Packaging Performance Qualification—A Risk-Based

PEER-R EV IEW ED
Packaging Performance
Qualification—A Risk-Based
Approach
Steen Howaldt Christiansen and Jesper Bønnelycke Torp Jensen
ABSTRACT
This paper describes a risk-based performance qualification (PQ) concept exclusively based on the fundamental
requirements. The result is a cookbook describing a general
methodology for deciding the size and number of PQ runs
needed. The fundamental philosophy is that PQ must
simulate normal production, including the challenges typically seen in that connection. Consequently, the actions
and interventions arising in normal production contexts
are tested rather than a set of specific machine parameters.
The methodology description is intended to be
operational.
This paper focuses on packaging performance qualification as an example, but in practice the concept can
be introduced for all mechanical processes because the
process characteristics are all similar.
In the longer term, this methodology will be proposed
as “Annex C” to the Global Harmonization Task Force’s
(GHTF) Quality Management Systems–Process Validation
Guidance (1).
INTRODUCTION
Since the first US Food and Drug Administration requirements for validating pharmaceutical processes appeared
back in the 1980s (2), and especially in recent years,
validation seems to have become more and more of a
scientific discipline in itself. Books have been written,
magazines and articles have been published, courses
have been held, and an army of consultants have offered
their expertise to pharmaceutical companies.
For more Author
information,
go to
gxpandjvt.com/bios
Often the approach has entailed philosophical considerations of the more or less concrete statements published by the authorities. These considerations always
result in statements such as “It is up to you or your company to decide” or “You have to develop the rationale
for doing things ... and you are the one who knows the
process.” These statements provoke a similar response
from “hands on” people: “Yes, we do want to establish
documented evidence that provides a high degree of
assurance that a specific process will constantly produce
a product that meets its predetermined specifications
and quality attributes (2), but how do we do it at the
operational level?”
The same scenario has been evident in numerous companies. Standard operating procedures (SOPs) dealing
with validation have become more and more philosophical, moving away from the operational approach. And
as the pharmaceutical companies learned the lessons
through the 1990s and accepted “validation” as part of
the everyday business, the routine solutions became more
and more complex and full of rationales for fulfilling
unclear requirements.
To close the gap between the philosophical considerations and the operational performance of validation, the
GHTF published its process validation guidance back in
1999 (ed. 1) and 2004 (ed. 2) (1). This guideline answered
a lot of the questions, but it also left a few unanswered,
such as the following:
•W
hat is the minimum performance quali-
fication (PQ) batch size for assembly and
[
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ABOUT THE AUTHORS
Steen Howaldt Christiansen is a project manager at Novo Nordisk A/S Denmark—Diabetes Finished
Products/Manufacturing Development/Finished Products. He can be reached by e-mail at [email protected]. Jesper Bønnelycke Torp Jensen is an engineer at Novo Nordisk A/S Denmark—Diabetes
Finished Products/Manufacturing Development/Finished Products. He can be reached by e-mail at
[email protected].
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packaging processes? The PQ batch should be
of commercial size (3), but for packaging operations
some customers order three units and other customers order 500,000 units. So is it OK to run the PQ
batches with three units each?
Well 500,000 units seem to be the worst-case scenario. But actually it is not, because when the line
is up and running it is doing the same thing again
and again, irrespective of whether it has to do it for
three units or for 500,000 units. So what kind of
considerations and rationales can be used to determine the relevant batch size for PQ runs?
•H
ow many PQ batches are needed as a minimum? It is clear that “three” is not a “wild guess”
answer (4, 5), but what kind of considerations and
rationales can be used to determine the required
PQ runs?
While Annex A (“Statistical Methods and Tools for
Process Validation”) and Annex B (“Example Validation”)
of the GHTF process validation guidance (1) very clearly
and sufficiently suggest installation qualification (IQ)
and operational qualification (OQ) methodologies for
fulfilling the philosophical requirements, the PQ section
lacks operational methodology. This paper therefore
focuses exclusively on the PQ aspects and proposes a
general methodology for translating the philosophical
PQ definitions into operational terms.
The scope of this paper is to define and describe a
risk-based approach to performance qualification for
packaging processes for medical devices and pre-filled
devices. This paper does not include IQ or OQ, but only
touches on the purpose of theses stages of a validation
process. This paper concentrates on packaging processes
as an example.
SCOPE
The scope of the GHTF process guideline, Quality Management Systems—Process Validation Guidance (1), is limited to
medical devices, but what about assembly of pre-filled
devices and packaging in general? Pre-filled devices are
usually registered as a drug and, hence, are covered by
FDA in Current Good Manufacturing Practice in Manufacturing Processing, Packaging or Holding of Drugs, 21 CFR–Parts
210 & 211 (6), but the process characteristics for assembly
of pre-filled devices and packaging processes are much
more similar to the processes used for medical device
manufacturing rather than pharmaceutical processes.
So, as also questioned in “Validation—How Much is
Required?” by Sharp J (7), is it then fruitful to adapt the
meaningful testing principles used for pharmaceutical
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processes to the field of mechanical processing, where
the process characteristics are different? The obvious
answer is no. Assembly and packaging processes are
much more similar to medical device processes than to
pharmaceutical processes.
As packaging processes are characteristically
mechanical processes that handle a few items at a time
in a serial sequence (i.e., often checked and controlled
after each step), the approach can be extended to cover
assembly processes in general because the process characteristics are the same. These process characteristics
are somewhat in contrast to traditional pharmaceutical
processes characterised by chemical reactions and mixing operations. It is up to the reader to judge whether
the proposed principle methodology is meaningful
for pharmaceutical processes.
PACKAGING VALIDATION
Packaging is mentioned in both FDA code 21 CFR
210&211 (Drugs) (6) and FDA code 21 CFR 820 (Medical
devices) (8). While FDA code 21 CFR 210&211 (Drugs)
essentially focuses on labelling information and content,
FDA code 21 CFR 820 (Medical devices) also addresses
the package itself.
FDA code 21 CFR 820.130 (Medical devices) states:
“Each manufacturer shall ensure that device packaging
and shipper containers are designed and constructed
to protect the device from alteration or damage during the customary conditions of processing, storage,
handling and distribution.”
This definition means that the entire (package) chain
(see Figure 1) must be “ensured to work as intended.”
The functions of a package are basically to contain,
carry, and protect a product. To transfer a particular product from the place of manufacture to the point of use
requires some kind of container—not only to contain it,
but also to protect it from external damage. If the product
is not intended for immediate consumption, it must be
preserved by some appropriate process. Accordingly,
the package will also serve as a barrier to separate the
preserved items from outside contamination and spoilage. Furthermore, in a modern society the packaging is
used for communication purposes such as promoting,
justifying, glamorising and, especially in the case of
pharmaceutical products, differentiating the content.
All these aspects apply to general packaging, but what
is special about pharmaceutical products is that they are
much more tightly regulated than the rest of the industry
in general.
Figure 1 illustrates the package lifecycle. While packaging validation in a classical context solely applies to the
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S T E E N HOWA L D T C H R I S T I A N S E N A N D J E S P E R B Ø N N E LYC K E T OR P J E N S E N
Figure 1: Package chain.
Local
distribution
Wholesaler
Warehouse
Retail
Production
Consumer
Process Development—Design
Qualification
Package construction and design must be qualified. This is typically done using a simulated
transport test, a stressed transport test, a real
life transport test, and a customer handling
test. To some extent these test procedures are
standardized in the International Organization for Standardization (ISO) series related to
transport (9).
Commercial Production—Materials
And Suppliers Must Be Qualified
Carton
As the holder of a marketing authorisation is
responsible for the final product, the company
is also responsible for the entire supply chain, including
whatever a subcontractor may have delivered. And it is
common for raw materials for packaging operations (e.g.,
product labels, inserts, and cartons) to be provided by
subcontractors or suppliers, in which case the company
is not only responsible for the physical materials themselves, but also for the printed information. Quality and
safety in the supply chain are normally ensured through
an entire set of specifications defining the correct physical
properties and correct information of a given delivery.
In the design phase, it must be ensured that the specification set-up reflects the correct aspects of functional
and marketing criteria, manufacturing and cost criteria, the buyer and supplier relationship, and the quality
control principle.
Commercial Production—Packaging
Process Qualification
A typical high-speed packaging line consists of several
pieces of specialized machinery, usually in series, connected by a moving belt. Figure 3 shows a generic packaggxpandjv t.com
One unit
One unit
Product
Insert and
accessories
Carton
Product
Distribution
Long
haul
Packaging/Unpackaging
packaging process (i.e., labelling, insert, cartoning, wrapping, and case packaging), “package
process validation” covers the entire distribution
chain as well.
Following the general validation model
shown in Figure 2 (5), the package process
validation is the sum of all the activities (i.e.,
qualification, certification, and verification) to
determine that the entire package construction
will work as intended. According to the model
in Figure 2 (5), that means each element in the
entire package lifecycle (i.e., process development as well as commercial production) must
be qualified.
Insert and
accessories
ing line. Depending on the specific set-up, the line can
include more or less of these main processes. In some
cases the line is divided into more stand-alone units,
and in certain cases some of the processes are carried
out manually.
Validation Steps
As illustrated in Figure 2, the qualification of equipment
is carried out in the following well-established steps:
• IQ verifies that the equipment is installed correctly
in accordance with instructions (usually the manufacturer’s instructions)
• OQ verifies that the equipment is able to operate as
expected under all anticipated conditions, including worst case. Clearly the IQ should be completed
before OQ begins.
• PQ verifies that the equipment consistently produces acceptable products under normal operating
conditions. The OQ should be completed before
PQ begins.
• Routine production monitors the trend in daily production data and market feedback data.
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Figure 2: General validation model (5).
Process Validation Timeline
Commercial production
Process development
Prepare
Install equipment
Installation
qualification
IQ
DQ
Operational
qualification
OQ
Develop
Process
Start up
Process
qualification
PQ
Discontinue
Routine production
Monitor trend
Monitor
Validation
instrument
calibration
equipment
Product
development
Operations
Validation
Product
Time
Using the model for package process validation, the validation will not only include validation of the packaging equipment,
but also qualification of the package design as well as of the raw materials and the suppliers (5).
While IQ and OQ seem to be manageable, PQ often
seems to be problematic and challenging. This has been
pointed out in various places. For example, Carol DeSain
states, “This does not mean an endless number of demonstration runs with each parameter pushed to a minimum
or maximum limit” (10, page 22). Also, Jerry Lanese
states, “How many runs do we have to make to validate
this process? This question is asked every time there is a
discussion about a validation project. Three is the stock
answer. This response is misleading…” (4, Introduction).
So how can PQ also be made manageable?
Definition Of Performance Qualification
Following the leading principle in Validating Medical
Packaging by Ronald Pilchik (11), a strategy for removing the complexity from a system that has become too
complicated is simply to wipe the blackboard, return to
basics, and ask the following:
• What are the exact fundamental requirements we
are going to fulfil? No more, no less.
• How can we translate these requirements, statement
by statement, into meaningful operational terms?
• How can we implement these terms, statement by
statement?
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Going back to fundamental requirements, these are
translated into operational terms, ending up with the
recommendation in GHTF.SG3.N99-10, process validation guidance (1). Here, the following definition of
performance qualification is clear (section 2.3):
“Performance qualification (PQ): Establishing
by objective evidence that the process, under anticipated
conditions, consistently produces a product which meets
all predetermined requirements.”
This definition is translated into the following key
objective of the PQ phase (1, section 5.5):
“In fulfilment of this definition, the key objective
of the PQ activity is to demonstrate that the process
will consistently produce acceptable products under
normal operating conditions, and challenges
to the process should simulate conditions that
will be encountered under actual manufacturing conditions. Challenges must include the range of
conditions that will occur during normal production
as they are defined by the actions and interventions
allowed in written standard operating procedures
(typically established in the OQ phase). The challenges
should be repeated enough times to ensure that the
results are meaningful and consistent.”
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Figure 3: Typical packaging sub processes.
Generic Packaging Line
Leaflet
Product
Upper foil
Product
label
Lower
foil
Labelling
Blistering
Preheat
Stretch
Form
Cool
Perforation
Folding
Cartoning
Price
sticker
Price
tagging
Shipper
box
Wrapping
foil
Stretch
banding
Case
packaging
Palletising
Shipper label
Pallet label
Carton
This interpretation gives operational meaning: First we
have to define what normal operating conditions are and
second we have to identify what kind of typically challenging conditions we observe during normal production. A
list of typical influencing factors is suggested in Quality
Management Systems—Process Validation Guidance (1). The
list in the guidance can be used for inspiration and crosschecking, but Jerry Lanese (5) suggests a more systematic
and consistent methodology for identifying variables that
affect “normal production.” The suggestion is to use the 5Mmethodology (i.e., man, material, machine, method, and
measurement) or a fishbone diagram. Combining these
two methodologies, a risk-based PQ concept can be developed. In this context the proposed concept is an alternative
to the “normally used” method: run three medium-size
batch orders using intensified sampling.
Risk-Based PQ Concept Description—
Methodology
The risk-based PQ concept illustrated in Figure 4 reflects
a normal production order lifecycle and the challenges
seen in that connection.
The steps are as follows:
1) Define normal production
2) Identify potential influencing conditions
3) Ensure all aspects are covered
4) Remove irrelevant influencing parameters from
the list with a rationale
5) Identify the challenging conditions by carrying out
a risk evaluation for each influencing parameter
6) E stimate repeatability for each challenging
parameter
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Check
weighing
Wrapping
foil
7) E
stimate and define “stable” production
8) Simulate normal production, including the challenges identified
9) Calculate a PQ sequence that simulates normal
production, including challenges
10) Determine the number of PQ runs required.
Define Normal Production
Normal production means that a complete production
order lifecycle must be simulated. A normal production order lifecycle comprises the following three
major steps:
• P reparation includes: Initiate order; pick materials from stock; check materials (ready-for-production); line-clearance; and, adjust production
line format.
• Production includes: Adjust processing parameters;
check calibrations; start-up procedure; execute order;
document production; empty line; reconciliation;
line clearance; and, inline process control (IPC).
• Shut down includes: Batch documentation; return
exceeding materials; samples for inspection; and,
offline process control (OPC).
Each step in the lifecycle will have its own challenges. Machine parameters are typically identified
during OQ.
Identify Potential Influencing Conditions
Competent and experienced group members must be
appointed. Different brainstorming techniques can be
used such as mind map and paper cards.
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Figure 4: Risk-based PQ concept.
Estimate Repeatability For Each
Challenging Parameter
Estimate how many times a challenging condition
should be repeated to ensure that the results are meaningful and consistent. For example, if a production
order typically includes cartons from three different
batches, then this challenging condition should be
simulated three times within each PQ run to be consistent with normal production.
Shut-down:
• Batch doc
• Samples for insp.
• Reconciliation
Preparation:
• Pick from stock
• Ready for pack
• Line clearance
• Adjust format
Estimate “Stable” Production
When running PQ, stable production is defined as
the period between two interventions where you can
confirm that the previous intervention had no impact
on the next.
Simulate Normal Production, Including
The Challenges Identified
Production:
1.0 Machine
2.0 Method/Procedure
3.0 Environment
3.6 Temperature
1.7 Wear
1.5 Over wrapper process parameters
3.5 Humidity
2.5 Presence of SOP
1.4 Carton machine process parameters
1.2 Labeller process parameters
3.4 Vibration
2.4 Rollowing SOP
1.3 Blister process parameters
3.3 Light
2.3 Stop for X min
3.2 Variation in pneumatic supply
2.2 Recycling of products
1.1 Line speed
2.1 Emergency stop
3.1 Variation in electrical supply
Rejectable production
5.1 Refill of product
4.1 Weight is out of callibration
4.2 Heat sensor is out of calibration
4.3 Vision is out of calibration
5.2 Carton
5.3 Leaflet/insert card
5.4 Change of label rolls
6.1 Day/night shifts
6.2 Different technicians
6.3 Training
5.5 Change of PET rolls
5.6 Change of ALU rolls
5.7 Foil for over wrapper
5.8 Shipper box
4.0 Measure
5.0 Material
6.0 People
Ensure All Aspects Are Covered
To ensure that all aspects are covered, the fishbone diagram can be used to represent the following:
• Machine
• Method (procedure, SOP)
• Environment
• Measure
• Material
• Man (People).
Figure 5 shows an example of a traditional packaging
process. Other structured methodologies can be used.
Remove Irrelevant Influencing Parameters
Each identified parameter must be evaluated. It may be
possible to judge some parameters as irrelevant based
on an obvious argument and rationale.
Identify The Challenging Conditions By
Carrying Out A Risk Evaluation
Each influencing parameter is evaluated in a “quality
impact/possibility risk grid” (see Figure 6). The evaluation of probability/quality impact must be based on
experience. If the combination of quality impact and
possibility is “LOW/LOW”, then the specific challenge
parameter can be excluded from PQ. The challenging
parameters are the ones above the diagonal line.
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When the machine is running without any actions
or interventions in the production sequence, it will
repeat itself precisely, again and again. That is the
nature of a machine.
The challenges will only arise when there are
actions or interventions in the production line or in
the environment. Everything in between will be the
same. Accordingly, the “in-between periods” can be
shortened to simulate stable production.
Calculate A PQ Sequence That Simulates
Normal Production, Including Challenges
A simulation sequence might be as follows:
• Run the production line stably for XX minutes
with a yield comparable to normal output
• Simulate the set of challenging conditions one
by one the number of times estimated in item 6
in a random sequence
• Run the production line stably between each
simulation to avoid interactions between each
challenge.
Finally, calculate the required number of items to be
sure that the entire set of challenging conditions will
be covered combined with a simulated “stable period”
between each simulated challenging condition.
PQ simulating normal production is illustrated
in Figure 7. The simulation must include the same
main elements: preparation, production, and shut
down. But while normal production is characterised by regular actions and intervention in the line
during production, these aspects are simulated by
“constructed” challenges.
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Figure 5: Example of a fishbone diagram.
1.0 Machine
2.0 Method/Procedure
1.6 Wear
3.0 Environment
3.6 Temperature
1.5 Over wrapper process parameters
3.5 Humidity
2.5 Presence of SOP
1.4 Carton machine process parameters
1.3 Blister process parameters
1.2 Labeller process parameters
3.4 Vibration
2.4 Rollowing SOP
3.3 Light
2.3 Stop for X min
3.2 Variation in pneumatic supply
2.2 Recycling of products
1.1 Line speed
3.1 Variation in electrical supply
2.1 Emergency stop
Rejectable production
5.1 Refill of product
4.1 Weight is out of calibration
4.2 Heat sensor is out of calibration
4.3 Vision is out of calibration
5.2 Carton
5.3 Leaflet/insert card
5.4 Change of label rolls
6.1 Day/night shifts
6.2 Different technicians
6.3 Training
5.5 Change of PET rolls
5.6 Change of ALU rolls
5.7 Foil for over wrapper
5.8 Shipper box
4.0 Measure
Define The Number Of PQ Runs Required
As the PQ as a whole should simulate normal production, the number of PQ runs should reflect the number
of main formats or main variations that the technicians
are setting up in between the different orders.
“Consistently” is the central word in the definition of
performance qualification. Evidence can be established
by running the main format three times as an industrial
standard—and afterwards monitor the daily production performance using the ongoing batch data reviews
because these activities have to be carried out anyway
as they are an integrated part of all good manufacturing
practice (GMP) or ISO-regulated productions.
Once the format has been changed, adjusted, and
run in, then the machinery will do the same again and
again. Consequently, there is no need to test this more
than once. The challenging parameter is the technician
who will actually do the format changes, adjusting
and running in the next format. This must be tested
for all formats.
Figure 8 illustrates the proposed PQ run model. The
number of PQ runs required must reflect the number
of main formats that are possible.
The main format configuration will depend on the
main purposes of the equipment, usually defined by certain commercial parameters. Some typical main format
configurations for packaging are listed as follows:
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5.0 Material
6.0 People
•D
ifferent products. Packaging lines can be used
to package multiple products as long as the main
shape of the product and the primary containers
are similar, for example equally shaped tablets with
different active pharmaceutical ingredient (API).
This will typically require different infeed systems
and/or different processing parameters because the
physical and/or chemical properties will vary from
API to API. Furthermore, the barriers to mixing up
tablets with different API and packing with correct
packaging materials might be a challenge.
• Different quantum sizes. The line could be
designed to pack 3 ml as well as 10 ml, or it could
be designed to pack 10, 100, and 500 tablets per
bottle. This will generally require some format parts
to be replaced in the labelling handling unit.
• Different number of units per carton. Often a
product is sold in different unit sizes, for example 3,
5, or 10 pieces per carton and often a 1-piece sample
pack as well. This will typically affect the carton
machine formats that need to be changed.
• Different sizes of insert to be packed with
the product. As different countries have different
requirements for content and a number of countries
require the insert text to be printed in all official
languages (or in some countries three languages), the
size of the insert can obviously depend on this.
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Figure 6: Example of a risk grid.
Impact on quality
2.1
0.2
2.1
2.2
2.3
2.3
3.1
3.2
4.3
5.0
2.2
High
2.3
0.2
4.3
2.4
5.1
3.1
Medium
5.4
6.1
3.2
5.6
5.5
Line clearance
Emergency stop
Recycling of products
Stop for X min
Following SOP
Variation in electrical supply
Variation in pneymatic supply
Vision is out of calibration
Materials
5.1 Refill of product
5.4 Change of label rolls
5.5 Change of PET rolls
5.6 Change of ALU rolls
5.8 Petfoil for over wrapper
6.1 Day//night shift
6.2 Different technicians
6.2
Low
5.8
Probability
Low
Medium
High
Figure 7: Normal production sequence. Each PQ run should simulate a normal production sequence,
including the challenges normally seen.
End
Start
Normal production
Ready for pack
Production, actions and interventions
End of packaging
PQ simulating normal production
Order initiated
End of packaging
Production
Ready for pack
Empty of line
Start production
Providing materials
Challenge 1
Line clearance
Line clearance
Collect batch documentation
Stable production
Entering production data
Challenge 2
Fill up materials
Return of material to stock
Stable production
Approval of batch documentation
etc
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Figure 8: The PQ run model.
CHANGE
FORMAT
PQs simulating normal production
Ready
Production
End
CHANGE
FORMAT
PQs simulating normal production
Ready
Production
PQs simulating normal production
End
Ready
Production
End
Number of PQ runs reflects the number of possible main formats to be changed in between the orders
• Different package configuration. As advertising
is allowed in some countries and prohibited in others, it is often convenient to be able to pack more or
less informational or promotional material.
CONCLUSION
This paper has developed a risk-based PQ concept based
on fundamental requirements. The result is a cookbook
describing a methodology for defining a set-up for PQ
runs that simulate normal production in an operational
way, including the PQ batch size and the number of
PQ runs.
The methodology focuses on the characteristics of
normal production and the associated challenges. Consequently, the interventions and actions seen in connection
with normal production are tested rather than specifying
a set of specific machine parameters.
This paper has focused on the packaging performance
qualification as an example, but in fact this concept could
be introduced for all mechanical processes because the
process characteristics are all similar.
In the longer term, this methodology will be proposed
as Annex C to the process validation guidance (1).
REFERENCES
1. GHTF/SG3/N99-10:2004 (Edition 2); Quality Management
Systems—Process Validation Guidance; The Global Harmonization Task Force (by Taisuke Hojo); January 2004.
2. FDA, Guideline on General Principles of Process Validation, May
1987, reprinted February 1993, http://www.fda.gov/CDER/
GUIDANCE/pv.htm.
3. Institute of Validation Technology Standards Committee,
“Proposed Validation Standard VS-1, Nonaseptic Pharmaceutical Processes,” Journal of Validation Technology, Volume
6, No., February 2008.
4. Lanese, Jerry, “Three Times Is Not Even the Beginning,”
Journal of Validation Technology, Vol. 7, No. 2, February
2001.
gxpandjv t.com
5. Lanese Jerry, “Three Times Is Not Even The Beginning—
2008 Update,” Journal of Validation Technology, Vol. 14, No.
2, Winter 2008.
6. FDA, Current Good Manufacturing Practice in Manufacturing
Processing, Packaging or Holding of Drugs, 21 CFR – Parts
210 & 211.
7. Sharp J., “Validation – How much is required?” PDA Journal
of Pharmaceutical Science and Technology, May/June 1994.
8. FDA, Quality System Regulation, Good Manufacturing Practice for Medical Devices & In Vitro Diagnostic Products, 21
CFR Part 820.
9. ISO, ISO2206:1987 ed. 2, Packaging—Complete, Filled Transport Packages—Identification of Parts When Testing, 1987.
ISO, ISO2244:2000 ed. 3, Packaging—Complete, Filled Transport Packages and Unit Loads—Horizontal Impact Test, 2000.
ISO, ISO2247/ISTA2B: 2000 ed. 3, Packaging—Complete, Filled
Transport Packages and Unit Loads—Vibration Tests at Fixed
Low Frequency, 2000.
ISO, ISO2248:1985 ed. 2, Packaging—Complete, Filled Transport
Packages—Vertical Impact Test by Dropping, 1985.
10. Carol DeSain, Charmaine Vercimak Sutton, Validation
for Medical Device and Diagnostic Manufacturers; ISBN 0935184-64-3.
11. Ronald Pilchik, Validating Medical Packaging, CRC Press,
ISBN 1-56676-807-1, 2003. JVT
ARTICLE ACRONYM LISTING
API
FDA
GMP
IPC
IQ
ISO
OPC
OQ
PQ
SOP
Active Pharmaceutical Ingredient
US Food and Drug Administration
Good Manufacturing Practice
Inline Process Control
Installation Qualification
International Organization for Standardization
Offline Process Control
Operational Qualification
Performance Qualification
Standard Operating Procedure
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