Executive Summary
This report captures the insights and expertise contained in presentations by
drug delivery technology industry leaders at three conferences organized by The
Center for Business Intelligence (CBI): Drug Delivery Systems, July 24-25, 2000;
Emerging Drug Delivery Technologies, April 5-6, 2001; and The Business
Case for Drug Delivery Systems, July 23-24, 2001. Each chapter in the first two
sections of this report is based on the material presented and also contains
editorial commentaries and figures. Each chapter in the third section focuses on
a specific drug delivery route or system and includes a technical overview by
the editor, Dr. Natalie Rudolph, followed by summaries of company-specific
presentations on their technologies.
Section I - Business Strategies and Market Drivers
Drug delivery (DD) technology deals now account for about one in seven
pharmaceutical deals, according to Fintan Walton of PharmaVentures,
Ltd. In Chapter 3, he describes ways to identify and evaluate
promising new technologies, considerations when preparing for a collaboration,
and the role and elements of feasibility agreements. The value of a new drug
deliver technology depends on how critical it is to the development of new drugs
that meet specific medical needs. A pharma company usually requests a
feasibility study to demonstrate how well a proposed new delivery technology
works for its own drug(s) before making a collaborative commitment. However, Mr.
Walton points out that if a collaboration is managed well and supported by
appropriate written agreements, it can set the stage for a long-term
relationship that builds value for both parties.
In Chapter 4, Christopher Dick of Elan Pharmaceutical
Technologies describes his company' s corporate strategy of forming a large
network of strategic alliances. He explains the use of feasibility studies,
pointing out that while they are generally "low risk," they are not "no
risk" : These studies entail the risk of giving away know-how, the risk of
failure ? And the risk of success. In the latter case, the pharma company may
license the technology and developed in-house or with a different partner. Mr.
Dick presents advantages and disadvantages of fully integrated internal drug
development programs from discovery through product launch ("mind-to-market"
programs), as well as advantages of full co-development and licensing
agreements. He also discusses life-cycle management, revenue sources from
development and licensing, and the role of technology transfer and joint
ventures.
Chapter 5 addresses market trends in the DD industry. According to Cornelis
Winnips of SkyePharma AG, there are new pressures on pharmaceutical
companies to increase their profits. DD companies need to understand how pre-
and post-launch profit drivers influence management and marketing decisions
about new drug products, and their impact on the establishment of drug
delivery-related partnerships between pharma and device companies. Dr. Winnips
lists technical and market factors that affect valuation of second-generation
products based on new delivery formulations. He points out advantages of
strategic partnerships to both types of companies to support his assertion that
drug delivery partnerships are the most effective way to develop successful
second-generation drugs.
Between 2000 and 2002, at least 13 major pharmaceuticals, accounting for
about $20.5 billion in annual sales, will have lost or will lose patent
protection. The loss of market exclusivity offers tremendous opportunities 1) to
generic drug companies to enter the market with lower-priced generic versions,
and 2) to drug delivery companies to develop second-generation drugs based on
proprietary delivery systems. In Chapter 6, Steven L. Hamilton of IOMED,
Inc., describes competitive and pricing pressures caused by patent
expirations and by consolidation within both the pharma and drug delivery
industries. In the face of these pressures, strategic alliances between these
two types of companies can be a way to enhance the value of both partners and to
help them meet their strategic needs. Such alliances can include mergers and
acquisitions, collaborations, licensing deals, marketing and co-promotion
agreements, and deals to expand patent protection.
In Chapter 7, J. Gregory Ford of RTP Pharma, Inc.,
describes a stepwise approach to building a drug delivery technology platform
into a successful commercial strategy. Short-term goals can be achieved by
establishing technology-development partnerships that help extend the life cycle
of a partner' s key product(s). This can expand to intermediate-term programs
that leverage the drug delivery technology platform to enable the development of
new drug products and to establish proprietary positions for both partners.
Ultimately, some companies will successfully develop their own pipelines of
proprietary products by applying drug delivery technologies to existing generic
drugs with formulation or delivery problems that limit their clinical
applications. These companies may seek partnerships or out-licensing agreements
for clinical testing, regulatory approval and market launch.
Development partnerships in the area of drug delivery technologies are
critical to Inhale Therapeutic Systems, Inc.' s long-term success, and
in Chapter 8, Ajit Gill explains how his company positions its
technology development programs to build value for itself and its partners. A
new drug delivery mode can rescue lagging drug sales for a secondary market
player and can convert a promising but impractical drug candidate into a
marketable product. Understanding the risks and benefits of developing drug
delivery technologies, both from the perspective of drug delivery and pharma
companies, can help technology companies select the best pharma alliance
partners and become desirable partners themselves. Mr. Gill also describes four
trends likely to shape the drug delivery industry in the near future.
In Chapter 9, Patrick Bols of PR Pharmaceuticals describes
inherent inequalities between small DD companies and their large pharmaceutical
partners in terms of the biblical story of David and Goliath. Both parties may
jockey for control over intellectual property, licensing rights, financial terms
and goals for future expansion. Even if they are not equal, however, small DD
companies and large pharma companies can establish successful relationships if
the parties focus on mutual strengths, synergistic capabilities, and strong
complementary needs that the companies can fill for each other. Dr. Bols also
details actions that pharma and drug delivery companies should and should not
take when establishing drug delivery development partnerships.
Pfizer Global Research Division represents the pharma side of a drug
delivery partnership: a large multi-national pharma company that in-licenses
drug delivery technologies from small companies to manage its R&D portfolio.
In Chapter 10, editor Dr. Natalie Rudolph summarizes Mak S. Jawadekar' s
overview of drug delivery technologies and partnerships from the perspective of
a large pharma company. This overview describes the criteria that a large
company uses to select new delivery systems for its drug products and defines
important factors when establishing and maintaining successful partnerships
between large and small companies. Large pharma companies are likely to have
large product and R&D portfolios containing drugs that are delivered by a
variety of routes with unique formulation or delivery challenges. Therefore,
pharma companies will form partnerships with multiple drug delivery partners to
gain access to the best delivery technology for each product.
Section II - Capitalizing on Outcomes Research
Michael Pollock of CareScience advocates the use of health
outcomes research to substantiate efficacy claims of pharmaceuticals and drug
delivery systems. Such studies can be used to promote and market drugs and their
delivery systems. Chapter 11 describes how managed care organizations
decide which new drugs and delivery systems they will reimburse, and how they
use information about clinical, economic and humanistic outcomes in this
decision-making process. Pharma or drug delivery companies should include health
outcomes studies as part of ongoing clinical trials and use the resulting data
to develop a convincing argument for the cost effectiveness of their new drugs,
devices or procedures.
Section III ? Advances in Drug Delivery Technologies
Chapter 12 discusses new developments in oral delivery. Oral
tablets are attractive for drug delivery because this mode of delivery is an
easy, convenient, noninvasive and familiar method of taking a drug. The
intestinal epithelium has a total surface area of about 200 m2, which is a very
large target for delivering drugs. However, some drugs cannot be delivered
orally because they are unstable in the stomach or inefficiently absorbed by the
intestine, because they are too short-lived in the circulation to be
therapeutically effective, or because their delivery must be timed to coincide
with the circadian rhythms of certain physiological events. The sections in this
chapter describe several approaches to increasing the efficiency of oral
delivery for special applications, including:
Chemical carriers to increase gastrointestinal absorption for oral delivery
of macromolecules, (Emisphere Technologies);
Rapid-dissolve waterless tablets, sustained-release oral delivery and
colon-specific drug delivery systems (Yamanouchi Pharma Technologies);
Three different technologies for fast-dissolve tablets, two of which use
effervescence to increase the rate of onset of drug activity (CIMA);
Oral controlled-release system (Penwest Pharmaceuticals Co.);
High-energy mechanochemical activation, which uses amorphous and
nanocrystalline composites to improve solubility (Eurand).
Chapter 13 addresses pulmonary delivery, which can be used to
administer drugs for both localized respiratory therapy and for noninvasive
systemic delivery of certain drugs that cannot be delivered orally. Although
metered dose inhalers (MDIs) have been used for almost 40 years, there is an
ongoing phaseout of the most common propellant because environmental concerns
necessitate new formulations and technologies. Following an overview of
pulmonary delivery of macromolecules by Michael Placke of Battelle Pulmonary
Technologies, the remaining parts of this chapter introduce new technologies
for pulmonary delivery, including:
Electrohydrodynamic devices for pulsatile pulmonary delivery (Battelle
Pulmonary Technologies);
Pocket-sized dry powder inhalers (DPI) that are breath-actuated and
motorized (Dura Pharmaceuticals, Inc.);
Breath-actuated metered-dose inhalers (MDI) and powder formulations
for dry powder inhalers (DPI) (SkyePharma AG);
Adaptive aerosol delivery that adjusts drug dosing to patients' breathing
patterns during delivery (Profile Therapeutics, Inc.);
Novel dry powder technology for small and portable MDI and PDI devices (Inhale
Therapeutic Systems, Inc.).
Transepithelial systems can be used to administer drugs across the skin (transdermal
delivery) or the mucosal lining of the nose and mouth (transmucosal
delivery). Chapter 14 describes the advantages of transepithelial
systems for convenient, noninvasive sustained drug delivery. Some of the newer
devices and formulations include:
Aqueous mist delivery of oral insulin (Generex Biotechnology Corp.);
Small patches for transdermal and transmucosal drug delivery (Noven
Pharmaceuticals, Inc.);
Novel films and polymers for topical or systemic delivery via the skin or
mouth (Atrix Laboratories);
Novel formulations to enhance nasal absorption of peptides and vaccines (West
Pharmaceutical Services);
Buccal patches for drug delivery across the mucosal lining of the cheek and
gum (3M Drug Delivery Systems);
Transdermal patches for sustained relief of chronic pain (3M Drug Delivery
Systems);
Needle-free drug and vaccine delivery by high-velocity dry powder injection (PowderJect
Pharmaceuticals plc);
Iontophoresis for transdermal treatment of acute local inflammation (IOMED,
Inc.);
Programmable iontophoresis system for active transdermal drug delivery (Vyteris,
Inc.);
Electrotransport for transdermal protein delivery (ALZA Corp.).
For drugs that are effective against their disease targets but limited by
acute systemic toxicity, targeted delivery by liposomes may provide the
best solution for efficacy and safety. After more than 20 years of development
efforts, liposomal drugs have been marketed for selected applications in cancer
and life-threatening systemic fungal infections, and more applications are in
development. Chapter 15 describes new technologies for stabilizing
liposomes. Extending their circulation time may enable the use of antibody and
ligand tagging for targeted liposomal delivery to distant or cryptic disease
sites in the body. Two examples of liposomal delivery systems are:
Liposomes for drugs to treat cancer (ALZA Corp.);
Liposomes that extend circulation time to deliver proteins (Genzyme Corp.).
In Chapter 16, Dr. Natalie Rudolph of Rudolph Biomedical
Consulting describes the development of polymers and microparticles for drug
delivery. These methods were originally designed to sustain drug delivery by 1)
prolonging the residence time of the drug in the circulation or 2) providing a
biodegradable or removable drug reservoir that releases the drug consistently
over an extended period of time. Among the subjects Dr. Rudolph covers in this
chapter are the "ideal" delivery system, types of polymers and polymer
particles used and particle life in vivo. She describes how polymer particles,
like liposomes, can be targeted to specific therapeutic sites by passive or
active mechanisms, and how the drug is released by polymer carriers. Because of
their large size and fragility, protein drugs present challenges for drug
delivery that can be met by the use of polymers. Also included are company
descriptions of two drug delivery systems that employ polymers:
Injectable microspheres made from biodegradable polymers and nanospheres for
oral delivery (PR Pharmaceuticals);
In situ implant depot for local or systemic drug delivery (Atrix
Laboratories Inc.).
The last chapter of this report, Chapter 17, summarizes two additional
technologies that have broad applications for improving drug delivery by
various routes. These drug delivery technologies include:
Gene-profiling technologies to characterize drug uptake by M cells in
Peyer' s patches (Digital Gene Technologies, Inc);
Insoluble drug delivery technologies for formulating water-insoluble drugs to
improve oral, injectable, topical and pulmonary delivery (RTP Pharma).
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