Corrective and Preventative Action Programs, Beyond Deviation Management

Too often Corrective and Preventative Action (CAPA) programs are considered solely with regard to Deviation Management programs. Modern Quality Systems, including CAPA programs, have been a focus of international harmonization efforts and the FDA’s 21st Century Initiative Program. Both initiatives seek to align the industry, and promote aggressive, proactive programs that drive toward continual process improvement.CAPA Programs are intended to monitor processes at all times, not only in the event of an atypical occurrence. The expectation is that atypical occurrences are more clearly recognizable and preventable if advanced data collection and evaluation practices are routinely conducted. CAPA Programs are intended to move all processes (manufacturing and control) toward continual improvement.

The legislative branch of our government is responsible for the scope and language of Title 21, the FDA is responsible for measuring the industry members’ compliance to the regulations. Title 21 defines the GMPs, while FDA adds granularity to the model of quality manufacturing by incorporating current practices and standards (the little “c”). The little “c” is used to render the model measurable, in order to enable a functional inspection program.

For this reason, it is helpful to review the language of Title 21 in detail as changes are made, and to seek out information from FDA, with regard to their definition of the current standards.

Toward that end, let’s first review current use of language, from FDA’s Glossary of Terms;

• Corrective and Preventative Action (CAPA): is a system of quality procedures required to eliminate the causes of an existing nonconformity and to prevent recurrence of nonconforming product, processes, and other quality problems.

• Nonconforming Material or Process (Discrepancy): Any material or process that does not meet its required specifications or documented procedure.

• Correction: Refers to repair, rework, or adjustment and relates to the disposition of an existing nonconformity.

• Corrective Action: To identify and eliminate the causes of existing nonconforming product and other quality problems.

• Preventive Action: To identify and eliminate the causes of potential nonconforming product and other quality problems.

• Continual Improvement: To facilitate and control product quality improvements, process variability reduction, innovation, and quality system enhancements, thereby managing the risks related to product quality and the quality system.

Now let’s review the evolution of the Modern Quality System with regard to CAPA Programs;

• 1997: CAPA Programs are incorporated into law within the Medical Device Quality Systems Regulations, specifically, CFR Part 820, Subpart J, sec. 100

• 2002: FDA launched the 21st Century Initiative Program, publically announcing their intent to integrate the Quality System model into the definition of the little “c” (current industry standard) GMPs. – this was the first major reinvention of the cGMPs since 1978.

• The QS working group (heading the initiative) mapped the existing cGMPs to models in CDRH, the EPA, ISO and use of advanced technology within the industry

• 2004: FDA and ICH collaboratively publish Q10, Quality Systems and USFDA draft Guidance document on Q10 (finalized 2006), clearly defining the new meaning of “current,” setting the standard against which, all inspections would be measured.

Now let’s review how FDA trains their inspectors;

If there is any doubt remaining with regard to FDA’s expectations regarding CAPA Programs, industry can also review the manuals used within FDA, to train Quality System Inspectors;

“The purpose of the corrective and preventive action subsystem is to collect information, analyze information, before a problem occurs and identifying and investigating product and quality problems, and take appropriate and effective corrective and/or preventive action to prevent their recurrence. Verifying or validating corrective and preventive actions, communicating corrective and preventive action activities to responsible people, providing relevant information for management review, and documenting these activities are essential in dealing effectively with product and quality problems, preventing their recurrence, and preventing or minimizing failures. One of the most important quality system elements is the corrective and preventive action subsystem.”

[Taken from “QSIT Corrective & Preventive Actions,” Quality System Inspection Techniques (QSIT) Guide, August 1999.]

Now let’s review what has happened since the introduction of the Quality Systems Model, and the training of inspectors on the inspection of Quality Systems;

In the past five years the FDA has focused its enforcement efforts on correcting CAPA programs.

In 2008 alone:

• 84% of Warning Letters issued cited multiple CAPA program issues

• 100% of Consent Decrees required external management and control of CAPA programs

• Deficiencies in CAPA programs were the 2nd leading source of observations/findings
These percentages have remained virtually unchanged for the past 5 years.

Now let’s review what FDA tells us are the most common falls in CAPA programs:

 Responsibilities not clearly defined. Who does what?

 Inputs not adequately defined. Are you considering all sources of data routinely?

 Decentralized CAPA Programs or system components. Local systems do not talk to each other.

 Inadequate employee training. Many times, employees are simply required to read the procedure and depending upon their role, this may not be sufficient.

 Preventive action takes a back seat and is rarely addressed.

 Verification of effectiveness is lacking or confused with verification of implementation.

 Arbitrary deadlines that are not linked to complexity of the problem.

[Excerpt from presentation by Joseph C. Famulare, Acting Deputy Director, Office of Compliance, USFDA, presented Fall 2007]


CAPA Programs, Scope and Objectives
When reviewing the regulations, with a clear understanding of the legal definition of the relevant terms, the evolution of the law, the agency’s public statements and the subsequent inspection techniques and enforcement actions, a clear picture of the scope and objectives of CAPA Programs emerges;

• CAPA Program scope is not limited to the resolution of deviation investigations. Deviation investigations are only 1 of many CAPA Program Quality Inputs

• CAPA Programs are intended to monitor processes at all times, not only in the event of an atypical occurrence, the expectation is that atypical occurrences are more clearly recognizable, and preventable, if advanced data collection and evaluation practices are routinely conducted

• CAPA Programs are intended to move all processes (manufacturing and control) toward improvement, continually, on an on-going basis

The Fundamental Elements of a CAPA Program

Once the scope and objectives have been aligned with FDA’s expectations, it becomes easier to recognize the fundamental elements that we should require of our CAPA Programs;

• Ensuring that data is continually monitored or collected and analyzed, such that non-conformities in product, deviations from procedures, specifications and/or standards, or process capability trends can be easily identified

• Guaranteeing that real time, reliable, and consistent investigations into root cause of process capability trend excursions, failures and deviations are conducted

• Timely identification and implementation of corrective and preventive actions

• Organizing and overseeing a monitoring system that ensures the effectiveness of actions taken is known and reacted to.

Product Lifecycle Stages and the Applicability of the CAPA Program

When defining a Quality System, we often first look to scope and objectives, then to an elemental definition of the system, and after that, we must determine the points in time at which the system is involved with operations.

FDA has communicated their expectations with regard to at which stages of the product lifecycle, and in what capacity, CAPA Programs are expected to be applicable, within their Guidance Document on Q10;

• Development: Product or process variability is explored. Corrective actions and preventive actions are incorporated into the iterative design and development process.

• Technology Transfer: CAPA can be used as an effective system for feedback, feed forward and continual improvement.

• Manufacturing: CAPA should be used and the effectiveness of the actions should be evaluated.

• Product Discontinuation: CAPA should continue after the product is discontinued. The impact on product remaining on the market should be considered as well as other products which might be impacted.

[Taken from USFDA, Guidance Document, Q10, Pharmaceutical Quality System, Section 3]
In Summary

As a modern Quality System, CAPA Programs have been well defined, and clearly go far beyond those actions implemented following a deviation from procedure and/or specification. The scope of the CAPA Program is comprehensive, the nature technological, the methods, data driven and the intent, increased control and predictability. It is a constant process, that seeks to actively integrate with every stage of production, and provide us the following benefits;

Expected Benefits of the Modern Quality System
• Technical Innovation

• Post-approval changes that can be managed through internal change management processes.
• Design Space, Control Strategy and PAT
• New approaches to process validation that benefits from lifecycle improvements including Continuous Quality Verification where feasible

• Meaningful investigations

• Effective CAPA Program

[Excerpt from presentation by Joseph C. Famulare, Acting Deputy Director, Office of Compliance, USFDA, presented Oct 2006]

As we view this language from FDA, it is worth calling out the individual words selected for use in the agency communication. This group of words provides a tremendously clear summary of the nature of the modern CAPA Program;

• Technical
• Innovation
• Design
• Control
• Improvements
• Continuous Quality Verification
• Meaningful
• Effective

Note that the entire GMP Initiative was begun as the industry had itself modernized since the previous definitions were put into place. It is clear that the agency feels that input from industry, and field observations made, has proven to them, that control is more effective, if it is technological, proactive, and continuous.

As always …

 Do What You Say, Say What You Do
 Reflect Reality
 Quality Product is Born of a Quality Process

© Coda Corp USA 2009. All rights reserved.
Gina Guido-Redden
Chief Technical Officer
Coda Corp USA
(p) 716.751.6150 (m) 716.550.2579
[email protected]

“Quality is never an accident; it is the result of high intention, sincere effort, intelligent direction and skillful execution. It is the wisest of many alternatives.”


CAPA Programs, The Fundamentals, Presentation by Gina Guido-Redden, November 11, 2009

USFDA, Guidance Document, Q10, Pharmaceutical Quality System, Section 3, ii

Guide to Inspections of Quality Systems, August, 1999,

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