auditing activities. The AOs are appointed by the RAs and a list of the currently approved AO’s is published on the FDA website. Most AOs offer a broad range of management system certification services, beyond just medical devices. Manufacturers should verify that prospective AOs are clearly trained and perform MDSAP audits of medical devices.

AOs have the final word as to whether a manufacturer has met the requirements for the MDSAP during the execution of the audit and generation of the associated reports summarizing the results. MSDAP RAC participating RAs have the final decision regarding all development, implementation, maintenance, and expansion activities associated with the program.

Although an unannounced visit by an AO is rare, it can happen in circumstances where high-grade nonconformities have been detected.

To continue reading this eBook including a detailed look at the MDSAP audit process and grading, pros and cons of the approach, and how to get started please register to download the full version.

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.