The doctor is always amazed when he examines a CAPA system in which the owners swear up and down that their super-charged system is capable of “obviating” (look-it-up) all of their organizational woes. Sorry folks, but injecting the CAPA programs with steroids isn’t the answer. In fact, the more complex the CAPA system, the more opportunities for Dr. D’s good friend, Mr. Murphy to raise his head and unleash organizational mayhem. Please keep in mind, FDA, Health Canada, MHLW, the Competent Authorities in Europe, etc., want a system that actually works. That being said, Dr. D’s opinion is that it is best to keep the system simple. Simple CAPA system, good! Complex CAPA system on steroids, bad!
The doctor recommends pursuing Dr. D’s 7-Step Model encompassing: (a) problem definition and scope; (b) initial investigation; (c) root-cause analysis; (d) proposed solution; (e) verification, validation, and implementation, (f) verification of effectiveness, and (g) documenting and sharing CAPA information. Remember to keep in mind the potential impact to product safety and efficacy, regulatory compliance, and overall quality system effectiveness, resulting from CAPA-driven changes to product, processes, and procedures.
Recent warning letter
The doctor has taken the liberty of extracting an excerpt from a March 5, 2013 warning letter, issued by our good friends from the agency.
Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, the corrective and preventive action procedure titled, “Improvement,” Chapter 7 of PP8 Quality Management System procedure Rev. 0.9, has the following incomplete or missing requirements:
a) missing and incomplete requirements in Section 7.1, “Scope:” addressing the analysis of sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems, and does not identify all sources of potential causes of nonconforming product or other quality data sources in the procedure;
b) no requirements for verifying or validating corrective or preventive actions prior to implementation, to ensure the actions do not adversely affect the devices;
c) missing requirement for assurance that all required activities are to be documented; and
d) no requirements for investigating the cause of nonconformities relating to processes, products, and the quality system.
Review of (b)(4) Corrective Action record, CAPA No. (b)(4), related to a U.S. marketed device, the Lumix 3 Ultra/Plus, did not reveal any of the required information as described above.
Problem definition and scope phase
In this initial phase, the CAPA owner is doing nothing more than providing some initial framework for the CAPA. Basically, the CAPA form is opened and critical information surrounding the non-conformance is collected. Depending on the nature of the problem, initial target dates may be identified. However, moving into the initial investigational phase should occur as quickly as possible.
Initial investigation phase
The initial investigation phase associated with CAPA is pretty cut and dry. The QSR requires device manufacturers to investigate the cause of ALL product issues (nonconformities), process issues, and quality system issues. Remember, device manufacturers are not free to pick and choose the problems they want to resolve. Device manufacturers need to fix all nonconformities that have been identified. Additionally, device manufacturers need to exhibit a sense of urgency in executing investigations. One year, or even longer, is just too damned long to complete an initial investigation. Furthermore, if the agency determines the approach to CAPA investigations is unsatisfactory, the device manufacturer can expect to receive a Form 483, during their next friendly FDA inspection.
Root-cause analysis phase
So what are regulators looking for in regards to root-cause analysis? In short, regulators want device manufacturers to continually monitor all aspect of their operation and use the results, if warranted, as quality inputs into the CAPA system. For example, unfavorable trends in yields discovered on the manufacturing floor, a nonconformance discovered during an internal quality audit, returned product, and product complaints are a few examples of quality inputs requiring input into the CAPA system. The QSR specifically adds a callout for “other sources of data” and “other quality problems.” These catchall phrases equate to considering all potential and actual quality problems for inclusion into the CAPA system or an “all encompassing approach.” Remember two of the salient purposes of CAPA are; (a) to prevent problems from occurring, and (b) prevention of problem recurrence once a problem has occurred.
However, please do not forget, root-cause is root-cause. What? Seriously folks, there is no value in providing a less than robust root-cause analysis. Feel free to employ the tools the QA gods, such as Dr. Deming gave to us all. So why is root cause so darned important? If you have to ask then you are in the wrong business. If root cause does not correctly identify the underlying problem, the proposed solution is probably not going to work. Simply stated; “A crappy investigation results in the development of a crappy solution.”
Proposed solution phase
The expectation of regulators is that once a CAPA investigation is complete and root-cause identified, the appropriate actions needing to correct nonconformities should be identified. The doctor would like to warn the readers against using too many concessions such as “no-further action is required due to an isolated incident” or and oldie but a goody “no obvious trend.” Device manufacturers that frequently invoke concessions are typically awarded with Form 483s observations questioning the effectiveness of their CAPA system. That said, once the appropriate actions have been identified, Dr. D strongly recommends moving into the validation, verification, and implementation of the proposed solutions.
Validation, verification, and implementation phase
Although device manufacturers are typically pretty confident when they move into their implementing solution phase, they must first determine if the proposed action is going to have a negative impact on product safety and efficacy of finished devices. Dr. D is pretty positive, well maybe somewhat positive; device manufacturers do a good job performing in-depth root-cause analysis, while identifying potential corrections to problems. However, regulators want device manufacturers to be absolutely sure there is no potential negative impact to finished devices, prior to implementing changes.
Moving to implementation, device manufacturers need to ensure all changes are documented. Dr. D’s not so secret approach is to employ the change request process that feeds the document control system. All changes need to be reviewed and approved. Additionally, changes made to product need to be captured within the Design History File (DHF). Furthermore, ensure FMEAs are reassessed for potential changes in levels of risk and/or occurrences. Finally, make sure your organization’s regulatory affairs group is involved with reviewing all product changes. Why? Product changes, depending on device class and regulatory authority involved, may require pre-approval prior to releasing the product into the market place, e.g., PMA supplement for Class III product in the US.
Verification of effectiveness (VOE) phase
Now Dr. D is going to climb out on a limb here and assume the readers are performing VOE phase. If not, what are you waiting for? If the CAPA resulted in a minor change to a procedure or a dimensional change to a mechanical drawing, then VOE can occur ASAP. However, if the change driven by CAPA was to correct a systemic issue, then 90-days is a realistic approach for returning to the proverbial “scene of the crime” and verifying that actions taken were effective and suitable for the risk. Over the years, the doctor has examined far-too-many CAPA systems were the VOE step is missing from the process.
Documenting and sharing CAPA information phase
Information is and always will be a powerful tool. It should be incumbent upon all device manufacturers to ensure information associated with quality problems, nonconforming product, and potential quality issues be disseminated amongst the proverbial ranks. Successful dissemination of information, i.e., Kaizen circles, etc, will result in the prevention of problem recurrence. For example, if there have been MDRs or vigilance reports opened that identify tip separation from a catheter, and the failure investigation determines the root-cause is process related, the operators on the manufacturing floor need to be made aware of the process problem. Otherwise, “history will repeat itself.”
I think the most important takeaway, for this edition of DG, is to use the CAPA system to fix all of your quality problems. A strong CAPA system will allow organizations to track quality problems to closure. Additionally, when problems are identified or potential problems noted, device manufacturers need to act quickly. If you ever want to see Dr. D angry, one way to do it quickly is to place a problem or other nonconformance into the CAPA system; and then take over a year to resolve an issue that should have been corrected in a few days or worst case a couple of weeks. In fact, that type of performance will quickly grab the attention of regulators as well. Remember CAPA is not rocket science. You identify problems and you fix problems. In closing, cheers from Dr. D. and best wishes for continued professional success.
- Code of Federal Regulation. (2012, 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.
- Devine, C. (2011). Devine guidance for complying with the FDA’s quality system regulation – 21 CFR, Part 820. Charleston, SC: Amazon.
- FDA – U.S. Food and Drug Administration Website. (2013). Warning letters. Retrieved March 29, 2013, from http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/