Regulatory aspects of orphan drugs devolpments

1. REGULATORY ASPECTS OF
ORPHAN DRUGS AND
DEVELOPMENTS
JITHIN K JOY
REG :140090441
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Guide:
Mr.Manoj.K
Assistant professor of pharmacy

2. OUTLINE
 INTRODUCTION
 DEFINITION FOR ORPHAN DISEASES IN VARIOUS
COUNTRIES
 NEED FOR ORPHAN DRUG REGULATION (ODR)
 INDIAN PRESPECTIVE
 CHALLENGES FACED BY ORPHAN DRUG
 THE INTERNATIONAL SCENARIO
 US ODA
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3.  JAPANESE ODR
 AUSTRALIAN ORPHAN DRUG ACT (ODA)
 ORPHAN DRUG DESIGNATION PROCESS
 FEW ORPHAN DRUGS & DISEASE PRESENT IN INDIA
 CURRENT SITUATION IN INDIAAND NEED FOR
ORPHAN DRUG REGULATION IN INDIA
 CONCLUSION
 REFERENCES
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4. INTRODUCTION
 Any drug is developed to treat an orphan or
rare disease condition is called an orphan drug
 A rare disease occurs infrequently in a
population, but there is no universal definition.
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5.  3 Elements to the definition as used in various
Countries are as follows:
1. The total number of people having
the disease
2. Its prevalence
3. Non-availability of treatment for the
disorder
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6.  A specific treatment of the orphan condition
was not lucrative for the pharmaceutical
industry
 Because these medicines would be used only by
a small number of patients
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7.  The absence of specific treatment for orphan
disease causes psychological distress to the
patient and the family, and a feeling of
hopelessness sets in.
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8.  USA was the first nation to propose a legal
framework to encourage development and
availability of orphan drugs
 The orphan drug act (ODA) was passed on
January 28, 1983
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9. Country Definition
UNITED STATES
The Orphan Drugs Act (ODA) is a federal law concerning rare
diseases that affect fewer than 200,000 people or are of low
prevalence (less than 5 per 10,000 in the community).
EUROPE
According to the Orphan Drug Regulation in Europe, an orphan
disease is a disease or disorder that affects fewer than 5 in
10,000 citizens.
AUSTRALIA
In Australia, orphan drugs are drugs used to treat diseases or
conditions affecting fewer than 2,000 patients annually (0.2%).
CANADA
Canada has no official “orphan disease” status. Based on
international standards it could be defined as diseases with a
potential patient population between 3,300 to 22,500.
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10. NEED FOR ORPHAN DRUG
REGULATION
 Absence of treatment for orphan disease
 To propose a legal framework to encourage
development and availability of orphan drugs
 To stimulate the research, development and
approval of products that treat orphan diseases
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11. THE MAIN INCENTIVES OF ACHIEVING
ORPHAN DRUG STATUS (ODS) INCLUDE
 Tax incentives for clinical research
 Study design assistance from FDA
 Exemption from application-filing fees
 Grant for phase I and II clinical trials
 Seven years of marketing exclusivity after the
approval of the drug or biological product
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12. IMPACT OF THE ACT
 Nearly 1100 drugs and biological products have
been designated as orphan products
 The FDA has approved over 231 of these for
marketing
 Facilitating treatment for an estimated 11 million
patients in the USA
 The FDA has so far offered 370 extra clinical grants
totalling more than $150 million for orphan product
developers
 A decade after in 1993, japan took similar initiative
followed by australia in 1999. Currently, singapore,
south korea, canada, and new zealand are also
having their country specific ODA.
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13. INDIAN PERSPECTIVE
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14.  About 6000-8000 rare diseases, mostly genetic in
nature have been identified in India
 Many of these diseases still do not have any cure
 Every day millions of Indians will continue to suffer
from ‘orphan diseases’ without treatment, in the
absence of an appropriate policy framework in the
country for ‘orphan drugs’
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15. Essential Vs Orphan drugs
 Essential medicines ,as defined by the world
health organization (WHO) are “Those drugs
that satisfy the health care needs of the
majority of the population; they should
therefore be available at all times in adequate
amounts and appropriate dosage forms at a
price the community can afford”
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16. Comparison Of Orphan Drug &Essential
Medicines Development
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17. CHALLENGES FACED BY
ORPHAN DRUGS
 High prices of ‘orphan drugs’
 Small patient population
 Delay in diagnosis & deficient diagnostic
systems
 Limited treatment availability
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18. CHALLENGES FACED BY ORPHAN DRUGS
 Lack of knowledge & training
 Disease is poorly understood
 Lack of adequate expertise and review by
authorities
 Limited public awareness
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19. THE INTERNATIONAL SCENARIO
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20. US ORPHAN DRUG ACT
 The US ODA, passed in 1983 and subsequently amended
in 1984, 1985, 1988, 1990, and 1992
 It was the first concrete step in the development of orphan
drugs
 Includes exempting the designated orphan drugs from
paying new drug application fee
 Waivers for post approval annual establishment and
products fees,
 Provision of tax credits on clinical research
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21.  Exclusive marketing rights for up to the period of 7
years
 Introduction of office of orphan products
development (OOPD) within the FDA
 It helps smooth out the process of granting the
orphan drug status
 The success of ODA is illustrated by a simple fact that
the figure of only 38 orphan drugs that were in the
market until 1983, almost increased by 10 times by
the end of 2014
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22. JAPANESE ORPHAN DRUG
REGULATION
 Introduced in 1993 October 1
 Japanese ODR include reimbursements up to 50%
of the development costs, in addition to a 6% tax
waiver for R&D into rare diseases
 Separate government funds provide the necessary
fillip into orphan disease and drug research
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23. AUSTRALIAN ODA
 Australia is another country to have introduced orphan
drugs regulations in 1997
 The Australian therapeutic goods administration
(TGA), being the leading agency, possesses the ability
to grant the orphan status to the drugs
 The exclusive marketing period provided by TGA is
5 years
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24. ORPHAN DRUG DESIGNATION
PROCESS
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25. 1. Sponsors have to first send request to the office of
orphan products development (OOPD) to grant
orphan designation to their drug or biological product
to take advantage of financial incentives available for
further product development
2. And then send NDA (new drug application) to the
centre for drug evaluation and research (CDER) or
the centre for biologics evaluation and research
(CBER) to market their orphan drug or biological
product
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26. After designation request is submitted
1. Typical review cycle ~ 90 days (often less)
2. Will either receive :
-designation letter OR deficiency letter
Once designated, sponsor is required to submit annual
reports until drug is approved
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27. FEW ORPHAN DRUGS &
DISEASES PRESENT IN INDIA
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28. Adapted from the Rare Diseases List provided by the Foundation for Research on
Rare Diseases and Disorders (accessed May 7, 2015)
Disease Per 100,000
Acatalasmia 3
Acromegly 5
Alkaptornuria 3
Alpa-1 antritrypsin 25
Grave disease 50
Parkinson disease 15
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29. ACATALASMIA ACROMEGLY
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30. Alkaptornuria
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31. Orphan drugs in
development
Disease Drug Company
Achondroplasia BMN-111 Biomarin
Cushing Disease SOM230 Novartis
Duchene Muscular
dystrophy
HGT4510 Shire
Fabry Disease Amiga GSK
Homozygous familial
Hypercholesterolemia
Kynamro
(Nipomersen)
Genzyme
Hunter syndrome HGT2310 Shire
Metachromatic
Leukodystropy
HGT1110 Shire
Pompe Disease BMN-701 Biomarin
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32. Marketed orphan drugs
Rare disease Name Drug available
Marketing
Authorization Holder
Phenylketonuria Kuvan Biomarin
Pancreatic
Neuro endocrine tumours
Sutent Pfizer
Non-small cell lung
cancer
Xalkon Pfizer
Gaucher disease Vpriv
Gerezyme (Imigluserase)
Sfire
Genzyme
fabry disease
Replagal
Fabrazyme (Agalsidase
beta )
Shire
Genzyme
Chronic lymphocytic
leukemia Arzerra GSK
Chronic Idiophatic
Thrombocytopenia
Promacta GSK
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33. CURRENT SITUATION IN INDIA AND NEED
FOR ORPHAN DRUG REGULATION IN INDIA
 India has approximately 70 million cases of orphan
diseases
 Every day millions of Indians keep suffering from
debilitating orphan diseases, for lack of any
regulatory guidelines on orphan diseases
 Orphan drug developmental is also a costly
process. Industries show negligible interest in the
development of treatment for rare diseases as there
is less return on investment
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34.  India is still in developing phase, there is setback in
regard to regulation and development in orphan
diseases research
 India, like many developing countries, currently has
no standard definition. Considering the large
population of India,
 The world Health Organization (W.H.O) has
suggested that a rare disease should be defined as one
with frequency less than 6.5 – 10 per 10,000 people
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35.  400 US FDA approved orphan drugs and about 80 EMA approved
orphan drugs are available in India and world-wide.
 Most of them are either not accessible to most patients in India or
are unaffordable.
 Still effective research is not widespread in India.
 The National Institute of Pharmaceutical Education and Research is
getting into research on ‘orphan drugs’ to solve the rare diseases
problem in India
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36. CONCLUSION
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37.  Government of India (GoI) should come up with a
clear, separate orphan drugs act or an addendum to
drugs and cosmetics act specifying the definition of
orphan diseases and other related things.
 GoI should provide special incentives to industries
for the research and manufacturing of orphan
drugs.
 GoI should motivate and support NGO’S to import
the available drugs for rare diseases at affordable rates.
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38.  GoI should have a special program on rare
diseases to be run by government
organizations like primary health centres and
community health centres to provide special
care to the patients of rare diseases.
 GoI should run awareness campaigns regarding
rare diseases
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39. REFFERENCE
 Reddy DS, Pramodkumar TM, Reddy Y,Sirisha K. Orphan
Regulations For Orphan Drug Development In India.Asian
Journal Pharm 2014; 8:130-2.
 Agarwal S,Bhattacharjee D ,Patil N,Bairy Kl,Orphan Drugs
The Current Global And Indian Scenario,Asian J Pharm Clin
Res , 9,(4),2016;46-50.
 Randhawa G K,Orphan Diseases And Drugs,Indian J
Pharmacol, 38,(3), 2006,171-176
 Kumar H,Sarma P, Medhi B,Orphan Drugs:Indian
Perspective,Indian J Pharmacol, 49,(4),2017,267-269,
 Sharma A, Jacob A, Tandon M, Kumar D. Orphan drug:
Development trends and strategies. J Pharm Bioallied Sci
2010;2:290-9
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40. THANK YOU
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