Alcami parenteral experts recently contributed to an article in Pharmaceutical Outsourcing titled, "An Interview with Alcami."
As new parenteral products are introduced into the market, what are some of the challenges parenteral manufacturers have faced, and how do they solve these challenges?
If current trends hold, it is expected that new parenteral products will be increasingly complex, requiring nonstandard manufacturing technologies subjected to higher standards of regulatory scrutiny and market expectations. With the emphasis on precision medicine— an emerging approach of disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person— there will be a greater number of biologic 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 facility, environmental controls, and operator training that is not commonly available in many of today’s manufacturing facilities. These new parenteral products will bring with them the challenges of new packaging technologies far removed from standard stoppers and vials. Even the vial manufacturers themselves are creating glass engineered to be stronger, more inert, and highly scratch resistant. Process Analytical Technology (PAT) will need to evolve to keep pace with the control strategies employed with more complex treatments. It is possible, with the appropriate use of PAT, a solid understanding of critical process parameters, and a robust control strategy, that drug products could be released parametrically (not only terminally sterilized products). This ultimately would greatly reduce the time it takes to reach a patient. (CPG Sec. 490.200 Parametric Release of Parenteral Drug Products Terminally Sterilized by Moist Heat)
Regarding finished dosage forms, are there any types products that are seeing more interest – such as self-administered drugs, combination products, etc.?
As noted previously, the therapeutic landscape is rapidly changing, 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. In a global survey of leaders in the pharmaceutical industry conducted by the consulting firm PwC (PwC Strategy&Precision Medicine Study-2017), 92% of the respondents identified precision medicine as an opportunity, and 84% have it on their corporate agenda. Regarding specific therapeutic areas where precision medicine will likely be viable over the next five years, the top two responses were oncology and orphan diseases. The resultant 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 comprising diagnostic testing and drug products; “smart” drug delivery systems comprising drug-device combinations; specialty “convenience” packaging for an increasing geriatric population; high potency compounds; and, of course, a shift to large molecule therapeutics including proteins, monoclonal antibodies (mAbs), fragment antigen-binding fragments (Fabs), and single-chain variable fragments (scFvs). In addition, there will be a greater need for targeted drug delivery systems such as liposomes, multiparticulates, trigger, and activated drug delivery systems and ancillary routes of parenteral administration more amenable to self-administration, controlled, and sustained release. Finally, there will be a transformative introduction of digital technology for remote and real-time monitoring of drug treatment. This cutting-edge digital technology is still speculative or evolving and, hence, the impact on pharmaceutical manufacturing is not yet clear.
Do you see the market becoming more niche in nature? Are there more specialty manufacturers of parenteral products? Is it wise for a sponsor to seek the services a of specialty parenteral manufacturer or a company with broader experience? Can you explain?
A corollary to the scenario portrayed as a consequence of precision medicine is an increasing emphasis on open innovation involving greater industry-academia collaboration. With the spiraling cost of drug discovery and high attritions in early development, it is expected that a greater proportion of cutting-edge, innovative research will be conducted by small biotech and inventors often referred to as “two scientists 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 that will be picked up by large pharma’s for expensive, downstream development and commercialization. On the other hand, large pharma’s deploy sophisticated due diligence assessments that require innovators and inventors to demonstrate high probability of technical success and develop ability of their asset. Many of these inventors are likely to be academicians, investors, and basic scientists with scant chemistry, manufacturing, and controls (CMC) background. Therefore, these customers are likely to expect from manufacturers of parenteral products a high degree of CMC expertise manifest by successful regulatory applications (investigational new drugs [INDs], Canadian clinical trial applications [CTAs], clinical trial exemptions [CTXs]) and de-risking of critical technical issues that could delay scale-up and downstream development (i.e. time to market). Parenteral manufacturers of the future will need to provide not just manufacturing services but also end-to-end formulation development, CMC, and technology transfer services including the creation of viable due diligence information packages for out-licensing.
What do you see as the future of parenteral manufacturing?
If the scenarios painted above even hold partly true, we expect the importance and value proposition of parenteral manufacturing to exponentially increase in the next decade and the foreseeable future. Most importantly, parenteral manufacturers need to move away from a myopic “fill-finish” 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 since it will be too late otherwise. This will take innovation, courage, and collaboration across R&D and placing smart bets for a win-win.
Imran Ahmed, Ph.D., Senior Director of Formulations Development at Alcami
Mark Petyak, Director of Technical Services at Alcami
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