Varian, Inc. Analytical Instrument Qualificationgazanaliz.ru/manuals/Varian/service/pif/7_aiq/2289_draft.pdf3.1 Development of Varian, Inc. Instruments 23 3.2 Development of the Varian,

Varian, Inc. Analytical Instrument Qualification

Overview

8510228900 Issue 3 February 2008

Varian, Inc. Analytical Instrument Qualification Overview

Page 2 of 36 Publication no. 8510228900, Issue 3, February 2008

Varian, Inc. – Serving Industries Worldwide

Biosciences

Pharmaceuticals

Clinical Research and Forensics

Food and Agriculture

Chemical Analysis

Environmental

Fuels and Energy

Material Sciences

Sales and Service Contact Details

North America: 800.926.3000, 925.939.2400

Europe, The Netherlands: 31.118.67.1000

Asia Pacific, Australia: 613.9560.7133

Latin America, Brazil: 55.11.3238.0400

Varian, Inc. Web Site

www.varianinc.com

Varian, Inc. is the owner of copyright on this document and any associated software. Under law, the written permission of Varian Inc must be obtained before either the documentation or the software is copied, reproduced, translated or converted to electronic or other machine-readable form, in whole, or in part.

First published December 2005. Updated in February 2008.

Factor Four, Inspiring Excellence, Varian and the Varian logo are trademarks or registered trademarks of Varian, Inc. in the US and other countries.

© 2005-2008 Varian, Inc.


Publication no. 8510228900, Issue 3, February 2008 Page 3 of 36

Contents

Varian, Inc. Industry Awards........................................................ 5

Preface - Varian, Inc. ..................................................................... 7

Introduction to Varian, Inc. 7

History of Varian, Inc. 8

Real World Applications 9

Financial Status 10

Document Overview ................................................................... 11

1. Quality Systems at Varian, Inc. ......................................... 13

1.1 Quality Management System 13

1.2 Auditing Procedures 14

1.3 Employee Qualifications and Training 14

2. Regulatory Compliance and Analytical Instrument Qualification ................................................................................ 15

2.1 Good Laboratory Practice 15

2.2 Current Good Manufacturing Practice 16

2.3 Analytical Instrument Qualification 16

2.4 When is AIQ Required? 17

2.5 FDA 21 CFR Part 11 Electronic Signatures and Records 18

2.6 Design Qualification 19

2.7 Installation Qualification 20

2.8 Operational Qualification 21

2.9 Performance Qualification 21

2.10 Preventative Maintenance and Re-qualification 22

3. Analytical Instrument Qualification at Varian, Inc............ 23

3.1 Development of Varian, Inc. Instruments 23

3.2 Development of the Varian, Inc. Software 25



3.3 Pre-installation 27

3.4 IQ Documentation Provided by Varian, Inc. 27

3.5 OQ Documentation Provided by Varian, Inc. 28

3.6 Re-qualification 29

3.7 AIQ Package Provided by Varian, Inc. 30

3.8 Summary of Purchase and Qualification Procedures with Varian, Inc. 31

3.9 Regulatory Compliance 32

4. Customer Support ............................................................... 33

4.1 Global Sales and Support 33

4.2 Varian Customer Training Courses 34

4.3 Support Agreements 34

4.4 Consumables and Spare Parts 35

4.5 Instrument Installation Procedure 35



Varian, Inc. Industry Awards

Varian, Inc. Awards:

2004 Varian, Inc. is named Analytical Instrumentation Company of the Year by Frost and Sullivan – Excellence in Industrial Technology Awards

2002 Business Week rank Varian, Inc. among the Nation’s top growth companies

2002 Scientific Computing and Instrumentation Magazine voted Varian UV spectrophotometers the best in quality, reliability and value

2001 AusIndustry – Certificate of Achievement ICP Project (Development of next generation ICP spectrometers)

1999-2000 Applied Biosystems recognizes Varian Vacuum Technologies with the Outstanding Supplier Award

1999 Australian Institute of Engineers - Engineering Excellence Award for Vista ICP Instrument

1998–1999 Vankel Technology Group Recognition Award – Partnerships – Cooperation and support in the advancement of Dissolution Automation “Total Solution”

1998 Industrial Research 100 Award – Cary 50 UV-Vis Spectrophotometer

1998 Silver Award – Strategic Industrial Research International (Instrument Business Outlook) – Excellence in Industrial Design – Cary 50 Spectrophotometer

1997 Industrial Research 100 Award - SuperProton Probe

1997 Australian Institute of Engineers - Engineering Excellence Award for the Cary 50 and SpectrAA 220FS

1997 Vacuum Products – Massachusetts Quality Award

1997 Industry Week Magazine – names the Lexington MA site as one of America’s best plants

1994 Industry Week magazine names NMR among the Top 10 List in its America’s Best Plants competition



1994 Australian Institute of Engineers – Highly Commended - Engineering Excellence Award for UltraMass ICP Mass Spectrometer

1991 Stockholm, Sweden – Richard Ernst Awarded the Nobel Prize in Chemistry (Varian, Inc. employee from 1963–1968) He and Wes Anderson developed Fourier Transform NMR – the Discovery that made Magnetic Resonance Imaging practical

1987 Industrial Research 100 Award - VXR wide line solids accessory

1986 Varian Australia wins Australian Export Award

1984 Industrial Research 100 Award - NMR spectrometer XL series data system

1983 Australian Institute of Engineers (Victorian Branch) - Engineering Excellence Award for the GTA-95


1977 Industrial Research 100 Award for SuperScan 3 UV-Vis Spectrophotometer

1975 Industrial Research 100 Award - Model EM-390 NMR spectrometer

1973 Industrial Research -100 Award for the PortaTestTM Leak Detector


1971 Industrial Research 100 Award - Model EM-300 NMR spectrometer

1971 Industrial Research 100 Award for Model 61 Carbon Rod Atomizer

1970 Industrial Research 100 Award - XL-100 NMR spectrometer

1967 Industrial Research 100 Award for AR-200 Atomic Absorption Spectrophotometer

1966 Industrial Research 100 Award for AA-4 Atomic Absorption Spectrophotometer

1964 Industrial Research 100 Award - NMR system model HRSC-1

1963 Industrial Research 100 Award - Industrial Research superconducting Magnet to achieve 65,000 Gauss



Preface - Varian, Inc.

Introduction to Varian, Inc.

Inspiring Excellence™ is at the Heart of Our Business.

Varian, Inc. is a diversified, global technology leader helping customers innovate with confidence, enhance their competitiveness, and boost their efficiency.

The headquarters of Varian, Inc. are in Palo Alto, California. Varian, Inc. manufactures in twelve locations throughout North America, Europe and the Pacific Rim and has sales and service offices worldwide. It is a major supplier of analytical instrument solutions, NMR systems, vacuum products, and associated services.

Our businesses — Scientific Instruments and Vacuum Technologies — bring together high quality, innovative and user-friendly products with industry-leading service and support to create genuinely inspired solutions. Each person at Varian, Inc. is dedicated to our credo — Inspiring Excellence™. This calls on us to always act with integrity and with absolute commitment to our customer’s needs and dreams. At Varian, Inc. we are inspired by our customers and strive to inspire others in all we do.

Our people, products and solutions enable customers to meet increasingly complex challenges in life sciences and industry.

Varian, Inc. provides leading edge tools and solutions for diverse, high growth applications in life science and industry.



History of Varian, Inc. The roots of Varian date back to 1948 when two brothers, Russell and Sigurd Varian, put their heads together to start their own company. Russ was a Stanford University graduate and inventor, and Sig was a Pan American Airlines pilot. Their innovation and enterprise built one of the primary companies in Silicon Valley, Varian Associates. Russ’ invention, the klystron tube, which helped make airborne radar possible before World War II, was the company's first product. For the next fifty years Varian Associates grew, renowned for its innovation. By 1999, the three primary business segments had grown enough to become independent organizations. Varian Associates split into three separate companies: Varian Semiconductor, Varian Medical Systems, and Varian, Inc., all retaining a name with a great legacy.

Today, backed by our global team of product and applications experts, Varian is ideally suited to meet the mounting analytical challenges in these and other scientific communities:

• Biosciences

• Pharmaceuticals

• Clinical Research and Forensics

• Food and Agriculture

• Chemical Analysis

• Environmental Analysis

• Fuels and Energy

• Material Sciences



Real World Applications The following examples provide an overview of the diversity of Varian instruments and technologies when applied to daily life.

• Varian Australia Pty Ltd has met our customer’s needs by providing the world’s first fully-functional LC/MS equipped mobile pre-race testing laboratory. This enables the track-side drug testing of racing animals at horse racing events.

• ICP-MS technology is used to test the purity of our drinking water. This includes testing for trace elements as recorded on the labels of bottled water.

• Pharmaceutical companies worldwide rely upon Varian equipment to continuously monitor and critical quality control processes. In particular, for tablet testing and dissolution testing.

• The FactorFourTM GC capillary column product lines are used to test for trace analysis of volatile and semi-volatile compounds for selected US Environmental Protection Agency (EPA) and US Pharmacopoeia (USP) methods.

• Environmental laboratories world-wide use both Varian LC/MS and GC/MS to test for pesticides and toxins in agricultural products, keeping the food supply safe.

• Varian’s NMR systems are used world-wide in imaging applications for oncology, cardiology, angiography and drug effect studies.

• Varian HPLC columns are used in a broad range of industries including pharmaceutical, environmental and food testing. Applications include, quality control of pharmaceutical products using USP methods; analysis of clinical samples for diagnostic and metabolism studies, analysis of soil and water according to EPA methods and the quality control of food.

• Varian Micro GC technology has become one of the most important techniques to monitor energy -the calorific value- of Natural Gas. Energy metering is used for billing of natural gas consumption of households and industry and the optimization of turbines in gas-electric power plants.



Financial Status For the fiscal year ending September 2006, Varian, Inc. had sales of $921 million. Overall, company expenditure on R&D was $65 million, accounting for 7% of revenue.

Varian, Inc. fiscal 2007 revenue grew by 10.7% over fiscal year 2006. A strong mix of new products, from both internal development and complementary acquisitions, as well as our global presence, helped fuel this growth. The Company is in an advantageous position and is headed into fiscal 2008 with an increased backlog for both the Scientific Instrument and Vacuum Technologies segments.

Varian, Inc. is listed on NASDAQ as VARI Common Stock.

Additional financial information about Varian is available on the Varian, Inc. Web site: www.varianinc.com



Document Overview

This document provides an outline of the commitment to Quality at Varian, Inc., through its Quality Management System (QMS). It:

• Provides an overview of the Quality Management Systems at Varian, Inc.

• Introduces the concept of Analytical Instrument Qualification and relates it to regulatory compliance and quality assurance.

• Breaks down the qualification process into defined activities and clarifies the vendors’ and customers’ roles, expectations, and responsibilities for each.

• Explains Varian, Inc.’s approach to the Qualification process.

• Clarifies the scope of the Analytical Instrument Qualification Packages provided by Varian, Inc.

• Provides an overview of Services and Customer support provided by Varian, Inc.

• Provides clear, concise responses to a series of Frequently Asked Questions, as well as references to relevant publications from Varian, Inc.



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1. Quality Systems at Varian, Inc.

This chapter provides an overview of the structure of the quality systems at Varian, Inc.

1.1 Quality Management System At Varian, Inc., we are guided by several principles that define what we do and how we do it.

Each of the Varian, Inc. manufacturing sites are ISO9001:2000 certified. Visit the following www.varianinc.com website to view the certificates:

http://www.varianinc.com/products/iso/index.htm

Our Quality Policy states:

‘Varian, Inc. and its people are committed to meeting or exceeding customer requirements for high-quality, competitive products, services and solutions to their most pressing technical and process challenges.

We will achieve this by focusing on continuous improvement in everything we do, listening to our customers, and responding to them with dedication and innovation.’

The Quality Management System (QMS) is supported by department procedures including Policies, Processes, Standard Operating Procedures (SOPs), Protocols, Forms, and Checklists that cover all aspects of the business. The degree and level of documented process is compatible with the type of work, methods used, and skill of the personnel.



Policies, processes, and their supporting documentation are in place to preclude the use of obsolete or non-applicable documents. Retained obsolete documents are suitably annotated. Appropriate processes are implemented to standardize the formatting issue, approval, distribution, control and subsequent maintenance of the QMS documentation.

1.2 Auditing Procedures Varian, Inc. ensures the effective implementation of the documented procedures through regular internal and external audits.

As a matter of policy, Varian, Inc. conducts planned and documented internal quality audits to verify compliance with authorized procedures and to assess the effectiveness of the quality system. To ensure that corrective or preventative action is effective, trending analysis and follow-up audits are conducted. Auditing procedures ensure that quality records are maintained as evidence that the required controls have been satisfactorily applied. External audits include certification audits, audits of our suppliers, and auditing of us by customers.

Varian, Inc. also undergoes bi-annual compliance audits and triennial system re-certification audits conducted by an external standards body, to ensure that it continues to meet the requirements of the ISO9001:2000 standard.

1.3 Employee Qualifications and Training Varian, Inc. ensures that all staff members are suitably qualified to perform their role on the basis of education, job training, and experience. Varian identifies and provides additional training where necessary, ensuring that all personnel perform their jobs to a standard of excellence.

Varian, Inc. representatives undergo an extensive training program that includes formal theoretical and practical laboratory training. They must pass an examination at the completion of training before they can be accredited to work on a specific instrument, model, or technique. These formal training programs include manuals and training aids that are prepared in accordance with Quality Procedures at Varian, Inc. Throughout their careers, Varian, Inc. representatives receive ongoing training in order to stay technically proficient with new instruments, new technologies, and software changes.



2. Regulatory Compliance and Analytical Instrument Qualification

This chapter provides a basic overview of regulatory compliance and Analytical Instrument Qualification.

2.1 Good Laboratory Practice Good Laboratory Practice (GLP) can be defined as a system of processes and conditions under which laboratory tests and/or experiments are planned, performed, monitored, recorded, and reported. GLP aims to ensure a defined level of quality, accuracy, reproducibility, and validity within laboratories. GLP relates to the organization, processes, and conditions, under which studies are planned, performed, monitored, recorded, and reported. Compliance with GLP also ensures that an auditor can easily audit a laboratory’s records. An auditor should be able to determine why, how and by whom the work was done, who authorized the results, what equipment was used, the calibration of equipment, and the results obtained. An auditor also needs to be able to see Out Of Specification (OOS) results or atypical results and the Corrective Action and Preventative Action process (CAPA) associated with these results.

GLP is more generally applicable to drug development and manufacture in the pharmaceutical industry. The US code for GLP is described under the FDA in 21 CFR Part 58.



2.2 Current Good Manufacturing Practice Current Good Manufacturing Practice (cGMP) is a standard of Quality Assurance (QA) and Quality Control (QC) associated with the manufacturing process. It ensures that products are consistently produced to a set standard appropriate to their intended use. The FDA code of cGMP for pharmaceutical applications is described in 21 CFR Parts 210 and 211.

The most significant difference between GLP and cGMP is archiving requirements for test samples and data. The cGMP relates to the part of Quality Assurance that assures that products are consistently produced and controlled to the standards appropriate for their intended use.

The FDA regulations for GLP and cGMP are internationally recognized as the benchmark standard for pharmaceutical manufacturing.

2.3 Analytical Instrument Qualification Analytical Instrument Qualification (AIQ) activities can be viewed as an integral part of a QA program. AIQ is one of the most important components and requirements of GLP and cGMP regulation. AIQ is a continuous evaluation of processes, products or methods ensuring compliance with product or method requirements.

Analytical Instrument Qualification includes:

• The assessment of equipment hardware, software, and systems.

• The assessment of methods and data acquisition.

• The checking of functions related to data integrity, security, and traceability.

Analytical Instrument Qualification covers the entire lifecycle of a system, from the initial definition, design requirements, and specifications to the cessation of its operation. AIQ includes on-going change control procedures and archiving and retrieval of data.

The system is qualified at the following times:

• As it is developed and tested.

• As it is installed and commissioned.

• Whenever significant changes are made.



• Periodically, under routine operation.

Analytical Instrument Qualification requires testing of:

• The individual instrument and each component of the system.

• The computer when connected to the system.

• The entire system working together.

AIQ is typically made up of Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), Performance Qualification (PQ), Re-qualification and Preventative Maintenance (PM).

Qualification is an efficient, scientific-based approach to providing documented evidence that an instrument or procedure consistently operates or runs within established limits and tolerances. Qualification includes the proper maintenance (including PM) and calibration of the instrument.

2.4 When is AIQ Required? Analytical Instrument Qualification is commonly required by government regulation of the pharmaceutical industry and by quality assurance schemes within the industry itself.

Regulatory compliance is complicated by a number of factors:

• Legislative requirements between different countries.

• Each particular aspect of design, manufacture or operation of an instrument may be regulated under a number of jurisdictions, including drug authorities, environmental authorities, and Health and Safety authorities.

• Within individual regulatory agencies, there may be variation in the way the legislative instruments are administered, depending on the personnel involved.

• Much of the regulation is outcome-based. Therefore, providing the objectives of the regulation are met, you can choose the appropriate means to get there (this is in contrast to prescriptive regulation, which details precisely how to do something on the assumption that if the directions are followed, then the desired outcome automatically results). As a result, it is possible that the outcome-based legislation can be interpreted in different ways.

Instrument hardware should be qualified prior to routine use, after repair and at pre-defined regular intervals, as should be detailed in SOPs. Computer systems should be qualified during and at the end



of the development process, during installation, prior to and during routine use, and after software updates. Computerized systems and data validation, with respect to consistency, security, integrity, and traceability, is one of the most critical steps within computerized systems. It includes authorized and traceable access to systems, applications, methods and data as well as the electronic audit trail and mechanisms to delete or change records (electronic change control management).

Analytical systems should be tested for system suitability prior to and during routine use.

The final AIQ Report with respect to the use of an instrument will include the DQ, IQ, and OQ Protocols.

Note: The qualification of analytical methods is outside the scope of this document. Each user’s method will be different, depending on the requirements of their application. This document provides some information on system features that the user will find helpful during their method validation.

2.5 FDA 21 CFR Part 11 Electronic Signatures and Records The FDA has developed a guidance document for a standard of electronic signatures and records called 21 CFR Part 11.

‘An electronic record is any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved or distributed by a computer system.’

‘An electronic signature is a computer data compilation of any symbol or series of symbols, executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual’s handwritten signature.’

FDA 2005: www.fda.gov

With a general move within the analytical instrumentation industry towards electronic signatures and records, compliance with 21 CFR Part 11 is becoming increasingly important across the analytical scientific industry, in particular in the pharmaceutical industry.

Varian, Inc. is committed to assisting customers in complying with the FDA, 21 CFR Part 11 rule. In order to achieve this, Varian, Inc. has developed specific software which can assist instrument operators in setting up their testing under 21 CFR Part 11 conditions.



For details on how we assist users to achieve 21 CFR Part 11 compliance, refer to the following publications:

• 21 CFR Part 11 Electronic Records, Electronic Signatures Compliance with Varian, Inc. Spectroscopy Instruments, publication number 8510191800.

• 21 CFR Part 11 Electronic Records, Electronic Signatures Compliance with Varian, Inc. Spectroscopy Instruments, For ICP Expert II and UV Dissolution software, publication number 8510226300

• Regulatory Compliance in Galaxie™ Chromatography Data System Software

2.6 Design Qualification Analytical Instrument Qualification starts with Design Qualification. This involves:

• Description of the analysis problem.

• Selection of the analysis technique.

• Establishing that the instrument is the correct choice for the intended purpose, application, and business requirement.

• That ‘fitness for purpose’ is built into the procurement process.

• Planning and documenting the specifications for the user’s requirements.

• Detailing the required instrument functions and intended use.

• Specifying the required final performance from the instrument.

• Selection of the supplier.

• Preliminary selection of functional and performance or operational specifications (technical, environmental, safety).

• Refining testing parameters for new techniques.

• Developing the instrument Hardware/Operation Manual, Pre-installation Manual, Service Manual, etc. for the final instrument.

Design Qualification defines the functional and operational specifications of the instrument and details the conscious decisions in the selection of the supplier. It includes the development and documentation of the final functional and operational specification.



The purchaser should prepare a list of instrument requirements and parameters, both operational and functional. The vendor is chosen and the system purchased according to these requirements.

The vendor provides the operational and functional specifications and information of the available system. This ensures that the system meets the user’s own specifications and requirements.

Upon request, the vendor will supply details of:

1. The use of rigorous design and specification methods during system development.

2. Fully documented quality control and quality assurance procedures.

3. The use of suitably qualified and experienced personnel.

4. Comprehensive planned testing of the system.

5. The application of stringent change control, error reporting, and corrective procedures.

2.7 Installation Qualification The IQ Protocol is documented verification that all hardware and software components have been correctly installed and adhere to the system specification and to the appropriate local statutory requirements, for example, equipment, software, wiring and gas supply.

Installation Qualification verifies and documents that the instrument has arrived as specified in the purchase order documentation, that it has been properly installed in the selected environment, and that the environment is suitable for the operation and use of the instrument. The IQ Protocol is divided into pre-installation specifications and requirements for use during the installation process.

Pre-installation instructions from the instrument supplier specify the following:

• Environmental requirements for the instrument, including temperature control, humidity, dust-controlled environment.

• Water, gas, or electrical requirements.

• Ventilation around the instrument.

• Magnetic interference or Radio Interference (RI) from or to the instrument.

The IQ includes switching on the instrument and checking error message responses.



2.8 Operational Qualification The OQ Protocol is documented verification that the system functions and performs in the user’s laboratory in accordance with the operational specification, throughout all anticipated ranges in the selected environment, as defined by the DQ.

2.9 Performance Qualification The PQ Protocol is documented verification that the total instrument system has been demonstrated to consistently perform to a specification appropriate to its routine and intended use. The PQ focuses on the instrument’s reliability, accuracy, and reproducibility of data and test results.

On-going PQ includes PM and regular tests such as system suitability and quality control analyses with the creation of QC charts for tracking test results and trend analysis of the data. For computer systems, it also includes regular data backup, virus checks, and change control procedures.

The user generally defines a series of tests that are necessary to demonstrate that the system is functioning properly, both for the initial OQ and for ongoing PQ. These tests will be clearly documented and include:

1. Rationale for tests selected and not selected for the PQ.

2. Tests specific to individual components.

3. Tests specific to the entire system.

4. Frequency, both routine and as triggered by event/change.

5. Expected results, Acceptance criteria - Pass/Fail status.

6. How the tests are documented.

7. Required qualifications of the operator.

8. Action to be taken in the event of failure of a test.

Verification is required within the intended operating ranges within the laboratory environment.

Varian, Inc. may assist with PQ through the OQ Analytical Qualification Protocols and suggested PM and routine maintenance measures.



2.10 Preventative Maintenance and Re-qualification Preventative maintenance, as a standard routine procedure, can assist in the reduction of incident failure or breakdown. The aim of PM is to detect potential instrument problems before a breakdown occurs including the replacement of consumables and spare parts at an appropriate, early stage. Routine PM testing can assist in the reduction of Out Of Specification and Atypical test results, due to the instrument. Undertaking trend analysis over time will help to identify any minor issues before they become major issues.

Re-qualification is necessary after spare part replacement, instrument repair or moving the instrument. Depending on the change made to the instrument, a complete OQ may not be necessary. It may only be necessary to perform components of an OQ Protocol procedure.

Usually the manufacturer will provide information with respect to the extent of OQ necessary during repair procedures.

On moving an instrument, a partial OQ is sufficient with respect to verification of the performance and function of the instrument components that may have been affected during the move.

Re-qualification is the repetition of specific qualification processes, as triggered by events such as:

• Replacement of parts.

• Movement or relocation of equipment.

• Addition of new equipment.

• Modification, for example, instrument upgrades or enhancements.

• Updated software.

• A change of use.

• A new procedure.



3. Analytical Instrument Qualification at Varian, Inc.

This chapter provides an overview of Analytical Instrument Qualification procedures at Varian, Inc.

3.1 Development of Varian, Inc. Instruments Analytical Instrument Qualification requires a history of the instrument and the processes involved in its design and development, including firmware.

The product development of all Varian, Inc. instruments and accessories is controlled by the Quality procedures in place under ISO 9001:2000 certified Quality Management System. Product Development follows a five phased process:

1) Product proposal To become part of the company’s product development strategy, an idea for a new or enhanced product must be formally proposed in writing, and the documents must be reviewed and approved by senior management.

2) Feasibility, product specification and planning The approved product concept or idea then needs verification to ensure that technical risk is minimized. This is done prior to the design and development phase. In conjunction with this, factors relating to market timing, costs, project planning, and customers’ needs are explored in greater detail. Out of this verification, Marketing generates a Product Requirements Specification in conjunction with R&D. A Product Design Concept, which defines the product system concept and details at a high level the major modules (mechanical, electronic, optical, firmware) and their interactions, is also prepared by R&D. Typically, a Program Manager/Project Leader is appointed at this stage.



3) Detailed design, development and evaluation Detailed product design and design verification is conducted to meet the Product Requirements Specification. This involves prototyping and performance testing to verify that the design meets product performance, safety, and statutory requirements specifications. Design engineers are required to keep fully logged details of relevant design drafts and calculations, tests, and experiments. Throughout the product development process, Program and Project Managers convene regular and frequent project status meetings. Attendees include the engineers and marketing representatives whose work is being reviewed, the relevant engineering manager, and other staff as selected by the project manager. During these meetings, design validation and project progress is reviewed to ensure that the final instrument meets the regulatory, quality, performance, safety, reliability, and durability requirements.

4) Product introduction A small number of units (typically five) are built to specification to confirm that the design can be produced from the formal design documentation package. It also allows the development and verification of production fixtures, production routings, assembly instructions and work centre layouts. Design Validation is carried out using pilot units to test for conformance to requirements.

Pre-production Run (PPR) or Pilot Run is undertaken in conjunction with the R&D department to confirm that the instrument can be made in a reproducible manner and that the designed quality and testing procedures are adequate to eliminate any future manufacturing or operational issues. PPR includes the assembly and test procedures (including SOPs and WIs), equipment and/or routings, factory floor layout, training of shop floor personnel, and provides a final validation that the product meets specifications and is ready for release to the market. Once the PPR has been completed and any problems raised have been addressed, responsibility for maintenance of the product and Quality Control transfers to Manufacturing.

5) Routine production and manufacturing During the early stages of production, any problems encountered with instrument assembly or testing are addressed through a variety of meetings. These meetings consist of a team of suitably qualified personnel, whose task it is to isolate and overcome any problem(s) found.



Once any issues associated with the release of the product have been rectified, any concerns raised by customers and/or technical and service staff are addressed by a Corrective Action Team (CAT). The CAT is made up of various specialists from every aspect of product release. They meet regularly to deal with any production or hardware problems, and ensure that all Varian hardware is subject to continuous improvement. Issues addressed at the CAT meetings are recorded along with a brief description of the problem, actions to be taken, and responsibility for the actions. Problems are ‘closed out’ once appropriate corrective and preventative action has been effectively put in place.

Varian, Inc. can provide you (for vendor selection purposes) or the authorities (for regulatory compliance purposes), with access to detailed information and records relating to an instrument or system. Information relating to the development of instrument hardware is housed at Varian, Inc. and is available for review by customers upon request — subject to their signing the appropriate non-disclosure agreements. This information includes project requirements, time lines, status reports, tests and test results undertaken during development, instrument schematics, and reports.

3.2 Development of the Varian, Inc. Software Standard application software (as supplied by Varian, Inc.) is validated by Varian, Inc. during its development. It is the user’s responsibility to validate user-developed software. In instances where the software allows the user to export the analytical results to another format, for example ICP Expert II converted to an ASCII file, any further process of this data is entirely specific to, and validated by, the user and falls outside the scope of this package.

The software development life-cycle process is detailed in the Software Product Development procedure in the ISO 9001:2000 certified Quality System. The cycle is an auditable process that ensures each project stage can be revisited at any time during the project for further refinement.



Development of the Varian, Inc. software is concentrated into four stages, as follows:

1. Requirements

2. Analysis and Design

3. Implementation

4. Evaluation and Release

When all of the deliverables for each stage are complete, a formal review and approval process is conducted. This process allows a set of project checkpoints to control the development process and ensures that the relevant managers are assessing compliance and Quality procedures throughout the development cycle. Checkpoints ensure that the requirements of a stage have been met, reviewed, and approved before the next stage is commenced.

1) Requirements A definition of the user requirements for the Varian, Inc. software is established. This involves a series of meetings between the Marketing and Research and Development departments. The meetings address design and development planning, and produce an agreed set of Product Requirements. In order to tailor the Varian, Inc. software to the needs of customers, extensive user input is also incorporated into the system design and development.

2) Analysis and Design The Software Requirements Specification document is analyzed to determine the possible problems and constraints of the software system. This analysis forms the basis of the analysis model, which is used to define the scope of the software system.

System design, which commences once analysis design is complete, provides the structure of the Varian, Inc. software for use on Varian instruments. Documentation outlining the overall framework of the software, including its interfaces, is also developed.

3) Implementation The source code for the Varian software is developed, modified, and maintained in accordance with work instructions outlined in the Varian, Inc. Quality System. These instructions ensure that reliable and consistent software is produced.

For security purposes, the source code files are kept on a central file server during software development. Only project staff involved



in developing the software have access to these files. The code is regularly backed up onto safe storage and kept onsite in a fireproof safe and at an offsite location.

4) Evaluation and Release

Evaluation includes testing of requirements outlined in the specifications for both hardware and software. The software is thoroughly tested and evaluated to detect and eliminate any potential ‘bugs’ in the system in accordance with work instructions outlined in the Varian, Inc. Quality System. Once this process is complete, the software is released.

3.3 Pre-installation Varian, Inc. provides a Pre-installation Manual to all customers when an order is verified. This manual includes all the information required for the customer to prepare their site for the arrival and installation of the instrument or system.

It is the customer’s responsibility to ensure that the computer system to be used is appropriate for the requirements of the instrument system purchased; when requested, Varian, Inc. can provide the personal computer. Validation of systems and software from Varian, Inc. assumes that the computer hardware and its operating system are correctly functioning.

Further information can also be provided by your local Varian, Inc. representative.

3.4 IQ Documentation Provided by Varian, Inc. Varian provides an IQ Protocol that details all necessary test procedures required to qualify the assembled equipment. The IQ Protocol ensures the equipment is installed as specified in the selected environment and that the environment is suitable for the operation of the equipment. The IQ Protocols are specific to each type of instrument installation and are designed to help customers meet their GLP and cGMP requirements.

Each IQ Protocol contains a section specifically dedicated to 21 CFR Part 11 (where applicable). This section exists only for products that include 21 CFR Part 11 software. The 21 CFR Part 11 section is designed to assist the customer with setting up the instrument to assist with compliance to the 21 CFR Part 11 requirements.



The Varian Installation Qualification Protocol package includes:

• Tests to be performed, addressing process critical components, site requirements, and media connections.

• Sequence of test execution.

• Acceptance criteria.

• Change control procedures for documentation.

• A Variation List for results that vary from the expected criteria, with appropriate identification and resolution sections.

• A standard method for recording raw data from the execution of the Protocols, specific to each test. This includes acceptance criteria, comment fields, and signature blocks.

• Completion of the IQ Protocol so that the OQ testing can commence.

Completion of an IQ Protocol is the responsibility of the user. However, for the majority of Varian instruments, Varian, Inc. provides IQ Protocol documentation. For the majority of Varian systems, the Varian Service Representative will install the instrument and components, and assist the customer with the IQ Protocol. In most instances, the Varian Service Representative will perform the complete IQ Protocol with the customer watching and learning about the instrument and its operation.

3.5 OQ Documentation Provided by Varian, Inc. Varian, Inc. provides an OQ Protocol containing the critical steps for OQ Validation, ensuring on-going trouble-free operation of the system. Protocols check for proper functioning of the system. The OQ Protocols are specific to each type of instrument and are designed to help customers meet their GLP and cGMP requirements.

The Varian Operational Qualification Package includes:

1. Sequence of test execution.

2. Acceptance criteria for all tests.

3. A standard method for recording raw data from the execution of the Protocols, specific to each test. This includes acceptance criteria, comment fields, and signature blocks.



Completion of the OQ is the responsibility of the user. However, for the majority of their instruments, Varian, Inc. provides OQ Protocol documentation. For the majority of Varian systems, the Varian Representative will perform the complete OQ with the customer watching and learning about the instrument and its operation.

3.6 Re-qualification The process of re-qualification and the frequency of this procedure is the responsibility of the customer to perform and to document in their internal quality system. For the majority of Varian instruments, re-qualification information and lists can be provided. Contact a local Varian Representative for assistance with re-qualification. Where necessary, a Varian Representative can perform re-qualification procedures on request.

Contact the Original Equipment Manufacturers (OEM) of the accessories for assistance with re-qualification of those accessories.

The user’s company should have a quality assurance program following basic GLP and cGMP principals in place to prevent, detect, and correct problems. This should include:

• Change control program.

• Security plan.

• Backup and data recovery plan.

• Training program, including the assessment of training, training records, and a procedure for on-going refresher training.

• Periodic re-evaluation of the system as a whole, and components within the system.

• QMS and Documentation Control systems.

• Preventative maintenance, calibration procedures, and re-qualification plans.

• Procedures for how to handle defective equipment, OOS results, atypical results and equipment breakdown.

Refer to the instrument Operation Manuals/User Manuals provided by Varian, Inc. for advice on setting up your maintenance program.



3.7 AIQ Package Provided by Varian, Inc. Varian’s Analytical Instrument Qualification Package is made up of:

1. AIQ Overview — containing company information

2. Installation Qualification (IQ)

3. Operational Qualification (OQ)

Note: Varian does not provide IQ/OQ instructions for non-Varian manufactured items. Limited instructions may be supplied. If IQ/OQ of an accessory is required, contact the appropriate manufacturer.



3.8 Summary of Purchase and Qualification Procedures with Varian, Inc.

• Varian, Inc. launches new instrumentation.

• Upon request, Varian, Inc. provides details of the DQ and development of the instrument.

• An order is placed for the Varian, Inc. system.

• The customer receives the Pre-installation Manual containing a Pre-installation Checklist.

• The customer ensures the site meets the conditions outlined on the Pre-Installation Checklist.

• The customer may receive the Analytical Instrument Qualification package prior to or with the delivery of the instrument.

• The customer is briefed on the Analytical Instrument Qualification package. The IQ and OQ requirements at installation are confirmed.

• The customer prepares their plan for verifying and maintaining system performance (PM, PQ, and Re-qualification).

• The Varian system is delivered.

• The Varian Representative goes to the customer’s site, ensures that all pre-installation requirements have been met, and installs the instrument.

• As requested, IQ and OQ Protocols are completed.

• The customer completes their Quality plan for on-going instrument qualification, PM, PQ, and Re-qualification.

• The Analytical Instrument Qualification package is used as a reference throughout the life of the system.

• Varian, Inc. provides on-going support, service, extended warranties, training, and re-qualification as requested.



3.9 Regulatory Compliance Varian, Inc. is committed to assisting their customers in achieving compliance with regulatory bodies. Although Varian, Inc. is knowledgeable and experienced in the regulatory requirements of many countries, including the FDA and TGA, and pharmacopoeia method requirements as in the USP, BP, EP, JP and other regulations and methods, information provided in this document does not guarantee complete regulatory compliance. The information in this document and the tools provided by Varian, Inc. provide a foundation on which the user can build. They can also be used to assist in meeting particular regulatory requirements specific to the regulations at a specific location. Although the user is ultimately responsible for validation of the Varian instrument or system at their site, as the manufacturer, Varian, Inc. provides appropriate information, documentation (Protocols), and services to assist in this task.

For details on how we assist users to achieve 21 CFR Part 11 compliance, refer to the following publications:

• 21 CFR Part 11 Electronic Records, Electronic Signatures Compliance with Varian, Inc. Spectroscopy Instruments, publication number 8510191800.

• 21 CFR Part 11 Electronic Records, Electronic Signatures Compliance with Varian, Inc. Spectroscopy Instruments, For ICP Expert II and UV Dissolution software, publication number 8510226300.

• Regulatory Compliance in Galaxie™ Chromatography Data System Software



4. Customer Support

This chapter provides an overview of Customer Support Services provided by Varian, Inc.

4.1 Global Sales and Support The company’s global direct sales force remains one of the core competencies that have resulted in the success of our multi-product and multi-application business. Our global presence and our ability to provide customers with a wealth of technical expertise and applications know-how, contributes directly to our continuous worldwide growth. We will continue to invest in our global distribution and support capabilities to help further drive our growth and to consistently support our customers.

Varian, Inc. offers a variety of analytical instrument support agreements to accommodate a range of customer needs and budgets. In some countries, a technical support hotline is provided free of charge with all warranty and support agreements.

We believe that our Customer Service and Support are an integral part of our competitive strategy. As part of our services, our applications and technical staff provide individual assistance in supporting the specific application needs of customers, solving analysis problems. We offer training courses and routinely send our customers information on applications development.

The customer support organization of Varian, Inc. is one of the largest, most widespread support networks in the industry. The Field Support Group located at Varian, Inc. factories are available to assist the Varian representative resolve issues that arise.

Varian, Inc. provides customer service and support throughout the life cycle of the instrument. The customer support team will assist with all stages of instrument usage, from the initial instrument inquiry, the purchase of the instrument, the follow-up of the purchase and on-going support. Additional service warranties, support agreements, and training are available on request.



Various methods for obtaining information are available depending on your country, including the following:

• Varian, Inc. Web site is a primary source of information

• Newsletters

• Customer surveys

• Notification of software upgrades or hardware updates

• Regulatory compliance – notification of upgrades

• E-inspirations

• PlasmaNet

Support will vary depending upon the country and the type of service contract provided. Contact your local Varian office for information about the services that can be provided locally.

4.2 Varian Customer Training Courses Varian, Inc. offers a variety of training courses for varying levels of proficiency, ranging from basic instrument operations, maintenance and troubleshooting to advanced applications. Details of the dates and locations of such courses can be obtained from the Varian Web site, or by contacting local support offices. Alternatively, customers can arrange for a Varian instructor to visit their facility and conduct a user-specific training program.

See www.varianinc.com for further details.

4.3 Support Agreements Varian, Inc. has a global network of service offices, providing local language support. The type of services these offices provide will vary depending on the country. Information regarding specific details of support agreements and their costs is available from your local Varian representative.

Our products generally include a 90-day to one-year warranty, but in some countries, for some products, we offer longer warranties. Support agreements may be purchased by customers to cover equipment no longer under warranty. Service work not performed under warranty or support agreement is generally performed on a time-and-materials basis. We install and service our products primarily through our own field service organization, although certain distributors and sales representatives are able to, and are contracted to perform some field services.



4.4 Consumables and Spare Parts With ever-changing developments in technology, new instruments, software and systems are continuously being developed at Varian, Inc. in response to industry demands.

Varian, Inc. provides full spares support for all instrumentation, software and systems currently in production. Varian, Inc. provides full spares support for discontinued instruments and accessories, for a minimum period of five years from the date of production of the last instrument or accessory, or from the official date that the instrument, or accessory was replaced with a superseding model.

The supply of spare parts after the minimum five-year period is on an ‘as available’ basis. That is, the part will be supplied as a spare if the part is on the Varian Price List, or if the part is used in the production of a current product.

Varian is dedicated to adapting new software versions for superseded instrumentation where possible, particularly with respect to 21 CFR Part 11 compliance.

4.5 Instrument Installation Procedure Varian Quality Procedures define the requirements for the installation of a Varian product at a customer’s location. Customers will be provided with a Pre-installation Checklist, which must be reviewed and the site set up appropriately as per these requirements. Varian will then schedule and perform the instrument installation, and ensure that any installation problems are satisfactorily resolved.

Varian systems are designed to be installed with the assistance of a Varian representative. The following procedure applies only when a Varian representative carries out the installation. At installation, the Varian representative will perform tests to ensure that the system is performing to stated specifications. Customers will be given a copy of these test results. The Varian representative will also demonstrate the basic operation of the system to the customer.

See Chapter 3, Sections 3.3 to 3.6 for more information.



End of Document.

Documents

Varian, Inc. Analytical Instrument Qualificationgazanaliz.ru/manuals/Varian/service/pif/7_aiq/2289_draft.pdf3.1 Development of Varian, Inc. Instruments 23 3.2 Development of the Varian,