API and IP Newsletter

 Contents


FDA activities in last three quarters


We analyse FDA approvals (for small molecules), ANDA approvals and DMFs filed by Indian companies and publish our view point each week. 


FDA publishes data about actions each month. One can find summary on FDA website. Here.


GDUFA YEAR (Receipts)

21-Oct

21-Nov

21-Dec

22-Jan

22-Feb

22-Mar

22-Apr

22-May

22-Jun

22-Jul

22-Aug

22-Sep

FY-2022

Actions This Month

Refuse to Receive (RTR) - Originals

3

3

3

3

9

3

5

5

6

*



40

Standard - GDUFA II

3

2

1

1

8

3

3

5

5

*



31

Priority - GDUFA II

0

1

2

2

1

0

2

0

1

*



9

GDUFA I

0

0

0

0

0

0

0

0

0

*



0

Acknowledgement - Original

61

63

45

83

91

62

70

94

77

*



646

Refuse to Receive (RTR) - PAS

0

1

0

0

0

0

1

0

0

*



2

Withdrawals (all original ANDAs)

201

5

31

17

10

25

30

25

20

*



364

Approved ANDA

193

0

18

12

2

15

4

16

16

*



276

Unapproved ANDA

8

5

13

5

8

10

26

9

4

*



88

Withdrawals (PAS)

8

7

24

5

18

8

10

7

5

*



92

Approvals

49

67

34

61

59

63

45

84

52

65



579

First Time Generics

6

8

5

7

7

14

11

30

6

6



100

Not First Time Generics

43

59

29

54

52

49

34

54

46

59



479

First Cycle Approvals

12

13

4

17

8

10

8

11

13

*



96

Not First Cycle Approvals

37

54

30

44

51

53

37

73

39

*



418

Tentative Approvals (TA)

14

8

22

19

12

18

17

10

19

13



152

First Cycle TA (included above)

2

0

2

1

2

0

3

0

1

*



11

Complete Responses (CR)

152

168

108

195

141

141

168

125

159

171



1528

Information Requests (IR)

365

353

308

377

422

466

324

409

391

*



3415

Originals

210

233

194

236

260

284

193

264

228

*



2102

Supplements

155

120

114

141

162

182

131

145

163

*



1313

Discipline Review Letters (DRL)

188

201

202

165

168

243

141

184

314

*



1806

Drug Master File Completeness Assessment (DMF CA)

57

73

38

42

44

58

36

32

45

*



425



GDUFA YEAR (Receipts)

21-Oct

21-Nov

21-Dec

22-Jan

22-Feb

22-Mar

22-Apr

22-May

22-Jun

22-Jul

22-Aug

22-Sep

FY-2022

Submissions This Month

Abbreviated New Drug Applications (ANDA) +

24

51

135

61

50

125

64

74

58

60



702

Amendments

220

188

236

200

225

261

205

218

213

*



1966

Major

95

77

101

68

76

95

84

95

91

*



782

Minor

57

45

78

65

77

83

63

72

67

*



607

Unsolicited Amendments ++

68

66

57

67

72

83

58

51

55

*



577

Pre-Submission Facility Correspondence

14

2

2

11

2

6

4

2

10

*



53

CBE Supplements

811

753

821

643

548

748

669

665

691

*



6349

PAS Supplements +++

120

105

114

95

85

138

108

95

131

*



991

DMFs - Type II

49

50

77

55

58

82

48

52

65

*



536

Controls ++++

322

332

252

318

341

347

349

306

312

*



2879

Requests for Clarification

1

2

3

4

2

1

3

0

0

*



16

Post CR Meeting Requests This Month

5

3

5

3

4

4

7

4

7

*



42


General observations: 

  1. About 700 new ANDAs submitted in last 9 months and about 600 ANDAs are approved by FDA during same period

  2. About 20% of ANDA approvals are tentative approvals. Most of them must wait till patent expiration dates, or till the agreed launch date with innovator. 

  3. The real value for generic company lies in seeking approval for first time generics. One must notice less than 15% of the approvals (barring couple of exceptional months) are for first time generics.

  4. About 50-60 DMFs (Type -II) filed each month and about 35-40 DMFs are assessed by FDA. In other words, this could mean, about 30-40% of filed DMFs don’t generate revenue for their organisations. They could be classified as Non Preforming Assets in famous (or infamous) term used in recent days. 



General information


Merck's oral COVID-19 drug sees India's Everest Organics hit start on production


Indian generic drug maker Everest Organics started manufacturing active pharmaceutical ingredients for Merck’s oral COVID-19 treatment.

News of the production rollout comes in tandem with Merck filing for emergency use authorization from the FDA for the antiviral, molnupiravir, which would be the first newly developed oral treatment to stave off COVID-19.


News here.



University of Cincinnati researchers develop new treatment for common knee injury


Each year in the U.S., more than 500,000 people sustain tears in their meniscus, a piece of cartilage in the knee that cushions and stabilizes the joint. The tears often require invasive surgeries that frequently do not achieve the desired outcome.

Researchers at the University of Cincinnati are developing therapies that use a regenerative approach to meniscal tears that could benefit soldiers, athletes and weekend warriors by making those surgeries more reliable.


News here.


Intellectual Property 


Vasopressin:  CAFC affirmed the District of Delaware’s decision that Eagle’s vasopressin product does not infringe


Eagle is first to file an Abbreviated New Drug Application (ANDA) for Vasopressin, which had total U.S. sales of $786 million in 2020. 


OB listed patents are as below.


Patent No

Patent Expiration

Drug Product

Patent Use Code

Submission Date

9375478

01/30/2035


U-1857

06/28/2016

9687526

01/30/2035


U-1857

06/27/2017

9744209

01/30/2035


U-1857

08/29/2017

9744239

01/30/2035


U-1857

08/29/2017

9750785

01/30/2035

DP


09/05/2017

9937223

01/30/2035


U-1857

04/10/2018


In May 2018, Par sued Eagle for infringement of several patents. Mainly the claims 1, 4, 5, and 7 of the #209 patent and claims 1, 5, and 8 of the #785 patent were asserted. 


The trial was held in July 2021. 


A broad claim 1 of the #209 patent is as below: 

A method of increasing blood pressure in a human in need thereof, the method comprising administering to the human a unit dosage form, wherein the unit dosage form comprises from about 0.01 mg/mL to about 0.07 mg/mL of vasopressin or a pharmaceutically acceptable salt thereof, wherein: the unit dosage form has a pH of 3. 7-3.9;…………


During the stability study of batches, for one of the batches (SVA-001), Eagle recorded a pH level of 3.69 (which rounds to 3.7) at the 24-month mark-i.e., at the very end of a shelf life.


In response to the single out-of-specification pH test result for one batch, 

  1. Eagle "optimized" its manufacturing process "to assure tighter control of pH. To achieve this optimization, Eagle adjusted its manufacturing process. 

  2. Eagle added a new pH stabilization step after the pH adjustment step to ensure pH uniformity.

  3. Further, Eagle narrowed the in-process pH specifications for the pH measurements taken immediately before and after a filtration step from 2.5-4.5 (for the pre-optimization batches) to 3.42-3.54 (for the post-optimization batches). 


Thus, Eagle's optimized manufacturing process achieved its goal of assuring a tighter control over pH.

Table

Description automatically generated with medium confidence



On the other hand, Par has not demonstrated by a preponderance of the evidence that vasopressin manufactured according to Eagle's optimized process will have a pH that does not meet the stability pH specification.


So, Court found that Eagle does not infringe claims 1, 4, 5, and 7 of the #209 patent and claims 1, 5, and 8 of the #785 patent. This is the gist of the case; more details could be found here


Par appealed. 


On appeal, Par alleges the district court’s finding is clearly erroneous because “actual, real-world evidence” shows that the pH of products released at the upper end of the pH range identified in Eagle’s release specification will inevitably drift up into infringing territory. 


CAFC opined, the district court’s finding that there was no upward pH drift in Eagle’s post-release pH data was not clear error. The court thoroughly considered the post-release pH data Par cited, along with Eagle’s expert testimony assessing that data, and found that, while the pH measurements fluctuated over time, there was no discernible trend—and certainly not an inevitable upward trend—in the fluctuations. 


CAFC affirmed the District of Delaware’s decision that Eagle’s vasopressin product does not infringe on any of the patents asserted by Par Pharmaceutical.


Eagle had already commenced marketing its product in January 2022 based on the District Court’s decision. 


CAFC decision is here









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