On Thursday, June 21, 2012, St. John’s University hosted the
Sixth Annual Dr. Charles I. Jarowski Industrial Pharmacy Symposium
on the Queens campus. This year’s symposium was opened by Robert A.
Mangione, ’77P, ’79GP, ’93PD, ’99Ed.D., Dean of St. John’s College of Pharmacy and Health Sciences, who welcomed the
participants and introduced the topic, Drug Product Value
Enhancement Strategies. Noting that the number of new drug
molecules approved for marketing every year continues to remain
very low, Dean Mangione stressed that the future of the
pharmaceutical industry depends greatly on the value of the
products it develops. The distinguished scientists, academics,
entrepreneurs and R&D executives gathered at the symposium
spent the remainder of the day discussing the scientific,
strategic, business and regulatory aspects for enhancing the
value of drug products.
David R. Taft, Ph.D.
Our Distinguished Guest Speaker, David R. Taft, Ph.D., Dean and
Professor at Long Island University’s Arnold and Marie Schwartz
College of Pharmacy and Health Sciences, began the series of
presentations with his lecture entitled Innovation and Value
Enhancement in Drug Product Development: The Role of Academia in
Meeting Present and Future Challenges. Dean Taft discussed how
academia is positioned for an expanded role in supporting
innovation and value enhancement in drug product development. He
noted that the pharmaceutical industry continues to play an
important role in ensuring that educational institutions are
training the next generation of industrial scientists, and stressed
that effective collaboration requires open communication between
academia and the industry in order to establish mutually beneficial
partnerships. Dean Taft underscored potential areas of
collaboration, including material characterization/performulation,
solubilization/stabilization, formulation development,
manufacturing processes, animal studies (both PK and
Biopharmaceutics), advanced analysis (IVIVC and PK/PD modeling),
and supplying nontraditional expertise. Currently, models exist
that demonstrate how these collaborations could be organized, such
as the National Institute for Pharmaceutical Technology and
Education (NIPTE) and the Center for Pharmaceutical Development
(CPD). By bringing together the resources of the industry with the
manpower and time afforded to academia, new collaborative ventures
would create virtual win-win scenarios for both parties.
Kenneth Phelps
This year’s Keynote Presentation was given by Kenneth V. Phelps,
President and CEO of Camargo Pharmaceutical Services, who focused
the discussion on a look at a new regulatory pathway made available
to the industry in his presentation 505(B)(2): Who Says You Can’t
Teach an Old Dog New Tricks. The 505(b)(2) is a new drug
application from the Food and Drug Administration (FDA) that
contains full safety and effectiveness reports, but allows at least
some of the information required for approval to come from studies
not conducted by or for the applicant. This method gains approval
for new drugs in a fraction of the time and cost required by
traditional pathways, particularly for those that represent a
product that has a limited change from an existing or approved
drug. Utilizing this regulatory pathway, Phelps noted that a drug
can make it to market in as little as three years, improving
industry pipelines.
Mahendra G. Shah ’77GP,
’85Ph.D.
Following Mr. Phelps was St. John’s University alumnus Mahendra
G. Shah, ’77GP, ’85Ph.D., Partner at Vivo Ventures, whose address
was entitled Repurposing Drugs. According to Dr. Shah, repurposing
a drug is a low risk business strategy. Using this strategy, a
pharmaceutical company can take a Food and Drug Administration
(FDA) approved drug and develop it using a new pathway, a new route
of administration, a new dosage form or a new dosing regimen, then
combine it with another drug, reduce its side effects, develop it
as a single isomer, or create a deuterated analog. To accomplish
this, interested parties would require a comprehensive team to
create a development plan, determine an approval pathway, create a
patent strategy, and work out a commercialization plan. Dr. Shah
suggested that any new venture also spend time upfront in
developing this strategy, and to seek FDA input as early as
possible on the project in order to avoid any unexpected
developments. With the right team of scientists and investors,
determined individuals could develop a significant business plan
simply by repurposing drugs.
Sesha Nervannan, Ph.D.
The morning session closed with Sesha Nervannan, Ph.D., Vice
President of Pharmaceutical Development at Allergan Inc., whose
presentation was entitled Innovation Strategies in Drug
Repositioning and Life Cycle Optimization. Dr. Nervannan offered
ideas on how to expand drug pipelines with new strategies in life
cycle management. He differentiated between two particular
approaches for expanding one’s market share—the “Red Ocean”
strategy and the “Blue Ocean” strategy. To make the value-cost
trade-off within a “Red Ocean” strategy, one competes within an
existing marketplace using formulation tweaks, attempts to beat the
competition through different cost-saving methods, and attempts to
exploit existing demand by improving patient convenience.
Alternately, in the framework of the “Blue Ocean” strategy, one
seeks to break the cost-value trade-off by developing an
uncontested marketplace through new indications or routes of
administration, by making competition irrelevant by utilizing novel
molecules with highly differentiated benefit-to-risk profiles, and
by creating and capturing new demand through incorporating a
sustained delivery formation that enables new approaches. The “Blue
Ocean” strategy seeks product innovation without necessarily
needing technological innovation, without requiring cutting-edge
technology as a defining feature, and without having to necessarily
seek distant markets. As an example of a “Blue Ocean” strategy, Dr.
Nervannan discussed the story of onabotulinumtoxinA—known popularly
as BOTOX®—and how its cosmetic applications were an accidental
discovery that opened up a new market opportunity with no
pre-existing competition. The selection of which strategy to be
employed will be dependent upon the product and company in
question. However, Dr. Nervannan suggested that the industry should
seek innovative ways to expand or create new market shares,
particularly by incorporating principles of open innovation in
order to overcome the problems posed by “zero gravity”
thinking.
Salah U. Ahmed ’85GP, ’90Ph.D.
After returning from lunch, participants began the afternoon
session, beginning with a presentation entitled Fixed Drug
Combination DDS: Formulation and Technology Consideration, given by
President and CEO of Abon Pharmaceuticals, LLC and St. John’s
University alumnus Salah U. Ahmed, ’85GP,’90Ph.D. Fixed Drug
Combination (FDC) provides many advantages in patient care for
acute and chronic illnesses. According to Dr. Ahmed, the rationale
of FDC is based on the pharmacokinetic and pharmacodynamic
properties of individual drug components to optimize their
therapeutic benefits. Currently, there are increasing numbers of
FDC products in Phase III studies. FDC offers a preferred way for
the line extension of drugs facing patent expiration by lowering
development costs while maintaining high success rates, by
simplifying treatment regiments, improving clinical effectiveness,
enhancing patient compliance, reducing administration costs,
and preventing the emergence of drug resistance for
infectious diseases. Dr. Ahmed, however, warned that in spite of
the proven success of individual drugs, the combined system may not
necessarily achieve business success, as was seen with Metformine
and Pioglitazone or Dutasteride and Temsulosine. Regardless, FDC is
becoming an important means for pharmaceutical companies to extend
the patent life and line extension of existing drugs.
Gary Liversidge, Ph.D.
The next speaker was Gary Liversidge, Ph.D., the Chief
Technology Officer and Vice President of R&D at Alkermes, Inc.,
who spoke on the Application of NanoCrystal® Technology in the
Development of Value-Enhanced Dosage Forms of Poorly Water Soluble
Drugs. He noted that a significant percentage of active
pharmaceutical ingredients identified through discovery screening
programs are poorly soluble in water. These molecules are difficult
to formulate using conventional approaches, and are associated with
countless formulation-related performance issues, such as a lack of
dosage proportionality, poor oral bioavailability, and the slow
onset of action. For parenteral routes of administration, these
molecules are often formulated with co-solvents, which often
exhibit undesirable side effects. However, by utilizing
NanoCrystal® Technology to reduce the surface area of drug
particles to less than 2,000 nm, the nano-formulation has better
bioavailability than a micronized formulation of the same drug
where bioavailability is dissolution rate limited. Improved
bioavailability, in turn, results in practical benefits, such as an
increased rate of absorption, a reduction in required dose,
education in fed/fasted variability, improved dose proportionality,
smaller and more convenient dosage forms, and rapid formulation
development. Through the application of NanoCrystal® solubility
enhancing technology, the industry can expect to improve
dissolution and oral bioavailability, enable the preparation of
tablets with no extemporaneous preparation by patients, allow for a
wider range of patient options, and maintain patent protection.
J. D. Pipkin, Ph.D.
Following Dr. Liversidge was J. D. Pipkin, Ph.D., Senior
Director of New Product Development at Ligand Pharmaceuticals, who
presented The Captisol® Experience: A Drug Product ‘Value
Enchancement’ Technology. Faced with the challenge of the
solubility of drugs, Dr. Pipkin offered the use of
chemically-modified cyclodextrin as a solution. Captisol® is a
sulfobutyl ether derivative of β-cyclodextrin with a range of six
to seven sulfobutyl ether groups per cyclodextrin molecule. Because
of the very low pKa of the sulfonic acid groups, Captisol® carries
multiple negative charges at physiologically compatible pH values.
Captisol® offers the following benefits: increased solubility,
which allows formulation of water-insoluble APIs in all dosage
forms (including injectable, ophthalmic, and nasal) and enables
high levels of API to reach dosing targets; rapid onset, which has
the potential to enable faster acting versions of many currently
approved oral products and enables aqueous formulation of many
water insoluble API’s as injectable or inhalable medications;
improved bioavailability and delivery efficiency, which permits
lower dosing of API’s; improved safety and convenience, as it has
no known adverse reactions, a simplified preparation process, an
elimination of the need for refrigeration in some commercial
products; and an improved stability, as interactions with Captisol®
protects API from oxidative and hydrolyric degradation as well as
the effects from such elements as heat and light.
Tapan Sanghvi, Ph.D.
Our final presenter was Tapan Sanghvi, Ph.D., Scientific Fellow
at Vertex Pharmaceuticals, who spoke on The INCIVEK® Story:
Development in a QbD World. Using the development of the drug
Telaprevir, an NS3-4A protease inhibitor for treating the genotype
1 chronic hepatitis C virus, Dr. Sanghvi demonstrated how a
“Quality by Design” development strategy was implemented
successfully. Collaboration drove innovation by defining a
formulation approach, understanding the product’s stability and
overcoming processing challenges. Examining the drug’s development
path from discovery to production, he showed how collaboration at
various junctures led to Telaprevir’s successful development. He
demonstrated how collaboration between formulation, analytical,
process chemistry, materials characterization experts, and tech ops
determined the root cause of its instability and developed models
to predict stability, how collaboration with the excipient
manufacturer improved the final washing process to reduce levels of
excepient impurity and lowered surface pH, and how specifications
set to ensure excellent stability led the supply chain to negotiate
the ordering specs well within PAR. The success of INCIVEK® could
act as a model for other companies within the industry to follow as
they search to develop their own pipelines.