Parioforma. Pharmaceutics Landscape - summary. (formerly RM Consulting) April 2005

Transcription

1 Parioforma (formerly RM Consulting) Pharmaceutics Landscape - summary April 2005 Parioforma Ltd 55 Princes Gate Exhibition Road South Kensington London SW7 2PN United Kingdom Tel: +44 (0) charles.rowlands@parioforma.com

2 Pharmaceutics Environment Pharmaceutics is that area of biomedical and pharmaceutical sciences that deals with the design and evaluation of contemporary pharmaceutical dosage forms (or drug delivery systems) so they are safe, effective, and reliable. It is much more than a single area of science; it encompasses a spectrum of diverse scientific disciplines including analytical chemistry, formulation and dosage form development as well as manufacturing (process development, scale-up and validation). The market was defined according to: Pre-formulation Physical characterization Method development Method validation Dosage form development Process validation Scale-up Clinical supplies manufacture, packaging, labelling and blinding Coatings Stability studies Technology transfer Life cycle management Regulatory support services 2

3 Pharmaceutics Environment The dosage form and delivery system used are key components to the successful development of new drugs and therapies. Managing the formulation process without iteration is the secret to reducing development time and the right decision, made by the right person at the formulations development stage, can have a dramatic impact on the movement of that product through the rest of the development process they can either accelerate it or slow it down. In addition, a satisfactory dosage form must be allied with an efficient and cost-effective manufacturing process formulations that require new types of equipment for manufacturing will add to a product s cost and time to market. To avoid later stage re-formulations, process changes and stability failures, drug developers may conduct preformulation studies. Such studies are aimed at providing as much relevant information as possible about the physical and sometimes chemical properties of a compound before a dosage form is selected - considering these variables at a very early stage the development of a better formulation. Factors considered include: Oxygen sensitivity ph stability Solvents and co-solvent systems or surfactants Ways to enhance the compound s solubility or stability Methods of sterilization A critical pre-formulation concern is confirmation that each batch of API has the same crystalline structure, and that this crystal form remains constant throughout the formulation and life of the drug product. 3

4 Market segments pharmaceutics services Off-Patent Products NCEs/NMEs Generics Drug Discovery Marketing Approval Line Extensions Reformulations On-Patent Products DEVELOPMENT & MANUFACTURING SALES & DISTRIBUTION 4

5 Market trends & drivers Pharmaceutical industry leaders are downsizing and outsourcing. Their need to focus on drug discovery and large scale commercial production has transferred a significant amount of their formulation development work into the hands of smaller, more focused companies with relevant expertise to coordinate and participate in the formulation and clinical trial supplies operations. In addition, more virtual biotechs are being formed. However, as the levels of outsourcing in drug development increase, some vendors now anticipate a change in behaviour routine outsourcing is expected to go offshore; but more strategic, value-added outsourcing is expected to remain domestic. Demand for outsourcing services is currently geared towards manufacturing this is in part due to the cyclical nature of drug research the industry generally goes in 10 year cycles so that the fruits of R&D activity in the late 1990 s are now in the latter stages of development. The cycle is expected to come back around to early-stage research over the next few years, after the new drugs now at the tail end of development hit pharmacy shelves. A trend supported by the fact that service firms are reporting more outsourcing of the final steps in drug development there is increasing demand for manufacturing services particularly for production used for clinical trials. Clinical trial supplies is now a lucrative area, with in excess of 50 companies operating in this sector in North America (RM top level research we anticipate that the true number could be in excess of 70+). More emphasis is now being placed on formulation formulation can differentiate a drug in today s highly competitive pharmaceutical marketplace, or salvage promising compounds that have been shelved due to formulation difficulties. In addition, the complexity and size of drug molecules and problems in their delivery have grown, providing new and expanded challenges for formulation scientists. Protein pharmaceuticals and gene delivery methods are providing additional exciting opportunities. 5

6 Market trends & drivers The increasing demands and the new challenges facing formulators means that expertise is not always available in-house there is now a growing need to look beyond conventional formulations and to suppliers who can provide the relevant expertise, innovation and novel drug development technologies. Generic companies are also following this trend - they no longer need the formulation of the name brand drug, they want something better. The result has been the emergence of a large number of companies offering formulation services there are in excess of 80+ companies operating in North America in this sector not including offshore operators. A hot area of formulation development is early stage pre-formulation this stems from the need to evaluate very early the druggable qualities of a lead compound in order to make go/no-go decisions and to kill unlikely compounds as soon as possible before heavy investments in time and money are made. Pre-formulation represents the interface between the drug substance and the drug product - yet on examining pipeline data, pre-formulation has yet to make an input on reducing late stage failures. One of the biggest problems in pre-formulation is solubility solubility has been the hottest and biggest trend in formulation over the past few years. This trend is being driven in the main by the increasing numbers of Biotechnology products in pipelines large molecules tend to have solubility problems. However, in addition between 40-50% of traditional drug candidates synthesized each year by pharmaceutical companies are poorly water-soluble. Most of these otherwise promising compounds are discarded because they are not sufficiently absorbed or bioavailable and are refractory to traditional formulation approaches. Formulation development remains a slow process because much of it still depends on traditional experimentation approaches, without the benefits of information technology, informatics, or the high-throughput methods used in drug discovery. 6

7 Market trends & drivers Over the next 5 years a shift from traditional medicine to targeted, biologic solutions is expected this will have an associated impact on the pharmaceutics market placing more demand on the need for innovative, functional formulations. Traditional 1 st line therapy Usually oral Mass population Mainly NCEs Chronic conditions Mostly symptom relief High Density 2 nd line therapy Specialist administered Clinically defined population Mainly biologics Mainly chronic conditions Mainly disease modifying Targeted Treatment 1 st & 2 nd line therapy Multiple delivery systems Targeted populations Diagnostics & biologics Chronic & acute conditions Disease modifying & preventative 7

8 Market trends - summary Market Trend Notes Formulation development is beginning earlier A more systematic approach is being used drug developers now realize that cutting corners in the preformulation phase of development may lead to trouble later. Testing of the API rather than a formulated clinical supplies To reduce API demand and shorten the time to begin clinical trials for a new compound, some pharmaceutical companies are testing pure API instead of formulated clinical supplies during proof-ofconcept or early Phase I studies. Increasing requests for reformulation Increasing emphasis on lifecycle management A drug may undergo reformulation as it progresses through development, especially after Phase I. For an existing drug product, pharmaceutical companies may request reformulation to change the route of administration. The pace of blockbuster launches and NCE approvals has slackened in recent years. Big Pharma now realize the importance of maximizing their ROI of existing products through managing and extending the lifecycles of those products nearing the end of their patent protection protecting against generic competition for as long as possible. Outsourcing formulation development is increasing Outsourcing formulation development is becoming increasingly common even among companies that employ their own formulation scientists. 8

9 Market trends - summary Market Trend Complete packages on the increase Notes A common solution for start-ups and virtuals, but service providers note that Big Pharma are increasingly requesting complete package drug solutions including formulation, analytical development and in some cases manufacturing and packaging. Complex formulation challenges Drug molecules have grown in complexity and size e.g. protein therapeutics. In addition, formulators are being asked to develop more novel or more demanding dosage forms to improve marketability or to compete with other products. Increasing numbers of small pharmaceutical firms Start-up companies, generics companies, biotech, virtual companies, and university research groups are also active in seeking formulation solutions. The number of contract service providers is increasing The number of companies already in or trying to enter the contract service business is at an all-time high. These range from full service contractual organizations to specialized fee-for-service firms, each building its own unique selling proposition in formulation-development capabilities. 9

10 Market sizing assumptions In 2004, R&D spending in the US was estimated at US$30.6 billion. A further US$8.2 billion was spent abroad, but this was not included in the market sizing exercise. When factoring in research and development by American biotechnology firms, an estimated $41.1 billion was invested in R&D in the US in Outsourced ~ $0.7 $0.8 bn Dosage Form Development & Stability Testing $3.4 bn Outsourced ~ $0.7 $0.9 bn Process Development & Quality Control $3.7 bn Typically, 8.2% of R&D spending is on dosage formulation and stability testing including analytical support Typically, 9.1% of R&D spending is on Process development and quality control including analytical support PhRMA 10

11 Competitor landscape US 2005 Dow Chemical Company Diosynth API MANUFACTURERS CLINICAL TRIAL SUPPLY Fisher Clinical Services CTS CONTRACT MANUFACTURERS PARIOFORMA Cangene Corp DSM Patheon Emerson Resources FORMULATORS FluidAir/ PharmaPro MANUFACTURING CONTRACT PACKERS McKesson ProClinical West Pharma TECHNOLOGY COMPANIES Drug Delivery Baxter BioPharma Charles River PPD Quintiles SFBC Xenobiotic KPT CONTRACT RESEARCH ORGANIZATIONS UP M University of Iowa Formatech ACADEMICS DEVELOPMENT SSCI PHARMA- CEUTICS The Pharmaceutics Marketplace TESTING ABC Whitehouse Laboratories PHARMACOS/ GENERICS With excess capacity CONTRACT LABORATORIES Abbott Laboratories Quality Chemical Labs Northview Biosciences Dr Reddys Metrics Inc Exygen Newport Scientific 11