NOVARTIS PHARMACEUTICALS CORPORATION
`
`
`
`
`
`
`
`
`
`
`
`
`Date of mailing (day/month/year)
`20 September 2011 (20.09.2011)
`Applicant’s or agent's file reference
`
`International application No.
`PCT/EP2010/060011
`
`International filing date (day/month/year)
`13 July 2010 (13.07.2010)
`
`1. The following indications appeared on record concerning:
`
`the applicant
`(CJ
`Name and Address
`
`CO theinventor
`
`[] the agent
`
`( the common representative
`State of Nationality
`State of Residence
`
`Telephone No.
`
`Facsimile No.
`
`E-mail address
`
`2. The International Bureau hereby notifies the applicant that the following change has been recorded concerning:
`(J the residence
`(C1 theperson
`C1 the name
`(J the address
`CL]
`the nationality
`Name and Address
`State of Nationality
`State of Residence
`NOVARTIS PHARMACEUTICALS CORPORATION
`Patent Department
`One Health Plaza
`Building 101
`East Hanover, NJ 07936
`United States of America
`
`Telephone No.
`+1 862 778 1601
`Facsimile No.
`+A1 61 322 75 32
`E-mail address
`
`Further observations, if necessary:
`All future correspondence should be sent to the address for correspondenceindicated in Box 2. Advance copies of future
`notifications will also be sent in electronic form via e-mail to the e-mail address indicated above.
`
`pip_inbox.phchbs@novartis.com
`DQ Notifications by e-mail authorized
`
`. Acopy of this notification has been sent to:
`the receiving Office
`the International Searching Authority
`the Authority(ies) specified for supplementary search
`
`the International Preliminary Examining Authority
`the designated Offices concerned
`the elected Offices concerned
`
`PCT/EP2010/060011 20.09.2011
`Copy for (DO-US) 36
`PCT/EP2010/060011
`PATENT COOPERATION TREATY
`ADVANCE E-MAIL
`
`From the INTERNATIONAL BUREAU
`
`PCT
`
`NOTIFICATION OF THE RECORDING
`OF A CHANGE
`
`(PCT Rule 92bis.1 and
`Administrative Instructions, Section 422)
`
`Patent Department
`One Health Plaza
`Building 101
`East Hanover, NJ 07936
`ETATS-UNIS D'AMERIQUE
`
`other:
`
`The International Bureau of WIPO
`34, chemin des Colombettes
`1211 Geneva 20, Switzerland
`
`Authorized officer
`
`Facsimile No. +41 22 338 82 70
`Form PCT/IB/306 (January 2009)
`1/T6MDAEPY11
`
`
`Nissen Diana
`e-mail diana.nissen@wipo.int
`Telephone No. +4122 338 8054
`
`Regeneron Exhibit 1252.001
`Regeneron Exhibit 1252.001
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
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`Regeneron v. Novartis
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`wo&wy=yet.ESSh&&BSgop
`eee“wee<3wffeieSes.£5reyoteff @webeaj
`FilBacoehy
`
`NohgQ-
`
`Regeneron Exhibit 1252.011
`Regeneron Exhibit 1252.011
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`
`
`

`

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`Regeneron Exhibit 1252.012
`Regeneron Exhibit 1252.012
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`
`
`
`
`
`
`

`

`Electronic Patent Application Fee Transmittal
`
`Title of Invention:
`
`Surface Decontamination of Prefilled Containers in Secondary Packaging
`
`
`
`
`
`First Named Inventor/Applicant Name: Juergen Sigg
`
`
`
`Filer: Andrew K. Holmes/Andrea Jacquin
`
`Attorney Docket Number:
`
`Filed as Large Entity
`
`U.S. National Stage under 35 USC 371 Filing Fees
`
`ene|meeoema |
`
`ee
`
`meni
`a
`
`
`
`Independentclaims in excess of 3
`
`1614
`
`Miscellaneous-Filing:
`
`Regeneron Exhibit 1252.013
`Regeneron Exhibit 1252.013
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`eg:
`
`.
`
`id jaunt
`
`Sub-Total in
`
`UsDIs)
`
`1990
`
`Extension-of-Time:
`
`
`Patent-Appeals-and-Interference:
`
`Post-Allowance-and-Post-Issuance:
`
`Miscellaneous:
`
`Total in USD ($)
`
`Regeneron Exhibit 1252.014
`Regeneron Exhibit 1252.014
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`Electronic AcknowledgementReceipt
`
`a
`
`Title of Invention:
`
`Surface Decontamination of Prefilled Containers in Secondary Packaging
`
`
`
`
`
`First Named Inventor/Applicant Name: Juergen Sigg
`
`1095
`Customer Number:
`
`
`
`
`Filer: Andrew K. Holmes/Andrea Jacquin
`
`
`
`Filer Authorized By: Andrew K. Holmes
`
`Attorney Docket Number:
`
`
`
`ReceiptDate: 05-JAN-2012
`
`Filing Date:
`
`Time Stamp:
`
`14:56:16
`
`
`
`Application Type: U.S. National Stage under 35 USC 371
`
`Paymentinformation:
`
`Submitted with Payment
`
`yes
`
`Charge any Additional Fees required under 37 C.F.R. Section 1.21 (Miscellaneous fees and charges)
`
`Deposit Account
`
`190134
`
`The Director of the USPTO is hereby authorized to charge indicated fees and credit any overpayment as follows:
`
`Charge any Additional Fees required under 37 C.F.R. 1.492 (National application filing, search, and examination fees)
`
`Regeneron Exhibit 1252.015
`Regeneron Exhibit 1252.015
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`File Listing:
`
`Document
`sae
`:
`File Size(Bytes)/
`
`
`
`
`Number Message Digest|Part/.zip| (if appl.) DocumentDescription File Name
`..
`2982460
`53689_US_PCT_FilingPaperwo
`k_2012Dec5.pdf
`
`b21bbf63fada3b0d661 9cfd677cfOceef668
`aa?
`
`Multipart Description/PDF files in .zip description
`
`DocumentDescription
`
`Transmittal of New Application
`
`Oath or Declaration filed
`
`Information Disclosure Statement (IDS) Form (SBO8)
`
`
`Transmittal Letter
`
`
`26911
`
`
`Preliminary Amendment
`
`Specification
`
`Abstract
`
`Claims
`
`Applicant Arguments/Remarks Made in an Amendment
`
`Application Data Sheet
`
`Foreign Reference
`
`1_EP1433486A1.pdf
`
`Foreign Reference
`
`2_W00520847A2.pdf
`
`Foreign Reference
`
`3_W09744068A1.pdf
`
`Warnings:
`Information:
`
`Information:
`
`Information:
`
`= =
`
`=
`
`= ~!
`
`= ~
`
`1153643,
`
`dcb1469a395f8589445020564Ibfdf3adb74
`5971
`
`2134336
`
`€637047 2ce1 Sad56f2be69e80c3cAd3c544
`
`1068300
`
`2¢9753707b668e9a674aede6422b6db101
`
`
`
`Regeneron Exhibit 1252.016
`Regeneron Exhibit 1252.016
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`Information:
`
`Information:
`
`Foreign Reference
`
`4_EP1283061A1.pdf
`
`1909877
`
`9e086185f9d4bf0640bcc2d28dfe2e57665)
`Aa
`
`873344
`
`
`
`Foreign Reference
`
`5_EP1944044A1.pdf
`
`6abfe0d40c5f6fe665da5ee7ddd16839820G
`
`Warnings:
`Information:
`
`Foreign Reference
`
`6_W00877155A1.pdf
`
`1087219
`
`2b4b8615abc20ea9682bc208BRd 192d9e7
`Qecalb
`
`Warnings:
`Information:
`
`Fee Worksheet (SB06)
`
`fee-info.pdf
`
`Abdchdf49a7ddebe3cNee7dN9d 3ca8thN6s]
`49159
`
`Warnings:
`Information:
`
`This Acknowledgement Receipt evidences receipt on the noted date by the USPTO ofthe indicated documents,
`characterized by the applicant, and including page counts, where applicable. It serves as evidence of receipt similar toa
`Post Card, as described in MPEP 503.
`
`New Applications Under 35 U.S.C. 111
`If a new application is being filed and the application includes the necessary components for a filing date (see 37 CFR
`1.53(b)-(d) and MPEP 506), a Filing Receipt (37 CFR 1.54) will be issued in due course and the date shownon this
`Acknowledgement Receiptwill establish the filing date of the application.
`
`National Stage of an International Application under 35 U.S.C. 371
`If a timely submission to enter the national stage of an international application is compliant with the conditions of 35
`U.S.C. 371 and other applicable requirements a Form PCT/DO/E0O/903indicating acceptance of the application asa
`national stage submission under 35 U.S.C. 371 will be issued in addition to the Filing Receipt, in due course.
`
`New International Application Filed with the USPTO as a Receiving Office
`If a new international application is being filed and the international application includes the necessary componentsfor
`an international filing date (see PCT Article 11 and MPEP 1810), a Notification of the International Application Number
`and of the International Filing Date (Form PCT/RO/105)will be issued in due course, subject to prescriptions concerning
`national security, and the date shown on this AcknowledgementReceiptwill establish the international filing date of
`the application.
`
`Regeneron Exhibit 1252.017
`Regeneron Exhibit 1252.017
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property Organization
`International Bureau
`
`UDAATO TAAAA
`
`20 January 2011 (20.01.2011)
`
`(43) International Publication Date
`
`(10) International Publication Number
`WO 2011/006877 Al
`
`(51) International Patent Classification:
`A61E 2/00 (2006.01)
`A6IL 2/08 (2006.01)
`AGILE 2/20 (2006.01)
`BOSB 55/08 (2006.01)
`B65B 53/10 (2006.01)
`oe
`.
`.
`(21) International Application Number:
`
`.
`PCT/FP2010/060011
`
`(22) International Filing Date:
`
`(25) Filing Language:
`
`13 July 2010 (13.07.2010)
`English
`
`(26) Publication Language:
`(30) Priority Data:
`EP
`14 July 2009 (14.07.2009)
`09165456.6
`(for ail designated States except US): NO-
`(71) Applicant
`VARTIS AG [CII/CII]; Lichtstrasse 35, CII-4056 Basel
`(CH).
`
`English
`
`(72)
`(75)
`
`Inventor; and
`Jiirgen
`(for US only): SIGG,
`Inventor/Applicant
`[DE/CH]; c/o Novartis Pharma AG, Postfach, CH-Basel
`(CID.
`
`CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO,
`DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT,
`TIN, [IR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP,
`KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD,
`ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NL
`NO, NZ, OM,PE, PG, PII, PL, PT, RO, RS, RU, SC, SD,
`SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR,
`TT, TZ, UA, UG,US, UZ, VC, WN, ZA, ZM, ZW.
`(g4) Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG,
`2M, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU,TJ,
`TM), Duropean (AL, AT, BL, BG, CII, CY, CZ, DE, DK,
`EE, ES, FL PR, GB, GR, HR, HU, IE, IS, IT, LT, LU,
`LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK,
`SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,
`GW, ML, MR, NE, SN, TD, TG).
`Declarations under Rule 4.17:
`
`— as to applicant's entitlement to apply for and be granted
`a patent (Rule 4.17(ti))
`Published:
`
`(74) Agent: SPINNER, David, Richard; Novartis Pharma — with international search report (Art. 21(3))
`AG,Patent Department, CH-4002 Basel (CH).
`— before the expiration of the time limit for amending the
`(81) Designated States (unless otherwise indicated, for every
`claims and to be republished in the event of receipt of
`kind of national protection available): AE, AG, AL, AM,
`amendments (Rule 48.2(h))
`AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ,
`
`(54) Title: SURFACE DECONTAMINATION OF PREFILLED CONTAINERS IN SECONDARY PACKAGING
`
`(57) Abstract: Methods and systems for the terminal sterilization and surface decontamination ofprefilled containers containing
`sensilive drug products, such as biotech drug products that are otherwise temperature or radiation sensitive, and thus not suitable
`for terminal sterilization by classical methods involving steam or gamma rays. The methods and systems are especially suited for
`prefilled containers in secondary packaging. Methods include terminalsterilization by exposing prefilled containers in secondary
`packaging to tunable-beta radiation and further include terminal sterilization by exposing pretilled containers to controllable va-
`porized-hydrogen peroxide, including application of measures to reduce or prevent diffusion of vaporized-hydrogen peroxide into
`prefilled containers.
`
`Regeneron Exhibit 1252.018
`Regeneron Exhibit 1252.018
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`
`
`WoO2011/006877AdININMINTNININAAATTALAAA
`
`

`

`WO 2011/006877
`
`PCT/EP2010/060011
`
`Surface Decontamination of Prefilled Containers
`in Secondary Packaging
`
`FIELD OF THE INVENTION
`
`This invention relates to a method and system for terminal sterilization of the
`
`outer surface and/or surface decontamination of prefilled containers in secondary
`
`packaging, wherein the prefilled container contains a pharmaceutical or biological drug
`
`product.
`
`BACKGROUND
`
`10
`
`Prefilled containers are a type of medical device that are filled by the
`
`manufacturer at the time of assembly and provided to the end user, generally a health-
`
`care provider or a patient requiring treatment, in a sterile condition.
`
`Prefilled containers offer several advantages over
`
`traditional packaging of
`
`therapeutics, including ease of use, reduced risk of contamination, elimination of dosing
`
`15
`
`errors,
`
`increased drug supply and reduced waste. Of the various types of prefilled
`
`containers, prefilled syringes are the most common and best suited for parenteral
`
`administration of therapeutic products.
`
`Various methods of sterilization of medical devices are known, but not all
`
`methods work with syringes, especially syringes prefilled with a drug or protein solution.
`
`20
`
`Steam sterilization is commonly employed for sterilizing medical devices, which
`
`typically involves heating the device in a steam autoclave. The heat and pressure
`
`generated in the autoclave, however, can have an adverse effect on the device and,
`
`more importantly, on the integrity of the drug productfilled into the device. Steam
`
`sterilization may compromise the aesthetics of
`
`the product due to packaging
`
`25
`
`degradation from high temperature steam treatment. Moreover, the high temperatures
`
`of the process (e.g. 120° C — 132° C) preclude its use with heat sensitive materials,
`
`such as biotech drug products, specifically protein or other biological solutions.
`
`Radiation exposure is also commonly employedfor sterilizing medical devices,
`
`in which the product
`
`is subjected to ionizing radiation, such as gamma irradiation.
`
`30
`
`Radiation exposure results in harmful damage to sensitive solutions, specifically
`
`causing destruction to sensitive biologicals such as proteins, as well as generation of
`
`massive amounts of peroxides in aqueous solutions that in a secondary reaction further
`
`Regeneron Exhibit 1252.019
`Regeneron Exhibit 1252.019
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`WO 2011/006877
`
`PCT/EP2010/060011
`
`may damage the active ingredient. Further, sterilizing doses of gamma rays cause a
`
`brown discoloration of glass parts of the device, and is prone to damage elastomeric
`
`materials like plunger stoppers. This destruction of the elastomers leads to increased
`
`stickiness of the components thus impairing the functionality of the system. Thus
`
`radiation is not an appropriate means for sterilizing prefilled containers, such as
`
`syringes, containing a biotech drug product.
`
`Cold sterilization is a term collectively used for sterilization methods carried out at
`
`temperatures substantially below those of the steam process; attempts have been made
`
`to use ethylene oxide and hydrogen peroxide vapors as sterilants for this treatment.
`
`10
`
`Treatment with sterilizing gasses, however, bears the risk of insufficient removal of the
`
`oxidizing gas. Diffusion of gas into the product container affects the stability of the drug
`
`product through chemical modification by gas vapors, such as alkylation and oxidation.
`
`Prefilled syringes, although filled under aseptic conditions, are not packed into
`
`their secondary packaging in an aseptic environment and are therefore likely to be
`
`15
`
`microbiologically contaminated at
`
`their outside. Terminal
`
`sterilization of prefilled
`
`containers in secondary packaging is one wayto provide the device to an end user with
`
`a low bio-burden and low risk of contaminants, for safe application of the product by the
`
`end user. Moreover there is a strong market need for terminally antimicrobially-treated
`
`medical devices, such asprefilled syringes usedfor intravitreal injections.
`
`Due to the sensitive nature of certain drug products, such as proteins,
`
`it is not
`
`possible to perform terminal sterilization and surface decontamination of containers
`
`filed with such products using current methods,
`
`like steam,
`
`irradiation or cold
`
`sterilization.
`
`Specifically, high temperatures are known to denature proteins and
`
`gamma radiation has been shown to chemically modify biological solutions. Radiation
`
`techniques, such assterilization using gamma or beta radiation causes discoloring of
`
`packaging material and affects the long term stability of therapeutic agents such as
`
`protein or peptide solutions. As discussed above, oxidizing gases, while efficient for
`
`killing bacterial contamination, also harm biological molecules in sensitive therapeutic
`
`solutions.
`
`As protein and biological molecules will be more and more developed for
`
`20
`
`N nn
`
`30
`
`
`
`
`
`
`
`therapeutic use, a_terminalthe need for surface sterilization and surface
`
`
`
`
`
`
`
`Regeneron Exhibit 1252.020
`Regeneron Exhibit 1252.020
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`WO 2011/006877
`
`PCT/EP2010/060011
`
`decontamination method that is not harmful to the drug productwill continually increase
`
`in the near future. Moreover, as regulatory agencies may require higher levels of sterility
`
`assurance, pharmaceutical and biotech companies will seek alternative procedures to
`
`approach or meet mandated-microbiological purity levels, without compromising the
`
`safety and efficacy of pharmaceutical preparations.
`
`SUMMARY
`
`Described herein is
`
`a_
`
`terminal
`
`sterilization and surface decontamination
`
`treatment of prefilled containers, specifically for sterilization of prefilled containers
`
`10
`
`containing sensitive solutions, such as a drug product or biological therapeutic, within
`
`secondary packaging. In one embodiment, terminal sterilization is achieved by treating
`
`prefilled containers within secondary packaging with controllable vaporized-hydrogen
`
`peroxide (VHP). The principle is
`
`the formation a vapor of hydrogen peroxide in
`
`containment and a subsequent removal or inactivation of vapors in a controlled manner.
`
`15
`
`Prior to removal or inactivation, VHP condenses on all surfaces, creating a microbicidal
`
`film that decontaminates the container surface.
`
`It has been discovered that by varying the parameters of the antimicrobial
`
`treatment, for example — temperature, humidity, treatment duration, pressure, etc.,
`
`conditions are generated that prevent the leaching of VHP into the syringes. As an
`
`20
`
`example,
`
`the application of a vacuum at the end of the treatment will
`
`inverse the
`
`diffusion direction and reduce,
`
`if not stop, leaching of hydrogen peroxide through the
`
`rubbers. Further, inclusion of a gas plasma treatment after completion of the vaporized
`
`hydrogen peroxide cycle will further degrade all potentially remaining hydrogen peroxide
`
`residues. Prevention or reduction of leaching of detrimental concentrations of hydrogen
`
`N nn
`
`peroxide into the protein solution in the syringe, either by removal of vapors or
`
`inactivation of vapors, ensures that
`
`the long-term stability of
`
`the protein is not
`
`compromised. It further has been found that among the commercially available primary
`
`packaging components, there are only very few packaging material combinations that
`
`provide the required tightness of the system such as to avoid ingress of sterilizing
`
`30
`
`gasses into the pharmaceutical liquid enclosed by the prefilled container.
`
`Regeneron Exhibit 1252.021
`Regeneron Exhibit 1252.021
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`WO 2011/006877
`
`PCT/EP2010/060011
`
`Further described herein is
`
`terminal sanitization or sterilization and surface
`
`decontamination of prefilled containers within secondary packaging by tunable electron
`
`beam (low-energy beta-ray)
`
`irradiation technologies as an alternative to aseptic
`
`inspection and aseptic secondary packaging operations.
`
`In one embodiment, the use of low penetration depth radiation from a low-energy
`
`electron beam generator for a new application to sterilize the surface of secondary
`
`packaged drug product containers avoids aseptic packaging.
`
`In another embodiment,
`
`the penetration depth of electron beam radiation is tunable by adjustment of the
`
`accelerator voltage of the irradiation generator.
`
`10
`
`Generally,
`
`the concepts presented herein are applicable to all drug products
`
`having requirements or desirability for absence of viable organisms of the drug product
`
`container surface. The method and system described herein decontaminate or, more
`
`preferably render sterile an outside surface of primary packaged drug products within a
`
`secondary pack, thereby improving safety of products for critical administration (e.g. use
`
`15
`
`in a surgical suite or for intravitreal injections).
`
`The foregoing summary provides an exemplary overview of some aspects of the
`
`invention.
`
`It
`
`is not
`
`intended to be extensive, or absolutely require any key/critical
`
`elements of the invention.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`The detailed description is explained with reference to the accompanying figures.
`
`In the figures, the left-most digit(s) of a reference number identifies the figure in which
`
`the reference number first appears.
`
`Fig.
`
`1 shows an exemplary prefilled container in secondary packaging that is
`
`decontaminated on surfaces according to the methodsdetailed herein.
`
`Fig. 2 illustrates a block diagram of an exemplary system for surface
`
`decontamination of prefilled containers using vaporized-hydrogen peroxide.
`
`Fig. 3 illustrates a block diagram of an exemplary system for surface
`
`decontamination of prefilled containers using tunable-beta radiation.
`
`20
`
`N nn
`
`30
`
`DETAILED DESCRIPTION
`
`Regeneron Exhibit 1252.022
`Regeneron Exhibit 1252.022
`Regeneron v. Novartis
`Regeneronv. Novartis
`IPR2021-00816
`IPR2021-00816
`
`

`

`WO 2011/006877
`
`PCT/EP2010/060011
`
`The method and system described herein are for the sterilization and surface
`
`decontamination of prefilled containers containing sensitive solutions, such as drug
`
`products that are otherwise temperature or radiation sensitive or are sensitive to traces
`
`of oxidizing substances, and thus not suitable for terminal sterilization by classical
`
`methods involving steam, gamma or beta rays or sterilization with oxidizing gases or
`
`liquids. The method and system described herein are especially suited for prefilled
`
`containers that have been filled under aseptic conditions and been subject to additional
`
`processing, such as product labeling and subsequent secondary packaging. Methods
`
`include terminal
`
`sterilization and surface decontamination by exposing prefilled
`
`10
`
`containers in secondary packaging to tunable-beta radiation and further include terminal
`
`sterilization and surface decontamination by exposing prefilled containers to controllable
`
`vaporized-hydrogen peroxide, including measures to reduce or prevent the diffusion of
`
`vaporized-hydrogen peroxide into prefilled containers. The methods also include an
`
`optional step of actively destroying any residual peroxide molecules, for example, by
`
`15
`
`meansof gas plasma.
`
`Definitions
`
`In describing and claiming the terminal sterilization and surface decontamination
`
`method, the following terminology will be used in accordance with the definitions set
`
`20
`
`forth below.
`
`“Aseptic”
`
`conditions
`
`refer
`
`to
`
`conditions
`
`free
`
`of bacterial
`
`or microbial
`
`contamination.
`
`“Administration” refers to the method of administering treatment to a subject or
`
`patient in need thereof, such as parenteral administration, intravenous administration
`
`N nn
`
`and intravitreal administration.
`
`“Beta irradiation” refers to sterilization methods using beta rays.
`
`“Cold sterilization” refers to sterilization techniques employing chemical agents,
`
`gases, or irradiation. A requirement of cold sterilization is that the technique is carried
`
`out at temperatures below those used for steam sterilization, such as autoclavation.
`
`30
`
`“Container”, as used herein, is meant to include vials, syringes, bags, bottles, or
`
`other means useful for storage of medical treatments, such as drug products, whether in
`
`Regeneron Exhibi