Japan is a critical participant in the global medical device market. As you know, on March 11, 2011, a massive earthquake and tsunami occurred near the northeastern coast of Japan, followed by various aftershocks, causing extensive damage to this region. The United States Food and Drug Administration (FDA) regrets any destruction or loss caused by this unforeseen disaster.
The FDA’s Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) want to alert you to possible effects that the above series of events may have on medical devices, electronic products and device components intended for market in the United States (US). At this time, neither CDRH nor CBER has been notified of any defective product or serious adverse events associated with the use of a device related to this disaster.
Given the extent of the devastation, CDRH and CBER have concerns about manufacturing conditions as a result of the earthquake and tsunami that could impact the safety and effectiveness of medical devices exported from Japan, intended for import into the US. Our concerns include, but are not limited to, the potential for the following:
- Radioactive contamination of devices and/or device components, particularly those derived from animals, such as bovine serum albumin. Contamination in products can occur through uptake of radioisotopes from water or soil to animals through feed. Also, there is the potential for radioactively contaminated device implants to act as reservoirs for internal radiation exposure of patients,
- Contaminated water supply that could result in defective products that fail to meet your device specifications,
- Loss of electrical power, a source of disruption in the manufacturing process, which directly impacts all components/ devices, specifically those that require refrigeration or temperature controls, such as tissue-based devices,
- Compromise in sterile products during or after production, including stored finished product,
- Compromise in the reliability of product performance (e.g., electrical connectors, microprocessors, alarms, sensors),
- Damaged and/or disrupted medical device manufacturing facilities in the affected and surrounding region may result in a shortage of components and/or finished devices.
CDRH and CBER want to remind manufacturers of finished devices that they must assure that their products comply with FDA regulations. In addition, we request that all manufacturers of components and unfinished devices, do the same. Specifically, we urge all device manufacturers and initial distributors of medical devices to take increased precautions to provide reasonable assurance of the safety and effectiveness of their devices as described in Title 21, Code of Federal Regulations (CFR), Part 820. Such actions might include increased sampling and enhanced testing of incoming raw materials and components, as well as of finished diagnostic and other medical devices prior to product release. Similarly, 21 CFR 1010.2(c) requires that electronic product certification be based on either a particular performance standard (21 CFR Part 1020) or on good manufacturing practices. Such practices would include the evaluation of raw materials and components as well as the finished product.
CDRH and CBER recommend that electronic product and medical device component manufacturers, finished electronic product and device manufacturers, and initial distributors of electronic product and devices, intended for market in the US immediately take the following precautions:
- Assess incoming products and supplies to ensure that the product conforms to your specifications and quality requirements.
- Closely monitor your purchasing and acceptance activities including inspections, sampling, and testing. Carefully check all products for contamination or compromise, including device integrity such as cracks, breech in sterility, filth, defective equipment, or package integrity (dampness, water residue, mold, unpleasant odors, discoloration, or unreadable labels).
- Check all power cords and batteries, and electric monitoring devices to make sure that they are not damaged by water.
Some products, components, and other materials used in the manufacture of a medical device require a temperature controlled environment (e.g. refrigeration). For these items we recommend that you take the following precautions:
- If you are not sure that the product is safe, run quality control checks. This applies to all products including disinfectants and sterilants, dental products (e.g., bone filing materials), intra-ocular lenses that require refrigeration, blood grouping reagents, In-Vitro Diagnostics (e.g.
HIV-1/Enzyme Immuno Assay) and other such products.
- Heighten assessment of all animal-derived products (e.g., raw heparin) and other raw materials prior to finished device production.
- When possible, screen and assess the potential risk to safety associated with unfinished and finished products.
If you have a pending purchase order for components, parts, or finished electronic products or devices, from the affected areas, we suggest that you take the following steps:
- Ensure that the manufacturer/supplier in Japan is operational.
- Ensure that pending device orders comply with the Quality System regulation if you intend to market the device in the US.
- If the product or device was manufactured or stored in a location that was flooded, check the product for signs of water damage or exposure to water.
- If the product or device was manufactured in a location that was flooded for a short period of time, the location’s water treatment system might have been contaminated. Determine if the municipal water supply was acceptable or that the affected firm used filtration, deionization, reverse osmosis, etc., to treat water during the manufacturing process. If the municipal water supply or the water treatment system was contaminated, it is practically impossible to manufacture acceptable product.
- If the manufacturer indicates that the water supply is acceptable, obtain documented evidence as verification.
- Determine if the manufacturer has an adequate restart procedure addressing one or more power outages during production.
- Determine the disposition of components or devices that were in production during the time of blackouts, especially devices undergoing sterilization.
- If a product or device was reworked, assure that the firm has adequate standard operating procedures for this process.
- If you label a device with a shelf life, determine if the declared shelf life will be compromised.
- If a device is intended to be sterile, validate the effects of re-sterilization on the finished product.
To determine the potential impact of the earthquake and tsunami on the supply of medical devices distributed in the US, CDRH and CBER suggest the following:
- Evaluate the immediate and long term potential for shortages of parts, ingredients, components, and finished devices. Especially, unique products such as tubing, software, circuit boards, etc., that is currently manufactured by a sole supplier. If a shortage is anticipated, will it affect life sustaining devices, as those used in dialysis or infusion pumps? If so, notify your customers immediately.
- If the primary supplier is not operational, or is currently unable to meet your specifications for any reason, you may want to identify, qualify, and validate a secondary source of components or finished devices.
If you determine that there is a need for an alternate supplier for your parts, ingredients, components or finished devices, evaluate the need for a Premarket Approval Application Supplement, 21 CFR 814.39, or a new Premarket Notification [510(k)], 21 CFR 807.81. You may want to refer to the following guidance documents: Guidance for Industry and FDA Staff - Modifications to Devices Subject to Premarket Approval (PMA) - The PMA Supplement Decision-Making Process and Deciding When to Submit a 510(k) for a Change to an Existing Device.
To determine if the alternate supplier is required to register and list, please review 21 CFR, Part 807, Subpart B, Procedures for Device Establishments, to ensure that the supplier is in conformance with these requirements. Additionally, be alert to false or misleading claims by suppliers and advertisements on the internet, when attempting to locate an acceptable alternate part, accessory or component.
Report any adverse event (malfunction, injury or death), associated with the use of a medical device to the FDA in accordance with the Medical Device Reporting (MDR) regulation, 21, CFR, Part 803. Also, you are encouraged to report unlawful sales of product, including unapproved devices or counterfeit product, through FDA’s Voluntary MedWatch Reporting Program, or by calling 1-800-322-1088.
If you have any questions regarding this letter, specific concerns, including projected shortages, or relevant information relating to the safety and effectiveness of medical devices as a result of the devastation in Japan, please contact the CDRH, Division of Small Manufacturers, International and Consumer Assistance (DSMICA) at (301) 796-7100 or 1 800-638-2041, or by email at email@example.com. To report actual or impending device shortages to CBER, contact (301) 827-4239. For any other questions, concerns or to report information regarding biologic products, please contact the CBER, Office of Communication, Outreach and Development (OCOD) at 1 800-835-4709, or you may email inquiries to firstname.lastname@example.org.
Jeffrey Shuren, M.D., J.D.
Center for Devices And Radiological Health
Karen Midthun, M.D.
Center for Biologics Evaluation and Research