Alcami Corporation

Imran Ahmed

Changing R&D Landscape

The pharmaceutical product landscape is rapidly and fundamentally changing with profound impact on research and development strategy and technology needs. After a precipitous fall in new drug approvals during the last two decade of the 20th century, there has been a gradual recovery going into the second decade of the 21st century. Figures 1 and 2 map drug approvals by molecule type and route, excerpted from the publication by Ouyang et al(1) based on 34,673 drug products approved by the FDA over a 37-year period from 1980 through 2017. The number of biopharmaceutical products shows considerable growth, accounting for nearly a quarter of the new molecular entities approved in 2017. While oral delivery route (62%) is still the most prevalent amongst marketed drug products, alternative adminstrations such as injection (22%), cutaneous, mucosal, inhalation, and others are making up a greater percentage as the industry works to improve bioavailability and subsequent efficacy.

Emerging Technology Needs

New pharmaceutical products are increasingly complex requiring nonstandard manufacturing technologies and subjected to higher standards of regulatory scrutiny and market expectations. Notably, with the emphasis on precision medicine- an emerging approach of disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyles for each person- there will be a greater number of biologics drugs, multidrug combination products, drug-device combinations, and targeted drug delivery systems introduced to the market. Parenteral manufacturing of these complex drug products will require special equipment, technologies, and control strategies. It will also require highly skilled process engineers, manufacturing operators, and quality assurance personnel. Furthermore, a greater number of new molecules will be highly potent requiring special containment facilities, environmental controls, and operator training that is not commonly available in many of today's manufacturing facilities. These new products will bring with them the challenges of new packaging technologies far removed from standard stoppers and vials. Process Analytical Technology (PAT) will need to evolve to keep up with the control strategies employed with more complex treatments. It is possible, with the appropriate use of PAT, firm understanding of critical process parameters, and a robust control strategy, that drug products could be released parametrically (not only terminally sterilized products) which would greatly reduce the time to patient. (CPG Sec. 490.200 Parametric Release of Parenteral Drug Products Terminally Sterilized by Moist Heat)

“Manufacturers need to move away from a service mentality to a fully integrated development mindset that is in line with client expectations, patient needs, and regulatory requirements”

With the advent of precision medicine, certain types of finished dosage forms are gaining importance – such as self-administered drugs and combination products. The therapeutic landscape is rapidly shifting away from a "one size fits all" to a "personalized and precision medicine" paradigm that will integrate basic science, diagnostic testing, and clinical management of complex health conditions with the primary focus on prevention. The resulting impact on drug products of the future will be an increasing need for patient-tailored flexible dosing; fixed- dose and free combination multidrug treatments; kits containing diagnostic testing and correlary drug products; "smart" drug delivery systems comprising drug-device combinations; specialty "convenience" packaging for an increasing geriatric population; high potency compounds; and a shift to large molecule therapeutics including proteins and antibodies. In addition, there will be a greater need for targeted drug delivery systems such as liposomes, multiparticulates, controlled and sustained release, trigger and activated drug delivery systems, and ancillary routes of parenteral administration more amenable to self-administration.

Value Proposition for Strategic Partnership with CDMOs

As a consequence of precision medicine there is an increasing emphasis on open innovation. With the spiraling cost of drug discovery and high attritions in early development, it is expected that a greater proportion of cutting-edge research will be conducted by small biotech and inventors often referred to as "two people and a patent." The goal will be to rapidly advance promising candidates to first-in-human, proof-of-concept studies to create attractive licensing opportunities. Research and development sponsors operating in increasingly virtual states are seeking more strategic partnerships with CDMOs with the capability and skill sets to provide full scope, end-to-end CMC services to support early phase clinical studies all the way through market launch. Many of these inventors are likely to partner with CDMOs with a high degree of CMC expertise and capability of de-risking critical technical issues that could delay scale-up and downstream development (i.e. time to market). It is no longer a transactional technology transfer model, but rather a technology creation partnership.

We expect the importance and value proposition of manufacturing to exponentially increase in the next decade and the foreseeable future. Most importantly, manufacturers need to move away from a service mentality to a fully integrated development mindset that is in line with client expectations, patient needs, and regulatory requirements. It will require "out of the box" thinking and strategic, at-risk investments to remain ahead of the curve. This will take innovation, courage, and collaboration across R&D and placing smart bets for a win-win.