API and IP Newsletter

 Contents

• ANDA approvals in August 2022

• General information

• CBI chargesheet in Biocon case raises questions about how India manages drug trials

• Evolving real-time dissolution prediction and product release

• Intellectual Property

• The SPC application for EP(UK) 1809343 B1 (The decision of UK Court)

ANDA approvals in August 2022

We analyse ANDA approvals every month.

In August there are about 104 approvals and about 20% of those were tentative approvals. 

ANDA	Company	Sidvim comments
IVERMECTIN	ZYDUS	The approval is for Cream; Topical 1%, two other ANDAs approved. Ivermectin 1% topical cream is used to treat lesions of rosacea. Rosacea is a skin disease that causes redness and pimples on your nose, cheeks, chin, and forehead. IQVIA June 2022 data, the company said Ivermectin cream had annual sales of $176 million in the US. This ANDA approval might not be big contributor to Zydus US business.
CYCLOSPORINE	STRIDES PHARMA	Approval is for capsules, 25 mg, 50 mg and 100 mg. There are three other approved ANDAs. According to IQVIA MAT data, the US market for cyclosporine capsules USP, 25 mg, 50 mg, and 100 mg is approximately US$ 91 million. This means this approval might not fetch very significant market for Strides.
PEMETREXED DISODIUM	AMNEAL	Alimta is the trade name for generic drug name Pemetrexed. Block buster product in US. There was vitamin regimen patent which expired in May 2022. The patent covered the cancer treatment use of pemetrexed alongside vitamin B therapy.  After expiration it opened gate for generic such as Viatris and Apotex. DRL launched in May 2022. There are other 4-5 ANDA approvals in OB and soon there will be few other of Gxs in market.
BUMETANIDE	MSN	Bumetanide belongs to a group of medicines called loop diuretics or "water pills.". There are other half dozen approvals and launched products in US.
VASOPRESSIN	AMNEAL	Vasopressin had U.S. sales of approximately $878.5 million in December 2021 according to IQVIA. In February 2022, Dr. Reddy’s launched its authorized generic version of vials. Eagle had commenced marketing its product in January 2022 based on the District Court’s decision. We covered vasopressin decisions in Newsletters dated 12 September and 29 August 2022.  Two other ANDA approved. It could be good ANDA approval for Amneal to grab significant market share.

General observations:

1. Amneal was far ahead than others in August 2022 in seeking FDA approvals. There are overall 9 approvals, including two tentative approvals. 

2. At second place is Eugia. There are 3 approvals, two are for medroxyprogesterone acetate. 

3. DRL received three approvals.

4. Rubicon received two approvals but for old drugs like acyclovir oral suspension and Oxcarbazepine oral suspension.

General information

CBI chargesheet in Biocon case raises questions about how India manages drug trials

One of the CBI’s allegations is that in this recommendation, the word “protocol” (emphasised in text above) replaced the word “data”.

 

“Dr. S. Eswara Reddy, JDC has manipulated the Minutes of the Meeting of SEC held on 18.05.2022 by changing the word “Data” to “Protocol” in the recommendations and thereby causing substantial wrongful gain to M/s Biocon Biologics Limited, Bangalore,” the FIR, which ThePrint has accessed, says.

 

However, industry experts indicate that the correct word in this context is indeed “protocol”, and not “data”.

News here.

Evolving real-time dissolution prediction and product release

 

Researchers have developed a deterministic permeation model (DPM) that predicts the in vitro release profile of an active pharmaceutical ingredient (API) embedded in hydroxypropyl-methylcellulose (HPMC) matrix tablets. The model, based on Raman spectra, has the potential to process in real-time data yielded by process analytical technology (PAT) sensors, which could allow it to be utilised for real-time release testing (RTRt).

 

In the study, the researchers showed that the developed mechanistic model “is capable of accurately predicting the dissolution profile of extended-release tablets manufactured with various settings” by comparing the predicted dissolutions with measured values. Thus they deemed it “the first utilisation of such a model… to predict dissolution profiles based on data provided by PAT sensors”.

News here.

Intellectual Property 

 

The SPC application for EP(UK) 1809343 B1 (The decision of UK Court) 

APPLICANT Ethicon, Inc., and Omrix Biopharmaceuticals, Inc

ISSUE: Whether application for supplementary protection certificate SPC/GB14/029 meets the requirements of Article 3(d) of the SPC Regulation

What is SPC? 

A supplementary protection certificate (SPC) is a sui generis intellectual property (IP) right that extends the duration of certain rights associated with a patent. It enters into force after expiry of a patent upon which it is based. 

In simple term it is patent term extension in Europe to compensate the regulatory delay. 

This is the issue regarding EP1809343 B1, entitled “A reinforced absorbable multi-layered hemostatic wound dressing and method of making”, was filed on 17 October 2005, with the earliest priority date of 20 October 2004, and it was granted on 15 August 2012. The expiry date of this patent is 16 October 2025.

This patent relates to EVARREST, which is a hemostatic patch is clinically proven to achieve hemostasis. 

The invention disclosed in this patent relates to a multi-layered wound dressing comprising (among other things) ORC, thrombin and fibrinogen. The patent teaches desirability of keeping the ORC separate from the thrombin and fibrinogen components 

In short, the product comprises ingredients “thrombin, fibrinogen and oxidised regenerated cellulose (ORC)”. 

In the examiner’s opinion, as ORC is only referred to as an excipient, and owing to the absence of any mention in the SmPC and the EPAR of either a pharmacological, immunological or metabolic action of ORC, the medicinal product at issue should therefore be correctly identified as the combination of two active ingredients, namely thrombin and fibrinogen. 

This interpretation has the effect that a supplementary protection certificate (SPC) cannot be granted in this case, as the application would not satisfy Article 3(d) of the Regulation, since the combination of just thrombin and fibrinogen has already been the subject of two earlier marketing authorisations: EU/1/04/277 and EU/1/08/473. 

The applicants do not agree with the examiner’s interpretation 

They argue that, in line with the case law, the determination whether ORC is an active ingredient should be made in the light of all the facts. This has the consequence that, not just the SmPC and EPAR should be considered, but that it is appropriate, if necessary, to rely on evidence outside these documents, such as that provided by the applicants in the present case, in order to show that ORC can be considered an active ingredient. Since there has been no earlier marketing authorisation for the triple combination of fibrinogen, thrombin, and ORC, they submit that the application should be allowed to proceed. 

In the absence of any pharmacological effect and given the Judge’s (Hearing Officer) interpretation of the relevant case law, he did not consider that ORC could be deemed as an active ingredient within the meaning of Article 1(b) of the Regulation. Since it cannot be considered an active ingredient, the only active ingredients in EVARREST are thrombin and fibrinogen. 

As a consequence, this application does not meet the requirement of Article 3(d) of Regulation 469/2009 and application for SPC was rejected.  

Here