Distribution and installation are extremely important processes that ensure approved, safe, and effective medical devices make it into the hands of healthcare practitioners. In this edition of Devine Guidance (DG), Dr. D continues with his guidance for 21 CFR, Part 820, Subpart – L (Handling, Storage, Distribution, and Installation), specifically 820.160 (Distribution) and 820.170 (Installation).
Building on the theme established in the previous edition of DG, once handling and storage processes have been perfected; device manufacturers need to get finished medical devices into the hands of healthcare professionals. Distribution channels and installation become salient processes required to satisfy patient needs as well as the regulatory requirements of FDA, through documented compliance with the Quality System Regulation (QSR).
In recent years, Dr. D has developed a great deal of approbation (look-it up if you must) for supply chain professionals tasked with managing the entire distribution cycle. Once regulatory approvals have been received from FDA, distribution of devices into the U.S. market poses a modest challenge. Couple the aspects of U.S. distribution with the extended supply chain lines associated with the European Union, Japan, Canada, Australia, Asia, and all of the appropriate approvals needed from the competent authorities, MHLW, Health Canada, etc., the distribution cycle becomes a monumental challenge. The installation of capital equipment, and in many cases disposable medical devices, the ongoing servicing and repair, upgrades, replacements, etc., result in the same challenges.
Warning letter violations
Dr. D is really growing tired of surfing FDA database on warning letters and finding the constant barrage of observations commencing with; “Failure to establish and maintain procedures.” The garrulous pose depicted in these observations point to the same conclusion, repeatedly. Can you guess what that conclusion might be? If you said a lack of, or missing procedures, you would be correct. Device manufacturers, please read the QSR.
Device manufacturers please generate written procedures to support compliance to the QSR. Device manufactures please, please, and pretty please, understand that compliance to the QSR is not optional, it is mandated by law. Dr. D would like to opine that all editions of DG are worthy of reading, although I strongly suggest reading installment six, and brushing up on the doctor’s rules. In this case, DG Rule # 1: Compliance to regulations is not optional, it is mandatory and dictated by law is quite appropriate.
Additionally, the 19 observations awarded to the owner of the first warning letter extraction is unacceptable. Where is the management representative for quality??? The doctor is going to assume that this individual was meeting with his or her tailor for a custom-fitted orange jumpsuit. Can you say consent decree?
As for the second warning letter, this device manufacturer should not take solace in knowing they received only nine observations. That is still way too many observations. Maybe the management representatives from these manufacturers share the same tailor (sorry – just some bad humor from Dr. D). At the end of the day, the truth in labeling becomes a major factor in this second warning letter observation. If the manufacturer’s specification (product spec) delineates specific storage requirements, these requirements, after being substantiated through testing, need to make their way onto the labeling. Otherwise, how can this device manufacturer guarantee the expected performance requirements for product shelf life were achieved?
Warning letter One (March 2010): Observation 12 of 19 – Failure to establish and maintain procedures for control and distribution of finished devices to ensure that only those devices approved for release are distributed and to maintain distribution records which include or refer to the location of (1) the name and address of the initial consignee; (2) the identification and quantity of devices shipped; (3) the date shipped; and (4) any control number(s) used, as required by 21 CFR 820.160. For example, when requested, procedures for controlling and distributing finished devices and distribution records for products released into distribution for 2008 and 2009 were not provided.
Warning Letter Two (August 2009): Observation 6 of 9 – Failure to assure that you have not distributed devices that have deteriorated beyond acceptable fitness for use as required by 21 CFR 820.160(a). For example, one of the components used in manufacturing hundreds of different products in the “Ultralite” line including different variations of colostomy, urostomy and ileostomy pouches is at (b)(4). According to the manufacturer’s specifications for this product (b)(4), the component has a 3-year shelf life when stored at 70 F, 50% relative humidity and out of direct sunlight. You used this information to establish and label a 3 year shelf life for their products, but you did not include a temperature or humidity requirement on your label and have not performed any in-house validation activities to support the expiration date of the products.
Quality System Regulation – 21 CFR, Part 820
QSR – Subpart L – Handling, Storage, Distribution, and Installation
Section 820.160 Distribution
(a) Each manufacturer shall establish and maintain procedures for control and distribution of finished devices to ensue that only those devices approved for release are distributed and that purchase orders are reviewed to ensure that ambiguities and errors are resolved before devices are released for distribution. Where a device’s fitness for use or quality deteriorates over time, the procedures shall ensure that expired devices or devices deteriorated beyond acceptable fitness for use are not distributed.
(b) Each manufacturer shall maintain distribution records which include or refer to the location of:
– The name and address of the initial consignee;
– The identification and quantity of devices shipped;
– The date shipped; and
– Any control number(s) used.
Section 820.170 – Installation
(a) Each manufacturer of a device requiring installation shall establish and maintain adequate installation and inspection instructions, and where appropriate test procedures. Instructions and procedures shall include directions for ensuring proper installation so that the device will perform as intended after installation. The manufacturer shall distribute the instructions and procedures with the device or otherwise make them available to the person(s) installing the device.
(b) The person installing the device shall ensure that the installation, inspection, and any required testing are performed in accordance with the manufacturer’s instructions and procedures and shall document the inspection and any test results to demonstrate proper installation.
“Each manufacturer shall establish and maintain procedures for control and distribution of finished devices.” This quote is right out of the QSR and is invoked throughout the entire QSR. That said, how could device manufacturers fail to have written procedures? As delineated within 820.160, FDA wants to ensure device manufacturers release only approved devices for distribution. Additionally, FDA wants to ensure adequate review and diligence is pursued in regards to filling purchase orders.
If device manufacturers really want to endear themselves to their customer base, ship the wrong product to a doc. Even better, go on backorder and not have a device to ship, a.k.a., helping the competition. Better yet, ship a product that has or will shortly reach end-of-life, a.k.a., expired shelf life. Furthermore (broken-record time), all product shelf life should be validated through testing; accelerated aging to get the product to market and real-time aging to substantiate the results. If a device manufacturer has not performed aging studies, the product should not be released for sale and distribution. Can you say RECALL? Yes, once again Dr. D has invoked the curse of that nasty 6-letter word.
Records, manufacturer’s best defense
Broken-record time again, no pun intended, documented evidence (records) is always a device manufacturer’s best defense during a friendly visit by the agency. Remember, FDA visits are investigations, not audits. The evidence collected during these investigations can be employed in support of further enforcement or potential criminal action against device manufacturers. That said, some of the records requiring to be retained in support of medical device distribution are:
- The name and address of the initial consignee (Dr. D. also strongly recommends a telephone number and point of contact, just in case a recall becomes necessary);
- Device part numbers, quantity shipped, batch numbers, serial numbers, etc.;
- The date the product shipped (Dr. D also recommends recording the carrier and method of shipment, tracking numbers, waybill numbers, etc.); and
- Control numbers employed (as appropriate.
“Each manufacturer of a device requiring installation shall establish and maintain adequate installation and inspection instructions, and where appropriate test procedures.” Once again, extracted right out of the QSR, the need for instructions and procedures is clearly depicted. Now typically, installation is a task associated with capital equipment, e.g., cardiac ablation system; however, the personnel in the Catheter Lab are not just going to power up the system and allow the attending physician to ablate away. The expectation is that an established protocol, hopefully in the operator’s manual or Instructions for Use (IFU), is going to be comprehended and followed.
It is up to device manufacturers to ensure this information is available and accurate. Additionally, the installation and use information should accompany the piece of equipment or device, as the QSR specifically requires these instructions to be available to personnel performing the installation. Furthermore, if a finished medical device (e.g., disposable catheter) is to be integrated with a piece of capital equipment, the IFU needs to be available to ensure the overall installation; capital equipment, disposable device, and other ancillary devices, if appropriate are correctly installed prior to their use.
Documentation is important
Once again, record keeping, a.k.a., documentation, is important. For starters, Dr. D strongly suggests that individuals performing the installation be adequately trained and the training documented. Additionally, once installation has been successfully completed, the results, test, inspection, etc. shall be documented. Another key component of the installation process is to ensure these records, where appropriate, make their way back to the device history record (DHR).
When dealing with capital equipment, configuration and configuration control are critical pieces of information needed to support servicing. For example, if a software, firmware, or hardware change is required as part of a refurbishment effort, understanding the current configuration, while ensuring all proposed changes have been made is an extremely critical process. The last thing a field-service technician wants to see in the field is an old piece of equipment missing previously required upgrades. A device manufacturer that fails miserably in the fine art of configuration control can expect to experience the pain associated with a RECALL.
Takeaways: Ensuring approved, safe and effective devices reach healthcare practitioners
Distribution and installation are extremely important processes that ensure approved, safe, and effective medical devices make it into the hands of healthcare practitioners. There is no point in designing and developing devices if manufacturers fail at effectively executing these salient tasks. Dr. D will jump back onto his soapbox and emphatically state; “You need written procedures to participate in the medical device industry, it is part of the price of admission.” In fact, if there are no written procedures, in Dr. D’s humble opinion, “no quality system exists.”
In closing, thank you again for joining Dr. D and I hope you find value in the guidance provided. Until the next installment of DG, when I begin providing guidance for Subpart – M (Records), specifically 820.180 (General Requirements) – cheers from Dr. D. and best wishes for continued professional success.
- Code of Federal Regulation. (2009, April). Title 21 Part 820: Quality system regulation. Washington, D.C.: U. S. Government Printing Office.
- Devine. C. (2009, July). Exploring the effectiveness of defensive-receiving inspection for medical device manufacturers: a mixed method study. Published doctoral dissertation. Northcentral University. Prescott Valley, AZ.
- FDA – U.S. Food and Drug Administration Website. (2010). Warning letters. Retrieved September 17, 2010, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/