Regulatory Compliant Performance Improvement for Pharmaceutical Plants

AIChE New Jersey Section

01/13/2004

Murugan Govindasamy

Pfizer Inc.

Overview:

• Introduction• Significance of Regulatory compliance and guidelines• Automation Project – How to make it successful?• Downtime Monitoring• Conclusion • Discussion

Significance of

Regulatory Compliance and Guidelines

Regulatory Basis

Food, Drug & Cosmetic Act

Section 501(a)(2)(B) of the Food, Drug & Cosmetic Act deems a drug product to be adulterated if :

“the methods used in, or the facilities or controls used for, its manufacture, processing, packaging, or holding do not conform to or are not operated or administered in conformity with current Good Manufacturing Practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength and meets quality and purity characteristics, which it purports or is represented to possess.”

The Code of Federal Regulations (CFR) is a codification of the general and permanent rules published in the Federal Register by the Executive departments and agencies of the Federal Government. Title 21 of the CFR is reserved for rules of the Food and Drug Administration. Each title (or volume) of the CFR is revised once each calendar year.

PART 211 - Current Good Manufacturing Practice for Finished Pharmaceuticals – ‘the regulations in this part contain the minimum current good manufacturing practice for preparation of drug products for administration to humans or animals.’

CGMP - Current Good Manufacturing Practice

REGULATORYBASIS

FD&C ACT1962

21CFRPART11

21 CFRPART 211

21CFRPART 820

21 CFR11.10

21 CFR211.68

21 CFR 211PROPOSED

AMMENDMENTS

QUALITYSYSTEM

REGULATIONS

PROCESSVALIDATION ANALYTICAL

METHODVALIDATION

CONTAMINATION TESTINGQC

RESPONSIBILITIES

21 CFRPART 320

CLINICALSTUDIES

COMPUTERSYSTEMS

AUTOMATEDSYSTEMS

MEDICALDEVICES

Code of Regulation - General:

21CFR210 - Current Good Manufacturing Practice in Manufacturing, Processing, Packing or Holding of Drugs: General

21CFR211 - Current Good Manufacturing Practice for Finished Pharmaceutical

Automation specific:

21CFR211 - 68 - Automatic, mechanical, and electronic equipment

21CFR211 - 11 - Electronic Records; Electronic Signatures

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Guidelines:

GAMP4 - Good Automated Manufacturing Practice Guidelines

Regulatory Guidelines:

GAMP:

• Excellent tool for a project• Streamlines the requirements• Value adding activities• Common Language

Definitions

Validation“Validation is defined as establishing documented evidence that provides a high degree of assurance that a process, system, equipment or assay will consistently produce the desired results according to predetermined specifications and quality attributes.”

Qualification“Qualification is defined as the documented evidence that the equipment and systems will work correctly and consistently, leading to expected results.”

USER REQUIREMENTSSPECIFICATIONS

PERFORMANCEQUALIFICATION

FUNCTIONALSPECIFICATIONS

INSTALLATIONQUALIFICATION

DESIGNSPECIFICATIONS

OPERATIONALQUALIFICATION

SYSTEM BUILD, INSTALLED, &CONFIGURED

Verifies

Verifies

Verifies

V Model

Validation Project Plan- A Life Cycle Approach

• Pre-Qualification Process• Qualification/Validation Process – IQ, OQ & PQ• Commissioning/Implementation• System Maintenance• Change Control• Re-Validation Criteria• Retirement of the System

What to follow?

• GMP• Regulatory Documents• Regulatory Guidance• Industry Guidance• Internal Policies and Procedures

Quality People + Quality Process

= Quality Product

Automation Project

- How to make it successful?

Automation Projects - Requirements for a successful project

• Clear Business Objective• Root Cause Analyzed, better than alternatives • Justified Investment• Well defined project plan• Champion to lead - from start to finish• Management Support

Major Objectives: (Objectives which directly relates to the efficient

Manufacturing)

• Throughput Increase – Cycle time reduction, Capacity Increase, High-speed

• Quality Control / Improvement – Product Quality, Compliance Requirement, Info. for decision making

• Cost Control – Asset utilization, Efficiency Improvement, Waste Reduction, COGS

• Inventory Control – JIT, Scheduling, Push to Pull• EHS – Safety Requirement, Ergonomics • Specific – Product Launch, Process Optimization,

Information for Management

Automation Projects - always good to…

• Avoid purchasing Serial #1 – Look for history• Know the alternatives and the consequences• Know the bottlenecks and pitfalls• Plan phased approach - if applicable• Enforce company standards and specifications wherever

possible. Alternate standards can be used if justified. • Select the suitable vendors who can establish long term

partnership• Select the most suitable hardware & software. They may

not be the best in the market

Automation Projects - Watch out for…

• Scope creep – not a surprise in any automation project• Validation Issues – Good planning in the beginning will

avoid this• No user buy in - forced automation (typically an

automation engineer carries the project on his/her shoulder).

• No major objective (project - just for a sake of automation)

• Right solution or just a band aid?

"Do it right or do it twice."

Automation Projects - Challenges…

• Return On Investment • Keeping up with technology • Validation Scope • Risk Assessment• Adopting to change (Automation)

Efficiency Improvement through Downtime Monitoring

– a brief discussion

Downtime Monitoring

• Automatically capturing machine downtime and the reasons for analysis

• Key Performance Indicators (KPI)• Downtime monitoring – Excellent tool, good opportunity

for automation, success is measured on the use• Use: Problem solving through Root Cause Analysis

Can be scaled to fit

Utilization and Efficiency Improvement- Business Model for performance tracking

Conclusion

• Understand the regulations• Follow the guidelines and Procedures• Plan Automation as a tool to improve a process• Design and qualification are key to success• Automation project is a success only when it ‘produces’

Discussion