Future State CAPA Management a Productivity Improvement Tool

Special Edition: Corrective and Preventive Action Vol. II

Future State CAPA Management- A Productivity Improvement Tool

By Kamal Biswas

ABSTRACTThe top spot in the Food and Drug Administration

(FDA) observations (FDA 483) list has almost per-

manently been taken by Corrective and Preventive

Action (CAPA). Being a major subsystem of FDAs

Quality System Inspection Technique (QSIT), CAPA

is audited in all FDA inspections. Effective CAPA

management is a top priority to ensure compli-

ance. While compliance need is given, it should be

viewed with a broader outlook to use it as a pro-

ductivity improvement tool. That way it could get all

the stakeholders buy-in, hence better compliance

would result. CAPA should not be regarded as the

headache of the quality functions; it should become

an integral part of operations.

EXECUTIVE SUMMARY

CAPA has been a major stumbling block for many phar-maceutical companies, mainly to manufacturing opera-tions. About 40% FDA 483s seen in the industry relate to CAPA - the highest single category of FDA non-compli-ance. Therefore, the FDA does a thorough check during every inspection it performs in a company. If companies know that CAPA is a major non-compliance issue, why are they not taking adequate safeguard measures? It is the authors opinion that current CAPA measures are failing because CAPA is often considered a compliance need rather than as an important mechanism to improve operational excellence.

Effective CAPA management will not only save pharma companies in compliance audits, its preventive measures can help companies improve productivity by radically re-ducing rework. Effective CAPA management could bring on time analysis of process execution data to identify de-viations and take early action improving quality and pro-ductivity. CAPA needs to be viewed with a broader outlook and made a key focus area for corporate, away from the traditional view of a point-in-time localized function. Com-panies can get substantial benefits by taking an enterpris-ing view of CAPA.


Kamal Biswas

INTRODUCTION

What is CAPA?FDA regulations for CAPA for the pharmaceutical com-pany are defined in Code of Federal Regulations (CFR) 21 section 211, as part of the Quality System Regula-tions (QSR). This process identifies reported and poten-tial causes of product SQUIP- Safety, Quality, Integrity, Potency or Purity - performs root cause analysis of devi-ations, and determines appropriate corrective and pre-ventive actions to eliminate repetition of failure. The pro-gram ensures that corrective and preventive actions get implemented through proper management reporting and review. FDA views this as a linkage to the entire quality management process. That is why the FDA makes sure that CAPA audit is done without any deviation at all lev-els of its inspection in all pharma companies.

Industry TrendCAPA is a very important function, but it does not get sufficient attention because it does not fall under core production processes.

FDA reports show that 30%-50% of observations (FDA 483s) are related to CAPA. In Quality Systems In-spection Techniques (QSIT), management function is given importance and made responsible for observa-tions, thereby bringing many CAPA management issues under the management umbrella and reducing CAPA is-sues, but even the lowest percentages show that CAPA needs to be addressed with greater priority.

Figure 1 QSIT Inspections - Graphical Analysis

CAPA: 50

PAPC: 30

Records: 20 Records: 10

PAPC: 20

CAPA: 30

Management: 40

Non-QSIT Inspections QSIT Inspections


Kamal Biswas

Figure 2 Complex Compliance IssuesToo complex a situation for efficient compliance - multiple regulations, multiple products, multiple locations

Operations

ContinuousImprovementEngineering

Support

Purchase

Customer Care

HR

Quality

EHS

ITY

R&D

Field Services

Legal

Sales

Finance

Marketing

LOCATION-1

FDA

EPA

ICHOSHA

Location 2 Location 3

Location 4Location 5

Drivers of the Current Situation

Pharma Companies View Numerous manual processes required to produce the

final product hamper the CAPA process. Managing the parent-child relationship in raw materials

across products is challenging. This problem increases many fold in dispersed operations.

A proliferation of regulations makes compliance cum-bersome, expensive and often confusing if not con-tradictory.

Proposed View

The pharma industrys view is correct, but there is jus-tification for another view. While pharma companies highlight operational difficulties as the major reason for CAPA non-compliance, there are many other causes:

CAPA is seen in the narrow light of a compliance need, and therefore, is considered as extra work by all except the compliance group.

It is not part of core production processes, and there-fore is dis-integrated from core operations.

It is taken as a point-in-time localized problem, not as part of an enterprise initiative that can bring more focus.

CAPA plays a big role in corporate risk. It can radically disrupt businesses, but it does not appear in corporate risk management programs and remains the responsi-bility of production managers.


Kamal Biswas

DESIGN CAPA WITH A BROADER PERSPECTIVE

While CAPA covers remedial corrections of an identi-fied problem, root cause analysis with corrective action to help understand the cause of the deviation and potentially prevent recurrence of a similar problem, and preventive action to avert recurrence of a similar poten-tial problem as part of Quality Systems, it needs to be expanded with a broader outlook and go beyond quality systems into core operational excellence. The following four major steps can make this happen:

Make CAPA part of core operations Integrate CAPA review as part of Corporate Risk Man-

agement Make it mandatory for all business divisions to partici-

pate in and collaborate with the CAPA program Make the CAPA program part of the financial turn-

around

Make CAPA Part of Core OperationsTo make CAPA part of core operations, it must, as a system, provide added value to operations.

Use it as a productivity improvement tool Uti l ize the program to increase operational

success predictability

CAPA Review as Part of Corporate Risk ManagementDesign the CAPA program as part of the corporate mandate. The CAPA program must be seen as a core operation that can put the organization at risk if not properly acted upon. Corporate risk management needs to mandate all CAPA incidents to be reported at the cor-porate level and must include CAPA incidents as part of performance metrics. They should be as critical as other business performance metrics such as top-line and bot-tom-line growth. Ineffective CAPA management can truly impact the top- and bottom-lines of companies.

Figure 3 Productivity improvement functionEarly stage detection of problems can improve throughput and make operations more productive.

A B C DStep A Step B Step C

80% yield 80% yield 90% yield

If product D fails in final quality check, it needs to be reprocessed that sheds ~20%of Product D. This reduces the overall yield to 46%.

CAPA can detect the problem early enough in the reaction lifecycle that will helpavoiding the reprocessing-hence the overall yield improved to 58%. Elimination ofreprocessing improves the production productivity.

ReactionSteps

Hypothesis

ThroughputProductivity

Example: How CAPA can help improve productivity and throughput



Due to deviation in process, some of the reaction steps may remain incompleteleading to more impurities in product D.

Routine QC checks are designed to test pre-defined tests that may not be enoughto detect impurities due to process deviation. A robust CAPA system can find thedeviation early to enable appropriate remediation steps.

ReactionSteps

Hypothesis

Quality

Example: How CAPA can help improve product quality


Kamal Biswas

Some of the sample metrics that can be tracked include:

Product reprocessing loss CAPA incidents with potential impact on product qual-

ity Impact on regulatory commitments Impact on validation status Other product or lots potentially impacted Need for an NDA Field Alert report or recall

Pre-defined periodic monitoring of metrics at the Corpo-rate Risk Management Council would surface CAPA trend and loss of productivity. The visibility at top management on the productivity loss could bring more seriousness into the CAPA initiative to make it more successful.

Make it Mandatory for all Business Divisions to Participate and CollaborateCAPA programs must be implemented across business functions such as manufacturing, engineering, main-tenance, automation, safety, and even research and development. Many functions, such as early stage R&D, do not follow CAPA because they are viewed as compli-ance functions. But, if CAPA is treated as a mechanism to identify the root causes of failures, it can help R&D functions become more productive; for example: CAPA applies to protocol deviation as well as GCP Note to File investigations and remediation. A robust electronic quality management system would accommodate all GXP, not only cGMP.

Figure 4 Predictability of Occurrence and Impact on SQUIP- Safety, Quality, Identity, and Purity or PotencyUse enterprise CAPA system to improve predictability of success, both in terms of quality and cost of the final product.



If product D fails in final quality check, it needs to be reprocessed that sheds ~20%of Product D. This reduces the overall yield to 46%.

CAPA can detect the problem early enough in the reaction lifecycle that will helpavoiding the reprocessing-hence the overall yield improved to 58%. Elimination ofreprocessing improves the production productivity.

ReactionSteps

Hypothesis

ThroughputProductivity

Example: How CAPA can help improve productivity and throughput



Due to deviation in process, some of the reaction steps may remain incompleteleading to more impurities in product D.

Routine QC checks are designed to test pre-defined tests that may not be enoughto detect impurities due to process deviation. A robust CAPA system can find thedeviation early to enable appropriate remediation steps.

ReactionSteps

Hypothesis

Quality

Example: How CAPA can help improve product quality


Kamal Biswas

Figure 5 Move from Corrective to Preventive Action

PreventiveAction

CorrectiveAction

CorrectiveAction

PreventiveAction

Make it Part of Financial TurnaroundAccountants must report the loss of revenue due to CAPA incidents. This should include direct productivity loss as well as loss of time. FDA regulations do not allow release of a product until all CAPA issues for that batch are closed. This, at times, increases inventory at the manufac-turing plant and creates shortage of product supply in the market, thereby reducing cash flow the throughput impact due to rework increases manufacturing cost significantly. These important metrics fortracking the performance of the whole organization can be improved by placing more importance on CAPA.

HOW INFORMATION TECHNOLOGY CAN HELP

Information Technology (IT) can help pharma companies reduce CAPA incidents and improve quality, while improv-ing productivity by detecting issues very early in produc-tion.

The Vision Make CAPA a part of core activities and provide a sys-tem to execute the program efficiently.

The strategy to develop an efficient CAPA program is accomplished by changing the 90%+ corrective action scenario to 90%+ preventive action mode. Information Technology (IT) systems can help achieve this.

The System Requirements Well defined requirements specifying the internal and external needs must be covered. They must include the proper handling of quality deviations, process devia-tions, audit findings, Non Conformance Reports, opera-tional disruptions, change management, quality assur-ance checks, and customer complaints.

It is very important to include all business functions and their processes to monitor and track CAPA incidents. CAPA architecture must be robust to scale enterprise needs. It must also be flexible to accommodate process customiza-tion for multiple sites, regions, countries, or regulations.

0 Special Edition: Corrective and Preventive Action Vol. II

Data analysis to help resolve CAPA incidents has to be built into the system to make the system critical enough for operational teams.

Create the system keeping in mind a future state of compliance - make it 21 CFR Part 11 compliant. This will help the company in taking a step forward to electronic submissions and Process Analytical Technology (PAT).

The Solution A well defined requirement can help in building a sys-tem that meets all business needs.

Define user requirement specifications and a strong business case to support development of the system. Ex-ecutive sponsorship is a must for a successful program and early user buy-in makes the program useful. A strong business case and a change management initiative are always useful.

Kamal Biswas

Process Variables Description Current Future Delta

1. Number of CAPA incidents 5

4

20%

2. Average time spent in looking for documents, templates

25%

5%

20%

3. Average time spent in document handling 10%

0%

10%

4. Average time spent in status tracking-meetings, phone calls

20%

5%

15%

5. ...

...

...

Benefit Calculation Description Current Future Delta

Reduction in CAPA management time 2.80%

0.85%

1.95

Annual Cash Flow Benefit $146,250

Figure 6 Sample Business Case Parameters


System Features The IT system should be able to continuously moni-

tor data against the standard and create deviation alerts.

The system must be able to provide features that dive deep into earlier data and help solve CAPA issues.

It must show CAPA status on a real-time basis. CAPA players should be able to manage all actions

using the workflow. All required data must be accessible from the systems.

Manual collection of data and its upload into the sys-tem will reduce its popularity.

The system should be self-sufficient to manage CAPA end-to-end.

SUCCESS STORY

Effective CAPA design can have a major impact in product release cycle time. This has been observed for a major U.S. pharma company. The author was involved in helping them to design, develop, and roll out a product release and CAPA system for their manufacturing unit. The system helps the product release team create a single view of manufacturing artifacts with all CAPA incidents and their status. Key metrics collected to support the companys decision to invest in the CAPA initiative included:

60% reduction in product release time Extensive reduction in CAPA incidents Increased confidence in product release with all re-

Kamal Biswas

CAPA Action and Closure

Deviation Flag

Compare with Standards

CAPA Monitoring

An

alysis

Historical data analysis

CAPA resolutionKnowledge base

Failure analysis

Figure 7 System Features Interact


Kamal Biswas

Figure 8 CAPA Management Control Chart

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quired documents compiled and stored online to en-able easy retrievability for audits

Production database created to analyze historical data and for use as a knowledge base

A step toward FDA e-submission

The problem was viewed as an end-to-end manufac-turing problem and provided a solution not only to re-duce compliance issues but also improve operational ef-ficiency.

The system has separate CAPA components for R&D and manufacturing to keep the two processes separate. The system is designed to get data from existing applica-tions with a provision for manual entry as well. It has a deviation monitoring component to send alerts to con-cerned stakeholders and for workflow-driven end-to-end CAPA tracking.

CONCLUSION

Historically, pharma companies have not provided enough attention to CAPA programs and CAPA manage-ment. The compliance focus needs to be strengthened by adding CAPA as a part of the core activity. Production team should use this as a productivity improvement func-tion and not just as a compliance need. Making it a key performance indicator for corporate risk management will help in monitoring it more closely. Company finance teams must be more vigilant to this function and must report loss of revenue due to it.

Good CAPA management improves compliance and productivity, and also builds the image of a good quality system practices company. This helps in building a brand that drives customer excellence and satisfies regulatory authorities. An enterprise-level CAPA strategy, backed by strong IT system support, can help achieve this.

REFERENCES

1. QSIT workshop material on Corrective And Preventive Actions: http://www.fda.gov/cdrh/comp/qsitpage.html

2. Internal Research- Infosys Technologies Ltd: http://www.info-sys.com

3. Food and Drug Administration : http://www.fda.gov

ABOUT THE AUTHOR

Kamal Biswas is with Life Sciences Consulting in Infosys Technologies Limited. Kamal is an expert in Pharma IT strategy and regulatory compliance in FDA regulated industry. He has over a decade experience in phar-maceutical manufacturing operations and IT. He is a thought leader in pharma IT strategy, IT enabled produc-tivity in pharmaceutical manufacturing operations, and regulatory compliance transformation. Kamal is based in New York City /New Jersey, USA, and can be reached at [email protected].

Kamal Biswas


Article Acronym ListingCAPA Corrective Action Preventive Action

CFR Code of Federal Regulations

cGMP Current Good Manufacturing Practice

FDA Food and Drug Administration

GCP Good Clinical Practice

CGXP Current Good Clinical, Laboratory, Manufacturing Practice

IT Information Technology

NDA New Drug Application

PAT Process Analytical Technology

QSIT Quality System Inspection Technique

QSR Quality System Regulation

R&D Research and Development

SQUIP Safety, Quality, Identity, Purity/Potency

U.S. United States

Kamal Biswas

Originally published in the October 2007 issue of The Journal of GXP

Future State CAPA Management a Productivity Improvement Tool

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