Transcript Drugs for medical abortion: where we are now

Drugs for medical abortion:
Where we are now
Peter Hall
Chief Executive Officer
Concept Foundation
Bangkok, Thailand and Geneva, Switzerland
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
• What products are available for medical
abortion?
• Making quality product available at an
affordable price: Concept’s Access-toMedicines programme for medical abortion
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
• What products are available for medical
abortion?
• Making quality product available at an
affordable price: Concept’s Access-toMedicines programme for medical abortion
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Medical abortion is important
– this we know
• It offers a safe and effective choice of method
for termination of pregnancy.
• Choice of method is important not only for
women but also to make service provision less
problematic for many providers.
• It encourages health systems to make abortion a
primary care service.
• It can make abortion: earlier; more accessible;
safe; less traumatic; less expensive; and be
provided by most healthcare workers.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
So “Where we are now”
or is it “Where are we now?”
THIRTY YEARS after Roussel-Uclaf undertook
its clinical trials on mifepristone (RU-486) for
early abortion, where are we now?
Are affordable products of assured quality for
medical abortion widely available to poor
women throughout the world?
Or do we have a critical healthcare technology
which follows the “norm” where the rich can
always access quality products and services but
the poor remain without them?
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
The world as seen by relative MMR
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Product availability - misoprostol
• Searle (part of Pfizer), registered misoprostol
(as Cytotec) worldwide, India, most of Africa, the
Middle East and central Asia, for the prevention
of gastric ulcers associated with NSAIDs.
• Misoprostol is widely available as generic
formulations and, in many countries, cheaply.
• Has begun to be registered for obstetric
indications in several countries but in few for
termination of pregnancy.
• Included on WHO EML for induction of labour,
incomplete abortion; in combination with
mifepristone for early abortion.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Availability of drugs for medical abortion
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Product availability - misoprostol
Ipas undertook a desk exercise which listed
some 50 manufacturers of misoprostol
worldwide. But excluded many countries.
Likely to more than 60 manufacturers.
(Fernandez MM et al. Int J Gyn Obs. 2009)
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Where are misoprostol products made?
Finished products (misoprostol only)
Argentina, Bangladesh, Brazil, China,
Colombia, Egypt, France, India,
Indonesia, Mexico, Nepal?, Russia,
South Korea, Spain, Taiwan, UK,
Uruguay, USA, Viet Nam, +?
Active pharmaceutical ingredient
China, India, Ireland(!), Taiwan, USA
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Product availability - mifepristone
• Mifepristone has limited availability – is
approved and sold in >40 countries.
• Mifepristone API is expensive, relatively complex
synthesis, small-scale and low yield; and small
sales volume outside India and China.
• In some countries, it remains so expensive, it
cannot be provided in the public sector. In
South Africa, it is $45/tablet.
• Included on WHO EML, in combination with
misoprostol for early abortion.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Availability of drugs for medical abortion
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Product availability - mifepristone
• Exelgyn (Europe, South Africa) and Danco (USA)
serve high-income countries at high “market” prices.
• Entry into these markets for developing country
manufacturers comes with very high opportunity
costs. (stringent regulations for drug approval)
• Developing country manufacturers serve their
own markets where:
– Opportunity costs are lowest (China, India).
– High opportunity rewards and large potential
markets exist (China, India).
– Ease of registration.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Where are mifepristone products made?
Finished products
• China
• France
• India
• USA
• Viet Nam
Active pharmaceutical ingredient
• China
• France
• India
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Mifepristone and misoprostol in India
Mifepristone
2009: 10.5 million
200mg tablets
Misoprostol
2009: 39 million
200μg tablets
Abo Pill
Mefipil
Mifebort
Mifegest
Mifeprin
MTPill
Relezed
Rempreg
Undo
Unwanted
Cure Quick
Piramal HC
Taj Pharma
Zydus Alidac
Sun Pharma
Cipla
Zee Lab
Redson
FDC
Mankind
Aboprost
Cytolog
Kontrac 200
Mesopil
Miso
Misobort
Misogon
Misogent
Misolast
Misoprost
Misotrax
Prestakind
Zitotec
Cure Quick
Zydus Alidac
Fourrts Labs
Piramal HC
Bestochem
Taj Pharma
German Remedies
Aristo Pharma
FDC
Cipla
Genetica
Mankind
Sun Pharma
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Product availability
But what is the overall situation on what
misoprostol products are available, their quality,
and the potential of misoprostol manufacturers to
meet international quality and safety and efficacy
requirements? And what do we know about the
stability of misoprostol formulations in tropical
climates or even above 25°C?
Concept is undertaking a study with the support
of Gynuity Health Projects.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Conclusions of study
• Most companies manufacture products
according to outdated requirements that do not
conform to CGMP, or even “older” GMP. Many
have inadequate understanding of, and ability to
implement and invest, in quality assurance.
Some should be closed!
• Most are not in a position to supply products into
international markets, not having considered
regulatory approval for their products outside
their home markets.
• This was for hormonal contraceptives – why
would we expect misoprostol to be different?
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Regulatory requirements
If an innovator product, must have complete:
• Clinical module, with full clinical studies and expert clinical
review.
• Toxicology and preclinical module, with expert toxicology
review.
• Chemicals, manufacturing and controls module, detailing
full manufacturing process, quality assurance (includes
CGMP), API Drug Master Files.
If a generic product must:
• Demonstrate safety and efficacy and undertake
bioequivalence studies against innovator product.
• Chemicals, manufacturing and controls module, detailing
full manufacturing process, quality assurance procedures
(includes CGMP), API Drug Master File.
Catch-22, the innovator is not registered for this indication.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Regulatory dossiers approved by stringent
drug regulatory agencies
Mifepristone
• Exelgyn (Nordic Trading): Europe, Tunisia, S Africa
• Danco: USA
Misoprostol
• HRA Pharma: France, Tunisia
Mifepristone + misoprostol
• Sun Pharma: India, Nepal, Cambodia, Zambia.
Under review by 15 EU/EFTA DRAs
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
• What products are available for medical
abortion?
• Making quality product available at an
affordable price: Concept’s Access-toMedicines programme for medical abortion
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
What does Concept Foundation do?
• Concept Foundation is a not-for-profit organization,
based in Bangkok and Geneva, with the mission to:
“ensure that low income women worldwide have
access to sexual and reproductive health products
of assured quality at the lowest possible cost .”
• This goal is met through design and implementation of
Access-to-Medicines (ATM) programmes for selected
products for reproductive health, through the
establishment and support of: Public-Private
Partnerships (PPPs) with pharmaceutical companies;
and a systematic and coordinated approach to
product introduction.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Getting from research to people
Under its collaborative agreement with WHO, agreed to:
• Price – Co-packaged product with preferential price to
public sector, making it affordable to many more
women.
• Quality - Manufactured in USFDA/EMEA compliant
facility, meeting international current Good
Manufacturing Practice (cGMP).
• Regulatory issues – Misoprostol used “off-label”
(except France and India), regulatory agencies
welcome formal registration of misoprostol for use in
medical abortion; clinical part of registration dossier
based on WHO clinical trials.
• Ease of use – co-packaged product easier for both
provider and woman.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
How does Concept Foundation achieve it?
• Manages technology transfer and key
components of pharmaceutical manufacturing.
• Acts as “guardian” of product quality and access
to public sector agencies at an affordable price,
through specific agreement on quality,
availability and pricing with the manufacturer.
• Names licensee in its Lloyds liability insurance.
• Monitors how public sector price is implemented
in each country.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
How does Concept Foundation achieve it?
• Concept provides and manages key components for
pharmaceutical manufacturing and marketing, such as:
technology transfer, cGMP protocols, data from pivotal
clinical studies, GCP-compliant clinical research, ICHcompliant regulatory documentation, regulatory dossier
submissions, and identifying importers and distributors.
• In return, the commercial partner agrees to serve underdeveloped and normally unprofitable markets with
products of assured quality at the lowest possible cost.
• Concept Foundation negotiates a transparent ex-factory
supply price for public sector agencies and ensures that
appropriate strategies have been developed for the
introduction of a product.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Regulatory dossier
Clinical module
• Undertook additional analyses of data from
WHO clinical trials; undertook bioequivalence
studies against innovator products; prepared
expert clinical review.
Toxicology and preclinical module
• Undertook additional genotoxicity studies;
prepared expert toxicology review from
published data of mifepristone and misoprostol
and the preclinical part of dossier
Completed dossier in an ICH-compliant format.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
What has been achieved?
Collaborative agreement with
WHO; creation of a PPP with
Sun Pharma, India; and
funding by DfID, Norad,
Minbuza, Packard Foundation
and an “anonymous donor”
allowed development,
registration and introduction
of an affordable product of
assured quality
Medabon®
Product website launched
www.medabon.info
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Where is Medabon being registered?
Registered
Nepal
India
In process
Ethiopia
Ghana
In preparation
Viet Nam
Tunisia
Planned
Cuba
Georgia
Cambodia
Zambia
Mozambique
Colombia
Mongolia
South Africa
Moldova
Benin
Burkina Faso
Guyana
Kazakhstan
Tajikistan
Uzbekistan
Turkey
15 countries
Armenia
Macedonia
in EU/EFTA
Kyrgyzstan
Brazil
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
So “Where are we now?”
THIRTY YEARS after Roussel-Uclaf undertook its
clinical trials on mifepristone (RU-486) for early
abortion, where are we now?
Are affordable products of assured quality for
medical abortion widely available to poor women
throughout the world? No, some progress but….!
Or do we have a critical healthcare technology
which follows the “norm” where the rich can always
access quality products and services but the poor
remain without them? In many countries, the
answer remains yes and is a key issue we MUST
continue to address.
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010
Visit www.conceptfoundation.org
and www.medabon.info
International Consortium on Medical Abortion
Lisbon, 2-4 March 2010