Microbiology Event of the Year

For Pharmaceutical, Biotech, Medical Device, and Cosmetic Industries
June 7-11, 2004
Alexandria, VA

HOTEL INFORMATION:
Radisson Hotel - Old Town
901 N. Fairfax Street • Alexandria, VA 22314
(703) 683-6000 • (703) 683-7597
www.radissonoldtown.com
A special room rate has been prearranged for conference participants. Call the hotel
directly at the above number and mention IVT to receive the reduced room rate.

Pre-Registration
Sunday, June 6, 2004 • 6:00 PM – 7:00 PM

Full-Day Interactive Workshops
Monday, June 7, 2004

8:00 AM Registration

8:30 AM – 9:30 AM
Breakfast Discussion: USP and EP Update
General Microbiology Update by the USP
Roger Dabbah, PhD, Director, Complex Actives Division, Information and Standards Development, U.S. Pharmacopeia
David Porter, PhD, Associate Director, Complex Actives Division & Liaison to the Analytical Microbiology Expert Committee, U.S. Pharmacopeia
• Chapters in PF-Status
• Chapters in USP
• Chapters in Development
General Microbiology Update of the EP
Klaus Haberer, Managing Director and Senior Consultant, Compliance Advice and Services in Microbiology GmbH, Expert of the European Pharmacopoeia, Convenor of ISO 198 Working Group 9 Aseptic Processing, Member of the PDA Working Group on Steam Sterilization
• Microbiological tests in the European Pharmacopoeia (EP)
• International harmonisation
• The position of EP on the microbiological limits test and tests for absence of specified microorganisms.

Full-Day Interactive Seminars A, B, C, D
10:00 AM Course Begins
12:00 PM – 1:00 PM Luncheon
3:00 PM – 3:30 PM Refreshment Break
5:00 PM Course Ends

Seminar A • 10:00 am – 5:00 pm

cGMP Testing Requirements in a Pharmaceutical Laboratory
Karen S. Ginsbury, President, PCI Pharmaceutical Consulting Israel Ltd.
I. cGMP Testing Requirements in a Pharmaceutical Laboratory
• Interactive exercise: Participants will review European and FDA regulatory requirements.
• Training and qualification of technicians and supervisors
• Facility requirements
• Equipment qualification, calibration, cleaning, and maintenance
• Reagent, culture controls, including types of water used in testing
• Test methods and specifications
• Documentation and reporting requirements
• Retained samples and stability programs
• Method validation, Statistical Process Control (SPC) and Out-of-Specification (OOS) results, (including rounding numbers)
II. Controls, Standards, Cell Culture Collections, and OOS Results
• Purchasing procedures for laboratory reagents
• Water quality for testing
• Cell culture collections, passage of bacteria, maintenance
• Positive and negative controls, duplicates, replicates, and averaging results
• Maintenance of LAF hoods for testing and cleanroom for sterility testing
• Specifications, trends, and OOS results
• Positive and negative controls, duplicates, replicates, and averaging results
• Specifications, trends, and OOS results (developing a procedure, invalidating results, sampling and handling of samples, and retesting)
III. Interactive Exercise: OOS Results,
Investigation, and Documentation
Case studies will be presented, and participants will work in small groups to resolve typical problems encountered in pharmaceutical/biotech environment. The solution will be discussed with the whole class, so as to provide tools for handling similar situations as they arise in your own facilities.

Seminar B • 10:00 am – 5:00 pm

Identification and Characterization of Microorganisms Using Molecular Methods
Stacy Montgomery, Ph.D., Director of Marketing,
ACCUGENIX
Michael Waddington, Director of Laboratory Operations, ACCUGENIX
I. Overview of Molecular Methods
• Deoxyribonucleic Acid (DNA) extraction
• Theory and practical applications of Polymerase Chain Reaction (PCR)
• Automated fluorescent DNA sequencing
II. Introduction to Microbial Phylogeny
• History of microbial phylogeny
• Phylogenetic interpretation of rDNA sequence data
III. Comparison of Methods for the Identification of Microorganisms in the Pharmaceutical Manufacturing Environment
• Accuracy and reproducibility of genotypic versus phenotypic identification system
• Accuracy of known and unknown environmental isolates
IV. Validation of DNA Sequence Methods for Microbial Identification
• cGMP compliance issues with DNA sequencing
• Private versus public DNA sequence databases
• Validation protocol examples
• DNA sequence-based trending and tracking for environmental monitoring
• Utility of using DNA sequences for tracking and trending environmental monitoring data
• Strengths of an environmental monitoring system based on DNA sequences, rather than microorganism names

Seminar C • 10:00 am – 5:00 pm

nvestigating Process Deviations and Failures: Implementing Corrective and Preventative Actions (CAPA)
Trevor Deeks, Ph.D., M.R.Pharm.S. Senior Validation Consultant, Skanska Construction UK Ltd.
There is an increasing emphasis by worldwide regulatory authorities looking at the way in which companies handle process deviations and GMP and product failures. The emphasis is on the need to ensure that affected batches are secure, and that recurring problems are prevented. CAPA activities may involve implementing changes to the process, and also require that a validated status is maintained.
I. International Regulatory Requirements for Investigation of Process Deviations and Failures
• Regulations surrounding process deviations and GMP and product failures
• What are the inspector’s expectations?
• Reworking and reprocessing
• OOS investigations
II. Examples of Process Deviations and Failures
• What might cause a deviation or failure?
III. Interactive Exercise: Deviation Case Study
This session involves attendees working together in small groups to solve a process problem. The problem is presented in two sections, and the intention is to emphasize the methodology, rather than the specific technology.
IV. Resolving Deviations Using Review Teams – Team Roles
• Team structure – who should be involved?
• How should the team function? (timing and frequency of meetings, reporting structure, and documentation)
• Example of an investigation team in action
V. Essential Elements for Closing Out and Investigation – CAPAs
• Defining responsibilities
• Determining and implementing CAPAs
• Maintaining processes and facilities in a validated state

Seminar D • 10:00 am – 5:00 pm
Strategies for Establishing a Compliant Environmental Monitoring Program; Implementing the New FDA Initiatives on Aseptic Processing
David Vincent, CEO, Validation Technologies, Inc.
Francesco Boschi, QC Microbiology Manager, Monza
Operations, Patheon Italia

The objective of this full-day, intensive seminar is to provide a solid understanding of regulatory requirements for an EM program, and to develop methods for documentation and data management of test results.

I. Environmental Monitoring; the U. S. Perspective
• Writing policies, SOPs, and protocols
• Managing, tracking, and trending EM data
• Developing EM performance qualification protocols
• Quarterly and annual EM reports
• Setting-up specifications
• Action and alert limits
• Out-Of-Action Limits (OALs)
• Corrective and Preventative Action (CAPAs)
• Classification of Cleanrooms
• Meeting federal and ISO standards for cleanrooms
• Cleaning and disinfecting for cleanroom environments
• Developing an EM program for various cleanroom environments

II. Environmental Monitoring: the European Perspective
• Comparison between U.S. and EU regulatory
requirements
• EU-GMP Annex 1
• A EM program for a brand new cleanroom
• Setting and managing action/alert levels
• Action/alert levels excursions: investigations and effective corrective actions
• Microbial identification in an EM program
• Qualification of cleaning and disinfection SOPs
• EUGMP - based inspections
5:30 PM – 6:30PM
Reception sponsored by:ACCUGENIX

Half-Day Interactive Workshops
Tuesday, June 8, 2004

7:30 AM – 8:15 AM
Optional Videotaped Breakfast with the FDA -- Regulatory Update: Current Microbiology Initiatives and Trends
Bryan S. Riley, Ph.D., Review Microbiologist, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Science
• FDA’s "Pharmaceutical cGMP’s for the 21st Century"
• FDA’s Process Analytical Technologies (PAT) initiative
• Rapid methods in microbiology
• Current issues in review and inspection

Half-Day Interactive Workshops: E, F, G, H
7:30 AM Continental Breakfast
8:30 AM Course Begins
10:00 AM – 10:30 AM Refreshment Break
12:00 PM – 1:30 PM Luncheon

Workshop E • 8:30 am – 12:00 pm
Aseptic Processing – Current Regulatory Requirements
Trevor Deeks, Ph.D., M.R.Pharm.S. Senior Validation Consultant, Skanska Construction UK Ltd.
I. Current Regulatory Requirements for Aseptic
Processes – What is New?
• Comparing PIC/S, European Union (EU) and FDA requirements with industry practices
• Examples of FD-483 observations
• Developing an approach for global compliance
II. Performing Media Fills – A Practical Approach
• What is the worst case?
• Establishing the size and frequency of the media fill
• Environmental monitoring programs
• Establishing what is good practice
• Performing incubation and inspection
• Interpretation of results – establishing action and alert levels
• Performing investigations of action and alert levelsIII. Interactive Exercise: Risk Assessment – Managing
Validation Activities
This session is a group exercise in which attendees will perform a risk assessment for a hypothetical multi-product facility. The objective of the exercise is to determine the optimum approach to validate a hypothetical multi-product facility, and the aseptic processes within the facility.

Workshop F • 8:30 am – 12:00 pm
Validation of Microbiological Test Methods
Robert F. Guardino, M.S. M.T.(ASCP), Director of
Microbiology, aaiPharma®
I. Sample Dependent Method Selection
• Non-sterile product requirements
• Sterile product requirements
• Raw material, WIP, and final product
• Process-related microbiological testing
• Environmental testing
II. Interactive Exercise
Attendees will design a microbiological testing plan for solid oral dosage forms and aseptic-fill products. Relevant and applicable methods will be evaluated and discussed. Attendees will learn how to evaluate processes and products to implement a comprehensive microbiological testing strategy.
III. Validation Requirements
• Regulations and guidance documents for method validation
• Compendial requirements; current and proposed
• Setting appropriate acceptance criteria for validation
• Determining product specifications
IV. Microbial Method Validation; Theory and Practice
• What do we mean by validation?
• Validation strategy and hurdles
• Neutralization of antimicrobial properties
• Preparing a validation protocol
• Performing and evaluating method validation studies
V. Interactive Exercise
Attendees will select a method to validate, and with the aid of validation templates, will devise a validation protocol. Attendees will work in pairs, and the partner will review and critique the validation protocol, and offer suggestions for improvement.

Workshop G • 8:30 am – 12:00 pm
Implementing an Electronic Environmental Monitoring Data Management System – A Client/Vendor Perspective
Clients: Parsa Famili, Sr. Manager Quality Control, Draxis Pharma
Ross A. Caputo, CEO, Pharmaceutical Systems Incorporated
Vendor: Susan Cleary, B.Comp.Sc., Associate Director of Product Development, Novatek International
All sections of the workshop will be interactive. Attendees will have the opportunity to ask questions of either the client or vendor at the conclusion of each section.
I. How to Select the Right Environmental Monitoring System
Client:
• Technical information requests
• New system or upgrade existing
• Auditing the vendor
• Making the decision
Vendor:
• Providing system functionality information
• System documentation
• Company background
• Escrow source code
II. How to Implement the Pilot Environmental Monitoring System
Client:
• User acceptance testing
• Configuration requests
Vendor:
• System training
• Configuration control logs
• System modifications
III. How to Validate the Environmental Monitoring System; Meeting 21 CFR Part 11 Requirements
Client:
• Gap analysis
• Who defends the system during an FDA audit
Vendor:
• Approvals
• IQ, OQ, PQ traceability matrix
• Validation test scripts
IV. Launching the EM System
Client:
• Making the transition to the new system
• Choosing a fully electronic or hybrid system
Vendor:
• Technical support services
• Re-validations on upgrade

Workshop H • 8:30 am – 12:00 pm
Microbiological Method Development for Non-Sterile Pharmaceuticals
Rick Jakober, Laboratory Manager, Perritt Laboratories, Inc.
I. Compendial Requirements for Validating Microbiological Methods for Non-Sterile Pharmaceuticals
• European Pharmacopeia (EP), United States Pharmacopeia (USP) and Japanese Pharmacopeia (JP) requirements for validating microbiological methods for new compounds
• Developing guidelines for setting specifications for new materials and products.
• Regulatory expectations for new method development
II. Preservative Systems for Pharmaceutical Products
• Preservative systems for non-sterile pharmaceutical products
• Neutralization steps for chemically preserved samples
• Strategies for neutralization of preservative systems
III. Method Development for Microbial Content Tests and Presence of Objectionable Organisms
• Techniques for validating microbial plate counts
• Validating enrichment tests for objectionable organisms
• Case studies of unusual plate count and enrichment procedures
IV. Method Development for Antimicrobial Effectiveness Testing (AET)
• Review AET test categories
• Preservative neutralization strategies for AET testing
V. Interactive Exercise:
Type of Neutralization Strategies
In this exercise, participants will be give a variety of scenarios with different types of neutralization strategies for validations of plate counts, and enrichments for microbial content tests, enrichment tests for objectionable organisms, and preservative challenge tests. Participants will perform calculations and determine the optimal methodology for each type of product.

Half-Day Interactive Workshops: I, J, K, L
1:30 PM Course Begins
3:00 PM – 3:30 PM Refreshment Break
5:00 PM Workshops Conclude

Workshop I • 1:30 pm – 5:00 pm
Proactive System-Wide Microbiological Control in Ambient Temperature Purified Water Systems
Jim Russell, Senior Process Engineer, Bionostics, Inc.
Bob Livingston, President, Arion Water, Inc.
I. Microbiological Control Philosophy
• The importance of pharmaceutical water systems and validation of a manufacturing facility
• Water system performance as a touchstone of the efficacy
• Ambient temperature purified water systems and microbiological problems
• Purified water system design options
• Designing to EU High Purity (HP) requirements, and its inherent advantages
II. Pretreatment Microbiological Control
• Learn what can be accomplished (TNTC is excessive)
• Learn what cannot be accomplished (< 20 cfu/ml is not practical)
• Learn why common approaches are often the worst thing to do
III. Reverse Osmosis/CDI Microbio Control
• Why hot water sanitization is not required
• Learn why RO biofouling is a symptom of a correctable problem
IV. Point of Use Configuration
• Options for sampling, design, and materials of construction
• Maintaining microbiological integrity, despite variation in point-of-use design
V. Post Treatment, Storage, and Distribution Piping
• Providing less than 1 cfu/ 100 ml ambient product water without sanitizations
• Preventing storage tank microbiological excursions
VI. Interactive Exercises
Participants will learn to actually size and design a purified water system using the straight-forward design approaches outlined in the course.
OR
Participants will learn to quantify the bacterial status of distribution loops with exceeding low bioburden counts with high volume microbiological sampling techniques.

Workshop J • 1:30 pm – 5:00 pm
Laboratory Equipment Qualification and GMP Compliance
Trevor Deeks, Ph.D., M.R.Pharm.S. Senior Validation Consultant, Skanska Constructin UK Ltd.
I. Current Regulatory Requirements, Expectations, and Inspection Procedures in the Control Laboratory
• Distinguishing between GMP and GLP
• The functions of the control laboratory
• The requirements for premises and equipment
• Practices and procedures for laboratory inspections
II. Validating New Laboratory Equipment
• Determining the level of CSV required
• IQ, OQ, and PQ testing requirements
• Performing Part 11 assessments
• Maintenance, calibration, and change control
III. Interactive Exercise:
Risk Analysis – Selecting and Validating New Laboratory Equipment
Participants will work as a group to perform a risk analysis of what equipment needs to be qualified. The same groups will evaluate the IQ and OQ requirements for an HPLC system.

Workshop K • 1:30 pm – 5:00 pm
User-Friendly and Cost-Effective Solutions for Automating Your Microbiology Laboratory
Sebastien Manuel, Eng., Applications Manager,
Microbiologist, AES-Chemunex, Inc.
I. Production of In-House Culture Media
• Automating this labor-consuming step of the analysis
• How to be more productive and efficient
• Guaranteeing a full traceability of your reagents preparation
II. Sample Preparation
• How the new standards could impact this step
• Preparing more samples in the same time and without more lab technicians
• Guaranteeing a full traceability
III. Monitoring of Laboratory and/or Manufacturing Equipment
• Learn how a wireless GLP and CFR11 compliant central temperature monitoring system will let you save hours, and eliminate the risks of incubator and refrigerator failures
• Implementing this monitoring system in your facility
• Using this system for mapping your equipments
• Qualifying this system (calibration, validation)
• The benefits of such a device for your traceability
IV. Interactive Exercise:
Participants will implement the above solutions in the lab

Workshop L • 1:30 pm – 5:00 pm
Microbiological Control in Pharmaceutical and Biotech Manufacturing
Lucia Clontz, Director of QC Microbiology/Environmental Services and Raw Materials, Diosynth Biotechnology
I. Microbial Contamination
• Identifying possible sources of microbial contamination
• Implementing microbial control measures
• Regulatory expectations and guidelines
II. Cleaning and Disinfection
• Factors to be considered when selecting a disinfectant
• Regulatory expectations and guidelines regarding cleaning requirements and use of disinfectants
III. Environmental Monitoring (EM)
• Implementing and managing an EM program
• Regulatory expectations
• Data trending and presentation during inspections
IV. Interactive Exercise:
Investigating EM Excursions
Case studies dealing with EM excursions will be discussed. Participants will break into groups, perform root cause analysis, and propose CAPA plans.

5:00 PM – 5:30 PM
Ask the USP!
Roger Dabbah, PhD, Director, Complex Actives Division, Information and Standards Development, U.S. Pharmacopeia
David Porter, PhD, Associate Director, Complex Actives
Division & Liaison to the Analytical Microbiology Expert
Committee, U.S. Pharmacopeia
This informal group discussion hosted by USP representatives will attempt to answer everything you always wanted to know about the USP, but were afraid to ask. Get valuable, "direct-from-the-source" information about interpretations, harmonization, specific procedures, USP service as members of Expert Committees, the revision process and you.

90-Minute Interactive Sessions Wednesday, June 9, 2004

8:00 AM – 8:45 AM
Optional Videotaped Breakfast with the FDA -- Regulatory Update: Current Microbiology Initiatives and Trends
Bryan S. Riley, Ph.D., Review Microbiologist, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Science
• FDA’s "Pharmaceutical cGMP’s for the 21st Century"
• FDA’s Process Analytical Technologies (PAT) initiative
• Rapid methods in microbiology
• Current issues in review and inspection

Session 1 • 9:00 am – 10:30 am
Endotoxin Limits: Finished Product and In-Process Materials
Michael E. Dawson, Ph.D., Director of Manufacturing Development, Associates of Cape Cod, Inc.
I. Introduction to Endotoxin, LAL, and the Need for Endotoxin Limits
• Introduction to endotoxin and the LAL test methods
• Comparison between the rabbit pyrogen test and the bacterial endotoxins (LAL) test
• Why are endotoxin limits necessary?
II. Calculation of Endotoxin Limits
• Limits for compendial drug products
• Limits for clinical trial materials
• Limits for in-process materials
III. Interactive Exercise: Calculation of Endotoxin Limits of the Various Components of a Drug Product
Participants will learn how to set appropriate limits for drug product components, including the active pharmaceutical ingredient and the individual excipients.

Session 2 • 9:00 am – 10:30 am
Development of a Viable Environmental Monitoring Program for a Non-Sterile Pharmaceutical Manufacturer
Robert Reich, President, PSI (Pharmaceutical Systems, Inc.)
I. Understanding Industry Guidelines and Practice
• Sterile product guidelines and standards
• Non-sterile product guidelines and standards
• Non-sterile viable monitoring regulatory expectations
• Industry practices
II. Creating the Protocol and Executing the Program
• Sample site rationale
• Sampling procedure and frequency
• Sample handling and incubation
• Data analysis and trending
• Establishment of alert and action levels
III. Interactive Exercise: Non-Sterile EM Program
Participants will review the challenges in development of a viable environmental monitoring program for a non-sterile pharmaceutical manufacturer.

Session 3 • 9:00 am – 10:30 am
Practical Approaches To Sterility Testing
Robert F. Guardino, M.S. M.T.(ASCP), Director of
Microbiology, aaiPharma®
I. Understanding the Sterility Test
• What it tells you, what it does not
• Why is it performed?
• Relevance for the aseptically filled product
• Relevance for the terminally sterilized product
II. Regulations and Guidance
• European regulations
• CFR and GMPs
• EP/USP monographs and general chapters
• Changes in sterility testing as a result of harmonization
• Environment and monitoring during sterility testing
III. Bacteristasis / Fungistasis Testing
• Selecting the appropriate method
• Suitability of culture media
• Sample preparation and microbial survival
IV. Sterility Testing and Test Failures
• Test preparation
• Laboratory Investigation of OOS results
• Communication between contract lab and client
• Documentation practices
V. Interactive Exercise
This session will examine method development and validation of difficult products. The effect of various sample preparation techniques on microbial survival will be discussed.

Session 4 • 9:00 am – 10:30 am
A System-Based Approach: Risk Assessment and Risk Management Due to Microbial Contamination During Aseptic Manufacturing
Dilip Ashtekar, Ph.D., Director, Corporate Microbiology, MedImmune, Inc.
I. Risk Assessment
• Safety and efficacy of products
• The total quality system
• Regulatory expectations
II. Risk Approaches for Microbial Contamination in Aseptic Manufacturing
• Failure Mode and Effects Analysis (FMEA)
• Hazard Analysis Critical Control Points (HACCP)
III. Risk Determinations Due to Microbial Contamination in Aseptic Manufacturing
• Severity of risk
• Occurrence of risk
• Method of detection of risk
• Tools required for performing such an analysis
• Product impact assessment and documentation
10:30 AM – 11:00 AM – Refreshment Break

Session 5 • 11:00 am – 12:30 am
Microbial Contamination of Non-Sterile Pharmaceutical Products - A Review
Luis Jimenez, Ph.D., Director of Microbiology and Application Development, Genomic Profiling Systems
I. Microbial Contamination in the United States
• FDA recalls from 1995 to 2003
• Types of microorganisms present in contaminated products
• Are the indicators present?
II. Microbial Contamination in Europe and Asia
• Reported cases around the world
• Types of microorganisms present in contaminated products
• Are the indicators present?
III. Microbial Limits Testing
• Compendial methods
• ATP bioluminescence methods
• Polymerase Chain Reaction (PCR) methods
• Immunoassays
• Growth Direct
IV. Interactive Exercise: Microbial Limits Testing
Participants will discuss several ways to optimize microbial limits testing.

Session 6 • 11:00 am – 12:30 am
Auditing for GMP Compliance
Lucia Clontz, Director of QC Microbiology/Environmental Services and Raw Materials, Diosynth Biotechnology
I. Audits and Inspections
• The value of audits
• How forms of audits can be used to evaluate, monitor, and ensure compliance with cGMPs and company SOPs
II. Regulatory Inspections
• Areas of deficiencies as determined by regulatory agencies
• Current regulatory inspection trends
• Differences between European and FDA inspections
III. Preparing for Inspections
• How to prepare for successful inspections
• Presentations and behavior during audits and inspections
• The value of internal audits
• Common pitfalls
IV. Interactive Exercise:
Creation of Internal Audit Checklists
Participants will break into groups, and create checklists for QC laboratories, manufacturing, and quality assurance areas.

Session 7 • 11:00 am – 12:30 am
Current Issues in Pharmaceutical Water System Microbiology
Karen Ginsbury, President, PCI Pharmaceutical Consulting Israel Ltd.
I. Regulations and Guidance
• Where to look for guidance: USP, Ph. Eur, FDA, other
II. Current Issues in Water
• Validation of sampling techniques (does sampling match usage, how long are samples held until testing, and under what conditions?)
• Media types, recovery of damaged micro-organisms, incubation temperatures, and identification of organisms
III. Interactive Exercise:
Handling Water Results
• Trending and out-of-trend or above alert action level results
• "Retesting?" or obtaining additional data
• Seasonal trending

Session 8 • 11:00 am – 12:30 am
Understanding and Using Disinfectants for Cleaning
Fred Marsik, Ph.D., ABMM, Microbiology Consultant, Currently employed as a microbiology reviewer for the FDA in the Division of Anti-Infective Drug Products
Note: Dr. Marsik's participation is in his own private capacity as a microbiology professional. No official support by the FDA is intended or inferred.

I. Understanding Disinfectants Effectively
• Importance of proper disinfection
• The various classes of disinfectants
• Mode of action and inactivation
• Microorganism resistance to disinfectants
II. How to Choose a Disinfectant
• Microbiological, physical, and environmental factors
• What's in a label?
III. Validation of Efficacy
• What needs to be considered?
• Methods
VI. Interactive Exercise
During this session, participants will learn about the various classes of disinfectants, how to choose a disinfectant, and how to evaluate the efficacy of a disinfectant.
12:30 PM – Luncheon

Session 9 • 1:30 pm – 3:00 pm
mpact of Risk-based Approach on FDA Inspections and Preparing for a Successful PAI
Sandy Mohan, Ph.D., Director, Quality Assurance, CV Therapeutics.
I. Understanding the Risk-Based Approach
• Improving integration of PAI and cGMP inspections
• Revision of PAI priorities
• Site selection and focus of inspections
• Establishment of Pharmaceutical Inspectorate (PI)
• Systems inspections
II. A Contract Manufacturing Organization (CMO)
as a Partner
• Role of the CMO; role of the sponsor
• Drivers for a successful PAI in a contract setting
• CRO-sponsor relationship
• Key elements needed for a successful PAI
• SME preparation, systems checklist, document checklist
• Sharing the success
III. How to Prepare for a PAI
• PAI readiness team
• Roles and responsibilities (inspection coordinators, subject matter experts)
• Mock PAI
• Agenda management during inspections
• Post inspection issues
IV. Interactive Exercise
Based on the principles covered in the previous sections,
participants will have an opportunity to assemble a mock
PAI team (appoint coordinators, scribes, runners etc.,), and discuss ways of handling an inspection.

Session 10 • 1:30 pm – 3:00 pm
The Place of the Microbiologist in the Cleanroom
Karen Ginsbury, President, PCI Pharmaceutical Consulting Israel Ltd.
I. Cleanroom Microbiology
Microbiology as applied to a pharmaceutical cleanroom environment.
II. Microbiological Issues in the Cleanroom
• Microbiology of environmental monitoring
• Microbiology of water monitoring
• Bioburden
• Filter validation
• Microbiology of equipment validation
• Identification of organisms
III. Interactive Exercise:
Microbiologists and Investigations
This session will analyze a contamination event and consider how microbiologists can assist in resolving the deviation/investigation.

Session 11 • 1:30 pm – 3:00 pm
Bioburden Testing of Pharmaceutical Preparations and Raw Materials
Eva D’Haese, Ph.D., Research Associate, Laboratory for Pharmaceutical Microbiology, Ghent University, Belgium
I. EP and USP Requirements for Microbiological Testing of Non-Sterile Products
• USP: microbial limit test
• EP: total viable aerobic count, and test for specified microorganisms
II. How to Control the Validity of Bioburden Tests
• Testing the effectiveness of culture media
• Testing the validity of the counting method
III. How to Determine the Bioburden of Problem
Substances
• Presentation of selected case studies
• Laser Scanning Cytometry: a valuable alternative?
• How to deal with regulatory requirements
IV. Interactive Exercise: Bioburden Testing
Attendees discuss their own bioburden testing experiences.

Session 12 • 1:30 pm – 3:00 pm
Determining Endotoxins on Elastomeric Closures
Renaud Janssen, Ph. D., R&D Manager, Helvoet Pharma Belgium N.V.
I. Elastomeric Closure Manufacturing Process
• Raw materials
• Steps in the manufacturing process
• Washing elastomeric closures
• Monitoring systems for closure manufacturing environment
II. Washing Validation
• Regulatory requirements/expectations
• Depyrogenation of elastomeric closures
• Log 3 endotoxin reduction and endotoxin limit values
III. Endotoxin Determinations on Elastomeric Closures
• Principles and overview of determination method
• Endotoxin recovery at high spike and at low spike
• Impact of closure geometry
IV. Interactive Exercise
Starting from a survey of methods that are applied by different labs, attendees will discuss their own in-house endotoxin determination methods for primary packaging components for parenteral use, and the rationale for applying them.
3:00 PM – Refreshment Break

Session 13 • 3:30 pm – 5:00 pm
GMP Training and Compliance Strategies
Jason Hier, Senior VP Consulting Services, Bovis Lend Lease - Life Sciences Division
I. Everyone Needs to be a Microbiologist
• Determining who needs training, what training is needed, and how is it recorded?
• Human Resources (HR) and Quality Assurance (QA) responsibilities
II. Understanding Microbiological Risk
• What microbes are a threat to non-sterile product?
• Cleaning validation and microbiological risk
• Ensuring compliance through effective design
• Designing of utilities and facilities to reduce microbiological risk
III. Ensuring Compliance Through Effective Systems
• Using the deviation system as an improvement tool
• Ownership of the customer complaints
IV. Interactive Exercise:
Personnel Monitoring
Using a case study from the device industry, participants will learn how to manage personnel monitoring failures from a case study of tableting manufacture – final product microcount failure due to design flaws

Session 14 • 3:30 pm – 5:00 pm
How to Handle OOS Microbiological Results for
Bioburden, LAL, and Sterility Test Results
Dilip Ashtekar, Ph.D., Director, Corporate Microbiology, MedImmune, Inc.
I. Understanding the OOS Draft Guidance
II. Regulatory Expectations and cGMP Compliance
of OOS Results
• Adequate investigation
• Root cause analysis
• Robust Corrective and Preventative Actions (CAPA)
III. Strategies for Handling OOS Results for
Microbiology Test Results
• LAL, bioburden, and sterility
• Essential strategies and steps to identify laboratory error
• What to do when assignable cause is identified, and when no assignable cause is identified?

Session 15 • 3:30 pm – 5:00 pm
Practical and Simple Microbiology for the Non-sterile OTC Pharmaceutical Industry
Judy Bateman, BSMT (ASCP), M.Ad., QA Microbiologist, C.B. Fleet Co., Inc.,
I. Expectations of the Microbiologist in the Non-Sterile OTC, Cosmeceutical, or Personal Care Industry?
• Micro personnel guidelines for the cosmetic industry
• USP directed microbiological testing on non-sterile product
• What is "rapid" microbiology, and, how can the smaller lab afford it?
II. ICH Microbiological Testing Changes; How to Become Pro-Active in a Regulatory Setting
• The formulation and nature of ingredients
• Consider consumer risk and abuse of product
• Collaborating with production and processing to assure process control.
• The power of observation and quality testing
III. Applying New Ideas to the "Old" Micro Lab —
What is Expected of Me?
• Incorporating some ideas from the cosmetic industry into the pharmaceutical laboratory
• How can we come up with some less costly rapid micro methods?

Session 16 • 3:30 pm – 5:00 pm
Microbial Limits Test – Harmonization Review and Impact of Changes
Beth Brescia, Associate Director QC Microbiology, Alkermes, Inc.
I. Harmonization Process
• Pharmacopeial discussion group
• ICH expert working group task force
• Consensus microbial limits document
II. Microbial Limits Test
• Overview, and history of changes
III. Proposed Changes and Potential Impact
• Microbiological examination of non-sterile pharmaceutical products
• Microbial enumeration tests
IV. Interactive Exercise
During this exercise, participants will break into groups and develop a Phase (I-III) appropriate microbiological examination program for two different non-sterile pharmaceutical products.
6:00 PM Bus Trip to Downtown Washington, DC

Rapid Methods Conference
Thursday, June 10, 2004

7:30 AM – Registration and Continental Breakfast

8:00 AM –Chairperson’s Welcome and Opening Remarks
Michael J. Miller, Ph.D., Microbiology Leader - Standards and Technology, Eli Lilly and Company

8:15 AM
Interview with FDA/CDER's Microbiology Team
Edward A. Fitzgerald, Ph.D., Senior Consultant, Fitzgerald Consulting, LLC, former CBER/FDA employee, USP Analytical Microbiology Expert Committee
• FDA/CDER Perspective Related to Rapid Microbiology
• FDA/CDER's Point of View on Rapid Method Validation
• How FDA's Process Analytical Technology (PAT) Guidance Will Affect Rapid Microbiology
• FDA's Initiative on Product Quality for the 21st Century

9:15 AM
Live Tele-Presentation from Germany
Alternative Microbiological Methods: Still Just Around the Corner - Positions of Authorities, Industry, and Suppliers in Europe
Dr. Klaus Haberer, Managing Director and Senior Consultant, Compliance Advice and Services in Microbiology GmbH, Expert of the European Pharmacopoeia
This session will address recent developments in the application of alternative microbiological methods in pharmaceutical quality assurance. What is the reason that alternative methods have been an imminent revolution to the microbiological laboratory for many years? The reasons for hesitance of authorities and users and the problems of suppliers of new methods will be discussed. The latest developments in the regulatory field will be highlighted. Ways to overcome real and imagined obstacles to the application of new methods will be presented.

10:00 AM — Refreshment Break

10:15 AM
Current USP Perspective on Alternative Microbiological Methods
Roger Dabbah, Ph.D., Director, Complex Actives Division, Information and Standards Development, U.S. Pharmacopeia
David Porter, Ph.D., Associate Director, Complex Actives Division & Liaison to the Analytical Microbiology Expert Committee, U.S. Pharmacopeia
USP refers to alternative methods in its General Notices. This means that you can use an alternative method to a USP microbiological procedure, provided that you can show that the alternative is equal or better than the pharmacopeial procedure. This also includes automated methods and rapid methods. The USP Expert Committee on Microbiology has developed and published in PF for public comments a procedure to show that an alternative method is equal or better than the pharmacopeial procedure. It reviews the parameters involved in such a protocol making a differentiation among qualitative methods, qualitative methods, and identification methods.

11:00 AM
In-Depth Validation Strategies for Rapid Microbiological Methods
Michael J. Miller, Ph.D., Microbiology Leader - Standards and Technology, Eli Lilly and Company
Pharmaceutical companies are breathing a sigh of relief because regulatory agencies have started to accept the concept of rapid microbiological methods. Recent initiatives, such as the FDA's Process Analytical Technology (PAT), have given companies the incentive to identify and put in place rapid methods in support of manufacturing and QC activities. However, developing a validation strategy for new rapid microbiological methods might be challenging, due to the presence of a variety of technical reports, compendial guidelines, and "industry best practices." This presentation will provide a clear direction and in-depth review of how to develop and implement a meaningful validation program for rapid microbiological methods.

12:00 PM — Luncheon

1:30 PM
Newer Technologies, Methods, and Applications of Rapid Microbiology
Jeanne Moldenhauer, Pharma Consultant, Vectech Pharmaceutical Consultants, Inc.
This presentation will provide an overview of some of the technologies available for rapid microbiology testing and potential uses for these technologies. The focus of the presentation will be on those new additions to the equipment manufacturers and/or methods being evaluated for a rapid system. Some issues with validation/implementation of these systems will also be discussed.

2:30 PM
Points to Consider in the Validation of an Automated Sterility Testing System
Gary C. du Moulin, Ph.D., M.P.H., Vice President, Quality Systems, Genzyme BioSurgery
The BacT/Alert Microbial Detection System has been evaluated and presents a suitable option as an alternate test method. This presentation will focus on a number of areas pertinent to the validation and acceptance of alternative testing paradigms:
• Elements of quality control sterility testing unique to patient specific, short shelf-life products that require immediate patient administration
• Comparison of incompatibilities to compendial and CFR testing methodologies
• Feasibility of this rapid microbiology system for novel therapeutic modalities
• Elements of validation necessary for determining comparability and acceptance as an alternate test
• Technology transfer, implementation challenges, and acceptance criteria

3:15 PM – Refreshment Break

3:30 PM
Utilizing Quantitative PCR for Mycoplasma Testing of
Biopharmaceutical Products
Audrey Chang, Ph.D., Senior Director, Biologics and LADS, BioReliance
The presence of mycoplasma is a common phenomenon that can interfere with major metabolic systems of host cells. From a safety and regulatory standpoint, it is important to ensure biopharmaceuticals produced are free from such contamination.
• Mycoplasma contamination in biologics
• Traditional detection methods of mycoplasma
• Detecting mycoplasma with rapid methods

4:15 PM
Rapid, Sensitive Detection of Mycoplasma Species Contamination Using a Hybridisation Protection Assay System
Dr. Peter Ball, Director, Strategic Marketing, Pall Life Sciences
Detection of Mycoplasma species has traditionally involved growth-based methods, which are very slow (up to 45 days) staining, which requires specialised skills, or PCR. We report on the sensitivity of an alternative rapid method based on detection of a ribosomal RNA (rRNA) sequence conserved across all Mollicutes, which uses the Gen-Probe Hybridisation Protection Assay. Learn about equivalent sensitivity to both 'conventional' PCR and (with appropriate sample concentration) nested PCR.

5:00 PM – 6:00 PM
Reception sponsored by: PSI

Rapid Methods Conference
Friday, June 11, 2004

Rapid Method Vendor and User Workshops with
Inclusive ‘Hands-On’ Equipment Demonstrations

Workshop A • 8:30 am – 10:00 am
Implementation of Rapid Microbiology in the Real World
Vendor: Jaimie Russo, Applications Scientist for Rapid Microbiology, Field Service and Validation Manager, Millipore Corporation
Industry User: To be announced
I. The Technology:
• Rapid enumeration of micro-colonies using ATP Bioluminesence
• How the appropriate design, including CCD image analysis and semi-automated work stations, can make this technology applicable to the "Real World"
II. Applications:
• Final product testing, in-process testing, water testing
III. Validation and Regulatory Perspectives
• Developing a User Requirement Specification (URS)
How the "Milliflex Rapid" was validated
IV. Data Review
• The data to support the validation of the system
• Using the data available to simplify your validation
V. Industry-User’s Perspective
• The experience of an industry-user of this technology, and user applications
VI. Hands-On Demonstration
• Experience the new "Milliflex Rapid" system

Workshop B • 8:30 am – 10:00 am
Get Real-Time Results in Microbiology without Sacrificing Sensitivity and Accuracy
Vendor: Pascal Yvon, Pharm.D., CEO, AES – Chemunex, Inc.,
Industry User: To be announced

I. How Does ScanRDI Work?
• Cell labeling and cell enumeration
• The total time to result is 90 minutes, with sensitivity down to 1 single cell
II. Where and When Can It Be Implemented?
• Process-water monitoring
• Cell culture process monitoring
• Environmental monitoring
• Learn how ScanRDI can support your quality processes
III. How to Implement It Now?
• Scan RDI is 21 CFR Part 11 compliant.
• Drug master file
• Validation package available
IV. Scan RDI Demonstration
• Scan RDI is a reliable tool that can be used for a wide variety of samples to effectively replace traditional analysis methods at every step of the pharmaceutical manufacturing process – from raw materials to cleaning and sanitation.
10:30AM — Refreshment Break

Workshop C • 11:00 am – 1:00 pm
Validation Under the Regulatory Requirement of a Rapid Detection Method Utilized for Releasing Products
Vendor: Dr. Lucia Ceresa, European Marketing Manager, Pall Life Sciences
Industry User: Gilberto Dalmaso, Microbiological Laboratory Head - GlaxoSmithKline Italy
I. ATP Rapid Technology
• Using ATP Bioluminesence detection system
• Instrumentation, and the reliability of the fast results
II. Applications: Where the Pallchek System Can Be Used
• In-process production testing, water testing, fast final product releasing
III. Validation Study: Meet the Regulatory Requirements
• How to approach the validation studies
• How the Pallchek System is validated according to relevant industry guidelines published by the USP and PDA
• Validation data and real data in routine use
IV. Industry User’s Perspective
• Experience of a pharmaceutical industry-user about the completed validation and approval of the new method
V. Hands-On Demonstration
• Using PallchekTM system: luminometer and kits
• The complete MicroFunnel device completely validated under USP requirement, and the new MicroFunnelTM Plus
• The new strategy; using traditional and new microbiological products together

Workshop D • 11:00 am – 1:00 pm
Utilizing DNA Fingerprinting to Identify, Characterize, and Track Bacterial Contamination in Pharmaceutical Manufacturing Environments
Patrick T. McCarthy, Pharmaceutical Market Manager, DuPont Qualicon
I. Understanding the Technology, Process, and Capabilities of the RiboPrinter® System
• Exploring the benefits of a fully automated system
• How Ribotyping is different than 16s sequencing
• The advantages of DNA over Phenotypic-based
ID technologies
• Creating a microbial knowledge database
II. Utilizing the RiboPrinter® System’s Strain Level Information for Pharmaceutical Applications
• Root cause analysis; OOS investigations; routine identifications; microbial mapping to track and trend contamination; product development
III. Experience RiboExplorer® Firsthand
• Using RiboExplorer‚ in compliance with 21 CFR Part 11
• Accessing sample pattern histories and source information
• Using the DuPont database to support investigations
• Communicating data, export data, and generating offline reports
• Creating a custom identification database
• Establishing a globally networked database

_________________

User Case Study: Validation and Implementation of the Qualicon RiboPrinter® in a Quality Control Laboratory
Amy McDaniel, Ph.D., QC Manager, QC Microbial Science & Technology, Wyeth BioPharma
In this session, attendees will hear from an industry leader and learn about their first-hand experience using the strain level tracking capabilities of the DuPont Qualicon RiboPrinter® system.

REGISTRATION:

Monday, June 7, 2004
___8:30 am Breakfast USP & EP Update Full-Day Interactive Seminars . . . . . . . . . . . . . . . . . .$995.00
10:00 am – 5:00 pm ___A. ___B. ___C. ___D.

Tuesday, June 8, 2004
___7:30 am — I will attend the Video Breakfast:
FDA Regulatory Update

Half-Day Interactive Workshops . . . . . . . . . . . . . . . . . .$595.00
8:30 am – 12:00 pm ___E. ___F. ___G. ___H.

Half-Day Interactive Workshops . . . . . . . . . . . . . . . . . .$595.00
1:30 pm – 5:00 pm ___I. ___J. ___K. ___L.
___5:30 Ask the USP

Wednesday, June 9, 2004
___8:00 am — I will attend the Video Breakfast:
FDA Regulatory Update

Expanded Sessions
9:00 am – 10:30 am ___1.___2. ___3. ___4. . . . .$395.00

Expanded Sessions
11:00 am – 12:30 pm ___5. ___6. ___7. ___8.. . . . $395.00

Expanded Sessions
1:30 pm – 3:00 pm ___9. ___10. ___11. ___12.. . . $395.00

Expanded Sessions
3:30 pm – 5:00 pm ___13. ___14. ___15. ___16.. . . $395.00

Thursday – Friday, June 10-11, 2004
___RAPID METHODS Conference - . . . . . . . . . . . . . . $1,795.00

TOTALS

Monday, June 7
Full-Day Interactive Workshop_____x $995.00: $ ___________

Tuesday, June 8
Half-Day Interactive Workshop(s)___x $595.00: $___________

Wednesday, June 9
Expanded Session(s) ________ x $395.00: $___________

Thursday, June 10 and Friday, June 11 Rapid Methods
Conference : ________ x $1,795.00: $___________

TOTAL Enclosed: $___________
* Early Bird Discount -10%: $___________

TOTAL ENCLOSED: $___________

The Ultimate Passport . . . . . . . . . . . . $2,595.00
A complete conference package is available
which includes all 5 days:

*Early Bird Discount: Register early and send in payment before April 12, 2004 and receive a 10% discount.

Multiple Registrations: Send three attendees and the fourth is FREE!
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Method of Payment:
Please note that payment is required in advance of the conference. Please make checks (in U.S. funds drawn on a U.S. bank) payable to Institute of Validation Technology. Confirmation of your registration will be sent. Full payment must accompany registration form. Registrations received without payment will not be processed.

Cancellations/Substitutions:
Your registration form may be transferred to a member of your organization at any time. Requests for cancellations (by mail or fax) must be received by May 24, 2004 in order to receive credit for attending another IVT event. Please be aware that cancellations will not be accepted after that date. All cancellations are subject to a $325.00 processing fee. IVT reserves the right to cancel an event. IVT is not responsible for any airfare, hotel, or other costs incurred by registrants. Speakers subject to change without notice.