Parenteral drugs are those which are administered by injection, usually subcutaneously, intramuscularly, intravenously, or intrathecally. Parenterality brings with it advantages of avoiding digestion and first-pass metabolism effects, which could degrade the therapeutic molecules. While patients respond (in surveys) that they really dislike the idea of injections, there’s no getting around the fact that it’s a powerful and effective route of administration for some of the most advanced therapies our industry has to offer. In fact, even the placebo response to injections is stronger than that of other dosage forms.

What follows is a quick primer on the overall forecast of the parenterals segment of the industry, and where we’re going.

Supply Chain: You can’t make what you don’t have

At the front-end of the parenteral drug manufacturing process (writ large) is Supply Chain. Changes because of—and despite—COVID-19 have both helped and hindered contemporary parenteral drug production. Many parenteral manufacturers have designed their systems and processes to rely on the lean method of Just-In-Time (JIT) production. Inventory management done in a JIT manner are designed to carry only as much inventory as is needed to produce to customer demand (takt) time.

The issue that became an emergent situation for parenteral manufacturing (and semiconductors, etc.) was that of inventory stock-outs. By having a goal of a minimum inventory meant that many companies had no buffer inventory to make their production processes resilient to market fluctuations due to the pandemic. It wasn’t really ever a weakness of lean production tools, though; JIT was designed to also include problem-solving methodologies to forecast demand, potential supply chain disruptions, and any other factors which may make minimum inventory much more resistant to departures from normality.

Nevertheless, CDMOs, CMOs, and Sponsor companies have spent together billions of dollars to invest in buying inventory of the most commonly-used materials in order to insulate their production processes from shortages. This mass buy-up has, unsurprisingly, in itself created additional shortages and shipment delays owing to the sensitivity of complex systems to local and discrete moves of major players.*

A Growing Market: MAbs and beyond

The parenterals market is one which is poised to continue growing, with monoclonal antibodies (MAbs) representing the largest share of the market (~21% of revenue). A thorough report by Fact.MR suggests that the global parenteral drugs market will reach or exceed $802 billion by 2029. That’s a huge market. In fact, if you laid out 800 billion $1 bills end-to-end, you could circle the earth at the equator over 3,100 times. We’re currently on-track to exceed this figure by the close of the forecast period, and there’s no slowing to the potential use of parenteral routes of administration for advanced and novel therapies. This is indeed the case in the vaccines market, where mRNA technologies and others are bringing a once-legacy segment of the industry to bear on more diseases and conditions than ever before (cf. vaccines to target certain forms of cancer).

A Pretty Fair Pie: Small vs. large molecule

In this trend, we see that large molecule drugs represent about 52% of the market, and small molecule therapies represent about 48%, which combined would make for a pretty boring pie chart (and the exact reason one isn’t included here). With that said, the large molecule slice of the pie is estimated to increase by about 10% to about 62% of the market in the next year. So, the immediate growth trend is clear, pie chart or not. Large molecule treatments have the benefit of a very high incremental revenue opportunity per-unit-dose, which makes them a very attractive target for future development.

New Molecular Entities: The future is (trending) parenteral

Parenterals have recently represented almost half (40-50%) of New Molecular Entity (NME) drug approvals. The architecture is showing that companies are looking at their development timelines, margins, and advancements in therapeutic designs, and deciding more-and-more that the future is best suited to be more parenteral. This in no way besmirches the rich efficacy of other dosage forms (such as oral solid doses) but is simply a reading of the shape of the trends describing what future is likely to unfold before us.

Oncologity

In the parenterals world, the majority of NMEs are for oncology therapeutics (27.5%), with about 10% for infectious diseases, and about half that (~5%) for cardiovascular. The remainder of the statistical distribution of therapeutic areas has a fat right-tailed skew full of a variety of met and unmet disease states and conditions which are variously-populated across clinical trial phases. Oncology as a therapeutic area continues to be a rich source of drug targets, owing to the incredible phenotypic and genotypic variation found among different types of cancer and patients around the world.

mRNA as Parenteral

In a scant 2-year period of time, the market capitalization of the 5 top mRNA-focused companies increased 20-fold from approximately $15 billion to over $300 billion. Not only for COVID-19 (and boosters), this technology platform will also be producing vaccines for other diseases (RSV, influenza, etc.), including personalized cancer therapeutics. Trends and public acceptance still remain to be seen, as for example the last mRNA facility I visited had active protesters outside decrying the technology.

Outsourcing

Given the infrastructure and expertise (talent, experience, etc.) required for pharmaceutical fill-finish, a great deal of partnerships have been, and continue to be, struck between Sponsors and CDMOs/CMOs. Fill-finish itself is a slice of the market worth more than $3 billion, with a CAGR of approximately 15%, and is only forecast to increase given the therapies in the overall industry pipeline now.

So?

Given the state of the industry, and in particular the state of parenterality, it’s humbling to participate in the network of bringing next-generation medicinal therapies to patients in need. These treatments don’t discover, develop, and manufacture themselves, and our highly-networked industry becomes reciprocally busy with the modernization of our approaches to new drug production. Understanding the nature of these trends and the “why” behind them helps to keep the industry connected and better prepared to make smarter decisions. 

*Side note on complexity: Complexity theory can properly map those things which could (or should) have been forecasted. Its closely related cousins, Decision Theory and Game Theory, are both involved in proper assessment of how best to operate in a complex system with finite resources and variably-networked competitors.