STERILE INJECTABLE MANUFACTURING - Solving Complexity & Strategies for Commercial Success

INTRODUCTION

The sterile injectable (SI) market is evolving rapidly, with sig­nificant growth being driven by trends ranging from the continued rise of biologics, biosimilars, and peptide therapeutics to the in­creased demand for patient-centric delivery formats.

As more complex SI therapies progress through late-stage clinical phases, the transition to commercial readiness is bringing new technical and operational challenges. As well as regulatory expectations becoming more rigorous, manufacturing facility in­frastructure must now support a wider range of formats and sen­sitive formulations without compromising quality. Manufacturers also need to maintain sterility while delivering at greater volumes and speeds. Successfully navigating this shift calls for a strategic, forward-looking approach.

The following explores the key forces driving change in the SI space and outlines the core considerations manufacturers must address to deliver safe, effective therapies at commercial scale and the growing reliance on contract manufacturers to help nav­igate complexity with confidence.

THERAPEUTIC INNOVATION IS RESHAPING MANUFACTURING EXPECTATIONS

The SI market is entering an exciting era of growth and op­portunity. Valued at approximately $732 billion in 2023, the SI market is projected to nearly double, reaching $1.4 trillion by 2030.1 However, as the landscape evolves, manufacturers are facing new complexities. The therapies moving through pipelines today are not only more advanced but also more sensitive and specialized. This rising complexity is being driven by several key trends:

• The Expanding Biologics Market: Biologics have revolution­ized treatment for complex, immune-mediated, and rare chronic conditions (eg, severe asthma, inflammatory bowel disease), offering targeted therapies where small molecules often fall short. Despite significant market growth, these prod­ucts introduce challenging manufacturing requirements. These include the need for specialized processes, controlled environ­ments, and advanced handling procedures across the supply chain.
• A Growing Demand for Biosimilars: The biosimilar market is also expanding, providing more cost-effective access to essen­tial therapies. Although they offer a different route to market, biosimilars must still meet the same standards for product con­sistency, comparability, and regulatory compliance as their ref­erence products.
• Novel SI Therapeutics Entering the Pipeline: Exciting new therapeutics, including peptides like GLP-1 analogues, are en­tering the market. With strong demand and accelerated de­velopment timelines, these therapies are advancing quickly. As they move toward commercial scale, they bring specific chal­lenges related to product sensitivity, cold chain logistics and process control.

In addition to these trends, SI devel­opers and manufacturers must also navi­gate the rising need for patient-friendly delivery formats, particularly as the de­mand for self-administration options rises. As a result, pre-filled syringes, cartridges, and autoinjectors are becoming more common across a range of therapeutic areas.

While these formats improve the pa­tient experience, they also introduce added complexity for manufacturers. Fill-finish operations, for example, must be flexible enough to support multiple configurations while maintaining sterility and consistency. Additionally, these new container-closure systems will need to be validated for com­patibility. Production processes must also be robust enough to support commercial-scale volumes without compromising product quality.

A GROWING RELIANCE ON EXTERNAL MANUFACTURING EXPERTISE

As the complexity of SI manufacturing continues to rise, the combination of ad­vanced product requirements, accelerated timelines, and evolving delivery formats is placing unprecedented pressure on inter­nal capacity and capability.

As a result, many pharmaceutical companies are turning to contract manu­facturing organizations (CMOs) for sup­port. This growing demand is reflected in the SI contract manufacturing market, which was valued at approximately $15.96 billion in 2024, and is projected to reach between $31.9 billion and $50.38 billion by 2030 to 2034.2

To effectively meet the needs of in­creasingly complex SIs, these CMOs need to offer more than operational capability. They must provide a strategic approach to commercial manufacturing, one that an­ticipates complexity and embeds flexibility while supporting consistent delivery throughout commercial supply.

HOW CMOS ARE HELPING TO PREPARE FOR SI MANUFACTURING COMPLEXITY

Achieving commercial readiness for increasingly complex SIs relies on the abil­ity of manufacturers to overcome a range of technical, regulatory, and operational hurdles. CMOs can help SI developers re­spond effectively to these challenges by applying strategic, experience-led ap­proaches that anticipate complexity rather than react to it, taking into account the fol­lowing four key areas:

1. Managing Regulatory Complexity: The regulatory environment for SIs has al­ways been stringent, built to protect pa­tients by mandating consistent high-quality and safety. However, in recent years, ex­pectations have become even more strin­gent. The introduction of the revised EU GMP Annex 1 has raised the bar for con­tamination control, environmental moni­toring, and aseptic processing. These up­dates reflect a wider regulatory shift toward greater scrutiny of sterility assur­ance, especially in light of more complex products, formats, and production envi­ronments. In parallel, the growth of com­bination products, including autoinjectors and pre-filled syringes, has introduced a different challenge. These products are subject to dual regulatory oversight, re­quiring compliance with both pharmaceu­tical regulations and medical device standards, including 21 CFR Part 820 and ISO 13485. From design control and human factors validation to labelling, traceability, and post-market surveillance, these overlapping requirements affect every stage of commercialization. Many CMOs are taking a proactive approach to managing these increasing regulatory de­mands:

Positioning regulatory expertise at the core of project planning: By integrating regulatory specialists early into cross-func­tional teams, CMOs can influence critical decisions around facility design, environ­mental control, and aseptic processing from the outset. This early involvement helps align operations with current regulatory standards while building the flexibil­ity needed to adapt to future expectations.

Developing a unified compliance ap­proach for combination products: Ad­dressing dual regulatory pathways from the outset is essential for SI commercial success. CMOs can reduce complexity and avoid delays on the pathway to market by developing clear, integrated roadmaps that align pharmaceutical and device requirements within a single, coordinated framework.

Designing documentation for inspection from day one: By developing validation master plans, audit trails, and process jus­tifications that reflect a risk-based ap­proach, CMOs can reinforce control across critical operations and build confi­dence in the robustness of their manufac­turing processes. This level of documenta­tion supports inspection readiness while also demonstrating a proactive commit­ment to quality.

2. Tech Transfer With a Risk-Based Mind­set: For CMOs supporting SI products, tech transfer is a strategic, high-stakes process that can make or break a com­mercial launch. Success relies on ap­proaching tech transfer with structure, discipline, and a clear understanding of product- and process-specific risks from the outset. Experienced CMOs will apply a backward design approach to tech trans­fer, starting with the final critical quality at­tributes (CQAs) that define patient safety and product performance. Every aspect of the transfer, from material flow to environ­mental control, must be assessed against these CQAs to ensure that what works at development scale can be executed reli­ably at commercial volumes. These CMOs will also carry out early, detailed gap analyses to identify potential disconnects between the sending and receiving sites, including differences in equipment, process parameters, facility design, and documentation. Addressing these proac­tively helps prevent avoidable deviations and delays once production begins. SI tech transfer strategies must also reflect an in-depth understanding of product sensitivity. CMOs should incorporate controls to mit­igate known risks such as temperature ex­cursions, oxygen exposure, and shear stress during filling. These variables, if not carefully managed, can compromise product integrity and quickly erode confi­dence in the commercial process.
3. Ensuring Sterility at Scale: Maintaining sterility is essential in sterile injectable manufacturing, but it becomes more chal­lenging as products move from late-stage clinical to commercial production. As batch sizes grow and fill speeds increase, there is greater potential for variability. To help ensure sterility and product quality at scale, manufacturers must implement tightly controlled, well-optimized processes designed to deliver precision and consis­tency every time. For biologics and pep­tide-based therapies like GLP-1 analogs, the demands are even higher. These prod­ucts are often sensitive to temperature fluc­tuations, shear forces, and oxygen exposure, all of which are amplified under commercial manufacturing conditions. Even minor deviations during fill-finish op­erations, such as during capping or in­spection, can impact product integrity and lead to costly delays or rework. To address these risks, CMOs with extensive experi­ence supporting complex SIs will apply a deliberate, science-led strategy:

Validate fill-finish performance under commercial conditions: By replicating commercial batch sizes, line speeds, and container types during process develop­ment, CMOs can uncover and address sources of variability before routine pro­duction begins, reducing the risk of sterility failures later on.

Design processes around product-spe­cific sensitivities: Whether it’s temperature shifts, oxygen exposure, or shear stress, experienced CMOs can tailor handling and process controls to match the unique characteristics of each molecule. These sensitivities inform every aspect of fill-finish set-up, including container selection and line configuration.

Control critical variables with real-time oversight: Maintaining sterility at scale de­pends on precise control of fill volumes, container closure integrity, and line speed. By applying in-line monitoring and rigor­ous process control, CMOs can help en­sure every batch meets exacting quality standards, right from the start.

4. Infrastructure & Equipment Readiness: As SI therapies become more intricate, the infrastructure and equipment required to support commercial production must keep pace. Many of today’s complex SI prod­ucts, including lyophilized formulations, sensitive biologics, and device-integrated presentations, demand more than a tradi­tional cleanroom set-up. Isolator-based fill-finish systems, format-flexible equip­ment, and advanced automation are be­coming essential features of modern manufacturing environments. For CMOs, deliberate investment in fit-for-purpose in­frastructure is needed to accommodate this complexity. Facilities must be designed to support a range of formats without trig­gering full-scale revalidation with each new configuration. This kind of flexibility is critical for efficiency as well as for main­taining sterility and quality across varied presentations. Retrofitting older facilities to meet these needs can introduce significant challenges, including equipment compat­ibility issues, extended timelines, and limits on future scalability. Experienced CMOs will take a forward-looking approach, one that ensures equipment specifications align closely with product handling re­quirements from the outset. The goal is not just to deliver operational readiness, but to create a manufacturing environment built to adapt as product portfolios evolve.

SETTING THE FOUNDATION FOR FUTURE COMMERCIAL SUCCESS

The SI market faces a future defined by increasing complexity, significantly es­calating the demands placed upon com­mercial manufacturing capabilities. Meeting these sophisticated challenges ef­fectively calls for a growing reliance on contract manufacturing organizations (CMOs) that apply proactive, strategic ap­proaches to manufacturing. By engaging with CMOs capable of managing this complexity with proven, practical strate­gies, SI developers can help ensure vital therapies reach the patients who need them.

Jenny Gattari is Global Business Development Lead at Pfizer CentreOne and has over 30 years of experience across manufacturing, supply chains, R&D, and business development in the pharmaceutical field. As part of her role, she is responsible for identifying and securing new business opportunities for Pfizer’s contract manufacturing business. Starting her career in manufacturing, her passion for delivering life-changing results for patients across the globe saw her transition into R&D. In this role, she led the launch of a successful clinical chemistry and immunoassay analyzer for chronic diseases. Having held distinguished positions at Abbott, Hospira, and Pfizer, she has been instrumental in building a global network, devising investment strategies, creating profitable product pipelines, and mentoring up-and-coming academics for Pfizer’s community program.