Medical device manufacturers own responsibility for every step of their global supply chain when it comes to buying raw materials, finished devices, components and services from overseas suppliers. Therefore, when a manufacturer chooses to utilize overseas or domestic suppliers, it should ensure control over any product or service obtained from such suppliers as defined within their Quality Management Systems. Based upon risk, these controls may extend further if a supplier subcontracts work.
While manufacturers are responsible to comply with the 21 Code of Federal Regulations (CFR) Part 820 and ISO 13485: 2016 for Purchasing Controls and Acceptance Activities, it’s important they understand that FDA and U.S. Customs play instrumental roles in the monitoring of quality systems and products, respectively. Random inspections are done before products cross the border into the U.S., and inspections of medical device QMS are ongoing.
With that knowledge, this article outlines the roles of individual manufacturers selling in the U.S., FDA and U.S. Customs, as they relate to the increasing scrutiny of international purchasing controls.
The Push for an FDA and U.S. Customs’ Presence
Today, with 300,000 foreign facilities from more than 150 countries exporting FDA-regulated products to the U.S., FDA works beyond U.S. borders to ensure that products coming into the country are safe and effective. Customs works on U.S. borders to sample regulated devices, raw materials, components, etc. before releasing these products for use in the U.S.
FDA established foreign offices in 2008, posting staff in strategic locations around the world, including China, Europe, India and Latin America. FDA overseas offices work closely with their respective foreign governments, industries and other stakeholders to help FDA more effectively protect U.S. consumers.
Steps in FDA’s strategy to address the complex issues posed by globalization include:
- Develop new enforcement and regulatory tools
- Conduct more foreign inspections
- Increase collaboration with foreign regulators and other sponsors
- Develop internationally-harmonized standards and standards linkages
- Educate foreign industry about FDA requirements
- Increase transparency and accountability in the supply chain
Foreign manufacturers must meet applicable medical device regulations in order to ship devices into the U.S., even if the product is authorized for marketing in another country. These requirements include registration of establishment, listing of devices, manufacturing in accordance with the quality system regulation, medical device reporting of adverse events and premarket notification 510(k) or premarket approval, if applicable.
In addition, foreign manufacturers must designate a U.S. agent. As with domestic manufacturers, foreign manufacturing sites are subject to FDA inspection. Investigators conduct onsite inspections of regulated foreign establishments to proactively ensure the safety and efficacy of products manufactured abroad and sold in the U.S. From about 2013 to today, overseas FDA inspections conducted by investigators based in-country have been mainly concentrated in the areas of food and human drugs.
Overseas medical device firms inspected by investigators based in-country represent less than 5% of the total number of these types of inspections. This program has received much hype because it is a worthwhile undertaking, as opposed to adulterated products reaching domestic shores that are found to be unacceptable for human use. Customs checks these products, but is heavily involved with sampling plans that represent only a portion of what is cleared for use by American consumers and industry.
The Initial Importer
The initial importer of the device must register its establishment with FDA. An initial importer is any importer that furthers the marketing of a device from a foreign manufacturer to the person who makes the final delivery or sale of the device to the ultimate consumer or user, but does not repackage or otherwise change the container, wrapper or labeling of the device or device package.
Initial importers are also subject to Medical Device Reporting (MDR) under 21 CFR 803; Reports of Corrections and Removals under 21 CFR 806; and Medical Device Tracking under 21 CFR 821, if applicable. Under MDR regulations, importers are required to report incidents in which a device may have caused or contributed to a death or serious injury as well as report certain malfunctions. The importers must also maintain an MDR event file for each adverse event. All product complaints (MDR and non-MDR events) must be forwarded to the manufacturer.
FDA and Customs Monitoring Process
Most importers ask that domestic brokers (or filers) complete the appropriate forms electronically and make the submissions on their behalf. Filers have access to the Operational and Administrative Systems for Import Support (OASIS), which is FDA’s computerized import system. OASIS is the electronic interface between FDA and Customs’ Automated Commercial System that replaced the process of reviewing the paperwork for import entries manually.
When an entry is filed with Customs, a copy of the entry is also provided to the local FDA district office. The FDA district office then determines if the product complies with FDA requirements. The Food, Drug and Cosmetic Act (FD&C Act) statutorily authorizes FDA to detain a regulated product that appears to be out of compliance with the act. Upon entry, FDA may examine certain devices to assure their safety and effectiveness. When this occurs, FDA will again issue a notice to the importer of a record on a form titled “Notice of FDA Action.” Sampling may involve examining the product at the port of entry or physical collection of a statistical portion of the lot for analysis by an FDA laboratory. If the sample is violative, or determined to be out of compliance with required specifications, the device will be detained along with the importer of record.
If a product appears to be out of compliance, the FDA district office will also issue a “Notice of FDA Action” specifying the nature of the violation to the owner or consignee. The owner or consignee is permitted to have an informal hearing in order to provide testimony regarding the admissibility of the product. If the owner fails to submit evidence that the product is in compliance or fails to submit a plan to bring the product into compliance, FDA will issue another “Notice of FDA Action,” refusing admission to the product. The product then has to be exported or destroyed within 90 days. Failure to do so within this timeframe may result in issuance of a Customs Redelivery Notice and an assessment for settled damages for up to three times the value of the lot.
Under certain conditions, the importer of record of a device that has been detained is given an opportunity to submit application for authorization, to bring the device into compliance with the FD&C Act. If FDA permits reconditioning, another sample may be collected and analyzed. If the device is then determined to be in compliance, it will be released.
Only the FDA district office at the port of entry has the authority to authorize reconditioning or to release the shipment. The foreign company must provide the proper documentation or bring the products into compliance under the authorization from the authorized district office.
A company may import device parts, components, subassemblies, etc. for further processing or incorporation into unapproved devices which are to be subsequently exported. A company may not import a finished device without prior marketing clearance, even if the device is to be imported solely for subsequent export. The terms “further processing” and “incorporation,” as detailed in the Regulatory Procedures Manual, are moderately broad in interpretation. For example, a device imported for further packaging or labeling would fall into this category; a device that is simply stored without any further action prior to export would not fall into this category.
The provisions for import for export under section 801 of the FD&C Act have been amended by the section 322 of Bioterrorism Act of 2002. Importers wishing to import devices (including components or an accessory of a device or other article of a device requiring further processing, which is ready or suitable for use for health-related purposes) that are intended for further processing or incorporation into another product and subsequent export must provide FDA with certain information at the time of initial importation. The information includes a statement that confirms the intent to further process such article or incorporate such article into a product to be exported and identifies entities in the chain of possession of the imported article. At the time of initial importation and before delivery to the importer, initial owner or consignee, a bond must be executed providing for discharged damages in the event of default, in accordance with Bureau of Customs and Border Protection requirements. The initial owner or consignee of the article must maintain records of the use or destruction of such imports and must submit the records or a report to FDA upon request.
Dun and Bradstreet Also Plays a Role
Interestingly enough, FDA has contracted the services of Dun & Bradstreet to conduct onsite verification of medical device facility information provided to the agency by registered and listed medical device manufacturers. As part of these services, Dun & Bradstreet may look to verify information such as a facility’s Data Universal Numbering System (DUNS), various addresses, establishment type and products.
Dun & Bradstreet may also contact firms not registered with FDA that the agency has learned may be involved in the manufacture of medical devices. Presently, participation is voluntary.
Continued Focus by FDA
Historically, recalls of medical devices due to failure of critical components and services supplied to device manufacturers continues to fuel FDA’s increased scrutiny of supplier purchasing controls.
- FDA continues to tell manufacturers that they bear responsibility for every step of their global supply chain. Recalls of medical devices due to failures of critical components and services supplied to device manufacturers prompted FDA’s increased scrutiny of supplier purchasing controls.
- FDA is not only focusing on U.S. manufacturers and suppliers, but also overseas suppliers. With more than 700 inspectors, the agency plans to ensure that it performs overseas inspections on a timely basis. Moving forward, OEMs need to think of their contractors as if suppliers were part of their inhouse production facility. Industry/FDA/Customs working like a team is the goal.
Regulatory Enforcement Trend–Aligning QMS
One recent enforcement trend is supplier process validation. As the International Medical Device Regulators Forum (IMDRF) or the Global Harmonization Task Force (GHTF) guidance documents indicate, “Regulatory requirements call for processes to be validated where the resulting output cannot be verified by subsequent monitoring or measurement.” Regardless of who actually performs the process validation, it is the manufacturer’s responsibility to ensure that the validation is properly performed, and that it cross-references the IMDRF (GHTF) Guidance on Process Validation SG3/N99–10:2004.
There is another important consideration to be made regarding validation requirements performed on supplier processes. OEMs must ensure that validation processes employed by their suppliers meet the minimum requirements of the validation processes of the OEM, as part of either the qualification of the supplier by the OEM or through the review of validation protocols conducted by the supplier for the manufacturer. This process would include all aspects of validation, including process output performance levels (e.g., acceptance criteria), statistical requirements, review or resolution of deviations, etc.
Process Points for Manufacturers Controlling Suppliers
According to the IMDRF (GHTF), the process of establishing controls for products and services obtained from suppliers typically comprises six phases:
- Selection of potential suppliers
- Supplier evaluation and acceptance
- Finalization of controls
- Delivery, measurement and monitoring
- Feedback and communication, including Corrective Action and Preventive Action process
Manufacturers are responsible for the evaluation and monitoring of their suppliers from concept and feasibility to and including time periods indicated on quality agreements/supplier documentation. Manufacturers must realize that FDA and U.S. Customs are keeping an eye on suppliers, using evaluation and monitoring techniques that are both preventative and reactionary in nature. The goal is to ensure that medical device products manufactured or distributed in the U.S. are safe and effective for human use. It’s as simple and as complicated as that.
MidWest Process Innovation, LLC