tI) NO V A RT I S
`
`Technical R&D / Chemical & Analytical Development
`
`Rivastigmine
`(ENA713-NXA, Base)
`Drug substance
`
`RSR3008059.001 Data-A (MN 116655)
`
`Registration stability report - Data tables
`
`Author(s): (cid:9)
`
`Giron Danielle
`
`Valid date: (cid:9)
`
`Date of approval
`
`Number of pages: 30
`
`Property of Novartis
`Confidential
`May not be used, divulged, published or otherwise disclosed
`without the consent of Novartis
`
`CONFIDENTIAL (cid:9)
`
`N0002374
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
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`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 2 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Table of contents
`Table of contents (cid:9)
`1 Introduction (cid:9)
`2 Analytical tests procedures and requirements (cid:9)
`2.1 (cid:9)
`Overview tests and requirements (cid:9)
`2.2 (cid:9)
`Test methods and validation (cid:9)
`2.2.1 (cid:9)
`Test methods and validation description and changes (cid:9)
`2.2.2 (cid:9)
`Extent of replication (cid:9)
`3 Results of tests (cid:9)
`3.1 (cid:9)
`Long term stability and accelerated testing (cid:9)
`3.1.1 (cid:9)
`Stability in deep freezer (- 20 degree C) (cid:9)
`3.1.2 (cid:9)
`Stability in refrigerator (5 degree C) (cid:9)
`3.1.3 (cid:9)
`Stability at 30 degree C/75% RI-1 (cid:9)
`Stability testing under light exposure (cid:9)
`Stress tests (cid:9)
`3.3.1 (cid:9)
`In liquid state 1 month at 40 degree C and 50 degree C, each at
`<30% RH and at 75% RH (cid:9)
`In liquid state 1 month at 80 degree C (N2, 02, added water) (cid:9)
`3.3.2 (cid:9)
`Forced decomposition (cid:9)
`3.3.3 (cid:9)
`3.3.4 (cid:9)
`Racemization study (cid:9)
`Hygroscopicity (cid:9)
`3.3.5 (cid:9)
`4 Interpretation of data. (cid:9)
`4.1 (cid:9)
`Interpretation of the data of long term testing and accelerated testing (cid:9)
`4.2 (cid:9)
`Interpretation of results of stress testing/ degradation pathways (cid:9)
`5 Chronology and changes to previous edition (cid:9)
`5.1 Chronology (cid:9)
`5.2 (cid:9)
`Changes to previous edition (cid:9)
`
`3.2 (cid:9)
`3.3 (cid:9)
`
`.... (cid:9)
`
`2
`3
`3
`3
`4
`4
`4
`5
`5
`5
` 12
`19
`25
`26
`
`26
`27
`28
`29
`29
`29
`29
`30
`30
`30
`30
`
`CONFIDENTIAL (cid:9)
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`IPR2014-00550
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`(cid:9)
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`

`

`Novartis (cid:9)
`Confidential
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 3 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Introduction
`
`The Registration stability report RSR3008059,001 Data-A is valid for Rivastigmine base and
`presents all data that are referenced in the Summary part RSR3008059.001 Summary-A.
`
`2 (cid:9)
`
`Analytical tests procedures and requirements
`
`Overview tests and requirements
`
`2.1 (cid:9)
`The following quality characteristics have been tested in the course of the stability study:
`
`Code
`10001,01
`
`20521,01
`54001,01
`
`Test
`Appearance by visual
`examination
`Identity by IR (film)
`Related substances by HPLC
`
`32001.01
`35801.01
`36311,01
`
`39001.01
`39011.01
`54001.01
`
`Enantiomer 208-87 by HPLC
`Water (Kari Fischer)
`Specific optical rotation, based
`on anhydrous substance
`Clarity of the solution
`Colour of the solution
`Assay by HPLC, calculated on
`anhydrous basis and
`corrected for solvents
`
`Requirements
`Viscous, clear, colourless to yellow to very slightly brown
`liquid
`Corresponds to the reference
`226-90 (cid:9)
`8-90 (cid:9)
`Unspecified individually (cid:9)
`Unspecified total (cid:9)
`Total related substances (cid:9)
`Not more than 0.3%
`Not more than 0.5%
`-44.0° to -38,0°
`
`Not more than 0,3%
`Not more than 0.1%
`Not more than 0.10%
`Not more than 0.3%
`Not more than 0.5%
`
`Clear
`Not more intensely coloured than Y5, BY5, B5, GY5
`98.0 - 102.0%
`
`CONFIDENTIAL (cid:9)
`
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`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 4 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`2.2 (cid:9)
`
`Test methods and validation
`The stability data between initial value and 3 months have been obtained by using the
`Analytical Information 1/95 approved 13 Dec 1995, the 6 months data have been obtained
`using the analytical information AI2/97 approved 14.04_97_ Other data have been obtained
`using the analytical information A13/98 approved 13.05.98 and the control procedure
`CP3008059.037.01-E0.01 approved 8.03,99. There are no difference between AI3/98 and
`CP3008059.037.01-E0.01 for the tests used. There are no relevant difference with the testing
`monograph DS_3008059_A_R_1 dated 27 Sep 2004. The same test Identity by IR (film) is
`used throughout stability: 1 drop of test substance is placed between 2 potassium bromide
`windows. In the development the test was named Identity by IR (KBr).
`
`Test methods and validation description and changes
`2.2.1 (cid:9)
`The test methods are laid down in the Testing Monograph DS 3008059 A_R 1 dated 27 Sep
`2004. Method validation are described in VDS 3008059 A R_1.
`
`The HPLC method used first for ENA713 base until 6 months time point used the mobile
`phase :
`
`A: potassium dihydrogen phosphate 0.02M /triethylamine 1000:2 adjusted to pH 5.0 using
`phosphoric acid
`
`B: potassium dihydrogen phosphate 0.02M /acetonitrile/triethylamine 500:500:2 adjusted to
`pH 5.0 using phosphoric acid
`
`Gradient profile:
`Time min.
`0
`%A
`70
`%B
`30
`
`20
`25
`75
`
`31
`25
`75
`
`32
`70
`30
`
`46
`70
`30
`
`as described in A11/95. From the 9 months time point the same validated HPLC method as in
`the current monograph was used.
`
`The current method is a reversed phase HPLC. The same detection at 214 nm is used. The pH
`of the mobile phase is 8.4 and it is not a gradient.
`
`The mobile phase is: 0.05M disodium hydrogen phosphate/methanol 42:58 (VN) adjusted to
`pH 8.45 with phosphoric acid. The validation has been updated accordingly.
`
`2.2.2 (cid:9)
`
`Extent of replication
`
`One replicate:
`
`Appearance, IR, clarity of solution, colour of solution
`
`Two replicates:
`
`Specific optical rotation, water (Karl Fischer), related substances, enantiomer, assay (HPLC)
`
`CONFIDENTIAL (cid:9)
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`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 5 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`3 (cid:9)
`
`3.1 (cid:9)
`
`Results of tests
`
`Long term stability and accelerated testing
`
`Stability in deep freezer (- 20 degree C)
`3.1.1 (cid:9)
`Batch 96905
`- 20°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`viscous, clear,
`no change
`no change
`no change
`colourless liquid
`-40.6°
`complies
`0.12%
`clear
`<Y6, <BY5, <Be,
`<GY5
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`-
`-
`0.10%
`clear
`complies
`
`-
`-
`0.17%
`clear
`complies
`
`-41.1°
`-
`0.10%
`clear
`complies
`
`12 months
`no change
`
`-40.1°
`complies
`0.12%
`clear
`colourless (<13s)
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`-
`101.3%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`101.2%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`
`100.2%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`100.5%
`
`CONFIDENTIAL (cid:9)
`
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`IPR2014-00550
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`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 6 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`- 20°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`3 years
`18 months
`2 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown liquid
`brown-yellow
`brown-yellow
`liquid
`liquid
`- 40.7°
`- 38.7°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 40.8°
`
`Batch 96905
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`-
`0.13%
`clear
`approx. Bs
`
`complies
`0.17%
`clear
`approx. Bo
`
`complies
`0.11%
`clear
`approx. B9
`
`-
`0.09%
`clear
`approx. Bo
`
`complies
`am%
`clear
`approx. Bo
`
`0.07%
`<0.05%
`<0.05%
`0 07%
`0 07%
`-
`100.3%
`
`0.06%
`<0 05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.0%
`
`0.06%
`<0.05%
`<0.05%
`0 06%
`0 06%
`<0.1%
`100.2%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`99.2%
`
`0.06%
`<0 05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.1%
`
`CONFIDENTIAL (cid:9)
`
`N0002379
`
`NOVARTIS EXHIBIT 2062
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`IPR2014-00550
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`(cid:9)
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`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 7 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Batch 96907
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`Batch 96907
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`- 20°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`no change
`viscous, clear,
`no change
`no change
`colourless liquid
`-40.3°
`complies
`0.06%
`clear
`<Y5, <BY5, <B5,
`<GY5
`
`-
`-
`0.08%
`clear
`complies
`
`-
`-
`0.11%
`clear
`complies
`
`12 months
`no change
`
`-39.7°
`complies
`0.11%
`clear
`colourless
`
`-
`-
`0.07%
`clear
`complies
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`101.0%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`102.1%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.9%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`< 0.1%
`100.4%
`
`-20°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`18 months
`2 years
`3 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown liquid
`brown-yellow
`brown-yellow
`liquid
`liquid
`- 39.8°
`- 38.9°
`complies
`complies
`0.20%
`0.08%
`clear
`clear
`approx. B9
`approx. B9
`
`-
`-
`0.08%
`clear
`approx. 09
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-
`-
`0.09%
`clear
`approx. B9
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 40.4°
`complies
`0.06%
`clear
`approx. B9
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.1%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`99.2%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.0%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`
`99.1%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`100.0%
`
`CONFIDENTIAL (cid:9)
`
`N0002380
`
`NOVARTIS EXHIBIT 2062
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`IPR2014-00550
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`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 8 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Batch 96908
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`- 20°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`no change
`viscous, clear,
`no change
`no change
`colourless liquid
`-39.8°
`complies
`0.12%
`clear
`<Y5, <BY5, <B5,
`<GY5
`
`-
`-
`0.1%
`clear
`complies
`
`-
`-
`0.1%
`clear
`complies
`
`12 months
`no change
`
`-39.8°
`complies
`0.11%
`clear
`colourless
`
`-
`-
`0.1%
`clear
`complies
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`100.1%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`101.6%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`100.3%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
` 100.3%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`100.1%
`
`Batch 96908 (cid:9)
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`- 20°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`18 months
`3 years
`2 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly brown
`brown-yellow
`brown-yellow
`liquid
`liquid
`liquid
`- 39.2°
`- 39.9°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 41.6°
`
`-
`0.09%
`clear
`approx. B9
`
`complies
`0.20%
`clear
`approx. Bg
`
`complies
`0.07%
`clear
`approx. Bg
`
`-
`0.08%
`clear
`approx. Bg
`
`complies
`0.07%
`clear
`approx. Bg
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.7%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.6%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`99.9%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`98.9%
`
`, (cid:9)
`
`0.08%
`<0.05%
`<0.05%
`0.08%
`0.08%
`<0.1%
`99.7%
`
`CONFIDENTIAL (cid:9)
`
`N0002381
`
`NOVARTIS EXHIBIT 2062
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`IPR2014-00550
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`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 9 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Batch 96905
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`-20°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`viscous, clear,
`no change
`no change
`no change
`colourless liquid
`-40.6°
`complies
`0.12%
`clear
`<Y5, <BY5, <B5,
`<GY5
`
`-
`-
`0.09%
`clear
`complies
`
`-
`-
`0.13%
`clear
`complies
`
`12 months
`no change
`
`-39.5°
`complies
`0.14%
`clear
`colourless
`
`-
`-
`0.12%
`clear
`complies
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`-
`101.3%
`
`<0.05%
`<0.05%
`<0.05%
`<0.05%
`<0.05%
`<0.05%
`99.9%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.9%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`100.8%
`
`- 20°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`18 months
`2 years
`3 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown-yellow
`brown-yellow
`brown liquid
`liquid
`liquid
`-39.8°
`-39.3°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-40.8°
`
`Batch 96905
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`-
`0.17%
`clear
`approx. B9
`
`complies
`0.22%
`clear
`approx. Bg
`
`complies
`0.13%
`clear
`approx. Bg
`
`-
`0.09%
`clear
`approx. B9
`
`complies
`0.15%
`clear
`approx. B9
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.6%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.1%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.7%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`99.7%
`
`0.08%
`<0.05%
`<0.05%
`0.08%
`0.08%
`<0.1%
`99.3%
`
`CONFIDENTIAL (cid:9)
`
`N0002382
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 9 of 30
`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 10 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Batch 96907
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`- 20°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`9 months
`Initial value
`3 months
`6 months
`no change
`viscous, clear,
`no change
`no change
`colourless liquid
`-40.3°
`complies
`0.06%
`clear
`<Y5, <BY5, <B5,
`<GY5
`
`-
`-
`0.11%
`clear
`complies
`
`-
`-
`0.11%
`clear
`complies
`
`12 months
`no change
`
`-39.8°
`complies
`0.14%
`clear
`colourless
`
`-
`-
`0.10%
`clear
`complies
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`101.1% _
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`100.3%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.5%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`100.4%
`
`- 20°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`18 months
`2 years
`3 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown-yellow
`brown-yellow
`brown liquid
`liquid
`liquid
`- 40.1°
`- 38.6°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 40.8°
`
`Batch 96907 (cid:9)
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`-
`0.11%
`clear
`approx. B9
`
`complies
`0.23%
`clear
`approx. Bg
`
`complies
`0.13%
`clear
`approx. Bg
`
`-
`0.10%
`clear
`approx. B9
`
`complies
`0.09%
`clear
`approx. Bg
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`98.9%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`98.6%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`98.9%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.3%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`99.2%
`
`CONFIDENTIAL (cid:9)
`
`N0002383
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 10 of 30
`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 11 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Batch 96908
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`- 20°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`9 months
`Initial value
`3 months
`6 months
`no change
`viscous, clear,
`no change
`no change
`colourless liquid
`-39.8°
`complies
`0.12%
`clear
`<Y5, <13Y5, <B5,
`<GY5
`
`-
`-
`0.10%
`clear
`complies
`
`-
`-
`0.14%
`clear
`complies
`
`12 months
`no change
`
`-39.6°
`complies
`0.13%
`clear
`colourless
`
`-
`-
`0.15%
`clear
`complies
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`100.1%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`101.5%
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`-
`99.8%
`
`0.08%
`<0.05%
`<0.05%
`0.08%
`0.08%
`-
`99.5%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`100.0%
`
`- 20°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`18 months
`2 years
`3 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly brown
`brown-yellow
`brown-yellow
`liquid
`liquid
`liquid
`- 39.6°
`- 38.7°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 41.0°
`
`Batch 96908
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`-
`0.16%
`clear
`approx. Bg
`
`complies
`0.25%
`clear
`approx. Bg
`
`complies
`0.13%
`clear
`approx. Bg
`
`-
`0.13%
`clear
`approx. Bg
`
`complies
`0.12%
`clear
`approx. Bg
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.3%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`99.8%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`99.7%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`99.5%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.7%
`
`CONFIDENTIAL (cid:9)
`
`N0002384
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 11 of 30
`
`(cid:9)
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 12 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Stability in refrigerator (5 degree C
`3.1.2 (cid:9)
`Batch 96905
`5°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`viscous, clear,
`no change
`no change
`no change
`colourless liquid
`-40.6°
`complies
`0.12%
`clear
`<Y5, <I3Y5, <135,
`<GY5
`
`-
`-
`0.10%
`clear
`complies
`
`-
`-
`0.15%
`clear
`complies
`
`-41.0°
`-
`0.13%
`clear
`complies
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`12 months
`no change
`
`-39.5°
`complies
`0.12%
`clear
`colourless
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`101.2%
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`-
`101.1%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`100.7%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.0%
`
`CONFIDENTIAL (cid:9)
`
`N0002385
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 12 of 30
`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 13 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`5°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`3 years
`18 months
`2 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown liquid
`brown-yellow
`brown-yellow
`liquid
`liquid
`-40.Y
`-38.8°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-41.5°
`
`-
`0.11%
`clear
`approx. Bs
`
`complies
`0.20%
`clear
`approx. Bg
`
`complies
`0.12%
`clear
`approx. B,?
`
`-
`0.10%
`clear
`approx. B9
`
`complies
`0.11%
`clear
`approx. Bs
`
`Batch 96905
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Unspecified (213-95)
`Enantiomer 208-87
`Assay by HPLC
`Legend: -
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`-
`100.2%
`not planned
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`<0.1%
`99.6%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`<0.1%
`99.8%
`
`0.10%
`<0.05%
`<0.05%
`0.10%
`0.05%
`0.05%
`-
`99.0%
`
`0.11%
`<0.05%
`<0.05%
`0.11%
`0.06%
`0.05%
`<0.1%
`99.7%
`
`CONFIDENTIAL (cid:9)
`
`N0002386
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 13 of 30
`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 14 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Batch 96907
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`5°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`viscous, clear,
`no change
`no change
`no change
`colourless liquid
`-40.3°
`complies
`0.06%
`clear
`<Y5, <0'115, <135,
`<GY6
`
`-
`0.09%
`clear
`complies
`
`-
`0.12%
`clear
`complies
`
`12 months
`no change
`
`-39.7°
`complies
`0.12%
`clear
`colourless
`
`-
`0.08%
`clear
`complies
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`101.3%
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`-
`101.9%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`100.3%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`100.1%
`
`5°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`18 months
`2 years
`3 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown-yellow
`brown liquid
`brown-yellow
`liquid
`liquid
`- 40.2°
`- 38.9°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 40.7°
`
`-
`0.10%
`clear
`approx. Bs
`
`complies
`0.17%
`clear
`approx. B9
`
`complies
`0.11%
`clear
`approx. B9
`
` 0.09%
`clear
`approx. B9
`
`complies
`0.08%
`clear
`approx. B9
`
`Batch 96907
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Unspecified (213-95)
`Enantiomer 208-87
`Assay by HPLC
`Legend: -
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.05%
`
`99.4%
`not planned
`
`nd
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.05%
`<0.1%
`99.0%
`not detected
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`<0.1%
`100.3%
`
`0.12%
`<0.05%
`<0.05%
`0.12%
`0.07%
`0.05%
`-
`99.5%
`
`0.12%
`<0.05%
`<0 05%
`0.12%
`0.07%
`0.05%
`<0.1%
`98.7%
`
`CONFIDENTIAL (cid:9)
`
`N0002387
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 14 of 30
`
`(cid:9)
`(cid:9)
`

`

`Novartis (cid:9)
`Confidential
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 15 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`Batch 96908
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`5°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`viscous, clear,
`no change
`no change
`no change
`colourless liquid
`-39,8°
`complies
`0.12%
`clear
`<Y5, <8'115, <85,
`<GY5
`
`-
`0.11%
`clear
`complies
`
`-
`0.14%
`clear
`complies
`
`12 months
`no change
`
`-39.8°
`complies
`0.14%
`clear
`colourless
`
`-
`0.09%
`clear
`complies
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`100.1%
`
`0.07%
`<0.05%
`<0.05%
`0 07%
`0.07%
`-
`101.6%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`99.9%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.4%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`100.6%
`
`5°C (Packaging E)
`Storage period (starting date: November 13th, 1996)
`18 months
`1 (cid:9)
`2 wars
`3 wars
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown-yellow
`brown liquid
`brown-yellow
`liquid
`liquid
`- 39.6°
`- 40.2°
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`
`complies
`0.20%
`clear
`approx. B9
`
`complies
`0.14%
`clear
`approx. 89
`
`0.09%
`clear
`approx. B9
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 41.4°
`
`complies
`0.08%
`clear
`approx. B9
`
`Batch 96908
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Unspecified (213-95)
`Enantiomer 208-87
`Assay by HPLC
`Legend: -
`
`0.07%
`clear
`approx. Bs
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0,05%
`
`99.8%
`not planned
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.05%
`<0.1%
`98.7%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.05% (cid:9)
`<0.1%
`99.7%
`
`_
`
`0.11%
`<0.05%
`<0.05%
`0.11%
`0.06%
`0.05%
`-
`99.0%
`
`0.12%
`<0.05%
`<0.05%
`0.12%
`0.07%
`0.05%
`<0.1%
`99.5%
`
`CONFIDENTIAL (cid:9)
`
`N0002388
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 15 of 30
`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 16 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`5°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`viscous, clear,
`no change
`no change
`no change
`colourless liquid
`-40.6°
`complies
`0.12%
`clear
`<Y5, <BY5, <B5,
`<GY5
`
`-
`-
`0.11%
`clear
`complies
`
`-
`-
`0.13%
`clear
`complies
`
`-
`-
`0.10%
`clear
`complies
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`-
`101.0%
`
`<0.05%
`<0.05%
`<0.05%
`<0.05%
`<0.05%
`<0.05%
`99.7%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.7%
`
`12 months
`no change
`
`-40.3°
`complies
`0.13%
`clear
`colourless
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`100.1%
`
`5 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-41.3°
`
`Batch 96905
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`Batch 96905
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`Related substances
`by HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`Legend: - not planned
`
`5°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`18 months
`2 years
`3 years
`viscous, clear,
`viscous, clear,
`viscous, clear,
`very slightly
`very slightly
`very slightly
`brown-yellow
`brown-yellow
`brown liquid
`liquid
`liquid
`-39.5°
`-38.7°
`
`-
`
`4 years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`-
`
`-
`0.09%
`clear
`approx. B9
`
`complies
`0.22%
`clear
`approx. By
`
`complies
`0.12%
`clear
`approx. By
`
`-
`0.09%
`clear
`approx. B9
`
`complies
`0.10%
`clear
`approx. By
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.1%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.1%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`99.7%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`99.6%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`<0.1%
`100.0%
`
`CONFIDENTIAL (cid:9)
`
`N0002389
`
`NOVARTIS EXHIBIT 2062
`Noven & Mylan v. Novartis & LTS Lohmann
`IPR2014-00550
`Page 16 of 30
`
`(cid:9)
`(cid:9)
`

`

`Confidential
`Novartis (cid:9)
`Rivastigmine (ENA713-NXA, Base) Drug substance
`Registration stability report - Data tables
`
`Page 17 of 30
`
`RSR3008059.001 Data-A (MN 116655)
`
`5°C (Packaging E) (under nitrogen)
`Storage period (starting date: November 13th, 1996)
`Initial value
`3 months
`6 months
`9 months
`viscous, clear,
`no change
`no change
`no change
`colourless liquid
`-40.3°
`complies
`0.06%
`clear
`<Y5, <BY5, <B5,
`<GY5
`
`-
`-
`0.09%
`clear
`complies
`
`-
`-
`0.11%
`clear
`complies
`
`-
`-
`0.11%
`clear
`complies
`
`0.05%
`<0.05%
`<0.05%
`0.05%
`0.05%
`<0.05%
`99.5%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`101.1%
`
`0.06%
`<0.05%
`<0.05%
`0.06%
`0.06%
`-
`100.3%
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`-
`99.5%
`
`12 months
`no change
`
`-39.8°
`complies
`0.13%
`clear
`colourless
`
`0.07%
`<0.05%
`<0.05%
`0.07%
`0.07%
`<0.1%
`99.3%
`
`S years
`viscous, clear,
`very slightly
`brown-yellow
`liquid
`- 42.0°
`
`Batch 96907
`
`Test
`Appearance
`
`Specific optical rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colour of the solution
`
`Related substances by
`HPLC
`Sum
`226-90
`8-90
`Unspecified sum
`Unspecified RRT 1.6
`Enantiomer 208-87
`Assay by HPLC
`
`Batch 96907
`
`Test
`Appearance
`
`Specific optical
`rotation
`Identity by IR (film)
`Water (KF)
`Clarity of the solution
`Colou