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820.130
Device packaging.
Each
manufacturer shall ensure that device packaging and shipping containers are
designed and constructed to protect the device from alteration or damage
during the customary conditions of processing, storage, handling, and
distribution. Interpretation:
The packaging industry is continuously evolving as
medical product companies institute changes in the design, development, and
manufacture of packaging systems. Thus, this chapter is not aimed at
providing an all-inclusive list of packaging procedures and/or materials.
Rather the goal is to instill an awareness of important packaging issues
involving both design and manufacture. This chapter will also provide a basic
understanding of the importance of validating processes and equipment, and
the continuing need to maintain control of established packaging processes.
The result should be a package that protects the device during handling and
shipping, and from the environment and microorganisms until the package is
opened. This includes allowing for any necessary sterilization. Packaging
contains the product identification and other information as described in
Chapter 11, Labeling. Packaging may also contain integral labeling and
instructions for use or these instructions may be in a manual or package
insert. Finally, when the consumer is ready to use this product, the package
should be easy to open without compromising the quality of the device. In the
end, a well designed package facilitates use of the device and contributes
substantially to the overall appeal of the product. It makes sense for the
manufacturer to invest in the development of a safe, user friendly package. The design of the device, the labeling, the
packaging and the manufacturing processes form the design output [820.3(g)].
These should be integrated. Manufacturers should consider the needs of the
user as required by 820.30, Design Controls. Manufacturers should document
these design outputs in the device master record then, procure, handle,
store, and use the specified materials according to the device master record.
FDA regulations are compatible with this total systems approach to device
process design, production, packaging, and labeling. Finally, manufacturers should perform quality
assurance tests or acceptance tests on samples of the finished packages and,
if sterilized, repeat the tests after sterilization. These tests should be
based on a statistically valid sample to insure confidence that the packaging
is capable of maintaining the integrity of the finished product. Where the
device is very expensive, or only available in small quantities, the
packaging tests may be performed on labeled, controlled packages that contain
identified, rejected or simulated devices, as appropriate. The results of
testing and/or inspection should be recorded in the device history record.
Correctly performing these activities can reduce or prevent customer
complaints, recalls, and product liability actions. PACKAGING DESIGN CONTROLS Package design should be an integral part of the
product development program. Waiting until the end of the development process
to design packaging can result in severe delays in getting the product into
distribution. The whole idea is to "build quality in." The total
device and package system should be considered with respect to: device
characteristics, sterilization process if any, sealing, labeling, secondary
packaging, handling, shipping, environment, storage, federal regulations, and
end use. Defective packaging and seals have been a major
cause of medical device recalls. This type of recall can often be avoided by
correct package design including validation of the packaging and sealing
processes. Packaging and sealing machines should be set up according to
written procedures that are based on the known capability of the
manufacturing system. It is important to be aware of the state-of-the-art in
sealing methods and packaging materials, including their physical, chemical,
biological, and compatibility characteristics and, of course, cost.
"Wet" devices require high-barrier package materials and sealants
with impermeability; resistance to solvents, grease, chemicals, and heat; and
the ability to contain wetting agents, reagents, oils, or fragrances. Thus, the
ability to seal in the presence of liquid components, if spillage occurs in
the seal area, is important. Some peelable adhesives are highly
solvent-resistant and also remain intact during radiation sterilization. If
necessary, obtain guidance from suppliers, technical literature, and
consultants. After the process has been developed and validated, the
packaging aspect of production should be performed according to GMP
requirements in order to maintain a state of control. The design controls established by 21 CFR 820.30
and, particularly 820.3(g), define packaging as part of the device design
output. This means the design phase of packaging shall include the
application of quality systems requirements and the documentation of these
applications. Control over package design shall be performed according to
820.30 for any Class II or Class III devices, devices automated with computer
software, and the following Class I devices:
Manufacturers of other Class I devices should
establish and maintain procedures for ensuring that their device design is
correctly translated into production specifications. They may use 820.30(h)
as guidance. For these Class I devices that require design controls,
packaging design is performed according to 820.130. The nature of the device
as well as the sterilization method(s), intended use, shelf life, transport,
and storage all affect package design. The following activities are important to maintain
control of package design: 1. Planning for the design and development of
packaging; and defining responsibility for implementation of design
activities and controls. These plans should identify the different groups and
activities providing input into the design process. Periodic review and
approval is necessary as the package design evolves. 2. Establishing design input and output procedures,
including review, documentation, signature, and date, that are appropriate
for the intended use and the needs of the user and the patient. The
procedures shall include safeguards for addressing concerns about the
proposed designs. 3. Ensuring that design review procedures for all
appropriate stages of the design development are conducted by qualified
individual(s) and include an individual not directly responsible (NDR) for
the design stage under review. This NDR person could be one of several people
on the design review committee. The design identification, review results,
reviewers, and date shall be documented in the design history file
[820.30(j)]. 4. Documenting design verification/validation to
confirm that the design output meets the design input requirements in the
design history file. This documentation must include the reviewers and date
of review. 5. Establishing and maintaining design transfer
procedures that insure that the package design is correctly translated into
production specifications. The correct translation, of course, may be
directly done as part of the design output. 6. After the package design is accepted,
controlling changes according to company change control procedures. The
manufacturer shall establish and maintain procedures for the identification,
documentation, validation or where appropriate verification, review, and
approval of design changes before their implementation. A significant part of
this control is achieved when design controls are followed. 7. Establishing a design history file to
demonstrate the design was developed and approved according to plan. This, of
course, should show that the design output meets the design input -- a fact
which should be obvious from data presented during the final design reviews. Design controls require that a packaging design
undergo considerable validation, review, and documentation. However, the end
result is a smooth transfer into production with increased package safety and
efficacy, resulting in greater customer satisfaction and cost savings and
reduced liability. In addition to the GMP requirements, manufacturers
should always study current packaging practices for products similar to
theirs to determine current favorable practices and to prevent user packaging
problems. For example, customary use may dictate the use of double primary
packaging for some sterile devices. Finally, any packaging used for medical
devices should satisfy the end user or customer requirements, which
automatically satisfies one of the design GMP requirements. This is a key
point to be considered during the design phase. User Preference In the Medical Device and Diagnostic Industry
magazine, the article, "Hospital-User Preference in Sterile Device
Packaging," reports the results of a survey of nurses from operating
room and central services areas of hospitals. Several conclusions from the
test results are listed below that should be of interest to sterile device
manufacturers.
Package features that might favorably influence
practitioners in the selection of a sterile medical device include:
The nurses believe that being able to see and
clearly identify a device is a "very important criterion of user
preference." Also, as stated above, double primary packaging is
preferred for some sterile devices. PACKAGING MATERIALS Fulfilling the design control procedures discussed
above should include using the most appropriate packaging materials available
for the device. Although requirements for components, device master records,
environmental control, etc., that affect the selection and use of packaging
appear throughout the Quality System (QS) regulation, the specific
requirements for packaging are in section 820.130. Also the design
requirements for Class II, Class III, and the few Class I devices that
require design control extend to the broad requirements in 820.30. Device
packaging and shipping containers should be designed and constructed to
protect the device from adulteration or damage during the customary
conditions of processing, storage, handling, and distribution. Closely
related label integrity requirements are in section 820.120. Also, the
quality of packaging should be considered in relation to the 21 CFR Part 812,
Investigational Device Exemptions (IDE's) for clinical evaluations; Part 814,
Premarket Approval (PMA) applications; Part 807, Premarket Notification
[510(k)] submissions and, of course, customer requirements. Failure to meet
these packaging requirements renders a device adulterated and has resulted in
recalls of sterile devices. The package and device should be designed together
so that all factors in the product and package system can be considered, such
as device sharp edges and severe vacuum stresses. Some other factors to
consider are:
It is important that sterile devices and their
packaging material meet the requirements of the sterilization process,
package sealing method, and intended use. For example, radiation
sterilization may discolor packaging and sealing materials, or reduce their
functional capabilities. All plastics are somewhat affected by radiation
sterilization, occasionally positively, frequently negatively. Consideration
should be given to the effect produced and the radiation dose needed to
produce an effect. Complete storage and stability data should be compiled for
sterile device packaging subjected to radiation or should be obtained from
the supplier. Ethylene oxide (EO) sterilization requires
packaging material of sufficient porosity to allow air to leave the package and
the gas to rapidly permeate the package, sterilize the product, and then
leave the package. Adverse levels of EO residues left on the device harm the
patient. Air washing at the end of the cycle reduces residues. Evacuation of
the sterilization chamber for air removal, gas fill, and air washing can
induce package stress, particularly when the cycle calls for high
temperature, pressure, and rapid pressure changes before and after the gas
exposure (dwell) period. PACKAGE VALIDATION Package validation involves two separate
validations: 1) the design validation of the package as a component of the
device and 2) the process validation of the packaging process. Design
validation uses evidence to establish what design specifications will conform
with the user needs and the intended use(s) [830.3(z)(2)]. Process validation
establishes by objective evidence that a process consistently produces a
result or product that meets predetermined specifications [820.3(z)(1)]. The regulation, of course, refers to establishing
evidence that the manufacturing steps involved in packaging the device will
consistently produce packaging which meets specifications. For example, the
process capability of packaging and sealing equipment should be determined
during process validation and documented. Validation of the package design
shall be performed under actual or simulated use conditions that show the
package conforms to its stated intended uses. Risk analysis shall also be
included where appropriate. Design validation results shall include: the design
identification, name of the individual(s) performing the validation,
method(s) used, and the date. All of this information should be recorded in
the design history file. If any significant change is made in the packaging
or packaging operation after validation, the new process will need to be
revalidated. One of the most difficult aspects of package
validation is determining how many samples to test. The goal is not to over
test because of cost considerations while still running sufficient tests to
provide statistically valid sampling. Statistical methods of analysis are
important in process validation. The following decision tree from Medical
Device and Diagnostic Industry, "Streamlining Package-Seal
Validation," October 1992, provides various methods of statistical
analysis. The manufacturer is challenged with determining which statistical
method is most applicable to their individual needs. The resulting validation
plan should identify, measure, and evaluate the key processes and variables
that will require assessment to complete a validation or revalidation of the
packaging and the packaging process. PROCUREMENT, ACCEPTANCE, AND STORAGE The packaging associated labeling, sealing methods,
acceptance tests, etc., are part of the design output. These design output
documents are part of the device master record. The device master record
(820.181) should contain appropriate specifications so that the desired
packaging components may be purchased, properly stored, and properly used.
Suppliers are selected according to 820.50, Purchasing Controls.
Manufacturers shall have adequate procedures for approval or rejection of all
incoming packaging components such as adhesives, wrapping materials, corner
protectors, pouches, cartons, etc. (820.80, discussed in Chapter 10). The
supplier may test these components and provide the manufacturer with a
protocol for testing and the test results for each batch (i.e., certificate
of conformance to purchase specifications). The manufacturer could accept
this specific data as sufficient certification based on his assessment of the
supplier along with the review of the certificate or order his own testing. Incoming components should be examined for damage
and identity before being used. At a minimum, this examination should include
visual inspection. Thereafter, the packaging should be handled and stored in
such a way that it is kept clean and safe from damage. Packaging and devices
to be sterilized should, obviously, be kept clean before sterilization. For
transfusion and infusion assemblies, devices that come in contact with
circulating blood or cerebrospinal fluid, intraocular lenses and the surgical
instruments used in their implantation, and any device labeled as
"pyrogen free" or "nonpyrogenic," the manufacturer should
carefully and appropriately control the environment to which the associated
packaging materials are exposed in order to minimize bioburden and cellular
debris from dead bacteria. Pyrogens primarily arise from cellular debris of
gram-negative bacteria. PACKAGING PROCESS The packaging operation is a manufacturing process
as described in Section 820.70, Production and Process Controls. Other GMP
sections also apply to packaging including, but not limited to:
These sections require adequate controls for
components, processing, and test/inspection. The controls necessary for all
devices should assure that:
The controls required will vary with the type of
device packaged. For example, when a sterile device is packaged, a
manufacturer's considerations should include:
For a product to be sterilized in-house, either a
physical quarantine area or label control should be used to prevent shipment
of devices marked sterile, but not yet sterilized. The required level of
control is very high. The stringent control also extends to give-away samples
not intended for actual use on patients -- samples should be sterile if so
labeled because they might be used. One approach is to sell samples at zero
cost so that the samples are subjected to all of the company finished product
controls. A written procedure is required by 801.150(e) for
interstate contract sterilization. The purpose of this requirement is to
help prevent the erroneous release of packaged and labeled
"sterile" devices that are not yet sterilized even though they
appear to be sterile and ready for release. Regardless of whether 801.150(e)
applies, the QS regulation requires sufficient controls as necessary to prevent
mixups in complex situations such as contract sterilization. For consistency,
a contract is commonly used by manufacturers for interstate and intrastate
shipments. Such a contract, and compliance with it, satisfies the applicable
GMP requirements. Section 820.181(d) requires that the device master
record include packaging methods and processes. Written instructions should
be provided to assure that the necessary controls are understood and
consistently implemented. The need for, and the extent of, written
instructions should be determined based on the complexity of the operation
and the nature of the product. Some products such as radioimmunoassay test
kits can deteriorate during packaging if the process is not timed properly.
In such cases, written instructions should describe how the device(s) should
be handled and expedited during packaging in order to prevent delays, and
thus deterioration. The procedure for testing and/or
inspection of finished packages shall be written [(820.80(d)]. To the extent
feasible, the testing of finished packages should be quantitative. The
packaging of sterile devices should be tested and/or inspected before and
after sterilization. This testing is done on a sampling basis. Sampling plans
are valid only when a process is in a state-of-control; therefore, the device
must be manufactured and packaged using a quality system as described in the
FDA guidance. Reference: www.FDA.gov The information provided here is for "public consumption" and is open to interpretation. MedicalDeviceSchool.com is not responsible for the content or the accuracy of the information. For all official interpretation and accuracy we ask that you consult the FDA's website directly and that you consult with your legal and regulatory experts on all matters of interpretation. |
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