Making products available for medical abortion and strategies for

their introduction

Peter HallActing CEO

Concept FoundationBangkok, Thailand

The mission of Concept Foundation

To provide access to products for sexual

and reproductive health of assured quality

to the public sector of lower and middle

income countries at the lowest possible cost.

Concept Foundation was established as an

international, charitable, not-for-profit

organization in Thailand in 1989.

To achieve its mission, Concept Foundation designs

and implements access-to-medicines programmes to

make quality product available at an affordable cost.

This involves:

- the establishment and support of Public-

Private Partnerships with pharmaceutical

companies in developing countries; and

- a systematic and coordinated approach to

product introduction.

What is Concept Foundation?

4

What does a PPP need to achieve?Private enterprises need togenerate financial success

Public sector needs access to lowcost drugs of assured quality

?

High MarginPreferential

PriceHow to balance?

Financial support from donors:• Clinical research• Technology transfer• Quality assurance• Registration filing, etc.

Cost benefitto public sector:•Affordable

public sector pricing

Conditions of agreement between WHO and Concept Foundation

• 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”, 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.

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, ICH-compliant regulatory documentation, regulatory dossier submissions, and identifying country-based importers and distributors. These activities save significant investments for the commercial partner and speed up time to market.

• In return, the commercial partner agrees to serve under-developed 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.

Some 150 million vials of the once-a-month injectable contraceptive, Cyclofem, have provided an additional choice to women in Asia and Latin America. Concept’s portfolio has also included a HIV diagnostic test and emergency contraception. Currently, Concept is making available a co-packaged mifepristone (1x200mg tablet) and misoprostol (4x200μg tablets) product, Medabon.

What have Concept’s PPPs achieved?

Regulatory issuesRegulatory documentation generally comprises of 3 sections: • clinical evidence of safety and efficacy - requires data from

pivotal GCP-compliant clinical research, also a key requirement for manufacturers of generic drugs is that they demonstrate that the products they produce are bioequivalent to the original, innovator product.

• preclinical and toxicological evidence of safety; and • data on chemicals, manufacturing and control (CMC). The

CMC component of an ICH-compliant regulatory dossier is difficult for many manufacturers to meet. It requires full information on the Active Pharmaceutical Ingredients (APIs); the manufacturing process; and all quality assurance procedures, including compliance with cGMP.

Regulatory issuesClass 1:  ICH-compliant dossier. Full data from original safety

and efficacy trials (NDA) or BE study (ANDA); full preclinical and toxicological data; full CMC data, evidence meet cGMP and a DMF for API; GMP inspection of factory

• South AfricaClass 2:  Abbreviated dossier; no original safety data but

clinical review summarizing all clinical data and results of BE study; summary of preclinical/clinical data; BE study required; manufacturing process validation; DMF for API

• Ethiopia, Algeria, Morocco, Tunisia, Egypt (may request additional data like Class 1 and manufacturer site visit);

• The 14 countries of the South African Development Community (SADC) have formally adopted harmonized guidelines. But it will be some years before these countries meet similar standards to those required by South Africa.

Regulatory issues• 13 out of 14 SADC countries (14th is South Africa),

Angola, Botswana, Democratic Republic of Congo, Lesotho, Madagascar, Malawi, Mauritius, Mozambique, Namibia, Seychelles, Swaziland, Tanzania, Zambia and Zimbabwe are at various stages between classes 2 and 3;

• Ghana, Kenya and Uganda are also between classes 2 and 3.

Class 3: Abbreviated dossier; overview and summary of preclinical/clinical data; no BE study; and no DMF required

• WAHO is attempting to harmonize requirements in 15 countries, Benin, Burkina Faso, Cape Verde, Côte d’Ivoire, The Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone, and Togo but is a lot further behind. Ghana is the furthest ahead.

Class 4:  No formal regulatory dossier required.• The remaining 19 African countries fall under Class 3 and

a few under Class 4.

Objectives of an introductory strategy• Provision of medical abortion in the context of CAC in

all facilities meeting the requirements of the national guidelines. In the initial phase this will be undertaken in selected healthcare facilities.

• Development of a training curriculum for the provision of comprehensive abortion care, in particular of MVA and medical abortion and including values clarification.

• Development of IEC materials for professionals and users.

• Development of an advocacy strategy for CAC.

• Implementation of operations research to allow planning for scaling up to other health care facilities.

What has happened to date?Introduction of medical abortion into the public

sector has suffered from either: • activities being undertaken by various national

and international organizations in an ad hoc

and uncoordinated manner; or • by undertaking a clinical trial or small OR study

in lieu of a coordinated introductory strategy –

neither addressing key service delivery needs

nor guaranteeing the availability or affordability

of product.

An optimal approach to product introductionTo achieve the stated objectives, it is necessary

to develop and implement an appropriately

designed introductory process. This requires:• a systematic and incremental approach; and• coordination and collaboration between the

public health system and all key stakeholders -

synchronization of activities is the key to

building an appropriate and supportive health

system for the provision of medical abortion.

This has begun in Nepal.

What is a supportive health system?• Drugs for medical abortion can be provided by

trained mid-level providers but, in the few cases of incomplete abortion or excessive bleeding, there is need for access to referral services.

• The health system must ensure access to a provider trained in the use of manual vacuum aspiration (MVA) and to blood transfusion services.

• The health system must be prepared to provide training of all levels of health care providers and values clarification with providers.

• Abortion remains a sensitive issue in many countries and there is a continuing need for advocacy with providers as well as the broader society.

Project managementTCIC

Policy

Advocacy

Materialdevelopment

Training

Service delivery

Productavailability

OperationsResearch

Sun Pharma

Concept

NHTC/DHS

All listed CAC service providersPublic & private

FHD/MOHTCIC/Ipas NESOG

NHIECC TCIC/Ipas

TCIC/Ipas

FHD/MOH MSI FPAN

PSI CREHPA

NESOG Ipas

NESOG Nursing CouncilMedical Council

PSI

CREHPA

partners

Training curriculumdevelopment

TCIC/IpasNHTC/DHS

NESOG Nursing CouncilMedical Council

Regional/districthealth authorities

Nepal

Evidence now shows 24 hours is adequate

Day 1 Day 2 Day 3

0800 2000 0800 2000 0800

24h 48h

Evidence from WHO studies show the efficacy of the mifepristone-misoprostol regimen to be similar for intervals from 24-48 hours post-mifepristone, when misoprostol is given vaginally. Similar with sublingual administration.

Frequently asked clinical questions about medicalabortion. World Health Organization, Geneva 2006www.who.int/reproductive-health/publications/medical_abortion/index.html

The need for information - providers/policy makers WHO organized a meeting ofexperienced researchers andclinicians working on medicalabortion. They responded to alist of the most frequently askedquestions about medical abortionfrom health-care personnelproviding abortion services. They reviewed those questionsand compiled answers based onscientific literature and their ownexperience.

The need for informationPATH, Ipas, Concept and WHO/HRP are finalizing materialsfor health care providers and programme managers who areworking to introduce Medabon®. They are also intended toreach policy makers and the media and include:• Medical Abortion & Medabon®: Key Talking Points• Medabon®: Frequently Asked Questions (FAQ)• Medabon®: What You Need to Know (sample patient

brochure)• Medabon®: Medical & Service Delivery Guidelines• Medabon®: Background for Providers of Emergency Care• Medabon®: A Framework for Introduction• Medical Abortion: Selected ReferencesWill be put on www.medabon.info in April 2009

Accessto

medicines

Distributor/importer

selection

Registration

IntroductionIntroductory

activities

Routineprovision

Scaling up

Trademark

Making medical abortion available - ideal

Accessto

medicines

Distributor/importer

selection

Registration

IntroductionIntroductory

activities

Routineprovision

Scaling up

Trademark

Making medical abortion available - usual

The need for product

Concept, together with its commercial partnerSun Pharmaceuticals, is in the process ofregistering Medabon® in Ghana, Ethiopia,Mozambique, Zambia, Tunisia and will begin in2009 in Benin, Burkina Faso and South Africa.

Where else could it be registered and introduced?In any country with any indication for abortion, eg,rape, incest or the life of the woman, ie, in mostcountries in Africa. How can we get it done?