Pharmaceutics landscape


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Pharmaceutics landscape

  1. 1. PARIOFORMA Parioforma (formerly RM Consulting) Pharmaceutics Landscape - summary April 2005Parioforma Ltd55 Princes GateExhibition RoadSouth KensingtonLondon SW7 2PNUnited KingdomTel: +44 (0)
  2. 2. PARIOFORMA 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 2
  3. 3. PARIOFORMA 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 pre- formulation 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. 4. PARIOFORMA Market segments – pharmaceutics services Off-Patent Products NCEs/NMEs Generics Drug Marketing Discovery Approval Line Extensions Reformulations On-Patent Products DEVELOPMENT & SALES & MANUFACTURING 4
  5. 5. PARIOFORMA 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. 6. PARIOFORMA 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. 7. PARIOFORMA Market trends & driversOver the next 5 years a shift from traditional medicine to targeted, biologic solutions is expected – this will havean associated impact on the pharmaceutics market placing more demand on the need for innovative, functionalformulations. Traditional High Density Targeted Treatment  1st line therapy  2nd line therapy  1st & 2nd line therapy  Usually oral  Specialist administered  Multiple delivery systems  Mass population  Clinically defined population  Targeted populations  Mainly NCEs  Mainly biologics  Diagnostics & biologics  Chronic conditions  Mainly chronic conditions  Chronic & acute conditions  Mostly symptom relief  Mainly disease modifying  Disease modifying & 7
  8. 8. PARIOFORMA Market trends - summary Market Trend NotesFormulation development is A more systematic approach is being used – drug developers now realize that cutting corners in the pre-beginning earlier formulation phase of development may lead to trouble later.Testing of the API rather To reduce API demand and shorten the time to begin clinical trials for a new compound, somethan a formulated clinical pharmaceutical companies are testing pure API instead of formulated clinical supplies during proof-of-supplies concept or early Phase I studies . A drug may undergo reformulation as it progresses through development, especially after Phase I.Increasing requests for For an existing drug product, pharmaceutical companies may request reformulation to change the routereformulation of administration. The pace of blockbuster launches and NCE approvals has slackened in recent years.Increasing emphasis on Big Pharma now realize the importance of maximizing their ROI of existing products through managinglifecycle management 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 Outsourcing formulation development is becoming increasingly common even among companies thatdevelopment is increasing employ their own formulation scientists. 8
  9. 9. PARIOFORMA Market trends - summary Market Trend Notes A common solution for start-ups and virtuals, but service providers note that Big Pharma are “Complete packages” on increasingly requesting “complete package” drug solutions including formulation, analytical the increase development and in some cases manufacturing and packaging. Drug molecules have grown in complexity and size – e.g. protein therapeutics. Complex formulation In addition, formulators are being asked to develop more novel or more demanding dosage forms to challenges improve marketability or to compete with other products. Increasing numbers of Start-up companies, generics companies, biotech, virtual companies, and university research groups are small pharmaceutical firms also active in seeking formulation solutions. The number of companies already in or trying to enter the contract service business is at an all-time The number of contract high. service providers is These range from full service contractual organizations to specialized fee-for-service firms, each increasing building its own unique selling proposition in formulation-development 9
  10. 10. PARIOFORMA 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 2004§. Outsourced Outsourced ~ $0.7 – ~ $0.7 – $0.8 bn $0.9 bn Dosage Form Process Development & Development & Stability Testing Quality Control $3.4 bn $3.7 bn Typically, 8.2% of R&D spending is on Typically, 9.1% of R&D spending is on dosage formulation and stability testing Process development and quality control including analytical support§ including analytical support§ § PhRMA 10
  11. 11. PARIOFORMA Competitor landscape – US 2005 Fisher Clinical Services CTS Dow Chemical Company CLINICAL TRIAL Cangene Corp SUPPLY API CONTRACT MANUFACTURERS MANUFACTURERS DSM Diosynth Patheon Emerson Resources FluidAir/ CONTRACT McKesson PharmaPro MANUFACTURING PACKERS FORMULATORS ProClinical KPT West Pharma Formatech Abbott Laboratories PHARMACOS/ TECHNOLOGY COMPANIES GENERICS Drug Delivery Dr Reddys With excess capacity PHARMA- Baxter BioPharma Quality CEUTICS Chemical LabsCharles River DEVELOPMENT TESTING Metrics Inc CONTRACT PPD CONTRACT RESEARCH LABORATORIES ORGANIZATIONS Exygen Quintiles Newport SFBC ACADEMICS ABC Scientific The Xenobiotic UP Pharmaceutics Northview Whitehouse M Marketplace Laboratories Biosciences University SSCI of Iowa 11