SYRINGE PACK AND METHOD OF PACKING A PREFILLED SYRINGE

Abstract

A syringe pack with a prefilled syringe (1) and a packaging (2) comprises: a barrel part (11) with an orifice (113) at a proximal end and a flange portion (112) at a distal end; a plunger part (13) extending through the distal end of the barrel part (11) into the barrel part (11); a stopper (12) adjacent to a proximal end of the plunger part (13) and arranged inside the barrel part (11) such that a dosage chamber (111) is formed inside the barrel part (11); and a drug substance arranged inside the dosage chamber (111), wherein the prefilled syringe (1) is arranged in the packaging (2) and the packaging (2) is configured to allow external sterilization of the prefilled syringe (1) arranged in the packaging (2). The packaging (2) comprises a containment part (21) having a fixing structure (211) which holds the barrel part (11) of the prefilled syringe (1) in a defined fix position; a constraining structure (23) which acts on the plunger part (13) of the prefilled syringe (1) to block a movement of the plunger part (13) of the prefilled syringe (1) in a distal direction; and a cover part (22) tightly closing the containment (21).

Claims

1. Syringe pack with a prefilled syringe and a packaging, the prefilled syringe comprising: a barrel part with an orifice at a proximal end and a flange portion at a distal end; a plunger part extending through the distal end of the barrel part into the barrel part; a stopper adjacent to a proximal end of the plunger part and arranged inside the barrel part such that a dosage chamber is formed inside the barrel part; and a drug substance arranged inside the dosage chamber, wherein the prefilled syringe is arranged in the packaging and the packaging is configured to allow external sterilization of the prefilled syringe arranged in the packaging, wherein the packaging comprises: a containment part having a fixing structure which holds the barrel part of the prefilled syringe in a defined fixed position; a constraining structure which acts on the plunger part of the prefilled syringe to block a movement of the plunger part of the prefilled syringe in a distal direction; and a cover part tightly closing the containment part.

2. The syringe pack according to claim 1, wherein the plunger part is distally ending in a thumb portion and the constraining structure of the packaging is configured to act on the thumb portion of the plunger part of the prefilled syringe to block the movement of the plunger part in the distal direction.

3. The syringe pack according to claim 1, wherein the constraining structure of the packaging applies a force on the plunger part of the prefilled syringe such that the dosage chamber inside the barrel part of the prefilled syringe is compressed.

4. The syringe pack according to claim 3, wherein the force applied to the plunger part of the prefilled syringe by the constraining structure of the packaging moves a proximal end side of the stopper of the prefilled syringe by about 0.2 mm to about 1 mm, preferably by about 0.3 mm to about 0.8 mm, more preferably by about 0.3 mm to about 0.7 mm and, particularly, by about 0.5 mm towards the orifice of the prefilled syringe.

5. The syringe pack according to claim 1, wherein the constraining structure of the packaging comprises a rigid blocking element acting on the plunger part of the prefilled syringe.

6. The syringe pack according to claim 5, wherein the rigid blocking element is integral with the containment part of the packaging.

7. The syringe pack according to claim 5, wherein the rigid blocking element is integral with the cover part of the packaging.

8. The syringe pack according to claim 1, wherein the constraining structure of the packaging comprises an insert acting on the plunger part of the prefilled syringe.

9. The syringe pack according to claim 8, wherein the insert of the constraining structure of the packaging is made of an elastic material and is arranged between the thumb portion of the plunger part of the prefilled syringe and the containment part of the packaging.

10. The syringe pack according to claim 8, wherein the insert of the constraining structure of the packaging is a fluid filled cushion and is arranged between the thumb portion of the plunger part of the prefilled syringe and the containment part of the packaging.

11. The syringe pack according to claim 8, wherein the insert of the constraining structure of the packaging is a pad having a series of slots and the thumb portion of the plunger part of the prefilled syringe is arranged in one slot of the series of slots.

12. The syringe pack according to claim 11, wherein the pad of the constraining structure of the packaging comprises a series of teeth and one slot of the series of slots is formed between each two neighboring teeth of the series of teeth.

13. The syringe pack according to claim 1, wherein the constraining structure of the packaging comprises a series of slots integral with the containment part of the packaging and the thumb portion of the plunger part of the prefilled syringe is arranged in one slot of the series of slots.

14. The syringe pack according to claim 1, wherein the constraining structure of the packaging comprises a rib integral with the containment part of the packaging and abutting the thumb portion of the plunger part of the prefilled syringe.

15. The syringe pack according to claim 1, wherein the constraining structure of the packaging comprises a containment holder and a plunger press, wherein the containment part is held in the containment holder and the plunger press acts on the thumb portion of the plunger part of the prefilled syringe via the containment part.

16. The syringe pack according to claim 15, wherein the containment holder of the constraining structure of the packaging comprises a base plate equipped with the containment holder and the plunger press.

17. The syringe pack according to claim 15, wherein the plunger press of the of the constraining structure of the packaging comprises a spring element tensioned such that a force is applied to the containment part and transferred to the thumb portion of the plunger part of the prefilled syringe.

18. A method of packing a prefilled syringe, comprising: obtaining a prefilled syringe having a barrel part with an orifice at a proximal end and a flange portion at a distal end, a plunger part extending through the distal end of the barrel part into the barrel part, and a stopper adjacent to a proximal end of the plunger part and arranged inside the barrel part such that a dosage chamber is formed inside the barrel part in which a drug substance is arranged; obtaining a packaging configured to allow external sterilization through the packaging; providing the packaging with a containment part having a fixing structure, a constraining structure and a cover part; arranging the prefilled syringe in the containment part of the packaging such that the fixing structure holds the barrel part of the prefilled syringe in a defined fixed position and such that the constraining structure acts on the plunger part of the prefilled syringe to block a movement of the plunger part of the prefilled syringe in a distal direction; and tightly closing the containment part of the packaging with the cover part.

19. The method according to claim 18, wherein arranging the prefilled syringe in the containment part of the packaging comprises applying a force on the plunger part of the prefilled syringe such that the dosage chamber inside the barrel part of the prefilled syringe is compressed.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0053] The syringe pack according to the invention and the method of packing a prefilled syringe according to the invention are described in more detail herein below by way of exemplary embodiments and with reference to the attached drawings, in which:

[0054] FIG. 1 shows a schematic view of contamination problems involved with a stopper moving due to varying pressure during external sterilization;

[0055] FIG. 2 shows a perspective view of a first embodiment of a syringe pack according to the invention;

[0056] FIG. 3 shows a perspective view of a second embodiment of a syringe pack according to the invention;

[0057] FIG. 4 shows a perspective view of a third embodiment of a syringe pack according to the invention;

[0058] FIG. 5 shows a perspective view of an alternative fluid filled cushion to be used in the syringe pack of FIG. 4;

[0059] FIG. 6 shows a perspective view of another alternative fluid filled cushion to be used in the syringe pack of FIG. 4;

[0060] FIG. 7 shows a cross-sectional view of a fourth embodiment of a syringe pack according to the invention;

[0061] FIG. 8 shows a perspective view of a fifth embodiment of a syringe pack according to the invention and of a detailed section thereof;

[0062] FIG. 9 shows a perspective view of a sixth embodiment of a syringe pack according to the invention and of a detailed section thereof;

[0063] FIG. 10 shows a cross-sectional view of a seventh embodiment of a syringe pack according to the invention and of a detailed section thereof;

[0064] FIG. 11 shows a top view on the syringe pack of FIG. 10;

[0065] FIG. 12 shows a top view on an external constraining structure of an eighth embodiment of a syringe pack according to the invention; and

[0066] FIG. 13 shows a perspective view of the syringe pack of FIG. 12.

DESCRIPTION OF EMBODIMENTS

[0067] In the following description certain terms are used for reasons of convenience and are not intended to limit the invention. The terms “right”, “left”, “up”, “down”, “under” and “above” refer to directions in the figures. The terminology comprises the explicitly mentioned terms as well as their derivations and terms with a similar meaning. Also, spatially relative terms, such as “beneath”, “below”, “lower”, “above”, “upper”, “proximal”, “distal”, and the like, may be used to describe one element's or feature's relationship to another element or feature as illustrated in the figures. These spatially relative terms are intended to encompass different positions and orientations of the devices in use or operation in addition to the position and orientation shown in the figures. For example, if a device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be “above” or “over” the other elements or features. Thus, the exemplary term “below” can encompass both positions and orientations of above and below. The devices may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein interpreted accordingly. Likewise, descriptions of movement along and around various axes include various special device positions and orientations.

[0068] To avoid repetition in the figures and the descriptions of the various aspects and illustrative embodiments, it should be understood that many features are common to many aspects and embodiments. Omission of an aspect from a description or figure does not imply that the aspect is missing from embodiments that incorporate that aspect. Instead, the aspect may have been omitted for clarity and to avoid prolix description. In this context, the following applies to the rest of this description: If, in order to clarify the drawings, a figure contains reference signs which are not explained in the directly associated part of the description, then it is referred to previous or following description sections. Further, for reason of lucidity, if in a drawing not all features of a part are provided with reference signs it is referred to other drawings showing the same part. Like numbers in two or more figures represent the same or similar elements.

[0069] FIG. 1 shows four situations of a prefilled syringe 1.sub.0 (PFS) within an external sterilization process. The PFS 1.sub.0 has a glass barrel 11.sub.0 in which a stopper 12.sub.0 is positioned. The stopper 12.sub.0 has three axially spaced sealing ribs 121.sub.0 completely extending about the stopper 12.sub.0. The distance between the uppermost and lowermost sealing rib 121.sub.0 defines a span H.sub.SB which can e.g. be 2.3 mm. The stopper 12.sub.0 tightens the barrel 11.sub.0 into an upper portion and a lower portion. The upper portion can, e.g., be provided with a plunger (not visible in FIG. 1) to facilitate a movement of the stopper 12.sub.0 for activating the PFS 1.sub.0. The lower portion can form a dosage chamber in which a drug substance is arranged.

[0070] In the left-hand illustration, the PFS 1.sub.0 is depicted before or in the beginning of the external sterilization. Thereby, it can be seen that since the upper portion of the barrel 11.sub.0 is not tightly sealed a contaminant 9.sub.0 can travel to above the stopper 12.sub.0. As can be seen in the second illustration from the left, when the pressure is reduced around the PFS 1.sub.0, e.g. to efficiently apply vaporized hydrogen peroxide (VHP) for sterilization, the pressure inside the dosage chamber and in the headspace of the stopper 12.sub.0 is higher than above the stopper 12.sub.0. As indicated by the wide arrow, this forces the stopper 12.sub.0 to move upwardly. Thereby, the contaminant 9.sub.0 may get between the top and middle sealing ribs 121.sub.0 of the stopper 12.sub.0.

[0071] As can be seen in the second illustration from the right, when the pressure is raised again around the PFS 1.sub.0 to the original atmospheric pressure, the stopper 12.sub.0 is moved back downwardly to its original position as indicated by the wide arrow. In a next sterilization step shown in the right-hand illustration, the pressure around the PFS 1.sub.0 is lowered again, e.g. to a vacuum pressure of about 4 mbar, and the stopper 12.sub.0 is upwardly moved again. Thereby, the contaminant 9.sub.0 gets between the lower and the middle sealing rib 121.sub.0 of the stopper 12.sub.0.

[0072] Continuing such cyclic pressure drop and raise, which is beneficial for an efficient external sterilization by means of VHP, bears a substantial risk that contaminants 9.sub.0 end up inside the dosage chamber and, thus, in the drug substance. However, such risk has to be eliminated which can be done by the syringe pack according to the invention and, for example, the embodiments thereof described below.

[0073] In FIG. 2 a first embodiment of a syringe pack according to the invention is shown. The syringe pack comprises a prefilled syringe (PFS) 1A and a packaging 2A. The PFS 1A has a barrel 11A as barrel part, a plunger 13A as plunger part, a stopper 12A, a tip cap 15A and an extended finger flange 14A. The barrel 11A is essentially cylindrically shaped and made of glass. It has an orifice at a proximal end, a flange portion 112A at a distal end and a dosage chamber 111A in its interior. At the distal end the interior of the barrel 11A is completely open.

[0074] The stopper 12A has a cylindrical body about which circumferential sealing ribs 121A extend. The sealing ribs 121A are spaced from each other along an axis of the stopper 12A. The stopper 12A is advanced through the open distal end of the barrel 11A such that it is positioned in the interior of the barrel 11A. Thereby, a proximal front face 122A of the stopper 12A limits the dosage chamber 111A of the barrel 11A. More specifically, the dosage chamber 111A of the barrel 11A extends between the proximal end of the barrel 11A or its orifice and the front face 122A of the stopper 12A. Inside the dosage chamber 111A a drug substance is arranged.

[0075] The plunger 13A is embodied with a rod portion 132A, a thumb portion 131A forming a proximal end 133A and a distal end 134A. The thumb portion 131A has an enlarged diameter and is shaped to accommodate a thumb of a user of the PFS 1A. The rod portion 132A extends through the open distal end of the barrel 11A such that the distal end 134A contacts the stopper 12A inside the barrel 11A and the thumb portion 131A is outside the barrel 12A. In particular, the distal end 134A of the plunger 13A is connected to the stopper 12A such that any axial movement of the plunger 13A moves the stopper 12A as well.

[0076] The tip cap 15A is mounted to the orifice of the barrel 11A. Thereby, it covers a tip or spout of the barrel 11A which forms the orifice. The tip cap 15A is embodied to tightly and safely close the orifice and to protect the orifice. The extended finger flange 14A is clipped on the flange portion 112A of the barrel 11A. In use of the PFS 1A, it allows for receiving fingers of a hand of the user such that a counter pressure can be generated opposite to a pressure applied to the thumb portion 131A.

[0077] The PFS 1A is arranged in the packaging 2A. The packaging 2A is configured to allow external sterilization of the PFS 1A inside the packaging 2A. Thereby, the packaging 2A comprises a containment 21A as containment part and a cover as cover part which tightly closes the containment 21A. In FIG. 1, the cover is removed from the containment 21A such that an interior of the latter is visible.

[0078] In particular, the containment 21A is equipped with a chamber body 212A dimensioned to receive the PFS 1A and a horizontal skirt 213A limiting the chamber body 212A. The skirt 213A is sealed to the sheet-like cover in order to tightly close the packaging 2A. Inside the chamber body 212A the containment 21A has two transversal and one back fixing braces 211A as fixing structure. The fixing braces 211A have recesses shaped in correspondence to an outer form of the PFS 1A or of specific parts thereof. More specifically, the left most brace 211A has a central recess holding the barrel 11A at the dosage chamber 111A, the middle brace 211A has a central recess to hold the barrel 11A adjacent to the extended finger flange 14A and the back brace 211A has a recess to accommodate a section of the plunger 13A which extends out of the barrel 11A. Between the back brace 211A and the middle brace 211A there is a slot in which the extended finger flange 14A is positioned such that the barrel 11A is immovable along its axis.

[0079] The back brace 211A further forms a rigid section as constraining structure abutting the thumb portion 131A of the plunger 13A. In particular, the rigid section acts on the proximal end side 133A of the plunger 13A. Thereby, the plunger 13A is forced into a distal direction along its axis such that the pressure in the dosage chamber 111A is raised. More specifically, the headspace of the PFS 1A is compressed by the rigid section of the back brace 211A acting on the thumb portion 131A of the plunger 13A. In that status, the PFS 1A is pre-compressed. A movement of the plunger 13A and the stopper 12A caused by a change of pressure in the containment 2A is thereby essentially reduced or even eliminated.

[0080] The packaging 2B is manufactured in a process similar to a conventional blister packaging process. In particular, the containment 21A is made from a thermoformed or cold formed plastic. The cover is made of a gas permeable but liquid tight synthetic foil such as a foil made of a high-density polyethylene material also known under the trademark Tyvek.

[0081] In order to avoid repetitive description the following applies: Unless specified to be different, the components or structures of the syringe pack shown in a specific Fig. are identical to the corresponding components and structures of the syringe pack of a previous Fig. More specifically, the components or structures of the syringe packs shown in the Figs. are provided with reference signs consisting of a numeral and a letter. Thereby, the numeral represents the particular component or structure and the letter represents the embodiment of the syringe pack according to the invention shown in the associated Fig. For example, the reference sign 1A represents the PFS (numeral 1) of the first embodiment of the syringe pack according to the invention (letter A). Thus, unless described to be different, the components and structures of a particular embodiment provided with reference signs are identical to the corresponding components and structures of a previous embodiment. For example, if the following description does not mention the plunger 13B of the second syringe pock shown in FIG. 3, it is identical to the plunger 13A of the syringe pack shown in FIG. 2.

[0082] FIG. 3 shows a second embodiment of a syringe pack according to the invention. The syringe pack comprises a PFS 1B and a packing 2B with a containment 21B and a cover. The PFS 1B and the cover of the packaging are embodied the same way as the PFS 1A and the cover of the first embodiment of the syringe pack described above in connection with FIG. 2. Also, the containment 2B of the packaging 2B is similar to the containment 2A of the first embodiment of the syringe pack described above in connection with FIG. 2.

[0083] However, a back fixing brace 211B of the containment 21B is shaped to receive a compressive insert 23B as constraining structure. The insert 23B is made of an elastic material. It is arranged between a thumb portion 131B of a plunger 13B of the PFS 1B and a right-hand end of the containment 21B. Thereby, it is compressed to a certain extent such that it acts on the plunger 13B of the PFS 1B by pushing it in a distal direction. Like this, a pressure in the dosage chamber 111B is raised and the headspace of the PFS 1B is compressed.

[0084] In FIG. 4 a third embodiment of a syringe pack according to the invention is shown. It comprises a PFS 1C and a packaging 2C. The packaging 2C has a containment 21C with a back fixing brace 211C shaped to receive an air-filled cushion 23C as constraining structure. The insert 23C is made of two foils sealed at their borders and filled with air to a certain extent. It is positioned between a thumb portion 131C of a plunger 13C of the PFS 1C and a right-hand end of a containment 21C of the packaging 2C. Thereby, it is compressed to a certain extent such that it acts on the plunger 13C of the PFS 1B by pushing it in a distal direction. Like this, a pressure in the dosage chamber 111C is raised and the headspace of the PFS 1C is compressed.

[0085] FIG. 5 and FIG. 6 show two further embodiments of air filled cushions 23Ci, 23Cii to be used in the packaging 2C. In particular, cushion 23Ci has a circular general shape and cushion 23Cii a squared general shape.

[0086] FIG. 7 shows a fourth embodiment of a syringe pack according to the invention. It comprises a PFS 1D and a packaging 2D. The packaging 2D has a containment 21D with an elevated bottom towards the right-hand end instead of a back fixing brace. The elevated bottom has a series of three transversal slots 23D as constraining structure integral with the containment 21D. In the middle slot 23D a thumb portion 131D of a plunger 13D of the PFS 1D is arranged. Like this, the plunger 13D is axially fixed such that an axial movement is prevented. In particular, the plunger 13D is fixed such that a pressure in a dosage chamber 111D of a barrel 11D of the PFS 1D is elevated and the headspace of the PFS 1D is compressed to a certain extent.

[0087] As can be seen in the cross-sectional view of FIG. 7, the orifice of the barrel 11D of the PFS 1D has a spout 113D with a central passage. The tip cap 15D is rigid and houses a sealing plug 16D, which tightly seals the central passage of the spout 113D. In particular, the spout 113D is closed by the sealing plug 16D which is protected by the tip cap 15D. Furthermore, it is depicted in FIG. 7 that the distal 134D of the plunger 13D is shaped as a plug which is received in a central cavity of the plunger 12D. Like this, the plunger 13D and the stopper 12D are firmly connected. The PFS of the other embodiments of syringe packs shown in the Figs. have an identical arrangement of spout, sealing plug, tip cap and plunger-stopper connection.

[0088] In FIG. 8 a fifth embodiment of a syringe pack according to the invention is shown. It comprises a PFS 1E and a packaging 2E. The packaging 2E has a containment 21E with a back fixing brace 211E shaped to receive a pad 23E as constraining structure. The pad 23E is equipped with a series of transversal slots 231E separated by respective walls 232E. A thumb portion 131E of a plunger 13E of the PFS 1E is arranged in one of the slots 231E of the pad 23E. Like this, the plunger 13E is axially fixed by the two walls 232E neighboring the slot 231E such that an axial movement of the plunger 132E is prevented. In particular, the plunger 13E is fixed such that a pressure in a dosage chamber 111E of a barrel 11E of the PFS 1E is elevated and the headspace of the PFS 1E is compressed to a certain extent.

[0089] FIG. 9 shows a sixth embodiment of a syringe pack according to the invention. It comprises a PFS 1F and a packaging 2F. The packaging 2F has a containment 21F with a back fixing brace 211F shaped to receive a pad 23F as constraining structure. The pad 23F is equipped with a series of transversal slots 231F separated by respective teeth 232F. A thumb portion 131F of a plunger 13F of the PFS 1F is arranged in one of the slots 231F of the pad 23F. Like this, the plunger 13F is axially fixed by the tooth 232F distally neighboring the slot 231F such that an axial movement of the plunger 132F in a distal direction is prevented. Due to provision of teeth 232F in the pad 23F, it is possible to advance the thumb portion 131F into a proximal direction but movement in the distal direction is blocked. Like this, the plunger 13F can be proximally forwarded until it is fixed in a position where a pressure in a dosage chamber 111F of a barrel 11F of the PFS 1F is elevated and the headspace of the PFS 1F is compressed to a certain extent.

[0090] In FIG. 10 and FIG. 11 a seventh embodiment of a syringe pack according to the invention is shown. It comprises a PFS 1G and a packaging 2G. The packaging 2G has a containment 21G and a cover 22G. The containment 21G does not have a back fixing brace 211G. The cover 22G is equipped with a gripping bulge 23G above the top end of a thumb portion 131G of a plunger 13G of the PFS 1G as a rigid blocking element of a constraining structure integral with the cover part 22G. The bulge 23G receives the thumb portion 131G of the plunger 13G. Like this, the plunger 13G is axially fixed such that an axial movement is prevented. In particular, the plunger 13G is fixed when a pressure in a dosage chamber 111G of a barrel 11G of the PFS 1G is elevated and the headspace of the PFS 1G is compressed to a certain extent. The cover 22G is further provided with two parallel bonding strips 221G extending into a chamber body 212G of the containment 21G. The strips 221G are located at either side of the thumb portion 131G. Like this, the thumb portion 131G can be securely held.

[0091] FIG. 12 and FIG. 13 show an eighth embodiment of a syringe pack according to the invention. It comprises a PFS 1H and a packaging 2H with a containment 21H and a cover. The containment 21H is not equipped with a back fixing brace 211H. The syringe pack further comprises an external constraining structure 23H with a base plate on which a containment holder 231H and a plunger press 232H are arranged. The containment holder 231H comprises two lateral blocks formed to receive the containment at one of its fixing braces 211H in between. Thereby, the containment 21H is held in the containment holder 231H. The plunger press 232H has a stamp part in a housing. A spring drives the stamp part towards a back side of the containment 21H such that it acts on a thumb portion 131H of a plunger 13H of the PFS 1H via the containment 21H. Like this, the plunger 13H is proximally forwarded and the headspace of the PFS 1H is compressed.

[0092] This description and the accompanying drawings that illustrate aspects and embodiments of the present invention should not be taken as limiting—the claims defining the protected invention. In other words, while the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. Various mechanical, compositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this description and the claims. In some instances, well-known circuits, structures and techniques have not been shown in detail in order not to obscure the invention. Thus, it will be understood that changes and modifications may be made by those of ordinary skill within the scope and spirit of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below.

[0093] The disclosure also covers all further features shown in the Figs. individually although they may not have been described in the afore or following description. Also, single alternatives of the embodiments described in the figures and the description and single alternatives of features thereof can be disclaimed from the subject matter of the invention or from disclosed subject matter. The disclosure comprises subject matter consisting of the features defined in the claims or the exemplary embodiments as well as subject matter comprising said features.

[0094] Furthermore, in the claims the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single unit or step may fulfil the functions of several features recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. The terms “essentially”, “about”, “approximately” and the like in connection with an attribute or a value particularly also define exactly the attribute or exactly the value, respectively. The term “about” in the context of a given numerate value or range refers to a value or range that is, e.g., within 20%, within 10%, within 5%, or within 2% of the given value or range. Components described as coupled or connected may be electrically or mechanically directly coupled, or they may be indirectly coupled via one or more intermediate components. Any reference signs in the claims should not be construed as limiting the scope.