G x P S y s t e m s

T h e R e g u l a t o r y C o m p l i a n c e

E x p e r t s

With a proven track record on global

compliance projects, our people

help companies keep their

systems in a state of

validated compliance

without losing

operational flexibility

and productivity.

Our Advantages Work for You • Fixedscopeprojects,ontimeandwithinbudget

As we provide fixed scope/cost projects you will never have to worry about going over budget or missing your deadlines

• Continuousknowledgetransfer Your success is our success, so we make sure that your team has the knowledge they need to keep your systems in regulated compliance

• Effectiveculturechange Not only do we help you achieve regulatory compliance, we ensure your teams understand and appreciate the significance of their daily approach to quality

• ToplevelpersonalisedattentionOur management team have a wealth of experience in the life science industry so we can provide the highest level of attention and service to you

• ProjectfollowupWhen we have completed the project we are available to discuss and address any additional concerns you may have

• SupplyofmetricsWe supply valuable metrics to our partners for use in enhancing the performance of your processes and adding value to your business

GxP Systems provides world-class validation and compliance

services to multinational clients in regulated life science industries. Leading

businesses in the biotech, medical device and pharmaceutical industries

choose GxP Systems to achieve regulatory compliance.

We have earned a reputation for excellence and reliability by maintaining

a team of the top engineering and project management experts

in the life science industry. This expertise enables us to create

strategic solutions and deliver results in compliance and

competitiveness.

Established in 1997, GxP Systems has European

headquarters in Cork, Ireland and U.S. headquarters

in Boston, MA, with a number of regional

offices.

. 1

COMPLIANCEGlobal businesses in regulated industries, like yours, turn to GxP Systems to achieve compliance within an increasingly complex regulatory environment. With a proven track record on global compliance projects, our people help companies keep their systems in a state of validated compliance without losing operational flexibility and productivity. In fact, GxP Systems teams are regularly recognized by our customers as having delivered on time, within budget and with energy and commitment.

Our successes from continuing audits by worldwide regulatory bodies are a testament to the quality and relevance of our approach for compliance for every client. Our compliance services meet your specific needs due to our unique approach:

ComprehensiveRiskAssessment/Analysis• PFMEAs, Root cause analysis

• Risk index calculations

• Functional risk assessment

• Site-applicable risk assessment

HolisticProjectApproach• Based on global industry regulations such as FDA, EMA, IMB

• Full gap analysis

• Protocols, work instructions, and standard operating procedures development

• Effective knowledge transfer

• On-going managed services

ProvenProjectLifeCycleExpertise• Extensive library and repository of industry-related documents, processes and

guidelines

• Long history of experience in the life sciences sector

• Basis for continuous compliance throughout project phase(s) and beyond

• Expectation of successful future audits and compliance inspections

2 . c o m p l i a n c e

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Client: Withheld-Medical Device Company that received an extensive 483 Warning Letter from the FDA regarding their CAPA System.

Summary: Remediation for CAPA System as a result of an FDA 483 Warning Letter.

Issue: The FDA wrote in the 483 Warning letter that the clients Investigation SOP stated that the purpose was to fully investigate all events to determine the root cause and implement the appropriate corrective and preventive actions (CAPA). The SOP did not instruct the user on how to achieve this. Further, the investigations did not determine root causes, did not justify dismissing some possible root causes as improbable, and therefore did not implement CAPAs that were successful in preventing repeat occurrences.

Solution: Using Six Sigma tools, GxP Systems examined the Events and CAPA process, eliminated the non-value added steps, re-issued the procedures and trained personnel on the use of them. Further, we coached and mentored the users during the months after the process went live.

Result: Time to investigate events was reduced by one third, and re-occurrences of the events was reduced to less than 5%, evidence that the investigation process was determining correct root causes and appropriate CAPAs were implemented.

c o m p l i a n c e . 3

FDA 483 WARNING LET TER REMEDIATION PROjEC T CASE STUDY

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VALIDATIONGxP Systems has a successful track record of introducing a right-sized validation approach to our life science customers. Whether it is introducing a new product, transferring a line, or bringing an existing line into a state of validation, our expert validation teams will provide you with up-to-date policies and procedures.

You will benefit from our right-sized validation approach:

AccurateScopeDetermination• Inventory list preparation

• Inventory classification based on risk assessment

• Assessment of policies and procedures

• GAP assessment

CustomizedValidationActivities• Identification of key customer personnel

• Remedial development of policies and procedures

• Remedial design of validation templates

• Project plan

• Project execution

• On-going monitoring of project performance

• Knowledge transfer during and after entire project life cycle

• Project close out and handover

• Optional post-project services

LeanValidationusingASTM2500Many companies have ‘leaned out’ their validation programs. However, validation costs remain high and at times prohibit the advancement of some capital upgrades. Saving on ‘lean validation’ requires a new look and a different approach to this activity. GxP Systems is your source for revitalizing your validation process to the new globally competitive marketplace and ASTM 2500 is the accepted industry alternative to the traditional IQ/ OQ/PQ and lean validation model.

By adapting the ASTM 2500 model to validation, we are able to provide the following:-

• Substantial business savings on the cost of validation to our clients

• A more streamlined commissioning and qualification process

• More focus on the critical aspects of product quality, safety and efficacy

• A level of effort, formality and documentation that is relative to the level of risk involved

Whether it’s for the verification of new or existing systems, GxP Systems takes the following steps:

• Establish verification process for the site

• Risk-assess existing validation tests

• Apply verification to existing process

• Apply risk assessments to URS and FDS

• Develop Master Verification Plan

• Design reviews, FAT, SAT & commissioning

• Determine minimum required for testing and complete

This new approach allows our clients to enjoy savings on the costs of re-validation, annual product reviews, events, change control and other sustaining processes. We also use this approach for other forms of validation.

4 . v a l i d a t i o n

ValidationServicesOur extensive range of validation services will meet your unique needs:

EQUIPMENT VALIDATIONThrough our equipment validation services, we document the verification and qualification of all equipment as it is used in your manufacturing environment and ensure that the validation status of the equipment is maintained throughout the lifecycle of the validated system. Typically, our equipment validation projects incorporate the following deliverables:

• Validation policies and procedures

• Validation master plan and project plans

• User and functional requirements/specifications

• Risk assessment procedures and methods

• Development of design and test case qualification protocols including traceability matrices, if required

• Test protocol execution and summary reports

• Deviation and change control management

• Periodic review and validation monitoring

• Roll-out of knowledge transfer program

COMPUTER SYSTEMS VALIDATIONOur computer systems validation services document the verification and qualification of all software and software-controlled systems as they are used in your operational environment. Through our services, we ensure that the validation status of these software elements is maintained throughout the lifecycle for the validated system. Typically, our systems validation projects incorporate the following deliverables:

• Validation policies and procedures

• Validation master plan and project plans

• User and functional requirements/specifications

• Risk assessment procedures and methods

• Development of design and test case qualification protocols and traceability matrices

• System code review and unit acceptance testing

• Integration testing and performance qualification

• Test protocol execution and summary reports

• Deviation and change control management

• Periodic review and validation monitoring

• Roll-out of knowledge transfer program

FACILITIES VALIDATIONWith a team of highly skilled engineers, possessing vast experience across electrical, construction and environmental engineering disciplines, GxP Systems has a multi- disciplinary approach to facilities validation services. Using this approach, we prove and document that equipment or ancillary systems are properly installed, function as designed, and lead to the expected results. This process will establish and provide documentary evidence that your premises, supporting utilities, equipment, and processes have been designed, installed and operate in accordance with the requirements of cGMP.

v a l i d a t i o n . 5

PROCESS VALIDATIONGxP Systems performs validation of new processes, equivalent processes, process improvements and process changes to be introduced into your manufacturing area—all while meeting the domestic and international regulatory compliance requirements for process validation. Each process validation will vary in its scope, based on the reason for the validation, criticality and complexity of the process and associated equipment.

SUPPLY CHAIN VALIDATIONWith the increased emphasis on supply chain quality, companies are finding it a challenge in ensuring that their supply chain is compliant with all regulations. We will execute through the supply chain validation process, including auditing, verifying, validating and monitoring, to ensure your suppliers’ processes and systems meet domestic and international regulatory compliance requirements by overcoming supply chain challenges such as:

• Adverse standards of compliance by suppliers

• Insufficient knowledge of the CMO regarding supply chain compliance

• Poor monitoring of supply chain quality

• Wrong-sized incoming quality inspection processes

POLICY AND PROCEDURE DEVELOPMENTOur team of experienced life sciences consultants will help you with the development and design of compliance policies, processes, procedures and subsequent supporting documentation to suit your operational and regulatory needs.

VALIDATION CASE STUDY 1Client: Multinational Med Device Company

Summary: Managed validation service for 10+ years

Solution: We create & maintain a balanced team of resources, from graduate to project management level leading to consistently high quality service and significant cost savings.

From URS stage, we take control of validation.

GxP Systems develop/author Validation Processes & procedures with dynamic resource balancing, including project utilisation of 100% for all engineers.

We provide consistent forecasting of cost of validation to Fixed Price model.

We take away the headache & consistently deliver the right result.

6 . v a l i d a t i o n

VALIDATION CASE STUDY 2Client: Confidential (Multinational Pharmaceutical Company)

Summary: Client required a Product Track and Trace System that would:

a) Record the batch, filling and packing data of the products on each truck

b) Print barcodes to the truck card

c) Ensure that each steriliser is automatically updated with qualified codes and dates

d) Provide validation checks at key points in the process

e) Integrate with the existing calibration database

f) Flexible, open architecture allowing other systems to be easily added in the future

g) Product real-time and historical reports

h) Open and non-proprietary data logging methods

i) Incorporate business rules into the control of the sterilisation process. This would ensure that all products are sterilised in a correct and standard method

Issue: The client required a Product Tracking system to gather manufacturing data which would help them achieve high quality and control during the manufacturing process.

Solution: GxP Systems supplied system software and hardware to the client. We designed and configured a database to receive and store information, which works with the HMI to provide real-time data. All aspects of the software development lifecycle was completed by GxP Systems. This included designing, configuring, integrating, installing, testing and validating the new Product Tracking system. The Unified Software Development Process with the Unified Modelling Language was used to develop the software module

Result: The client now has a fully functional Product Tracking system at its manufacturing plant. This gives the company more control over the sterilisation process, ensuring that their products retain their world-renowned quality level. The system has improved the sterilisation process by reducing the risk of human error, and increasing productivity and efficiency.

v a l i d a t i o n . 7

VALIDATION CASE STUDY 3 (CSV )Client: Confidential (Multinational Pharmaceutical Company)

Summary: Client required an upgraded Product Inspection Validation System that would achieve 21 CFR Part 11 compliance for:

a) Store date of eye test and results

b) Store date of product inspection validations and results for each product

c) Standard security permissions and audit trail facilities that can be utilised by all new and upgraded systems

It must also be a central user repository facilitating centralised administration and security management that is:-

a) Web-based, has a user-friendly interface that is accessible via the company intranet

b) Automatically alerting users prior to a scheduled test being due

c) Flexible, open architecture allowing new and upgraded systems to be easily added

d) Able to produce flexible historical reports

Issue: The client has a Product Inspection Validation system which stores information on the training history and eye test results for each Packaging Process Operator. The function of an operator is to inspect and remove defect vials from a line running at a pre-determined speed. Operators must have annual eye tests and training to ensure that they can carry out this function.

Solution: GxP Systems supplied system software and hardware to the client. We designed and configured a database to receive and store information, which works with the HMI to provide real-time data. All aspects of the software development lifecycle was completed by GxP Systems. This included designing, configuring, integrating, installing, testing and validating the new Product Tracking system. The unified software development process with the unified modelling language was used to develop the software module.

Result: The clients’ manufacturing systems are now fully compliant with all the required regulations, including 21 CFR Part 11. Information pertaining to qualifications and testing for operators can be processed centrally. The web-based interface is user-friendly requiring less training for new employees. In the future, new systems can be easily added and integrated with existing system architecture at a reduced cost and with minimum development and validation effort.

8 . v a l i d a t i o n

VALIDATION CASE STUDY 4Client: Confidential (Multinational Pharmaceutical Company)

Summary: The client had a requirement to execute the appropriate validation for the completion of a highly prestigious molding project which was to form part of the manufacturing process for a new combination product. GxP Systems were appointed as project managers for this molding project.

Issue: GxP Systems were focused on achieving a fully validated system.

Solution: GxP Systems proposed an approach that incorporated GAMP principles and expert validation knowledge to achieve the objective. A team of validation engineers under the supervision of a GxP Systems Program Manager was assigned to carry out the required activities. Progress reports were provided to management on a monthly basis. Project metrics were produced and submitted to the client.

Result: The client now has a fully validated molding system at its manufacturing plant. As the project was delivered on time and within budget, the client began manufacturing in accordance with their own projected deadline.

v a l i d a t i o n . 9

QUALITYGxP Systems highly experienced team of quality experts develops, rolls out and maintains the Quality Management Systems required for the organizational structures, procedures, processes and resources to implement quality management at your manufacturing sites.

QualityEngineeringGxP Systems provides an in-depth knowledge of a wide range of quality support systems to support on-going process improvement.

QualityManagementSystems(QMS)With extensive experience in developing and supporting quality management systems (QMS), GxP Systems can help you with:

• Change control

• Periodic review

• CAPAs

• Auditing

• SOPs

• Document control

• Deviations

• Validation

Our approach through an integrated set of processes, such as QSIP, delivers a compliant quality program as well as introducing various quality improvement initiatives (Quality Improvement Plan).

1 0 . q u a l i t y

Client: Confidential, (Multinational Medical Device Company)

Summary: GxP Systems developed a QSIP (Quality System Improvement Plan) for a company on the verge of a product recall.

Issue: Failure in Design Control, Validation and Compliance

Solution: 1. GxP Systems completed an audit leading to Gap Analysis

2. We developed a QSIP plan comprising the customer’s processes of; Management review, complaint database, CAPA, purchasing controls, training, change control, device tracking database, clinical database, etc.

3. We managed all related activities

4. GxP Systems effected a cultural change in the organisation and provided a full knowledge transfer throughout the project

5. We also carried out a trial FDA Audit for the client.

Result: Potential product recall was reduced to a field safety action. The clients’ quality system and procedures were completely overhauled and re-designed. This led to a significant improvement in the quality of production and a fully compliant system. The system improvements showed that the company had properly addressed the root cause of the problem and that it will not be an issue in the future.

q u a l i t y . 1 1

QUALIT Y & COMPLIANCE CASE STUDY

1 2 . r e m e d i a t i o n

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REMEDIATIONIf you’ve received a warning letter or consent decree, it’s a relief to know that expert help is just a phone call away. With in-depth knowledge of regulatory guidelines and our superior ability to return systems to a state of validated compliance, we excel at remediation services.

We offer a complete range of remediation services, focusing on improving your operations and enabling you to stay compliant in an ever-changing and challenging regulatory environment. From initial gap analysis and remediation planning for existing systems to prospective assessments of new systems, our experienced teams will help determine the regulatory relevance and requirements for compliance.

If you’re in need of remediation, you will benefit from our proven approach to remediation:

ComprehensiveObjectivesandPriorityDefinition• Determine nature of work

• Preliminary meetings to address your compliance concerns

• Review of specific audit findings

• Scope identification and high-level plan development

AccurateGapAssessment• Determination of any underlying issues

• Analysis of internal or external audit findings, customer complaints or adverse operational events

• Clarification of core problems and shortcomings

• Gap assessment report

EffectiveFormalPlans• Gathering information from your team

• Formal project plan that identifies timeframes, team requirements, project roles and responsibilities

• Agreement between all principle stakeholders

• Complete project visibility

SuccessfulProjectExecution• Execution of individual project tasks to agreed timelines and standards, with

participation from your team

• Weekly reports to enable transparency, progress tracking and effective knowledge transfer

• Monitoring of project performance to demonstrate the project is executed in a timely and compliant manner without any compromise on quality

• Supervision and inspection by our senior management team through internal reporting and on-going quality review of all completed work

ProjectFollow-Up• On-going consulting and advisory services

REMEDIATION CASE STUDYClient: Confidential (Multi National Medical Device Company)

Summary: Multi-site Remediation for a Medical Device company under a warning letter and partial consent decree.

Issue: FDA stated the client was deficient in their response to customer complaints which stemmed from issues with the specific devices.

Solution: GxP Systems provided the following services to the client:-

•Audit leading to Gap Analysis

•Redesigning of their QMS

•Site Inclusive Manufacturing Validation and Commissioning project

•Roll out of QMS to other sites.

•Project Management of all related activities

•Partnership approach with both our client and 3rd party auditors.

•Knowledge Transfer throughout the project.

•Cultural change

•Training workshops

Result: Third party auditors certified the clients’ Equipment & Process Validation Procedures were compliant. The client resolved the issues to the satisfaction of the FDA and resumed business as usual.

r e m e d i a t i o n . 1 3

AUDITINGOur team will make your team audit ready. With an impending audit, you can rest assured that GxP Systems can and will provide you with expert auditing services. Specializing in multi-site and global supplier audits, we have auditing experts who can help you with all of your auditing needs:

• Multi-site audit programs

• Periodic review to assess and report on the performance and validated state of all of your systems and equipment

• Risk assessment using a wide range of techniques including FMEA and PFMEA to identify and quantify the appropriate level of validation

• Software quality assurance/practices to report on processes and methods used by all key software project stakeholders

• NDA, 510(k) and CMC compliance ensures all your new and existing products comply with all applicable regulations

• FDA remediation programs address 483s, warning letters and consent decrees by auditing your programs and strategies, followed by implementation and execution of required activities

• 21 CFR Part 11 & Annex 11 compliance that creates, maintains and supports controls to ensure data authenticity and integrity

• Global supplier audit programs evaluate compliance of your suppliers against FDA standards

• Contract Manufacturing Organization (CMO) audit makes sure your outsourced manufacturers’ procedures are consistent with regulatory requirements

• Pre-UAT, pre-go live readiness audit and post go-live audit services ensures your readiness to begin an operation

• Internal quality audit providing unbiased and independent reports, highlighting all relevant issues

• Policy and procedure review against all current GMPs ensures compliance with all relevant regulatory standards

• GMP, GLP, GCP program auditing

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1 4 . a u d i t i n g

AUDITING CASE STUDYClient: Confidential, (Multinational Med Device Company)

Summary: GxP Systems was hired to coach and mentor the client before, during and after their first FDA Audit.

Issue: GxP Systems first conducted a trial audit of the client’s Quality Systems, validation program, equipment records and site to establish a base line.

Solution: Having identified a number of non-conformances, we recommended a series of CAPAs to resolve them. Furthermore, we coached and mentored the client’s personnel on how to behave, respond and interact with the FDA.

Result: No 483 warning letter was issued; GxP Systems’ improved the Quality Systems through use of Six Sigma tools and reduced manpower required to complete change controls, deviation, document revisions and validation.

a u d i t i n g . 1 5

1 6 . t e c h n o l o g y t r a n s f e r

TECHNOLOGY TRANSFERIf your company has a need to ensure a smooth transfer of technology or equipment, GxP Systems efficiently transfers and validates skills, knowledge and technologies among life science manufacturing sites to ensure the delivery of compliant processes. We leverage our high level of expertise to analyze existing and new sites to enable a smooth Technology Transfer from site to site.

To ensure that transfer of equipment, line or train of equipment will consistently produce a result that meets pre-determined acceptance criteria, our Technology Transfer services include:

ProductionLine/EquipmentMoves/Transfers• Location-to-location, either internally or externally

• As-is assessments

• Decommissioning activities

• Target location/process requirements

• Risk-based and right-sized qualification and requalification activities

Our successes from continuing audits by

worldwide regulatory bodies are

a testament to the quality and

relevance of our approach for

compliance for every client.

© 2014, GxP Systems. 4/14

www.gxpsystems.com

Europe

The Atrium Blackpool Cork Ireland

P +353 21 4215 050

E  info@gxpsystems.com

UnitedStates

Cambridge Innovation Center One Broadway, 14th Floor Kendall Square Cambridge, MA 02142   USA 

P +1 617 401 2128

E  info@gxpsystems.com