Determining appropriate corrective actions

In any root cause investigation of a product or quality system nonconformance, the ability to determine the appropriate corrective actions can mean the difference between an effective CAPA that successfully addresses the issue and an ineffective CAPA that is doomed to be repeated. Too often, investigators, either in a rush to complete the investigation by its due date, or as a result of a lack of experience, may determine actions that are not appropriate in addressing the root cause of the nonconformance.

It is a given reality that root cause investigations must be completed in a timely manner and corrective and preventive actions must be implemented and verified in order to prevent recurrence of this event. However, compliance to the timeliness of an investigation and determining appropriate corrective actions do not have to be an “either / or” situation. It is possible to complete the investigation within the allotted time and identify appropriate corrective actions to prevent recurrence. Here’s how:

1- Develop an investigation plan at the onset of the investigation and ensure that each person with responsibilities are held accountable for meeting due dates. Why is this step important? Too often, investigations fail to meet its due date not due the complexity of the event, but rather, due to a lack of planning. Remember the old adage: “if you fail to plan, then you plan to fail.” This axiom holds true in the investigation world as well. The significance of an investigation plan is that it is a tool which aids in the tracking and planning of activities and it monitors actions toward completion. This visual aid, if you will, helps keep everyone on the same page and moving towards a unified goal.

2- Ensure that the action address the root cause of the nonconformance and not a symptom. This means that you must drill down to the core of the issue by brainstorming all probable causes and not simply stop at the first cause which “seems” most likely. Drilling down also means gathering input from other applicable SMEs or affected group members to ensure that brainstorming sessions are productive and that all possible scenarios have been evaluated.

3- Verify that the actions are effective in producing the anticipated outcome. On many occasions I have seen investigators come up with proposed actions that either do not address the root cause or are not executable for a variety of reasons. The act of verification may entail communicating with other impacted departments to determine whether the proposed solution may be implemented by the other group. I like to call this “a dry run”. The time to figure out whether an action will work is not during the roll out or implementation phase. A bit of pre-planning can spare you months of aggravation and possibly, another instance of a reportable nonconformance.

Four Simple Steps

In my last blog I discussed the importance of drilling down to the root cause in any nonconformance investigation and how to distinguish between a root cause and a contributing cause. In today’s blog, I will discuss four simple phases in the investigation process to follow once you have identified your root cause that will ensure a thorough investigation and effective corrective and preventive actions.

1. Plan
Once the root cause of the nonconformance has been identified via a thorough investigation, a plan must be identified that will effectively eliminate the root cause for this event. This plan must take into account all of the outcomes from the investigation; i.e., “what broke down?” or “what failed to occur?” The plan must evaluate each of the areas of noncompliance and with input from appropriate subject matter experts, identify a strategy by which each of the identified deficiencies will be remediated.

2. Verify / Validate
Once the plan has been developed, it must be verified / validated to ensure that the action(s) as identified will in fact correct the issue. This step is essential because it provides you with critical information early in the process that will alert you of potential gaps/flaws in your proposed plan. This may include gaps related to lack of resources, ambiguous interpretation / wording, or unrealistic expectations, to name a few. This early notification step allows you to make necessary modifications to a proposed plan that may not be executable as initially projected.

3. Implement
Once the plan has been finalized and approved, the actions have been verified / validated, it is now time to implement the changes. With implementation comes proper documentation to ensure that all affected parties have been appropriately notified, the necessary trainings have occurred, and there is evidence to show that the training is effective.

4. Monitor
This final phase of the process is not only a critical one but also one that is often overlooked by many well meaning quality investigators. The monitoring phase is important because it allows you to see (in real time) how effective your actions have been. Many people falsely conclude that because an activity/ action have been “validated” then it must be effective. This is clearly not the case. Validation is simply “confirmation by examination and provision of objective evidence that the particular requirement for a specific intended use can be consistently fulfilled.” Unfortunately, once that validated activity enters the production environment, deviations may occur resulting in the reporting of a nonconformance.

Investigating Cause – Drilling down to the root cause

In any nonconformance investigation, identifying the root cause is an integral part of the process. Identifying the root cause enables one to:

*Implement effective corrective actions
*Accurately trend data for process monitoring
*Implement effective preventive actions
* Develop effective strategies for continuous improvement

With so many different benefits of identifying the root cause of a nonconformance, it is imperative that the investigator does his/her due diligence to ensure that appropriate measures are taken.

One of the biggest challenges that various pharmaceutical / medical device companies face is that oftentimes, investigations stop at the first, immediate cause and fails to drill down further to address the systemic underlying cause(s). Or, their investigation may identify several contributing causes but fails to identify the root cause of a nonconformance. How can you tell the difference between a contributing cause and a root cause? Experience, Experience, Experience!

Experience is a critical factor in any comprehensive root cause investigation of an identified nonconformance. The key to differentiating between a contributing cause and a root cause lies with:

1. Experienced Investigators—they are an integral part of the process in that they are able to bring rational, sound judgment to the table. They have intimate knowledge of what works, what does not work and what requires improvement. They are not prone to “shoot at the hip” and stop the investigation after they have answered the first “why” an event occurred.

2. Experienced Mentors—coupled with an experienced investigator, experienced mentors are crucial in bringing unbiased, thorough, and systematic approach to a nonconformance investigation. They help the experienced investigator drill down even further into their process and to identify potential gaps and areas for process improvement.

3. Experienced Quality Oversight—The Quality dept. must give final approval of any nonconformance investigation and this individual must possess the necessary education, knowledge and experience in order to effectively carry out this quality function. Quality is the final reviewer of the investigation and as such, an experienced Quality reviewer will bring to the table a fresh viewpoint that ensures the comprehensiveness of the investigation.

Investigating Cause - Are nonconformance Investigation Procedures Followed?

In my last blog I discussed the importance of evaluating responsibilities in an investigation and the associated documentation required as supporting evidence. Today’s blog will discuss investigating root causes as it relates to following established protocol and procedures.

In any failure or nonconformance investigation, the procedure(s) that govern the process under investigation play a key role in the determination of root causes. Once a nonconformance has been obtained, the investigation procedures must be detailed enough to answer or address the following:

-What are the necessary steps to control product disposition?
-What are the required approvals?
-Timeframes for acquiring approvals and product disposition?
-Timeframes for actual investigation?
-Development of a plan of action

Nonconformance investigation procedures must clearly define product disposition and the necessary approvals for the actions taken. Depending on the nature of the nonconformance, the risk that the organization is willing to assume, as well as the governing procedures, product disposition may dictate: use-as-is, quarantine, scrap, or rework. Whatever option is selected, the rationale for this decision must be clearly evident and governed by departmental procedures. A decision to use-as-is, for example, should not be left to the discretion of individuals who are not authorized to make such decisions, nor provide the justification for such use.

Nonconformance investigation procedures must also dictate the timeframes for acquiring approvals as well as the disposition of the product. In any nonconformance investigation, time plays a critical role and any unnecessary or timely delays may result in loss of vital information critical to the investigation. Therefore, it is essential that the investigator or other applicable personnel adhere to the established timeframe requirements in order that the flow of critical information may be evaluated in a timely fashion.

Nonconformance investigations procedures must also establish some clear foundation for a plan of action. This plan of action is not required to be so prescriptive as to prohibit or hinder the normal investigative flow. However, it should lay the preliminary foundation for the way in which the investigation is to flow. Action plans may incorporate as appropriate, to retest or resample; responsibilities for evaluating the data; as well as the required approvals of the data.

Depending on the nonconforming product as well as the procedures governing such products, each company must evaluate its own process and procedures for nonconformance investigation and revise as necessary to ensure that they continue to operate in a consistent state of control.

Evaluating Responsibilities

In last week’s blog, I discussed an oftentimes overlooked but nonetheless, significant element of a thorough QS or GMP investigation, namely, accurately defining the problem description, which is the nature of the nonconformance. In today’s blog, I will discuss the importance of evaluating responsibilities in an investigation and the associated documentation required as supporting evidence.

Once a determination has been made that a nonconformance has occurred, whether it be a product or process nonconformance, the responsibilities associated with the activities involved play a key role in the investigation process. The task of evaluating responsibilities is important for several reasons, but of significance are the following:

1. it helps to quickly define the tasks at hand and identify key roles and responsibilities
2. it sheds light on areas in the process that may be vulnerable to potential nonconformance
3. helps to establish a process for continuous improvement of the quality management system

In attempting to evaluate the responsibilities of the individuals involved in a process, one must evaluate the procedures associated with the tasks, in addition to conducting interviews with the respective individuals. I will briefly describe the relevance of each activity.

Evaluating responsibilities as it is defined in a given procedure is relevant in that it allows you to clearly identify the requirements as they are documented for a process. This sets the foundation for providing the evidence to substantiate the activities taken. Recall my motto in previous blogs: “if it’s not documented, it’s a rumor”. So, the fact that the responsibilities are defined in a given procedure is great, but do not stop there.

Next, you must interview the appropriate individuals to determine the “unwritten” responsibilities that are often a part of many activities in a given function. Those are what I like to call the “fluid” responsibilities that are often performed by individuals in order to: (a) clarify a task, (b) increase output, (c) facilitate better time management, and/or (d) “other”, which can include a host of other reasons. While any person working in an FDA regulated environment will quickly admit that following the procedure is foremost in their responsibilities, upon further investigation, you may find that points “a – d” above also is a factor in the way in which activities are performed in this environment.

In order for an investigation to be effective in determining the root cause of a nonconformance, the responsibility factor must play a key role. It must be made clear however, that in the process of evaluating responsibilities the individual(s) involved must feel secure enough to be open and honest about the activities that they have performed, both documented and undocumented. If individuals are fearful of losing their jobs, feel intimidated by the investigator, or are concerned that the outcome of the nonconformance may have a negative impact on future advancement opportunities within the company, then the effectiveness of this activity will be significantly diminished. Individuals must be made to feel that this is an activity that seeks to identify gaps/weaknesses in the process, not in the individual themselves.

Elements of a Thorough Investigation- Part 3

In Elements of a Thorough Investigation- Part 2, I discussed the second aspect of a through Quality System or GMP investigation, and that is, determining the difference between people and process driven activities as they relate to a comprehensive investigation. In today’s blog, I will discuss an oftentimes overlooked but nonetheless, significant element of a through QS or GMP investigation, namely, accurately defining the problem description, which is the nature of the nonconformance.

Throughout my years in the industry evaluating investigation reports, I have found that many investigations do not clearly describe the nature of the nonconformance, i.e., the problem statement. Why is having a clearly defined and succinct problem statement so critical? Well, it can mean the difference between an effective investigation that identifies and eliminates the root cause of the nonconformance; and an ineffective investigation that identifies symptoms of a much larger problem and fails to identify the root cause.

In the former case, a clearly identified problem statement that describes the nature of the nonconformance is likened to an arrow hitting its targeted bulls’ eye every time. When you have clearly identified your problem, it helps to establish a laser-like focus in the investigation that is less likely to stray from the true intent of what is being investigated. A well-defined problem statement also helps guard against scope creep and facilitates the identification of the true root cause of the problem as opposed to addressing the symptom of the problem.

In the latter case, an ill-defined problem statement often leads the team astray as they focus their attention on various aspects of the problem that may not be relevant to the root cause. In such instances, the nonconformance is likely to reoccur requiring additional resources, time, effort, and energy in trying to resolve a matter that has not been clearly defined in the first place.

So, how do you ensure that you have drafted a clearly defined and concise problem statement? Well, you can begin by asking the following questions:
• What is the nonconformance that has been identified? E.g, product “X”
failed to meet its specification of “Y – Z”.
• When did the nonconformance occur?
• How was the nonconformance identified?
• At what point in the process was the nonconformance identified?

As you evaluate and begin to answer each question, it is important that you keep the focus on answering the specific question at hand and not attempt to offer any conclusions or potential causes at this point. In other words, your problem description should not say: “Product “X” failed to meet its specification of “Y – Z” due to operator error”. That is a conclusion that will be brought out during the course of the investigation and its validity either confirmed or eliminated with objective evidence.

Elements of a Thorough Investigation- Part 2

In last week’s blog, I discussed the importance of Documentation as one of the elements of a thorough investigation. In this blog, I will discuss the second aspect of a through Quality System or GMP investigation, and that is, determining the difference between people and process driven activities as they relate to a comprehensive investigation.

The distinction between “people and process” driven activities is an important one in that it directly impacts your ability to clearly identify the root cause of a nonconformance as well as identifying appropriate corrective actions.

Let me clarify. A process is a sequence of repeatable steps that lead to some desired end or output. When you have a clearly defined and documented process, the outcome is not dependent upon an individual “remembering” to carry it out. Any individual (provided that they have the proper “education, training, and experience, or any combination thereof”) can come into the environment and perform the activity as it is defined and reach the same outcome.

People driven activities on the other hand are:
- Often not documented
- Subject to variation in interpretation and execution
- Often play a crucial role in the identification of the root cause of the nonconformance

An activity that is “people driven” may or may not be reproducible, regardless of the “education, training, and experience, or any combination thereof” of the individual. An activity that solely relies on an individual’s memory to be successfully executed is often wrought with variation in how it is carried out resulting in significantly different outcomes. Such activities will often play a major role in the root cause of a nonconformance. That is, the individuals who are tasked with completing this activity may interpret the steps differently, or place different emphasis on such task and when it is necessary to carry them out.

Therefore, in investigating a nonconformance, you must determine whether the critical parameters are dependent upon the individual, i.e., “people” or a clearly defined “process”. You must still investigate each, regardless of the outcome, but the importance of this step is that it will provide you with an in-depth view of your process and take appropriate actions; i.e., to draft procedure for critical process parameters that are not well defined or documented.

Elements of a Thorough Investigation

Nonconformances are an inevitable part of any process. Whether it is in a manufacturing, production or laboratory environment, at some point, you will encounter an observation or result that is contrary to its pre-determined requirements or specifications. In such instances, some type of an investigation will be required. The subject of this week’s blog is to outline some of the elements of a thorough investigation that supports compliance to the regulations and provide some brief examples.

A comprehensive quality system or GMP investigation must be substantiated by documented evidence. Documentation provides the necessary objective evidence to support any claims or findings of the investigation. Documentation is what provides an investigator or auditor, the assurance that the claims that you are making in support of the root cause(s), or corrective action(s) are valid.

Documentation also serves as proof of what element or process or idea that has been eliminated as potential root causes. And in the eyes of an investigator, “if it is not documented, it’s a rumor”. Your investigation packet can contain all of the elements to show how the product was manufactured, packaged, or tested in a laboratory setting; but unless you can show via documented evidence the actions taken and relate those actions back to your investigation, then you do not have the necessary evidence required to support your claim.

What does documentation consist of and what sorts of actions require documentation? Well, Documentation consists of written records that guide activities and prove what has occurred. Documentation in support of an investigation must clearly demonstrate the actions that were taken, when they taken, who executed such actions, as well as the qualifications of such individual. If you recall, personnel qualifications is mandated by both the GMP and QS regulations. 21 CFR 211.25 states the following in regards to personnel qualification:

(a) "Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. Training shall be in the particular operations that the employee performs and in current good manufacturing practice (including the current good manufacturing practice regulations in this chapter and written procedures required by these regulations) as they relate to the employee's functions. Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them."

Next, the documentation to support your investigation must clearly show the sequence of events and conclude whether they confirm or eliminate a root cause. This can be easily accomplish by a heading or a brief footer that describes what this data support. It should not be left to the auditor to “guess” at what the data support. They may arrive at a different conclusion than you intended. Be upfront and clear at all times.

Finally, documentation of your corrective actions must not only comply with the points above but must also support your root cause. That is, the documentation that you are including as part of your investigation packet to support the validity of your corrective actions must clearly tie back to your root cause(s). If it does not, the investigation leaves the door open to potential causes that remain unexamined and the possibility that the given nonconformance may reoccur.

Is it really a Training Issue?

When it comes to identifying the root cause of a nonconformance, invariably, training will always be evaluated as a potential cause of the event. While I completely agree that training must always be evaluated as a potential root cause, I must caution the investigator to go further. Going further means not to accept at face value that training is the culprit in every nonconformance event. It means challenging the notion that “training” or “training effectiveness” played a role in the identified nonconformance. It also means having an established guideline / process for measuring training effectiveness within your organization.

Identifying the root cause of a nonconformance as a “training” issue happens very often in the investigation world with little to no supporting evidence to justify this position. I believe that many organizations sign off on these investigations for several reasons:

(1) It is an easy way out—many companies incorporate a 20-working day due date for the investigation which includes: identifying the problem, determining the root cause, evaluating trends, implementing corrective and preventive actions and monitoring for effectiveness of the actions. This extremely limited time period often forces well-meaning investigators and approvers to simply accept “training issue” as a rationale for the root cause of the event.

(2) Organizations do not have a pre-established guideline and/or process for measuring training effectiveness. The question of how does an organization measure training effectiveness is one that many shy away from. Is training effectiveness measured by simply reading the SOP? Is an instructor-lead training the best vehicle to execute training? Is an acknowledgement of “read and understood” for a given procedure equivalent in comprehension to an instructor-lead training?

Before you signoff on your investigation and accept the root cause of the nonconformance as being attributed to “training” or “training effectiveness”, be sure to:

*Evaluate all other potential root cause
*Perform a trend analysis to determine whether there is a trend that may require

further evaluation
*Evaluate your current training program to determine how training is disseminated
and the mechanism for evaluating effectivenessChallenge, challenge, challenge!

Verifying or Validating CAPA

The topic of verifying or validating CAPA is a very important step in the investigation process and one that is often overlooked. Many investigations will adequately investigate the nonconformance, determine the root cause, may identify actions needed to correct and prevent the recurrence of the nonconformance, but will often fall short of the mark when it comes to the verifying or validating the corrective and preventive actions to ensure that the actions taken are effective.

Verification or validation of a corrective and preventive action is mandated by the quality system regulations as defined in 21CFR820.100 (a) (1) (4):

Verifying or validating the corrective and preventive action to ensure that
such action is effective and does not adversely affect the finished device;

What this means is that once you have clearly identified the actions that you need to take in order to correct and prevent this problem, you must take it one step further and verify or validate that the action(s) will in fact work to fix the issue at hand. Why is this an important step in the investigation process?

Well, first of all, investigations are to have what I like to call a “defined lifecycle”. By that I mean:
(1) Identify the nonconformance.
(2) Contain the nonconformance. That is, immediately identify how you are going to contain this nonconformance to ensure that nonconforming product does not enter the marketplace.
(3) Next, you will investigate the nonconformance to identify the root cause
(4) Identify and implement certain actions to correct the nonconformance
(5) Finally, you must validate or verify that those actions will work and will not adversely affect the product

This “defined lifecycle” is supposed to be part and parcel of a clearly defined process that will not only investigate the issue at hand, but also to ensure that when investigated correctly, you should not have a recurrence of this same issue. Hence, the importance of verification or validation of the actions identified in the investigation. Where there is no verification or validation that the actions will work, then the likelihood of a recurrence of this same issue is not only probable, but inevitable.

An investigation is supposed to be a finite event that leads you not only to identify the root cause, but whatever actions are taken should prevent a recurrence of the nonconformance. If it does not, then you can rest assured that there has been a break in the “defined lifecycle” and the nonconformance is likely to repeat itself.

Identifying Actions

Having explored the topics of “Why Investigate?” Because it is mandated by both Good Manufacturing Practice (GMP) regulations —21CFR211 and Quality Systems regulations—21CFR820. “What to Investigate?” You are required to investigate the cause(s) of nonconformities relating to product, process, and the quality system. “When to investigate?” As soon as the non-conformance has been identified; I’d like to shift the focus now to the topic of identifying the actions that are required in order to correct and prevent the recurrence of non-conforming products from entering the marketplace.

The step of identifying actions plays a critical role in the investigation process. The purpose of this step is to identify the best permanent and systemic corrective actions to eliminate the root cause of the event and prevent its recurrence both now and in the future. Based on the level and extent of the investigation as well as the root causes identified, a decision will be made that will serve to provide overall the greatest benefit while ensuring that the lowest risk have been identified.

Once you have thoroughly investigated your event of noncompliance and have identified the root cause of your problem, you need to identify the action(s) necessary to correct the problem. Actions may fall into the following categories: (1) initial correction(s) that once taken will correct the problem; (2) permanent corrective action(s) which may be more systemic in nature and may involve longer-term action(s) to eliminate recurrence of the problem; and (3) preventive action which are actions taken to eliminate a potential non-conformity and will usually involve systemic changes that will help to ensure that there are systems in place to sustain the identified actions over time.

Let’s take a look at each type of actions. “Initial corrections” are those actions that are clearly and easily identifiable as steps to be taken that will “correct” the problem. “Correction” refers to repair, rework, or adjustment necessary and relates to the disposition of an existing nonconformity. Those actions fall under the category of what I like to refer to as “stop the bleeding”. For example, a piece of equipment that had been fully operational suddenly springs a leak due to a worn out gasket. An immediate initial correction to the problem may be to shut the equipment off and replace the gasket. This correction is immediate, will resolve the urgency of the situation and will return the equipment to its normal operating state. However, it does nothing towards identifying the second type of action which is long-term, corrective action.

"Corrective action" relates to the elimination of the causes of an existing nonconformity. Corrective actions that seek to eliminate the cause of an existing nonconformity are more systemic in nature and may involve process related changes; changes that impact the way in which the daily operations take place; and/or changes to procedures, work instructions, etc.

“Preventive actions” are those actions that identify and eliminate the causes of potential nonconforming product and other quality problems. These actions may involve analyzing your current processes, work operations, and other quality records to ensure that these actions would indeed prevent a recurrence of the event.

Regardless of which type of action(s) are taken to correct the problem and prevent the recurrence of non-conforming products and other quality problems, verification or validations of these actions is the final step in this process. You must verify or validate the actions in order to ensure that the fixes or potential fixes will in fact address the root cause of the event and does not adversely affect the finished product.

When to Investigate?

In last week’s blog, I talked about “what to investigate” when dealing with non-conformities relating to a product, process, or the quality system. In investigating these non-conformities, FDA’s expectations of the manufacturer / producer are as follows: (1) investigate to identify the source of the non-conformity; (2) contain the non-conforming product to ensure that it does not reach your customers (subsequent blogs will discuss containment at length); (3) Identify the action (s) needed to correct the problem and prevent recurrence of nonconforming product and other quality problems; (4) Verify or validate such actions to ensure that they are effective and does not adversely affect the finished product; and finally (5) Implement the changes that you have deemed as valid during the course of the investigation and monitor for effectiveness.

This week, I want to focus your attention on the question of “when to investigate?” The issue of timeliness of an investigation plays a critical role in any investigation process. The first twenty-four (24) hours after the identification of a non-conformance is of significant importance and goes a long way in ensuring that you will be able to identify the root cause of the problem (as opposed to a symptom of a much larger problem) and implement effective corrective actions.

Whether you are in an Analytical Laboratory conducting chemical analysis or in a manufacturing facility that produces medical devices, the timeliness within which you identify the non-conformance and officially begin your investigation is extremely important.

Critical information may be lost or rendered “inconclusive” when an investigation into a non-conformance is delayed. This lost or “inconclusiveness” of information may be due to that fact that the stability or shelf-life of the material(s) used in the analysis is unstable. For example, if the sample in question has a 24 – 48 hours shelf life and you begin your analysis on Friday, re-analyzing this same sample on Monday morning (once you have identified that you have a non-conformance) may not provide sufficient insight during the course of the investigation in the determination of a potential root cause. A re-sampling and re-analysis may provide passing results but the validity of the original sample preparation remains “inconclusive” since that sample is now technically expired.

The same principle holds true for a medical device manufacturer. One example which I have seen in my past experience is in manufacturing a device in which a process has been validated as time dependent. That is, there is documented evidence to show that a delay in the execution of an activity may yield unfavorable or nonconforming results. If this activity step is to be carried out within let’s say, 24 hours, the evaluation of the outcome of this activity should be conducted shortly thereafter. When it is not, timeliness of the investigation becomes an issue and results in greater difficulties in attempting to arrive at a root cause.

Therefore, the answer to the question of “when to investigate” depends upon the process, product, or quality system under scrutiny. When should you investigate? Most definitely, as soon as the non-conformance has been identified. However, A good rule of thumb is to begin your investigation at least, within the first twenty-four hours post completion of the activity in question.

What to Investigate?

The answer to the question of “what to investigate” is clearly defined in the regulations. A manufacturer is required to “investigate the cause of nonconformities relating to product, process, and the quality system.”

For most companies, the ability to identify non-conforming product is relatively simple—that is, they have established pre-defined specifications (i.e. limits) and they test according to those specifications. When a result is obtained that falls outside of a set limit (i.e., release, alert, or action), an investigation usually ensues based upon that company’s operating procedures. Most companies will investigate that failure to determine the root cause for the failure and implement corrective actions to fix the problem.

One of the more prevalent issues that I find in the companies that I have worked with, in particular, those with significant compliance violations, is that they often do not delve deep enough into the investigation to identify the root cause of this event; or they fail to identify the much larger process related non-conformance which failed to prevent the issue from occurring in the first place. I call this the “reactive vs. pro-active” approach to quality systems investigations. Let me explain further…

Many companies take a “reactive” position when they have a product-related non-conformance. That is, they rush to conduct an investigation and in an effort to meet unrealistic, self-imposed time constraints, they hurriedly close the investigation once they have identified what preliminary indications show to be a “root” cause. Oftentimes, this initial cause is rarely the “root” cause but more likely, a symptom of an underlying systemic cause (I will discuss the difference between a root cause and a symptom of the root cause in subsequent blogs).

The “pro-active” approach to investigations dictates that in any product/process/quality system-related non-conformance, the investigative team delves deep enough into the investigation to not only identify the true “root cause” (as opposed to a symptom of a much larger issue) but also ask the tougher systemic-related questions that will enable the team to effectively implement corrective and preventive actions in order to prevent future recurrence.

Therefore, as a product manufacturer, what should you investigate? Here are a few examples:
*Any product / process / quality system non-conformance
*Any trend that may indicate that your product / process / quality system is or may potentially trend towards non-compliance
*Any complaints (verbal, written, or electronic)

Why Investigate?

As an industry expert consultant (pharmaceutical, biotech, & medical device) with more than 20 years of experience, I find that one of the difficult challenges faced by many companies is in the area of investigation compliance. The industries that I mentioned in my opening are all regulated by the Food and Drug Administration (FDA) and are therefore required to comply with the regulations that govern the manufacturing and release of their products.

A quandary that many companies face is that their growth has increased exponentially (to the delight of their shareholders) but their compliance to the regulations has not kept pace with their growth. As some companies struggle to meet the rising demand for their product, one may find that compliance to sound investigational practices that support root cause(s) and corrective and preventive actions are oftentimes deficient. This deficiency derives from several factors including: Why investigate? What to investigate? When to investigate? How to investigate and document the findings which supports the root cause of the event? Let’s first take a look at “why investigate”.

Why investigate?

Investigation is mandated by both Good Manufacturing Practice (GMP) regulations —21CFR211 and Quality Systems regulations—21CFR820. Investigations play an integral part in any manufacturing process and while some companies would rather not investigate when they have a product or process non-conformance (as a result of issues I shall identify and discuss in subsequent blogs), the information that may be obtained when an investigation is carried out according to GMPs and QS regulations can prove to be invaluable to the company’s bottom line. This week, let’s take a look at the QS regulations on investigations and Corrective and Preventive Actions.

21CFR820 Subpart J—Corrective and Preventive Actions:

Each manufacturer shall establish and maintain procedures for implementing corrective and preventive action. The procedures shall include requirements for:
(1) Analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems.
(2) Appropriate statistical methodology shall be employed where necessary to detect recurring quality problems;

The procedures shall also include requirements for:
· Investigating the cause of non-conformities relating to product, processes, and the quality system;
· Identifying the action (s) needed to correct and prevent recurrence of nonconforming product and other quality problems;
· Verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device;
· Implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems;
· Submitting relevant information on identified quality problems, as well as corrective and preventive actions, for management review.
· All activities required under this section, and their results, shall be documented.

Investigation of product or process non-conformances helps to ensure:
· The safety and efficacy of the products that you distribute to the market
· That your products consistently meet internal requirements and external customer expectations
· That existing issues of nonconforming product or other quality problems are identified and corrected
· The root cause(s) of nonconforming products or other quality problems are effectively identified and eliminated
· That with appropriate and relevant trending of data, potential nonconforming products and other quality problems may be immediately identified and subsequently eliminated.

The answer to the question “why investigate” is several-fold: it’s mandated by law; it helps to identify and resolve issues that may drain an organization’s resources; it helps to identify potential issues of non-conformance, thereby helping the organization to bring these issues to light before they become major problems.

Ultimately, the best answer that I can give to the question of “why investigate” is the one that matters most to you and I, namely, our safety. Millions of individuals each day take a prescribed or over-the-counter medication, or give such medicines to a young child or elderly parents. Or, some of us have medical devices that have been implanted into our bodies. At the end of the day, the best reason to investigate is because investigations help to ensure that these products are safe for us to use, consume, and implant!


Marie