language: Deutsch   Français   italiano   Español   Português   日本語   russian   arabic   norwegian   swedish   danish   Nederlands   finland   ireland   English  

Process Verification vs. Process Validation: What You Need to Know complaint definition fda

Process Verification vs. Process Validation: What You Need to Know by Andrew Snow, Momentum Solutions, LLC and Walt Murray, MasterControl, Inc. May 10, 2012 | Free Downloads | |

Note: The views expressed in this article are those of the authors and do not necessarily represent those of their respective employers, GxP Lifeline, its editor or MasterControl, Inc.

Process validation officially became part of the FDA's Quality Systems Regulation in 1997. Fifteen years later medical device manufacturers still struggle with determining which processes require validation. The confusion traces back to two words, "fully verified." What does "fully verified" mean? What do I do if I determine that process can't be "fully verified?" And, equally important, what are the FDA's expectations when I can't?

The answer to the "fully verify" question can have big consequences. Failure to identify a process that requires validation can cause compliance issues, including warning letters, delays in pre-market submissions and field actions. A conservative approach of validating everything can be costly. And worse yet, some people erroneously think that if they can fully verify something, the verification has to be 100%. This approach, unless automated, may be a statistically invalid approach because even manual 100% inspection is statistically not 100% effective.

This article is related to: MasterControl Quality and Compliance Consulting (QCC) Validation Services . To get the full details, please download your free consulting services material.

A clear intent of the regulation is that quality cannot be inspected into a product. This has been firmly established in quality thinking. In essence, this requirement is stating that for some processes, inspection alone may not be sufficient.

The goals of this article are:

To clarify how to determine if something can be fully verified How to plan validation and process controls for those that can't be fully verified; and How to monitor and control processes using a risk-based approach

This will be accomplished by:

Revisiting some definitions of key terms and the regulatory requirements Describing how we determine what's critical to quality (CTQ) Dissecting the terms "fully verified" and describing the criteria for determining if something is fully verifiable Describing how to plan validation for processes that can't be fully verified Outlining a risked-based approach for controlling processes that can be fully verified Definitions and Regulatory Requirements

The requi mcgvrenw. mens moncler acorus down jacket blackrements for process validation established in the FDA's Quality Systems Regulation states in Part 820.75 (a) 1 :

"Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures."

A clear intent of the regulation is that quality cannot be inspected into a product. This has been firmly established in quality thinking. In essence, this requirement is stating that for some processes, inspection alone may not be sufficient. This is particularly true when the defect only becomes apparent or manifests after the product is in distribution or use. This could be because verification is not possible (e.g., reliability or durability) or it is not sufficient (e.g., requires destructive testing). The core of this requirement is that in order to gain confidence that the likelihood of these types of defects is small, we must use the capabilities of a process. This is clarified when we look at the definition of process validation in the regulation which states process validation is 2 :

"...establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications."

Thus, we'll see that this requires understanding the sources of variation, reduction and control of variation to establish a process that is capable of consistently meeting specifications. Such specifications and their associated acceptance criteria are determined using adequate design controls.

Design Controls and Process Validation

Before we dissect the term fully verified we need to go back and see how we determine what specifications are of concern. This determination should be established using effective design controls. Most professionals typically make the connection between design transfer and process validation while they overlook essential design outputs, which are the key design outputs that we must produce. So, one of the critical connections between process validation and design controls is that design outputs define the "predetermined specifications" or the results a process needs to meet.

One of the requirements for documenting design outputs is that they contain or reference acceptance criteria. These are sometimes referred to as critical to quality (CTQ) characteristics. In this sense, quality is defined as "the totality of features and characteristics that bear on the ability of a device to satisfy fitness for-use, including safety and performance." 3 These features and characteristics form the basis for acceptance criteria.

While there are many tools that can be used for developing CTQs, such as Design for Six Sigma (DFSS), Quality Function Deployment (QFD), and focus groups, from an FDA perspective a risk-based approach is imperative. Using such process tools as Fault Tree Analysis (FTA) or Design Failure Mode Effects Analysis (DFMEA) when linking product hazards to specifications is a thorough approach to effective post-control measures. So, for example, in DFMEA we ask: what are the effects of a design failing to meet its design requirements? If the failure results in a safety hazard to a patient or end user, then that specification becomes a CTQ. It is these characteristics that we'll focus on when asking if they can be fully verified.

Dissecting Fully Verified

To help understand the term "fully verified," we can go to the Global Harmonization Task Force's (GHTF) Process Validation Guidance document 4 . This document shows a decision tree which may be helpful in determining which process should be validated. When we look at Figure - 1, there are two fundamental questions to be answered: is the output (CTQ) verifiable and is verification sufficient and cost effective?

Most quality characteristics can be verified. Verification methods run the gamut from chemical tests such as pH or conductivity, physical tests such as tensile strength, dimension, or hardness, to electrical measurements such as voltage and impedance. In some cases, the measurements can't easily be done on routine production. Thus such dimensions are not effectively "detectable" and therefore, not capable of reliability or durability. This is the main concern for detectability as a key component of an FMEA. In other cases, the verifications are not sufficient because the method is destructive and reasonable sampling schemes may not be sufficient. One simple test to apply is asking if sampling "could be" 100% and in the case of destructive method the answer would be no. Finally, some tests (detection) lack the sensitivity to be effective as part of routine production.

Figure 1 - GHTF Process Validation Decision Tree

The cost effectiveness of the verification can also be an important consideration. In many cases, it may be more prudent to validate the process upfront to understand and control variation, thereby improving process capabilities, increasing yields and lowering scrap. These factors generally will outweigh even reducing the cost of inspection, making a strong business case for validation.

The GHTF Guidance gives us several examples of processes that should be validated, including:

Sterilization processes Aseptic filling Sterile package sealing Lyophilization Heat treating Plating processes Plastic injection molding

It's worth noting that the guidance says "should be." It is incumbent upon the manufacturer to understand the CTQs for its product through Quality by Design (QbD) and assess whether verification is sufficient. However, the FDA will be expecting that these processes will be validated, so if you determine that verification is sufficient, your rationale will need to provide appropriate documentation.

Planning for Validation

The best place to document your validation decisions is in the Master Validation Plan (MVP). While not required, it is best practice to document your decisions and outline the plan for processes that will need to be validated accordingly. The plan should scope out the validation effort, including the facilities, processes, and products covered by the plan. All the equipment under that scope of the plan should be identified, including any utilities such as electrical, water, and air compressors. It should also include the process equipment and any environmental controls such as clean rooms or Electro-static Discharge (ESD) controls. It is also common to include test methods and software used to automate processes . Plans will spell out the Installation, Operational and Performance Qualifications (i.e., IQ, OQ and PQ) to be done for each process. It is also common to see test methods and software used to automate processes included in the lifecycle of the product, although these may not be stated as IQ, OQ or PQ requirements.

The installation qualification shows that the equipment is installed according to its specifications. This document is typically comprised of checklists and simple verifications such as fixture inspections, gauge calibration or preventive maintenance checks. If automated software is used in the process, the IQ will check to make sure the right version is installed and validated. One can look at the requirements in Production and Process Controls Part 820.70 5 to use as a basis for making a good IQ checklist.

The OQ and PQ are the heart and soul of process validation. Once assured that the equipment is installed to specification, the manufacturer has greater confidence that the equipment is operating properly and can start to use the equipment to understand the sources of variation and work towards establishing a capable process. The goal of process characterization during the OQ is to understand the effects process inputs (e.g., temperature, time, and pressure) have on the outputs (e.g., burst strength for a sterile package seal).

GHTF Guidance Figures 4, 5, and 6 help illustrate the concepts. These are adopted below in Figures 2 and 3.

Figure 2 - Moving from an Unstable to a Stable Process during the OQ

The goal of the OQ is to understand what causes the instability in GHTF Figure 4 and reduce and control that variation to produce the stable process on the right. We should conclude through conformation runs that the stable process has the potential to meet our capability requirements. These results are typically achieved through designed experiments which seek to explore a wide range of possible input variables through screening experiments and then refine and optimize the most significant variables to produce a stable process with acceptable process potential capabilities. While it is tempting to cut straight to the vital few variables based on knowledge and experience to eliminate some of the experimental steps, these assumptions should be carefully documented in a risk-based process model and supported by scientific and historical data that clearly shows the relationships between input and output variables. A high-risk consequence condition can trump a Pareto approach.

The goal of the PQ is to show that process is capable under conditions anticipated during manufacturing. These conditions may include multiple shifts, operators, material lots and other factors that represent potential sources of uncontrollable variation. The purpose of process validation is not so much to show you have excellent process capabilities but to demonstrate you know why you have excellent process capabilities.

Once process validation is completed, the manufacturer is required to establish monitoring and control to ensure the validated state of control is maintained (Part 820.75(b) 6 ). The manufacturer should document that the validated process was performed by qualified operators and note the monitoring and control methods, data, date performed, the individuals performing the process, and the major equipment used.

Figure 3 - Demonstrating a Capable Process during the PQ Risk-Based Approaches to Monitoring and Controlling Processes

Whether you have validated a process or determined that verification is sufficient process, monitoring and control are required. For validated processes, this is established in Part 820.75(b) and for all processes it is established in Part 820.70(a):

"Where deviations from device specifications could occur as a result of the manufacturing process, the manufacturer shall establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications. Where process controls are needed they shall include among other things 'monitoring and control of device parameters and component and device characteristics during production.'"

Fundamental validation concepts are the same, while additional requirements may be commensurate with a validated process during monitoring and control. A risk-based approach is used for such special requirements which can then be developed as part of a control plan based on a process FMEA.

If you don't validate, do you have to do 100% inspection in order to fully verify? No - the regulation doesn't say this. It does say (820.70) "Where deviations from device specifications could occur as a result of the manufacturing process, the manufacturer shall establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications." Where process controls are needed, they shall include, among other things, "monitoring and control of device parameters and component and device characteristics during production." It also tells us in 820.80 that we need to establish in-process and final acceptance activities. Finally in 820.250, statistical techniques are delineated - "Where appropriate, each manufacturer shall establish and maintain procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics."

There has been at least one warning letter for not 100% testing if not validating but interpreting requirements based on one or two warning letters is difficult. In 2009, the Cincinnati District office of the FDA issued a warning letter to Hammill. The warning letter states that Hammill's response to not validating certain cleaning, passivation processes and CNC equipment because they did in-process and final inspections/test was "inadequate because you are not testing every device to assure it meets specifications." 7 Of course. Reading the warning letter without the 483, let alone the Establishment Inspection Report, is difficult. We don't know about the acceptance criteria (CTQs), how they were measured, whether the testing was destructive and hence, whether subsequent inspection or tests were sufficient. So it is difficult to make the leap to a requirement that all processes that are not validated must be 100% tested. In the end the regulation clearly states that process controls should be based on appropriate statistics, which require some knowledge of risks in order to be applied properly.

An example will help illustrate how to establish controls based on risk and the significant role validation plays in establishing the basis for control. For example, the CTQ for burst strength is tied to the risk associated with non-sterile packaging due to package seal failure as shown in Figure - 4. To achieve an acceptable risk level, we had to establish better than six sigma process capabilities during process validation. The trick is to establish process monitoring that has a low risk of not detecting a shift to an unacceptable level of process capabilities of five sigma, or a greater likelihood of generating defective seals. Using statistical process control (SPC) we establish a control plan that indicates an effective control measure of burst tests will be performed on a sample of 25 units every hour of production. We are concerned with a 1.0 sigma shift in the process average burst strength as this would reduce risk to an unacceptable level. We can calculate the beta risk or risk of not detecting the shift using the beta risk formula below 8

β = φ(L-kûn) - φ(-L-kûn)


β = Beta Risk L = The number of sigma in the lower and upper control limits, typically 3 φ() = Cumulative Standard Normal Distribution k = Process shift in sigma units û = square root of n = Sample size

For our example above, if we assume the typical binomial three sigma limits for the control limits and a desire to detect a 1.0 sigma shift, the beta risk is estimated at 0.002, giving us high probability of detection or 2 versus a 1 almost certain to detect. This, along with the occurrence ranking of 1, gives us acceptable risk. From this we can see that the combination of acceptable process capabilities and process monitoring are required to make risk acceptable.

This is just one example of how to estimate the beta risk and set SPC control measures. Average run length, or the average number of samples necessary to detect a shift can also be used, which helps bring sample frequency into the equation.

Figure 4 - Example Risk-based Control Plan for Burst Strength Conclusion

The key to understanding whether a process requires validation is to understand if it is verifiable and assessing the sufficiency of verification. It is best practice to document these decisions and plan the validation effort. Some tests cannot be done on a routine basis, are destructive or lack the sensitivity to be sufficient. The heart of validating a process is ensuring it is installed to specification, while characterized and optimized to be under control and capable of consistently meeting specifications. The risk-based approach shows that understanding how to achieve excellent process capabilities reduces the likelihood of defects in the first place. In addition, process monitoring with low beta risk assures detectability if there are problems to be addressed as necessary. Verification alone may not be sufficient to produce acceptable levels of risk.

References 1. Medical Devices; Current Good Manufacturing Practice (CGMP) Final Rule; Quality System Regulation, Federal Register, Vol. 61, No. 195, Monday, October 7, 1996, Rules and Regulations, p52659 2. Medical Devices; Current Good Manufacturing Practice (CGMP) Final Rule; Quality System Regulation, Federal Register, Vol. 61, No. 195, Monday, October 7, 1996, Rules and Regulations, p52656 3. Id . 4. Quality Management Systems - Process Validation Guidance, GHTF/SG3/N99-10:2004 (Edition 2) 5. Medical Devices; Current Good Manufacturing Practice (CGMP) Final Rule; Quality System Regulation, Federal Register, Vol. 61, No. 195, Monday, October 7, 1996, Rules and Regulations, p52658 6. Supra note 1. 7. Food and Drug Administration, Warning Letter, Hammill Manufacturing Company, 01/06/09 8. Introduction to Statistical Quality Control, 5th Ed., Douglas C. Montgomery, John Wiley & Sons, 2005, p 217.

Andrew Snow has more than 25 years' experience directing and leading operations, quality, and process design-development for medical device companies, contract manufacturers, suppliers and several successful start-up ventures. He is president of Momentum Solutions, LLC a consulting firm specializing in solutions for design control, risk management and process validation for medical device companies.

Andrew has championed several lean and Six Sigma programs reducing cycle time, improving process capability, reliability, order delivery and customer satisfaction. He is an instructor with the Association for the Advancement of Medical Instrumentation (AAMI) and was recently the subject matter expert for revisions to their process validation course. He is a graduate of Northwestern University where he obtained a master's degree from the School of Industrial Engineering and University of Arizona with a certificate in Systems Engineering.

Walt Murray is MasterControl's director of quality and compliance services. He is a specialist in the quality and regulatory professions with more than 25 years' experience to his credit, working with nationally-recognized organizations including Aventis-Pasteur, Merck, Pfizer, Stryker, USANA, Del Monte Foods and the American Red Cross National Labs. He is certified in quality systems auditing, problem solving, and process control using Six Sigma principles that support lean enterprise, including kaizen improvement and advanced planning principles. His extensive audit experience covers several industries and he's successfully brought several medical device companies to full registration under the ISO process model standard. Murray has also worked extensively in risk and supplier management.

A graduate of the University of Richmond, Murray is a member of the Society for Manufacturing Engineers (SME); Regulatory Affairs Professions (RAPS); the American Society for Quality (ASQ); and the Intermountain Biomedical Association (IBA).

Share This Article

Watch Related Videos

900){$('#vid22').ekkoLightbox({type: 'webpage', title: 'Reducing Risk with MasterControl'})}else{$('#Mvid22').ekkoLightbox({type: 'youtube', title: 'Reducing Risk with MasterControl'})}};"> 900){$('#vid22').ekkoLightbox({type: 'webpage', title: 'Reducing Risk with MasterControl'})}else{$('#Mvid22').ekkoLightbox({type: 'youtube', title: 'Reducing Risk with MasterControl'})}};"> Reducing Risk with MasterControl (3:18) 900){$('#vid28').ekkoLightbox({type: 'webpage', title: 'Trouble-Free Validation with MasterControl'})}else{$('#Mvid28').ekkoLightbox({type: 'youtube', title: 'Trouble-Free Validation with MasterControl'})}};"> 900){$('#vid28').ekkoLightbox({type: 'webpage', title: 'Trouble-Free Validation with MasterControl'})}else{$('#Mvid28').ekkoLightbox({type: 'youtube', title: 'Trouble-Free Validation with MasterControl'})}};"> Trouble-Free Validation with MasterControl (1:38) Download Free Resources Product Data Sheet : Validation Services Product Data Sheet : Validation Services and Solutions - What Sets MasterControl Apart White Paper : How Regulated Companies Can Improve the Contract Management Process to Increase Efficiency and Reduce Risks White Paper : Noncompliance to FDA Quality Standards: What's the Risk to Executives? Promotional : Brochure: MasterControl Risk™ Product Data Sheet : MasterControl Risk™ Product Data Sheet : MasterControl Risk Analysis™ Access Content

Related Links

Bill of Materials (BOM) Software Systems Document Control Software Systems Audit Management Software Systems Training Software Systems Corrective Actions - CAPA Software Systems Change Control Software Systems Nonconformance Management Software Systems Food Safety Software Systems Customer Complaint Management Software Systems Quality Management Software Systems Risk Management Software Systems
complaint definition fda

moncler mens sneakers
moncler sweater
moncler outlet new york city
discount moncler usa Home Regulatory Requirements for Europe, USA, Canada and Globally Career FAQs Blogs BONEZONE Articles Webinars Free SOPs, Whitepapers and Webinar Downloads SOPs Contact Us Testimonials Consulting Team Careers at Medical Device Academy Blog

Home → Complaint Handling Archive for Complaint Handling

Case Study Part 1: Packaging Complaint Investigation Posted by Rob Packard on November 9, 2015

More Facebook Email Google+ 1 Twitter Linkedin 27


This article explains how to perform a packaging complaint investigation using a case study example of flexible packaging that was found open by a customer. This is part one of a two part article. The second part will focus on the CAPA Process. Specifically, containment measures, corrections, corrective actions and preventive actions.

This case study example involves a flexible, peelable pouch made of Tyvek and a clear plastic film. This is one of the most common types of packaging used for sterile medical devices. In parallel with the complaint investigation, containment measures and corrections are implemented immediately in order to prevent the complaint from becoming a more widespread problem. The investigation process utilizes a “Fishbone Diagram” to identify the root cause of the packaging failure. This is just one of several root cause analysis tools that you can use for complaint investigations, but it works particularly well for examples where something has gone wrong in production process controls, but we are not sure which process control has failed.

Once the root cause is identified, for the packaging complaint, then you need to implement corrective actions to prevent recurrence. In addition, FDA Clause 21 CFR 820.100 and ISO 13485, Clause 8.5.3 require that you implement preventive actions to detect situations that might result in a potential packaging failure in the future and implement preventive measures so that similar packaging failures are not able to occur.

Packaging Incident

The incident that was reported was reported by a distributor. The distributor told customer service that two pouches in a box containing 24 sterile devices were found to have a seal that appeared to be delaminating. Unfortunately the distributor was unable provide a sample of the delaminated pouches or the lot number of the units. Packaging issues and labeling issues are typically two of the most common complaint categories for medical devices. Often the labeling issues are operators errors or a result of labeling mixups, while the packaging errors have may be due to customers that accidentally ordered or opened the wrong size of product and therefore they may complain about packaging when there was actually nothing wrong. It is important to be diligent in the investigation of each packaging complaint, because if there is a legitimate packaging quality issue then there may be a need or a product recall as part of your corrective action plan.

Reporting of Packaging Complaint Investigation

A lot of clients do not want to report packaging issues as a Medical Device Report or MDR, because they are concerned about potential action by the agency or the negative publicity of the reported adverse event. Even if an injury or death did not occur with a sterile medical device, the quality issue should still be reported as an MDR in accordance with 21 CFR 803 because it could cause an adverse event such as a serious infection that could result in sepsis and death. If you think that this is an extremely conservative approach, you might be surprised to learn that 225 MDRs were reported in just October of 2015 for packaging issues. One random example is this report of a leaking contact lens vial in the following report:

Event Description

“It was reported that the lens vial was found to have little or no saline storage solution. This was discovered upon receipt and the product was not used.”

Manufacturers Narrative

“The lens and lens vial were not returned for evaluation. The lot history record was reviewed and there were no non-conformities or anomalies related to this complaint. Based on the information currently available the most likely root cause of the event is related to a leaking lens vial. The type of lens vial associated with this report has been discontinued and a new (redesigned) vial was implemented.”

Packaging Complaint Investigation when product IS NOT returne d

What the narrative above does not elaborate on is what was the specific investigation details for “lot history reviewed.” One of the most useful tools for performing this type of investigation is the “Fishbone Diagram”. There are six parts “6Ms” to this method:

materials, method, machine, “mother nature” or environment, “manpower” or people, and measurement.

Here are a couple of things that could have been done:

review the complaint log for other complaints with the same lot number and/or from a similar time period, lot of raw materials or packaging machine review the device history record for the lot to make sure that the number of units rejected as part of normal in-process and final inspection did not exceed pre-established thresholds for monitoring of the sealing process if retains of the lot are available, these might be retested to verify that the testing results after real-time aging remain acceptable the maintenance and calibration records of the equipment for manufacture and for testing may be reviewed to verify that no repairs were required and no equipment was identified as out-of-calibration

If all of the above fail to identify a potential cause for a packaging failure, then you might have a problem related to people or the environment. People includes the people sealing the product package and the users. The environment includes the temperature and humidity for storage of packaging raw materials, packaged product, sterilization conditions, storage conditions after sterilization and shipping conditions–including any temporary extremes that might occur during transit.

In our case study the product was not returned and we did not have the lot number. Therefore, we may need to review distribution records to that distributor and/or the customer to narrow down the possible lots to one or more lots. Then we would need to perform the same type of review of lot history records for each potential lot. In the future, the UDI bar codes that are on products and product labeling will facilitate the identification of lots, because the UDI bar codes will be scanned into each patient’s electronic medical record and the production identifier (PI) portion of the code will tell manufacturers exactly which production lot was involved.

Packaging Complaint Investigation when product IS returned

Sometimes you are fortunate enough to received returned product. The product should be immediately segregated from your other products to prevent mix-ups and/or contamination. After it has been determined that the product is safe to handle, the assigned investigator may inspect the product packaging to confirm packaging issues and to possibly destructively test the packaging to verify that the packaging returned meets the specifications.

Additional Resources

There are an enormous number of articles and studies on the topic of package testing and package design for sterile medical devices. If you have a question, you can probably find a dissertation or two on any obscure aspect of packaging you are interested. For example, Jordan Montgomery is a packaging engineer/technical fellow with Medtronic. He performed a thorough investigation comparing testing methods for the EN ISO 898-5 with the ASTM F88 method . A dissertation I read also attempted to correlate between burst test results and peel testing results for the same packaging.

Related Blogs

If you are interested in learning more about root cause analysis, then you should visit the following articles specifically written about this topic: Tweet Pin It

Posted in: Complaint Handling

Leave a Comment (1) → Complaint Investigation Case Study (21 CFR 820.198): Part 2 Posted by Rob Packard on January 27, 2015

More Facebook Email Google+ 7 Twitter Linkedin 11


This article is part 2 of a two-part series specific to complaint investigation requirements as specified in 21 CFR 820.198 ( ) of FDA QSR. This second part explains how to perform a complaint investigation and provides a complaint investigation case study.


Last week’s blog  reviewed the requirements for a complaint investigation, while this blog includes the following information on how to conduct an investigation:h

How thorough should your investigation be? Investigation Methods Verification of the Cause Documenting Your Investigation Complaint Investigation Case Study

How thorough should your investigation be?

The depth of investigation should be appropriate to importance of the complaint. If a previous complaint of similar nature has already been investigated, the investigation may only gather enough information to verify that complaint has the same root cause. However, if a complaint involves an adverse event (i.e., is reportable under 21 CFR 803 ), then additional information needs to be recorded in the complaint record as per 21 CFR 820.198d:

Does the device fail to meet specifications? Was the device used for treatment or diagnosis? What was the relationship, if any, between the device and the reported event?

If the person gathering information from the complainant cannot immediately identify a cause code, or the incident involves a serious injury or death, then it is important to gather as much information as possible. Typically, the complainant will be asked to return the device to determine if the device malfunctioned.

Investigation Methods

A complaint investigation is not any different from any investigation you perform for a CAPA. The most critical first step is to determine the cause of the complaint. In order to determine the cause, you need to sample additional records and inspect the device if it is available. If the device is not available, you might also look at other product from the same lot that remains in inventory. The following article I wrote suggests seven ways to investigate a complaint when a device is not returned: .

One of the methods described in the article above is a Ishikawa Diagram or “Fishbone Diagram.” This is one of the five root cause analysis tools that I teach in my CAPA webinar ( ). Ishikawa Diagrams are an ideal tool for root cause analysis if you have no idea what the cause of the complaint is, because this tool provides a systematic process for narrowing down the potential causes, to the narrow few that are most likely. You are not required to use this tool, but you should describe in your complaint record what type of root cause analysis was performed.

Verification of Cause

Once you have identified the root cause, or at least narrowed your list to the most likely causes, you should then verify that the cause will actually result in the observed malfunction by recreating the scenario if possible. Ideally, you should be able to simulate the event that resulted in the complaint and demonstrate that you can reproduce the problem. This is important, because if you cannot verify the cause of a device malfunction, then you will have difficulty verifying effectiveness of corrective actions for an infrequent complaint.

Documenting Your Investigation

There is no specific format for the way a complaint investigation is documented, but most complaint records have a small section on the complaint form that allows them to write a short paragraph summarizing the investigation and the results. Unfortunately, most of the spaces provided on forms are completely inadequate for the amount of information that should be recorded. Therefore, the best approach is often to write, “See attached complaint investigation.” This is especially true if the complaint is reportable (i.e., requires MDR under 21 CFR 803 ). Good documentation is quantitative and specific. You need to identify which records were sampled as part of the investigation, and you should demonstrate that you have expanded your initial search to determine if the problem exists in multiple production lots of the same product code, multiple product codes within the same product family and any other product families that may use similar raw materials, design features, equipment, testing methods or procedures.

Complaint Investigation Case Study

If your company manufactures cast orthopedic implants for the knee and you receive a complaint for an implant that has a small imperfection in the bearing surface of the femoral implant, you may need to perform an investigation–especially if this has not occurred previously. You should request a return of the implant for inspection to verify that the imperfection is nonconforming and not just a cosmetic defect.

Your investigation should include review of the lot history record for the entire lot of implants–as well as any other parts that they may have been cast at the same time. All the process conditions identified throughout the manufacturing process should be compared to the validated process parameters. Special attention should be given to the inspection results that were recorded for the castings (i.e., radiographic inspection, fluorescent penetrant inspection and metallurgical inspection). Ideally, these inspection methods should be repeated for 100% of the production lot to ensure that the inspection results meet the acceptance criteria. Documentation of the investigation should include copies of all records that were reviewed and photos if visual inspections were repeated.

If you are interested in learning more about complaint handling, you might be interested in downloading the webinar that Medical Device Academy recorded last year for complaint handling and vigilance reporting ( ). Leo Lagrotte, a former FDA investigator that works on our team as a consultant, also recorded a webinar related to CAPA and complaint investigations ( ). We can also help you one-on-one with a current complaint investigation you are conducting. Please don’t hesitate to contact me. Mobile: 802.281.4381 or .

Tweet Pin It

Posted in: Complaint Handling

Leave a Comment (0) → FDA Inspections-Complaint Investigation Requirements-Part I Posted by Rob Packard on January 19, 2015

More Facebook Email Google+ 4 Twitter Linkedin 22


“FDA Inspections-Complaint Investigation Requirements-Part I” is a two-part series which provides an overview of 21 CFR 820.198 requirements. 

Last week, I received a message from someone asking for advice on how to perform a complaint investigation. She has a complaint handling procedure that explains how to determine if complaints are reportable ( ), and she is the complaint coordinator. Her procedure includes a list of pre-determined cause codes for the most common complaints the company has received in previous years. Her system does not require a complaint investigation if an existing cause code is identified. She would like to know how to perform an investigation if she receives a complaint that does not fit one of the existing cause codes.

Is It a Complaint?

Most discussions about complaint handling begin with the definition of a complaint [i.e., 21 CFR 820.3(b); ]. However, if a complaint is received during investigation of a device rather than use of the device, the FDA will still consider this as being “after release for distribution.” The reason is that release for distribution occurs at final inspection. If the device breaks during installation, the device was still distributed.

One last question. Is it correct to consider a complaint only when the device is live and not during the settings and installation process of the device? (The definition states “after it is released for distribution”, what do they mean by this?).

What is Required?

The FDA QSR section specific to complaint handling is 21 CFR 820.198 ( 8). There are seven subsections (i.e., “A” through “H”) that comprise the regulation.

Manufacturers shall maintain complaint files and establish procedures for complaint handling. Manufacturers must review and evaluate if an investigation is needed. Manufacturers must perform an investigation automatically for any complaint involving a device malfunction–unless an investigation has already been performed for a similar complaint. Separate files shall be maintained for complaints that involve adverse events that are reportable under 21 CFR 803 ( ). The content of a complaint investigation record is specified in this subsection. When the complaint handling unit is located at another facility, the records of investigations shall be reasonably accessible to the manufacturing establishment. When the complaint handling unit is located outside the USA, then the records must be reasonably accessible at a U.S. manufacturer or the location of an initial distributor. What Does the FDA Expect to See?

FDA inspectors are guaranteed to sample complaint records and CAPA records during every routine inspection. The complaint records sampled will typically be limited to a specific product family that has been selected as the focus of the investigation. Most companies have an electronic log of the complaints, and the investigator may request a sorted list that only includes complaints specific to that one product family. The investigator will already be aware of all of your reported adverse events associated with the product family, and there may be one or two records they specifically want to investigate. The investigator will also review the complaint log to see if there are any complaints with a description that sounds like it might be reportable–even though the complaint was not reported.

The investigator will verify that each complaint record includes the content specified in subsection “E”:

name of the device; date the complaint was received; any device identification(s) and control number(s) used; the name, address and phone number of the complainant; the nature and details of the complaint; the dates and results of the investigation; any corrective action taken; and any reply to the complainant.

In my response to the question that I received, I also included advice for how to conduct an investigation. In general, the investigation is no different than an investigation for any CAPA. The first step is to perform a root cause analysis. The second part of this article will explain the investigation process in more detail.

Register to receive email notification of new blog postings ( ), so you can read the second part of this article next week. If you are interested in learning more about complaint handling, you might be interested in downloading the webinar that Medical Device Academy recorded last year for complaint handling and vigilance reporting ( ). Leo Lagrotte, a former FDA investigator that works on our team as a consultant, also recorded a webinar related to CAPA and complaint investigations ( ). We can also help you one-on-one with a current complaint investigation you are conducting. Please don’t hesitate to contact me and ask for help: Mobile: 802.281.4381 or .

Tweet Pin It Tags: FDA inspections of complaint handling, FDA inspections-complaint investigation requirements-part I, medical device complaint handling, medical device complaint investigation requirements

Posted in: Complaint Handling

Leave a Comment (0) → A Medical Device Complaint Management Auditing Approach Posted by Rob Packard on May 2, 2014

More Facebook Email Google+ 2 Twitter Linkedin 24


In this blog, “A Medical Device Complaint Management Auditing Approach,” the author focuses on the benefits of utilizing the 7-step process approach.

Auditors typically focus on the requirements of how to handle complaints, but what do you do with complaints after the investigation? If the only reason why you “handle” complaints is because it is a requirement, you are extremely unlikely to gain product benefits from reviewing complaints.

Audit Checklists

Are you using an audit checklist to verify that your complaint handling process is compliant with the regulations and that your records include all eight requirements of 21 CFR 820.198(e)?

Audit checklists encourage auditors to ask close ended (i.e., yes/no) questions. For example:

Did you document your investigation? Did you document corrective actions taken? The Process Approach

The process approach to auditing is a seven-step process where the auditor interviews the process owner and individuals performing the process being audited ( ):

What is the process? What are the inputs to the process? What are the outputs of the process? With what resources is the process performed? With whom is process performed? How is the process done? Which process metrics are important?

Each step of the process systematically gathers information about the process. More importantly, however, the process approach identifies how the process being audited interacts with other processes. Evaluating the effectiveness of linkages is one of the primary benefits of the process approach. For example:

Which records are used as inputs to the complaint handling process? How many corrective action(s) were initiated in response to complaints?

Sometimes, an auditor using the process approach will find a “broken link.” If there is no connection between servicing of devices and the complaint handling process, this is a link that needs to be “repaired.”

The Most Valuable Step

Of the seven steps to the process approach, the last step frequently provides the most proactive suggestions for process improvements. The last step is when the auditor asks the process owner, “Which metrics do you gather for this process?” Often, this question is met with a blank stare. If the process is not being measured, then the process owner cannot proactively make adjustments before mistakes are made. Instead, the process becomes reactionary.

A reactionary process for post-market surveillance and monitoring of complaints allows the number of complaints to increase and cause additional problems. Therefore, each complaint should be categorized, and data analysis should be performed. Ideally, each complaint category should have a maximum threshold established for the frequency of complaints and the severity of complaints. The frequency and severity would be documented in your risk management file. You may even establish quality objectives for the length of time it takes to process complaints, and number of actual complaints.

Adjacent Link Auditing

Adjacent Link Auditing is an extension of the process approach to auditing. The principle behind Adjacent Link Auditing is that each process has adjacent processes in the process workflow. The process owners managing the previous process step (i.e., “upstream”) are internal suppliers, because they provide the records and physical product that is used in the process being audited.   Process owners managing the subsequent process step (i.e., “downstream”) are internal customers, because they receive records and physical product from the process being audited. Internal “Suppliers” and “Customers” have a stronger connection to the process than other departments, because they are directly connected to the process. Adjacent processes are intimately involved in creating process inputs or using the process outputs for the next adjacent step in the process. If you are interested in learning more about Adjacent Link Auditing Theory, please click here to read an article in OrthoWorld’s BoneZone magazine.

If you are interested in downloading an example of a complaint handling procedure, please click here . For learning more about the process approach to auditing, you can purchase a webinar on the topic (Recording May 2, 2014. Please email  to order. Cost is $129).

Tweet Pin It Tags: complaint handling, complaint handling auditing, complaint management auditing approach, medical device complaint handling, medical device complaint handling auditing approach

Posted in: Complaint Handling

Leave a Comment (0) → Complaint Handling and Medical Device Reporting Common Mistakes Posted by Rob Packard on April 1, 2014

More Facebook Email Google+ 6 Twitter Linkedin 46


This blog, “Complaint Handling and Medical Device Reporting Common Mistakes” reviews complaint investigations, MDR procedures and adverse event reporting.  

You should already be well aware that deficiencies in complaint handling and Medical Device Reporting are two of the most common reasons why the FDA issues 483 inspection observations and Warning Letters ( ). Recently, I posted a blog about “Where to Focus your Medical Device Complaint Handling Training” ( ). The following is a summary of my responses to reader questions.

Complaint Investigations

What criteria do you think should be used to determine whether a complaint should be investigated or not?

There is only one acceptable rationale for not conducting an investigation of a complaint. If you don’t investigate complaints when required, then you might receive an FDA Form 483 observation worded like this…

21 CFR 820.198(c) – Complaints involving possible failure of labeling to meet any of its specifications were not investigated where necessary. Specifically, a missing IFU was reported in customer complaints, but no investigation was conducted. The rationale documented in the complaint record was “the missing IFU presented no patient risk.”

A missing IFU is “failure of labeling to meet any of its specifications.” Therefore, 21 CFR 820.198(c) requires you to conduct an investigation “unless such investigation has already been performed for a similar complaint and another investigation is not necessary.” This is the only rationale that is acceptable for skipping your investigation. To ensure that no one forgets to investigate a complaint, make sure you include a space in your complaint handling form that is specifically labeled as “S ummary of Complaint Investigation. ” This space should also include an option to cross-reference to a previous complaint record where a similar investigation is already documented.

A missing IFU is also considered misbranded product that requires correction (e.g., sending the customer a replacement IFU) or removal (i.

Health Product Complaint Process - Summary

Reporting a Complaint Involving a Health Product

Health Canada's mandate is to help Canadians maintain and improve their health. With this in mind, the Inspectorate is committed to verifying complaints from consumers and industry regarding the quality and/or safety of health products. Health products include pharmaceutical drugs, medical devices, biologics (including human blood, cells, tissues, donor semen, and organs), radiopharmaceuticals, and natural health products.

Report a complaint

As the Inspectorate deals with numerous product-related issues, all complaints are prioritized according to the health and safety risk. High-risk complaints receive priority attention. Actions taken by the Inspectorate are consistent with the Inspectorate's compliance and enforcement policy ( POL-0001 ) with the objective of achieving compliance using the most appropriate level of intervention. Not all complaints will lead to further action from Health Canada.

A complaint typically relates to the quality and/or safety of a health product and also may include a trade complaint which can relate to the products and/or the activities of a competitor.

When the Inspectorate receives a complaint, the information is reviewed to determine if the report falls within the Inspectorate's mandate. If it does, you will be sent an acknowledgement letter that the complaint was received.

If a complaint does not fall within the Inspectorate's mandate, it will be directed to the appropriate authority or you will be provided with the appropriate authority to contact.

Types of Products / Complaints the Inspectorate does not Address Products / Complaints Activities Contact

Adverse event in Humans (side effect to prescription and non- prescription medicines (i.e., over-the-counter))

All suspected adverse reactions (ARs) to human drugs marketed in Canada, including prescription and non-prescription drugs, biologics, natural health products, radiopharmaceuticals, disinfectants, and sanitizers should be reported to the Canada Vigilance Program.

Canada Vigilance National Office

Adverse event in Animals (prescription and non-prescription medicines)

All suspected ARs to drugs used in animals should be reported to the Veterinary Drugs Directorate (VDD)

Veterinary Drugs Directorate

Serious and unexpected adverse event related to Clinical trial drugs in Humans

All suspected serious and unexpected ARs related to Clinical trial drugs, for example, biologics, pharmaceutical drugs, radiopharmaceuticals, natural health products should be reported to their respective office of Clinical Trials

Pharmaceutical Drugs, Biologics and Radiopharmaceuticals AR Reporting
Office of Clinical Trial
Natural Health Products
Natural Health Products

Food compliance and enforcement activities

Complaints / ARs to foods should be reported to the Canadian Food Inspection Agency (CFIA).

  Canadian Food Inspection Agency (CFIA)

Adverse event in Animals to biologics

All suspected ARs in animals to biologics, such as vaccines, bacterins etc. should be reported to the CFIA

  Canadian Food Inspection Agency (CFIA)

Tobacco compliance
(Tobacco Control Program)

Complaints concerning tobacco products should be submitted to the Tobacco Control Program. The department is responsible for monitoring and enforcing compliance with tobacco labelling regulations, educating the public and regulating industry on the   Tobacco Act and   Regulations , and in the management of funding related to the Prevention, Cessation and Educational activities.

Health Canada's Tobacco Control Program (TCP)

Consumer products, including cosmetics
(Product Safety Programme)

Complaints concerning consumer / cosmetic products should be submitted to the Product Safety Programme. The department monitors and enforces consumer and cosmetic compliance issues.
Consumer products: (examples: electronics, baby walkers, clothing, toys, children's furniture, small appliances, house wares, household chemicals, bicycles, playground equipment, pools, skates, scooters, hockey helmets, hot tubs, and tents)

Cosmetics products: (examples: include shampoo, tooth whiteners, shaving cream, lipstick, hair dyes and tints, depilatories, soaps, moisturizers, nail polish and removers, and self-tanning products)

Health Canada's Product Safety Programme

Pesticide regulation and registered pesticides

All Complaints / ARs to pesticides, whether it involves a human, an animal, or the environment, should be reported to PMRA.
Pesticides: (examples: insecticides, herbicides, fungicides, and various other substances (or mix of substances) used to control pests, such as insects, fungus, weeds, animal or bacterial organisms)

Pest Management Regulatory Agency (PMRA)

Convention on International Trade in Endangered Species (CITES)

The organization is responsible for ensuring that the international trade in specimens of wild animals and plants does not threaten the survival of indigenous species. Complaints concerning endangered species should be reported to CITES.

  Environment Canada

Biological samples, permits for importation of human pathogens

Please contact either the Public Health Agency of Canada or the Canadian Border Services Agency for additional information.

  Public Health Agency of Canada (PHAC)
  Canadian Border Services Agency (CBSA)

Medical Marijuana

The Marihuana Medical Access Program (MMAP) facilitates the medical use of marijuana a substance regulated under the CDSA.

Drug Strategy and Controlled Substances Programme, Healthy Environments and Consumer Safety Branch (HECSB)

  Controlled Drugs and Substances Act (CDSA) permits or licences, methadone authorization, notification lists

The Act that regulates the control and distribution of certain restricted substances and their precursors.

Office of Controlled Substances, HECSB

Special Access Programme (SAP) to Drugs and Health Products

Health Care Professionals can request access to health products which are unavailable for sale in Canada. Access is limited to life-threatening conditions for which conventional therapies have failed or are unsuitable.  

SAP-Medical Devices
SAP-Donor Semen

Complaints concerning practice of medicine

Complaints concerning the practice of medicine should be submitted to the respective provincial College of Physicians and Surgeons

  Newfoundland and Labrador
  Nova Scotia
  New Brunswick
  Prince Edward Island
  British Columbia
  Northwest Territories

Complaints concerning practice of pharmacy

Complaints concerning the practice of pharmacy should be submitted to the respective provincial College of Pharmacy

  Newfoundland and Labrador
  Nova Scotia
  New Brunswick
  Prince Edward Island
  British Columbia
  Northwest Territories

Report a problem or mistake on this page Privacy statement

The information you provide through this survey is collected under the authority of the Department of Employment and Social Development Act (DESDA) for the purpose of measuring the performance of and continually improving the website. Your participation is voluntary.

Please do not include sensitive personal information in the message box, such as your name, address, Social Insurance Number, personal finances, medical or work history or any other information by which you or anyone else can be identified by your comments or views.

Any personal information collected will be administered in accordance with the Department of Employment and Social Development Act , the Privacy Act and other applicable privacy laws governing the protection of personal information under the control of the Department of Employment and Social Development. Survey responses will not be attributed to individuals.

If you wish to obtain information related to this survey, you may submit a request to the Department of Employment and Social Development pursuant to the Access to Information Act . Instructions for making a request are provided in the publication InfoSource , copies of which are located in local Service Canada Centres.

You have the right to file a complaint with the Privacy Commissioner of Canada regarding the institution’s handling of your personal information at: How to file a complaint .

When making a request, please refer to the name of this survey: Report a Problem or Mistake on This Page.

Thank you for your help!

You will not receive a reply. For enquiries,  contact us .

Date modified: 2014-06-27 Section Menu Problem Reporting Health Product Complaint Process - Questions and Answers Health Product Complaint Process - Summary Guide to Recall of Medical Devices (GUI-0054) Guidance on Investigation of Reported Medical Device Problems (GUI-0065) ARCHIVED - How to Submit a Trade Complaint How to Submit a Consumer Complaint ARCHIVED - Medical Device Problem Reporting by Health Care Facilities, Medical Professionals and other device users