Bo Kowalczyk, the Chief Commercial Officer at ApiJect, a global medical technology company creating the future of pharmaceutical injections, discusses sterile fill and finish market trends, and ApiJect’s platform technology. The ApiJect Platform brings together two globally trusted manufacturing technologies: Blow-Fill-Seal (BFS) aseptic filling and high-precision plastic injection molding.

Contract Pharma: How would you characterize the state of the sterile fill and finish market? 

Bo Kowalczyk: The sterile fill and finish market has been undergoing significant changes in response to the post-COVID “new normal.” The pandemic exposed vulnerabilities within a complex supply chain, and as of September 2023, discussions between vendors and sponsors continue to be largely driven by supply chain concerns. Supply chain constraints and failures were so widespread across many industries and sectors during COVID that Merriam-Webster added the term to its dictionary in 2022. And it’s no wonder. The pain was universal, and the sterile fill and finish of glass vials was severely impacted. We frequently heard and continue to hear stories of wait times to get on filling lines of 12-18 months. 

CP: What are the key drivers of growth in the sterile fill and finish market?

Bo: Changes in technology and patient needs are creating exciting opportunities for innovations in drug packaging and delivery. For one, the industry is seeing the emergence of novel primary containment materials that reduce its dependence on energy-intensive glass manufacturing, thereby reducing the environmental footprint. Additionally, there are injection formats designed for more convenient self-administration in home-based settings.

The use of biologics continues to grow, with the majority being delivered through injections. Today, injectables make up 55% of all new drug candidates in the global RandD portfolio. There are more than 5,000 biopharmaceuticals in the development pipeline alone.¹

Parenteral administration is one of the most prominent routes chosen to stimulate immediate immune response and ensure 100% bioavailability of pharmaceutical products. A steady rise in the development and market availability of parenteral drugs has propelled the demand for advanced, cost-effective drug delivery devices that promise ease of administration. In the past 10 years, there has been a noticeable increase in the development of parenteral drugs, especially with the introduction of several classes of biologics. This has led to an approximately three-fold increase in the consumption of prefilled syringes. The sustained preference for the prefilled syringe can be attributed to safety and ease of use of these products.¹

CP: What are some of the challenges faced by CDMOs in the sterile fill and finish space?
 
Bo: Supply chain constraints continue to be an issue impacting the entire manufacturing process for all contract development and manufacturing organizations (CDMOs). The larger established CDMOs have access to the necessary raw materials for sterile fill and finish, but increased demand has consumed their capacity for the next ~12 months. On the other hand, smaller sterile fill and finish CDMOs have capacity, but are challenged with procuring the raw materials in a timely manner. In either case, pharma and biotech companies that don’t already have contracts in place face long lead times, impacting product launch. This directly limits response to increased patient demand, as well as causing delays in clinical trials.

Energy costs in manufacturing as well as transportation and distribution, particularly in Europe where there is a reliance on Baltic Sea and Russian gas and oil pipelines, continue to create uncertainty. In a letter to the European Commission in September 2022, European Drug Manufacturers stated that electricity prices for drug manufacturers have risen 10-fold and that costs for raw materials are increasing between 50 and 160 percent.² This is impacting low-margin, affordable generic medicines with pharma companies assessing economic viability for these low margin products.

The industry needs to actively explore more energy-efficient fill and finish manufacturing methods and shift from energy-intensive products and processes like glass vial and PFS sterile fill and finish. Plastic vials have a lower energy consumption per unit during production compared to glass vials and prefilled syringes.

Another challenge in the fill and finish industry is limited surge capacity. Insufficient available capacity, known as surge capacity, hinders the industry’s ability to respond quickly to unforeseen spikes in demand, such as those witnessed during a pandemic or a bio-emergency like COVID, which caused delays in clinical trials due to capacity constraints. The reality is that creating additional capacity is both costly and time-consuming, and few companies are prepared to build capacity until there is tangible demand.

Lastly, CDMOs have to deal with the poor resilience of standard sterile fill and finish services. The current process for making and filling glass vials is a complex, multi-dozen step process, using up to 7 locations and depending on more than a dozen raw materials. Borosilicate glass, rubber stoppers, aluminum crimps, silicon, and other materials need to be sourced from vendors across the globe with each component being critical to complete the process. As observed during the COVID-19 pandemic, there were instances where international agreements were set aside in the interests of vaccine nationalism. Glass vial and prefilled syringe sterile fill is a complex process with demanding logistics that are challenging under normal commercial conditions, much less global emergencies. Contrast this with ApiJect’s compact supply chain, which consists of three (3) raw materials, all locally sourced and stockpiled, used to make prefilled injection devices in a small number of facilities (Figure 1) using the highly automated advanced aseptic blow-fill-seal manufacturing process.

CP: What is the ApiJect Platform?

Bo: ApiJect is a medical technology company with a mission of making injections safe and accessible for everyone, worldwide. The ApiJect Platform combines the trusted technologies of the aseptic sterile liquid filling process of blow-fill-seal (BFS) with plastic injection molding to create single-dose, high-quality, prefilled drug delivery systems, subject to FDA approval. 

The first device (Figure 2) made on the ApiJect Platform is a compact, prefilled, single-dose injector designed to scale quickly and efficiently. ApiJect is also making advancements in BFS temperature management so that a wider variety of temperature sensitive, sterile injectable drugs, including mRNA vaccines, can take advantage of this efficient advanced aseptic technology.


The ApiJect Platform, with potential fill volumes between 0.25ml and 5.0ml and beyond, is designed to serve a wide range of parenteral injection routes: intramuscular, subcutaneous, intradermal, and intravenous, as well as traditional BFS routes of oral, optic, and inhalation.

CP: How does the ApiJect Platform work?

Bo: The best way to understand the ApiJect Platform is to look at the first device our team is developing. The Prefilled ApiJect Injector is designed to combine BFS technology and a pen needle-style hub. The device is designed for ease-of-use; all a healthcare professional would need to do is push together the prefilled BFS container and intramuscular needle hub, causing the needle to pierce the BFS container. The healthcare professional (or patient, where allowed by regulators) can then perform the injection by squeezing the BFS container.

As a single-use, prefilled format, the Prefilled ApiJect Injector is designed to reduce dosing errors and help prevent needle reuse. And as a single-dose format, it has the potential to minimize drug wastage.

CP: What are the advantages of using ApiJect’s technologies?

Bo: The ApiJect Platform enables an entire new category of prefilled injection devices that can potentially make prefilled formats available to more drug products and markets—expanding access, safety, and revenues. This is because the ApiJect Platform designs injection devices that provide the safety and convenience of a prefilled format at the cost of a single-use vial and syringe. The entire process is supported by a simple, compact supply chain that relies on two readily available and widely used raw materials—plastic resin and stainless steel—both of which can be stockpiled.

The BFS manufacturing process creates, fills, and seals the drug container in one, continuous aseptic process that takes seconds and creates as many as 25 containers at a time. ApiJect combines the finished container with a proprietary, pen needle style hub to create a high-quality, ready to use injection device.

The key advantages are (1) an affordable prefilled format, (2) simple supply chain, (3) giant production scale, (4) short lead times, (5) a simple, easy to use design that opens the door to self-administration or use by community health workers in low and middle-income countries, and (6) lower carbon footprint by avoiding energy-intensive glass and using less plastic than a traditional syringe.

CP: What concerns do potential customers have about switching technology platforms?

Bo: Prospective customers’ primary apprehension is that the ApiJect Platform has not yet obtained FDA or EMA regulatory approval. The pharmaceutical industry is renowned for being a “fast follower” market, with few companies inclined to invest in new technology until it receives clearance by regulatory authorities.

To reduce this risk and lead the way, ApiJect is sponsoring a generic drug through regulatory submission in our product to demonstrate the platform’s regulatory compliance. We plan to submit our dossier to the FDA by Q4 2024. 

In parallel, ApiJect is working with several generic drug companies to transition their marketed drugs currently in single-use vials or prefilled syringes to the ApiJect Platform. The development and regulatory path mirror ApiJect’s generic drug development program. These companies perceive ApiJect’s Platform as a brand differentiator that enables them to increase their market share or market access. This is achieved by offering the safety and user-friendliness of a prefilled format while maintaining the cost of a single-use vial and syringe. ApiJect is sharing the risk inherent in a development program by co-funding these with the pharmaceutical partner.

For customers with drugs in clinical trial development, once proof of concept on efficacy and safety is achieved in Phase 2a, ApiJect’s Platform can be incorporated in Phase 2b studies to show device performance comparability to vials and syringes, thus allowing the use of our device in Phase 3 studies. 

Purely from a device perspective, for a marketed and approved injectable medicine or vaccine where a sponsor wants to transition to ApiJect’s Platform, we can apply for a biowaiver to avoid clinical trials, if during combination product development we can prove the following claims:

• First, that the ApiJect Platform and process do not affect the overall impurity or purity profile of the drug product.

• Second, the platform maintains equivalent shelf-life stability, meets extractables and leachables acceptance criteria, and exhibits equivalent dose delivery accuracy as the reference combination product.

The path is well-established and ApiJect has the expertise and resources to make it a success. 

CP: Can you provide details on specific projects or partnerships involving ApiJect?

Bo: In most cases, our contracts with drug sponsors preclude us from divulging their names and project details.   

One partnership we’re able to discuss is with HIPRA. HIPRA, a EU-based biotech pharmaceutical company, was developing a recombinant protein vaccine against SARS-COV-2 and was looking for an experienced partner to work with in order to improve the adoption of its vaccine in global markets. HIPRA’s vaccine has already received EMA approval.

The development of a unique combination of a very innovative device that can overcome some of the major barriers for vaccine uptake plus an excellent vaccine with a robust neutralizing antibody response brings many technical advantages to the market. The program is ongoing with an anticipated EMA submission date for the Drug Device Combination in Q1 2025. Beyond the COV-2 program, HIPRA’s expertise in vaccine development combined with the ApiJect prefilled delivery platform technology will bring much needed innovation to the vaccine markets worldwide. 

ApiJect is also working with several generic pharmaceutical companies to transition to the ApiJect platform for their marketed injectable drugs, which are either in single use vials or glass-based prefilled syringes. These programs are in varying stages of development, and we expect to announce these programs as they near FDA submission in late 2024 and early 2025. 

ApiJect remains engaged in collaboration with the U.S. Government to ensure that the U.S., including its military and frontline personnel, maintains access to vaccines for emergency response purposes.

In addition to pharma partners, ApiJect has two CDMO partners that are equipped with ApiJect’s platform installed on their BFS manufacturing lines to sterile fill and finish drug product or vaccines into ApiJect’s vials. One is The RiteDose Corporation in Columbia, SC, and the other is Fareva Excelvision in Annonay, France. Both partners are actively promoting the ApiJect platform. Furthermore, there are ongoing contract negotiations with additional CDMOs in advanced stages, and we anticipate announcing these collaborations in the coming months. 

CP: Are there any notable business highlights or innovations from ApiJect in recent years?

Bo: BFS has traditionally been used as a container technology. ApiJect has taken this 60-year proven technology and coupled it with high precision injection molding to create a medical injection device. The introduction of an injection device brings with it a range of performance characteristics, quality attributes, particulate inspection, and manufacturing reproducibility that the BFS industry has previously neither required nor been able to attain. To ensure that our BFS manufacturing process is sufficiently cool to protect the viability of many kinds of drug products, ApiJect has successfully developed a proprietary Temperature Management System. Using this system, ApiJect has been able to demonstrate process feasibility and stability for temperature-sensitive biologics such as mRNA vaccines, recombinant proteins, and mAbs (Figure 3).


Another challenge that needed to be addressed was implementing automated particulate inspection to comply with injectable drug standards set forth by the FDA and EMA. Glass-based vials and PFS are round and clear, with well-established inspection systems in place. The ApiJect container, made from semi-transparent LDPE, presented considerable challenges for automating particulate inspection due to its non-cylindrical shape.

Working with a leading particulate inspection vendor, ApiJect has successfully developed a high-throughput machine for both particle and visual inspection.

CP: What trends are shaping the future of the sterile fill and finish market and what is the potential impact of ApiJect’s technologies?

Bo: The market for medical injections continues to grow at a healthy pace. Experts estimate the current global demand at near 50 billion annual injections, a number that’s expected to grow to 70 billion over the next 5 years. Likewise, the global injectable drug delivery market size is expected to expand from $434 billion in 2022 to $1,040 billion in 2032, a 10.2% CAGR during the forecast period³ (Figure 4).


Prefilled formats are the fastest growing segment of this market (Figure 5). Patient trends are toward easy-to-use devices and self-injection, both of which ApiJect’s platform addresses. The increasing use of biologics, which are primarily administered through injection; the rising incidence of chronic disease; an aging population; and the growth of urbanization and medical infrastructure all indicate the market for injectable medicines will continue to expand. 


These projections point to a future where industry will need to meet growing demand by expanding its development and manufacturing capacity. Keeping up with growth can be challenging under the best conditions, but the COVID-19 pandemic created an environment we are still experiencing that is far from ideal. Absorbing COVID’s giant spike in demand created dangerous shortfalls in segments of the injectable medicines industry, which in turn has had knock-on effects both for drug development and patients world-wide. For example, clinical trial enrollment declined up to 70% between 2020 and Q1 2022 due to COVID quarantine protocols and diversion of resources to COVID-related therapies and vaccines.⁴

As the pandemic subsided, clinical trial enrollment rebounded to pre-pandemic levels, but other segments have not. Capacity and materials that would have otherwise gone to childhood vaccination programs were redirected to meet the demand for COVID vaccinations.⁵ This has created a crisis in which an estimated 50 million children have either missed their vaccines window entirely or have fallen behind.

Likewise, fill and finish for injectables, such as childhood vaccinations, is still struggling. And since demand for injectables continues to grow, the industry has had to simultaneously prepare for organic growth and play catch-up at the same time.

This is one area where ApiJect can greatly help. The compact supply chain, manufacturing efficiency, and scalability of the ApiJect platform means up to 15 million vaccines can be produced per month on each single ApiJect BFS manufacturing line. In a matter of months, in collaboration with vaccine producers and global health authorities we can ensure children in all markets world-wide have access to critical vaccines and injectable medicines.

References
1. Polaris Market Research and Consulting LLP, “Global Fill Finish Manufacturing Market Share, Size, Trends, Industry Analysis Report”, pp 23 [Figure 4-p19, Figure 5-p31]
2. European Union Ministers for Health. 2022.https://www.medicinesforeurope.com/wp-content/uploads/2022/09/Energy-Ministers-_-Open-Medicines-for-Europe-letter-ahead-of-the-Energy-Council_27-September-2022-.pdf
3. Reports and Data, “Injectable Drug Delivery Market”. 2023, https://www.reportsanddata.com/report-detail/injectable-drug-delivery-market
4. McDonald K, Seltzer E, Lu M, Gaisenband S, Fletcher C, McLeroth P, Saini K, “Quantifying the impact of the COVID-19 pandemic on clinical trial screening rates over time in 37 countries”. Trials 2023 24:254, p 3 https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07277-1
5. World Health Organization, “COVID-19 pandemic fuels largest continued backslide in vaccinations in three decades”, 2023, https://www.who.int/news/item/15-07-2022-covid-19-pandemic-fuels-largest-continued-backslide-in-vaccinations-in-three-decades

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