Dr. D would like to begin this edition of DG by wishing a Happy 235th Birthday to my fellow Marines. The United States Marine Corps was founded on November 10, 1775 in Philadelphia, PA at a fine drinking establishment known as Tun Tavern. Marine Corps Order 47 was written and issued on November 1, 1921 recognizing the birth of our beloved Corps and our glorious history. Major General John A. Lejeune signed the order, which requires the reading of Order 47 on the 10th Day of November, until the end of time. Semper Fidelis and Happy Birthday to all who served!

Dr. D is warming up to the introductory sentence of complaints, complaints, and more complaints, so the doctor will use it one final time. It is generally accepted, in the civilized world, that two events in life are expected to occur—death and taxes. Not unlike the inevitability of death and taxes, device manufacturers can expect to receive a complaint or two, or two thousand. The sooner device manufacturers face this reality, the sooner they can develop and deploy effective complaint-management systems that comply with the Quality System Regulation (QSR).

That said, device manufacturers might not physically maintain a complaint-handling system within the same four walls that house a device manufacturing plant. In fact, the processing of complaints may not even be in the same country or on the same continent.

This week Dr. D. will provide insight into remote complaint handling requirements, separated from the actual manufacturing plant and/or in a different country (a.k.a. outside of the United States – OUS). This edition will conclude the doctor’s exploration of 21 CFR, Part 820.198, which is the last element of Subpart M – Records.

One final comment, one of the doctor’s friend’s (yes-some dare to claim me as a friend) believes Dr. D might be suffering from Chronic Traumatic Encephalopathy, a.k.a. too many hits to the head, suffered during a wayward youth. This individual has reached this conclusion because of my penchant for ranting, scribbling, and writing week-after-week. I will let you folks be the judge in regards to the doctor’s potential brain damage, real or perceived.

Warning letter violations
In an effort to test my theory that violations of 820.198 are at the top of FDA’s observation list, Dr. D opened a couple of warning letters that were issued earlier this year. Just like the previous two editions of DG, each warning letter opened contained observations documenting a violation of 820.198. What a surprise!

In warning-letter one, the observation commenced with the customary “failure to establish and maintain adequate procedures.” For frequent visitors to DG, you know how the doctor feels about procedures, or should I say, “lack of procedures.” Additionally, the inspector documented six specific incidents identifying complaints that were never adequately investigated. As Dr. D has previously opined, “what is the point of having a complaint-management system if the complaints are not investigated, and the results employed to drive corrective action.” “Duh Duh-Duh,” gosh the doctor enjoys the comedic rants of Carlos Mencia.

Furthermore, this device manufacturer failed to provide documented evidence as part of their response to the agency. Can you say, “This device manufacturer is about to enter an interesting relationship with FDA?” Some might categorize this soon-to-be relationship with FDA as a bad dream. Do you remember the words to the Alice Cooper song circa 1975, “Welcome to my Nightmare?” Just change the words “my nightmare” with the “FDA’s nightmare.”

The second warning-letter recipient received a four-observation warning letter, with three of the observations specific to the lack of effective complaint management. Once again, an official “duh duh-duh” is in order. This offender failed to; collect appropriate complaint information (Strike 1), complete adequate investigations (Strike 2), or determine if complaints were reportable to FDA under 21 CFR, Part 803 (Strike 3). This device manufacturer has struck out.

Warning letter One (July 2010): Observation 3 of 8 – Failure to establish and maintain adequate procedures for complaint handling to include review, evaluation, and investigation of any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications, as required by 21 CFR 820.198(c). For example, 6 out of 40 complaints reviewed during the inspection were not adequately investigated. Specifically:

a. Complaint 10818, dated 9/10/09, reported a patient that had received a 2nd degree bum from a Blanketrol III device, and was classified as a Category Three. Complaint Handling procedure SOP 7.2.3(M) Rev. 13, section 6.4.1.1 states “It is CSZ policy to retrieve alleged failed product to ensure adequate root cause determination and corrective action.” No fundamental cause for the device malfunction was reached.

b. Complaint 10637, dated 8/18/09, reported that a Blanketrol II device cooled past its setpoint when in automatic mode. The unit was set to 33°C and cooled to 30°C, and did not return to 33°C as expected. The unit maintained operation at 30°C. The complaint investigation did not include any evidence of the testing of the alleged defective unit, and you were unable to locate the RMA documentation that would support activities performed in an investigation.

c. Complaint 10668, dated 8/19/09, reported two complaints ofbums from the same device. Complaint Handling procedure SOP 7.2.3(M) Rev. 13, section 6.4.1.3 states “If product is not returned within 30 days (90 days for international return) and after three attempts, the customer will be notified of such… Document the three attempts …” You provided evidence the one attempt was made, and that a second attempt was discussed with no evidence of its completion within 90 days of having received the complaint.

d. Complaint 08836, dated 5/4/09, reported debris contained within a seal for a pouch of a sterile 11″ by 12″ pad. The debris in the seal was confirmed, but the cause of the debris was not investigated. You admitted that an investigation should have been performed for this complaint and was not.

e. Complaint 11020, dated 10/13/09, reported a Blanketrol 233 device had no display with the power switch on and that fuses had blown twice. Complaint Handling procedure, SOP 7.2.3 Rev. 13, section 6.4.1.3 states “If product is not returned within 30 days (90 days for international return) and after three attempts, the customer will be notified of such and advised that if the product is not received within 10 days (30 days for international return) the complaint will be closed and (if applicable) credit may not be given. Document the three attempts …” No evidence was provided that suggests the devices were asked to be returned for investigation and no investigation has otherwise been conducted.

f. Complaint Handling procedure, SOP 7.2.3 Rev. 13, section 3.1 “Definitions: Complaint” defines a complaint as “Any written, electronic or oral communication that alleges deficiencies related to the identity, quality, durability, safety or performance of a medical device that has been released for distribution.” In addition, SOP 7.2.3 Rev. 13, section 6.1.2.1 states that sources of complaints can include “returned goods form (RMA).” Return Material Authorization (RMA) 7526 states “CUSTOMER STATES THAT NEW BD HAS AN A/D ERROR RETRIED OLD BD -NO ERROR OF THIS TYPE CAT ONE-REPLACEMENT.” No complaint was opened for this RMA.

FDA’s Response to Observation 3 of 8 – We have reviewed your responses and have concluded that the adequacy cannot be determined. You opened a CAPA to address the identified complaint deficiencies. You have been in contact with the complainants for 10818, 10668, and 11020 to obtain further information. You have contacted the complainant for 10637 and are awaiting their testing results. Complaint 08836 was concluded with the opening of a CAPA, identification of the root cause of the debris in seals, and approval of the corrective action. Complaint Handling procedure, SOP 7.2.3 Rev. 16 was provided in your response and has altered the need to perform investigations to include all complaints. You created a Complaint Review Project Plan to perform a retrospective complaint review back to June 2009. However, documented evidence per Complaint Handling procedure, SOP 7.2.3 Rev. 13, section 6.4.1.3 was not provided for any of the proposed complaint investigations beyond the summary in your response. Additionally, preventive actions were proposed but the effectiveness of the actions has not been determined.

Warning letter Two (June 2010): Observation 1 of 4 – Failure to maintain complete complaint files and complete complaint handling procedures, as required by 21 C.F.R. § 820.198(a). Specifically, your firm is not always documenting enough information from the complainant so that an evaluation can be performed to determine if complaints are valid. Additionally, your “P001 Complaint Reception” procedure, dated 07/11/05 does not ensure that enough information is recorded from the complainant so that an initial review and evaluation of the complaint can be performed. For example, RMA 606698’s “Description of the Event” section states “Handpiece and Cord – 402JA233: Passed all tests – Returned (Not Under Warranty-402JA233)”. There is no description of the problem that the customer had with the device.
Observation 2 of 4 – Failure to fully investigate complaints involving the possible failure of a device, labeling or packaging to meet any of its specifications, as required by 21 CFR§ 820.198(c). Specifically, if a device fails outside the one-year warranty period, the error code is recorded but the device is not returned to the manufacturer to be investigated.

Observation 3 of 4 – Failure to establish complaint handling procedures that ensure that complaints are evaluated to determine whether the complaint represents an event which must be reported to FDA under part 21 CFR§ 803, as required by 21 CFR§ 820.198(a)(3). Specifically, your “P001 Complaint Reception” procedure fails to describe the information that must be obtained from the complainant to determine if an event is reportable under part 21 CFR§ 803 as a malfunction Medical Device Report.

Quality System Regulation – 21 CFR, Part 820
QSR – Subpart M – Records
Section 820.198 Complaints
(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.

(d) Any complaint that represents an event which must be reported to FDA under part 803 of this chapter shall be promptly reviewed, evaluated, and investigated by a designated individual(s) and shall be maintained in a separate portion of the complaint files or otherwise clearly identified. In addition to the information required by 820.198(e), records of investigation under this paragraph shall include a determination of:

1. Whether the device failed to meet specifications;
2. Whether the device was being used for treatment or diagnosis; and
3. The relationship, if any, of the device to the reported incident or adverse event.

(e) When an investigation is made under this section, a record of the investigation shall be maintained by the formally designated unit identified in paragraph (a) of this section. The record of investigation shall include:

1. The name of the device;
2. The date the complaint was received;
3. Any device identification(s) and control number(s) used;
4. The name, address, and phone number of the complainant;
5. The nature and details of the complaint;
6. The dates and results of the investigation;
7. Any corrective action taken; and
8. Any reply to the complainant.

(f) When the manufacturer’s formally designated complaint unit is located at a site separate from the manufacturing establishment, the investigated complaint(s) and the record(s) of investigation shall be reasonably accessible to the manufacturing establishment.

(g) If a manufacturer’s formally designated complaint unit is located outside of the United States, records required by this section shall be reasonably accessible in the United States at either:

1. A location in the United States where the manufacturer’s records are regularly kept; or
2. The location of the initial distributor  if any, of the device to the reported incident or adverse event.

Complaint management unit away from manufacturing site
The requirements for managing a complaint-handling unit detached from the actual manufacturing facility are pretty basic. For starters, a written procedure is a salient requirement. However, the actual dynamics of complaint management will differ versus a self-contained business unit.

The regulation, 820.198(f), requires two fundamental objectives be attained. Number one, the results of all complaint investigations should be readily accessible by the manufacturing facility. Number two, the complaint records should be readily accessible by the manufacturing facility. This task is relatively easy to achieve and can be accomplished by employing a single complaint receptacle for the entire organization. This can be broken down even further into specific business units. Several available electronic complaint management systems (Part 11 compliant) can be employed as a solution for complaint management for organizations both large and small. Additionally, pursing an electronic system approach, for complaint management, allows device manufacturers to trend and report results as part of the management-review process.

Remember, complaints must be included as an input to management review. Besides, Dr. D strongly believes that information gleaned from customer complaints should be used to drive continuous-improvement practices that improve the safety and efficacy of devices.

Complaint management unit located outside theU.S. (OUS)
Similar to complaint management and processing being performed at a location other than the actual manufacturing facility, a complaint management unit maintained OUS is acceptable, providing a robust-written procedure delineating the complaint-management process exists.

Once again, records of each complaint must be “reasonably accessible” within the United States. Therefore, if a device manufacturer’s complaint management center is located in Katmandu (being managed by Bob Seeger – just kidding), the device manufacturer needs to ensure complaint records are accessible at either: (1) a location identified within the states, where records are routinely stored; or (2) the location of the distributor that sold the medical devices (if applicable and linked to the actual complaint and/or adverse event). Basically, each device manufacturer must take control of their destiny in regards to complaints. Remember, it is not enough to have successfully opened, analyzed, investigated, compiled, and stored complaint records. Subsections (f) and (g), of 820.198, specifically requires complaint records to be accessible. In fact, the accessibility piece will become an important feature, not if but when FDA decides to pay a device manufacturer a friendly visit.

Trust Dr. D when I say, “If device complaints are being reported as adverse events; and the number of events are perceived to be excessive, expect a visit from the agency.” When your Chief Jailable Officer (CJO) is sitting across from the investigator, he will have a newfound appreciation for having complete, accurate, and accessible complaint records for the agency to review. Why? Because documented evidence of compliance with the QSR is always a device manufacturer’s best defense during an inspection. Otherwise, can you say, “Where do I sign the Form 483?”

Finally, if a device manufacturer cannot convince the agency that the complaint management system is effective; and that the adverse events are directly related to product safety and efficacy, be prepared for that ugly six-letter word “Recall!”

Takeaways: Complaints can be managed away from manufacturing, and even OUS
The key takeaways for this week’s edition of DG are (a) complaints can be managed by a separate organization located in a facility detached from manufacturing operations; and (b) complaints can be managed OUS. The salient point, when managing complaint externally, is the accessibility of complaint records, regardless of their location. This information needs to be accessible. The information collected as part of the overall complaint process will drive the decision-making process in regards to reporting adverse events; and the resolution of device issues through corrective and preventive action.

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 – N (Servicing), specifically 820.200 (Servicing) – cheers from Dr. D. and best wishes for continued professional success.

References:

1. Code of Federal Regulation. (2010, April). Title 21 Part 803: Medical device reporting.  Washington, D.C.: U. S. Government Printing Office.
2. Code of Federal Regulation. (2010, April). Title 21 Part 820: Quality system regulation.  Washington, D.C.: U. S. Government Printing Office.
3. 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. 
4. FDA – U.S. Food and Drug Administration Website. (2010). Warning letters. Retrieved October 27, 2010, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/