Complaints, complaints, and more complaints, extracted from the opening sentence from the previous edition of Devine Guidance, is also an appropriate introduction for this edition DG and Dr. D’s continued diatribe on complaint management covering Subsections ‘d’ and ‘e.’ There is really only one takeaway from this edition of DG, complaints “shall be promptly reviewed, evaluated, and investigated.

The Quality System Regulation (QSR) requirement for complaint handling (21 CFR, Part 820.198) contains a significant amount of granularity in regards to ensuring device manufacturers collect, investigate, and analyze complaints made against their manufactured medical devices. It is imperative that device manufacturers analyze the complaint information received in ascertaining the need to report adverse events (serious patient injury or death) to the agency.

Form3500(a) is the tool employed to ensure the timely reporting of adverse events, with the information making its way into FDA’s Manufacturer and User Facility Device Experience (MAUDE) Database. In fact, the omphalos (look-it up if you must) of an agency inspection is often complaints. If device manufacturers want to quickly ingratiate themselves with the agency, mismanage complaints or fail to file MDRs. Such stellar performance will be rewarded by a friendly visit from the agency, with a Form 482 in hand (a.k.a., notice of inspection).

Warning letter violations
Similar to the previous edition of DG, Dr. D was quickly able to screen through the FDA’s Warning-Letter Database and retrieve two additional violations of 820.198 to share with my readers. In fact, the doctor was once again able to find violations of this requirement embedded in the first two warnings letters issued to device manufacturers in October. That said, Dr. D is going to climb out on that proverbial limb and hypothesize that this just may be the number one observation noted by FDA during their inspections, or at least in the top five.

The first warning-letter winner “failed to establish and maintain adequate procedures.” Additionally, the recipient of this ominous letter from the agency logged complaints but never investigated the complaints. I guess that would beg Dr. D to ask the question, “What is the point?” Furthermore, what part of, “took care of the issue,” can remotely be construed as effective complaint resolution? “Took care of the issue” is an acceptable response from the doctor’s auto mechanic; however, a device manufacturer – not so much.

In throwing the proverbial gas onto the fire and fanning the flames, this device manufacturer also failed to provide a reasonable response to the agency. The poor response, coupled with the 11-observation warning letter, means this device manufacturer will remain in FDA’s doghouse for a very long time. Nice!

The second warning-letter recipient “failed to establish and maintain procedures.” Once again, Dr. D hopes the readers are connecting the dots and seeing the trend here. For those of you that are not seeing the trend, please commit to memory Devine Guidance Rule # 6 – All procedures, work instructions, drawings, specifications, etc. must be written, well-documented, and controlled with in a defined document control system. In fact, there just might be a test administered by Dr. D during the “Supplier Controls and Quality Management: Regulation and Best Practices in Medical Technology Conference” being held in Washington, DC in January 2011. Dr. D will be in attendance; and I hope my readers will be as well.

Continuing on, warning letter two is another fine example of a stellar device manufacturer not having a written procedure for complaints. In fact, this device manufacturer saw no real value or purpose in opening complaint files. I think this type of performance deserves a big “Duh, duh-duh,” thanks Carlos Mencia. Additionally, this manufacturer failed to provide the agency with effective corrective action addressing the deficiency, including evidence supporting the deficiency had been corrected. Similar to the recipient of the first warning letter, Dr. D believes this device manufacturer is also about to elevate their ongoing relationship with FDA to a new and interesting level.

Warning letter One (October 2010): Observation 4 of 11 – 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 failed to maintain complete complaint records as required by the law. A review of 35 complaints from 2009 and 2010 revealed none of the records met the quality system requirements for complaint files because there was no documentation to show the complaints were investigated and what action was taken following the investigation of the complaints. Listed below is an example of this deficiency of the complaint handling system of your firm:

• A complaint received on May 20, 2009, for the PACS device states, “…she tried merging a patient’s studies…But now that she has done that there are no studies under the patient’s profile.” The problem resolution is documented as “… took care of the issue.” There is no additional information maintained for this complaint.
• A complaint received on July 10, 2009, for the PACS device states”…Read Station is not allowing the user to lighten or darken images at window level… they can’t mark images as dictated… ” The problem resolution is documented as “…took care of the issue.” There is no additional information maintained for this complaint.
• A complaint received on January 19, 2010, for the PACS device states “… a study would not burn on a cd for a patient… ” The problem resolution is documented as “…took care of the issue…” There is no additional information for this complaint.

FDA’s Response to Observation 4 of 11: Your response states your firm ” …has evaluated customer complaints but has not followed a formal procedure with documentation. We will establish and implement quality procedures to document and evaluate customer complaints….A complete written, reviewed, and approved set of procedures and process implementation will be completed by August 31, 2010….” We have reviewed your response, dated June 2, 2010, and have concluded it is inadequate because your firm did not demonstrate implementation for receiving, reviewing, and evaluating complaints for the PACS device by a designated unit within the firm.

Warning letter Two (September 2010): Observation 3 of 6 – Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints and failure to maintain complaint files, as required by 21 CFR 820.198(a).

For example, you do not have a written complaint procedure nor do you maintain complaint files for the complaints stated to the FDA investigator that your firm received concerning the zIVF-AIRe™ 100C Photo-Catalytic Air Purifier.

FDA’s Response to Observation 3 of 6: Failure. We have reviewed your response and have concluded that it is inadequate. Your firm has not adequately addressed the requirements of 21 CFR 820.198(a) nor have you identified any systemic corrective actions regarding the lack of procedures for the receipt, review, and evaluation of complaints by a formally designated unit. Your firm has not provided a written complaint procedure nor have you provided complaint files for the complaints stated to the FDA investigator that you received concerning the zIVF-AIRe™ 100C Photo-Catalytic Air Purifier.

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 evaluation
Section 820,198 (d) delineates the requirement that reportable complaints, to FDA, “shall be promptly reviewed, evaluated, and investigated.” The expectation is that these investigations are prioritized and expedited. Taking three months to report a reportable event is just not going to work.

In fact, according to 21 CFR, Part 803 the requirement for adverse-event reporting is 30-days for manufacturers and 10-days for device users, unless it has been determined that the device poses an “unreasonable risk of substantial harm to the public health,” then the timeline is accelerated to five days. Based on the warning letters depicted above, device manufacturers that fail to adhere to the QSR requirements for managing complaints will receive a warning letter. Dr. D guarantees it.

Additionally, 820,198 (d) requires a designated individual(s) to promptly review, evaluate, and investigate all complaints. The doctor strongly suggests that the individual(s) performing this review is/are competent and capable of making fundamentally sound decisions, premised on the outcome of each complaint investigation. Furthermore, the results of each review, evaluation, and subsequent investigation need to be collected and placed into a complaint file. The doctor strongly recommends opening a separate complaint file for each complaint received. Finally, the complaint records, in addition to what will be covered in the next section, shall contain:

1. A determination as to whether or not the device failed to meet specification (a.k.a. product specification);
2. Whether the device was employed for a therapeutic or diagnostic application; and
3. The link between the device and the reported complaint (incident) and subsequent adverse event.

Complaint investigation records
In addition to the three items discussed in the previous section, FDA has additional requirements, delineated within the QSR, for basic complaint data. One salient point to remember is the link between complaints and the Corrective and Preventive Action System (CAPA). In many instances, the outcome of a complaint investigation will drive the need for CAPA to remediate a device performance issue, e.g., failure for a coronary stent to deploy. As part of the agency’s approach to inspections, the Quality System Inspection Technique (QSIT) will focus on complaints and CAPA as potential entry points into a device manufacturer’s quality system.

So what additional information should the complaint record contain? Not wanting to state the obvious, the complaint record should contain all information relevant to the complaint investigation. Additionally, the QSR requires:

1. The actual name of the device, e.g. Acme Super Catheter;
2. The date the complaint was actually received, reported, or the device manufacturer actually became aware;
3. Identifiers specific to the device, e.g., batch and control numbers;
4. The name, address, and telephone number of the individual and/or organization reporting the complaint;
5. The nature of the complaint augmented by obtaining as much detailed information as possible (hopefully something more than the device is broken);
6. The dates associated with the investigation and the results of the investigation (make sure the name of the investigator(s) is/are also captured);
7. Identification of the need to elevate the results of the investigation into the CAPA system (including CAPA number); and
8. A copy of the reply letter back to the person and/or organization making the complaint (Dr. D recommends sending the letters with proof of delivery required – FedEx, UPS, etc.).

Dr. D also recommends ensuring decision making in regards to MDR be included in the complaint record. An additional watch out, complaint data and complaint trending should be included in management review. Finally, the entire complaint management process should have a specified timeline as to how long complaint investigations take. If the device manufacturer puts into writing (a.k.a., a procedure) that the entire process will take 12 months, rest-assured, FDA will take exception to the length of time specified.

Considering the amount of time it may take to: (a) return a device back to the manufacturer; (b) complete a detailed investigation; (c) summarize the data in a written report; (d) open up a CAPA (if deemed appropriate); and (e) send a reply back to the complainant; Dr. D strongly opines the entire process should not exceed 60 days. However, most device manufacturers’ lean toward 90-days as policy; and Dr. D fundamentally disagrees with 90-days.  

Takeaway: Promptly review, evaluate and investigate complaints
There is really only one takeaway from this edition of DG, complaints “shall be promptly reviewed, evaluated, and investigated. Documenting the results is a given, maintaining accurate records is a given, reporting adverse events is a given, correcting problems is a given, and having a WRITTEN PROCEDURE is a given. However, failure to manage complaints in accordance with 820.198 is not a given; and can be equated to giving the agency an open invitation to show up on your doorstep with a Form 482 in hand.

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 f and g) – 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/