Mohamad Haitham Ayad Pharm.D – MSc

THE ROLE AND THE ADDED VALUE OF PROPER FORMULATION

DEVELOPMENT

23 June 2011Life Science Forum - Basel

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PRESENTATION OUTLINE

Formulation Science

Main steps of formulating a Drug Product

The role of Formulation Science in different stages of Drug Development

Trends and challenges in formulation development

Conclusion

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FORMULATION SCIENCE

Definition:

The science of transforming an Active Pharmaceutical Ingredient into a quality Drug Product in a specific dosage form

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WHY TO FORMULATE A DRUG SUBSTANCE

Basic requirement Patient needs: improve the test, add a color and

reduce the number of daily intake → Patient compliance

Industrial needs: improve the flowability, density and compressibility of API → Productivity

Advanced requirement Correct the poor drug-like properties of new

molecules identified mainly by HTS

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WHY TO FORMULATE A DRUG SUBSTANCE

To be absorbed to the systemic circulation, the drug should be soluble and permeable through the GI barrier

The introduction of HTS allowed identifying more specific molecules but bigger and more Lipophilic

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BIOPHARMACEUTICAL CLASSIFICATION SYSTEM (BCS)

Development pipelines compared with top 200 US marketed drugs

Source: L. Benet – Bulletin Technique Gattefossé - 2006

Class I

High solubility High permeability

~35% / 5%

Class II

Low solubility High permeability

~30% / 70%

Class III

High solubility Low permeability

~25% / 5%

Class IV

Low solubility Low permeability

~10% / 20%

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MAIN STEPS OF FORMULATION DEVELOPMENT

Preformulation Characterization of API (Solubility, melting point,

density….)

Formulation Choosing the quantitative formula and its process

of fabrication

Scale-up and process validation Transferring the process from laboratory to

industrial scale

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THE ROLE OF FORMULATION SCIENCE IN DIFFERENT STAGES OF DRUG

DEVELOPMENT PROCESS

Development Stage

Phase IIPreclinical Phase IHit-to-Lead/ Lead

Optimization

Assay

Dev/ScreeningPhase III Commercialization

Drug Discovery Clinical DevelopmentLife Cycle

Management

Preformulation

Formulation support for

Preclinical tests

Evaluating the

“Developability” of clinical

candidates

Formulation Development

On time supply of clinical

trail material

Indication expansion

Reformulation

Second generation

launch

Rx-to-OTC switch

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TRENDS AND CHALLENGES IN FORMULATION

DEVELOPMENT

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DRUG DELIVERY TECHNOLOGY

Formulation technologies that modify drug Pharmacokinetic for the benefit of improving product efficacy and safety, as well as patient compliance

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DRUG DELIVERY TECHNOLOGY

Growth of drug delivery market

Development duration and cost

YEAR 2000 2006 2009 2016 DRUG

DELIVERY MARKET ($bn)

26 60 101 199

DRUG DELIVERY

ENABLED PRODUCT NEW DRUG

Time to approval 6.7 Years 12-15 Years Clinical

Development and approval success rate

25% 16%

Development cost 98 (Million) 1200 (Million)

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OUTSOURCING

CMC (Chemistry, Manufacturing & Control) accounts for 5% of total R&D spend

40% of CMC activities are outsourced

The CMC outsourcing market is estimated at 2 $bn and shared by +280 CDMOs

Reference: PharmaSource estimates 2008

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INDIA vs. CHINARIDING ON A TIGER OR A DRAGON

In general, China is stronger in biology and is rapidly improving its skills. It has been the only country in the developing world to participate in the International Human Genome Project

India has more complete services in CMC (Chemistry, Manufacturing & Control), including formulation and analytical services, up to full development for international filings. (it has the highest number of approved FDA sites and ANDA outside of USA)

Reference: Frank Floether, On the Move: Pharmaceuticals R&D in Asia, 2009

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BIOPHARMACEUTICAL FORMULATION

Biopharmaceuticals are medicinal products created by Biotechnology

More than 150 Biopharmaceuticals are approved by FDA and more than 630 are currently in development

Most biopharmaceuticals are parenteral because of the acidity of the stomach and poor intestinal permeability

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BIOPHARMACEUTICAL FORMULATION

Oral route: EnteriPep® (Unigene) tablet includes an enteric coating, organic acid and

absorption enhancer Transdermal route: PassPort® (Altea) batch with

applicator uses electrical pulses to create microchannels through which Biopharmaceuticals can passes

Nasal Route: few Biopharmaceuticals are commercialized like Fortical® and Synarel®

Pulmonary route: Promaxx® (Baxter) combine the biopharmaceutical into a bioerodible protein microsphere

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CONCLUSION

The success of bringing a new medicine to the market isthe result of a complementary and equally important contribution of scientists working in different scientificfields.

As Formulation Development is part of the processof bringing every new drug to the market, thequality of formulation contribution is very critical inthe success of new drugs.

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THE ROLE AND THE ADDED VALUE OF PROPER FORMULATION

DEVELOPMENT

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