GMP Compliance Workshops with Dr. Ludwig Huber

Seminar at Peking University

• Equipment Qualification and Calibration in Laboratories

• Practical Computer System Validation and FDA Part 11 Compliance in Laboratories

September 3 to 6, 2009                                              photos

Graduate Program of International Pharmaceutical Engineering Management

The seminar was part of the Graduate Program of International Pharmaceutical Engineering Management at Peking University. The program is dedicated to quality management and regulatory science and provides an excellent opportunity to middle and senior management of pharmaceutical/API companies and government regulatory agencies. The objective is to produce highly trained professionals meeting international standard for the pharmaceutical industry and regulatory agencies of China.  The program is supported by the US FDA, the Chinese SFDA, and world leading Pharmaceutical companies. The course was sponsored by Agilent Technologies. 

Attendees

The seminar has been attendeed by 115 QC directors, and quality and lab managers from  pharmaceutical and API manufacturers. Amongst the audience were also four officials from the Chinese SFDA and by a delegate from the US FDA Beijing office.

The presenter Dr. Ludwig Huber (left) at lunch with  Dr. Brenda Uratani, Assistant Country Director US FDA China Offices, and with Accociate Prof. Mr. Wang Yamin, Center for Drug Evaluation, SFDA.

Course objectives

• Get a thorough understanding of FDA and international drug regulations and guidelines
• Systematically learn how to effectively implement and apply lab-equipment and computer system validation for day/-by-day lab operations
• Understand consequences of non-compliance
• Prepare your lab and organization for successful FDA and international GMP inspections
• Generate, maintain and archive analytical test results with highest accuracy, reliability and data integrity

Agenda Overview

• Day 1 and Day 2:
  Equipment Qualification and Calibration in Laboratories

• Day 3 and Day 4:
  Practical Computer System Validation and FDA Part 11 Compliance in Laboratories

Detailed Agenda Day 1 and Day 2:

Requirements and approaches for Equipment Qualification and Calibration

• Requirements and approaches for Equipment Qualification and Calibration
• Validation overview: equipment, computers, methods, system suitability testing
• FDA/EU requirements, expectations and enforcement
• USP Chapter <1058> : Analytical Instrument Qualification. ASTM 2500
• USP and EP requirements for system suitability testing
• Learning from the GAMP 5 and from the Good Practices guide for Laboratory System Validation
• The equipment qualification lifecycle

Going through the qualification phases

• Calibration/Qualification planning
• Design qualification, specifications, vendor assessment
• Installation and operational qualification
• Performance qualification
• System suitability testing: frequency, tests, acceptance criteria
• Maintenance, change control and updates
• Documentation

Requalification/recalibration - who, what, when, how much

• At regular intervals
• After hardware and firmware upgrades
• After moving the instruments
• When the equipment is used for other applications
• Before/after maintenance
• Who does it: vendor or user?

Going from simple to more complex examples

• Glassware - do we need any formal qualification?
• Balances, pH meter
• Ovens, refrigerator
• UV Spectrophotometer
• GC, GC/headspace, MS, Karl-Fischer Titrator
• Computerized systems
• Qualification tasks and documents for equipment categories

Vendor Contributions for Equipment Qualification

•  Helping to select the right equipment and specifications
• Development and manufacturing in a quality environment
• Preventive maintenance to ensure on-going performance
• Assistance for on-site qualification: IQ and OQ
• Software for system suitability testing

Detailed Agenda Day 3 and Day 4:
Practical Computer System Validation and Part 11 Compliance

Strategies for Cost Effective Computer System Validation:

• FDA/EU expectations and enforcement
• Recent warning letters and how to avoid them
• International requirements: Europe, Japan, Australia, Singapore
• Recommendations from Industry task forces, e.g., GAMP 5 ad ASTM 2500
• Developing an effective computer system validation program
• What’s important for planning, specifications, IQ/OQ/PQ, changes
• Review and revalidation: when, what, how

Validating special systems and applications

• Computer controlled analytical systems
• Chromatographic data systems, LIMS, Electronic Archiving Systems
• Excel spreadsheets
• Network infrastructure and systems
• Document management and enterprise content management systems

Risk based validation: optimizing your resources

• Risk management approaches
• Defining risk categories for laboratory systems
• Defining validation tasks for high/medium/low risk systems
• ‘Justify and document’ your decision
• Going through examples

Compliance with e-records/signature regulations

• How to comply FDA’s Part 11: now and in future
• Which systems need to comply with Part 11
• How to control and record access to computer systems and data
• How to sign records electronically
• How to define and maintain raw data
• How to archive data: paper vs. electronic data
• FDA’s biggest concern: integrity of electronic data – the problem and solutions

Vendor Contributions for Computer Validation and Part 11 Compliance

• Helping to select the right system and specifications
• Validation during development
• Software functionality: limited access, electronic audit trail, electronic signatures
• Solutions for long term archiving and retrieval
• Assistance for on-site validation
• Practical demonstration of compliance functionality (DQ, IQ, OQ, PQ)

Collaborative Exercises, Discussions and Examples

Practical examples, case studies and collaborative exercises where dispersed between the presentations. At least 50% of the time have been will be dedicated to practical sessions and discussions with life examples. Some of the outcome has been made available for all attendees on the special seminar reference website. The entire class has been divided into 7 groups. Each group worked on different projects, for example, on different equipment and computerized systems. each group presented the results to the class. Practical sessions include:

1. Which documentation should be developed when
2. Qualification of an HPLC and 6 other systems
   going through all steps of qualification
   (UV Dissolution, GC, IR, HPLC, GC and LC/MS, Stability Chamber, Vacuum Oven, Karl-Fischer Titrator)
3.  What to re-qualify after maintenance and upgrades
4. Validation of a chromatography data system  an d 6 other systems
   going through all steps of validation from panning to reporting
   (HPLC computerized Systems, GC computerized Systems, LIMS, Excel spreadsheet applications, E-record archiving systems, document management systems)
5. Risk assessment and risk based validation steps
6. Solutions to ensure and document record authenticity, accuracy and integrity
7. FDA compliant archiving of analytical raw data and other documents
8. Examples and analysis of FDA deviation reports and how to respond.

10+ Reference documents for easy Implementation

Reference documents will be made available on a special workshop reference website. The site is password protected and is available until end of September 2009. .
They include

• Risk Assessment Master Plan
• SOPs for equipment qualification, maintenance and change control
• SOP: Qualification tasks and documentation for instrument categories
• Qualification examples for an HPLC system (from planning to reporting)
  Table with qualification conditions, frequency of requalification and acceptance limits for 20 laboratory instruments
• SOP: Validation of laboratory computer systems
• SOP for Part 11 implementation
• Checklists for Part 11 and computer validation
• SOP: Retention and archiving of electronic records
• Validation examples for a chromatographic data system (from planning to reporting)
• Warning letters and/or Inspectional observations related to Analytical Laboratories

The seminar has been attended by 100 professionals

Middle and upper management including:

• Directors
• QA managers
• Regulatory affairs
• Lab managers

From

• Pharmaceutical industry
• API manufacturers
• Chinese regulatory agency - SFDA
• US FDA

About the speaker: Dr. Ludwig Huber

• Director and Chief Editor of the global on-line resource for validation and compliance: LabCompliance. Before retiring as a senior advisor for global regulatory compliance in 2008, he worked for Agilent Technologies as compliance program manager for more than 20 years. He is a team and review member of PDA's task forces for "21 CFR Part 11". He is author of the books “Validation and Qualification in Analytical Laboratories”, and "Validation of Computerized Analytical and Networked Systems". He has published more than 100 papers on validation and compliance and 21 CFR Part 11. He has given multiple presentations mainly on GLP/GMP, 21 CFR Part 11 and Validation around the world, including 2006 FDA cGMP China Training Program. He received his PhD in Chemical Engineering from University of Karlsruhe of Germany
• For more information on Ludwig Huber, click here.

Selected photos from previous events

	The seminar room room was fully packed with about 100 professionals. Attendees were directors, lab and QA  managers from industry and officials from SFDA.and US FDA.
	Ludwig Huber started with basics of equipment qualification. He then explained the approach of USP <1058> for analytical instrument qualification.
	The slides have been displayed on two screens: in English and in Chinese. All presentations have been simlutaneously translated into Chinese.
	The course was sponsored by Agilent Technologies. Agilent offers a wide rage of instrument hardware, software, consumables and services that help the industry with compliance and to increase productivity
	Attendees could practice what they had learned in workshop type exercises. This was group one working on HPLC system qualification.
	Group 3 worked on qualification of IR spectrometer.
	The audience presented results of workshop tasks. Here reports Ms. Lei Weili about the outcome of the Stability Chamber qualification workshop. the outcome has been discussed with the entire audience.
	For better illustration some groups used tables to draw the outcome of the discussions on  tables.
	Mr. Wy Dongdong not only translated a large portion of the slides from English into Chinese but also cared about the dual technique screen presentations. .
	Ms. Ting Chen, program coordinator,  (right) and Ms. Binyun Zhang did an excellent job in getting every thing organized. Ms Zhang did also take most of  these nice photos.
	Zhi-Xu Zhang of Agilent presented case studies on how Agilent's Services and product functionality help with compliance and improve efficiency in laboratories.
	The audience got quite interested in the Agilent compliance products. Zhi-Xu got many questions after his presentation.
	Group I working on qualification of HPLC systems, group II on GC systems.
	Mr. Luo Shizhong, Vice Director, Shandong Xinhua Pharmaceutical Company Limited, was one of the three assistant who helped Ludwig Huber to organize the workshops
	Ms. Ruoyu Thang (middle) made sure that the microphone was readily available to all discussion contributors.
	Every student got a headphone to listen to the simultaneous presentation.
	The seminar was attended by Dr. Brenda Uratani, Assistant Country Director FDA China Offices and by Prof. Wang Yamin, Center for Drug Evaluation, SFDA. Here at lunch with Dr. Ludwig Huber
	The whole session was video-taped such that other students can view part of the seminar .
	Attendees extensively used the breaks for individual discussions with Ludwig Huber.
	Prof. Gu picking up Ludwig Huber for an evening concert in the new Beijng opera hall. All was organized by Ms. Chen.
	On behalf of the attendees Mr. Shuquiang  Liu of Sigma Centrifuges (right)  thanked the program director Dr. Quiang Zheng from PKU (middle) for setting up this program  and Dr. Ludwig Huber for conducting the seminar.
	Ludwig Huber thanked the PKU and Dr. Zeng for invitation, all the PKU staff for the organization and the audience for many discussions.
	The audience seemed to be happy with the seminar and what they have learned.

More and larger photos going through the workshop from beginning to the end