Proposed ANDA Pipeline

TOFACITINIB CITRATE TABLET

IR Xeljanz ®
5 mg & 10 mg
 Tofacitinib Citrate Tablet
Business Information:

1 Market IQVIA MAT1120 $959.1million ~ 14.45 million tabs

8-10 including Zydus, Becken, Micro, Sun,

2 Competition
Prinston, Ajanta and AG

FY24 FY25 FY26 FY27 FY28

Unit Sales
3 - - - 0.19 0.25
(All Strengths & Packs) in Lacs

SKU wise NSP (All Strength) - - - $187.98 $165.43

RESTRICTED CIRCULATION 3
 Tofacitinib Citrate Tablet

Sr. No. Development Budget Quantity Kg /No’s Costing Remarks

1 Total API cost Including Development 1 2.0 lacs

2 Excipients for R & D Development -- 3.0 Lacs

3 Tooling for R & D development 2.0 Lacs

Fasting and Fed,

4 Pilot BE cost 16 Subject 19.0 lacs

5 Cost of RLD (5 mg) 120 Tablets 8.0 lacs $5157 /60 tablets

7 Cost of RLD (10 mg) 120 Tablets 8.0 Lacs $5157 /60 tablets

8 Cost of Pilot BE RLD 60 Tablets 4.0 lacs $5157 /60 tablets

Total Cost of Development 46.0 Lacs

5 mg Tofacitinib Citrate Equivalent to 8mg Tofacitinib

RESTRICTED CIRCULATION 4
 Tofacitinib Citrate Tablet
Technical Assessment
Product Name Tofacitinib Citrate Tablet

Gopal has proposed Potential in-license from Welding

1. The product can be developed at R&D with existing equipment.
2. The product can be transferred to a site having basic equipment for tablet manufacturing.
Conclusion:
3. Since the drug is BCS class III, a little efforts will be required to make it bioequivalent.
4. There are two drug substance patent expiry in 2023 & 2025 by the time we enter market
patents will expire.

RESTRICTED CIRCULATION 5
 Tofacitinib Citrate Tablet_Timeline

Sr. No. Milestone Tentative Timelines

1 Development completion Jun-22

2 Pilot BE Aug-22

3 Scale-up & exhibit batch Dec-22-Feb 23

4 Pivotal BE (in- vitro) May-23

5 6 months stability of EB Jul-23

6 ANDA submission Aug-23

RESTRICTED CIRCULATION 6
TOFACITINIB CITRATE ER TABLET
XELJANZ XR ®
11 mg & 22 mg
 Tofacitinib Citrate ER Tablet
Business Information:

1 Market IQVIA MAT1120 $2098.06million ~ 14.80 million tabs

8-10 including Zydus, Becken, Micro, Sun,

2 Competition
Prinston, Ajanta and AG

FY24 FY25 FY26 FY27 FY28

Unit Sales
3 - - - 0.10 0.43
(All Strengths & Packs) in Lacs

SKU wise NSP (All Strength) - - - $378.54 $329.14

RESTRICTED CIRCULATION 8
 Tofacitinib Citrate ER Tablet

Sr. No. Development Budget Quantity Kg /No’s Costing Remarks

1 Total API cost Including Development 1.5 3.0 lacs

2 Excipients for R & D Development -- 3.0 Lacs

3 Tooling for R & D development 2.0 Lacs

Fasting and Fed,

4 Pilot BE cost 16 Subject 19.0 lacs

5 Cost of RLD (11 mg) 120 Tablets 16.0 lacs $5157 /30 tablets

7 Cost of RLD (22 mg) 120 Tablets 16.0 Lacs $5157 /30 tablets

8 Cost of Pilot BE RLD 60 Tablets 8.0 lacs $5157 /30 tablets

Total Cost of Development 67.0 Lacs

5 mg Tofacitinib Citrate Equivalent to 8mg Tofacitinib

RESTRICTED CIRCULATION 9
 Tofacitinib Citrate ER Tablet
Technical Assessment
Product Name Tofacitinib Citrate ER Tablet

Gopal has proposed Potential in-license from Welding

1. The product can be developed at R&D with existing equipment.
2. Difficult to find osmotic site as it is osmotic product.
Conclusion:
3. BE study is not challenging.
4. Patent no. 10639309 expire in 2034 and it is difficult to bypass as it is covering
dissolution as well as osmotic system.

RESTRICTED CIRCULATION 10
Tofacitinib Citrate ER Tablet_Timeline

Sr. No. Milestone Tentative Timelines

1 Development completion Sep-22

2 Pilot BE Dec-22

3 Scale-up & exhibit batch Jun-23 to Sep-23

4 Pivotal BE (in- vitro) Oct-23

5 6 months stability of EB Mar-24

6 ANDA submission Apr-24

RESTRICTED CIRCULATION 11
 Tofacitinib Citrate Extended Release Tablet
Product Details
ACTIVE INGREDIENT: TOFACITINIB CITRATE
Proprietary Name: XELJANZ XR
Dosage Form; Route of
Tablet, Extended Release; Oral
Administration:
Market USA
Strength 11 mg & 22 mg
RLD: 11 mg & 22 mg
Reference Standard: 22 mg
BCS Class Class III
Application Number: N208246
Approval Date: Dec 12, 2019
Applicant Holder Full Name: PFIZER INC
6965027 (Expiry Date: 25/03/2023) (DS)
Patent No.: 10639309 (Expiry Date 14/03/2034) (DP)
RE41783 (Expiry Date: 12/08/2025) (DS)
Treatment of adult patients with moderately to severely active rheumatoid
Therapeutic Category:
arthritis.
Single-dose, two-treatment, two-period crossover in vivo fasting & fed
Bio-Study requirement
study EQ 22 mg Base

RESTRICTED CIRCULATION 12
GABAPENTIN TABLET
GRALISE ®
300 mg & 600 mg
 Gabapentin Tablets 300/600 mg
Business Information:

1 Market IQVIA MAT1120 $108.1million ~ 12.20 million tabs

2 Competition Teva plus 3-4 others

FY24 FY25 FY26 FY27 FY28

Unit Sales
3 - - 0.13 0.17 0.19
(All Strengths & Packs) in Lacs

SKU wise NSP (All Strength) - - $291.07 $253.25 $241.22

RESTRICTED CIRCULATION 14
 Gabapentin Tablets 300/600 mg
Budget for Development activity:

Sr. No. Development Budget Quantity Kg /No’s Costing Remarks

1 Total API cost Including Development 40.0 2.4 Lacs 6000/kg

2 Excipients for R & D Development -- 4.0 Lacs

3 Tooling for R & D development 2.0 Lacs

Fasting and Fed

4 Pilot BE cost 16 Subject 19.0 lacs

5 Cost of RLD (300 mg) 180 Tablets 1.35 lacs $ 886 / 90 tablets

6 Cost of RLD (600 mg) 180 Tablets 1.35 lacs $ 886 / 90 tablets

7 Cost of Pilot BE RLD 90 Tablets 0.7 lacs $ 886 / 90 tablets

Total Cost of Development 30.8 Lacs

RESTRICTED CIRCULATION 15
Gabapentin Tablets 300/600 mg
Technical Assessment
Product Name Gabapentin Tablets

Gopal has proposed Develop in-house.

1. The product can be developed at R&D with existing equipment.
2. The product can be transferred to a site having basic equipment for tablet
manufacturing.
Conclusion: 3. Since the drug is BCS class II, the drug is freely soluble in water and in alkaline and
acidic solutions, so BE study can be achieved by getting API with a predefined
particle size.
4. Since the patent expires in 2024 can be easily doable and by the time we enter the
market patents will expire.

RESTRICTED CIRCULATION 16
 Gabapentin Tablets _Timeline

Sr. No. Milestone Tentative Timelines

1 Development completion Jul-22

2 Pilot BE Oct-22

3 Scale-up & exhibit batch Feb-23-May 23

4 Pivotal BE (in- vitro) Jul-23

5 6 months stability of EB Oct-23

6 ANDA submission Nov-23

RESTRICTED CIRCULATION 17
Gabapentin Tablets 300/600 mg
Product Details
Active Ingredient: GABAPENTIN
Proprietary Name: GRALISE
Dosage Form; Route of
Tablet, Oral
Administration:
Market USA
Strength 300 & 600 mg
RLD: 300 & 600 mg
Reference Standard: 300 & 600 mg
BCS Class Class II
Application Number: N022544
Approval Date: Jan 28, 2011
Applicant Holder Full Name: Almatica Pharma Inc.

6723340 (Expiry Date: 25/10/2021) – (DP)

Patent No.: 7438927 (Expiry Date: 26/02/2024)
7731989, 8192756, 8252332, 8333992 (Expiry Date: 25/10/2022) – DP
Therapeutic Category Anticonvulsants

Bio-Study requirement Single-dose, two-way, crossover in-vivo fasting & fed on 600 mg strength

RESTRICTED CIRCULATION 18
OXCARBAZEPINE EXTENDED RELEASE TABLET
OXTELLAR XR ®
150 mg, 300 mg & 600 mg
 Oxcarbazepine ER Tablet 150/300/600 mg
Business Information:

1 Market IQVIA MAT1120 $198.5million ~ 13.67 million tabs

2 Competition

FY24 FY25 FY26 FY27 FY28

Unit Sales
3 - - - 0.05 0.15
(All Strengths & Packs) in Lacs

SKU wise NSP (All Strength) - - - $133.53 $121.71

RESTRICTED CIRCULATION 20
 Oxcarbazepine ER Tablet 150/300/600 mg
Budget for Development activity:

Sr.No. Activity Quantity Kg /No’s Costing Remarks

1 Total API cost Including Development 40 6.0 Lacs USD 200 / kg

2 Excipients for R & D Development -- 6.0 Lacs

3 Tooling for R & D development 3.0 Lacs

Fasting and Fed
4 Pilot BE cost 16 Subject 19.0 Lacs
$ 800.96 / 100
5 Cost of RLD (150 mg) 200 Tablets 1.2 Lacs
tablets
$ 800.96 / 100
6 Cost of RLD (300 mg) 200 Tablets 1.2 Lacs
tablets
$ 800.96 / 100
7 Cost of RLD (600 mg) 200 Tablets 1.2 Lacs
tablets
$ 800.96 / 100
8 Cost of Pilot BE RLD 100 Tablets 0.6 Lacs
tablets
38.2 Lacs
Total Cost

RESTRICTED CIRCULATION 21
Oxcarbazepine Extended Release Tablet
Technical Assessment
Product Name Oxcarbazepine Extended Release Tablet

Gopal has proposed Develop in-house.

1. The product can be developed at R&D with existing equipment.
2. The product can be transferred to a site having basic equipment for tablet
Conclusion: manufacturing.
3. Independent claim of the patent can be bypassed.
4. The patent expiry in 2027 by the time we enter market patents will expire.(???)
(Needs year wise market projection after 2027 from Gopal)

RESTRICTED CIRCULATION 22
Oxcarbazepine Extended Release Tablet_Timeline

Sr. No. Milestone Tentative Timelines

1 Development completion Sep-22

2 Pilot BE Dec-22

3 Scale-up & exhibit batch Jun-23- Sep 23

4 Pivotal BE (in- vitro) Oct-23

5 6 months stability of EB Mar-24

6 ANDA submission Apr-24

RESTRICTED CIRCULATION 23
 Oxcarbazepine Extended Release Tablet
Product Details
Active Ingredient: OXCARBAZEPINE
Proprietary Name: OXTELLAR XR
Dosage Form; Route of
Tablet, Extended Release; Oral
Administration:
Market USA
Strength 150 mg 300 & 600 mg
RLD: 150 mg 300 & 600 mg
Reference Standard: 600 mg
BCS Class Class II
Application Number: N202810
Approval Date: Oct 19, 2012
Applicant Holder Full Name: Supernus Pharmaceuticals Inc.

7722898, 8617600, 8821930, 9351975, 9370525, 9855278 (Expiry Date:

Patent No.: 13/04/2027) – (DP)
7910131, 9119791, 10220042 (Expiry Date: 13/04/2027)
Therapeutic Category Anti-epileptic drug

Bio-Study requirement Single-dose, two-way, crossover in-vivo fasting & fed on 600 mg strength

RESTRICTED CIRCULATION 24
 Oxcarbazepine Extended Release Tablet

STRATEGY
1) Patent No.: WO 2015/063670 Al
We can used same formulation i.e. Wockhardt filled for patent.
Sifting Oxcarbazepine, silicified microcrystalline cellulose, microcrystalline cellulose, polyvinyl pyrrolidone &
hydroxypropyl methylcellulose (K100M premium CR), separately dissolving sodium lauryl sulphate in water,
Granulating, drying & sifting, blending mixture with lubricant, coating the solid oral dosage form of with a
composition comprising methacrylic acid-ethyl acrylate copolymer

2) Combination of HPMC + Carbopol or grade of HPMC (One higher viscosity with lower)

3) Using Eudragit RSPO into Top spray granulation followed by lubrication with solubilizing agent than coating.

4) Use of Macrogol 4000 (PEG) Instead of SLS.

5) Avoid use of surface active agents, complexing agents, cyclodextrins, pH modifying agents, and hydration
promoting agents to avoid patent claim while remaining same.

RESTRICTED CIRCULATION 25
ENALAPRIL ORAL SOLUTION
EPANED ®
1mg/mL
 ENALAPRIL ORAL SOLUTION
Business Information:

1 Market IQVIA MAT1120 $42.5million ~ 12.56 million units

2 Competition Bion 10%

FY24 FY25 FY26 FY27 FY28

Unit Sales
3 - - 809 9671 20090
(All Strengths & Packs) in Packs

SKU wise NSP (All Strength) - - $158.41 $141.09 $134.56

RESTRICTED CIRCULATION 27
 ENALAPRIL ORAL SOLUTION
Budget for Development activity:

Sr. No. Activity Quantity Kg /No’s Costing Remarks

1 Total API cost Including Development 0.160 0.03 Lacs 16280 / kg

2 Excipients for R & D Development -- 6.00 Lacs

3 Tooling for R & D development 3.00 Lacs

4 Cost of RLD 20 0.06 Lacs $3.80 /Units

Total Cost of Development 9.10 Lacs

RESTRICTED CIRCULATION 28
ENALAPRIL ORAL SOLUTION
Technical Assessment
Product Name ENALAPRIL MALEATE ORAL SOLUTION

Gopal has proposed Develop in-house.

1. The product can be developed at R&D with existing equipment.
2. The product can be transferred to a site having basic equipment for liquid
manufacturing.
Conclusion:
3. All patents are interdependent and having independent claims for concentration of
Enalapril, concentration of preservatives (Covering all preservatives) and
concentration of buffer. Also all patents cover the pH range from 0 – 4.5 targeting a
pH of about 5 and change in concentration of buffer will bypass this patents.

RESTRICTED CIRCULATION 29
ENALAPRIL ORAL SOLUTION_Timeline

Sr. No. Milestone Tentative Timelines

1 Development completion Jun-22

3 Scale-up & exhibit batch Oct-22-Dec 22

4 6 months stability of EB Jun-23

5 ANDA submission Jul-23

RESTRICTED CIRCULATION 30
ENALAPRIL ORAL SOLUTION
Product Details
Active Ingredient: ENALAPRIL MALEATE
Proprietary Name: EPANED
Dosage Form; Route of Administration: SOLUTION; ORAL
Market USA
Strength 1mg / mL
RLD: Yes
Reference Standard: Yes
BCS Class Class III
Application Number: N208686
Approval Date: Sep 20, 2016
Applicant Holder Full Name: Azurity Pharmaceuticals Inc.

9669008, 10039745, 10772868, 10786482, 11040023, 11141405

Patent No.: (Expiry : 25/03/2036) – (DP)
9808442, 10154987 (Expiry : 25/03/2036)
Therapeutic Category Hypertension

Bio-Study requirement Not Mentioned

RESTRICTED CIRCULATION 31
ENALAPRIL ORAL SOLUTION
Description of Reference Product
Product Name ENALAPRIL MALEATE ORAL SOLUTION

Citric Acid, Mixed Berry Flavor, Purified Water, Sodium Benzoate, Sodium Citrate, and
Inactive Ingredients Sucralose. It may also contain Hydrochloric Acid or Sodium Hydroxide for pH
adjustment.
Packs Each bottle contains 150 mL.
Manufactured For Azurity Pharmaceuticals Inc.

API Solubility Sparingly soluble in water, soluble in ethanol, and freely soluble in methanol.

t1/2 The effective half life following multiple doses is 11-14 hours

Plasma protein binding

It is reported that less than 50% of enalaprilat is bound to human plasma proteins,
Clearance
Following oral administration in healthy male volunteers, the renal clearance was
approximately 158 ± 47 mL/min.8 It is reported that enalapril and enalaprilat are
undetectable in the plasma by 4 hours post-dosing

API Cost USD 220 / Kg

API Source Neuland Laboratories Limited

RESTRICTED CIRCULATION 32
 ENALAPRIL ORAL SOLUTION

STRATEGY

1) Formulation without preservative i.e. to be stable at 2-8°C . Not chance for microbial growth

2) Need preservative i.e. effective at pH 3.0 to 4.0.

3) Potassium sorbate which most active at pH 4.4

4) Use combination of buffer system i.e. Citric Acid and Potassium Citrate instead of Sodium Citrate.

5) Nisin is a natural preservative. It has been reported that nisin is most stable and efficient at pH 3

RESTRICTED CIRCULATION 33
Sucralfate Oral suspension 1g/10 ml
Sucralfate oral suspension 1 gm/10 ml

Business Review
Business Segment Wockhardt USA
Market Size ($mn) $208 million ~ 0.6 million liters
Competition (No of players) Amneal 52%, Endo 33%; Carafate 12%
Forecast
Year FY25 FY26 FY27 FY28
SKU wise NSP $ 32.91 $ 29.27 $ 27.84 $ 27.29
SKU wise Unit Sales
(Pack: 420mL Bottle) 93,361 157,605 195,459 185,686

Manufacturing
(Third party/In-house) TBD
Current Status

1. Formulation development- Finalised

2. Invitro Pilot BE study to be conducted in the US :Target date of initiation 1st feb 2022

Sr.No. Test Remarks

Data for C, H, S, Al by elemental analysis on Test API, data on C/S ratio

To be outsourced
and C/Al ratio
In-House /completion by 15
FTIR/ UV/XRD
Jan2022
API
characterizati Solid State Al NMR , DSC & TGA
1 To be outsourced
on
(Sameness) Acid neutralizing capacity In-House/ Completd
Aluminium content In-House/Completed
In-House/Completed
Sucrose Octasulfate & limit of Sucrose Heptasulphate

Comparative pH
Comparative specific gravity
Comparative viscosity profile of untreated formulation
Comparative change in apparent viscosity with addition of acid In-House/Completed
Pharmaceutic
2.
al Sameness
Comparative re-dispersibility (time required to re-disperse,
sedimentation time and volume)
Comparative acid neutralizing capacity
Comparative aluminum release at pH 1.2
Costing & Timelines

SN Milestone Projected Status in dec

Timelines in
Sep
1. Development completion Dec 21 Completed
2. API characterization (Sameness) Dec 21 Ongoing
3. Pharmaceutical Sameness Dec 21 ongoing
4. Pilot BE (In- vitro) Jan 2022 On time
Oxcarbazepine Oral Suspension
Trileptal®
300 mg/5ml
Oxcarbazepine Oral Suspension

Business Review
Business Segment Wockhardt USA
Market Size ($mn) $78.3 million ~ 183 million ml
Competition (No of players) 3
Forecast
Year FY25 FY26 FY27
Sales ($ Mn) 1.2 3.10 3.20
Units (ml) 0.9 million 2.0 million 2.6 million
Unit Sales (bottles), 250 ml 30,370 84,153 91,922
Manufacturing IH, MGP
(Third party/In-house)
DMF Sources Indian: Aurore, CTX, Amoli, Jubilant, SUN, DASMI,
Glenmark, MSN
Foreign: Polpharma, Humanwell, Archemia, FIS
Fabbrica, Signa

RESTRICTED CIRCULATION 39
Oxcarbazepine Oral Suspension
Status
• Aurore API Finalised
• Batch submitted to ARD for Method development. Method development to be completed by
15 Jan 2022
• 2 bottles of Innovator sample are available for initial characterization studies .

40