Complaint, complaints, and more complaints, if you want to play in the medical-device industry sandbox, device manufacturers better get use to the concept. Complaint and complaint handling is a daily part of life for medical device companies. Customer complaints run the complaint gamut, with some being as simple as the ink smeared on a device-package label or problematic such as a sterile-barrier breach.

Complaints can also be categorized as major or significant when a device problem results in patient injury or death (a.k.a. adverse events). As many of you already know, complaints also drive input into the FDA’s Manufacturer and User Facility Device Experience (MAUDE) Database, as adverse events are required to be reported employing FDA Form 3500(a). Device manufacturers should have robust procedures that define their specific program requirements in regards to post-market surveillance activities.

Regardless, complaints require a significant organizational commitment to ensure a fastidious and consistent approach to complaint management is sustained. In this edition of Devine Guidance (DG), Dr. D will begin analyzing and providing insight and guidance needed for maintaining an effective compliant management system. Because the complaint requirement delineated within the QSR contain a significant amount of granularity, this edition of DG will contain guidance for complying with 820.198, subsections a, b, and c. All of the requirements device manufacturers are mandated by law to comply with can appear as a farraginous (look-it-up if you must) assortment of regulations, mandates, and statutory requirements; however, remember this, Dr. D will never steer the readers in the wrong direction.

Warning letter violations
Letting Dr. D loose in the FDA Warning-Letter Database, to extract violators and their violations of 820.198, can be equated to letting the proverbial fox loose in the hen house. There are just far too many violations being racked up by device manufacturers and their management, or should the doctor emphatically state “mismanagement,” of complaints (hint-hint). In fact, the first three-warning letters the doctor opened contained violations of 820.198. As with most violations of the QSR, these observations commenced with the customary statement pertaining to procedure adequacy or in general, a lack of a written procedures. As my dedicated readers already know, not having a written procedure is a clear violation of the QSR; and Dr. D’s Rule # 6 – All procedures, work instructions, drawings, specifications, etc. must be written, well-documented, and controlled within a defined document control system.

The recipient of warning-letter one definitely endeared themselves to the agency. Not only was the agency thrilled with the lack of an effective procedure, this was a repeat violation from a previous investigation. The agency clearly did not approve of the written response provided. So overall, Strike One was an ineffective procedure, Strike Two was a repeat violation and Strike Three was an unacceptable response to the agency. In baseball terms (World Series time), these three strikes equate to a strikeout in the eyes of FDA. Striking out coupled with a 10-observation warning letter equates to this device manufacturer about to enter a very long and interesting relationship with the agency.

The recipients of warning letters two and three also failed to establish what FDA perceives as effective written procedures in support of complaint handling. To make matters worse, the recipient of the third warning letter failed to respond back to the agency within the 15-day timeframe. Give me a break folks; I cannot believe that a device manufacturer would be willing to place their entire organization at risk by failing to respond to the agency within 15-days. What were they thinking?

Warning Letter One (September 2010): Observation 9 of 10 – Procedures for receiving, reviewing, and evaluating complaints by a formally designated unit have not been adequately established as required by 21 CPR 820.198(a). The Customer Complaint and Return Authorization Instructions, RA-WI-001 Revision 00, was insufficient. For example:

i. The procedure did not ensure that complaints were evaluated to determine whether the complaint constituted an event required to be reported under 21 CFR 803, Medical Device Reporting;
ii. The procedure did not require that all complaints were evaluated to determine if an investigation was necessary;
iii. The procedure did not require that when no investigation was conducted, the reason and name of individual responsible for the decision not to investigate was recorded;
iv. The procedure did not require that when a complaint represented an MDR reportable event, that the complaint was promptly reviewed and evaluated by a designated individual and that the subsequent investigation include a determination of whether the device failed to meet specifications, was being used for treatment or diagnosis, and the relationship of the device to the reported event.

FDA Response to Observation 9 of 10 – The same observation was made during the previous inspection of July 2006.Your response included a revised Customer Complaint and Return Authorization Instructions procedure, RA-WI-001, Rev. 01, dated 8/15/10. We cannot determine whether or not the revised procedure and customer complaint form will be satisfactory under actual conditions of use, nor have you provided any evidence that appropriate training has been conducted for all groups listed (quality, sales, customer service, and management) on the revised procedure, and associated requirements and procedures, such as MDR reporting. Furthermore, the response again cites the promised corrective actions regarding management reviews, and as stated previously, we do not consider that response to be sufficient.

Warning letter Two (September 2010): Observation 5 of 5 – Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).

Naturalyte Acid Concentrate products:
For example, on June 09, 2009, your company received a complaint (PIR 200901506) regarding a possible dialyzer reaction incident that occurred on April 6, 2009 in which a dialysis patient experienced lose of pulse/consciousness and CPR was required. Related complaint, PIR 200901614 was received on June 10, 2010, and referenced a second occurrence of a possible dialyzer reaction on April 20, 2009 in which the patient loss consciousness again, and required CPR a second time. The patient ultimately died on May 08, 2009 due to coronary artery disease, end stage renal failure, and sepsis.

The second complaint was voided, contrary to your own SOP S100006-01, even though two events were clearly reported. The original complaint file was subsequently closed on July 17, 2009 without investigation to determine that the event was not reportable under 21 CFR Part 803. The file did not include any documentation that your devices did not cause the events described in the two separate incidents. We are concerned that you relied on your own internal assessment to make such a decision, without further investigation or contact with the complainant.

Also, your firm received a complaint on June 23, 2008 (PIR 200801118) involving Naturalyte products (08-4017) which indicated that since the labels look the same, “the wrong product actually has been used on one occasion”. The complaint did not include any documentation that indicated an attempt was made to follow-up with the complainant to determine whether a patient reaction was involved.

Warning letter Three (September 2010): Observation 3 of 8 – Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example, your firm’s (b)(4) does not state how to receive, review, and evaluate complaints in a timely manner.

FDA Response to Observation 3 of 8 – Your response dated June 14, 2010, was received after the 15 day time frame for consideration; therefore it has not been reviewed at this time.

Quality System Regulation – 21 CFR, Part 820
Section 820.198 Complaints (Subsections a, b and c)

(a) Each manufacturer shall maintain complaint files. Each manufacturer shall establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit. Such procedures shall ensure that:

1. All complaints are processed in a uniform and timely manner;
2. Oral complaints are documented upon receipt; and
3. Complaints are evaluated to determine whether the complaint represents an event which is required to be reported to FDA under part 803 of this chapter, Medical Device Reporting.

(b) Each manufacturer shall review and evaluate all complaints to determine whether an investigation is necessary. When no investigation is made, the manufacturer shall maintain a record that includes the reason no investigation was made and the name of the individual responsible for the decision not to investigate.

(c) Any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications shall be reviewed, evaluated, and investigated, unless such investigation has already been performed for a similar complaint and another investigation is not necessary.

Complaints
So let Dr. D begin with broken-record time, what part of not having effective written procedures and adhering to written procedures do device manufacturers still not understand? As with all of the requirements delineated within the QSR, the establishment and management of complaint files requires written procedures. Additionally, because the management of complaints is really a unique process, the FDA expects device manufacturers to establish a dedicated functional group for managing complaints. Furthermore, the agency’s expectation is that all types of complaints; (a) formal (e.g., from a physician or patient); (b) oral (e.g., a simple phone call); (c) complaints identified in a magazine, paper, or periodical, a.k.a. literature review; or (d) complaints coming from a third party (e.g. family or friend) find their way into the complaint management system. Finally, Dr. D strongly recommends opening a complaint file for each complaint received. It is much easier to manage and track complaints when this approach is pursued.

Procedure elements
As a starting point, the QSR requires three salient components for inclusion into the complaint management system. The first element of the complaint system should address the manner in which all complaints will be managed. For example, the procedure should contain specific references, such as:

1. Time required for processing complaints, including closure;
2. The time required for the actual complaint investigation;
3. Specific elements addressing the investigational process when product is not returned for evaluation; and
4. In general the overall handling, or as the QSR states,”uniform” handling of complaints.

As depicted in the previous paragraph, the complaint procedure must clearly delineate the process in which “ALL COMPLAINTS” are entered into the complaint management system. The procedure must be robust enough to ensure complaints that represent an adverse event (serious patient injury or death) make their way into the MAUDE database in accordance with 21 CFR, Part 803. If the conclusion reached, as part of the complaint investigation process, points to an adverse event, an MDR is required. It is Dr. D’s professional opinion, it is always better for device manufacturers to pursue a conservative approach when reporting MDRs. “Confucius say it is always better to over-report and stay in the good graces of the FDA then to under report and receive warning letter,” just kidding on the Confucius part. 

Complaint investigation
As many of you already know, Dr. D strongly believes compliance to the QSR does not entail rocket science. That said, here is another rocket science moment, FDA actually expects device manufacturers to investigate the complaints they receive. Additionally, device manufacturers are required to keep accurate records of the complaint investigations pursued. If a decision is made not to open or pursue an investigation, that decision still needs to be captured and retained. Why? Because documented evidence of compliance is always a device manufacturer’s best defense during one of the friendly visits from the FDA. Furthermore, if a decision is made not to investigate, the QSR demands that the decision maker’s name be documented as part of the decision process. Can you say Chief Jailable Officer (CJO)? It is Dr. D’s recommendation that some level of review occur for each complaint. The information gleaned from this exercise will be extremely useful when it comes time to execute complaint trending and documenting the root-causes of complaints. Besides, without an effective complaint investigation process, how can device manufacturers ever be expected to fix potential problems associated with device safety and efficacy?

Complaints associated with device failure, labeling or packaging
If a received complaint is directly related to a device failure, accuracy of the labeling, or concerns over device packaging (e.g., sterile barrier breach), the device manufacturer better be prepared to pursue a robust investigation. In short, if the device, device labeling, or device packaging, fails to meet the documented and approved product specification pursuing an investigation is in order. Now granted, 820.198 – subsection (c) allows device manufacturers some latitude in regards to previously documented complaints; however, a pointer must be clearly made back to these previously analyzed complaints. If the agency feels that there are far too many incidents pointing back to previously analyzed complaints, and these complaints are directly related to adverse events, the device manufacturer should probably begin preparations for a “for-cause” or should I say, “Directed” visit from the agency. If the complaints being received point to the device in question injuring patients, be prepared to execute that six-letter word “RECALL.” There goes the doctor invoking that nasty word again. When creating a procedure for complaint management, Dr. D always prefers the use of flow charts and decision trees. With the help of engineers, clinicians, quality, regulatory and other functional organizations, that exude some influence over complaint handling and management, effective decision trees, with escalation clauses, e.g., file or not file an MDR, can be created.

Takeaways
Since the procedural requirement continues to be the most salient requirement associated with compliance with the QSR, there are five additional takeaways for this week.

1. Device manufacturers must ensure complaints from all potential sources are collected and entered into their complaint management system.
2. Each complaint needs to be reviewed and a documented decision made in regards to pursue or not pursue an investigation.
3. Where investigational results point to the conclusion that an adverse event has occurred, the device manufacturer must file an MDR.
4. Dr. D recommends a complaint file be opened for each complaint received.
5. Confucius says, “It is better to over report than under report MDRs.”

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 820.198 (Complaint Files – subsections d and e) – cheers from Dr. D. and best wishes for continued professional success.

References:

1. Code of Federal Regulation. (2010, April). Title 21 Part 820: Quality system regulation.  Washington, D.C.: U. S. Government Printing Office.

2. 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. 

3. FDA – U.S. Food and Drug Administration Website. (2010). Warning letters. Retrieved October 22, 2010, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/