Indian Pharma: Transitioning to Specialty Generics | 1 · 8 | Indian Pharma: Transitioning to Specialty Generics Indian pharma companies championed the art of manufacturing generic

Indian Pharma: Transitioning to Specialty Generics | 1

FINAL PHARMA 2017.indd 1 7/26/2017 7:13:25 PM


TITLE Indian Pharma: Transitioning to Specialty Generics

YEAR July, 2017

AUTHORS Life Sciences & IT Knowledge Banking Group, Corporate Banking , YES BANK

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Executive Summary 6

1. Journey of India Pharma-An Introduction 8

2. Specialty Generics 12 A. New Therapeutic Entities (NTE) 12 B. Complex generics 12

3. Topical Delivery System 16

4. Generic Injectables 18

5. Biosimilars 21

6. US Market Opportunities for Specialty Generics 23 A. Market dynamics 23 B. Market opportunity 24 C. R&D investments 24 D. Product filing pattern 25

7. Current & Future Opportunities 26 A. Disease portfolio for specialty medicines 26 B. Innovative drug delivery systems 26 C. Focused R&D to deepen anchorage 27 D. Understanding the market demands and 27

transforming rapidly

8. Recommendations & Way Forward 28

Bibliography 31

Abbreviations with their Expanded Forms 32

TABLE OF CONTENTS


6 | Indian Pharma: Transitioning to Specialty Generics

The journey of Indian pharma, and its transition from vanilla generics to specialty segment is encouraging, and at the same time filled with challenges as Indian companies navigate in uncharted waters. Especially, choosing differentiated generics and targeting one of the most stringent markets of the world in terms of quality, the US, has been very demanding. The severity of pricing pressure in the US generic space took Indian players’ off-guard and led to declining sales and profitability. The changing political scenarios in US have added to the woes. Indian pharma players are in their preparatory phase and have been investing in complex generic assets, as they are putting a lot of effort in biosimilars, complex injectables and inhalers.

Dual opportunity of demand & profitability

Staying profitably relevant in the market is the key as Indian players are investing on new product and technology acquisitions or identifying relevant business partners to ensure deeper penetration in the US market. US is by far the largest and the most diversified pharmaceutical market in the world. Its healthcare expenditure is also highest, which is about USD 3.12 TN (almost 17.4% of its GDP as in 2016). The US Generics market is valued at ~USD 70 BN with specialty generics having a significant share of the pie and increasing. The much appreciated greater participation of the government in-terms of investing in healthcare along with the ever growing demand of more effective treatments has created a

EXECUTIVE SUMMARY

Diverse US market:

steady demand &

dynamic political

scenario

Demands of specialized

therapeutic procedures

to handle disease

burden

Shrinking margins

of 'me too'

generics

Market

consolidation,

M&As to diversify

specialty portfolio

Boosting R&D

capabilities to

strengthen

specialty range

More thrust

towards quality

Trends Redefining Pharma Strategies



huge opportunity for the pharmaceutical sector to serve. Margins are healthy for such niche products which have fewer competitors. The generic market of injectable is USD 8 BN in US and has the potential to easily cross CAGR of 10 percent, especially with new technologies and improvised state-of-art delivery procedures. Consolidation is a trend which is also catching up to fuel rapid growth, as the bigger it gets the better it is to tide neck-to-neck competition.

Value creation with R&D

The rapidly ageing population and associated rise in chronic diseases, increased urbanization and higher disposable incomes are some of the reasons why the US market is a preferred destination for many international players. In past couple of years the specialty drugs in US are in higher demand, as almost two-thirds of the overall medicines spend are on specialty drugs or complex medicines in many households. Pharma companies in India are waking up to this opportunity. Indian pharma

industry can derive great value if it adapts its research and manufacturing capabilities and look for opportunities in niche therapies such as cancer, dermatology, ophthalmology, orphan diseases, etc. or those which involves superior drug delivery or usage of alternate routes of drug-administration.

To create a niche portfolio some bold Indian players have invested millions of dollars, as their overall R&D expense has gone up to 10 percent range which was a meagre ~3% five years ago. On the other side the USFDA has also strengthened its internal processes via GDUFA guidelines not only to ensure approvals come in time for the applicants, but also companies who are not complying to GMP gets heavily penalized.

We believe India pharma has the capabilities to overcome the near term hurdles and emerge victorious over the long run.

“

”




Indian pharma companies championed the art of manufacturing generic medicines in the past decades and were actively capturing markets with their differentiated strategies and strong adaptability in global markets. Its medicines were manufactured at a lower cost domestically as compared to its foreign competitors which helped India to carve its position in generic space. The Indian pharma companies clocked healthy sales in not only huge markets of US and Europe but also in the emerging markets of Latin America, ASEAN countries and CIS nations. The US market has been the strongest growth driver for the Indian pharma. Indian companies have managed to expand their outreach in tightly regulated markets, augmented their product portfolio and increased presence through brown field overseas acquisitions. The past decade was not only about flexing its muscles through top line and bottom line but also through the number of ANDA filings, and showcase diversity in the range of generic products serving a wide range of therapies the company offers. But that’s a thing of the past now, as there are compelling reasons to climb-up the value ladder.

A. Climbing the value ladder

Climbing the value ladder with the help of specialty generics remains the obvious choice for the Indian Pharma for further expansion, as India today stand globally 13th in terms of value while 3rd in terms of volume. This easily showcases the gap that India has to go a long way in terms of positioning itself in terms of value, and this can only be achieved through increasing its portfolio with a wide range of specialty products. Indian players were placed mostly in the traditional generic market, which

is already crowded. Additionally, there is an ever increasing competition and pricing pressure faced from global companies and new US regulatory policies emphasizing on price control measures and repealing Obama Care were adding more pressure to the existing as well as new players. Indian companies roughly contribute about 10 % (by value) towards US generic market. The market share of non-complex generics addressed to US population is just 20% (by value). The bigger piece is mostly specialized high value therapeutics. However, with increasing focus on the other half of the US generic market which consists of specialty generics, Indian players can sustain strong growth in long term as huge opportunities exist, going forward.

B. Securing position as a market leader

India along with many other players who were selling their products in the US market faced intense generic competition that had resulted in significant erosion of market share for many of such companies selling their branded products. Such commoditization has also given payers greater control over drug prices in primary care therapeutic classes, where close substitutes and potential generics were available. Specialty generics slowly picked up its pace from vanilla generics after its market capture with low-cost production capabilities, mostly from India. Their entry further firmed up due to the arising patent cliff (patent expiry of blockbuster medicines) which began from 2011 onwards. The patent cliff was a huge issue with the innovator companies while for generic player it was a blessing in disguise. Generic medicine is poised to drive 52 percent growth in global medicine spending from 2014-18 (IMS Report on Global outlook for medicines through 2018).

1. Journey of India Pharma - An Introduction



The pharmaceutical industry went through a huge change in the era of patent protection and when it was over, generic manufacturing came into focus and continues to do so. The patent cliff mostly began in 2011 and reached its peak in 2012. Block buster drugs like Lipitor (atorvastatin), Plavix (clopidogrel), and Singulair (montelukast) faced patent expirations and had increased competition in the US market. About USD 120 BN worth sales were lost due to patent expiration between 2009 to 2014 and more than USD 200-215 BN worth sales are soon to be at risk due to ongoing patent expiration between 2015-2020.

Figure 1: Global generics outlook (USD BN)

Figure 2: Worldwide sales at risk of patent expiration in USD BN (2008-22)

Source: Teva Investors Presentation, YBL Research

Source: Industry, YBL Research

206

236

253

272

292

220

China

Growth

Markets

EU + Japan

US

75

79

82

86

90

94

36

38

41

43

46

48

69

75

82

90

99

109

26

28

31

34

37

40

2015 2016 2017 2018 2019 2020

9%

10%

6 %

5%

CAGR , 15-20’

Percentage

16

26

29

33

52

29

35

48

50

34

32

40

18

23

52

12

10

9

20

38

23

21

17

24

19

16

20

16

12 12

3%

4%

4%

5%

7%

4%

5%

6%

6%

4%

4%

4%

2%

2%

5%

0%

1%

2%

3%

4%

5%

6%

7%

8%

0

10

20

30

40

50

60

70

80

2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022

Total Sales at Risk Expected Sales Lost %Market at Risk



C. US market insights

USA represents 30-40 percent of the global market and the highest spender on generated prescriptions. Last couple of decades were more profitable for the US-based pharmaceutical companies, especially because of the Affordable Care Act (ACA) or popularly known as the Obamacare, which came into law on 23rd March 2010. The Obamacare rapidly extended insurance coverage to a larger pool and covered acute and chronic conditions thus resulting in an increase in overall healthcare spending in US. It increased the sales of prescription-based drugs to about 4,368 MN in 2015 which is about increase of 1 percent from previous year and 2% rise from other previous years. Expansion of the Affordable Care Act through Medicaid Expansion was the main driver of retail prescription. The health expenses reached to USD 3.12 TN, which is approximately USD 10,000 per person and pegs the GDP to 17.4%. This clearly projects the huge opportunity in the US market with the ever-increasing demand. The healthcare spending are sometimes double when compared with other developed nations.

Pharmaceuticals and biotechnology companies along with public funded research institutes such as the National Institute of Health (NIH) are playing a key role in drug discovery in USA. The companies further undertake drug development and seek approval from Food and Drug Administration (FDA) to bring them to the market.

India based companies such as LUPIN is among the top 5 players in US generics along with other global giants like TEVA, Mylan, Pfizer, etc.

In US there are only few whole sellers who directly purchase from the pharma companies (in bulk) which are also the middlemen and further they sell to the retailers earning huge profits, who further sell it to the consumers directly. These consumers either buy the medicines directly at a steep market rate from retail pharmacies or present a ‘health card’ given by Pharmaceutical Benefit Managers (PBMs) or the TPAs (Third Party Administrators). Heath insurance companies outsource the prescription benefits to PBMs for creating formularies, corresponding co-pay levels, discounts and rebate arrangements.

Figure 3: Top US Generics players (by market share)

Source: Teva Investor Presentation, YBL Research

Source: YBL Research

Figure 4: US Pharma Distribution

3%

3%

4%

7%

10%

18%

Lupin

Endo

Pfizer

Sandoz

Mylan

Teva



Price erosion due to stiff competition in the US market by pharma companies brought a situation where 80 percent of the market was controlled by just three major whole sellers in US. Government’s focus on regulating prices over the past few years (which will also continue) has led to moderate growth in the generic pharma. The major buyers in US like the big retail giants including CVS Health Corp. and Walgreens Boots Alliance, etc. dominates the US Pharma market which resulted in shifting of the bargaining power from manufacturers to wholesalers fuelling price erosion while increasing the profit margin of the wholesalers. Such big buyers got even stronger and bigger with new acquisitions and mergers. Speciality generics are a respite as they are more insulated when compared to the simple generic which are commoditized in current market.

To neutralize the effect of such channel consolidation, an enhanced mix of speciality medicines, especially those in the difficult-to-develop space which can have fewer competitors seems to be the only way out

“

”

Buyers or whole seller dominate generic purchasing in US:

McKesson Corp bought Celesio AG for about $5 BN in 2014 in order to gain influence in drug distribution

Walgreens Boots Alliance Inc., through its collaboration with AmerisourceBergen Corp.

Wal-Mart Stores Inc.

CVS, through its partnership with Cardinal Health Inc.



2. Specialty Generics

Specialty generics are classified as high-cost, high complexity and/or high touch generics. Biologics that are injectables or infused and are used to treat complex or rare chronic conditions such as cancer, rheumatoid arthritis, haemophilia, psoriasis, inflammatory bowel disease (IBD), Hepatitis C, etc. are some common areas. There are two categories of specialty generics:

A. New Therapeutic Entities (NTE)

Value-added generics are the improved or enhanced version of approved drugs (patented or generics) developed through a new route of administration, strength, dosage form, and combinations or device innovations to address specific patient needs. Like

Complex generics could be classified into four categories:

pediatric dosage forms, fixed dose combination, modified release versions etc.

B. Complex generics

These are mostly large and complex (niche) molecules by nature and are made of complex active ingredients (may be a complex biological molecule) or may have a complex formulation process or a complex delivery system or an alternate delivery route involved or may be a combination of both complex drugs and device. Such complex or specialty generics are used to treat complex diseases which may be chronic by nature or life threatening like Hepatitis C, Cancer, CNS, etc.

Complex Active

Ingredients

Complex

Formulations

Complex Route

of Delivery

Complex

Drug-Device

Combinations

Peptides

Complex

Mixtures

Natural Source

Products

Liposomes

Iron Colloids

DPI

(Dry Powder Inhalers)

MDI

(Metered-Dose Inhalers)

Transdermal System

(Medicated Adhesive

Patch)

Locally Acting

Drugs



Some of the above mentioned complex generics are discussed below in details:

A peptide is a compound of two or more amino acids in which a carboxyl group of one is united with an amino group of another. Peptides regulate critical functions such as burning fat, building muscle, and serve as hormones and neurotransmitters. Some of the peptides have the capability to pass through cell membranes, they can deliver drugs that fight cancer and other serious diseases affecting the cardiovascular, respiratory, gastrointestinal, and nervous systems. Peptide-based drugs accumulate in low levels in body tissue, which reduce toxicity levels. They are highly selective which makes them effective at lower doses and, on such basis, with less serious side effects. Most are administered parenterally since their oral bioavailability is extremely low. Peptide production is still considered a young market with promising therapeutic capabilities and exciting potential for the API industry.

Natural source products also constitute as a key source of pharmacologically active ingredients in a variety of novel agents with therapeutic potential in a wide range of diseases. Pharmaceuticals containing natural products or compounds derived from natural product scaffolds or templates have to undergo the same stringent approval process as obtained from purely synthetic origin.

Liposomes are of the most promising among the existing drug delivery systems because of their biocompatible composition, as well as superior efficacy due to significant improvement in drug circulation and distribution. Liposomes are round bubbles consisting of an aqueous core encapsulated by natural or synthetic phospholipids. This structure turns liposomes into ideal drug carriers, since hydrophilic drugs tend to be entrapped in the core; while hydrophobic ones will be entrapped within the lipid bilayers. Doxil was among the first approved liposomal pharmaceutical product.

Iron colloids are a type of complex formulations where the API is a macromolecular complex with an iron containing core encased in a hydrophilic carbohydrate shell. Eg: Iron colloid such as ferric gluconate, chondroitin sulfate iron colloid, etc.

Locally acting drugs such as orally inhaled drug products are restricted to local site of application as they do not rely on systemic circulation. They can be a dry powder inhaler, metered-dose inhaler or a nebulisation product. Unlike traditional dosage forms, most inhalation products are designed to be locally acting.

A dry-powder inhaler (DPI) is a device that delivers medication to the lungs in the form of a dry powder. DPIs are an alternative to the aerosol-based inhalers commonly called metered-dose inhaler (or MDI). Most DPIs rely on the force of patient inhalation to entrain powder from the device and subsequently break-up the powder into particles that are small enough to reach the lungs. DPIs are commonly used to treat respiratory diseases such as asthma, bronchitis, emphysema and COPD although DPIs (such as inhalable insulin Afrezza) have also been used in the treatment of diabetes mellitus.

A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs, in the form of a short burst of aerosolized medicine that is usually self-administered by the patient via inhalation. A metered-dose inhaler consists of three major components; the canister which is produced in aluminium or stainless steel by means of deep drawing, where the formulation resides; the metering valve, which allows a metered quantity of the formulation to be dispensed with each actuation; and an actuator (or mouthpiece) which allows the patient to operate the device and directs the aerosol into the patient’s lungs. It is the most commonly used delivery system for treating asthma, chronic obstructive pulmonary disease (COPD) and other respiratory diseases. The medication in a metered dose inhaler is most commonly a bronchodilator, corticosteroid or a combination of both for the treatment of asthma and COPD.

Transdermal Drug Delivery System (TDDS) are self contained, discrete dosage forms which are also known as “patches”. When patches are applied to the intact skin, it delivers the drug through the skin at a controlled rate to the systemic circulation. TDDS are dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin. It reduces the load that the oral route commonly places on the digestive tract and liver. Benefits of TDDS are: 1) It improves bioavailability, 2) leads to more uniform plasma levels, 3) longer duration of action resulting in a reduction in dosing frequency and 4) reduced side effects and improved therapy due to maintenance of plasma levels up to the end of the dosing interval compared to a decline in plasma levels with conventional oral dosage forms.



Table: 1 An overview of list of companies and their complex generics portfolio

Table 3: Companywise complex generic filings

Table 2: ANDA filings overview for key Indian generics

Complex Generics Companies investing in the area

Peptides Aurobindo Pharma

Liposomes Sun Pharma, Dr. Reddy's Labs

Locally Acting Drugs Sun Pharma, Lupin, Glenmark

DPI (Dry Powder Inhalers) Cipla, Lupin

MDI (Metered Dose Inhalers) Cipla, Lupin, Glenmark

Transdermal System Cadila, Dr. Reddy's Labs

Company Name Molecule Brand Indication

Sun Pharma Oxycodone Oxycontin Moderate To Severe Pain

Sun Pharma Cinacalcet Sensipar Secondary hyperparathyroidism

Sun Pharma Abiraterone acetate Zytiga Oncology

Sun Pharma Atomoxetine Strattera ADHD

Sun Pharma Sodium Oxybate soln Xyrem Narcolepsy

Lupin Transdermal testosterone gel

Androgel 1.62% Hormone replacement therapy

Lupin Mesalamine Lialda Ulcerative Colitis

Lupin Sodium Oxybate soln Xyrem Narcolepsy

Lupin Ranolazine Ranexa Chronic Angina Pectoris

Lupin Colesevelam Welchol High Cholesterol

Dr Reddy's Glatiramer Acetate Copaxone Multiple Sclerosis

Dr Reddy's Imatinib Gleevec Chronic Myeloid Leukemia

Dr Reddy's Buprenorphine HCl and naloxone HCl

Suboxone sublingual film Maintenance treatment of opiod dependence

Dr Reddy's Cinacalcet Sensipar Secondary hyperparathyroidism

Dr Reddy's Daptomycin Cubicin MRSA (infections)

Cadila Healthcare Atomoxetine Strattera ADHD

Company Name No. of Complex Generics (CG)

Brand value of CG filed (USD MN)

Alembic Pharma 1 335

Alkem Lab 1 779

Aurobindo 9 6,349

Cadila Healthcare 15 4,796

Dr Reddy's Lab 25 18,335

Glenmark Pharma 9 5,278

Lupin 30 8,732

Natco Pharma 13 14,411

Sun Pharma 27 12,779

Torrent Pharma 4 6,871

Wockhardt 10 6,445

Source: YBL Research Source: YBL Research



Company Name Molecule Brand Indication

Cadila Healthcare Mesalamine Lialda Ulcerative Colitis

Cadila Healthcare Dexmethylphenidate HCl ER Capsules

Focalin XR ADHD

Cadila Healthcare Palonosetron Aloxi Chemotherapy Induced Nausea & Vomiting

Cadila Healthcare Rivastigmine transdermal Exelon Patch Dementia related to Alzheimer's disease

Natco Pharma Lenalidomide Revlimid Multiple myeloma

Natco Pharma Glatiramer Copaxone Multiple Sclerosis

Natco Pharma Imatinib Gleevec Chronic Myeloid Leukemia

Natco Pharma Fingolimod Gilenya Multiple Sclerosis

Natco Pharma Budesonide capsule 3mg Entocort EC Crohn's disease




Topical products are niche range of specialty medicines and involve alternate dosage forms and routes of administration. These products cannot be categorized therapeutic area-wise as several of these topical products are dermatology-related products while sometimes they are therapy focussed as well (including pain, allergy, CNS, respiratory, etc.). Topical products here refers to those products that are delivered by means of contact mostly with an external bodily surface like creams, ointments, gels, lotions, foams, nasal sprays, buccal tablets, suppositories, patches and inhalables.

An overview of the topical drug market and market consolidation

In the US market the top 10 generic topical players have a control of the 80 percent of the market share. The top players including Sandoz (Novartis), Sun/Taro, Perrigo, Akorn and Teva/ Actavis are well positioned as there have been steady rise in approval of generics. Below demograph depicting the most prominent ones in the generic topical space:

Figure 5: Companies with the largest number of topical ANDA approvals


6

8

14

14

16

19

20

23

39

48

60

61

81

88

122

0 20 40 60 80 100 120 140

Hikma

Lupin

Endo

Mylan

Wockhardt

Tolmar

Glenmark

Apotex

G and W Labs

Valeant

Teva/Actavis

Akorn

Perrigo

Sun/Taro

Sandoz

3. Topical Delivery System



The above chart shows the number of ANDA approvals of topical drugs depicting Sandoz as the undisputed leader with 122 ANDAs to its credit. However, the India based companies like Sun/Taro has 88 ANDAs to its credit, while Glenmark had 20, Wockhardt had 16 and Lupin had 8 ANDAs to

their credit in 2015, as per FDA Orange Book. The chart below shows the market share of the generic companies in 2015 based on the topical drugs prescribed which further reinstates performance of India’s Sun Pharma with a 7.1 percent of market share.

Figure 6: Top 10 players in topical drugs (by market share)

Source: Industry, YBL Research

Even though the US market had competition catching-up on topical drugs fronts, US stayed as the largest and the most crucial market poised to grow and further consolidation to take place to venture into alternate dosage forms to stay ahead of competition. To fuel such a high growth

Table 4: Key acquisition in the topical medicine area

Acquirer Acquired company Deal value (USD MN) Deal announcement Year

Teva Allergan (generics) 40,500 2015

Lupin Gavis Pharma 880 2015

Endo Par Pharmaceuticals 8,000 2015

Akom Versapharm 440 2014

Akom Hi-Tech Pharmaceutical 640 2013

Sandoz Fougera 1,525 2012

Watson Actavis 5,900 2012

Perrigo Paddock 540 2011

Sun Taro 454 2007

Wockhardt Pinwood 150 2006

the companies have been constantly equipping themselves with newer and focussed acquisitions like Novartis/Sandoz acquired Fougera, Akorn purchased Hi-Tech and Versapharma, Watson’s acquisition of Actavis, Endo acquired Par and Teva’s acquisitions of Actavis.


Sandoz

16.7%

Perrigo

11.3%

Valeant

10.0%

Akorn

9.5%

Hikma

9.1%

Apotex

7.2%

Sun/Taro

7.1%

Teva/Actavis

6.6%

Xttrium

2.4%

Wockhardt

2.2%

Others

17.9%

Sandoz

Perrigo

Valeant Akorn Hikma

Apotex

Sun/Taro

Teva/Actavis

Xttrium Wockhardt Others

Market share based on prescription of topical drugs



Complex injectables are also considered to be among the valuable specialty range of therapeutics which includes injections containing high potent drugs, some of them are lyophilized products delivered through innovative liposomal technology or with the help of other novel drug delivery systems (NDDS), long-acting suspensions manufactured through cutting edge technologies, etc. NDDS also includes injections such as user friendly self-injection devices or injection pens giving patients the extra comfort to use them on their own. Driven by patent expiry of key injectables like generic Vidaza, Dacogen, etc. and many others along with price erosion, especially after the product goes off-patent, the generic injectables have been a source of respite to earn significant revenue for many Indian generic companies.

Figure 7: Therapy wise injectable market break-up (%)

Company Injectable

Lupin 3

Dr. Reddys 12

Cadila healthcare 3

Sun Pharma 27

Aurobindo 33

Wockhardt 12

The US generic injectables market size is estimated at USD 8.4 BN and is expected to grow at ~10% CAGR between 2015-2020. A quick look at the therapy-wise break up given below:

Source: Orange Book, YBL Research


4. Generic Injectables

Table 5: Injectable portfolio of Indian companies

Beta-Lactam

antibiotics 8%

Generic

injectables

73%

Oncology 17%

Others 2%

Therapy wise market break-up (%)



A. Opportunity for Indian players due to shortage of injectables supply in US market

Shortage of injectable drugs in US were on rise as cost of production of old molecules were higher in US and so they shifted their base to low cost countries such as India and China and further to bring down the prices the US companies subsequently started consolidation by acquiring the smaller players. Rise of quality issues took place as post-consolidation set-up demanded rapid integration and streamlining

of the operations which created a gap in adherence to GMP protocols, and led to stricter actions by USFDA.

While on the other hand ongoing investments in maintaining quality standards were not justified by margins offered by various Government-run programmes such as Medicare, also which led to rationalization of product portfolio for several players. Drug shortages led to improved pricing power for the injectables industry and reflected in the contrasting volume and value growth during the 2008-2013 periods. Between 2008-2013 the injectables segment grew at a CAGR of 19.6% in terms of value, against the volume growth of mere 1.6%, which clearly indicates the supply shortage and the prevailing higher price during the period. While multiple companies have received approvals for launch of the products with improvement in supplies, generic injectables market continues to remain an attractive for Indian companies.

Manufacturing of injectables involved complex machineries and higher adherence to regulatory compliance which created high entry barriers. Companies could only survive through consolidation due to higher capital and operational cost which resulted in a market consolidation. The top five players controlled 73% of the market volume and 50 % by value (year 2015). Pfizer emerged as the largest player in the injectables category post acquisition of Hospira in 2018.

Figure 8: Key players in US injectable market (by market share)

Table 6: A quick look at the market consolidation activities through M&A

Source: Industy, YBL Research

Acquisition Year LocationPrice consideration (USD MN)

Rationale

Baxter Claris 2017 India 635To accelerate Baxter’s strategy to become a global leader in the injectable pharmaceuticals space

FosunGland Pharma

2017 India 1,477To bolster capability in technology used for injectable formulations

Pfizer acquired Hospira 2015 Global 17,000

To expand its presence and become the largest player in generic injectables and biosimilars category and grow its pipeline significantly.

Pfizer acquired Inno Pharma

2014 USA 360

To strengthen its capabilities in complex injectable manufacturing like injection pens, depot injections along with other delivery technologies.

Hikma Pharma Plc. acquired Bedford Laboratories (Assets)

2014 USA 375Strengthen its R&D pipeline and prepare it for US generic market.

0 5 10 15 20 25

Teva

Sagent

Baxter

Grifols

Dr. Reddys

Hikma

Mylan

Sandoz

APP

Pfizer (Hospira)

2012 2015

US Generic injectable Market Share (US$ Mn)



Table 7: M&A to stregthen injectables portfolio

Source: Investor Presentation, YBL Research

B. Investment by Indian pharma to improve positioning in the injectables market

Indian companies realized that injectables business has better margins to offer and the US market was facing shortage of such preparations. However, regulatory barriers were very stringent and facilities meeting such criteria along with the requirement of skilled human resource were a key issue for them.

Though capital investments are on the higher side for generic injectables when compared to the vanilla generics, gross margins have increased over the years. This justifies investment in terms of capex for adhering to USFDA cGMP standards and thus bringing a sustained growth pattern.

The best way to fill this gap was through focussed acquisitions during the juncture, however, US was a huge market and had wide range of players operating with a range of capabilities. Indian players decided to do several small acquisitions as the pocket size was not huge that time, but they had faith in the new technology. Below are some Indian players with their agile steps to strengthen their portfolio in generic injectables range:

Company Name Acquisitions done with rationaleStrategy: Strengthen foot hold in injectables

Sun Pharma

Acquired Pharmalucene Inc. in 2014 for their sterile injectables, which was also supported by their in-house R&D capabilities

Strengthen its portfolio of generic injectables to increase business not only in terms of volume but also in value-terms

Dr. Reddy’s Laboratories

Acquired OctoPlus NV (2013) having proprietary new drug delivery technologies such as automatic injectables and had a pipeline of complex sterile injectables

To enhance capabilities on new drug delivery systems and to strengthen its portfolio as market leader

LupinAcquired Naomi BV in 2014 which had a significant pipeline of sterile injectables

To foray into complex injectable products as they provide better insulation from price erosion

Hikma Pharma. Plc. acquired Ben Venue Labs. (Assets)

2014 USA NATo boost manufacturing and R&D in injectables

Par Pharmaceuticals Inc. acquired JHP Group Holdings

2014 USA 490

To expand its portfolio with 14 specialty injectable products and also boost its pipeline with another 34 products to secure a strong foot hold in the growing specialty market

Mylan Inc. acquired Agila Specialities

2013 Global 1,850

To expand its product portfolio with 1,200 approved injectable products globally along with addition of 900 more in product pipeline

Acquisition Year LocationPrice consideration (USD MN)

Rationale




5. Biosimilars

Manufacturing of biologics is a complex process as biological macromolecules are sensitive and are produced from living cells. The complex manufacturing procedures can require fermentation, aseptic processing, storage and testing. Although the active ingredient of a chemical pharmaceutical is usually a unique molecule subject to well-established analytical tests, but for biologics, the active component often is a portion of a large macromolecule. That macromolecule is in turn a modification of the original protein or polypeptide and other biological substances that may not be clearly characterized. Protein and polypeptide products can contain variable complexes, meaning that they have variable numbers of identical components in the molecules. Also, biologics may have differences in their surface sugars (glycosylation) or folding patterns, depending on how they are produced. With biologics, there is also potential for microbiological contamination of the starting materials.

Biologics are often heterogeneous molecules and/or polypeptides present, they have an impurity profile that depends on — and can vary with — the processes used to make and test each batch. With biologics, the protein mix must be defined, and the active agent and supporting agents must be characterized. In other words, the product does not need to be homogeneous if the biologic acts via a molecular group. Blood, for instance, is a biologic (according to U.S. Food and Drug Administration classification) which is not composed of a single uniform molecule.

However, this doesn’t mean that there is a lack of quality-control measures for biologic manufacture; actually, just the opposite is true. A typical manufacturing process for a chemical drug might contain 40 to 50 critical tests. The process for a biologic might contain 250 or more. Biologic

production uses specialized processes that do not always resemble facilities, machinery, or equipment used to produce chemical drugs. Construction and validation of new facilities is disproportionately expensive and also time consuming. This helps explain the global shortage of bio-manufacturing capacity and the cost differential between biologic and chemical drugs.

Some key categories of biological agents or complex medicines

Hormone

Monoclonal Antibodies

Interferons

Interleukins

A substance, usually a peptide or steroid, produced by one tissue and conveyed by the bloodstream to another to effect physiological activity, such as growth or metabolism.

A single species of immunoglobulin molecules produced by culturing a single clone of a hybridoma cell. Monoclonal Antibodies (Mabs) recognize only one chemical structure, i.e., they are directed against a single epitope of the antigenic substance used to raise the antibody.

Proteins that are normally produced by cells in response to viral infection and other stimuli.

A large group of cytokine proteins. Most are involved in directing other immune cells to divide and differentiate.



Dosage and distribution

Biologics can cost thousands of dollars monthly and require special handling, as they are often less stable than chemically derived drugs and require controlled temperature and light, as well as protection from jostling when in liquid form. For example, many large proteins cannot be shaken to reconstitute, as shaking can destroy the protein structure.

Biologics are medications targeted to specific genotypes or protein receptors. They are most commonly stored, handled, and delivered by specialty pharmacies, distributors that specialize in administering complex-molecule products for small populations and have specialized handling and processing and mailing processes in place to accommodate these complex medications. In many ways, biologics are considered designer drugs that are targeted for patients with uncommon diseases or for genetic subclasses of patients who have widely prevalent diseases.

Polypeptides

Proteins

Vaccine

Peptides containing ten or more amino acids. Typically, a peptide consists of fewer than 50 amino acids, while a protein has more than 50 amino acids.

Naturally occurring and synthetic polypeptides having molecular weights greater than about 10,000 (the limit is not precise).

An agent containing antigens produced from killed, attenuated or live pathogenic microorganisms, synthetic peptides, or by recombinant organisms. Used for stimulating the immune system of the recipient to produce specific antibodies providing active immunity and/or passive immunity in the progeny.

Dosage forms of chemical drugs are highly variable, and concentrations usually are easy to determine. Yet, because biologic molecules are too large to be taken orally without being destroyed before passing through the intestine into the blood stream, they usually are injected or infused. Also, potency is more difficult to quantify for biologic agents, and monitoring is a key component of early therapy.

New modes of administration, such as via food that is directly or indirectly transgenic, are being studied. An example of the latter is goat’s milk that produces an anti-malarial compound. Transdermally administered vaccines also are under investigation.

Regulatory issues

With biologic products, the manufacturing process is a part of the patent and is subject to regulatory approval. Process changes trigger the need for new clinical trials, yielding greater development costs. Partly to remedy this, the FDA’s Center for Biologics Evaluation and Research (CBER) has developed draft guidelines for a post approval comparability protocol allowing companies to combine several manufacturing changes into a single abbreviated post approval application when they change their process. Companies are not required to duplicate clinical studies after a drug manufacturing change, if they can show that it is bioequivalent and causes no new adverse reactions.

Within the USFDA there are two centers- Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) responsible for approving biologic products. CBER works on vaccines, gene therapies, antitoxins and blood, while CDER works on monoclonal antibodies, growth factors, enzymes and immunomodulators.



6. US Market Opportunity for Specialty GenericsIndian pharma’s most attractive market, the US still maintains its sheen, not just because it had the culture to invest in cutting edge R&D and innovation, but also because of ever-challenging demand of procuring medicines for its own citizens. India once again sees tremendous opportunity, but this time in specialty range, as the vanilla ones are no longer profitable due to the stiff competition.

A. Market dynamics

In order to understand why specialty generics are the new attraction for at least another 5 years, one has to understand the contrasting strategies of big pharma of the US market with complex or specialty pharmaceuticals. The big pharma companies existing in US market are all vertically integrated

companies and have capabilities to perform tasks right from scratch till finished products and covers global market. Their operations include drug discovery, drug synthesis, pre-clinical research, clinical development, and regulatory work, scale up and manufacturing. Such big pharmaceutical companies traditionally work in 4-6 therapy areas, as they have the bandwidth, as well as capital to fund the entire process. Midsized-to-smaller companies seek to commercialize drugs in new markets through acquisitions from academia, research institutions or other companies and focus on specialty range for quick success. However, in this dynamic scenario even the traditional-big pharma companies are also creating specialty divisions. Following are some key advantages of specialty range of medicines:

Higher margins due to entry barriers (regulatory / legal barriers & technology barriers) as non-oral solids or alternate dosage medicines encounter higher regulatory/ legal barriers and require complex technology for manufacturing which helps the generic manufacturer quote for a higher values and provide insulation from price-erosion to some extent.

First to market advantage to avoid pricing pressure associated with commoditization by targeting niche disease range with specialty group of medicines to gain the first mover advantage

Focused therapeutics for targeted patient populations, also including drugs related to orphan diseases which has benefits of quick approvals and extended patent life

Existence of complex diseases including chronic ones which requires personalized medicines, complex procedures and technological advancements have enabled such specialty range of medicines to be on a priority

1

2

3

4



B. Market opportunity

India, with its advantage of low cost-high quality generic manufacturing capability and being one of the largest provider of generic medicines, accounting for about 20 percent share of the global generics market supply (by volume) makes it optimally suited to for improve penetration into the US market. USA is the largest and the most crucial market India’s pharmaceutical exports contributing almost 27%, followed by the UK, South Africa, Russia, Nigeria, Brazil and Germany. India accounts for around 30% (by volume) and 10 per cent (by value) in the US$ 70 MN US generics market, while there is generic opportunity worth 20 BN dollars is knocking at the doors as patents of several key drugs are set for an expiry in USA. Many block-buster molecules lost protection, generating a huge opportunity for the generic medicines industry. This trend was at its peak in 2012, since then there were fewer major patent expiries (several of which were respiratory products associated with device). Indian companies have realized that specialty range of medicines oncology injectables, nasal sprays, vaccines, transdermal patches, etc. has better margins. Specialty medicines enjoyed protection from generic competition with sales of oral solid crossing ~USD 30 BN in 2016 represented 50% of the total US generics market (excluding branded generics). However, the number of players in oral solids is huge with intense competition.

C. R&D investments

In order to cope-up with the US market in terms of better value generation and to deal with price-erosion the large India pharmaceutical companies operating in the US market have stepped forward to make focussed investments in R&D towards strengthening their portfolio in specialty range. In the past few years the India’s business in US have been adversely impacted due to reasons such as currency fluctuation, price erosion, global competition, etc. and hence thinking out-of the-box was all the more necessary, especially from future perspective for long term benefit, hence companies like Sun Pharma, Lupin, Dr Reddy’s, started spending almost 10% of their sales in R&D. Indian companies are expected to spend overall more than ` 105 BN by FY 2017. Sun pharmaceutical is expected to invest close to 460 MN US dollars while other players like Lupin, Glenmark and Dr Reddy’s are also catching-up.

Table 8: Select dosage forms still represent attractive markets

Figure 9: Investment scenario in complex generics

Alternate Dosage Forms

Total Worldwide market size (USD BN)

Generic market in the US (USD BN)

Injectables370 (includes

biologics)8.0

Transdermal 30 1.5

Ophthalmic 25 1.3

Respiratory products

28 1.7

Implants 11 NA

Liquids NA 1.9

Dermatology 90 6.0

Nasals 11 0.5



Biosimilars

Respiratory

Complex Injectables

Dermatologicals

Transdermal

Injectables & Opthal

Modified-release dosage

Traditional generics

Delivery System

R&

D (D

elive

ry) C

om

ple

xity



Oral Solids

34%

Complex

oral Solid20%

Injectables

13%

Complex

Injectables /

Sterile 23%

Softgel/

Ophthal

5%

Topical/

Transdermal

5% Oral

Formulations

72%

Injectables &

Ophthalmics

24%

Penicillin Oral

& Injectables

1%

Penem

Injectables

2%

Oral

& Injectables

1%

Oral Solids /

Liquids, 59%

Inhalation, 8%

Controlled

Substances, 5%

Dermatology /

Topicals, 3%

Opthalmics, 3%

Injectables, 5%

Depot

Injectables, 2%

Biosimilars,

15%

% of Sales (` MN)

FY16 FY17

Sun Pharma 8.3% 7.6%

Lupin 11.8% 13.5%

Dr Reddy's 11.5% 13.8%

Cadila 8.0% 6.9%

Torrent 3.7% 6.9%

Glenmark 9.9% 11.7%

Cipla 7.7% 7.2%

Aurobindo 3.5% 3.7%

Alembic 9.0% 14.0%

Biocon 4.2% 4.2%

R&D Spends (` MN)

FY16 FY17

Sun Pharma 23,000 23,100

Lupin 16,038 23,101

Dr Reddy's 17,834 19,551

Cadila 6,810 6,653

Torrent 246 432

Glenmark 7,660 10,890

Cipla 10,353 10,305

Aurobindo 4,770 5,430

Alembic 2,646 4,216

Biocon 1,467 1,707

Total 90,824 1,05,385

D. Product filing pattern

There has been a change observed in filing pattern by Indian generic players in the initial phase of R&D expansion, while now it has given ways to change in dosage forms, their routes of administration, etc. For example Lupin’s R&D expansion, coupled with the Gavis acquisition, indicates a marked difference between filed products and those that are in

Table 9: Players in the specialty range in US

Dr. Reddy’s Aurobindo Lupin



development. The thrust, as seen in the chart below, is toward inhalers, injectables and ophthalmic products. Similarly, Dr. Reddy’s filing comprises products based on complex characterisation, novel regulatory pathway and large & complex clinical studies.

Figure 10: ANDA pipeline in FY17



High end drugs and complex treatment procedures for chronic and niche-acute conditions have given birth to specialty generics, having the potential to capture half of the market by 2020. Majority of Indian players growing in the range of 20% during the year 2010-15 were mainly due to the patent cliff advantage, along with their capability to manufacture low cost vanilla generics, through which they captured almost 25% of the US market. During the initial years only few companies managed to invest and create a portfolio in complex generics category which includes orals, injectables, nasals, derma, inhalers, etc., though the margin offered in regulated markets was way higher in these segments, in spite of the high entry barriers. An overview of the different approaches taken by the pharma industry to get into specialty segment are as given below:

A. Deep dive into specific disease portfolio for specialty medicines

Some bold Indian pharma companies started leveraging the opportunity and subsequently started diversifying their specialty portfolio in the following disease segments:

Oncology

CNS

Opthalmology

Pediatrics

Dermatology

Respiratory

Indian companies like Dr Reddy’s US subsidiary Promius Pharma manufactures dermatology product range, while Lupin is operating in pediatrics category with Alinia and Locoid lotion. Cipla came-out with its respiratory range of products through a licensed tie-up with Meda AB. Section 505 (b) (2) of the US Food Drugs and Cosmetics Act has been deeply

explored by Indian companies which allows filing NDAs for drugs and relies on data not developed by the applicant or the applicant has not obtained a right of reference. This pathway to approval saved pharmaceutical sponsors both time and money. The pathway approves the following modifications: new formulations, new combinations, new derivatives, new manufacturer, new indication, new molecular entities, etc. Indian companies having the desire to expand in specialty portfolio made use of the new formulations category, which is also the most sought after category driven by market need especially with qualities such as abuse deterrence, sustained release, etc

B. Innovative drug delivery systems for targeted delivery

The job of a drug delivery system is to develop products that could unleash the full potential of a drug (i.e. by releasing its active ingredients only in the target area of the body) with an aim to maximize efficacy, safety and convenience. Pharma players realized that a patented release or delivery technology or creation of a new dosage form can add tremendous value to the whole medicine and provide insulation from price erosion to some extent. Eg of such a technology-Sun Pharma’s Lipodox, which is a pegylated liposomal doxorubicin formulation (a generic version of Janssen’s Doxil). Sun Pharma sold the product prior to the patent expiry of Doxil in 2012 and still continues to be the only generics drug. The other forms of delivery system and their preference depend on the following: the desired effect, the type of disease and finally the type of product. Broadly drug delivery routes are commonly of four types:

Oral routes which are also the most common or oldest route for novel drug delivery. It is the most preferred one having the ease of administration, and are also the highly accepted ones by the patients.

7. Current & Future Opportunities in Specialty Products



Parenteral route, which refers to administering medicines into patient body using routes other than the oral ones. Such route includes commonly intramuscular, intravenous, intra-arterial, subcutaneous routes.

Transdermal route, through this route the medicine is applied on dermis or the skin or at the mucosal membrane. Such route of administration is significantly associated with local effect rather than systematic effect. Such routes directly transfer the active ingredients to the systemic circulation without involving liver or gastrointestinal metabolism.

Inhalation route is a preferred option mainly for respiratory diseases which is targeted to the lungs and bypass systemic effect.

Dr. Reddy’s, to capture global market in derma

range of products, signed licensing agreement with Foamix, an Israel based formulations major for development of novel foam based emollient

against Psoriasis.

Lupin is among the top Indian pharma players

making big acquizitions in US market. In the year

2015 Lupin acquired New Jersey based Gavis Pharmaceuticals LLC for

880 MN USD to strenthen its position in dermatology and controlled substances.

Glenmark, to fuel its growth in complex generics (in a limited competition

opportunity in 2016) collaborated with Particle Sciences, a US based company to develop and market a generic version of Celgene’s ABRAXANE product-paclitaxel

protein-bound particles for injectble suspension. Particle Sciences develops this product exclusively for Glenmark,

while Glenmark has obtained exclusive marketing and distribution rights.

Cadila made its mark into specialty pain management

segment by foraying into 8 BN USD pain management market of USA with the acquizition of

Sentynl Therapeutics, as it gets access to its distribution network

and customer base.

Lupin’s US subsidiary enetered into a strategic licensing agreement with MonoSol Rx in 2016 for its

proprietory PharmaFilm drug delivery technology to develop multiple pediatric

products.

Sun, the fifth largest global generic drug company had build

its strength in opthalmology through acquizitions. It acquired InSite Vison, USA for BromSite. In 2016, it also acquired Ocular

technologies to secure its rights for Seciera cyclosporine opthalmic solution for treatmnt of dry eye.

Quick moves in the market through licensing & partnerships

Strategic M&A to stay ahead of market

C. Focused R&D to deepen anchorage into specialty generics business

In the past 6-7 years some Indian companies realized that to stay relevant in the generic market they will have to make investments in R&D and secure their presence for longer period rather than focusing on short-term gains. Through a sustained investment in R&D, companies like Sun Pharma (with its presence in derma, sterile injectables), Dr Reddy’s (injectables and complex OSDs), Alembic Pharma (505(2) route) and Aurobindo (mainly in the injectables segment) have transformed themselves from a pure-play plain vanilla generic manufacturer to tide the growing competition and provide themselves with the necessary shielding from price erosion to carve a niche market with limited competition.

D. Understanding the market demands and transforming rapidly

Key strategies adopted by Indian players to keep themselves abreast in the specialty segment:



8. Recommendations & Way Forward

The Indian pharmaceutical companies operating in US have already tasted the low hanging fruits in the form of US patent cliff (which have significantly contracted with USD 120 BN worth products which has gone off patent by 2009 and rest close to USD 55 BN of drugs, including biologics going off patent within another couple of years). The Indian pharma players have already entered into a phase where they are following a differentiated market approach as some players have already stepped into manufacturing and distribution of complex range of products. To create a niche portfolio some bold Indian players have invested millions of dollars, as their overall R&D expense has gone up to 10 percent range which was a meager of 2-3% five years ago. On the other side the USFDA have also strengthened themselves as they had revised the GDUFA price not only to just ensure approvals come in time for the applicants, but also companies who are not complying to GMP gets heavily penalized. Few recommendations and suggestions pertaining to the specialty range are listed below:

A. Address concerns regarding regulatory interventions by USFDA

The US regulator in the past 2-3 years has increased their scrutiny on Indian pharma, which has dented confidence of many aspiring companies. These companies have just started to explore the US market with opportunities to play their respective innings, as the bigger firms are still battling with quality issues, some of them require immediate remedial measures failing which their reputations can be at a serious stake while for most of the others, it may possibly be a behavioral/ culture issue which can only be taken care with the intervention at the decision maker’s level.

B. Increase investment in R&D as a key to succeed in specialty generics

A considerable increase in R&D budget to stay ahead of competition potentially runs the risk of longer gestation period. Specialty drugs or the high-entry barrier drugs requires multi-pronged approach which includes following strict regime on areas such as safety and efficacy of drugs, navigation through patents (non-infringing), device acceptability, and higher clinical trial data requirements in regulated markets are some of the necessary features. Companies aiming to be leaders in the regulated market shouldn’t deter from high investments, also returns may not come immediately but in long term value appreciation is on the higher side.

C. Improving manufacturing capabilities

Availability of highly skilled manpower and infrastructure are important considerations for manufacturing specialty product range. Specialty drugs including biologics and plasma are highly sensitive molecules. For specialty biologics cold chain management and temperature controls are critical to the product being received by the end user in manufacturer-recommended conditions. Since, it is the manufacturer who chooses a distribution partner, a regular audit of these processes is very crucial. These external factors intensify the unique needs related to specialty distribution and supply chain. Increasingly, the Food and Drug Administration (FDA) is asking for Risk Evaluation and Mitigation Strategies (REMS) to be in place, in-order-to give a go ahead to the manufacturer for FDA approval for a new and/ or existing specialty drug.



Some companies are experts in niche therapeutic areas, orphan diseases, etc. focussing on segments which requires high end approach for therapy, especially complex therapeutic areas like genetic-metabolic disorders, cancer, rheumatoid arthritis, hepatitis C, etc.), others focus on reformulating their existing branded generic products to increased therapeutic effect. Some are portfolio adopter which identify product portfolio which are de-prioritized by big pharma, after carefully assessing market potential and future growth in terms of projected increase in sales volume by means of additional development investments and intensive marketing. Licensing experts focus on early and late stage development candidates, as they hand hold such candidates towards final approval. Drug delivery experts target generic molecules and strategize on reformulating them to enhance their therapeutic applications, availability, etc. are some examples of the various business models operating around specialty or complex range of therapeutics. Each of these business models provides various growth possibilities while combining them together represents the entire specialty range.

D. Exploring best-fit strategy to grow in specialty pharma

Indian pharma companies aspiring to grow big in the US market and to register a sustained growth in specialty segment can identify their core strengths in the following business models:

E. Strategic partnerships to climb up the value ladder

To augment pipelines and diversify portfolio the new and vibrant specialty pharma emerging today is going to significantly impact the overall industry with its functioning. Activities like M&A, strategic partnership, collaborations, cross licensing, etc. are going to be the key, as the trend is moving towards personalized medicines. On one hand a sound infrastructure with highly skilled workforce would be critical for growth, while on the other hand in a dynamic scenario the specialty pharmaceutical manufacturers will have to seek partners that have expertise in orphan drugs or partners who will take care of the supply chain management, inventory services across the board, etc. in order to have access to innovations and also adds on to capabilities that can drive future internal R&D and streamline processes.

Licensing Experts

Portfolio Adapter

Drug Delivery

Experts

Specialty Generic

Company



Some key characteristics to succeed in specialty generic space:

STRENGTHENING PRODUCT PORTFOLIO

• Understand&assessmarketsize,patientpopulation,epidemiologyandexploreopportunities,futurethreats and disruptors

• Understand and stay informed about late-stage pipeline activities like new dosage forms (newproduct technology) about to reach the market, readily assess the potential commercial success of the product

• Buildandmanageadevelopmentpipelineanddiversifyportfolio.Identifygapsintargetportfolioandacquire smaller portfolios to diversify and expand business. Manage a strong pipeline of company acquisitions to stay competitive

REGULATORY ADHERENCE

• Thoroughly understand and strictly adhere to regulatory compliance as per USFDA guidelines &procedures

• Monitorchangesinregulations&adaptaccordingly

• Understand IPR nuances such as the patent landscape, the overall associated risk involvement,creation of new patents, etc. Assess infringement risk, legal positioning, patent challenges, and freedom



BIBLIOGRAPHY

We would like to thank some of the illustrious bodies, news agencies and research journals with the help of whose publications we have been able to compile this report:

• CentersforMedicare&MedicaidServices(CMS.gov)

• OrangeBook,USFDA

• ZydusInvestorPresentation

• AnnualReport-DrReddy’sLaboratories

• AnnualReport-Lupin

• AnualReport-SunPharmaceuticalIndustries

• Dr.Reddy’sJPMorganAnnualHealthcareConference2016

• AnnualReport-TevaPharma

• ASSOCHAMConference:MEDCON2017

• PharmaceuticaAnalyticaActa

• JMFinancial–EnteringaNewRegime

• Recenttrendsinspecialtypharmabusinessmodel,JournalofFood&DrugAnalysis,Elsevier

• USGenericInjectablesMarket,ICRA

• Pharmergingmarkets,Quintiles-IMSHealth

• WhyweneedGenericMedicines,Quintiles-IMSHealth

• SpecialtyPharmaceuticals,J.P.Morgan

• Pharmatix

• IndiaPharmaceuticals,HSBCGlobalResearch

• Pharmaceuticals,Jefferies

• IndiaPharma,MacquarieResearch

• TNN,TimesofIndia

• IndiaPharmaSector,CreditSuisse

• SpecialtyPharmaceuticals,BankofAmerica-MerrillLynch

• FiercePharma(Questex)

• BusinessStandard

• WorldPreview2016,Outlookto2022,EvaluatePharma

• NirmalBangPharmaceuticalSectorReport2017



Abbreviations with their Expanded Forms

GDP Gross Domestic Product

USFDA United States Food and Drug Administration

GDUFA Generic Drug User Free Amendment

GMP Good Manufacturing Practice

ASEAN Association of South East Nations

CIS Commonwealth of Independent States

ANDA Abbreviated New Drug Application

CAGR Compound Annual Growth Rate

ACA Affordable Care Act

NIH National Institute of Health

FDA Food and Drug Administration

PBM Pharmaceutical Benefit Managers

TPA Third Party Administrators

HIV Human immunodeficiency virus

IBD Inflammatory Bowel Disease

NTE New Therapeutic Entities

DPI Dry Powder Inhalers

MDI Metered Dose Inhalers

CNS Central Nervous System

NDDS Novel Drug Delivery Systems

cGMP Current Good Manufacturing Practices

PCR Polymerase Chain Reaction

CBER Center for Biologics Evaluation and Research

CDER Center for Drug Evaluation and Research

NDA New Drug Application

REMS Risk Evaluation and Mitigation Strategies


NOTES


NOTES





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Indian Pharma: Transitioning to Specialty Generics | 1 · 8 | Indian Pharma: Transitioning to Specialty Generics Indian pharma companies championed the art of manufacturing generic