Master Validation Plan
For the
Fremont Extrusion Department
Table of Contents
1.0Purpose......
2.0Scope......
3.0Reference Documentation......
4.0Process Flowchart.......
5.0Validation Rationale- Extrusion......
5.1Process Control Documentation- Extrusion......
5.2Process Description- Extrusion......
5.2.1Beading (mandrel) extrusion......
5.2.2Single Lumen extrusion......
5.2.3Multi-lumen extrusion......
5.2.4Over-substrate extrusion......
5.2.5Co-extrusion/Gradient extrusion......
5.2.6Tapered Extrusion......
5.3Critical Process parameters- Extrusion......
5.3.1Rationale for selection of critical process parameters......
5.3.2Other process factors- extrusion......
5.4Component Grouping for OQ and PQ- Extrusion......
5.4.1Extrusion grouping criteria......
5.4.2Selection of challenge settings and components within groups......
5.5Extrusion OQ......
5.6Extrusion PQ......
5.7Representativeness of Batch Sizes for Extrusion OQ/PQ......
5.8Identification of Extrusion Lines......
5.9Interchangeability of Extrusion Equipment......
5.10Note concerning software validation for the purposes of Process Validation Remediation....
6.0Validation Rationale- Braiding......
6.1Process Control Documentation- Braiding......
6.2Process Description- Braiding......
6.3Critical Process Parameters- Braiding......
6.4Component Grouping for OQ/PQ- Braiding......
6.5Braiding OQ......
6.6Braiding PQ......
6.7Identification of Braiding Equipment......
6.8Interchangeability of Braiding Equipment......
6.9Note concerning software validation for the purposes of Process Validation
Remediation......
7.0Validation Rationale- Expansion......
7.1Process Control Documentation- Expansion......
7.2Process Description- Expansion......
7.3Critical Process Parameters - Expansion......
7.4Selection of Challenge Settings for OQ – Expansion......
7.5Component Grouping for OQ/PQ- Expansion......
7.6Expansion OQ......
7.7Expansion PQ......
7.8Identification of Expansion Lines......
7.9Interchangeability of Expansion Equipment......
7.10Note concerning software validation for the purposes of Process Validation Remediation..
8.0Acceptance Criteria......
8.1Definition of Acceptance Criteria......
8.2Sampling of OQ/PQ runs......
9.0Revalidation......
10.0Appendices......
1.0Purpose
The purpose of this Master Validation Plan (MVP) is to evaluate the risk from a process and design FMEA perspective and to define the validation requirements for each process for all components manufactured at Boston Scientific Fremont’s Extrusion Department.
This MVP will also document the processes used, and provide the justification and rationale for grouping of components for validation.
2.0Scope
This document will apply to components manufactured at the Boston Scientific Fremont Extrusion Department using the following technologies:
Extrusion
Single lumen extrusion
Dual/Multi lumen extrusion
Over-substrate extrusion
Co-extrusion
Tapered extrusion
Braiding
Expansion
Reference Appendix 1 for a complete listing of components covered by this MVP. Reference Section 5 of this MVP for definitions of the above technologies.
This document will also apply to the following manufacturing equipment used in the Fremont Extrusion Department:
Extruders and ancillary equipment
Braiders
Expansions lines
Reference Appendices 2-6 for a complete list of equipment covered by this MVP.
Finally this MVP will also address the validation requirements for both variable and attribute test methods as referenced in Appendix 10.6 (Note: Process Verification is not applicable to extrusion department processes as all are validated). Reports are referenced in the Master Validation Reports- ref. Section 3.0 of this MVP for MVR document numbers.
3.0Reference Documentation
Document Number / TitleSOP03554 / Process Validation SOP, Fremont site
90056169 / Master validation plan template
SOP03420 / Installation Qualification
S842771-00 / CORP SOP PROCESS VALIDATION
S842767-00 / Corporate Risk Analysis
SOP11184 / Equipment control
SOP11185 / Tool, Mold, and Fixture Qualification
SOP11186 / Test Method Validation
SLP03372 / Training and qualification
90030419 / Corp SOP Dsgn Verif/Prcs Valid Sampling
90117246 / Generic Extrusion FMEA, Fremont Extrusion Department
90117250 / Expansion FMEA, Fremont Extrusion Department
90158454 / Core-Rod (Mandrel extrusion) FMEA, Fremont Extrusion Department
90165244 / Braiding Process FMEA, Fremont Extrusion Department
90217920 / Corp SOP E&AS Life Cycle
90289854 / NVEXT Class III MVR
90337362 / NVEXT Class II MVR
90252432 / Fremont PVR Program Quality Plan
N/A / Polymer Extrusion, 4th edition. Rauwendaal, C.
Hanser. ISBN 1-56990-321-2
4.0Process Flowchart.
5.0Validation Rationale- Extrusion
5.1Process Control Documentation- Extrusion
As the extrusion process is largely generic, with process set points and minor tooling only varying by component, the extrusion process is controlled by generic work instructions in conjunction with component specific parameter setting sheets (EPPS- Extrusion Process Parameter Sheets). The information in the setting sheets is derived from the OQ/PQ activities, which are component or component group specific. Appendix 6 gives a list of generic extrusion work instructions and associated validation requirements. As validations for extrusion are focused on components or groups of components rather than processes, in general the validation requirements are met in the individual component OQ/PQ rather than a validation focused on a single procedure or procedural element.
5.2Process Description- Extrusion
Granulated polymeric material is loaded into the hopper at the feed end of the machine. For hygroscopic materials, a desiccant dryer is used to remove moisture from the resin in the hopper. This process is controlled by drying time and temperature. For each resin that requires pre-process drying, a minimum drying time and a drying temperature set point will be qualified. From the hopper the material is gravity fed onto the feed screw. The screw is situated within a barrel that is heated to a preset and controlled temperature. The screw consists of three sections: feed section, transition section and metering section. The root diameter of the screw increases from feed section to metering section and so, accordingly, the free volume reduces. As the screw rotates, material is conveyed along the screw from section to section in the manner of an Archimedean screw. The application of conductive heat from the barrel, mechanical shear and pressure generated from the change in screw geometry causes the material to be transformed from a granular state to a molten state. Typically 70-80% of the energy required to melt and homogenize polymeric melts is supplied by the mechanical shear of the rotating screw; the remainder is supplied by the barrel heaters (Rauwendaal; Polymer Extrusion 4th edition).
As the pressurized and homogenized melt stream exits the extruder barrel it enters a series of thermally controlled adapter blocks and is converted to an annular stream. The material exits to the atmosphere though the forming tooling (“tip and die”), which impart a specific geometry to the melt stream. The rapidly cooling melt stream is “drawn down” by the tractive action of a puller unit which pulls the melt stream into and through a temperature controlled cooling water bath. The extrudate loses thermal energy rapidly to the water setting the final cross sectional geometry and dimensions of the extrudate.
An alternative to the above process uses a melt pump. This is a positive displacement gear type pump which is used to more precisely regulate the volumetric flow of polymeric melt. When employed the melt pump is placed between the extruder barrel and the forming tooling.
After passing through the puller unit, the extrudate is either collected in discrete lengths, or is continuously spooled.
Subsets of the extrusion process are described below.
5.2.1Beading(mandrel) extrusion
In this variation of the extrusion process, a solid continuous rod is extruded, generally having a round profile.
5.2.2Single Lumen extrusion
In single lumen extrusion, the profile created is annular in cross-section. Pressurized air may be introduced into the tubing lumen to assist in maintaining roundness of the extrudate and in achieving target dimensions. Air pressure may be linked to a closed loop control system.
5.2.3Multi-lumen extrusion
In multi-lumen extrusion, the tooling is designed so as to create multiple discrete channels within the extrudate. Internal air may be used to assist in forming these lumen geometries.
5.2.4Over-substrate extrusion
In over substrate extrusion, a disposable core, or a subassembly requiring a polymer jacket, is used to form the interior features of the extrudate. The core is spooled through the extrusion tooling and is coated with molten polymer either within the crosshead (in pressure coating) or as it exits the tooling (as in over-jacketing).
5.2.5Co-extrusion/Gradient extrusion
In co-extrusion, multiple extruders are used in conjunction with the appropriate tooling to create an extrudate with multiple layers. These layers may be continuous, or in the case of Gradient, may vary in proportion over the length of the extrudate in order to create a component with varying stiffness or other properties with respect to length.
5.2.6Tapered Extrusion
In tapered extrusion, variations in tractive speed and internal air pressure are combined to create an extrudate which has a relatively constant shape but differing size the component length.
5.3Critical Process parameters- Extrusion
The critical process parameters determined for the extrusion process are:
- Zone Temperature setpoint(s)
- Output rate (Haul-off speed/screw speed)
- Drying temperature setpoint and minimum time
5.3.1Rationale for selection of critical process parameters.
There are two factors which contribute to the overall characteristics of an extruded tube; the material of construction (i.e. the resin) and the cross sectional geometry.
While the geometry is defined by the forming tool and the stability of the extrusion process in flow rate, the material properties for a given polymer are determined by the molecular weight. When a thermoplastic polymer is melt-processed, as in extrusion, it undergoes a reduction in molecular weight. The magnitude of this reduction is determined by the amount of thermal and mechanical degradation the material is exposed to in the extrusion process. Increasing temperature increases the rate of thermal degradation, while increasing the output rate directly increases mechanical shear and heating. Per Rauwendaal (Plastic Extrusion, 4th edition) the contribution of mechanical shear is the more significant in heating the melt. Local temperatures within the melt stream may be significantly higher than process temperature setpoints for the extruder due to frictional and viscous heating.By qualifying a maximum temperature and output rate, the maximum level of degradation to which the material may be exposed is limited.
The cross sectional dimensional process capability of the extrudate is largely dependent on the ability of the extruder to provide a consistent melt flow output without pulsing or surging. As the extruder screw is not a positive displacement pump, this ability is dependent on the melting behavior of the polymer, and the viscosity of the melt stream.The viscosity of polymeric melts decreases with increasing temperature and shear rate. The point of transition from solid to melt moves towards the feed section of the screw as temperature increases. Running at the lower extremes of temperature and output challenges the extruder’s output stability at the highest melt viscosity latest solid/melt transition, while running at the upper extremes challenges the output stability of the extruder at the lowest melt viscosity and earliest solid/melt transition.
For moisture sensitive resins, drying must be performed prior to melt processing. OQ/PQ runs will qualify, based on process history, a temperature setting and drying time as a “black-box” component of the extrusion process. Drying parameters will not be challenged at limits in the extrusion process. In order to add further assurance to the reliability of the drying process, a standalone OQ of the resin drying process will be performed to establish a minimum drying period at a fixed temperature setpoint beyond which the resin will have reached a moisture level low enough to allow processing, based on the resin manufacturers recommended maximum moisture levels. The actual in-process minimum drying times will be set thirty minutes longer than the times qualified in this OQ.
Note:Haul-off speed and screw speed parameters when combined define output. Haul-off speed and screw speed are interdependent (an increase in screw speed must be offset by a corresponding increase in haul-off speed to maintain tubing dimensions). Therefore constraining one parameter automatically constrains the other parameter. If one of the output parameters has an operating window defined, the other output may be set as reference.
5.3.2Other process factors- extrusion
Process components other than those selected as critical for OQ challenge will be fixed for the process during OQ/PQ and subsequently controlled by the EPPS (Extrusion Process Parameter Sheet) which will be released along with the successful validation report and linked to the component router. Such information may include (but is not limited to) the following:
- Tooling (tip, die, helicoid etc.)
- Extruder screw
- Water dam
- Cutter bushing
5.4Component Grouping for OQ and PQ- Extrusion
5.4.1Extrusion grouping criteria
Components will be grouped for validation in extrusion according to the following criteria:
- Same part type (i.e. single lumen, taper etc.)
- Same extruder
- Same resin
5.4.2Selection of challengesettings and components within groups
In order to validate the extrusion process for a component group, it is necessary to bracket the degree of thermal and mechanical work to which the polymer will be exposed. In order to select the representative components from the groupings defined in Appendix 1, the following criteria will apply:
For OQ-Low, the intent is to demonstrate dimensional stability for the process at the lowest acceptable exposure to the effects of heat and shear. Shear relates directly to output rate. Therefore for OQ Low, the component within the group with theleast volumetric output will be chosen as the OQ Low challenge component. Volumetric Output (VO) will be calculated as the product of cross sectional area (CSA) and linear output speed. The component with the least VO requires the least mass flow from the extrusion process. This component will be extruded at the lower temperature for the process group and the lowest output speed for this specific component. This will demonstrate that at OQ-Low settings the process is capable of producing components which conform to specification with a high degree of assurance.
Similarly, for OQ-High, the components with the greatest VO will be run at the upper end of the process setting for temperature for the process group and the highest output speed for this component. This will demonstrate that at OQ-High settings, the process can effectively produce components which conform to specification with a high degree of assurance.
5.5Extrusion OQ
For extrusion OQ, the following runs will be performed:
Process Setting / Temperature / Output speed / Part Cross Sectional AreaOQ High / High / High / High*
OQ Low / Low / Low / Low*
*Where a group has only one component, CSA will not be a challenge parameter.
For each validation grouping, there will be an OQ run at high temperature and output rate for the largest VO component and one at the low temperature and output limits for the smallest VO component for a total of two OQ runs per validation group.
For components validated individually, there will be two OQ runs; one each at high temperature/ output, and low temperature and output settings for that component.
5.6Extrusion PQ
To establish the capability and repeatability required for PQ as defined in S842771-00, the process will be repeated at nominal by running one lot of each component within the validation group at nominal temperature and output settings. For components with less than three components, repeat runs will be performed such that there are a minimum of three PQ runs completed for such groups.
5.7Representativeness of Batch Sizes for Extrusion OQ/PQ
Extrusion validation runs for OQ and PQ will be of sufficient duration to establish confidence that all of the major internalsources of variation inherent to extrusion processes are taken into consideration. The major sources of variations along with the associated cycle times are shown below (Rauwendaal; Polymer Extrusion 4th edition). Internal causes of variation relate to the screw speed, stability of the melting process and temperature fluctuations within the extruder. External causes of variation relate to environmental conditions.
The longest periodicity of internal causes of variation is given as 15 minutes.Validation runs should be at least twice this duration to establish confidence that the process is inherently stable when the validated parameters are used. Therefore a minimum of thirty minutes run duration is a requirement to establish the representativeness of a validation lot per the requirements of S842771-00. Production runs of longer duration may be carried out on the basis of the establishment of short term stability as the process controls are capable of detecting, reacting to and correcting longer term process drift.
5.8Identification of Extrusion Lines
The primary piece of equipment for each extrusion line is the extruder; these will not be interchangeable unless specifically qualified. For the purposes of linking extrusion equipment with OQ/PQ activity, each extrusion line is identified by a number. Appendix 2 of this MVP creates a link between this reference number and the EQP document for the relevant extruder. The currently assigned ancillary equipment will be listed by Extrusion Line in Appendix 2 for reference only. Refer to the Master Validation Reports referenced in Section 3.0 of this MVP for details of IQ reports for equipment.
5.9Interchangeability of Extrusion Equipment
Certain equipment within the extrusion department may be interchanged between lines without affecting the validation status of the equipment or the processes validated thereon*.Equipment which has been identified as such includes:
- Dryers and hoppers
- Chillers
- Lasermikes and other inspection equipment
- Puller/cutters
- Conveyors
- Spoolers/Payoffs
- Air boxes
This equipment has been identified as interchangeable as they are not an integral part of the extrusion line and providing they function correctly are suitable for use across all lines. All of this equipment is mobile and can operate in a standalone manner. They are not controlled or connected in any way by extruder control system.
*Where exceptions to the above statement exist (due to certain specific functionalities required for specific components) these will be detailed in the process control documents (Extrusion Process Parameter Street).
5.10Note concerning software validation for the purposes of Process Validation Remediation
Note: Per Fremont PVR Program Quality Plan 90252432, Section 6.3.2, “Software Validation for manufacturing equipment will be performed in accordance with the Corporate SOP as part of the Software Remediation module. Software will be considered “black box” and tested during IQ for the purposes of Process Validation Remediation.” This is to be held true whether or not it is explicitly stated in individual Installation Qualification protocols and reports.
6.0Validation Rationale- Braiding