Changes to the US FDA establishment registration and listings came into effect in October 2012 with profound implications for contract manufacturers. It is estimated that up to 750 additional companies – all based outside the US – have since been required to register with the FDA. Here, a spokesperson for the FDA’s Center for Devices and Radiological Health explains what these changes will mean for device companies that sell into the US market.
Medical Device Developments: Why was this change necessary, and what is the FDA hoping to achieve?
One of the key changes is that, if a device is going to be marketed in the US, the manufacturing facility will need to be audited, no matter where in the world it is.
The FDA relies on having a complete and accurate registration of device establishments, together with listing information for devices processed at those establishments, in order to accomplish a number of important statutory and regulatory objectives. For example, when an establishment experiences a problem, it can have a significant impact on the product lines for one or multiple firms with which it is contracted to provide manufacturing or sterilisation services. Knowing which products are manufactured or sterilised at the affected site could facilitate the recall of the impacted devices.
FDA also believes that knowing that these manufacturing sites exist could prove to be critical information when a device is in short supply or is needed in the event of a national emergency.
How are overseas contract manufacturers dealing with this new requirement? Have you had any feedback from CMOs, and is the agency offering any sort of assistance?
We regularly receive feedback from the industry and are available to assist through three mechanisms: via a feedback form on our main web page, by phone or by email [these contact details are listed in the ‘How do I register?’ box].
There is a wealth of information on the website, including answers to FAQs, and instructions on who has to register and list, and how it is done (see ‘Who must register, list and pay the fee?’ table and ‘How do I register?’ box). There is also a link to an online Center for Devices and Radiological Health (CDRH) Learn video course on the basics of registration and listing, with plans to add more detailed lessons in the near future.
Over the course of the 2013 fiscal year registration cycle, more than 23,000 establishments, including nearly 11,000 foreign establishments, successfully registered and listed their devices. Approximately 615 of these establishments were foreign contract manufacturers and sterilisers registering for the first time. Overall, in 2013, more than 3,000 foreign establishments registered with the CDRH to report contract manufacturing or sterilising activities.
With what other key regulations must these manufacturers now comply?
Most foreign contract manufacturers and sterilisers that shipped their product directly to the US prior to the changes implemented in 2013 were already required to register and list with us in order to get their products into the country. The most significant change for all foreign establishments is that they must identify and provide the FDA with information about their importers, and those they know of that offer their products for import into the US.
Another new requirement, which has a lesser impact in terms of numbers of registrants, is the elimination of the exemptions for shipping to establishments in foreign trade zones and import for export. These are both part of the implementation of the requirements of the Breakthrough Therapy Act.
What are the implications for medical device companies that sell into the US market and rely on these contract manufacturers? Are there any steps – compulsory or just good practice – that such companies should be taking?
There are a few things that medical device companies relying on these contract manufacturers can do. For a specification developer or other product owner that receives their device from their contract manufacturer, the most important thing to do is to review their own medical device listings and make sure that all their devices are listed, the activities or establishment types are accurate, and they have entered all of the proprietary or brand names under which their devices are marketed in the US. This will make it easier for the contract manufacturer to register their establishment and list their devices.
The medical device companies can also contact their contract manufacturers to ensure they understand the new requirements and provide any information that their contractor may need in order to comply. This may include the premarket number under which their product has been cleared or approved (510(k), PMA, NDA, PDP or HDE) and the proprietary names under which it is marketed in the US.
Since the changes came into force, have there been any areas of concern? If so, how is the regulator addressing these worries?
FDA has modified the electronic registration and listing system, the FDA Unified Registration and Listing System (FURLS), so that foreign, private-label distributors do not have to disclose their sources to their customers. FURLS has also been modified to allow companies to keep private – and off the FDA’s public website – the names of products that would disclose confidential business relationships.
Only contract manufacturers of finished devices are required to register and list. If a company only manufactures a component that cannot itself be considered a finished device, they are not required to register and list. As it relates to the identification of importers known to the foreign contract manufacturer, the foreign contract manufacturer must identify at least one party involved in the import process, even if that party is another foreign establishment that actually exports the device to the US.
What’s on the horizon? How would you characterise the future regulatory landscape for contract manufacturers, and are more changes still required?
Although they may not directly affect regulatory compliance for contract manufacturers, there are two initiatives in progress that could have a major impact on the production and formatting of medical device labelling.
To meet the growing need for medical device labelling to be delivered in a clear, concise and readily accessible format for patients, caregivers and healthcare providers, the CDRH is exploring the development of a searchable medical device-labelling repository, which would be accessible by the public and provide useful product information. Similar to the drug-specific labelling repository that is already available through DailyMed on the National Library of Medicine’s website, such a programme would require companies to submit device labelling electronically, possibly via FURLS, the FDA Electronic Submission Gateway or both.
On 24 September 2013, the FDA released a final rule requiring that most medical devices distributed in the US carry a unique device identifier (UDI). The system established by this rule requires the label and device package of each medical device to include a UDI, and that each UDI be provided in a plain-text version and in a form that uses automatic identification and data- capture technology.
A UDI system has the potential to improve the quality of information in medical device adverse-event reports, which will help the FDA identify product problems more quickly, ensure better target recalls and improve patient safety. More information about the new rule, its requirements and implementation schedule can be found on the FDA website.