PharmaConnect Africa Conference 2019

3 – 4 April 2019, Johannesburg, South Africa

ICGEB Transfer of Know-How Model

Dr. Nataša Skoko, Head Biotechnology Development Unit

Focus Points

ICGEB mission

Biologics

BIOSIMA for Africa

ICGEB Transfer of Know-How Model

Biosimilars

80+ Signatory Countries, 60+ Member States, 3 Components:

Trieste (Italy) - New Delhi (India) - CapeTown (South Africa)

An International Organisation within the United Nations Common System

18 Research Groups25 Research Groups

3 Research Groups

The ICGEB

mandate

1987-1995a special project

of UNIDO

1995-todayAn independent

international organisation

An International Organisation

for research, training and

technology transfer in Life

Sciences to promote

sustainable global

development

Developing KnowledgeICGEB Director, Arturo Falaschi with UNIDO Director General, Mauriciode Maria y Campos, 20 February 1996, Transfer of Assets UNIDO-ICGEB

www.icgeb.org

• Cutting-edge scientific research in its laboratories in Trieste, New

Delhi and Cape Town

• Advanced training supported by long- and short-term fellowships

for PhD and post-docs

• Organisation of International Meetings, Courses and Workshops

• Competitive research grants for scientists in Member Countries

including Early Career Return Grants

• Provision of technical assistance and capacity enhancement in

the regulation of biotechnology and its products

• Transfer of know-how to industry for the production of

biologics and diagnostics

ICGEB instruments of

action

Key Facts about diabetes according to WHO:

• In 2016, estimated 1.6 million deaths were directly caused by diabetes (7th leading cause of death)

• Almost 80% of diabetes deaths occur in low-middle income countries

• Dr Basu from Stanford University estimated that current levels of insulin access are highly inadequate compared to projected need, particularly in Africa and Asia

• It’ calculated that global insulin use was set to rise to 634 million 1,000-unit vials by 2030 from 526 million in 2018

Health news 2018

Biologics have tremendous health benefits and there is anenormous need for them, however many of these areunaffordable to the majority of people on Earth.

• A study published by medical

journal Lancet, has predicted

sub-Saharan Africa could see

an increase of 85% in the

number of cancer cases by

2030.

Biologics and Biosimilars

Frost&Sullivan Report, Global offering of WuXi Biologics shares, HK Stock Exch., 31 May 2017

A biosimilar is a biological medicinal product that contains a version of the active substance of an already

authorised original biological medicinal product (reference medicinal product).

Similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety

and efficacy based on a comprehensive comparability exercise.

First generation of biosimilars:

Interferons, Filgrastim, Erytropoietin,

Insulins, Growth hormone

Second generation of biosimilars:

Monoclonal antibodies, proteinsgenerated by fusion of antibody andreceptor moieties

Biosimilars opportunity

The trend in the price reduction with the launch of biosimilars resulted in

the increase in usage.

This increase in usage was heavily driven by the availability of biosimilars

as well as other factors, such as expanded indications.

Biosimilar development

Product developmentand comparative analysis

Process development and scale up

Nonclinical and clinical studies

Regulatory agencies review and approval

Time (years)

1-2 1-2 1-22-3Adapted from Bernstein

Research

AnalyticalAnalytical

ClinicalClinical

Preclinical

PK/PDPK/PD

Preclinical

Originator development

Biosimilars development

ICGEB model for Transfer of Know-How

MISSION:

Strengthen capacities and competencies of local partners

To accelerate the product availability at more affordable price

HOW:

Develop “in-house” expertise for production of API

Transfer of know-how with no exclusivity

Knowledge sharing

Successful

Technology

transfer

Training

protocol

and report

Analytical

methods

(QC)

Equipment

and facility

Upstream

process

Downstream

process

In house

training

Starting

material

Cell line

development

“Technology-in-a-briefcase”

Process development

Bacterial platform

Yeast platform

Mammalian cell platform

ICGEB developed technologies

Pegylated Granulocyte colony stimulating factorPegylated Interferon alfaInterferon beta 1b

InsulinsGrowth hormone

Pegylated ErythropoietinPegylated Interferon beta 1a

European Pharmacopoeia monographs

• European Pharmacopoeia (Ph. Eur.) monographs for

biotherapeutic products have existed since the 1990s

and remain the publicly available standard defining the

quality of these medicines.

• The Ph. Eur. lays down common, compulsory quality

standards for all medicinal products in Europe.

• Monographs are public standards; therefore, products

that do not comply with the monographs and

requirements of the Ph. Eur. are normally excluded from

the market.

• Compliance to a monograph does not mean

demonstration of biosimilarity.

BDG Std

Calibration Curve

Abs [Sialic Acid]

1 2 3 Average ug/mL

E 0.125 0.129 0.132 0.129 20

D 0.250 0.234 0.242 0.242 40

C 0.333 0.343 0.342 0.339 60

B 0.437 0.441 0.436 0.438 80

A 0.529 0.529 0.538 0.532 100

m 199.230

b -6.941R2 0.999

[Sialic Acid] [EPO] Relation average

Sample 1 2 3 average ug/mL M ug/ml M M Sial./ M EPO

Batch 2/09 0.396 0.413 0.417 0.409 74.48 2.41E-04 600 1.96E-05 12.292 11.47

Batch 2/09 0.213 0.205 0.209 0.209 34.70 1.12E-04 300 9.80E-06 11.454

Batch 2/09 0.114 0.113 0.121 0.116 16.17 5.23E-05 150 4.90E-06 10.675

y = 199.23x - 6.9413

R 2 = 0.9988

0

20

40

60

80

100

120

0.000 0.200 0.400 0.600Abs (580 nm)

Co

nce

ntr

atio

n (

ug

/mL

)

European Pharmacopoeia Monographs

scientific guidelines relating to quality

(physicochemical, immunochemical properties, biological activity, impurities)

PEG 20kDa activation and conjugation

MTPLGPASSLPQSFLLKCLEQ

VRKIQGDGAALQEKLCATYKL

CHPEELVLLGHSLGIPWAPLSS

CPSQALQLAGCLSQLHSGLFL

YQGLLQALEGISPELGPTLDTL

QLDVADFATTIWQQMEELGMA

PALQPTQGAMPAFASAFQRR

AGGVLVASHLQSFLEVSYRVL

RHLAQP

PEG

Std Bdg Std Bdg

GCSF

Transfer of know-how to industry

at ICGEB

STEPS:

• Signature of a Technology Transfer Agreement

• PHASE 1: Scientists from the Company spend 4-6 weeks in the ICGEB

Laboratories gaining hands-on experience in the production of selected

API. Supply of complete down and upstream procedures

• PHASE 2: Post training assistance to the industrial partner in establishing

the process at its own facility.

ICGEB Transfer of Know-How

SEARCH FOR DONORS:

• To upgraded BDU facility and purchase new lab equipment in order to

perform work and training in more pharma-like conditions.

• To cover the costs of training, so that ICGEB can in turn transfer the

technology to interested local manufacturers at no cost.

Successful

Technology

transfer

Training

protocol and

report

Analytical

methods

(QC)

Equipment

and facility

Upstream

process

Downstream

process

In house

training

Starting

material

Cell line

development

Pharma-like

facility/new

equipment

for Mabs/Fabs

development

Master Cell

Banks in GMP

QC tests under

GLP standards

“Technology-in-a-briefcase”

- BIOSIMA -Fostering domestic capacity for the production

of Biosimilars on the African Continent

Rationale: the project BIOSIMA tackles the poor access and scarce

availability of cost effective and quality life-saving drugs, a chief obstacle

to achieve universal health coverage in Africa

Objective: to increase access to safe, affordable and effective, quality-

assured biosimilars for the African population

How: fostering internal/local domestic production capacity in the field of

biopharmaceuticals, and, in particular, biosimilars, through a concerted

effort that will promote action on all key aspects, from capacity

enhancement in biotechnology development to regulatory settings

- BIOSIMA –In partnership with WHO and UNIDO, the Governments and local industry

ICGEB

Training and technology transfer to selected partners from target

countries in the development of processes for biosimilars production.

WHO

Promotion of the

implementation of

internationally

accepted biosimilar

guidelines, such as

those developed by

the WHO, within the

target

countries/region(s).

UNIDO

Assessment of the current

manufacturing capacity for

biosimilars for the

development of the sector

and market in target

countries.

Eensuring compliance with

WHO standards of Good

Manufacturing Practice

(GMP), including both

generics and biosimilars.

Nataša Skoko, PhD

Sotir Zahariev, PhD

Corrado Guarnaccia, PhD

Federico Odreman, PhD

Sulena Polez, BSc

Gordana Uzelac, PhD

Ventsislav Zlatev, MSc

Suzana Aulić, PhD

Živa Marsetić, PhD student

BDU team