The identification and traceability (sections 820.60 and 820.65) for products and finished medical devices, throughout the entire manufacturing process, including raw materials employed during the manufacturing process, and the subsequent sale and distribution of medical devices, are critical elements of the Quality System Regulation (QSR). In fact, maintaining batch control and if required, serial number control for specific medical devices are salient requirements of the regulation. Why? Because when the safety and efficacy of a finished medical device comes into question, medical device manufacturers must be able to quickly identify and recover the devices. Yes, Dr. D despises that dirty little word RECALL. However, a recall is inevitable in this business, as the mighty Mr. Murphy is always lurking in some corner. Additionally, without the ability to determine root cause either to a specific component failure, batch of components, raw material lot, or batch of finished medical devices, recalls can result in a substantial number of devices being withdrawn from market. Remember, recalls are expensive so effective identification and traceability can limit the fiscal exposure. Having said that, creating a rock-solid system for identification and traceability is always in the best interest of medical device manufacturers or as Dr. D would like to state; “a pay me now versus pay me later scenario.” Dr. D would never want to be that obstreperous (look-it-up time) quality or regulatory specialist having to explain a non-compliant approach for identification and traceability to the agency.
Warning Letter Violation
It took Dr. D a considerable amount of time to find an offender in regards to this week’s relevant warning letter. Exactly why, the good doctor is not sure so I will let you draw your own conclusions. They way I view this lack of observations noted by the FDA are rooted in two outcomes. In the first scenario, just about all medical device manufacturers understand the importance of identification and traceability and willingly comply with the requirement, e.g., medical device manufacturing Valhalla. In scenario two, the FDA is just not spending much time on this specific requirement because they are having too much fun issuing Form 483s and warning letters for the more egregious violations associated with design controls, process controls, and purchasing controls. Regardless of the reason, the outcome is in actuality self-evident; compliance to all of the requirements, delineated within the QSR, is mandatory. The offending party on the receiving end of this warning letter, lacked procedures and processes for all aspects of product identification, throughout all stages of production. On a very sad note, this was the 10th observation depicted in a very lengthy warning letter.
Warning Letter (March 2009)
10. Your firm has not established and maintained procedures for identifying product throughout all stages of receipt, production, packaging, distribution, and installation to prevent mix-ups, as required by 21 C.F.R. § 820.60.
10A: Your firm has no written procedures for incoming receipt and acceptance of raw materials. Your firm lacks traceability as to specific shipments of raw material used in product and testing of each lot of finished devices. No internal lot number or other control number is assigned to clearly differentiate each shipment of material received from other shipments, and supplier lot numbers are not recorded.
10B: Part numbers recorded on the work instruction forms for the raw material goat anti-mouse antibody and the Reagent Solution produced from that raw material were noted to be the same.
The lot number of the manufacturer’s raw material is used by the firm as its production lot number. Further, the firm uses the same manufacturer’s lot number for the raw material goat anti-mouse antibody to produce different concentrations of the Reagent Solution for Control Line, and continues to assign the same lot number to each batch of finished Reagent Solution for Control Line produced. In sum, unique lot and part numbers are not assigned in order to prevent mix-ups.
10C: Laminated sheets were observed to lack any product identification whatsoever.
Among other things, without a system to uniquely identify and clearly distinguish in-process materials, the incorrect material could be used in manufacturing resulting in production of a finished device which does not meet specifications. Quality System Regulation – 21 CFR, Part 820
QSR – Subpart F – Identification & Traceability
Sec. 820.60 Identification.
Each manufacturer shall establish and maintain procedures for identifying product during all stages of receipt, production, distribution, and installation to prevent mixups. Sec. 820.65 Traceability.
Each manufacturer of a device that is intended for surgical implant into the body or to support or sustain life and whose failure to perform when properly used in accordance with instructions for use provided in the labeling can be reasonably expected to result in a significant injury to the user shall establish and maintain procedures for identifying with a control number each unit, lot, or batch of finished devices and where appropriate components. The procedures shall facilitate corrective action. Such identification shall be documented in the DHR.
Identification and Traceability
They key to an effective system for identification and traceability is a well-defined approach to Material Requirements Planning (MRP) / Enterprise Resource Planning (ERP). My assumption is that all medical device manufacturers pursue an automated approach to MRP / ERP through the employment of SAP™, QAD™, or similar systems. The architecture of these systems supports the batch management of raw materials, components, chemicals, manufactured subassemblies and finished medical devices. Additionally, most MRP / ERP platforms contain functionality in regards to assigning specific serial numbers, when required. Furthermore, regardless of the approach to MRP / ERP, medical device manufactures must be able to retain accurate records in regards to product shipments to specific customers. Accurate records will be needed to facilitate a timely and organized recovery of medical devices should a RECALL become necessary.
The identification requirement of the QSR is not what Dr. D would categorize as a requirement rooted in rocket science. For starters (broken record time), medical device manufacturers must write and maintain procedures covering all functional areas and aspects of their business, including identification and traceability. The procedures must support claims of compliance to the e QSR. Trust Dr. D when I say, “the FDA will issue a Form 483 if procedures employed to support compliance with the regulations are absent or lack depth and clarity.” Remember D. G. Rule # 6 – All procedures, work instructions, drawings, specifications, etc. must be written, well-documented, and controlled with in a defined document control system.”
In support of the identification requirement, a few takeaways for compliance are depicted in the following six-bulleted points.
- Treat batch management as a mandatory requirement for raw materials, components, products, chemicals, etc. employed as part of the manufacturing process. A safe rule of thumb to pursue is that any procured item influencing the product (finished medical device), the packaging (finished medical device), or the labeling (product label, package label, Instructions for Use), should be controlled through a batch management system
- For age-sensitive material, storage conditions and expiration dates are critical to ensure service life is not exceeded. It is an important feature of any MRP system to be able to track and manage expiration dates. This holds true for finished devices as well.
- During production, batch management is equally important. Dr. D strongly recommends pursuing a robust line-clearance approach to prevent material and batch mixing during the manufacturing process. This includes the ability to segregate and quickly quarantine non-conforming products, which will be discussed in a future installment of D.G.
- As mentioned earlier in this edition of D.G., batch management and potentially serial number management is required to comply with the requirement. Additionally, the Device History Record (DHR) is the receptacle for the complete batch history of finished medical device(s) and must be retained as evidence of compliance to the regulation. Once again, you need to trust Dr. D as I emphatically state; “the agency will examine DHRs during their friendly visits.” Furthermore, if the visit is “for cause” because of a specific field action, aka, RECALL, the agency could spend days and potentially weeks examining DHRs, so a significant amount of effort must be exuded when compiling each DHR with evidence of strict adherence with the identification requirement, collectively.
- Identification is also required for “installation” and implies capital equipment must be clearly identified under the regulation. For example, a medical device manufacturer that manufactures radio-frequency (RF) ablation catheters may also sell the capital equipment, or in this example, an RF generator to support the disposable business. The manufacturer, as part of the installation process, is responsible for the identification of the RF generator. The piece of capital equipment should have a unique serial number and the manufacturer should compile and retain a DHR. If subsequent upgrades, firmware changes, software changes, etc are made, the manufacturer is not only tasked with incorporating the changes but ensuring the DHR captures all of the changes for a specific piece of capital equipment. Trust Dr. D when I say; “batch management of medical devices is a challenging task; however, management of capital equipment identification is down-right daunting.
- When in doubt, always invoke identification through the employment of batch control. An organization can always remove the requirement if it is determined batch control, for a specific item e.g., finger cots, is not required.
Similar to identification, Dr. D is going to invoke the not rocket science clause as the requirement for traceability is rooted in common sense. The requirement begins with clear pointers to the device: (a) being deployed as a surgical implant (placed into the body); (b) used to support or sustain life when properly (safety and efficacy) used (hopefully employed in a procedure by a trained and licensed physician); and (c) failure of the device to perform in accordance with the instructions for use (product labeling), which results in significant injury. If the manufactured medical device meets the criteria depicted in the previous sentence, the manufacturer better make damn sure the appropriate policies and procedures are in place to ensure the device has a batch number, lot number, serial number, control number or any number deemed appropriate to track the device back to its manufacturing roots. What Dr. D, back to the manufacturing roots? In short, traceability needs to be captured in the DHR. Additionally, traceability needs to be back to the component level and when deemed appropriate, all the way back to the supplier. Furthermore, the device traceability needs to be robust enough to be able to support corrective actions, up to and including a RECALL.
The salient points from this week’s edition of D.G. are: (a) a written procedure(s) describing identification and traceability is/are mandatory; and (b) place an emphasis on effective batch and if warranted, serial-number control. Additionally, the procedure(s) should focus on specific requirements identified for traceability:
- Product being deployed as a surgical implant (placed into the body);
- Product utilized to support or sustain life when properly (safety and efficacy) used (hopefully employed in a procedure by a trained and licensed physician); and
- Failure for the device to perform in accordance with the instructions for use (product labeling). 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 discussing Subpart – G, Section 820.70 (Production and Process Controls) – 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 June 10, 2010, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/