COMPLIANCE TO ISO 11607-1:2006
`
`DUPONTT” TYVEK®
`
`.f'
`
`'
`
`Regeneron Exhibit 1061.001
`
`

`

`
`
`CONTENTS
`
`Introduction .................................................................... 3
`
`ISO 11607-12006 Requirements ................................................... 4
`
`4. General requirements .......................................................... 4
`
`4.2 Quality systems ........................................................ 4
`
`4.3 Sampling ............................................................. 4
`
`4.4 Test methods .......................................................... 4
`
`4.5 Documentation ......................................................... 6
`
`5. Materials and preformed sterile barrier systems ................................... 6
`
`5.1 General requirements .................................................... 6
`
`5.2 Microbial barrier properties .............................................. 10
`
`5.3 Compatibility with the sterilization process .................................. 10
`
`5.4 Compatibility with the labeling system ..................................... 11
`
`5.5 Storage and transport .................................................. 11
`
`Regeneron Exhibit 1061.002
`
`

`

` INTRODUCTION
`
`
`
`Tyvek.
`
`
`
`DuPont” Tyvek® spunbonded olefin is intended for
`packaging of terminally sterilized medical devices.
`To guide the medical device manufacturers and sterile
`packaging manufacturers in their selection and use of
`packaging, the International Standards community has
`promulgated the ISO 11607—12006 Packagingfor
`terminally xterilized medical device; Part I: Materialx,
`xterile barrier syxtemx andpackaging syxtemx and
`ISO 1 I 607—22006 Packagingfor terminally xterilized
`medical device; Part 2: Hzlidation requirementxforforming,
`tealing and attembly procexxex.
`
`As the producer of Tyvek® for medical and pharmaceutical
`packaging, DuPont Medical and Pharmaceutical Protection
`has compiled documentation which demonstrates the
`compliance of Tyvek® with the materials portion of the ISO
`11607—12006 standard. This will allow medical device
`
`manufacturers and sterile packaging manufacturers to focus
`on the package material production, final package design
`qualification, and the device package process validation
`portions of the standard. The compliance is supported by
`a number of DuPont Technical Information Documents
`
`(TIDs) which contain the necessary experimental data.
`In this preamble, the documents are described and their
`applicability to the various sections of the ISO 11607—12006
`document are explained. The TIDs, which cover material
`testing for sterile barrier systems, can be used to demonstrate
`packaging compliance to this standard. Much of the
`information in the TIDs is presented in the DuPont Technical
`Reference Gaidefér Medical and Pharmaceutical Packaging
`located at http ://www2.dupont.com/Medical_Packaging/
`en_US / te ch_info /index.html
`
`The product characteristics of Tyvek® include:
`
`° Outstanding porous microbial barrier
`
`- Strength to weight ratio
`- Moisture resistance
`
`° Inertness to most chemicals
`
`- Air and water vapor permeability
`
`- Clean peeling seals
`
`- Low linting due to continuous filaments
`- Low fiber tear
`
`° Puncture resistance
`
`These characteristics provide high value in terminally
`sterilized packaging of medical devices sterilized by a
`wide variety of methods. Several package configurations
`containing Tyvek® are used within the medical device
`industry. Packages such as chevron peel pouches and header
`bags are composed of Tyvek® sealed to flat, unshaped, flexible
`film in a wide variety of length and width dimensions. In
`addition, Tyvek® is commonly used in packages made with
`a Form/ Fill/Seal (FPS) process and equipment using rigid
`or flexible forming films, as well as lidding material for
`preformed rigid trays.
`
`Both adhesive coated and uncoated Tyvek® are used in
`medical packaging. When uncoated Tyvek® is used, the film
`web contains the adhesive layer to form the seal between the
`film and the Tyvekg.
`
`A variety of converting steps may be required prior to
`using Tyvek® in medical packaging. Some will have the
`adhesive coated onto the Tyvek® prior to use, while most
`will be printed, slit or die cut before incorporation into
`the final package.
`
`The permeability and chemical inertness of Tyvek® allow its
`use in a variety of sterilization processes. The sterile barrier
`systems using Tyvek® are commonly sterilized using ethylene
`oxide (EO) gas, gamma and electron—beam radiation. In
`addition, steam sterilization may be used if temperatures
`are controlled to avoid melting the Tyvekg. Tyvek® has been
`shown to meet packaging criteria for steam sterilization
`under controlled conditions (250°F to 260°F [121°C to
`127°C] at 30 psi for 30 minutes). Emerging low—temperature
`sterilization methods such as: gas plasma with hydrogen
`peroxide, vapor phase hydrogen peroxide with peracetic acid,
`ozone and chlorine dioxide, require Tyvek® packaging because
`cellulosic porous materials are adversely affected by these
`strong oxidizing environments.
`
`This document is used to demonstrate the compliance
`of Tyvek® with the ISO 11607—12006 standard. Tyvek®
`falls under sections 4 and 5. This document lists each
`
`clause from ISO 11607—1 that contains a requirement,
`followed by compliance information for the requirement.
`There are other DuPont documents that are referred
`
`to in this document and they are all available at
`www.MedicalPackaging.DuPont.com
`
`Introduction
`
`3
`
`Regeneron Exhibit 1061.003
`
`

`

` ISO 11607—1:2006 REQUIREMENTS
`
`4. GENERAL REQUIREMENTS
`
`The numbers in the following sections refer to the
`specific clauses in ISO 11607-1.
`
`4.2. Quality systems
`
`4.2.1 The activities described within this part of
`ISO 11607-1:2006 shall be carried out within a
`
`formal quality system.
`
`Tyvek® production facilities located in Richmond, VA,
`and Luxembourg are ISO 9001:2008 certified. As a
`requirement for certification, both facilities have a
`Qliality Systems Manual. The Qliality Systems Manual is
`an evergreen document and the controlled copy is kept on
`file. Our performance against it is the subject of semi—annual
`audits as part of retaining ISO 9001:2008 Registration,
`and is available to the auditors of our facilities. Changes to
`the manual may only be made with appropriate approvals.
`The current ISO 9001:2008 Registration Certificates are
`available at WWW.MedicalPackaging.DuPont.com
`
`4.3 Sampling
`
`The sampling plans used for selection and testing
`of packaging systems shall be appropriate to
`packaging systems being evaluated. Sampling plans
`shall be based upon statistically valid rationale.
`
`All routine physical property tests run on bonded Tyvek®
`are performed in the in—area lab. Testing is intended to
`satisfy Product Characterization, Process Control, and
`Measurement Control.
`
`Samples are managed using the laboratory information
`management system (LIMS). Every sample is identified
`with a L1MS sample label. The sample label contains all
`necessary information needed to track a test result back
`to finished product.
`
`Tyvek® is produced in full mill rolls that are approximately
`10 feet wide and have a diameter of approximately three
`feet. These full mill rolls are then slit into multiple
`smaller packages according to the customer requirements.
`Full mill rolls are sampled uniformly across their width
`(typically 12 samples/full mill roll) to calculate roll
`averages. Thickness measurements are based on individual
`values (typically 112 samples/full mill roll) versus full
`mill roll averages. The average thickness is determined by
`pooling the ~112 data points from a roll with individual
`data points from other rolls and averaged. Test method
`variance related to equipment and analysis is included in
`the observed values. Other sampling plans and test methods
`may yield different values.
`
`4.4 Test methods
`
`4.4.1 All test methods used to show compliance
`with this International Standard shall be validated
`and documented.
`
`Sampling and physical property testing for Tyvek® 1073B,
`Tyvek® Asuron‘” (4070B), Tyvek® 1059B, Tyvek® 2FS"‘
`(4058B) and Tyvek® 4057B are conducted per procedures
`associated with ISO 9001:2008 quality systems registration.
`Samples of Tyvek® are taken at the bonder windup, identified,
`and delivered to the in—area lab for physical property testing.
`
`All physical properties of Tyvek® that are used to demonstrate
`acceptable material for packaging terminally sterilized medical
`devices are measured by validated DuPont test methods that
`are comparable to recognized, national and international
`standards. DuPont conducts testing as shown in Table 1.
`
`4 General requirements
`
`Regeneron Exhibit 1061.004
`
`

`

`
`
`Tyvek.
`
`
`
`Table I. Test methods used for measuring material properties
`
`Property
`
`Basis Weight
`
`Delamination
`
`Comparable Standard Test Methods
`
`Richmond, VA
`
`Luxembourg
`
`Deviations from
`Standard Test Methods
`
`ASTM D3776
`
`EN ISO 536
`
`Modified sample size.
`
`ASTM D2724
`
`ASTM D2724
`
`Modified for speed and gauge length.
`
`Gurley-Hill Porosity
`
`TAPPI T4601
`
`ISO 5636-52
`
`1. Modified sample size.
`2. Modified for sealing fluid characteristics.
`
`Opacity
`
`TAPPI T425
`
`ISO 2471
`
`Modified for different backing standards, area and illumination.
`
`Thickness (individual)
`
`ASTM D17771
`
`EN ISO 534
`
`1. 7.15 psi, 0.625-in. diameter presser foot.
`
`Tensile and Elongation
`
`ASTM D5035
`
`EN ISO 1924-2
`
`Modified for speed and gauge length.
`
`Elmendorf Tear
`
`ASTM D1424
`
`EN 21974
`
`Hydrostatic Head
`
`AATCC TM 127
`
`Mullen Burst
`
`ASTM D774
`
`EN 20811
`
`ISO 2758
`
`Bendtsen Air Permeability
`
`ISO 5636-3
`
`ISO 5636-3
`
`Rate of use: 60 cm HZO/min.
`
`Spencer Puncture
`
`ASTM D3420
`
`ASTM D3420
`
`Modified for 9/16-ll'l. (14.28-mm) probe
`
`4.4.2 Test method validation shall demonstrate
`
`the suitability of the method as used. The following
`elements shall be included:
`
`- Establishment of a rationale for the selection of the
`
`appropriate tests for the packaging system
`
`- Establishment of acceptance criteria;
`pass/fail is a type of acceptance criterion
`
`- Determination of test method repeatability
`
`- Determination of test method reproducibility
`
`- Determination of test method sensitivity for integrity tests
`
`Equipment calibration procedures for quality critical
`instruments and lab measurement control are conducted
`
`per internal procedures associated with ISO 9001:2008
`quality systems registration.
`
`The establishment of test methods was based on
`
`ISO 11607—1 Appendix B recommendations for test
`methodology. The accuracy and reliability of test results are
`highly dependent on the calibration of test equipment and
`the control of the testing environment, sampling process,
`and the testing process. The DuPont standard operating
`procedure specifies the calibration and control system for
`the in—area test lab equipment to ensure data is consistently
`accurate. The test data on routine production samples is
`used to certify product meets established standards and
`to control processing conditions that impact physical and
`chemical properties. All test equipment is calibrated on
`a specified frequency using gauges traceable to nationally
`recognized standards or locally developed standards.
`
`General requirements
`
`5
`
`Regeneron Exhibit 1061.005
`
`

`

` ISO 11607—1:2006 REQUIREMENTS
`
`The Tyvek® in—area lab controls the measurement system
`by using a standard sample to monitor the repeatability
`and stability of most instruments in the lab. This provides
`a reliable method for detecting significant deviations in
`instrument readings due to instrument failure. Following
`is a summary of the standard control procedure:
`
`- A standard sample roll is selected from routine
`production that represents a stable process condition
`in spinning and bonding.
`
`- Several samples from this roll are tested to establish
`control limits.
`
`- The standard sample is tested on a regular schedule
`on each instrument and the results are monitored.
`
`- Corrective action is taken when a drift is detected.
`
`4.4.3 Unless specified in test methods, test samples
`shall be conditioned at (23 1 1)°C and (50 1 1) %
`relative humidity for 24h.
`
`All samples used for product release are tested in a controlled
`laboratory environment. Because Tyvek® is hydrophobic,
`samples are not stabilized for 24 hours prior to testing.
`
`4.5 Documentation
`
`4.5.1 Demonstration of compliance with the
`requirements of this standard shall be documented.
`
`4.5.2 All documentation shall be retained for a
`
`specified period of time. The retention period shall
`consider factors such as regulatory requirements,
`expiry date and traceability of the medical device or
`sterile barrier system.
`
`All documents that illustrate the compliance of Tyvek® with
`ISO 11607—lz2006 are retained for a specified period of time.
`This time period varies depending on the type of document
`and is specified in our quality procedures.
`
`6 Materials and preformed sterile barrier systems
`
`5. MATERIALS AND PREFORMED
`
`STERILE BARRIER SYSTEMS
`
`Tyvek® has been used to package terminally sterilized medical
`devices in a variety of global climates since 1972. Because it
`is made of high—density polyethylene fibers, it is not affected
`by climatic changes in humidity, temperature, or atmospheric
`pressure. Because its melting point is 275°F (135°C),
`steam sterilization must be limited to <260°F (<127°C)
`
`temperature cycles. Exposure to UV light should be limited
`to less than one month. Normal shipping, handling and
`storage conditions should be used. Compatible ink offerings
`and labeling systems have been developed and most major
`manufacturers offer them to the market.
`
`The administration of essential ingredients is conducted
`per standard operating procedures, specifying responsibility
`leading to the implementation of a system for the set—up,
`receipt and release of essential materials. Each shipment
`of polymer is received with a Certificate of Analysis
`demonstrating that the specification parameters are met.
`
`5.1 General requirements
`
`5.1.3 The conditions under which the material and/or
`
`preformed sterile barrier system are produced and
`handled shall be established, controlled and recorded,
`if applicable, in order to ensure that:
`
`a) the conditions are compatible with the use for which
`the material and/or sterile barrier system is designed;
`
`b) the performance characteristics of the material and/or
`sterile barrier system are maintained.
`
`Tyvek® is a highly inert material and, once manufactured,
`it typically does not change unless directly exposed to
`UV light for more than 30 days.
`
`Regeneron Exhibit 1061.006
`
`

`

`
`
`g) Bioburden
`
`The process of manufacturing Tyvek® allows only short
`periods of time when the sheet is subject to airborne
`particulates and microbes; therefore, the bioburden on the
`surface of the Tyvek® is very low. This low bioburden does
`not add significantly to the required sterilization time.
`The typical bioburden of all Tyvek® medical packaging
`styles is less than 100 colony forming units (cfu) per ftz.
`
`h) Electrostatic conductivity
`
`In some processing steps, Tyvek® may generate static
`electricity unless treated with antistatic agents. Styles
`intended for medical packaging do not contain an antistatic
`agent. Untreated styles can build a static charge during roll
`or sheet handling and should not be handled in areas where
`there is the potential for explosive vapor/ air mixtures.
`
`5.1.5 The source, history and traceability of materials,
`especially recycled materials, shall be known and
`controlled to ensure that the finished product will
`consistently meet the requirements of this part of
`ISO 1 1607.
`
`The source history and traceability of incoming and
`outgoing materials are controlled by our quality control
`procedures. Recycled materials are not used to manufacture
`Tyvek® medical packaging styles.
`
`5.1.6 The following properties shall be evaluated:
`
`a) Microbial barrier
`
`The microbial barrier properties of Tyvek® are superior to
`medical—grade papers and are well documented in the DuPont
`Technical Reference Gaidefor Medical and Pharmaceutical
`Packaging (Section 3) located at http://www2.dupont.com/
`Medical_Packaging/en_US/tech_info/index.html
`
`5.1.4 As the minimum, the following shall
`be considered:
`
`a) Temperature range
`
`Toughness and flexibility are retained down to —100°F
`(—73°C). When exposed to heat, Tyvek® begins to shrink
`at approximately 270°F (132°C) and melts at 275°F
`(135°C). Under actual processing conditions, the
`temperature can influence the handling of the web and
`the range of exposures should be controlled or validated.
`It is suggested that the web temperature should not exceed
`175°F (79°C).
`
`b) Pressure range
`
`The ability to perform over a range of pressures is a critical
`characteristic of Tyvek® when incorporated into a sterile
`barrier system (SBS). Porosity is the fabric characteristic
`related to pressure an SBS may experience and allows
`for the equilibration of pressure differentials across a
`sealed SBS. The extent of the porosity necessary for an
`SBS is an attribute only a medical device manufacturer
`can determine based on the sterilization processing,
`shipping, handling and storage the packaging system will
`be exposed to during its life cycle.
`
`c) Humidity range
`
`Tyvek® is hydrophobic and is not affected by moisture.
`Tyvek® maintains its strength regardless of humidity.
`
`d) Maximum rate of change of the above,
`where necessary
`
`As a packaging material, the rate of temperature, pressure
`and humidity changes are not applicable. These elements
`must be considered once Tyvek® becomes part of an SBS.
`
`e) Exposure to sunlight or UV light
`
`Physical properties of Tyvek® are degraded with extended
`exposure to direct sunlight (ultraviolet rays).
`
`f) Cleanliness
`
`Tyvek® is composed of essentially continuous fibers and
`does not generate a significant amount of lint particles
`under conditions of ordinary use.
`
`Materials and preformed sterile barrier systems
`
`7
`
`Regeneron Exhibit 1061.007
`
`

`

` ISO 11607-12006 REQUIREMENTS
`
`b) Biocompatibility and toxicological attributes
`
`Biocompatibility and other toxicological attributes of Tyvek®
`medical packaging styles are acceptable and are documented
`in the DuPont Technical Reference Guidefor Medical and
`Pharmaceutical Packaging located at http://www2.dupont.
`com/Medical_Packaging/en_US/tech_info/index.html
`
`c) Physical and chemical properties
`
`The physical properties of Tyvek® styles intended for
`medical packaging can be found in specifications and
`miscellaneous properties tables in the DuPont Technical
`Reference Guidefar Medical and Pharmaceutical Packaging
`(Section 2) located at http://www2.dupont.com/
`Medical_Packaging/en_US/tech_info/index.html
`These specifications and miscellaneous properties serve as
`a guide for medical device manufacturers to determine
`
`the level of protection required for a particular device.
`
`Because Tyvek® is made of high—density polyethylene,
`it is relatively chemically inert. The chemical resistance
`of Tyvek® to various chemicals is available at http://
`www2.dupont.com/Tyvek/en_US/assets/downloads/
`tyvek_handbo ok.p df
`
`d) Compatibility with respect to forming and
`sealing processes
`
`Tyvek® has been used as a packaging material for medical
`devices since 1972. It is customary for the user of a sterile
`barrier system (SBS) to specify the strength requirements
`required for its use. It is intended that the package or SBS
`strength selected will be sufficiently strong so as to assure
`SBS integrity through the user’s distribution, handling and
`storage systems. The strength of a preformed SBS seal
`should be determined by the manufacturer of that system.
`The effect of aging on seal strength is documented in
`the DuPont Technical Reference Guidefar Medical and
`Pharmaceutical Packaging, which is available at http://
`www2.dupont.com/Medical_Packaging/en_US/tech_info/
`index.html
`
`e) Compatibility with respect to the intended
`sterilization process(es)
`
`Tyvek® medical packaging styles are compatible with all
`approved sterilization methods, including: ethylene oxide,
`electron—beam, gamma irradiation, steam (under controlled
`conditions), and low—temperature oxidative sterilization
`processes. The effects of sterilization on Tyvek® medical
`packaging styles are documented in the DuPont Technical
`Reference Guidefor Medical and Pharmaceutical Packaging
`(Section 4) located at http://www2.dupont.com/Medical_
`Packaging/en_US/tech_info/index.html
`
`f) Any shelf-life limitations for pre-sterilization
`and post-sterilization storage
`
`Tyvek® medical packaging styles should be stored under
`the same conditions as one would store a medical device.
`
`Tyvek® should not be exposed to direct sunlight for more
`than 30 days.
`
`Tyvek® is capable of maintaining package integrity and
`sterility for at least five years. The effects of post—
`sterilization storage are documented in the DuPont Technical
`Reference Guidefor Medical and Pharmaceutical Packaging
`(Section 5) located at http://www2.dupont.com/Medical_
`Packaging/en_US/tech_info/index.html
`
`5.1.7 Materials, e.g. wrapping materials,
`paper, plastic film, nonwovens, reusable fabrics,
`shall meet the following general performance
`requirements:
`
`a) Materials shall be non-leaching and odorless under
`specified conditions of use to such an extent that
`neither performance nor safety is impaired and the
`medical devices with which they are in contact are
`not adversely affected.
`
`Tyvek® is an article made of high density polyethylene
`(HDPE) and is odorless. Elemental analysis of selected
`Tyvek® styles shows various elements including heavy metals
`are in the range of trace amount or are non—detectable. Tyvek®
`medical packaging styles meet the extractable or composition
`requirements of various regulations such as 21CER 177.1520,
`Commission Regulation (EU) No 10/2011 and European
`Pharmacopoeia, Section 3.1.5.
`
`8 Materials and preformed sterile barrier systems
`
`Regeneron Exhibit 1061.008
`
`

`

`b) Materials shall be free of holes, cracks, tears, creases,
`
`or localized thickening and/or thinning sufficient to
`impair functioning.
`
`Standard operating procedures (SOPs) are used within
`the manufacturing facilities to identify and correct visual
`anomalies. A summary of the SOPs describing the types of
`anomalies seen in Tyvek® and the release standards for
`Tyvek® medical packaging styles are listed below. Corrective
`actions when an anomaly is detected are also defined.
`
`° Inspecting, grading, segregating and
`dispositioning ofproduct
`
`SOPs define the roles and responsibilities required
`to deliver the best product possible to our customers,
`including: guidelines for inspecting, grading, segregating
`and dispositioning Tyvekg; specifications for moving sheet
`and stationary sheet; inspections tables describing anomalies,
`their causes, detection methods; and instructions related
`
`to segregating and dispositioning product when anomalies
`are detected.
`
`°An0maly descriptions and possible causes
`
`SOPs are designed to give a detailed description and
`definition of each known anomaly, the frequency of
`occurrence, and detection process. There are two categories
`of anomalies:
`
`Minor:
`
`An anomaly that does not affect performance but should
`be eliminated. This anomaly will be recorded and action
`taken to correct and prevent the anomaly. This type of
`anomaly will ship to customers.
`
`Major:
`
`An anomaly that does affect performance and must not
`ship. This anomaly will be recorded and action taken to
`correct and prevent the anomaly. This type of anomaly
`will not ship to customers.
`
`° Tracing and clearing of anomalies
`
`Once a major anomaly is detected, the anomaly must be
`traced and cleared per SOPs. This prevents unacceptable
`material from shipping to customers.
`
`
`
`Tyvek.
`
`
`
`c) Materials shall have a basis weight (mass per unit
`area) which is consistent with the specified value.
`
`See the specification properties tables in the DuPont Technical
`Reference Guidefor Medical and Pharmaceutical Packaging
`(Section 2) which is available at http://www2.dupont.com/
`Medical_Packaging/en_US/tech_info/indeX.html
`
`d) Materials shall exhibit acceptable levels of
`cleanliness, particulate matter and linting.
`
`Internal processes specify release limits for cleanliness and
`particulate matter. Tyvek® does not generate a significant
`amount of lint particles under conditions of ordinary use.
`Refer to the DuPont Technical Reference Guidefor Medical
`and Pharmaceutical Packaging (Section 3), which is available
`at http ://www2.dup ont.com/Medical_Packaging/en_US/
`te ch_info /indeX.html
`
`e) Materialshall comply with established specific
`or minimum physical properties such as tensile
`strength, thickness variation, tear resistance,
`air permeance and burst strength.
`
`For Tyvek® medical packaging styles, the established
`specification properties are Gurley Hill, Delamination
`and Basis Weight. The specific values for these can
`be found in the DuPont Technical Reference Guide
`for Medical and Pharmaceutical Packaging (Section 2),
`which is available at http://www2.dupont.com/
`Medical_Packaging/en_US/tech_info/indeX.html
`Additional properties that are important when considering
`alternative materials for your specific applications can also
`be found in the DuPont Technical Reference Guidefor
`Medical and Pharmaceutical Packaging (Section 2).
`
`f) Materials shall comply with established specific
`chemical characteristics (such as pH value,
`chloride, and sulfate contents) to meet the
`
`requirements of the medical device, packaging
`system or sterilization process.
`
`Tyvek® is an article made of high density polyethylene
`(HDPE) and is odorless. Elemental analysis of selected
`Tyvek® styles shows various elements including heavy metals
`are in the range of trace amount or are non—detectable. Tyvek®
`medical packaging styles meet the extractable or composition
`requirements of various regulations such as 21CER 177.1520,
`Commission Regulation (EU) No 10/ 2011 and European
`Pharmacopoeia, Section 3.1.5.
`
`Materials and preformed sterile barrier systems
`
`9
`
`Regeneron Exhibit 1061.009
`
`

`

`
`
`ISO 11607—1:2006 REQUIREMENTS
`
`g) Materials shall not contain or release material known
`to be toxic in sufficient quantity to cause a health
`hazard either before, during or after sterilization
`under the conditions of use.
`
`5.2.3 Porous materials shall provide an adequate
`microbial barrier to microorganism in order to provide
`integrity of the sterile barrier and product safety.
`
`The toxicological attributes Of TWICE medical packaging
`styles are documented in the DuPont Technical Reference
`Gaiclefar Medical and Pharmaceutical Packaging (Section 4)
`located at http ://WWW2.dupont.com/Medical_Packaging/
`en_US/tech_info/indeX.html
`
`The microbial barrier properties of Tyvek® are superior to
`medical—grade papers and are well documented in the DuPont
`Technical Reference Guidefar Medical and Pharmaceutical
`Packaging located at http ://WWW2.dupont.com/Medical_
`Packaging/en_US/tech_info/index.html
`
`5.1.8 In addition to the requirements given in 5.1.1
`through 5.1.6, adhesive-coated materials shall meet
`the requirements listed below.
`
`Adhesive coated Tyvek® is sold by sterile packaging
`manufacturers and each will require a different set of
`process conditions to give the required package strength and
`integrity. The medical device manufacturer must validate
`the processes used for the coated product they are using.
`
`5.1.10 In addition to the requirements given in 5.1.1
`through 5.1.7, reusable containers shall meet the
`requirements given below.
`
`Tyvek® is not designed to produce reusable containers.
`
`5.2.1 The impermeability of a materialshall be
`determined in accordance with Annex C.
`
`Tyvek® is not considered to be an impermeable material.
`
`5.3 Compatibility with the sterilization process
`
`5.3.1 It shall be demonstrated that the materials
`and preformed sterile barrier system are suitable
`for use in the specified sterilization process(es) and
`l
`t
`cyc e parame ers.
`
`5.3.2 The performance of the materials shall be
`evaluated to ensure that the material performance
`remains within specified limits after exposure to
`all the specified sterilization processes.
`
`Tyvek® medical packaging styles are compatible with all
`approved sterilization methods, including: ethylene oxide,
`electron—beam, gamma irradiation, steam (under controlled
`conditions), and low—temperature oxidative sterilization
`processes. The effects of sterilization on medical packaging
`styles are documented in the DuPont Technical Reference
`Gaidefor Medical and Pharmaceutical Packaging located at
`http :/ /WWW2.dupont.com/Me dical_Packaging/en_US/
`tech_info/index.html
`
`5.2.2 Demonstrating that the material is impermeable —
`
`shall satisfy the microbial barrier requirements.
`
`Tyvek® is not considered to be an impermeable material.
`
`10 Materials and preformed sterile barrier systems
`
`Regeneron Exhibit 1061.010
`
`

`

`
`
`
`
`5.4 Compatibility with the labeling system
`
`5.5 Storage and transport
`
`The labeling system shall:
`
`a) remain intact and legible until the point of use;
`
`Ink manufacturers have developed specific inks to print
`on medical packaging styles of Tyvekg. To achieve consistent,
`high-quality print, the appropriate ink must be used.
`
`b) be compatible with the materials, sterile barrier
`system and medical device during and after the
`specified sterilization process(es) and cycle parameters
`and shall not adversely affect the sterilization process;
`
`c) not be printed or written in ink ofa type which can
`be transferred to the medical device nor react with the
`
`packaging material and/or system to impair the utility
`of the packaging material and/or system nor change
`colour to an extent which renders the label illegible.
`
`The labeling of product made by the Tyvek® manufacturing
`plants is aimed at meeting the needs of our customers and
`contractors. It must further account for and trace product
`through all manufacturing steps. Labels are applied to rolls
`of Tyvek® during the inspection and packaging operations.
`These labels provide sufficient information to identify
`the product and to trace product processing at the
`manufacturing site using the package number (bar—coded)
`as the primary identifier.
`
`Because the label is removed prior to final processing;
`the reaction of the ink and label material is not applicable.
`
`5.5.1 Materials and preformed sterile barrier systems
`shall be packaged to provide the protection necessary
`to maintain the performance characteristics during
`transport and storage.
`
`The material wrapping system used by DuPont is designed
`to provide the necessary protection to the rolls through the
`global supply chain. This would include transport by rail,
`truck, ocean containers and air. The rolls are wrapped with a
`polyethylene stretch film in either an axial or barrel method.
`
`These methods of wrapping protect the Tyvek® rolls
`from contamination and damage during distribution and
`handling. There are no restrictions on transport and storage
`of Tyvek® other than avoiding direct exposure to UV light
`for more than 30 days.
`
`5.5.2 Materials and preformed sterile barrier systems
`shall be transported and stored under conditions that
`ensure that the performance characteristics remain
`within specified limits.
`
`This can be accomplished by:
`
`a) demonstrating retention of these characteristics
`under defined storage conditions;
`
`b) ensuring that storage conditions remain within
`specified limits.
`
`There are no restrictions on transport and storage of
`Tyvek® other than avoiding direct exposure to UV light
`for more than 30 days.
`
`Materials and preformed sterile barrier systems
`
`11
`
`Regeneron Exhibit 1061.011
`
`

`

`
`
`
`
`Tyvek.
`
`
`
`For more information about DuPont” Tyvek®
`for medical and pharmaceutical packaging
`and to find out how we can help you with
`packaging and regulatory compliance, call us
`today at 1.800.44.TYVEK or Visit us at
`www.MedicalPackaging.DuPont.com
`
`You can also find links to other resources
`
`in your country and information in other
`languages at this website.
`
`The miracles ofscience“
`
`This information is based upon technical data that DuPont believes to be reliable. It is subject to revision as additional knowledge and experience are gained. DuPont makes
`no guarantee ofresults and assumes no obligation or liability in connection with this information. It is intended for use by persons having technical skill for evaluation under
`their specific end-use conditions at their own discretion and risk. Since conditions of use are outside our control, WE MAKE NO WARRANTIES, EXPRESSED OR IMPLIED, INCLUDING
`WITHOUT LIMITATIONS, NO WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR USE AND ASSUME NO LIABILITY IN CONNECTION WITH ANY USE OFTHIS INFORMATION.
`This information is not intended as a license to operate under or a recommendation to infringe any patent or technical information of DuPont or others covering any material or its use.
`
`Copyright © 2011 DuPont. All rights reserved. The DuPont Oval Logo, DuPont", The mir