pharmaceutics landscape
DESCRIPTION
TRANSCRIPT
www.parioforma.com
PARIOFORMA
Parioforma Ltd
55 Princes Gate
Exhibition Road
South Kensington
London SW7 2PN
United Kingdom
Tel: +44 (0) 207-225-3538 www.parioforma.com
Parioforma (formerly RM Consulting)
Pharmaceutics Landscape - summary
April 2005
www.parioforma.com
PARIOFORMA
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
www.parioforma.com
PARIOFORMA
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 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.
www.parioforma.com
PARIOFORMA
4
Market segments – pharmaceutics services
Drug
Discovery
Marketing
Approval
NCEs/NMEs
Line Extensions
Reformulations
Generics
On-Patent
Products
Off-Patent
Products
DEVELOPMENT &
MANUFACTURING
SALES &
DISTRIBUTION
www.parioforma.com
PARIOFORMA
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.
www.parioforma.com
PARIOFORMA
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.
www.parioforma.com
PARIOFORMA
7
Market trends & drivers
Traditional
1st line therapy
Usually oral
Mass population
Mainly NCEs
Chronic conditions
Mostly symptom relief
High Density
2nd line therapy
Specialist administered
Clinically defined population
Mainly biologics
Mainly chronic conditions
Mainly disease modifying
Targeted Treatment
1st & 2nd line therapy
Multiple delivery systems
Targeted populations
Diagnostics & biologics
Chronic & acute conditions
Disease modifying & preventative
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.
www.parioforma.com
PARIOFORMA
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 pre-
formulation 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-of- concept or early Phase I studies .
Increasing requests for
reformulation
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.
Increasing emphasis on
lifecycle management
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.
www.parioforma.com
PARIOFORMA
9
Market trends - summary
Market Trend Notes
“Complete packages” on
the increase
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.
www.parioforma.com
PARIOFORMA
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 2004§.
Dosage Form
Development &
Stability Testing
$3.4 bn
Process
Development &
Quality Control
$3.7 bn
Outsourced
~ $0.7 –
$0.8 bn
Outsourced
~ $0.7 –
$0.9 bn
§ PhRMA
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§
www.parioforma.com
PARIOFORMA
11
Competitor landscape – US 2005
DEVELOPMENT TESTING
MANUFACTURING
PHARMA-
CEUTICS
The
Pharmaceutics
Marketplace
ACADEMICS
TECHNOLOGY COMPANIES
Drug Delivery
FORMULATORS
CONTRACT RESEARCH
ORGANIZATIONS
CONTRACT
MANUFACTURERS
CONTRACT
LABORATORIES
API
MANUFACTURERS
CONTRACT
PACKERS
PHARMACOS/
GENERICS
With excess capacity
Metrics Inc
Northview
Biosciences
Newport
Scientific
Quality
Chemical Labs
Exygen
UP
M University
of Iowa
Quintiles
Charles River
SFBC
SSCI
Xenobiotic
PPD
Baxter BioPharma
Emerson Resources
KPT
Whitehouse
Laboratories
West Pharma Formatech
FluidAir/
PharmaPro
Dr Reddys
Abbott Laboratories
Fisher Clinical Services
Dow Chemical Company
Diosynth
CLINICAL TRIAL
SUPPLY
CTS
Cangene Corp
DSM
McKesson
Patheon
ProClinical
ABC