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Der Pharmacia Lettre, 2011, 3(2): 368-382
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ISSN 0975-5071
USA CODEN: DPLEB4

Investigating Out-of-Specification Results and Development

CAPA Program for Pharmaceutical Industries: An Overview
Vikram Chopra1, Anil Kumar Shukla2, Ravindran Aiyyer3, Piyush Trivedi4 and Mona Nagar5
1,3
Ranbaxy laboratory Limited, Dewas (M.P.)
2,4
School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal (M.P.)
5
Acropolis Institute of Pharmaceutical Education & Research, Indore, M.P
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ABSTRACT

A well designed and implemented corrective and preventive action (CAPA) offers a
mechanism for obtaining critical quality data in a timely manner to enable quick response to
out-of-specification (OOS), early warning of potential failures and redeployment of resources
to problematic areas. This article presents the key features of CAPA program and provides
the current thinking on how to evaluate out-of-specification test results that can lead to
detection and resolution of out-of-specification test results for pharmaceutical production. In
order to solve OOS, every organization must know how to conduct an effective investigation,
identify root causes and implement workable corrective action in a timely manner that can
help prevent potential problems in the future.

Key words: CAPA, OOS, FTA, QMS

___________________________________________________________________________

INTRODUCTION

CAPA is a fundamental management tool that should be used in every quality system. This
program provides a simple step by step process for completing and documenting corrective or
preventive actions. The result will be a complete, well documented investigation and solution
that will satisfy regulatory requirements and form the basis for an effective continuous
improvement plan for any company. Properly documented actions provide important
historical data for a continuous quality improvement plan and are essential for any product
that must meet regulatory requirements demanded by FDA and ISO and other quality systems
[1].

1.0 Quality Management System (QMS)

A quality system is a set of formalized business practices that define management
responsibilities for organizational structure, processes, procedures and resources needed to
fulfill product or service requirements, customer satisfaction and continuous improvement. A

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quality management system (QMS) is a set of interrelated processes used to direct and control
an organization with regard to quality. In other words, a quality system dictates how quality
policies are implemented and quality objectives are achieved [1].

Continuous improvement is the result of ongoing activities to evaluate and enhance products,
processes and the entire quality system to increase effectiveness. The organization must
continuously improve the effectiveness and efficacy of its QMS through the use of its quality
policy, quality objectives, audit results, analysis of data, corrective and preventive action
(CAPA) [1,2].

Quality systems are regulated by the Food and Drug Administration (FDA) under 21 CFR
Part 820, referred to as the “Quality System regulation” (QSR). In order to provide FDA
inspectors with guidelines on how to evaluate compliance with the issues outlined in the
QSR, the FDA produced the Quality Systems Inspection Technique (QSIT). QSIT focuses on
four key subsystems as primary indicators of QSR compliance and provides guidelines for
evaluating each. These four subsystems are management controls, design controls, corrective
and preventive action (CAPA) and production and process controls, are considered the basic
foundation of a quality system. The remaining three subsystems of the QSR (Facilities and
Equipment Controls, Materials Controls and Documents/ Records/Change Controls) can be
looked at while evaluating the other four [2,3].

2.0 Corrective And Preventive Action (CAPA)

Corrective action is one of the most important improvement activities. CAPA identifies
actions needed to correct the causes of identified problems and seeks to eliminate
permanently the causes of problems that have a negative impact on systems, processes and
products. Corrective action involves finding the causes of some specific problem and then
putting in place the necessary actions to avoid a reoccurrence. Preventive actions are aimed at
preventing the occurrence of potential problems. Correction of the problem is the third basic
element of the corrective and preventive action system [1,3,4].

CAPA is a widely accepted concept to any quality management system. Within the United
States, lack of adequate investigations, no true root cause analysis, lack of effective corrective
actions and lack of true preventive actions are common findings pointed out by FDA
inspectors. As evidenced by the significant number of problems related to this issue,
companies are facing many challenges in making the CAPA system work as planned. Life
sciences regulated companies must ensure that their CAPA system looks beyond product
issues and considers other quality issues including problems associated with processes and
systems. CAPA systems are inherently data driven. Without adequate, relevant data, it can be
difficult to draw definitive conclusions about systems, processes or product quality issues.
One of the challenges many companies face is the proliferation of uncorrelated data
repository systems within the organization [5]. By having a correlated CAPA system, a
company will be better able to diagnose the health of its quality system and will have a better
chance of recognizing and resolving important quality issues. Companies must establish
methods to evaluate both the nonconformance data (which will feed the corrective action
portion of the system) and the in-conformance data (which will be the basis of preventive
actions) [1,6].

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The four key CAPA definitions are:

CAPA (corrective and preventive action): A systematic approach that includes
actions needed to correct (correction), avoid recurrence (corrective action) and eliminate the
cause of potential nonconforming product and other quality problems (preventive action).

Correction: Action to eliminate a detected nonconformity. Corrections typically are
one-time fixes. A correction is an immediate solution such as repair or rework. Corrections
are also known as remedial or containment action.

Corrective action: Action to eliminate the causes of a detected nonconformity or
other undesirable situation. The corrective action should eliminate the recurrence of the
issues.

Preventive action: Action to eliminate the cause of a potential nonconformity or
other undesirable potential situation. Preventive action should prevent the occurrence of the
potential issues [1,9,10].

2.1 CAPA Relationship with Quality Subsystems

The CAPA system is a critical component of an effective QMS and it must maintain a close
relationship with other quality subsystems (Fig 1). The ultimate goal of any regulated
company must be to have a CAPA system that is compliant, effective and efficient. All
relevant subsystems that may produce non-conformances must be part of the process. Internal
processes encompass both non-conformance and in-conformance results, internal audits and
assessments, management reviews and so on. External sources of CAPA process inputs are
supplier audits and assessments, customer feedback and results from external audits and
assessment such as regulatory agencies, ISO and so on [1,11].

Fig 1 CAPA and manufacturing quality system

2.2 Central Role of the CAPA Subsystem

The CAPA subsystem (21 CFR 820.100), one of the most important quality system elements,
is the other major theme that makes QSIT a unique inspection process. The FDA views
CAPA as being directly linked to all of the other subsystems. Corrective action refers to
elimination of the causes of quality problems in order to prevent recurrence, preventive action
is the steps taken to eliminate the cause of a potential problem in order to prevent its
occurrence [2,12,14].

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Under 21 CFR 820.100, CAPA procedures should include requirements for:

Identifying existing and potential causes of quality problems: Internal data sources
may include inspection and test data, process control data, equipment calibration and
maintenance data, device history records, change control records, out-of-specification and
nonconforming material reports. External data sources can include field service reports, legal
claims, product warranties and complaints from customers, employees and the FDA.10%

Failure investigation: An investigation should be carried out to determine the root

cause of a quality problem. The investigation should ask whether procedures were followed
and whether there was appropriate control to prevent distribution of the defective product.
The magnitude of the investigation should correlate with the significance and risk of the
problem.

Determining appropriate corrective and preventive action: Actions should be

identified to correct the quality problem and prevent its recurrence. Similarly, procedures
should be in place to allow the recognition and solution of a potential problem to avoid its
occurrence. Such actions should be verified to ensure that they are effective and do not have
an adverse effect on the products [13,15].

Changing procedures: Methods and procedures should be changed to incorporate the

CAPA. People directly responsible for quality assurance should be provided with information
regarding quality problems and procedural changes [16].

Management review: Relevant information on problems and the corrective and

preventive actions taken should be submitted to management for review.

2.3 Benefits of Unified CAPA System [17]

1. Financial

Influence Technologies

Opportunities for prevention

Simplification through elimination of manual steps

Lowers cost through centralized functions

2. Consistency

Uniform processing

Common Language

3. Compliance

Readily retrievable information

Faster proactive analysis

Connects the dots to identify systemic issues

Visibility for cross-site issues (e.g. inspections and supplier problems)

4. Management Control

Early alert system that facilitates prevention

Instantaneous, real-time view of company-wide issues

Improved communication and teamwork

Facilitates integrated trending for large volumes of data

Linkage among sites for products that are sold as a system

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2.4 Importance of Management Controls
All problems can and will likely be traced to management:

design, process, product and CAPA

Management Controls encompass all other subsystems

Fig. 2 Management control

2.5 Inputs to CAPA System [17]

CAPA is central to the implementation of an effective, closed loop and continuous
improvement process that focuses on prevention and quality.

Fig. 3 Closed-loop compliance process control

2.6 Common CAPA Violations [4,22]

No established procedures for implementing CAPA

No true root-cause analysis, failure investigations inadequate

Complaint handling too specific, do not look at overall system

Failure to document CAPA action

No validation

Failure to designate & document executive responsibilities

Infrequent quality audits

Inadequate procedures for quality audits

Inadequate procedures for documenting CAPA

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2.7 When is CAPA Relevant [5,29]
Currently, there are five different types of information sources that can trigger a CAPA.

Complaints from customers, either direct or indirect users (consumers).

Process deviations as a result of a manufacturing inconsistency or production failure,
or an engineering non-conformity, which causes the defect relative to the production
deviation, non-conformance or out-of-specification that may occur [26].

Laboratory investigation or analyses.

Internal audits or audits from regulatory bodies such as the FDA that identify
differences or deviations from given standards in the business or production processes or
non-compliance to production validation guidelines.

Grassroots efforts by employees, e.g., an engineer who notices an oil spill and
organizes a corrective action.

2.8 CAPA News [17]

In CDRH Warning Letter observations between April and September 2006, CAPA ranks #1

Fig. 4 FDA and QSIT workshop on CAPA

3.0 Industry's Common Failings

It seems that one of the biggest challenges for companies is to complete investigations and
actions in a timely manner. In many cases, incorrect assumptions are made that everything is
an isolated incident. In other instances, problems are not corrected and everything is blamed
on a single employee or a simple laboratory error or the system fails to ensure that a problem
does not extend to other lots and the incident recurs. The ultimate criterion for adequate
correction is to ensure that it doesn't happen again. CAPA was adopted as a new quality
management tool following the introduction of the ICH Q10 guideline. According to the ICH
Q10 document, which was adopted by the FDA in April 2009 as an industry guideline, a
pharmaceutical Quality Management System (QMS) consists of four central elements:

Process performance and product quality monitoring

Corrective action and preventive actions

Change management

Management review of process performance and product quality.

The guideline states that a pharmaceutical company should have a system in place to detect
and evaluate non-conformances to take respective corrective and preventive actions. Among
other things, the information regarding non-conformances can result from complaints,
deviations, recalls, observations at audits and inspections, or from monitoring findings. The
examinations within the system must have the objective of determining the actual root cause.
As a result, the process and product should be better understood so that improvements can be
derived from it.

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The EU Commission has now published a suggestion for the revision of chapter 1 of the EU
GMP Guide to incorporate the recommendations of ICH Q10. Now, specific requirements for
a CAPA system shall be included. Accordingly, the extent of the actions, technical
complexity and documentation of the necessary CAPA actions has to be managed according
to a risk assessment.

4.0 FDA warning letter

An FDA warning letter serves as a formal means of communication for pointing out
violations that could lead to legal and administrative sanctions, if such violations are not
corrected promptly. While the ISO sector does not have an equivalent of a warning letter, a
nonconforming product that is not corrected properly could mean loss of ISO certification
and consequently, either loss of opportunities in overseas markets and end of business
contracts with customers that require ISO certification. In both FDA and ISO environments, a
nonconforming product that causes injury or death could also mean liability lawsuits for the
manufacturer [17,18].

4.1Warning Letters Observations

Failure to establish and maintain procedures for implementing corrective and preventive
action, as required by 21 CFR 820.100(a).

Specifically, you failed to verify or validate a corrective and preventive action to
ensure that such action is effective and does not adversely affect the finished device, as is
required by 21 CFR 820.100(a)(4).

Specifically, your firm failed to identify the action(s) needed to correct and prevent
recurrence of non-conforming product and other quality problems, as required by 21 CFR
820.100(a)(3).

Specifically, your firm failed to analyze 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, as required by 21 CFR 820.100(a)(1).

Specifically, your firm failed to investigate the cause of nonconformities relating to
product, processes, and the quality system, as required by 21 CFR 820.100(a)(2).

4.2 Impact of Warning Letters

Public Record

May affect all Company locations

Response involves preparation of a costly and lengthy document that provides plan to
remedy the problems

Impact of response can also be costly

Marred reputation can result in loss of investors, decline in stock value and market
share

Potentially sub-optimal organization resulting from higher turnover and more
difficulty in recruiting best talent

Lower morale/increased stress in work environment

If the manufacturer does not address the areas outlined in the warning letter, FDA can:

Seize goods

Declare products misbranded

Issue injunctions

Demand product recalls

Put a stop on application for exports

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Close facilities

Impose civil and criminal penalties extending to multiple levels of management
within the accused organization

4.3 Concluding and Remarks of Warning Letters

1. An effectively implemented centralized global CAPA System will seamlessly
integrate data from all quality sub-systems across sites for data collection, analysis, and
effective implementation
2. CAPA is a Company Process not a just a “Quality” process
3. The success of a company’s CAPA system is dependent upon ability to think
critically, caliber of its staff and organization’s commitment to the quality
4. A global CAPA program should be smarter:

Specific

Measurable

Action oriented

Regulation compliant

Timely

Effective, and Results driven

5.0 Out-Of-Specification And Capa Program

In 2006, FDA provides guidance “Investigating out-of-specification (OOS) test results for
pharmaceutical production” which provides current thinking on how to evaluate out-of-
specification test results. The term OOS results includes all test results that fall outside the
specifications or acceptance criteria established in drug applications, drug master files (DMF)
or by the manufacturer [6].

A common way of handling Out-of-Specification is by fixing the product or material.

Increasingly, however, manufacturers realize that they must not only fix existing problems,
but also avoid future recurrence of a similar nonconformance. In this sense, the
nonconformance disposition process is closely related to the CAPA process.

In the case of FDA-regulated medical device, pharmaceutical, and biotech companies, certain
regulations require them to implement CAPA as part of the resolution of material
nonconformance issues. Under QSR (21 CFR Part 820.100), medical device manufacturers
are required to establish a CAPA procedure that will investigate the cause of any product
nonconformance and identify action that would prevent the recurrence of such
nonconformance. The CGMP regulations for finished pharmaceuticals similarly require that
any failure of a batch, or any of its components, to meet specifications must be thoroughly
investigated and documented, including the investigation’s follow-up and conclusion (21
CFR Part 211.192).

5.1 Investigations of Out-of-Specification

FDA regulations require that an investigation to be conducted whenever an OOS test result is
obtained. The purpose of investigation is to determine the root cause of existing or potential
non-conformities and to provide recommendations of solutions. The scope of the
investigation should be adequate with the determined risk of the non-conformity. Good
practice shows that a documented plan should be in place prior to conducting the
investigation [7]. The plan should include:

Description of the nonconformity expressed as a problem statement

Scope of the investigation

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Investigation team and their responsibilities

Description of activities to be performed

Resources

Methods and tools

Timeframe

5.2 Requirements for Investigations [19]

Under 211.22 the quality unit is required to review production records and investigate
any unexplained discrepancies.

In addition, under 211.22 rejecting incoming materials, in-process materials and drug
products. If rejected must conduct an investigation.

Under 211.22 (a) QU is responsible for approving or rejecting products services
provided under 211.22 (a).

Under 211.192 a key component of a Quality System is handling nonconformities and
deviations.

In order to meet 211.192 the investigation’s Conclusions and follow-up must be
documented.

Meeting 211.192 also requires manufactures to set critical product attributes;
specified control parameters and strength as required.

The accurate measurement of the process and product attributes is also required to
meet 211.192.

5.3 FDA Inspections- Investigations

Quality Systems: required to be covered in every inspection whether abbreviated or
comprehensive.

Production Systems: is almost always also chosen by Drug Investigators.

Quality Systems Key Items Covered

Product reviews batches reviewed for each product, trends identified (investigations)

Complaint reviews (quality and medical)

Reprocess rework

Failures

Rejects

Corrective actions and preventive actions

Production Systems Key Items Covered

Justification and consistency of in-process specifications and drug product final
specifications

Master Production and control records

Batch production and control records

Documented investigations into unexplained discrepancies
Inspection findings that demonstrate that a firm is not operating in a state of control may be
used as evidence for taking appropriate advisory, administrative and or judicial actions.

Quality System is out of control if there is a pattern of failure to conduct
investigations and resolve discrepancies, failures, deviations and complaints.

Production System is out of control if there is a pattern of failure to document
investigations of deviations.

Laboratory System is out of control if there is a failure to document investigations of
deviations.

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Investigations of "Out of Specification results" have to be done in cases of:

Batch release testing and testing of starting materials.

In-Process Control testing: if data is used for batch calculations/decisions and if in a
dossier and on Certificates of Analysis.

Stability studies on marketed batches of finished products and or active
pharmaceutical ingredients, ongoing / follow up stability (no stress tests)

Previous released batch used as reference sample in an OOS investigation showing
OOS or suspect results.

Batches for clinical trials.

All solutions and reagents must be retained until all data has been second person
verified as being within the defined acceptance criteria.

Pharmacopoeia have specific criteria for additional analyses of specific tests (i.e.
dissolution level specification for S1, S2 & S3 testing; Uniformity of dosage units
specification for testing of 20 additional units; Sterility Testing).However if the sample test
criteria is usually the first level of testing and a sample has to be tested to the next level this
should be investigated as it is not following the normal trend.

The OOS process is not applicable for In-process testing while trying to achieve a
manufacturing process end-point i.e. adjustment of the manufacturing process. (e.g. pH,
viscosity), and for studies conducted at variable parameters to check the impact of drift (e.g.
process validation at variable parameters).

Out-of-Specification (OOS) Result: Test result that does not comply with the pre-
determined acceptance criteria (i.e. for example, filed applications, drug master files,
approved marketing submissions, or official compendia or internal acceptance criteria).

Test results that fall outside of established acceptance criteria which have been
established in official compendia and/or by company documentation (i.e., Raw Material
Specifications, In-Process/Final Product Testing, etc.).

Out of Trend (OOT) Result is generally a stability result that does not follow the
expected trend, either in comparison with other stability batches or with respect to previous
results collected during a stability study. However the trends of starting materials and in-
process samples may also yield out of trend data.

Aberrant and Anomalous Result: Results that are still within specification but are
unexpected, questionable, irregular, deviant or abnormal. Examples would be chromatograms
that show unexpected peaks, unexpected results for stability test point.

5.4 Laboratory Investigation [6]

FDA regulations require that an investigation be conducted whenever an OOS test result is
obtained (211.192). The purpose of the investigation is to determine the cause of the OOS
result. The source of the OOS result should be identified either as an aberration of the
measurement process or an aberration of the manufacturing process.

5.4.1 cGMP Concepts of Laboratory Investigations [19]

Lab investigations are conducted when there are questionable results.
1. Companies should conduct a review to identify a lab error or need for full investigation.
2. Items that should be evaluated:

Data-lab note books

Methods

Calculations

Equipment

Sample integrity

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Reagents, standards used in analysis

Training
3. Usually results in the following:

Correctable lab error-further investigation not needed. Error fixed and corrected
results used (example wrong calculations).

Non-correctable lab errors- invalidate results and testing repeated. Investigation
concluded.

No lab error detected- Full Investigation-Quality Review to determine what to do with
the batch; Manufacturing Investigation; Retesting performed and additional confirmation
testing performed.

5.4.2 Common Reasons for Lab Investigations:

Employee: SOP not followed; stability samples not pulled at right time; misreported
data; lack of training; analytical errors; calculation error.

Facility: Lab contamination; no quality management; power failures.

Methods: Unclear written methods; Method limitations; wrong methods used;
outdated methods used.

Equipment: calibration failure; calibration frequency inadequate; old equipment;
wrong equipment used for testing.

5.4.3 Laboratory investigation procedure: (As describe in figure no. 5)

Fig. 5 Laboratory investigation procedure

5.5 Full-Scale OOS Investigation

When the initial assessment does not determine that laboratory error caused the OOS result
and testing results appear to be accurate, a full-scale OOS investigation using a predefined
procedure should be conducted. This investigation may consist of a production process
review and/or additional laboratory work. The objective of such an investigation should be to
identify the root cause of the OOS result and take appropriate corrective and preventative
action. A full-scale investigation should include a review of production and sampling
procedures, and will often include additional laboratory testing. Such investigations should be
given the highest priority [6].

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5.5.1 cGMP Concepts of Manufacturing Investigations
Part 211.100 Written Procedures, deviations providing written procedures for production and
process control designed to assure that the drug products have the identity, strength, quality
and purity they purport to have.

Part 211.192 Production Record Review any unexplained discrepancy or the failure of its
batch or any of the components to meet predefined specifications.

Also any other events that can possibly affect product identity, strength, quality,
purity, or not following procedures should be investigated and documented. Also quality
issues with components, raw materials, bulk received from suppliers should also be
investigated.

Investigations/deviation reports should have a time frame for completion. Usually
within 30 calendar days.

Responsibility crosses groups in an organization. For instance many investigations
require the expertise of quality assurance, quality control, production, suppliers, engineering,
and technology.

Companies should have available for review extremely detailed procedures
establishing steps that should be followed when documenting deviations [19].

5.5.2 Typical reasons for deviation reports and investigations:

Deviations from manufacturing or packaging procedures

Product mix up

Wrong batch numbers

Not meeting specifications

Equipment malfunctions not meeting calibration schedules

Out of range for yields

Operating out of the set limits for a piece of equipment

No training/ employee errors

5.5.3 Full-Scale Laboratory investigation procedure: (As describe in figure no. 6)

Fig. 6 Full-Scale OOS Investigation

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6.0 CAPA procedures [20]
Implementing an effective corrective or preventive action capable of satisfying quality
assurance and regulatory documentation requirements is accomplished in six basic steps:

1. Identification
The initial step in the process is to clearly define the problem. It is important to accurately
and completely describe the situation as it exists now. This should include the source of the
information, a detailed explanation of the problem, the available evidence that a problem
exists.

2. Evaluation
The situation that has been described and documented in the “Identification” section should
now be evaluated to determine first, the need for action and then the level of action required.
The potential impact of the problem and the actual risks to the company and/or customers
must be determined. Essentially, the reasons that this problem is a concern must be
documented.

3. Investigation
In this step of the process a procedure is written for conducting an investigation into the
problem. A written plan helps assure that the investigation is complete and nothing is missed.
The procedure should include: an objective for the actions that will be taken, the procedure to
be followed, the personnel that will be responsible, and any other anticipated resources
needed.

4. Analysis
The investigation procedure that was created is now used to investigate the cause of the
problem. The goal of this analysis is primarily to determine the root cause of the problem
described, but any contributing causes are also identified. This process involves collecting
relevant data, investigating all possible causes, and using the information available to
determine the cause of the problem. It is very important to distinguish between the observed
symptoms of a problem and the fundamental (root) cause of the problem.

5. Action Plan
By using the results from the Analysis, the optimum method for correcting the situation (or
preventing a future occurrence) is determined and an action plan developed. The plan should
include, as appropriate: the items to be completed, document changes, any process,
procedure, or system changes required, employee training, and any monitors or controls
necessary to prevent the problem or a recurrence of the problem. The action plan should also
identify the person or persons responsible for completing each task.

6. Follow Up
One of the most fundamental steps in the CAPA process is an evaluation of the actions that
were taken. Several key questions must be answered:

Have all of the objectives of this CAPA been met? (Did the actions correct or prevent
the problem and are there assurances that the same situation will not happen again?)

Have all recommended changes been completed and verified?

Has appropriate communications and training been implemented to assure that all
relevant employees understand the situation and the changes that have been made?

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Is there any chance that the actions taken may have had any additional adverse effect
on the product or service?

7.0 Challenges of Implementing CAPA

Historically, most organizations have relied upon the wisdom and experience of their internal
experts to identify root causes. Experts attempt to solve all problems using their experience of
tried and true past solutions. The main pitfall of this strategy, however, is that their solution is
completely dependent upon and limited by their expertise. If the root cause happens to lie
outside the scope of their expertise levels, they are not likely to find it. Therefore, they must
design a series of closely monitored experiments to test their hypotheses and to determine if
they are on the right track in locating the root cause. The problem with designing and
implementing these experiments is that, they are invasive requiring personnel, equipment,
laboratory resources, down time and funding. If the experiment is a failure, the internal
experts must repeat the same costly process again: brainstorming another probable cause and
conducting yet another experiment. This process can be time-consuming and lower the
morale of those involved.

The companies are discovering that deductive reasoning and comparative analysis are faster,
easier and more cost-effective ways to identify root cause and implement a corrective action.
Several proprietary programs use deductive reasoning and comparative analysis. The primary
focus of such processes is improving a diagnostic technique through better data collection.
Data is collected using an observed and comparative questioning technique. A unique and
simple tool is used to synthesize the collected data into information that tells the root cause
story [23].

SUMMARY

In order to solve problems every organization must know how to conduct an effective
investigation, identify root causes and implement workable corrective and preventive action
in a timely manner. The CAPA process must provide a common model and language within
the organization, which allows investigators to master the process quickly and easily.
Management of non-conformances and CAPA processes are essential for pharmaceutical
companies, although scope of business, culture and existing processes will heavily impact the
quality of the product. An efficient CAPA process is a great tool to improve quality systems
and processes; the initial effort is worthwhile if it is well planned and performed correctly.

REFERENCES

[1] Perez jose Rodriguez, CAPA for the FDA regulated industry, ASQ quality press
milwaukee, Wisconsin, (2005) 1-25.
[2] Agile, Almaden Boulevard San Jose, (2002) 1-8.
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