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Development of A Validation Method For Thermoplastic Injection Molding Processes For The Contract Medical Device Manufacturer
Development of A Validation Method For Thermoplastic Injection Molding Processes For The Contract Medical Device Manufacturer
Catherine A. Petretich
A Project
May 2005
Committee:
John W. Sinn, Chair
Donna Trautman
Todd C. Waggoner
2
This project is dedicated to my parents, Catherine and Stephen Petretich, for instilling the
values of hard work and dedication, importance of education, and respect for others.
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I would like to extend sincere appreciation to the College of Technology, for the
opportunity to further my education, with a graduate assistantship in the Department of
Technology Systems. The appreciation extends to the graduate college and departmental
staff, especially Kim Strickland and Judy Jennings, who go above and beyond in keeping
customers satisfied.
Special thanks are entitled to Dr. Sinn, my committee chair and graduate advisor. I am
very grateful to have you not only as a teacher, but as a mentor as well. You have
developed my intellectual abilities and academic background. Additionally, you have
managed to contribute to my growth as a Quality Professional, by building my
confidence and reinforcing my capabilities. Thank you for expanding my knowledge of
this “weird stuff”!
I would like to thank my current employer, O-I, and especially Dennis Swary, my
supervisor, for encouraging my project topic and allowing me to present, at the
development park. Thank you for the opportunity to develop new skills, challenge
existing abilities, and advance professionally.
Finally, I am very thankful for my sisters: Debbie, Chris, Judy, and Cindy! I immensely
appreciated all of your charitable donations received during my early graduate school
days. Also, I especially appreciated your wisdom and encouragement. Thank you for
being my sisters and for your love and support!
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TABLE OF CONTENTS
Page
Objectives ………………………………………………………………. 8
Assumption …………………………………………………………….. 8
Terminology …………………………………………………………… 9
Endnotes ……………………………………………………………….. 10
Bibliography …………………………………………………………….. 31
CHAPTER I.
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INTRODUCTION
In order to keep a competitive edge, companies are attempting to expand their core
competencies. The core expansion may impact a company’s regulatory umbrella, since
it often involves expansion from industry with minimal regulations to industry with more
and stringent regulations. This is most evident in the medical device sector of the
practice for medical device manufacturers. A June 1999 poll identified that 80% of
medical device manufacturers reported outsourcing part of their business, 71% reported
use of contract services increased between 6 and 15% in the previous two years, and 35%
expected their outsourcing to increase by more than 10% within their companies in the
The statistics indicate an upward trend in the medical device market for polymer-
Such alliances can pose challenges to quality systems. The medical device manufacturer
measures into quality systems that assure compliance with their governing body, the
Food and Drug Administration (FDA). Changes to the good manufacturing practices
(GMPs) in 1996, by the FDA, put more emphasis on medical device manufacturers to
place controls on their component suppliers to assure that the components are safe and
effective for use as designed. Since then, device owners are requiring their suppliers to
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2001).
meeting expectations of process validation for plastic molding and component assembly
such as those instated by the FDA, must occur in order to be able to communicate with
the customer and to meet their needs. Furthermore, not all established quality
firms want to be able to evidence, to the FDA during audits, that their device components
manufacturer, must review their current infrastructure and quality system to determine
changes that must occur in order to achieve compliance to applicable FDA regulations
and in turn appeal to medical device manufacturers. One of their biggest undertakings
The Quality System Regulation is the FDA’s directive for medical device manufacturers.
When outsourcing part(s) of the manufacturing process, the device manufacturer often
The most delegated code requirement to the injection molder is section 820.75,
Process Validation. This section of the regulation dictates: “where the results of a
process cannot be fully verified by subsequent inspection and test, the process shall be
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procedures” (21CFR 820.75). This presents the molder with the challenge of how to
qualify related equipment, such as the mold and press as well as the injection process.
Although the FDA has published guidelines for process validation, see Quality
2). Contract molders struggle with creating an efficient and well documented method to
achieve validation of the molding process. For this reason, a procedure that describes
how to conduct, what tools to employ, and what data to document to achieve process
validation for injection molding, that is based on FDA guidelines and that would appeal
Problem Statement
In the United States, the overseeing body of medical device manufacturing is the
Food and Drug Administration (FDA). It is a public safety agency, which was
established to correct industry abuses in the early 1900s (Dickinson, 2000). The FDA’s
directive for medical device manufacturers is the Quality System Regulation, 21CFR-Part
820. Per the regulation, FDA advocates process validation, specifically, section 820.75
Process Validation. For medical device manufacturers, the regulation dictates: “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
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There is no doubt, that the validation rule, when applicable, is enforced by the FDA.
For instance, Vanguard Medical Concepts, of Lakeland, Fl, received a warning letter,
known as a “483”, from the FDA for failure to validate a cleaning process with a high
degree of assurance per 21 CFR 820.75(a) (Dickinson, 2000). During audits, FDA is
which explains the methods used to validate a process and a report, which interprets the
data collected during validation and concludes if the process has been validated or not.
FDA is expecting the device manufacturer to show that their processes are in control.
They will be expecting manufacturers to demonstrate that they can maintain control and
will be auditing to see how much control they have over their processes (Allen, 2004).
Therefore, the device manufacturer will have high expectations for their suppliers.
According to the injection molder Unimark’s Joe Pack, “a lot of customers are telling us:
‘You’re required to have your process in control’.” Injection molders, like DeRoyal
Plastics Group’s Bill Pittman, claims process monitoring “is a big selling point for them”
(Leventon, 2001).
Process validation is the basis for process control. A well orchestrated validation will
identify variables that impact the process significantly, challenge the process by assessing
performance at the processing extremes, and conclude the optimum processing window.
equipment, materials, inspection systems, and procedures that are required for
production. Once a process is defined and the impacting variables are identified, process
control can be achieved. Therefore, process validation not only ensures compliance to
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output. It also can reduce costs, which is good for business (Sahni-Larsen, 1996).
[Find and add stats. of: non-compliance citations to section 820.75 (483s). Cite molders
Objectives
For this project, four objectives were designed to address the problem. They are as
follows:
molding process.
process.
Assumptions
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Terminology
There are many terms utilized in the medical device and molding industries, as well as
in the process validation discipline. Terms unique to this project are listed below.
Footnotes were used to reference the sources, which can be found at the end of this
Acceptable Quality Level (AQL) - The maximum percent non-conforming (or the
maximum number of nonconformities per hundred units) that, for the purposes of
sampling inspection, can be considered satisfactory as a process average.⁴
Good Manufacturing Practices (GMP) - Original title of the code of federal regulations
for medical device manufacturing, today referred to as Quality System Regulation, 21
CFR Part 820. ²
Thermoplastic Injection Molding – A process by which, the plastic material is melted and
then injected into a mold cavity and cooled to a shape that reflects the cavity and core. ³
Validation Protocol – A written plan stating how validation will be conducted, including
test parameters, product characteristics, production equipment, and decision points on
what constitutes acceptable test results. ¹
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Food and Drug Administration (FDA) – The United States regulatory authority charged
with, among other responsibilities, granting IND and NDA approvals. ²
ENDNOTES
CHAPTER II.
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REVIEW OF LITERATURE
thermoplastic injection molding, and the tools used to conduct process validation.
PROCESS VALIDATION
Per the Quality System Regulation, 21CFR-Part 820, FDA advocates process
manufacturers, the regulation dictates: “where the results of a process cannot be fully
verified by subsequent inspection and test, the process shall be validated with a high
In addition to the regulatory requirements, there are many reasons for validating
processes. A properly validated process will yield little scrap or rework and result in
complaints and recalls. Also, the validation documentation will contain data that can
support improvements in the process or the development of the next generation of the
process (http://www.fda.gov/cdrh/dsma/gmpman.html).
type validation that is conducted prior to the distribution of either a new product, or
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product made under a revised manufacturing process, where the revisions may affect the
Before process validation can begin, there are preliminary activities that must occur.
These activities include defining the product to be produced and how it will be produced.
This includes defining the product in terms of performance characteristics, translating the
characteristics into specifications, and considering the product’s end use (Weese and
Buffaloe, 1998). Most of these activities are accomplished during product design and
Once the specifications are determined, process validation can begin. Process
validation can be broken down into three phases: Installation Qualification (IQ),
used in a process is constructed and installed according to the approved design criteria
(Schikora, 2000). It establishes by objective evidence that all key aspects of the process
and ancillary equipment adhere to the manufacturer’s approved specifications and that
the recommendations of the equipment supplier have been considered. Items to consider
for the IQ phase are listed in Table I. Some validation activities may be performed at the
equipment supplier’s site prior to shipping the equipment. However, it is usually not
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evaluating, challenging, and testing the equipment and deciding whether the equipment is
Safety features
Software documentation
The operational qualification serves to test any operational aspects of the installed
equipment. In addition, it also establishes the operating parameters for the process, in
this case- injection molding. The process parameters should be challenged to assure that
they will yield a product that meets all defined requirements under all anticipated
Items to consider including into the OQ phase are listed in Table II (GHTF/SG3/N99-
10:2004(Edition 2)).
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Process control limits (time, temperature, pressure, line speed, setup conditions, etc.)
Software parameters
Training
Short term stability and capability of the process (latitude studies or control charts)
After the IQ and OQ are completed, the performance qualification can begin. The
acceptable product under normal operating conditions. Items to consider for the PQ
phase are listed in Table III (GHTF/SG3/N99-10:2004(Edition 2)). During the PQ,
validations lots of the product are produced under both normal and worst-case process
parameters with normal operators and normal in-process controls (Schikora, 2000).
reasonable set of extreme operating conditions for the qualification. In addition, the
question of the number of lots or batches that should be made and sampled often arises
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during this phase. Statistical rationale should be utilized to determine the amount of
product to produce during the PQ run. In the absence of statistical rationale, the common
INJECTION MOLDING
the process requiring validation. Since the primary objective of this project is to develop
a method for validating an injection molding process, the injection molding process and
process by which plastic material is melted and then injected into a mold cavity. Once
the melted plastic is in the mold, it cools to a shape that reflects the mold cavity and core.
The form obtained is referred to as the finished part (TECH MOLD INC., 1993-1999).
Press
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There are several types of injection molding machines or “presses” available with
different methods for blending, melting, and injecting the polymer into the mold. They
are available in a range of sizes, offer choices in clamp tonnage, machine capacity, and
screw design, depending on the needs of the application (Miller, 1996). Injection
molding machines can generally be classified into three categories, based on machine
components
(http://www.scudc.scu.edu/cmdoc/dg_doc/develop/process/control/b1000001.htm).
The following provides a brief description for each of the major injection molding
machine components.
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Injection System
assembly, and an injection nozzle. Figure 2 illustrates the injection system. This system
contains and transports the plastic as it moves through the feeding, compressing,
(http://www.scudc.scu.edu/cmdoc/dg_doc/develop/process/control/b1000001.htm).
As illustrated by Figure 2, the hopper serves to hold the thermoplastic material that is
supplied to molders in the form of small pellets. The pellets are gravity-fed from the
hopper into the barrel and screw assembly. The barrel of the injection system supports
the reciprocating and plasticizing screw. This screw is used to compress, melt, and
convey the material. The nozzle connects the barrel to the sprue bushing of the mold and
creates a seal between the barrel and mold. The nozzle temperature should be set to the
Mold System
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The mold system is comprised of tie bars, stationary and moving platens, as well as
molding plates that house the cavity, sprue, and runner systems, ejector pins, and cooling
channels, as exhibited in Figure 3. The mold acts as a heat exchanger, where the melted
thermoplastic solidifies into the shape and dimensions of the cavity. The mold system, as
shown, is an assembly of platens and molding plates typically made of steel and shapes
the plastic inside the mold cavity, or cavities, and ejects the molded part
(http://www.scudc.scu.edu/cmdoc/dg_doc/develop/process/control/b1000001.htm).
Hydraulic System
The hydraulic system of an injection molding machine gives the power to open and close
the mold, build and hold the clamping tonnage, turn the reciprocating screw, drive the
reciprocating screw, and energize ejector pins and moving mold cores. The hydraulic
(http://www.scudc.scu.edu/cmdoc/dg_doc/develop/process/control/b1000001.htm).
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Clamping System
The clamping system serves to open and close the mold and supports and carries the
other mold parts. It also creates force to prevent the mold from opening
(http://www.scudc.scu.edu/cmdoc/dg_doc/develop/process/control/b1000001.htm).
Control System
injection speed, screw speed and position, and hydraulic position. The process control
has a direct impact on the final part quality and the process economics
(http://www.scudc.scu.edu/cmdoc/dg_doc/develop/process/control/b1000001.htm). This
Now that there is a basic understanding of the injection molding equipment, the
injection molding process must be understood. The injection molding cycle can be
broken down into four phases: fill, pack, hold, and cooling/plastication. See Figure 4.
The process begins with mixing and melting of resin pellets. The molten polymer moves
through the barrel of the machine and is forced, through injection, into the steel mold. As
the plastic fills and packs the mold, the part takes the mold’s shape and begins to cool.
The molded part is then ejected from the mold and ready for any finishing steps and/or
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Eject Fill
Pack
Hold
Cool/Plastication
Process Parameters
Machine selection, material properties, and part design are factors that can impact
the injection molding output. However, there are five specific injection molding
processing variables that can have as much or more impact on the process’s success. The
variables are: injection velocity, plastic temperature, plastic pressure, and cooling
temperature and time. Controlling these variables during the injection cycle’s phases,
can help to improve part quality, reduce part variations, and increase overall productivity
(Miller, 1996).
During phase 1, or fill, the screw advances and plastic flows into the mold. Flow
characteristics are determined by melt temperature, pressure, and shear rate. Injection
velocity, the rate at which the screw moves, is the most critical variable during the fill
velocity is too high, it can cause excessive shear and result in problems such as splay and
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jetting. Also, heat from a higher shear rate can degrade the plastic, which negatively
The way plastic flows during fill is also affected by their viscosity, or resistance to
flow. High viscosity polymers are thick and those with low viscosity are thin and flow
more easily. Melt temperature affects viscosity and should be maintained within the
Plastic pressure also plays a part during fill, since it increases sharply. The melted
plastic can be under greater pressure than is indicated by the hydraulic pressure.
Therefore, it is important to understand the flow characteristics of the material being used
In phase 2, or pack, the melted plastic is compressed and more material is added to
make-up for any shrinking during cooling. Approximately 95% of the material is added
during the fill phase and a remaining 5% is added during pack. Plastic pressure is the
impacting variable during the pack phase. The screw maintains the pressure for the melt,
making-up for any shrinkage, which can cause sinks and voids. Cavity pressure
variations are the main cause of deviations in plastic parts. Therefore, it is important to
completely fill the mold and to avoid over packing and under packing, since pack
pressure determines part weight and part dimensions. Over packing can result in
dimensional problems and difficulty in part ejection. On the other hand, under packing
can result in short shots, sinks, part-weight variations, and warping (Miller, 1996).
Phase 3, or hold, is impacted by all five process variables stated earlier: injection
velocity, plastic temperature, plastic pressure, and cooling temperature and time. After
the mold is packed, the plastic remains in the mold until it is partially solidified and the
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gate freezes. A drop in plastic pressure reveals the amount of shrinking that occurs from
cooling. This phase can be optimized by decreasing the hold time until the part weight
changes. At this time, the gate is no longer sealed and resin backflows out of the mold.
Continuing hold, after the gate seals, increases cycle time, which uses more time and
energy to produce the part. Therefore, it is important to maintain pressure on the plastic
Phase 4, or cooling and plasticizing, is usually the longest part of the molding cycle,
often 80% of the cycle time. Substantial gains in productivity can be yielded by
optimizing cooling time. Since gates are sealed during this phase, cooling temperature
and time are the only variables at work. The cooling phase can be optimized by
balancing the desire to cool rapidly against the quantity of molded-in stress that the final
As with most trades, it is advantageous to have tools that assist with accomplishing
the task at hand. The procedure created for this project describes the tools and their use
in validating the injection molding process. The following provides background on the
tools selected.
Validation Plan, or “MVP” as often referred to in the medical device field, is an essential
planning tool for the validation process. The MVP serves to outline all the
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project. Although the MVP can be formatted in many ways, it usually contains the
included.
described.
should be included.
project.
Design of Experiments
manufacturers can improve quality, cut costs, and increase confidence in results
Protocol
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Protocol = written document describing the method (s) utilized and data to be collected
Report
Report = written document that interprets data collected and concludes if/ if not the
CHAPTER III.
METHODOLOGY
This chapter lists the methods used to develop and to prove regulatory compliance of
a procedure for validating an injection molding process, which was the project’s focus.
This chapter begins with a restatement of the problem followed by research design,
procedure outline, documentation template outline, gap analysis, and the project timeline.
Problem Restatement
The problem for this study is to develop a validation procedure for thermoplastic
Research Design
Qualification. The following explains the phases with respect to injection molding.
Installation Qualification
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For injection molding, the installation qualification pertains to verifying that the
injection press is installed properly and capable of running the related mold. The
installation qualification protocol should describe the necessary test procedures to verify
that the press is installed as specified. These qualifications generally include check
sheets that describe: testing of emergency stops, guards, and interlock features, wiring
verification, and identification of critical spare parts (Schikora, 2000). The installation
qualification protocol template developed for the project will include checks for safety
supporting utilities.
Operational Qualification
four hour capability/mold acceptance run. Figure 5 displays the operational qualification
outline.
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Engineering S
Engineering tudies
Studies
• Viscosity Testing
• Gate Freeze Testing
• Hold Time Testing
• Process Characterization
As outlined in Figure 5, the press operational aspects are those key to running the
press. Test and critical instruments requiring calibration and used in the molding process
control system screen navigation features per the equipment supplier’s documentation.
Controls verification verifies that all system controls identified are functioning per the
equipment supplier’s documentation and assures parameter settings established for the
mold. Alarm verification serves to verify that they function as required. Reject
Training verification should be conducted to assure that all appropriate personnel are
to all of the described press operational aspects will be created and included in the
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parameters. It identified five specific molding processing variables that can have as
much or more impact on the process’s success. The variables were: injection velocity,
plastic temperature, plastic pressure, and cooling temperature and time. It was also noted
that controlling these variables during the injection cycle’s phases, can help to improve
part quality, reduce part variations, and increase overall productivity (Miller, 1996).
Based on the processing variables’ potential impact, the following verifications were
incorporated into the validation: Viscosity Testing, Gate Freeze Testing, and Hold Time
validation is challenging the process to determine what happens when conditions arise
that cause stress, worse case testing. These challenges are collectively referred to as
varied and sources of variation having the most impact on the process are determined.
The Design of Experiment technique is not new to the health-care industry. Medical
Recent focus by FDA on process validation highlights the need for well-planned
experimentation. Such experiments can provide data that will enable device
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both the mold and injection press. This testing, employing DOE, serves to identify the
influence of the equipment on the mold by understanding the effects of the process
parameters on critical part dimensions and quality characteristics. This method will
challenge the high and low settings with respect to the machine’s process parameters of
pressure and temperature. It will challenge the ability of the press and mold to produce a
capable part at the extremities, high and low, of pressure and temperature combinations.
The window study will be executed using the information developed and recorded in
the process data packet. The press settings will be set at each corner and centerline and
run for at least 1 hour. After a 15-minute settle time, samples will be labeled and
collected throughout the runs. Part critical quality characteristics, as determined by the
customer, will be sampled and evaluated according to ANSI/ASQC Z1.4, single, normal,
level II. In addition, there will be an inspection of critical part dimensions, as determined
The acceptance criteria for the window study will employ additional statistical tools,
Statistical Process Control (SPC) charting and process capability (Cpk). SPC charting,
used since the 1940s for monitoring production results, provides a visual method for
identifying samples that are outside of normal, expected variability. With sufficient
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sampling, a process capability index, Cpk, can be calculated to determine how well the
process results are centered within a specification range and how well variability is
controlled. When results vary greatly, a greater percentage of the results have the
tendency to fall outside the specifications. This means the process is less capable,
By employing the statistical tools of SPC charting and process capability (Cpk), the
through control charting for all critical part dimensions. 2) All critical part dimensions
must demonstrate a value of Cpk ≥ 1.33 per mold cavity and a Cpk ≥ 1.00 for overall
cavity to cavity average. 3) All critical quality characteristics must meet the accept/reject
It should be evident that the engineering studies are the key aspect of the operational
qualification phase. By executing the described phases, the result should be a processing
window that is well defined for the press and mold requiring validation. These results
can then be confirmed through a 4 hour capability study. The capability study is a 4 hour
run using the determined “optimum” process parameter settings. After a 15 minute settle
time, one full shot of parts will be collected every 10-minutes totaling 24-shots.
The acceptance criteria for the run are as follows: 1) All critical dimensions must
demonstrate a value of Cpk ≥ 1.33 for each individual cavity and a Cpk ≥ 1.00 for overall
cavity-to-cavity average and 2) All critical quality characteristics must meet the defined
AQL.
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Performance Qualification
developed for the project serves to address the reproducibility aspect. It will consist of
molding three lots of the desired product within the process parameters established from
production run with all operating procedures having been established and with all
participants having been trained in the applicable procedures. The protocol will define
the lot size. Part sampling for the customer required dimensional and attribute
1993 sampling plans. The acceptance criteria for each lot are as follows: 1) All critical
dimensions must demonstrate a value of Cpk ≥ 1.33 for each individual cavity and a Cpk
≥ 1.00 for overall cavity-to-cavity average and 2) All critical quality characteristics must
meet the defined AQL. If all three lots meet the acceptance criteria, the process will be
Procedure Outline
Standard operating procedures (SOPs) are essential for any plant’s effectiveness and
efficiently, and effectively. They describe processes and important steps in the
processes, and help workers remember how to perform tasks. Procedures are also useful
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The procedure created for this project will establish generalized process validation
standards and guidelines for medical classified product for a team oriented organization.
It will identify the following: Process Owner, Purpose, Scope, and Responsibilities. It
will describe the general validation activities from pre-validation to re-validation. It will
list related terminology, references, forms, and templates, with the most attention being
placed on the Injection Molding Template. This template will include evaluation criteria
and documentation for all three qualification phases: IQ, OQ, and PQ.
PROCEDURE ELEMENTS
Emphasizes critical steps and does not contain trivia, unimportant details, or fundamental
information that the user is certified as knowing from experience or training.
Defines responsibilities.
Lists activities sequentially. The core of a good procedure can be a process flow
diagram.
Is concise, ideally, 3-4 pages long. The likelihood of reading, remembering, and
complying decreases with the number of pages.
Is simple and should be written for 6th- to 8th-grade readability.
Makes liberal use of visual aids such as flow diagrams, photos, drawings, and color. A
chart that is appropriately numbered and controlled could be considered a procedure.
Includes forms that ideally are self explanatory.
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Gap Analysis
In order to prove that the procedure developed would meet the provisions for
process validation set forth by the Quality System Regulation 21 CFR-Part 820, a
Gap Analysis was created to assess the procedure’s content against the regulation’s
section for Process Validation, 820.75. Gap Analysis is a technique which permits a
The gap analysis created served to prove that the procedure developed was
Quality System Regulation, 21CFR-Part 820. This was identified as the desired state
in the gap analysis document. See Appendix X, for the “Process Validation Gap
Analysis” that was created to assess the procedure developed for this project.
developed from the regulation, 21 CFR-Part 820, Subpart G- Production and Process
statement form.
For response to the questionnaire, three options were provided: Yes, No, and N/A.
The “Yes” option was reserved for cases where requirements were met or guides have
been incorporated. The “No” option was reserved for cases where requirements were
not met, indicating a “gap”. It also indicated that the related procedural element
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required an adjustment, to meet a requirement. The “N/A” option was reserved for
situation. To support each response, the questionnaire allotted space for recording
evidence, as to whether or not the requirement was meant. The results of the gap
Project Timeline
A Gantt chart was developed to show the time allocated for each of the major
project activities.
2004 2005
TASK Sept. Oct. Nov. Dec. Jan. Feb. Mar. Apr.
Review of
Literature
Proposal
Development
Submit Proposal
Develop
Procedure
Outline
Develop
Documentatio
n Template
Prepare Final
Drafts
Formulate
Conclusion
and submit
project
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CHAPTER IV.
This chapter lists the developed procedure and all related supporting documentation,
as stated in the objectives of Chapter I. In addition, the results of the Gap Analysis are
stated, which was conducted to prove the procedure’s compliance to the 21CFR Part 820,
Deliverables
There were four objectives designed to address the problem. The project objectives
were met by creating ten deliverables. Table X lists all the deliverables and a brief
PROJECT DELIVERABLES
Deliverable Description
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Validation Procedure
The primary deliverable was the Validation Procedure, which can be found in
Appendix X. As stated in Chapter III, the procedure created for the project would
establish generalized process validation standards and guidelines for medical classified
product, for a team oriented organization. Therefore, the procedure was entitled
responsibilities, see page one of the procedure. It identifies a process owner, the
individual who would be responsible for overseeing the procedure. The procedure
defines a purpose and scope. It also lists the team members and their responsibilities.
Methods for the validation process begin on page two. Pre-validation activities are
explained, along with the use of the “Pre-Validation Checklist”. These activities
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serves to assure that all supporting items are in place prior to scheduling of an operational
qualification. The Qualification Log and the planning tool, Master Validation Plan
Page three of the procedure introduces the concept of a validation protocol, which is
defined as a document that describes the validation phase, the testing methods, and the
evaluative characteristics that will be utilized to qualify a process. It also lists the
protocol content that should be addressed at each validation phase. The protocol
templates for injection molding are mentioned, in this section as well. The significance
of acceptance criteria and data forms are presented, along with how to obtain protocol
Protocol deviations and discrepancies are explained on page five. Page five also
addresses validation scheduling and reporting, including report content and report
reference to the protocol addendum template. Page six of the procedure contains
definitions for terms that are unique to the validation topic. This page also provides
explanation of re-validation. Page seven contains sections for listing related references,
documents, records or forms, appendices, revision history, and suggested individuals for
training.
The master validation plan (MVP) is a planning tool for the validation process. See
Appendix X, for the MVP template developed for use with the procedure. This
document, which should be assigned a control number from the Qualification Log, is
designed to consider all equipment and processes requiring validation for a medical
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device project. It establishes guidelines for employing statistical tools for analyzing data
classifications, and acceptable quality levels (AQL), it states the basis for attribute and
Besides providing statistical and sampling rationale, the MVP contains a “Validation
Matrix”, see pages five and six of the plan, which lists all items to be qualified, such as
the qualification task needing performed, such as IQ, OQ, and PQ. For all validation
tasks identified, the matrix has a section for documenting the responsible party, for each
task.
Beginning with page seven of the MVP, sheets are provided for detailing each
qualification in its entirety. The sheets can be customized to account for each item’s
unique requirements. For example, a sample sheet is provided for a molded component.
It details each qualification phase, IQ, OQ, and PQ, that must be completed.
Subsequently, it lists the key quality characteristics, along with their acceptance criteria
that must be evaluated at each phase. There are also additional qualification outline
sheets that are provided for adapting to finishing equipment and purchased components.
Qualification Log
The purpose of the qualification log is to control all validation protocols and reports,
number for each. See Appendix X, for the log. The log is comprised of three sheets, a
sheet for each qualification type. There is a sheet to track all validations, known as the
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“Validation Control Log”. The Validation Control Log contains four columns. One
column, labeled “Document #”, documents the number assigned, along with the “VAL”
prefix to designate that it is a validation. In addition, there are columns for identifying
the related project, type of qualification (IQ, IOQ, OQ, or PQ), description, and
comments.
There is also a sheet for recording test method verifications, known as “Test Methods
Control Log”. This log provides for documenting numbers assigned to test method
will be verified prior to implementation. The number assigned will also contain a prefix,
“TM”, to designate that it is a test method verification. This sheet also contains columns
The log also provides a sheet for controlling all master validation plans, identified as
“Master Validation Plan Control Log”. This log provides for documenting numbers
assigned to master validation plans. The number assigned will also contain a prefix,
“MVP”, to designate that it is a master validation plan. This sheet also contains columns
Pre-Validation Checklist
The pre-validation checklist, see Appendix X, was created for use with the validation
activities were completed. A review of the checklist will indicate that key aspects to
achieving validation, such as specifications, training, and procedures, have been reviewed
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The installation and operational qualification requirements for injection molding were
and Operational Qualification” and abbreviated as IOQ. See appendix X, for the IOQ
The first five pages of the template consist of a cover page, which identifies the
identification log. An introduction section follows, which lists the objective, purpose,
and scope of the qualification. It also identifies responsibilities of the qualification team
and commonly used abbreviations. Another section, entitled “Data Collection and
while executing the protocol. It also explains the use of attachments, for documenting
the qualification data. Furthermore, there are sections that describe the use of the
The verifications are comprised of a test description, test procedure, acceptance criteria,
and test results. The verifications have a corresponding attachment for listing the items
checked, related acceptance criteria, actual results, and required sign-offs. A majority of
installation verifications are focused on safety and are based on the Plastics Machinery-
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systems that may comprise the injection system. There are verifications for electrical and
procedures and schedules. The template also has checks for verifying that a preventative
maintenance and spare parts program has been established for the injection system.
initial verifications in the OQ consist of verifying the operational aspects of the injection
press and the mold. The verifications are formatted similar to those for the IQ. They are
comprised of a test description, test procedure, acceptance criteria, and test results. They
also have a corresponding attachment for listing the items checked, related acceptance
criteria, actual results, and required sign-offs. The initial tests confirmed identification of
critical instrumentation and training and procedural aspects for the OQ. There were also
verifications that assessed that the control, alarm, and security features of the injection
The next section of the OQ is entitled “Engineering Studies”, see page 19 of the IOQ
template. The engineering studies involve activities required during initial process
development. These studies are formatted according to a test description, test procedure,
and criteria to proceed. The activities consist of identifying the required settings for the
window, viscosity, gate seal, and hold time tests. This development testing is described
in the “Process Development” sub-section of the engineering studies. The results are to
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studies. It is represented by a four corner window study. This study serves to identify
the influence of the equipment on the tool, by understanding what effects the process
parameters will have on the critical part dimensions and quality characteristics. It will
challenge high and low settings with respect to the machine’s process parameters of
The window study challenges the ability of the press and mold in producing a capable
part at the pressure and temperature combination extremes: high temperature / high
pressure, high temperature / low pressure, low temperature / high pressure, and low
temperature / low pressure. During these challenges, the molded parts will be taken to
their fracture point. A fracture is defined as a condition where the parts begin to exhibit
attribute defects. Once the fracture point is identified, the settings for both temperature
and pressure will be reduced until an acceptable molded part is obtained. These settings
will be considered the worse case parameters capable of producing a part within
specification. The corner settings established during the process development activities
and recorded on the processing sheet are used during the window testing.
Once the window study yields the four processing corners and a process centerline, a
mold acceptance run can be conducted. The acceptance run serves to confirm the settings
established during the process development phases. It consists of a four hour capability
study run at the process centerline. During the run, parts will be collected at required
intervals and inspected for the defined quality characteristics. All critical part
dimensions must achieve a Cpk ≥ 1.33 per cavity and a Cpk ≥ 1.00 for overall cavity-to-
cavity average. All part attributes must meet the required accept/reject criteria per the
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specified AQL. The acceptance run activities are described beginning on page 20 of the
template. They are formatted according to a test description, test procedure, and
section that offers concluding remarks and reporting instructions. This section is entitled,
serves to prove that a process is reproducible and effective. The PQ template describes
The template is formatted similar to the IOQ template. The first five pages of the
template consist of a cover page, which identifies the protocol number, a table of contents
follows, which lists the objective, purpose, and scope of the qualification. It also
instructions for data collection and documentation, while executing the protocol. It also
explains the use of attachments, for documenting the qualification data. Furthermore,
there are sections that describe the use of the deviation and discrepancy form and an
equipment listing.
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The X section of the template describes the practice of molding three lots of the
desired product within the process parameters established during the operational
qualification. The protocol will define a lot size. Part sampling, for the required quality
Lot acceptance is based on all critical part dimensions meeting a Cpk ≥ 1.33 per
cavity and a Cpk ≥ 1.00 for overall cavity-to-cavity average. In addition, all attributes
must meet the defined AQL. If all three lots meet the acceptance criteria, the process will
be considered validated. With the acceptance criteria being met, the product produced
A reporting template was created for use with the validation procedure. See
Appendix X, for the report template. For each executed protocol, per the procedure,
there must be an accompanying report. The report template can be used for any type of
validation protocol, IQ, IOQ, OQ, PQ, or even an addendum. The report summarizes
validation results and presents evidence that the protocol requirements were or were not
met.
results. It contains a section, labeled as the system description, for documenting the
equipment involved in the qualification. A testing results section is included for stating
the results of the protocol testing and explaining any deviations or discrepancies that
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might have occurred. A conclusion section is provided for stating whether or not the
requirements of the protocol have been met. There is also a section, entitled ongoing
controls, for assuring that the validated system remains in a state of validation. In
addition, an appendix can be created to file all data compiled during protocol execution.
original protocol, when the original protocol requirements were not met. See Appendix
A protocol addendum is similar to the original protocol, except that the introduction
should reference the original protocol and explain the discrepancy or incident that the
addendum is to address. The addendum may include all or part of the original protocol
and must be reported, reviewed, and approved. Each addendum must be assigned a
number from the validation control log. The number should be followed by the letters
Process Sheet
A form, entitled “Process Sheet”, was created for use with the validation procedure, for
documenting all key injection molding process parameters and information. See
Appendix X, for the form. The process sheet contains a general section for identifying
the mold, number of cavities, material, additives, shot weight, and cycle time. Specific to
processing, it contains records for plastic temperature, plastic fill rate, plastic pressures
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Another form, entitled “Discrepancy and Deviation Form”, was created for use with the
validation procedure. This form documents any case where the approved protocol
methods were deviated from, defined as a “deviation” by the procedure, or where the
stated protocol acceptance criteria was not met, defined as a “discrepancy” by the
procedure. See Appendix X, for the form. The top portion of the form identifies the
related protocol and allows for a selection between a deviation and a discrepancy.
Depending upon which is selected, the form user is directed to the appropriate section for
further completion.
number, the protocol section/page that was affected, and a brief description of the
change. Spaces are provided for the person making the entry, to date and sign. For a
discrepancy entry, a consecutive number must be assigned, the protocol section/page that
was affected, and a brief description of the occurrence must be completed. The person
entering must sign and date the entry as well. The investigation and root cause section
must be completed by an assigned individual, who should sign and date the entries. The
corrective action section should be completed by the assigned individual, who should
sign and date their entry. A section for documenting that the discrepancy was reviewed
For the project, a gap analysis was conducted to prove that the procedure developed
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820, Subpart G- Production and Process Controls, Section 820.75 Process Validation.
The questionnaire was designed to identify gaps in methods established for process
validation. Appendix X contains the gap analysis that was completed for the project.
Five questions were created for the assessment. All five questions were answered,
by the researcher. For each response, supporting evidence was provided. Supporting
documentation. The related documentation could have been forms, templates, plans,
or logs that were created specifically for use with the procedure.
The first question assessed whether a method exists for documenting validation
activities and results, including the date and signature of the individual(s) approving
the validation and where appropriate the major equipment validated. A “Yes”
response was noted, for the developed procedure’s compliance to this aspect of the
supporting evidence. Section 4.4 of the procedure stated that a protocol must be
procedure’s Section 4.12 stated that a report is required for summarizing the results.
Finally, Sections 4.8 and 4.13 of the procedure accounted for approval signatures.
established to monitor, maintain control of process parameters, and ensure that the
specified requirements continue to be met. A “Yes” response was noted, for the
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evidence was also noted. Section 4.1.4 of the procedure identified pre-validation
activities, which consist of verifying that the manufacturing process has been defined
Question three inquired if the validation procedure ensured that validated processes
were performed by qualified individuals. A “Yes” response was noted, for the
developed procedure’s compliance to this aspect of the regulation. Section 4.1.8 and
the protocol templates of the procedure were listed as supporting evidence. Section
4.1.8 stated that pre-validation activities consist of verifying that operators are trained
and that training is documented. Further, the IOQ and PQ protocol templates
and control methods, data, date performed, and where appropriate the individual(s)
performing the process or the major equipment used for validated processes. A
“Yes” response was noted, for the developed procedure’s compliance to this aspect of
the regulation. Section 4.1.4 and the process sheet of the procedure were listed as
consisted of verifying that the manufacturing process has been defined and
on the required documentation. The process sheet represents the data that should be
Question five inquired if the procedure addressed and provided documentation for
revalidation. A “Yes” response was noted, for the developed procedure’s compliance
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to this aspect of the regulation. Section 4.15 was listed as supporting evidence. This
CHAPTER V.
This chapter serves to establish that the objectives for the project were met. It
Conclusion
Chapter I listed four objectives that were designed to address the problem, which was
to develop a validation procedure for thermoplastic injection molding processes for the
1. To establish what parts of and related methods for validating an injection molding
process.
2. To establish a method for worse-case testing for the injection molding process.
3. To establish a procedure that describes the methods determined in objectives one and
two.
4. To establish a template for documenting data collected from performing the procedure,
The first and second objectives are represented by the procedure’s IOQ Template.
The template
Future Implications
Since validation is best achieved through a collaborative team effort, the planning
stage may require input from manufacturing, quality, purchasing, design, and the
business sectors. The validation planning stage permits each department to be engaged
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early in the product development process. A validated process should yield a well
defined process and identify any pitfalls of the process, further up stream verses
The results of proper process validation can yield useful information and assure input
early on, from all facets of the development team/manufacturing process. This aspect of
incorporate customer input into the product early on during development. For this
reason, it is often referred to as the “house of quality”. Process validation has the
BIBLIOGRAPHY
D Allen, “FDA Wants You in Control,” Pharmaceutical and Medical Packaging News,
(April 2004): 10.
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T Miller, “Injection Molding,” Medical Device & Diagnostic Industry, (April 1996): 2-5.
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Cathy,
Points to consider as you clean this up, take next steps, for presentation to committee:
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1. Need to make sure the indents and all other formatting issues and specifications
are on target per APA and BGSU guidelines and standards—must be sure all are
consistent—not bad be sure to double check all.
2. The work should be converted to be past tense throughout since you have done
the work now—it is past—or will be at the point of presentation.
3. Review of literature should be driven by assuring that all elements of the work
have been disclosed and pursued sufficiently—my sense is this is the case and
you can be done with this. May want to use a summary statement on the tail end
of the chapter to explain what was accomplished, consistent with what was
initiated at the outset, and done throughout, per key headings.
4. Headings used throughout, must be per APA and BGSU guidelines/standards to
identify level and type of importance assigned.
5. Chapter III, page 25, needs to be started as a fresh section.
6. Chapter III needs to present each objective and identify steps taken to address the
objective. Do not explain (in chapter III) what was found for each objective or
step, but simply what the steps were to address the objective.
7. At chapter IV, again state each objective, one by one, and what steps were taken
to address the objective (consistent with chapter III). However, now, at each step,
you should discuss what was found, how it was analyzed and so on.
8. At chapter V, similar to previous chapters III and IV, you now need to explain
what can be concluded based on the objectives and steps, and each set of findings
and analysis for the same—but as conclusions. These also become, then, and
therefore, the recommendations for other work to follow.
9. Parts 6, 7 and 8 above, while seemingly fairly redundant, are at the core of good
research—and if you will use the “threaded” logic inherent in this repetition,
generally this will help to flush out what was accomplished, and why, as well as
what then can be stated as legitimate findings, conclusions and recommendations.
10. Also based on points 6, 7 and 8 above, it is possible that the problem and
objectives will shift somewhat as you go back and actually state what you did.
11. Consider changing the problem statement, page 7, to, “The problem for this study
was to develop a validation procedure for thermoplastic injection molding
processes for medical device contract manufacturers”.
12. Consider changing first objective, page 9, to, “To establish what parts of, and
related methods, are necessary for validating an injection molding process”.
13. Bibliography needs to be started as a fresh section.
I suggest you make the adjustments identified by me, and that you had already indicated
in your email—or as agreed in the yellowed areas of your text, and get it finalized for
presentation—and let me see the final draft before you give others a copy.
JWS, 2-26-05
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