implement process validation

61

Click here to load reader

Upload: institute-of-validation-technology

Post on 07-May-2015

1.495 views

Category:

Health & Medicine


4 download

TRANSCRIPT

Page 1: Implement Process Validation

[ 1 ] CONFIDENTIAL

Institute of Validation Technology Validation Week- Philadelphia

Tanya Fletcher-Scott Validation Manager- Greenville SC Solutions Facility [email protected]

October 24, 2012

Session 4: Best Practice to Implement Process Validation in Device Manufacturing Enterprise-wide

Page 2: Implement Process Validation

[ 2 ]

Agenda

£  Getting Started-Overview £  Process Validation

£  Enterprise wide Roll Out of Process Validation

£  Interactive Exercise

Look out for the

Best Practice

Page 3: Implement Process Validation

[ 3 ]

Getting Started-Overview

o  The Rules- Review of Standards and Guidances for Process Validation of Devices

o  Tools- Risk Assessments and Statistics

o  The Team- Don’t go it alone!

o  The Docs- Documenting the process validation activities

Page 4: Implement Process Validation

[ 4 ]

Getting Started-Overview The Rules- Review of Standards and Guidances for Process Validation of Devices:

•  21 CFR 820 Quality System Regulators

•  ISO, EN ISO 13485 Medical devices- Quality management systems- Requirements for regulatory purposes

•  ISO, EN ISO 14971 Medical devices-Application of risk management to medical devices

• ISO, EN ISO 9001 Quality management systems —Requirements Best Practice:

Know your regs and

guidances

Page 5: Implement Process Validation

[ 5 ]

Getting Started-Overview The Rules- Review of Standards and Guidances for Process Validation of Devices:

•  GHTF, Global Harmonization Task Force- Quality management Systems-Process Validation Guidance*

•  SOR/98-282 Canadian Medical Regulators

•  93/42/EEC Medical Device Directive *Copy provided as bonus material

Best Practice: Know your regs and

guidances

Page 6: Implement Process Validation

[ 6 ]

Getting Started-Overview

The Rules- Review of standards and guidances for Process Validation of Devices: 21 CFR 820 Quality System Regulators Sec. 820.70 Production and process controls. b-Production and process changes. Each manufacturer shall establish and maintain procedures for changes to a specification, method, process, or procedure. Such changes shall be verified or where appropriate validated according to 820.75 (Process Validation), before implementation and these activities shall be documented. Changes shall be approved in accordance with 820.40 (Document controls).

Page 7: Implement Process Validation

[ 7 ]

Getting Started-Overview

The Rules- Review of standards and guidances for Process Validation of Devices: Sec. 820.75 Process Validation. a- Where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures. The validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated, shall be documented. b- Each manufacturer shall establish and maintain procedures for

monitoring and control of process parameters for validated process to ensure that the specified requirements continues to be met.

Page 8: Implement Process Validation

[ 8 ]

Getting Started-Overview

The Rules- Review of standards and guidances for Process Validation of Devices: ISO, EN ISO 13485 Medical devices- Quality management systems- Requirements for regulatory purposes 7 Product realization, 7.1 Planning of product realization The organization shall plan and develop the processes needed for product realization. Planning of product realization shall be consistent with the requirements of the other processes of the quality management system. In planning product realization, the organization shall determine the following, as appropriate: a) quality objectives and requirements for the product; b) the need to establish processes, documents, and provide resources specific to the product; c) required verification, validation, monitoring, inspection and test activities specific to the product and the criteria for product acceptance; d) records needed to provide evidence that the realization processes and resulting product meet requirements

Page 9: Implement Process Validation

[ 9 ]

Getting Started-Overview

The Rules- Review of standards and guidances for Process Validation of Devices: ISO, EN ISO 13485 Medical devices- Quality management systems- Requirements for regulatory purposes 7.5.2 Validation of processes for production and service provision The organization shall validate any processes for production and service provision where the resulting output cannot be verified by subsequent monitoring or measurement. This includes any processes where deficiencies become apparent only after the product is in use or the service has been delivered. Validation shall demonstrate the ability of these processes to achieve planned results. The organization shall establish arrangements for these processes including, as applicable a) defined criteria for review and approval of the processes, b) approval of equipment and qualification of personnel, c) use of specific methods and procedures, d) requirements for records and e) revalidation.

Page 10: Implement Process Validation

[ 10 ]

Getting Started-Overview

Tools- Risk Assessments and Statistics

Statistics Sec. 820.250 Statistical techniques. (a) Where appropriate, each manufacturer shall establish and maintain

procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics.

(b) Sampling plans, when used, shall be written and based on a valid

statistical rationale. Each manufacturer shall establish and maintain procedures to ensure that sampling methods are adequate for their intended use and to ensure that when changes occur the sampling plans are reviewed. These activities shall be documented.

Best Practice: Use your

statisticians

Page 11: Implement Process Validation

[ 11 ]

Getting Started-Overview

Tools- Risk Assessments and Statistics

ISO 13485 8 Measurement, analysis and improvement, 8.1 General The organization shall plan and implement the monitoring, measurement, analysis and improvement processes needed a)  to demonstrate conformity of the product,

b) to ensure conformity of the quality management system, and c)to maintain the effectiveness of the quality management system. This shall include determination of applicable methods, including statistical techniques, and the extent of their use.

Page 12: Implement Process Validation

[ 12 ]

Getting Started-Overview

Risk Assessments ISO 14971 Medical devices — Application of risk management to medical devices The ISO Standard defines risk as combination of the probability of occurrence of harm and the severity of that harm

Tools- Risk Assessments and Statistics Risk Analysis

Risk Evaluation

Risk Control

Evaluation of overall residual risk acceptability

Risk Management Report

Production and post-production information

Page 13: Implement Process Validation

[ 13 ]

Getting Started-Overview

Tools- Risk Assessments and Statistics Risk Management Tools

•  Preliminary Hazard Analysis (PHA) is a technique that can be used early in the development process to identify the hazards, hazardous situations, and events that can cause harm when few of the details of the medial device design are known.

•  Fault Tree Analysis (FTA) is especially useful in safety

engineering, early in the development stages, for the identification and prioritization of hazards and hazardous situations as well as for analyzing adverse events.

Page 14: Implement Process Validation

[ 14 ]

Getting Started-Overview

Tools- Risk Assessments and Statistics Risk Management Tools •  Failure Mode and Effects Analysis (FMEA) and Failure

Mode, Effects and Criticality Analysis (FMECA) are techniques by which an effect or consequences of individual components are systematically identified and is more appropriate as the design matures.

•  Hazard and Operability Study (HAZOP) and Hazard

Analysis and Critical Control Point (HACCP) are typically used in the latter stages of the development phase to verify and then optimize design concepts or changes.

Page 15: Implement Process Validation

[ 15 ]

Getting Started-Overview

The Team- Don’t go it alone!

The types of products manufactured in the Greenville facility are lens care solutions. When we are conducting a process validation to support a product transfer or significant formulation change, we need the support of a cross functional group inclusive of corporate and site wide subject matter experts.

Page 16: Implement Process Validation

[ 16 ]

•  Quality Assurance* •  Engineering* •  Manufacturing* •  Laboratory (Chemistry and Microbiology)* •  Technical Services •  Research & Development* •  Regulatory Affairs* •  Clinical Engineering •  Purchasing/Planning •  Process Excellence / Statistician* •  Project Manager* *B+L’s typical team core members for major process validation projects

The Global Harmonization Task Force- Quality Management Systems – Process Validation Guidance suggests the following subject matter team members:

Getting Started-Overview

The Team- Don’t go it alone!

Best Practice:

Project Managers are key to any success tech

transfer

Page 17: Implement Process Validation

[ 17 ]

Getting Started-Overview

The Docs- Documenting the process validation activities

Sec. 820.75 Process Validation. a- Where the results of a process cannot be fully verified

by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures. The validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated, shall be documented.

Page 18: Implement Process Validation

[ 18 ]

Getting Started-Overview

The Docs- Documenting the process validation activities

The Global Harmonization Task Force- Quality Management Systems – Process Validation Guidance suggests the following elements in your process validation protocols:

Elements Validation Strategy

IQ OQ PQ PV

Identification of the process to be validated X X X X X

Identification of device(s) to be manufactured using this process

X X X X X

Objective and measurable criteria for a successful validation

X X X X X

Identification of operators and required operator qualification

X X Best Practice: Validation

Strategies are a great tool for ‘big scope’ projects

Page 19: Implement Process Validation

[ 19 ]

Getting Started-Overview

The Docs- Documenting the process validation activities

The Global Harmonization Task Force- Quality Management Systems – Process Validation Guidance suggests the following elements in your process validation protocols:

Elements Validation Strategy

IQ OQ PQ PV

Length and duration of the validation X

Shifts, operators, equipment to be used in the process

X X

Any subjective criteria used to evaluate the product

X X X X

Identification of utilities for the process equipment and quality of the utilities

X X

Complete description of the process X X X X X

Page 20: Implement Process Validation

[ 20 ]

Getting Started-Overview

The Docs- Documenting the process validation activities

The Global Harmonization Task Force- Quality Management Systems – Process Validation Guidance suggests the following elements in your process validation protocols:

Elements Validation Strategy

IQ OQ PQ PV

Relevant specifications that relate to the product, components, manufacturing materials, etc

X X X X

Process parameters to be monitored, and methods for controlling and monitoring*

X X

Product characteristics to be monitored and method for monitoring*

X X

Any subjective criteria used to evaluate the product

X X

*Use of a Control Plan is a great tool and best practice. Example included in bonus material

Page 21: Implement Process Validation

[ 21 ]

Getting Started-Overview

The Docs- Documenting the process validation activities

The Global Harmonization Task Force- Quality Management Systems – Process Validation Guidance suggests the following elements in your process validation protocols:

Elements Validation Strategy

IQ OQ PQ PV

Definition of what constitutes non-conformance for both measurable and subjective criteria

X X X X X

Statistical methods for data collection and analysis

X X X X

Consideration of maintenance and repairs of manufacturing equipment

X

Criteria for revalidation X

When it’s all done, generate the final report summarizing all requirements, results, issues and conclusions

Page 22: Implement Process Validation

[ 22 ]

Agenda

£  Getting Started-Overview £  Process Validation

£  Enterprise wide Roll Out of Process Validation

£  Interactive Exercise

Page 23: Implement Process Validation

[ 23 ]

Process Validation

o  Creating a strategy/validation plan

o  Strategies for new and existing products

o  Runs and samples

o  When are you done?

Page 24: Implement Process Validation

[ 24 ]

Process Validation

Creating a strategy/validation plan A Validation plan which defines what needs to be validated (i.e. equipment, systems and processes) and how validation needs will be met for a given project. The strategy also provides a roadmap to follow ensuring the requirements are defined and agreed upon up-front and that all requirements are met prior to implementation or launch

Best

Practice: Wait until you

have created or updated your risk

assessment before generating

a strategy.

Page 25: Implement Process Validation

[ 25 ]

Process Validation

Creating a strategy/validation plan B+L’s validation systems does not require validation strategies for smaller, less complex validation projects whose strategy can be fully detailed within a protocol.

The strategy is useful to communicate completion of validation strategy activities and results of the testing performed to support product Launch or Design Change Implementation

<Let’s review the sample validation strategy in your bonus material>

Page 26: Implement Process Validation

[ 26 ]

Process Validation

Strategies for new and existing products New Products Per ISO 9001, all new products must under Design and development which includes: •  Planning •  Design and development inputs •  Design and development outputs •  Design and development review •  Design and development verification •  Design and development validation* •  Control of design and development changes* *At the completion of the design and development validation and before the control of design changes, product transfer and process validation occurs.

Page 27: Implement Process Validation

[ 27 ]

Process Validation

Strategies for new and existing products New Products During the product transfer process, the product is being evaluated at the manufacturing site for scale up. It is at this stage that the use of statistician can help evaluate process capability and readiness for process validation. Also helpful with defining acceptance criteria, number of samples, etc. Risk analysis can be a great tool in defining worse case conditions a process can potential see in routine manufacturing. These failure modes can be tested in product evaluation and/or validation trials. (reference validation strategy risk mitigation table)

Best Practice:

During the product transfer stage there needs to be high

engagement with site validation

Page 28: Implement Process Validation

[ 28 ]

Process Validation

Strategies for new and existing products New Products Process Validation Readiness should include the following: • Design review confirms process is capable

• All prerequisite validations are complete (e.g. equipment, facility, software, etc.)

• Process control plan has been created or updated*

• Risk analysis has been updated

*<Let’s review the sample control plan in your bonus material>

Page 29: Implement Process Validation

[ 29 ]

Process Validation

Page 30: Implement Process Validation

[ 30 ]

Process Validation

Strategies for new and existing products New Products Process Validation Readiness should include the following: • All procedures, batch records, inspection plans, specifications, drawings are updated and approved.

• All impacted personnel are trained on procedure, batch records, inspection plans, etc.

• All raw materials are procured and in approved status

• All new suppliers are in approved status

<Let’s review the sample readiness form in your bonus material>

Page 31: Implement Process Validation

[ 31 ]

Process Validation

Page 32: Implement Process Validation

[ 32 ]

Process Validation

Strategies for new and existing products Existing Products Existing products are defined as validated products that have been transferred to the manufacturing site for routine manufacture. For validations involving any existing product, B+L follows a global change management process.

Sec. 820.70 Production and process controls. b-Production and process changes. Each manufacturer shall establish and maintain procedures for changes to a specification, method, process, or procedure. Such changes shall be verified or where appropriate validated according to 820.75 (Process Validation), before implementation and these activities shall be documented. Changes shall be approved in accordance with 820.40 (Document controls).

Page 33: Implement Process Validation

[ 33 ]

Process Validation

Strategies for new and existing products Existing Products B+L’s global change management software tracks all changes for existing products. Depending on the scope of the change; a limited, extensive or full revalidation may need to be conducted. A key element of change control is the impact analysis. The impact analysis considers the impact of the change to the risk management file.

Best Practice:

A Validation representative

needs to evaluate changes impacting

validated state.

Page 34: Implement Process Validation

[ 34 ]

Process Validation

Strategies for new and existing products Existing Products A useful tip is to work with your Research and Development group or Technical Services group to evaluate the capability of the product device after proposed change. Pros: • Better process understanding • Greater confidence in the process to pass when you go into live validation.

Cons: • May require additional equipment, line time, resources, lab support to generate data • Cost of material/product that may need to be scrapped

It’s a Risk decision

Page 35: Implement Process Validation

[ 35 ]

Process Validation

Runs and Samples

How many runs do we need???

Page 36: Implement Process Validation

[ 36 ]

Process Validation

Runs and Samples

How many runs do we need???

How many samples do we need to take???

Page 37: Implement Process Validation

[ 37 ]

Process Validation

Runs and Samples

How many runs do we need???

How many samples do we need to take???

Can we runs this concurrent with production???

Page 38: Implement Process Validation

[ 38 ]

Process Validation

Runs and Samples

How many runs do we need???

How many samples do we need to take???

Can we runs this concurrent with production???

It depends on the scope, level of risk and confidence we have in the process. It’s a question of risk!

Page 39: Implement Process Validation

[ 39 ]

Process Validation

Runs and Samples For the number of runs, we use 3 as a starting point. We let our risk assessment drive the number of runs needed. Example:

There is a process change that will impact the manufacturing of a formulation in 2 different tanks. Our engineering data indicates that although the 2 tanks are the same size they are both designed differently and have different heating and agitation profiles. A risk analysis indicates that heating and agitation may have significant impact on product acceptance. For this process validation a minimum of 6 runs (3 runs/tank) may be recommended in addition to engineering trials to confirm capability of the formulation.

Page 40: Implement Process Validation

[ 40 ]

Process Validation

Runs and Samples In sampling, we target confidence level of at least 90%. We also let our risk analysis drive the number and type of samples needed. There needs to be an understanding of what’s important to your process. Let’s illustrate this point with the validation of Product XYZ

Page 41: Implement Process Validation

[ 41 ]

Runs and Samples

Overview of product and manufacturing process for Product XYZ

£  Raw Materials: •  Sterile Water •  NaCL •  Raw Material A •  Raw Material B (new) •  Excipients

£  Critical Quality Attributes (CQAs). •  Solution is safe and effective for intended purpose (attribute or go/no-go) •  Batch is homogeneous (variable data)

•  Raw Materials A and B must meet label claim (attribute or go/no-go)

Process Validation

Best Practice:

A key to the sampling rationale

is found in the CQA’s. They define what’s

important

Page 42: Implement Process Validation

[ 42 ]

Runs and Samples Product XYZ

Sterile Filling

Bulk Compounding

Packaging

Step 1

• Purified Water

• Add Excipents

• Heat sterilize mixture

CPPs=batch temp, agitation speed

Step 2

• Mix, dissolve and Sterile filter excipents

CPP=batch temp, mix time

Step 3

• Mix and Sterile filter Raw Materials A and B

CPP=batch temp, mix time

Step 4

• Mix dissolve and Sterile filter NaCL and excipients

CPP=batch temp, mix time

19,000 L

Tank

CPP=Critical Process Parameter

19,000 L

Tank

Process Validation

Page 43: Implement Process Validation

[ 43 ]

Runs and Samples

Sterile Filling

Bulk Compounding

Packaging

19,000 L

Tank

CPP= Line length, product conditioning volume, filling speed, etc.

Process Validation

Product XYZ

Page 44: Implement Process Validation

[ 44 ]

Runs and Samples

Sterile Filling

Bulk Compounding

Packaging

Case Study- Process Validation for Product XYZ

• Our product and process risk assessment identified both the bulk compounding and sterile filling process steps as having the highest potential risk. Critical Quality Attributes (CQAs).

•  Solution is safe and effective for intended purpose (most likely impacted in bulk compounding and sterile filling process)

•  Batch is homogeneous (most likely impacted in bulk compounding)

•  Raw Materials A and B must meet label claim (most likely impacted in bulk compounding)

• We focused more effort (sampling and runs) on these high risk process steps during scale up and process validation

Page 45: Implement Process Validation

[ 45 ]

Runs and Samples

Sterile Filling

Bulk Compounding

Packaging

Process Validation

• Based on historical data and information from our risk assessments, the heaviest use of statistics (sampling) was focused on the bulk compounding and sterile filling processes as we needed to demonstrate a high level of assurance at these stages.

• We used process capability data from similar products and development work to establish standard deviations for Raw Materials A and B.

• Our sample size was based on the use of standard deviations from engineering trials, 90% Confidence

• For batch and bottle homogeneity we demonstrated with 90%Confidence that batch and bottle sample sets were homogeneous.*

Page 46: Implement Process Validation

[ 46 ]

Process Validation When are you done?

Now that the execution is complete with your Process Validation and Final Report has been

written and approved, Are You Done?

Page 47: Implement Process Validation

[ 47 ]

Process Validation When are you done? According to GHTF - Quality Management Systems Process Validation Guidance, you should maintain a state of validation: •  Monitor and control •  Changes in processes and/or product

•  Continued state of control

Page 48: Implement Process Validation

[ 48 ]

Process Validation When are you done? Most companies including B+L are using the product quality review process to confirm medical device products are maintained in a state of control. Key attributes include: •  In process and final product manufacturing trend data

•  Complaints

•  Non-conformances

•  Corrective Preventive Actions

•  Stability

•  Changes and subsequent validations

Page 49: Implement Process Validation

[ 49 ]

Agenda

£  Getting Started-Overview £  Process Validation

£  Enterprise wide Roll Out of Process Validation

£  Interactive Exercise

Page 50: Implement Process Validation

[ 50 ]

Enterprise wide Roll Out of Process Validation

o  Enterprise-wide policies and procedures

o  Quality System standardization, design management, change management and validation

o  Train personnel

Page 51: Implement Process Validation

[ 51 ]

Enterprise wide Roll Out of Process Validation

Enterprise-wide policies and procedures The CFR requires established procedures to conduct process validation and support monitoring and control of process parameters.

Sec. 820.75 Process Validation. a- Where the results of a process cannot be fully verified by subsequent

inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures. The validation activities and results, including the date and signature of the individual(s) approving the validation and where appropriate the major equipment validated, shall be documented.

b- Each manufacturer shall establish and maintain procedures for

monitoring and control of process parameters for validated process to ensure that the specified requirements continues to be met.

Page 52: Implement Process Validation

[ 52 ]

Enterprise wide Roll Out of Process Validation

Enterprise-wide policies and procedures Best practices for a multi-site / global company to deploy process validation procedures is Enterprise-wide policies and procedures: Pros: • Provides clear instruction for ‘how things are done’. • Offers consistent approach to validation to train to and follow regardless of site location, manufacturing platform, products manufactured • Presents to regulators the company’s position on process validation • Capitalize on best practices at each site. • Ensures alignment to guidances, standards and industry best practices

Best Practice:

In addition to policies and procedures,

templates provide consistency

Page 53: Implement Process Validation

[ 53 ]

Enterprise wide Roll Out of Process Validation

Enterprise-wide policies and procedures Cons: • Difficult to gain consensus with multiple sites who have always ‘done it their way’. • Procedures and templates may not be flexible to meet needs of different products, manufacturing platforms • Learning curve and time to implement

Tips for Enterprise-Wide roll out are: • Getting engagement and feedback from stakeholders at the manufacturing site. Feedback should be from each type of manufacturing site. • Deploy procedures and templates on a trial basis to ‘validate’ its use. • Allow extended phase in period (60-90 days) for training

Page 54: Implement Process Validation

[ 54 ]

Enterprise wide Roll Out of Process Validation

Quality System standardization, design management, change management and validation The success of any Validation Program is contingent on a healthy Quality System. ISO 9001 identifies the some of the Quality Systems evaluated during management review:

5.6.2 Review input- The input to management review shall include information on: a) results of audits, (Internal and External Audits) b) customer feedback, (Complaints) c) process performance and product conformity, (NonConformance Management) d) status of preventive and corrective actions, (NonConformance Management) e) follow-up actions from previous management reviews, f) changes that could affect the quality management system, and (Change Mgmt) g) recommendations for improvement. (Continuous Improvement)

Page 55: Implement Process Validation

[ 55 ]

Enterprise wide Roll Out of Process Validation

Quality System standardization, design management, change management and validation ISO 9001 state the following responsibilities of Management Review:

5.6.3 Review output- The output from the management review shall include any decisions and actions related to: a) improvement of the effectiveness of the quality management system and its processes, b) improvement of product related to customer requirements, and c) resource needs.

Page 56: Implement Process Validation

[ 56 ]

Enterprise wide Roll Out of Process Validation

Quality System standardization, design management, change management and validation Standardization of key quality systems like design management, change management and validation ensures: • Provides clear instruction for ‘how things are done’.

• Offers consistent approach to train and follow regardless of site location, manufacturing platform, products manufactured

• Presents to regulators the company’s position on key quality systems

• Ensures alignment to guidances and standards

<Reference a sample global final report template in bonus material>

Page 57: Implement Process Validation

[ 57 ]

Agenda

£  Getting Started-Overview £  Process Validation

£  Enterprise wide Roll Out of Process Validation

£  Interactive Exercise

Page 58: Implement Process Validation

[ 58 ]

Firm is rebranding a legacy medical device product in a new bottle. Product is a sterile liquid. Bottle is being sourced from a new supplier. Bottle requires a different sterilization method. New equipment will be needed to run this bottle. Validation needs to be conducted to launch to ‘new product’.

What will the validation strategy be?

Interactive Exercise

Page 59: Implement Process Validation

[ 59 ]

•  Product ABC is currently filled in an oval and opaque HDPE. New bottle is round, transparent (without colorant) HDPE

•  Sterilization Method for current bottle is Ethylene Oxide. New bottle will require gamma irradiation

•  Bottle will be filled in Fill Room C. Fill Room C only has change parts for oval bottles.

•  Instead of using the checkweighing system, the firm would like to use fill volume sensors that were always integrated on Fill Room C but never used because firm uses opaque bottles.

•  Original validation for Product ABC was conducted 15 ago.

Interactive Exercise

Page 60: Implement Process Validation

[ 60 ]

Each team, take 5-10 minutes to develop a validation strategy. Demonstrate the use of the following: •  Success criteria

•  Team Members

•  Any necessary pre-work (engineering, develop studies, etc.)

•  Training

•  Proposed risk analysis

•  Proposed statistics

•  Process steps to focus validation effort

Interactive Exercise

Page 61: Implement Process Validation

[ 61 ]

Questions???