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