The Impact of Pharmaceutical Sciences on Healthcare Vinod P. Shah, Ph.D., Pharmaceutical Consultant

Transcription

1 The Impact of Pharmaceutical Sciences on Healthcare Vinod P. Shah, Ph.D., Pharmaceutical Consultant Southern African Regional and International Symposium SARI 2014 MCC/AAPS Symposium Pretoria, S Africa, March 11-13, 2014

2 International Pharmaceutical Federation Board of Pharmaceutical Sciences Activities commissioned by FIP/BPS In 2007: To develop a view on The Pharmaceutical Sciences in 2020 In 2010: Impact of Pharmaceutical Sciences on Healthcare: A Reflection Over the Past 50 Years

3 Outline of Presentation Pharmaceutical Sciences Impact of Pharmaceutical Sciences Regulations Global Impact Pharmaceutical Sciences in 2020 Conclusions

4 Pharmaceutical Science Pharmaceutical science is a broad scientific discipline which encompasses the scientific disciplines of drug discovery, formulation development, drug disposition, manufacturing and marketing of safe medicines. The later part also include drug approval process.

5 Evoluation of Pharmaceutical Sciences, in a very broad sense, can be viewed as The science of medicines

6 No safe and effective treatments of essential hypertension which increases chance of premature morbidity and death. [Reserpine, mercurial diuretics] Surgical treatment of peptic and duodenal ulcers with its attendant risks was relatively common State of Affairs in 1960 No effective drugs for many debilitating and lethal parasitic and viral diseases, especially in the developing world Many medicines were prepared extemporaneously

7 What has changed since 1960?

8 The Survey Five groups and associated co-ordinators were identified: Drug Discovery (Prof. Christian Noe) Pharmacokinetics and Pharmacodynamics (Prof. Geoffrey Tucker) Formulation Sciences (Prof. Daan Crommelin) Drug Regulation (Dr Carl Peck) Drug Utilisation (Dr Mario Rocci) Each coordinator invited leading pharmaceutical scientists in their field to identify The 5 most influential ideas/concepts/developments introduced by pharmaceutical scientists (in their field) over the last 50 years? 52 responses were received from the 75 individuals who were canvassed.

9 Structure of Report Divided into six sections : Drug discovery ADME (absorption, distribution, metabolism, and excretion) Pharmacokinetics and pharmacodynamics Drug formulation (Pharmaceutics) Dosage form development Drug regulation Drug utilization Personalized medicine each describing key contributions that have been made in the progression of medicines, from conception to use. Common thread: application of translational science to improvement of drug discovery, development and therapy. Final report compiled by Prof. Malcolm Rowland

10 Drug Discovery: Timeline of Key Developments Biochemistry and signalling pathways Molecular drug targets Computation Molecular biology High Throughput Screening

11 Formulation Science Drug Development Dosage form development formulation factors Formulation can influence the outcome of drug therapy Advanced equipment for the production of high quality classical pharmaceutical formulations Improved process design and development Biopharmaceutics biological factors first pass Dosage forms IR, DR, ER Routes of drug administration TDS, Pulmonary Targeted drug delivery

12 Formulations Importance of drug dissolution MR dosage forms Improved PK characteristics of the API Improved patient compliance OROS osmotic release oral system Liposomes Nanomedicines New (alternate) route of administration Parenteral Transdermal Pulmonary

13 Formulation Sciences: Timeline of introduction of key concepts and developments Transdermal Bioavailability Drug Targeting/ Nanoparticles/proteins PAT/QbD MDI OROS EPR BCS/Biowaiver DPI Pegylation of proteins/ nanoparticles MDI = metered dose inhaler DPI = Dry powder inhalation OROS = osmotic release oral system EPR = enhanced permeability and retention effect PAT/QbD = process analytical technology Quality by design

14 Bioavailability / Bioequivalence Concept Drug absorption, distribution, metabolism and elimination (ADME) Drug clearance concept Understanding of the impact of physiological and pathological changes on drug elimination Bioavailability and Bioequivalence Concept Scientific basis for improved drug design formulation and evaluation of therapeutic equivalence ADME/PK-PD modeling concept

15 ADME: Timeline of introduction of key developments The rise of druggibility Mechanism of drug absorption ph partition hypothesis (need to be lipoidal) Cell monolayers to predict permeability Structurefunction of drug metabolising enzymes CYP 450 shown to metabolise drugs Discovery of debrisoquine (CYP2D6) genetic polymorphism Drug-drug interactions ascribed to specific enzyme isoforms, substrates, inhibitors, inducers. IVIVE Toxicity Involvement in carcinogenicity Linkage to idiosyncratic drug toxicity Immunological basis for drug toxicity Role of transporters in drug disposition Active renal secretion recognised P-glycoprotein involvement in resistance to cancer drugs. Systematic function and genetic characterisationof influx and efflux transporter. BDDCS First industrial ADME departments dedicated to drug discovery. Introduction of Rule of five

16 Pharmacokinetics/Pharmacodynamics Body physiologically based PK modeling Pharmacokinetics and pharmacodynamics relationship - Linkage of PK and PD Enhanced interpretation of drug response Nonliner Mixed effect modeling ( Population PK ) Insight into population variability in response to PK and PD Whole body physiologically based PK modeling allows predictions of PK behavior and influence of patient variables; PK-PD tool for predicting drug response

17 Pharmacokinetics/Pharmacodynamics: Timeline of Key Developments Bioavailability & Bioequivalence Whole Body Physiological-based PK PK-PD Linking Clearance Molecular Concept biology Population PK/PD

18 Rationalizing Drug Administration Pharmacokinetics, PK Pharmacodynamics, PD Drug Dose Route Dosage Form Frequency Duration Concentration Time Effects Desired Adverse Pharmacokinetics: How body handles drug Pharmacodynamics : What drug does to body

19 Drug Regulations Pharmaceutical Sciences Provided the scientific basis for the 1984 Drug Price Competition Act Provided statutory authority to FDA for BE based approval of new generic drugs Provided scientific basis for accepting BE studies as a surrogate for clinical studies. Biopharmaceutics Classification System: Using the principles of BCS, provided justification for drug approval based on in vitro information.

20 ``````````````````````````````

21 Generic Drug Products FDA ensures that the generic drug products are safe and effective, are pharmaceutically equivalent and bioequivalent to the brand-name counterparts Generic drugs have to meet the same rigid standards and are manufactured under the same strict standards of FDA s good manufacturing practice regulations as required for innovator products. Generic products are approved with AB rating, and are TE and TI with brand name drug products.

22 Regulation Pharmacokinetics of the drug ADME, BA and BE concepts has been the focus for evaluation of different formulations of new drugs and also generic drugs. These concepts have provided strong scientific basis for BE based approval of all generic drugs. Principle of dissolution has been utilized as a product quality and performance tool. The scientific basis of BCS provides biowaiver for certain classes of generic drug products, thus reducing regulatory burden without sacrifycing drug product quality.

23 Regulations FDA - Bioavailability and Bioequivalence Regulations Bioequivalece (BE) concept critical basis for generic drug approval; bridging between clinical formulations and marketed product Biowaiver concept and in vitro dissolution as a surrogate BCS concept Lowering regulatory burden without lowering drug product quality. Regulatory Guidances

24 Drug Regulation: Timeline of introduction of key developments PK-PD Concepts & Techniques evolve in Academia Bioavailability/Bioequivalence regulations and Guidance Sweden Bioavailability/Bioequivalence regulations and Guidance USA PopPK-PD Concepts & Techniques embraced by FDA, EMA Modeling & Simulation Drug metabolism/transporterbased DDIs Biopharmaceutical Classification System IVIVC Guidances Pharmacogenetic-genomic Data Encouraged Biosimilars Legislation & Guidance

25 Personalized Medicine Pharmacogenetics + genomics personalized medicine Increasing emphasis on the identification, validation and use of differential biomarkers and disease state modeling. Better (targeted) treatment, reduced side effects Approach to drug development based on patient s attributes

26 Drug Utilisation: Timeline of introduction of key developments

27 Contributions of pharmaceutical sciences during past 50 years From description to mechanistic prediction. Targeting for specificity of action. Building druggability qualities into design. Optimising drugs, products, and dosage regimens for patients through PK/PD modeling. Building quality and reproducibility into drug delivery systems and products. Ensuring regulation reflects scientific developments. Delivering better medicines, including generics, to patients.

28 Impact of Pharmaceutical Sciences Innovations drives R & D bringing novel medicines to the market place and creating therapies that did not exist before. Advent of generic drugs have enabled the effective treatment of the disease at a reduced cost. Pivotal role in enabling the availability of Safe and Effective generic medicine.

29 Looking into future Need to enhance research and science base to develop validated methods for determining BE of complex dosage forms semisolids, aerosols and orally administered non-absorbed drug products. Application of nanotechnology to new medical products have the potential to be an anticancer agent. Individualized medicine Targeted medicines

30 Conclusions Along with scientists from other fields, pharmaceutical scientists have contributed significantly to the discovery and development of new drugs and drug preparations, and to improving the efficacy and safety of existing drugs and drug preparations. In particular, pharmaceutical scientists have been key players in facilitating the translation of these discoveries and developments into better healthcare

31 Impact of the Pharmaceutical Sciences on Health Care: A reflection over the past 50 years Malcolm Rowland, Christian Noe, Dennis Smith, Geoffrey Tucker, Daan Crommelin, Carl Peck, Mario Rocci, Luc Besancon, Vinod P Shah (1) J. Pharm Sci 101: , (2) International Pharmaceutical Journal, October, 2012

32 Pharmaceutical Sciences in 2020

33 Pharmaceutical Sciences in 2020 The Board of Pharmaceutical Sciences of FIP posed four main questions to address Pharmaceutical Sciences in 2020 : What major research activities will drive drug discovery and development? What will the enabling technologies be? What paradigm shifts will there be in drug discovery, development, regulation and usage? How will changes in education meet the demands of academia, industry and regulatory institutions? 33

34 Conclusions Globally operating companies will buy in technologies/concepts for new drugs from small private entrepreneurs and the academic world. Product development will be coordinated by these global players. Major activities will be outsourced to specialized companies and institutions. Quality of the work and speed will be decisive success factors. The classical high risk/high gain business model of innovative pharmaceutical companies may not be the best way forward for the industry. May lead to: more lean companies increasing partnering with other specialized companies, research organizations/institutions at various stages of drug development. more public-private-partnerships.

35 Conclusions Regulatory authorities will be more transparent in their decision-making process, and global harmonization will grow. Future therapeutic interventions will use new tools provided by a new enabling technologies. The paradigm of individualized medicine will be accepted as standard in many therapeutic fields, and the borderlines between diagnostics, drugs and medical devices will blur. Countries like India and China will become important global pharmaceutical players and users by 2020

36 Pharmaceutical Sciences in 2020 VP Shah, L Besencon, P Stolk, G Tucker, D Crommelin International Pharmacy Journal: 24(1), 1-16, The European J of Pharmaceutical Sciences: 38: , 2009 Pharmaceutical Research: 27: , 2010 Scenario Analysis: D Crommelin, P Stolk, L Besencon, VP Shah, K Midha, H Leufkens. Nature Reviews Drug Discovery: 9(2), , 2010 FIP website:

37 Thank You for Your Attention