The role and added value of proper formulation development

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 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

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The role and added value of proper formulation development

  1. 1. Mohamad Haitham Ayad Pharmacist – MSc THE ROLE AND THE ADDED VALUE OF PROPER FORMULATION DEVELOPMENT
  2. 2. M. H. Ayad 2 PRESENTATION OUTLINE  Introduction to Formulation Science  The role of Formulation Science in different stages of Drug Development  Trends and challenges in Formulation Development Drug Delivery Systems (DDS) Biopharmaceutical Formulation Outsourcing  Conclusion – Q&A
  3. 3. FORMULATION SCIENCE  Definition: The science of transforming an Active Pharmaceutical Ingredient (API) into a quality Drug Product, in a specific dosage form, by developing an appropriate Formula and Process M. H. Ayad 3
  4. 4. M. H. Ayad 4 WHY TO FORMULATE A DRUG SUBSTANCE (1)  Basic requirement Clinical need: Dosage Form adapted to the indication→ Clinical efficiency 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
  5. 5. M. H. Ayad 5 WHY TO FORMULATE A DRUG SUBSTANCE (2)  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 → Solubility and/or Permeability issues
  6. 6. M. H. Ayad 6 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%
  7. 7. M. H. Ayad 7 THE ROLE OF FORMULATION SCIENCE IN DIFFERENT STAGES OF DRUG DEVELOPMENT PROCESS Development Stage Phase IIPreclinical Phase I Hit-to-Lead/ Lead Optimization Assay Dev/Screening Phase III Commercialization Drug Discovery Clinical Development Life Cycle Management  Preformulation  Formulation support for Preclinical tests  Evaluating the “Developability” of clinical candidates  Formulation and Process Development  On time supply of clinical trail material  Reformulation  Indication expansion  Rx-to-OTC switch
  8. 8. M. H. Ayad 8 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
  9. 9. M. H. Ayad 9 TRENDS AND CHALLENGES IN FORMULATION DEVELOPMENT
  10. 10. M. H. Ayad 10 DRUG DELIVERY SYSTEM (DDS)  Formulation or a device that enables the introduction of a therapeutic substance in the body and improves its efficacy and safety by controlling the rate, time, and place of release of drugs in the body* *Source: Drug Delivery Systems - An Overview, Kewal K. Jain  Example of DDS:  Controlled Release (Matrix tablet, Osmotic pumps)  Solubility improving (Solid dispersion, Nano- technologies)  Technologies for fast- dissolving and taste-masking pills (Orodispersible)
  11. 11. M. H. Ayad 11 DDS – BUSINESS OVERVIEW  Growth of drug delivery market  Development duration and cost YEAR 2000 2006 2009 2016 DRUG DELIVERY MARKET ($bn) 26 60 101 199 DRUG DELIVERY ENABLED PRODUCT NEW DRUG Time to approval 6.7 Years 12-15 Years Clinical Development and approval success rate 25% 11% Development cost 98 ($Million) 2200 ($Million)
  12. 12. M. H. Ayad 12 BIOPHARMACEUTICAL FORMULATION  Biopharmaceuticals are medicinal products created by Biotechnology method  Accounted for only 12% Worldwide Pharmaceutical sales in 2003 but steadily increasing market share and expected to achieve 23 % in 2018*  Half of the top 100 selling drugs are expected to be of Biotechnology origin by 2018*  Most Biopharmaceuticals are parenteral because of the acidity of the stomach and poor intestinal permeability *Source: EvaluatePharma (29 May 2012)
  13. 13. BIOPHARMACEUTICAL DRUG DELIVERY BEYOND INJECTION  Oral route: Peptide tablet of Calcitonin (Unigene Laboratories) includes an enteric coating, organic acid and absorption enhancer  Transdermal route: PassPort® (Altea - Nitto) 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 (Insulin) into a bioerodible protein microsphere M. H. Ayad 13
  14. 14. 14 OUTSOURCING  Allow access to quantities and specific technologies which you do not have internally  Improve productivity and flexibility of internal R&D by leveraging external resources (knowledge, skills, FTE, etc) and reduce the drug discovery & development life cycle  Reduce the cost of R&D programs and lower over-all operating costs 40% of CMC activities are outsourced
  15. 15. M. H. Ayad 15 INDIA vs. CHINA RIDING 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
  16. 16. M. H. Ayad 16 CONCLUSION  The success of bringing a new medicine to the market is the result of a complementary and equally important contribution of scientists working in different scientific fields.  As Formulation Development is part of the process of bringing every new drug to the market, the quality of formulation contribution is very critical in the success of new drugs.
  17. 17. M. H. Ayad 17 THE ROLE AND THE ADDED VALUE OF PROPER FORMULATION DEVELOPMENT THANK YOU

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