INTERNATIONAL
`STANDARD
`
`ISO
`11040-4
`
`Second edition
`2007-02-01
`
`Prefilled syringes -
`Part 4:
`Glass barrels for injectables
`
`Seringues preremplies -
`
`Partie 4: Cylindres en verre pour produits injectab/es
`
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`Reference number
`ISO 11040-4 2007(E)
`
`© ISO 2007
`
`Regeneron Exhibit 1028.001
`
`

`

`ISO 11040-4:2007(E)
`
`PDF disclaimer
`
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`the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.
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`ISO 2007
`©
`All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
`electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or
`IS O's member body in the country of the requester.
`ISO copyright office
`Case postale 56 • CH-1211 Geneva 20
`Tel. + 4122 7490111
`Fax + 41 22 749 09 47
`E-mail copyright@iso.org
`Web www.iso.org
`Published in Switzerland
`
`© ISO 2007 -All rights reserved
`
`Regeneron Exhibit 1028.002
`
`

`

`ISO 11040-4:2007(E)
`
`Foreword
`
`ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
`(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
`technical committees. Each member body interested in a subject for which a technical committee has been
`established has the right to be represented on that committee. International organizations, governmental and
`non-governmental, in
`liaison with ISO, also take part in the work.
`ISO collaborates closely with the
`International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
`
`International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
`
`The main task of technical committees is to prepare International Standards. Draft International Standards
`adopted by the technical committees are circulated to the member bodies for voting. Publication as an
`International Standard requires approval by at least 75 % of the member bodies casting a vote.
`
`Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
`rights. ISO shall not be held responsible for identifying any or all such patent rights.
`
`ISO 11040-4 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection equipment
`for medical and pharmaceutical use.
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`This second edition cancels and replaces the first edition (ISO 11040-4: 1996) which has been technically
`revised.
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`ISO 11040 consists of the following parts, under the general title Preti/led syringes:
`
`Part 1: Glass cylinders for dental local anaesthetic cartridges
`
`Part 2: Plungers and discs for dental local anaesthetic cartridges
`
`Part 3: Aluminium caps for dental local anaesthetic cartridges
`
`Part 4: Glass barrels for injectables
`
`Part 5: Plungers for injectables
`
`© ISO 2007 - All rights reserved
`
`iii
`
`Regeneron Exhibit 1028.003
`
`

`

`ISO 11040-4:2007(E)
`
`Introduction
`
`For the parenteral use of liquid pharmaceutical products, at present ampoules and injection vials are mainly
`used. However, for the injection of the liquid pharmaceutical products contained in those vials, a hypodermic
`syringe combined with the appropriate injection needle is also needed. This means the liquid pharmaceutical
`product has to be transferred to the hypodermic syringe before its final use. This procedure is not only time(cid:173)
`consuming, but also presents a great number of possibilities for contamination.
`
`To ensure safe use of a liquid pharmaceutical product, prefilled syringes for single use are already on the
`market. Without doubt, such prefilled syringes permit immediate injection of the product contained after
`relatively simple handling.
`
`Based on diameter of the prefilled syringes, appropriate components, such as rubber plungers and aluminium
`caps, can also be standardized. The producers of filling machines can apply this part of ISO 11040 to achieve
`a degree of standardization in the equipment of the machines.
`
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`© ISO 2007 -All rights reserved
`
`Regeneron Exhibit 1028.004
`
`

`

`INTERNATIONAL STANDARD
`
`ISO 11040-4:2007(E)
`
`Prefilled syringes -
`
`Part 4:
`Glass barrels for injectables
`
`1 Scope
`
`This part of ISO 11040 applies to tubing-glass barrels (single-chamber design) for injection preparations and
`specifies materials, dimensions and performance details.
`
`Glass barrels from tubing glass in accordance with this part of ISO 11040 are intended for single use only. In
`conjunction with the right sealing components, they offer a safe system for parenteral use.
`
`2 Normative references
`
`The following referenced documents are indispensable for the application of this document. For dated
`references, only the edition cited applies. For undated references, the latest edition of the referenced
`document (including any amendments) applies.
`
`ISO 594-1, Conical fittings with a 6 % (Luer) taper for syringes, needles and certain other medical
`equipment - Part 1: General requirements
`
`ISO 594-2, Conical fittings with 6 % (Luer) taper for syringes, needles and certain other medical equipment -
`Part 2: Lock fittings
`
`ISO 720: 1985, Glass - Hydrolytic resistance of glass grains at 121 °C - Method oftest and classification
`
`ISO 4802-1: 1988, Glassware - Hydrolytic resistance of the interior surfaces of glass containers - Part 1:
`Determination by titration method and classification
`
`ISO 4802-2: 1988, Glassware - Hydrolytic resistance of the interior surfaces of glass containers - Part 2:
`Determination by flame spectrometry and classification
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`© ISO 2007 - All rights reserved
`
`1
`
`Regeneron Exhibit 1028.005
`
`

`

`ISO 11040-4:2007(E)
`
`3 Dimensions and designation
`
`3.1 Dimensions
`
`The dimensions of the glass barrel shall be as shown in Figure 1 and as given in Table 1 and in Annexes A
`and B.
`
`3.2 Designation
`
`The barrel designation shall comprise, in the following order, the descriptor "Barrel", a reference to this part of
`ISO 11040, the nominal volume, expressed in millilitres, the letters "lg" if the long version, a letter denoting the
`model and the glass colour.
`
`A barrel with a nominal volume of 1 ml long version (lg) with a 6 % Luer taper tip design (model A) made
`EXAMPLE 1
`of colourless glass (cl) complying with the requirements of this part of ISO 11040 is designated as follows:
`
`Barrel ISO 11040-4-1 - lg -A- cl
`
`A barrel with a nominal volume of 2 ml with 6 % Luer-lock taper tip design (model B) made of amber
`EXAMPLE 2
`glass (br) complying with the requirements of this part of ISO 11040 is designated as follows:
`
`Barrel ISO 11040-4- 2 - B- br
`
`A barrel with a nominal volume of 0,5 ml with a tip design for staked-needles (model C) made of
`EXAMPLE 3
`colourless glass (cl) complying with the requirements of this part of ISO 11040 is designated as follows:
`
`Barrel ISO 11040-4 - 0,5 - C - cl
`
`4 Requirements
`
`4.1 General
`
`Where national or regional regulations exist, e g Ph. Eur. or USP, the glass tubing shall comply
`
`4.2 Material
`
`The material shall be colourless (cl) or amber (br) glass of the hydrolytic resistance grain class HGA 1
`4.2.1
`in accordance with ISO 720:1985.
`
`It shall correspond to glass type I of the European Pharmacopoeia and United States Pharmacopoeia.
`
`If the glass tubing supplier intends to change the chemical composition or the colouring of the glass
`4.2.2
`material, the user of the primary packaging material shall be provided with information and samples for testing
`at least nine months in advance. Additional requirements concerning change control should be agreed upon
`between the glass tubing supplier and the user of the primary packaging material.
`
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`© ISO 2007 -All rights reserved
`
`Regeneron Exhibit 1028.006
`
`

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`FormA
`
`FonnB
`
`a Detail X: see Figure A.1 , Figure A-2 and Figure A.3.
`
`NOTE
`
`The design of the finger-flange should be agreed between customer and manufacturer.
`
`Figure 1 - Typical example of a glass barrel and glass fi nger-flanges for a prefilled syringe
`
`<=
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`
`© ISO 2007 - All rights reserved
`
`3
`
`Regeneron Exhibit 1028.007
`
`

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`Table 1 - Barrel dimensions
`
`Dimensions in millimetres
`
`Nominal
`volume
`
`ml
`
`0,5
`
`1a
`
`1b
`
`Glass barrel
`
`Finger-flange
`
`nom.
`
`6,85
`
`8,15
`
`10,85
`
`d1
`
`tol.
`
`± 0,1
`
`d2
`
`tol.
`
`± 0,1
`
`nom.
`
`4,65
`
`6,35
`
`8,65
`
`8,65
`
`d5
`
`min.
`
`4,40
`
`6,05
`
`8,25
`
`8,25
`
`11
`
`tol.
`
`±0,5
`
`nom.
`
`47,6
`
`54
`
`35,7
`
`49
`
`S1
`
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`
`1, 1
`
`0,9
`
`1, 1
`
`1, 1
`
`lz1
`
`d3
`
`d4
`
`nom.
`
`tol.
`
`±0,5
`
`1,8
`
`1,9
`
`2,2
`
`2,2
`
`nom.
`
`13,4
`
`13,8
`
`17,75
`
`17,75
`
`tol.
`
`± 0,4
`
`nom.
`
`10,5
`
`11
`
`14,7
`
`14,7
`
`tol.
`
`± 0,4
`
`2
`
`2,25
`
`3
`
`5
`
`10
`
`20
`
`10,85
`
`10,85
`
`10,85
`
`14,45
`
`17,05
`
`22,05
`
`± 0,2
`
`8,65
`
`8,65
`
`11,85
`
`14,25
`
`19,05
`
`8,25
`
`8,25
`
`11,45
`
`13,85
`
`18,40
`
`54,4
`
`72,2
`
`66,7
`
`87,25
`
`±0,75
`
`96,8
`
`1, 1
`
`1, 1
`
`1,3
`
`1,4
`
`1,5
`
`2,2
`
`2,2
`
`2,4
`
`2,5
`
`3, 1
`
`±0,5
`
`±0,6
`
`17,75
`
`17,75
`
`23
`
`27
`
`32,25
`
`±0,2
`
`±0,75
`
`± 1
`
`14,7
`
`14,7
`
`19,5
`
`21,5
`
`25,9
`
`±0,5
`
`±0,6
`
`a
`
`Called long version.
`b Called short/standard version.
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`ISO 11040-4:2007(E)
`
`4.3 Performance
`
`4.3.1 Hydrolytic resistance
`
`When tested in accordance with ISO 4802-1 or ISO 4802-2, the hydrolytic resistance of the internal surface of
`the glass barrel shall comply with the requirements of hydrolytic resistance container class ISO 4802-HC 1
`(ISO 4802-1/-2:1988) or, if required, glass type I Ph. Eur.
`
`Before conducting the test, the bottom end of the barrel shall be sealed with a suitable closure element, e.g. a
`silicon rubber closure.
`
`4.3.2 Annealing quality
`
`If the glass is annealed, the maximum residual stress shall not produce an optical retardation exceeding
`40 nm/mm of glass thickness when the glass barrel is viewed in a strain viewer.
`
`The test method for residual stress shall be agreed upon between glass manufacturer and customer.
`
`5 Marking
`
`Each package shall be labelled with the product code, designation, quantity and manufacturer's name.
`
`Further marking, e.g. product batch number, shall be agreed upon between customer and manufacturer.
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`© ISO 2007 - All rights reserved
`
`5
`
`Regeneron Exhibit 1028.009
`
`

`

`ISO 11040-4:2007(E)
`
`Annex A
`(informative)
`
`Head designs
`
`X
`
`Dimensions in millimetres
`
`a
`
`b
`
`Agreed between customer and manufacturer.
`Tolerance deviating from ISO 594-1.
`
`Figure A.1 - Model A: head design of a glass barrel with a 6 % Luer cone
`in accordance with ISO 594-1
`
`X
`
`Dimensions in millimetres
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`Undercut min. 0,03 mm, edges clear formed.
`Tolerance deviating from ISO 594-2.
`
`Figure A.2 - Model B: head design of a glass barrel with a 6 % Luer cone for Luer-lock
`in accordance with ISO 594-2
`
`© ISO 2007 - All rights reserved
`
`Regeneron Exhibit 1028.010
`
`

`

`ISO 11040-4:2007(E)
`
`X
`
`NOTE
`
`X dimension and internal shape of the bore are agreed upon between customer and manufacturer,
`
`Figure A.3 - Model C: head design of a glass barrel for staked-needle version
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`© ISO 2007 - All rights reserved
`
`7
`
`Regeneron Exhibit 1028.011
`
`

`

`ISO 11040-4:2007(E)
`
`Annex B
`(informative)
`
`Barrel total length
`
`Table B.1 - Barrel total length
`
`Dimensions in millimetres
`
`Nominal
`volume
`
`Total length
`
`l
`
`ml
`
`0,5
`
`1a
`
`1b
`
`2
`
`2,25
`
`3
`
`5
`
`10
`
`20
`
`nom.
`
`57,5
`
`64,0
`
`46,7
`
`60,0
`
`66,6
`
`84,4
`
`80,0
`
`100,5
`
`114,9
`
`tol.
`
`±0,5
`
`±0,5
`
`±0,5
`
`±0,5
`
`±0,75
`
`± 1,0
`
`±0,75
`
`± 1,0
`
`± 1,0
`
`a
`
`b
`
`Called long version.
`
`Called short/standard version.
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`© ISO 2007 -All rights reserved
`
`Regeneron Exhibit 1028.012
`
`

`

`ISO 11040-4:2007(E)
`
`Bi bl iog raphy
`
`[1]
`
`ISO 11040-5, Preti/led syringes - Parl 5: Plungers for injectab/es
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`
`9
`
`Regeneron Exhibit 1028.013
`
`

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