Drug Development Process

Mitä on tuotekehitys? A definition „

Tuotekehityksen vaiheet

„ „

Luennot helmikuu 2006 Helsingin Yliopisto, Farmasian tiedekunta, teknologia, lääkevalmisteblokki. FaT Marja Ritala

„ „ „

Tuotekehityksen vaiheet

Product development? Drug development? Technical development? Pharmaceutical development? Drug delivery technology? Chemistry and manufacturing?

M. Ritala 2006

Tuotekehityksen vaiheet

Drug Development Process PROOF OF CONCEPT

SAFETY AND EFFICACY

Tuotekehityksen vaiheet

Contents (1) „ „

DISCOVERY

PRE-CLINICAL

„ „

CLINICAL CLINICAL PHASE I PHASE II

CLINICAL PHASE III

PHASE IV

„ „

PHARMACEUTICAL DEVELOPMENT

MAINTENANCE

„ „ „

IND

NDA

Definitions Trends in the pharmaceutical industry Processes Preformulation Formulation Analytical development Specifications, quality Choice of manufacture Stability

MA, LAUNCH

PRODUCT LIFE CYCLE MANAGEMENT M. Ritala 2006

M. Ritala 2006

Tuotekehityksen vaiheet

Contents (2) „ „ „ „ „ „

„ „

Biostudies New chemical entities Life cycle management of products Generic drug substances and products Marketing authorisation applications Case studies of formulation and life cycle management Skilled people needed Pharmaceutical development in the future

Trends in the Pharmaceutical Industry

M. Ritala 2006

1

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Trends in the Pharmaceutical Industry (1)

Trends in the Pharmaceutical Industry (2) „

„ „ „ „ „ „ „

Market growth Mega mergers Consolidation Networking (emerging technologies) Biotechnology in addition to chemistry Cost containment of healthcare R&D productivity challenge

„ „

„ „ „

M. Ritala 2006

Fully integrated pharmaceutical companies Virtually integrated pharmaceutical companies Outsourcing „ strategic partnerships „ contract services Networking Spin-offs Intensive life-cycle management

M. Ritala 2006

Tuotekehityksen vaiheet

Drug Development Process PROOF OF CONCEPT

Processes

DISCOVERY

SAFETY AND EFFICACY

PRE-CLINICAL

CLINICAL CLINICAL PHASE I PHASE II

CLINICAL PHASE III

PHASE IV

PHARMACEUTICAL DEVELOPMENT

IND

MAINTENANCE

NDA

MA, LAUNCH

PRODUCT LIFE CYCLE MANAGEMENT M. Ritala 2006

Tuotekehityksen vaiheet

Drug Development Process

Tuotekehityksen vaiheet

Development data brings new information to the pharmaceutical development DISCOVERY

DISCOVERY

PRE-CLINICAL

PRE-CLINICAL PHASE I

Pharmceutical development

PHASE I

P II

PHASE III

P II

IND DRUG SUBSTANCE FORMULATION

NDA

PHARMACOKINETICS IN HUMANS AND DOSING

MA, LAUNCH

INDUSTRIMFR PROCESS DEVELOPMENT ALISATION

PRODUCT MAINTENANCE

PRE-CLINICAL ADME, PHARMACOLOGY TOX PROFILE

ANALYTICAL DEVELOPMENT STABILITY

M. Ritala 2006

PHASE III

PHASE IV

PRIMARY STABILITY

FOLLOWUP STAB.

MOLECULAR PROPERTIES

COMMERCIAL PRODUCT STRENGTH(S)

PHASE IV LIFE CYCLE MANAGEMENT AND BRAND DEVELOPMENT

TO BE USED FOR: - DRUG SUBSTANCE DEVELOPMENT - ANALYTICAL DEVELOPMENT - ADMINISTRATION ROUTE SELECTION - DOSAGE FORM SELECTION AND DESIGN - UNIT DOSES AND DOSING - ETC.

M. Ritala 2006

2

Tuotekehityksen vaiheet

Main Processes in Pharmaceutical Development „

„ „ „

„

„

Drug substance development Preformulation Formulation Development of Specifications Analytical methods development Stability studies

„

„ „ „

„

Manufacturing process development Industrialisation Process validation Documentation of data Project planning and management

Drug substance development

M. Ritala 2006

Tuotekehityksen vaiheet

Drug substance development „

„ „ „

„ „ „

A robust synthesis process with consistent batch-to-batch quality Selection of salt Analytical methodology Mastering the physical properties like particle size and polymorphism Stability Scaling up and technlogy transfer Documentation

Preformulation

M. Ritala 2006

Tuotekehityksen vaiheet

Preformulation „ „

„

„ „

„

„

Solubility (aqueous, pKa, log P, log D) Molecular optimization (salt, hydrate, solvate, new analogs,…) Crystal Engineering (polymorph, habit, size, surface characteristics…) Crystal structure determination Biopharmaceutical classification (BCS) (solubility, dissolution, absorption) Drug stability evaluation (physical, chemical, solution phase, solid phase, …) Compatibility analyses (drug substance, excipient, packaging materials)

Formulation

M. Ritala 2006

3

Tuotekehityksen vaiheet

Formulation „ „ „ „

Composition + process = formulation Product design Formulation determines how the drug is delivered A good composition „ „ „ „ „ „

„ „ „

is simple, but innovativeness may be needed utilises standard compendial excipients easy to manufacture good stability facilitates straightforward analytics protects the product against generic competition

Formulation work is based on information gained through preformulation and biostudies Laboratory scale work The guidelines of authorities give a roadmap

M. Ritala 2006

Tuotekehityksen vaiheet

Formulation work is based on science „ „ „

„ „ „ „

molecule properties physiology, biology delivery technology

The consumer needs are identified Target product profile is defined There is a clear view of the indication and target population There is an understanding of administration route, dose and dosage form

Tuotekehityksen vaiheet

„

Oral controlled release

„

Biovail, Elan, Alza (JJ), Skye Pharma, Cardinal Health...

Transdermal delivery „

Altea, Alza (JJ), 3M...

Respiratory delivery „

Nectar (Inhale), Biovail, Elan, Skye Pharma...

M. Ritala 2006

Tuotekehityksen vaiheet

Commercialised drug delivery technologies today „

„ „ „ „

Oral controlled release Transdermal Implants Quick dissolve Single isomers Liposomes

$$$$$$ $$$$$ $$$$ $$$ $$ $

M. Ritala 2006

Drug delivery companies and technologies „

ƒUnderpinning science must be sound ƒUniqueness ƒit solves a problem ƒcan be patented ƒcreates cost advantage ƒcan be used as an asset when forming exclusive partnerships ƒTechnology can be validated

„

M. Ritala 2006

„

Characteristics of a sound innovation

M. Ritala 2006

Prerequisites of a successful formulation : „

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

The largest drug delivery products of the 1990’s „ Drug

Developer

Peak sales

Marketer

Procardia XL

Alza

1,250 Mill.$

Pfizer

Duragesic

Alza

1,200 Mill.$

Johnson & Johnson

Lupron

Tap

1,100 Mill.$

TAP

Cardizem SR/CD Elan

1,000 Mill.$

Hoechst

Nicotine Patch

Several developers

800 Mill.$

Novartis

Nitro Dur

Key

600 Mill.$

Schering Plough

M. Ritala 2006

4

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Procardia XL: A pharmaceutical company's dream scenario „

Technology selection criteria

Instead of suffering a monumental loss when an important drug goes off patent, the company launches a new, vastly improved version that eclipses both the original drug and its generic competition. That's exactly what Pfizer did when it partnered with ALZA to develop Procardia XL®, which incorporates ALZA's OROS® osmotic technology.

„ „ „ „ „ „

„

„

ALZA's technology gave Procardia XL® several major advantages over Pfizer's original product, Procardia®, and generic nifedipine. As a result, the label indication for Procardia XL® was expanded to include treatment of both angina and hypertension. In Finland marketed under name Adalat Oros

„ „ „ „

M. Ritala 2006

Scientific understanding Similarity of compounds or problems addressed Realistic assessment of success Stage of development Freedom to operate (drug type, therapeutic area) Manufacturing capability Scope for intellectual property Development timescale Costs Predicted sales and profitability

M. Ritala 2006

Tuotekehityksen vaiheet

Why analyse products during development? Analytical development

„

„ „

Formulations are often fine-tuned after analysing concentrations of the drug and it’s metabolites in blood or target organ Stability study results determine the shelf-life Validated analysis methods are used to control and assure the quality of the drug

M. Ritala 2006

Tuotekehityksen vaiheet

Analytical development „

HPLC, TLC, IR, NIR, UV, GC, MS, CE... are the methods to analyse „ „ „ „ „ „

„

Assay of drug substance Degradation profile Identification Content uniformity Dissolution Organic volatile impurities

Specifications and quality

The methods are validated in regard to accuracy, sensitivity, robustness, selectivity... „

according to ICH

M. Ritala 2006

5

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

A typical specification for a tablet formulation (1) „

„

„ „

„ „ „

A typical specification for a tablet formulation (2)

Appearance: White film coated tablet, scored on both sides, engraving MR1 on one side Identification: HPLC: same as active standard solution TLC: same spot and Rf as active standard solution Mean weight: target mg±5%. Uniformity of mass: 90% of tablets between mean weight found ±5%. 100% of tablets between mean weight found±10%. Water content (KF): ≤2% Disintegration: water, <30 minutes Hardness: 140-160 N

„ „ „

Dissolution: 30 min Q>80% Assay (HPLC): Active substance 95-105% Chromatographic purity: „ „ „

„

Microbiological quality*: total aerobic bacteria≤10² moulds per gram or ml. Absence of E. Coli „

M. Ritala 2006

Known individual impurity ≤0,3% Unknown individual impurities ≤0,1% Total impurities ≤1%

*) the parameter is controlled once every 10 batches or at least once a year

M. Ritala 2006

Tuotekehityksen vaiheet

Choise of manufacture „

Choice of manufacture

„ „

„

Make, byu or outsource? Europe, U.S., China or India? Investment on new buildings, new machinery? Calculations on volumes and costs „ „ „

batch sizes? cost of goods? sourcing strategy?

M. Ritala 2006

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Manufacturing process development in different scales •Screening studies for identification of critical control parameters (CCPs)

•Update of CCPs

• FMEA

• Use of database

• Use of database

•Quality team meetings

• Optimisation study

„

• Update of FMEA

•Quality team meetings

Laboratory scale

Process development/Deliverables

Pre-pilot scale

Pilot scale

Process Validation & Production Commercial manufacture scale

„ „ „

„

Product eval. mtg 1 M. Ritala 2006

Product eval. mtg 2

Product eval. mtg 3

Product eval. mtg 4

Product eval. mtg 5

„

Quality targets and metrics specified for the product and manufacturing process Limits set for critical process control parameters Risk analyses (FMEA, statistical predictions) Process database system established to be used during commercial manufacture Finalised master formula Fine tuning of product specifications

M. Ritala 2006

6

Tuotekehityksen vaiheet

Common Tools for Successful Drug Development Work

„ „ „

„

„

„

Portfolio management Project management Scientific networks Knowledge management Information mgmt systems Well described processes Balanced Scorecard

„ „ „ „ „

„

„

Target Product Profile Drug Product Concept Statistical methods Optimisation methods Risk assessment and management Failure modes and effects analysis Six sigma

Stability

M. Ritala 2006

Tuotekehityksen vaiheet

Shelf-life of a product „ „ „ „ „ „

Shelf-life is the period during which drug product conforms to a given set of specifications Based on the results of stability studies Proposed and justified in regulatory documentation 12 month data from three batches required at the time of submission (NCE’s) 6 month data from two batches required for generic products Storage conditions to be studied: „ „ „

„

Biostudies

25˚C, 60% RH 40˚C, 75% RH 30˚C, 60% RH

Usually enough data gathered at the time of approval for a shelf-life of 24 months

M. Ritala 2006

Tuotekehityksen vaiheet

Biostudies „

Give important feedback for the formulators of „ „ „ „

dosage form selection and design selection of strengths in vivo-in vitro correlation bioequivalence of generic products

M. Ritala 2006

Tuotekehityksen vaiheet

Bioanalytics and pharmacokinetics Analysis of the drug and its metabolites from body fluids, tissues and excretions. ADME: A = absorption D = distribution M = metabolism E = excretion

Drug concentration in plasma 100 Concentration, µg/ml

„

0.25 mg/kg/day 2.5 mg/kg/day

10

2.5 mg/kg/day

1 0,1 0.01 0

1

3

6 Time, h

M. Ritala 2006

7

Tuotekehityksen vaiheet

Drug Development Process DISCOVERY

New chemical entities

PRE-CLINICAL

Pharmceutical development

PHASE I

P II

PHASE III

PHASE IV

DRUG SUBSTANCE NDA

FORMULATION MFR PROCESS DEVELOPMENT

LAUNCH

INDUSTRIALISATION

PRODUCT MAINTENANCE

ANALYTICAL DEVELOPMENT STABILITY

PRIMARY STABILITY

FOLLOWUP STAB.

M. Ritala 2006

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Keys to success with NCE’s in the pharmaceutical industry

New chemical entities „ „ „ „ „ „

how long from discovery to market? what does it cost? Who is financing it? is there a medical need? indications? target population? ...and risks?

M. Ritala 2006

„ „ „

„ „ „

High quality basic and biomedical research Sufficient R&D funding Experience in drug development resulting in proprietary medicines Sufficient number of skilled people Networking and collaboration Becoming international, global strategies

M. Ritala 2006

Tuotekehityksen vaiheet

Generic drug substances and drug products Generic drug substances and drug products

„ „ „ „ „

patents expiring how fast and how cheap can one do it? life cycle management using technological innovations Keys to success: „ „

be fast, be there when the patent expires have several products on the market and under development

M. Ritala 2006

8

Tuotekehityksen vaiheet

Marketing authorisation applications Marketing authorisation applications

„ „

„ „

FDA: NDA and ANDA EU: centralised and mutual regocnition procedures JAPAN Applications are written in CTD-formats

M. Ritala 2006

Tuotekehityksen vaiheet

Case 1: Development and life cycle management of Clarityn® (1) „ „ „ „ „ „

Clarityn from Schering Plough Inc. Originator of loratadin The largest allergy product? First pass metabolism over 50% Generic competition begun in 2001-02 well before that Schering Plough made an agreement with a drug delivery company R.P. Scherer (now Cardinal Health) of developing a new formulatoin which could be patented.

M. Ritala 2006

Tuotekehityksen vaiheet

„

„

Clarityn-S® (Claritin Reditabs) was developed „

„

„ „ „ „

Freeze-drying technology, called Zydis ®, was used in Clarityn-S ® Zydis ® technology is wery well protected by patents owned by Cardinal Health Ltd, UK. readily dissolving in the mouth can be taken without water ”speed of melting does not affect speed of relief”. is generic to Clarityn

M. Ritala 2006

Case 1: Life cycle management of Clarityn® (3) „

Tuotekehityksen vaiheet

Case 1: Life cycle management of Clarityn® (2)

Clarityn-S was registred in Finland already 1995 generic, but in Finland not exchengeable, because of different dosage form

Tuotekehityksen vaiheet

Case 1: Life cycle management of Clarityn® (4) „

Composition of Clarityn 10 mg tablet „ „ „ „

„

„

Loratadine Lactose Maize starch Magnesium stearate

„ „ „

Stability 3 years

„ „

„

M. Ritala 2006

Composition of ClaritynS 10 mg tablet, freeze dried Loratadin Gelatin Citric acid Mannitol Peppermint aroma

Stability 2y, after opening the foil: 6 months

M. Ritala 2006

9

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Case 1: Life cycle management of Clarityn® (5) „

Case 1: Life cycle management of Clarityn® (6)

Generic competition in Finland, prices 1.2.2006 and 1.1.2004 (10 mg, 30 tabs) „ „ „ „ „ „ „ „ „ „ „

Loratadin Durascan Geklimon Gea Loratadin Alpharma Loratadin Generics Tuulix, Verman Loratadin ratiopharm Loratadin Biochemie Loratadin Copyfarm Loratadin Hexal Clarityn, Schering Plough Clarityn-S

3.97 € not mark. 4.75 € 4.98 € 4.74 € 5.88 € not mark. 5.89 € 5.89 € not mark. 16.65 €

„

(4.26 €) (4.58 €) (4.58 €) (4.68 €) (4.98 €) (6.37 €) (7.34 €) not mark. not mark. (15.17 €)

„ „

„ „

M. Ritala 2006

Tuotekehityksen vaiheet

Composition of Aerius 5 mg tablet, film-coated „ „ „ „ „ „ „ „

„

Desloratadine is the active metabolite of loratadine Aerius® tablet containing 5 mg of desloratadine was approved by EMEA in January 2001 Well absorbed, no first pass metabolism Suspects of hepatic toxicity have been reported

M. Ritala 2006

Tuotekehityksen vaiheet

Case 1: Life cycle management of Clarityn® (7) „

The next step in life cycle management was desloratadine

Desloratadin Gelatin Mannitol Aspartame Polacrilin potassium Dye Opatint Red (red iron oxide, hypromellose) Flavour Tutti-Frutti Citric acid

Case 2: development of a generic product, simvastatin (1) „

„

„

Originator MSD, ZOCOR 10mg and 20mg tablets Molecule patent expired in 2003 Price in Jan. 06: 46.61 € (20 mg, 98 tabl) „

Price in Jan. 04 : 163.54 €

„

„

„

First generic approvals in Finland 2001 12 generic products on the market in Finland in Jan. 06 Cheapest generic price 9.90 € „ „

Stability 2years

M. Ritala 2006

21.42 € in Jan. 05 45.89 € in Jan. 04

M. Ritala 2006

Tuotekehityksen vaiheet

Case 2: development of a generic product, simvastatin (2) „

Composition of Zocor 20 mg „ „ „ „ „ „ „ „ „ „ „

Simvastatin* Butylhydroxyanisol* Ascorbic acid* Citric acid* Microcrystalline cellulose* Pregelatinised starch* Lactose* Magnesium stearate* Hypromellose* HPMC Titanium dioxide*, Yellow and Red iron oxide

M. Ritala 2006

„

„

„

Generic competition...

Composition of Simvastatin Alternova 20 mg „

„

Tuotekehityksen vaiheet

all ingredients marked * and Propylene glycol

Marketing authorisation in 2003 Their application probably consisted of a few trial batches in pilot scale, stability studies and a biostudy, where the bioequivalence criteria with Zocor was met. M. Ritala 2006

10

Tuotekehityksen vaiheet

Case 3: Concerta depottablets (1) „

„

Tuotekehityksen vaiheet

Oros-technology from Alza

Concerta® (methylphenidate HCl) CII oncedaily extended-release tablet for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients age six and older. Concerta® uses an advanced OROS® patterned-release delivery system to achieve the desired improvement in symptoms, eliminating the need for in-school and afterschool dosing.

M. Ritala 2006

Methylphenidate plasma concentrations

M. Ritala 2006

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Case 3: Concerta depottablets (2) „

Composition „ „ „ „ „ „ „ „ „

M. Ritala 2006

Methylphenidate HCl Butylhydroxytoluen Cellulose acetate Hypromellose Phosphoric acid Poloxamer Polyethylenoxide Povidone Sodium chloride

„

„ „ „ „ „ „ „

Stearic acid Black and yellow iron oxide Lactose Titanium oxide Carnauba wax Macrogol 400 Isopropyl alcohol Propylene glycol Purified water

M. Ritala 2006

Tuotekehityksen vaiheet

M. Ritala 2006

„

Tuotekehityksen vaiheet

M. Ritala 2006

11

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Case 4: life cycle management of Comtess (entacapone) (1) „ „ „ „

„

Case 4: life cycle management of Comtess (entacapone) (2)

Originator Orion Pharma Approved 1997-8 by FDA and EMEA COMT-inhibitor To be used together with levodopacarbidopa medication (Sinemet) dose of entacapone is always 200 mg, dose of levo-carbi varies depending on the severity of the disease

„

„

„

„ „ „

M. Ritala 2006

Tuotekehityksen vaiheet

Composition of Comtess „ „ „ „ „ „ „ „ „ „ „ „

Entacapone Microcrystalline cellulose Mannitol* Croscarmellose sodium* Hydrogenated vegetable oil Hypromellose* Polysorbate 80* Glycerol* Sucrose* Magnesium stearate* Red and yellow iron oxide* Titanium oxide*

Three strengths of Stalevo allow individual adjustment and makes the dosing simple Easy to swallow due to small size Stalevo was approved by EMEA and FDA in 2003 The formulation is patented

M. Ritala 2006

Tuotekehityksen vaiheet

Case 4: life cycle management of Comtess (entacapone) (3) „

The dose is adjusted individually and taken 28 times/day Stalevo from Orion Pharma contains entacapone, levodopa and carbidopa in one tablet

„

Composition of Stalevo „ „ „ „ „ „

Entacapone Levodopa Carbidopa Maize starch Povidone K30 and ingredients marked * in composition of Comtess

M. Ritala 2006

Case 4: life cycle management of Comtess (entacapone) (4) „

Comtess 200 mg „ „

„

stability 3 years price for 100 tablets 123.20 €* price for Sinemet 100 tablets 100/25 mg (Paranova) 34.57 €* „

„

„

„

Stalevo 100/25/200 mg „ „

stability 3 years price for 100 tablets 155.34 €*

originator MSD does not market their Sinemet in Finland anymore Sinemet does not have any generic competitors. Extensive formulation patents!

M. Ritala 2006

* price 01.02.2006 in Finland

Tuotekehityksen vaiheet

The products are developed by people Pharmaceutical development relies heavily on individual expertise!

Skilled people are needed... „

„ „ „

Continuous support for personal development and scientific training Continuous training of leadership Provide up-to-date tools and facilities Nurture the human resource

M. Ritala 2006

12

Tuotekehityksen vaiheet

Prerequisites for successful team work „

„ „

„ „ „ „

Shared company values Shared goals Clear roles and responsibilities Co-operation Commitment Empowerment Communication

„ „ „ „ „ „

Quality of work Professional skills Leadership Planning and scheduling Feedback Control and reporting

Tuotekehityksen vaiheet

To run drug development nice and smoothly (1): „

decision making: „

„ „ „

„

escape unnecessary regulations „ „

M. Ritala 2006

kill bad projects early enough (bad projects are not necessarily the painful ones) listen to the scientists do not spend too much time trying to find concensus kill a few comittees and meetings open, honest, professionel relationship with the authorities do not overdevelop

M. Ritala 2006

Tuotekehityksen vaiheet

To run drug development nice and smoothly (2): „

do POC properly, but be fast „ „

„

Pharmaceutical development in the future

maximise the molecule „ „

„

„

phase I and II a can give invaluable information use miniaturisation and micro dosing where ever you can do life cycle management early enough remember the dosage forms patiens –consumers- like: -transdermal, eye, oromucosal use the opportunities to develop polymorphs, enantiomers and controlled release formulations

watch the NIH syndrome!

M. Ritala 2006

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

Opportunities for formulators to aid flow of new products through smart drug delivery „

Increased emphasis on life cycle management „ „

new, improved products and indications product differentiation

„

Growing biopharmaceutical market

„

More new drugs (molecules!) with sub-optimal properties

„

„ „

„

high throughput screening and synthesis decreased compound attrition

Increased specificity of delivery systems „ „

„

simple parenterals will not satisfy the market

cellular targeting and programmed release individualised therapies (... but who can afford them?)

Environmental considerations M. Ritala 2006

M. Ritala 2006

13

Tuotekehityksen vaiheet

Important future technologies in drug delivery „

Oral „ „ „

„ „

„

„

„

oral inhalation (insulin!)

„ „

Improved macromolecules „

Inhaled insulin, Exubera „

controlled release improved solubility rapid absorption

Site specific implants Non-invasive protein/peptide delivery „

Tuotekehityksen vaiheet

Fast acting powder formulation of human insulin inhaled by a simple device Developed by Pfizer (and Aventis) and Nektar Therapeutics approved by FDA and EMEA in January 2006 long term pulmonary safety was a concern that delayed the approval for several years

sustained release injectable

M. Ritala 2006

M. Ritala 2006

Tuotekehityksen vaiheet

Tuotekehityksen vaiheet

The challenges of drug development have continued to grow ƒGlobal strategies ƒVirtually integrated companies ƒIncreasing R&D expenses and timelines ƒpoor productivity? ƒtrue value creation? ƒExpanding number of technologies ƒchallenging the traditional approaches ƒIncreasing need to deliver return to ƒinvestors, ƒpartners and ƒcustomers M. Ritala 2006

M. Ritala 2006

Tuotekehityksen vaiheet

Have a look at... www. „ „ „ „ „ „ „ „

„ nam.fi „ emea.eu.int „ fda.gov „ duodecim.fi „ orionpharma.com „ apteekit.net controlledrelease.org iirusa.com/drugdelivery partnerships

alza.com cardinal.com bdpharma.com nektar.com pharmaprofiles.co.uk ltslohmann.com

M. Ritala 2006

14