Primary Packaging for Gene Therapies and Cell Therapies

Introduction: The New Frontier in Pharmaceutical Packaging

Gene therapies and cell therapies represent one of the most transformative advances in modern medicine. Unlike traditional small-molecule drugs or even biologics like monoclonal antibodies, these advanced therapies are built from living cells or genetically engineered vectors that deliver therapeutic genes directly to patients. They offer personalized, often one-time treatments that can be life-changing—or even life-saving.

The global cell and gene therapy market is experiencing explosive growth. It is projected to grow from $21.33 billion in 2025 to $26.21 billion in 2026, representing a compound annual growth rate of 22.9%. The global cell therapy packaging market alone is estimated to grow from USD 404 million in 2025 to USD 1.22 billion by 2035, at a CAGR of 11.7%. Yet this remarkable growth brings with it an equally remarkable challenge: how to package therapies that are among the most sensitive, valuable, and patient-critical products ever developed.

Primary packaging for gene and cell therapies is not merely a container—it is an integral component of product quality, patient safety, and therapeutic efficacy. The container closure system must protect living cells or viral vectors from degradation, maintain sterility at ultra-low temperatures, prevent contamination, and ensure that the therapy reaches the patient in full potency.

For packaging partners like Vialab Pharmaceutical Packaging Co., Ltd. , understanding the unique demands of gene and cell therapy packaging is essential to delivering the safety, reliability, and innovation that this groundbreaking field demands.

The Unique Demands of Gene and Cell Therapies

Living Cells Require Living Packaging

Unlike conventional pharmaceuticals, cell therapies are made using living cells, which must be preserved in extremely cold environments to maintain their viability. Many cell and gene therapy (CGT) products require storage and transit at -150°C or below, typically achieved using liquid nitrogen (LN2) vapor-phase containers. This is a far cry from the refrigerated or frozen conditions used in standard cold chain logistics.

Gene therapies, while not always cell-based, involve viral vectors—such as adeno-associated virus (AAV) or lentivirus—that are equally sensitive to temperature, light, and container interactions. The packaging must protect these sensitive biological materials while meeting FDA and global regulatory standards.

The Autologous vs. Allogeneic Divide

Currently, all approved cell therapies are autologous, intended for individual patients, and frequently use cryobags as their primary packaging. However, as attention shifts increasingly towards developing allogeneic therapies—which entail significantly larger batch sizes—cryobags may not be suitable for fill-finish operations. This shift is driving innovation in primary packaging, with rigid containers and vial-based systems emerging as alternatives to traditional cryobags.

High Value, Zero Margin for Error

Gene and cell therapies are among the most expensive pharmaceuticals ever developed. A single dose can cost hundreds of thousands of dollars. With patient-specific therapies, there is no margin for error. A delay, a minor temperature deviation, or mishandling can lead to treatment failure or the need to restart a costly and time-consuming process.

The primary packaging must therefore deliver absolute protection—not just against contamination, but against the cumulative stresses of freezing, thawing, shipping, and handling.

The Challenge of Glass at Ultra-Low Temperatures

Why Glass Fails in Cryogenic Conditions

Glass has been used to store and deliver drugs for decades—in vials, syringes, cartridges, and other containers. Glass is readily available, relatively inexpensive, and, in many cases, works very well. However, at the low-temperature storage required by advanced therapies, glass is prone to failure.

The problems are threefold:

Breakage. Glass is intrinsically brittle. At low temperatures, it is even more brittle; glass vials are more likely to fracture. This is due in part to residual stresses from manufacture. Agitation from shipping and handling increases the likelihood of fracture, resulting in unusable product at delivery—an especially serious issue for a drug destined for a clinical trial, or worse, an autologous cell therapy.

Chemical interactions. Glass is not inert. It has a high-energy surface comprising functional groups (e.g., Si-OH) that can negatively interact with a drug product—especially biologics. In the case of biologics, resultant protein aggregation can potentially alter stability, purity or effectiveness. Another serious issue is delamination—the presence of glass flakes in drug product resulting from detachment of flakes from the glass surface. Since 2010, this has caused many product recalls.

Loss of container closure integrity (CCI). At cryogenic temperatures, glass and rubber are fundamentally incompatible—resulting in a high likelihood of CCI failure of a glass vial–rubber stopper system. The reason is the substantially different coefficients of thermal expansion. Upon going from room temperature (~20°C) to cryogenic temperature (~-180°C)—a change of ~200°C—a rubber component shrinks substantially more in volume than a glass component: 4.5% versus 0.2%. This difference can result in gaps between the rubber component and container, with concomitant risk of loss of CCI. In other words, rubber pulls away from glass at low temperatures.

The Particulate Problem

Particulates of visible and subvisible sizes can originate and accumulate from environmental contaminants, raw materials, consumables, and processes throughout manufacturing and the cold chain leading up to the point of care. Many currently used containers carry significant challenges on both performance—residual risk of particulates—and detectability of particulates. Particulates are a growing challenge in cell and gene therapy manufacturing, creating demand for innovative container options and new controls in manufacturing processes.

Cyclic Olefin Polymer (COP) Vials: A Superior Alternative

Material Properties That Matter

Cyclic olefin polymer (COP) has emerged as an ideal packaging choice for cell and gene therapies due to its unique performance advantages. COP has several features, the combination of which is unique, that makes it suitable for drug packaging:

Very good resistance to oxygen and water
Fracture resistance
Lack of interactions with biologic drugs
Ability to maintain CCI at low temperatures

Superior CCI at Cryogenic Temperatures

Perhaps the most critical advantage of COP vials is their ability to maintain container closure integrity under extreme cold. In contrast to glass, rubber and COP shrink at comparable rates—4.5% versus 4.1%—substantially reducing the risk of gap formation and loss of CCI.

Research has demonstrated experimentally what was expected theoretically: the superior CCI performance of COP at cryogenic temperatures. COP vials have been found to maintain CCI upon proper crimping after short-term (1 week) or long-term (24 month) cryogenic storage. This performance extends to both ultra-cold (-80°C) and cryogenic (≤ -150°C) storage conditions.

Low Particle Generation

Based on subvisible particle analysis via light microscopy and flow imaging microscopy, COP vials were found to have similar or fewer particle counts compared to ISO standard glass vials, polypropylene screw cap vials, and ethylene vinyl acetate (EVA) bags, with or without freeze-thaw. This low-particulate performance is critical for cell and gene therapies, where even subvisible particles can compromise product quality and patient safety.

Biocompatibility and Low Adsorption

COP vials contain minimal leachables, avoiding interference with cell viability or gene carriers (such as viruses or mRNA), and meeting the strict packaging standards set by regulatory authorities. The low protein adsorption and low temperature resistance of COP vials make them an ideal choice for cell therapy drug packaging.

High-value biopharmaceuticals can easily adsorb to glass surfaces, leading to inaccurate dosing. COP’s low adsorption profile ensures that the full therapeutic dose reaches the patient.

Emerging Packaging Innovations for CGT

Rigid Containers: Replacing the Cryobag

The traditional cryobag—the flexible plastic bag used for cryopreservation of cell therapies—has significant limitations. These include particulate generation, difficulty in inspection, and challenges in automated fill-finish operations.

New rigid containers have been developed specifically for the needs of cell and gene therapy primary packaging, designed to replace cryopreservation bags with a fracture-resistant, rigid construction built for both manual use and closed-system automation.

The CellSeal® CryoCase, for example, is the first ever cryo-compatible rigid container designed for closed-system fill and retrieval for larger volumes of fluid (<75 mL). The container is transparent, enabling improved end-user compliance with USP 790, USP 1790, and other international visible inspection methods. It is manufactured under strict environmental and processing controls designed to limit common sources of particulates in single-use disposable manufacturing.

Key features include:

Versatile fill volumes: 25 mL, 50 mL, and 75 mL
Transparent, glass-like structure for improved inspectability
Rigid design with inherent dampening mechanisms to protect samples
Built-in spike ports for closed-system retrieval
Superior durability, leak-proof construction, and fracture resistance when compared to cryobags
Comparable freezing and thawing rates to traditional cryobags

Hermetically Sealed Systems

Hermetically sealed COP vial systems represent another frontier in CGT packaging. These systems demonstrate suitability and advantage in not only low-particulate and cryogenic CCI performance, but also cryopreservation and recovery of several cell types representative of advanced therapy manufacturing.

Closed-System Automation Compatibility

As cell and gene therapies move from early-stage research to commercial-scale production, the ability to integrate primary packaging into automated, closed-system workflows becomes increasingly important. New containers are being designed with built-in features—such as spike ports, hanger mechanisms, and standardized dimensions—to facilitate closed-system fill and retrieval.

Extractables and Leachables (E&L) Considerations

The Regulatory Imperative

Extractable and leachable (E&L) studies have become an integral part of any drug development program and serve to ensure compatibility between the product and its packaging. As biologics, cell and gene therapies, and single-use bioprocessing systems continue to grow, understanding extractables and leachables has become increasingly important for manufacturers, quality teams, and regulatory agencies.

For cell and gene therapies, the E&L challenge is particularly acute. The biological materials are extremely sensitive to even trace levels of leachables, which can impact cell viability, vector infectivity, or gene expression.

USP Standards and Guidelines

The United States Pharmacopeia (USP) provides multiple chapters relevant to CGT packaging:

USP Chapter 661 provides guidance on plastic packaging systems and their materials of construction
USP Chapter 661.2 emphasizes the need for chemical and toxicological safety assessments for packaging systems
USP 1663 and USP 1664 provide essential guidelines for extractables testing and leachables assessment, establishing safety standards for pharmaceutical packaging and delivery systems

Combined, these chapters emphasize the importance of non-reactivity, material integrity, and compatibility with biologic products to prevent contamination and ensure product stability.

Regulatory Landscape for CGT Packaging

FDA Requirements

The FDA has specific statutory mandates for storage containers. For biologics, 21 CFR 610 Subpart G outlines the requirements for container and package labeling. Gene therapy products must follow USP <1207> (Container Closure Integrity Testing) and ICH Q5A (Stability of Biotechnological/Biological Products).

USP Monographs for Cell and Gene Therapies

While CGT-specific guidelines are still emerging, the industry relies on established pharmaceutical standards as benchmarks. USP <1046> covers the gamut of cell- and tissue-based therapy development and product manufacture, from the initial sourcing of cellular and tissue material to the quality assessment of intermediate products. USP <1047> addresses the need for stability testing to ensure that the potency and purity of the gene therapy product are maintained throughout packaging.

Advanced Therapy Medicinal Products (ATMPs)

In the European regulatory framework, Advanced Therapy Medicinal Products are regulated as other biological medicinal products but need more intensive follow-up of efficacy, adverse events, and traceability requirements for the market authorization holder. ATMPs, like any other medicinal product, must demonstrate quality, safety, and efficacy.

The Shift to Allogeneic Therapies and Scalable Packaging

From Batch-of-One to Commercial Scale

The current autologous model—where each patient’s own cells are harvested, modified, and returned—presents significant packaging challenges. Each batch is unique, requiring individualized labeling, tracking, and chain-of-identity documentation.

As the industry shifts toward allogeneic therapies—where cells are sourced from healthy donors and manufactured in large batches for multiple patients—the packaging requirements change dramatically. Larger batch sizes demand packaging that can be filled, labeled, and distributed at commercial scale while maintaining sterility and integrity.

RTU Vials for CGT Manufacturing

Ready-to-use vials offer significant advantages for CGT manufacturing. Pre-sterilized, pre-assembled containers eliminate in-house washing and depyrogenation, reducing contamination risk and accelerating time-to-market. For cell and gene therapies, where every handling step introduces risk, RTU configurations are increasingly favored.

Supply Chain and Cold Chain Considerations

Cryogenic Logistics

The cryogenic supply chain is a specialized segment of life science logistics that demands ultra-low temperature conditions and flawless execution. As the demand for CGT therapies increases globally, so does the need for robust, validated, and agile cryogenic transportation solutions.

Cryogenic shipping involves more than just sub-zero storage; it requires purpose-built packaging and validated handling procedures. Key infrastructure includes:

Liquid nitrogen dry shippers with 10+ day hold times
Real-time GPS and condition monitoring (temperature, orientation, shock, and light exposure)
Pre-qualified, reusable cryogenic containers from globally recognized manufacturers
End-to-end tracking systems that support chain-of-identity and chain-of-custody compliance

Risk Management

With patient-specific therapies, proactive risk management is essential. This includes:

Conducting route validation and simulation testing
Monitoring weather and geopolitical risks that may impact shipment timelines
Offering clinical trial logistics support with full audit trails and regulatory compliance
Training personnel on CGT-specific handling and emergency response protocols

Market Trends and Future Outlook

Explosive Growth

The cell and gene therapy market is experiencing exponential growth. The market size has grown exponentially in recent years and will grow from $21.33 billion in 2025 to $26.21 billion in 2026 at a CAGR of 22.9%. The global cell therapy packaging market is estimated to grow from USD 404 million in 2025 to USD 1.22 billion by 2035, at a CAGR of 11.7%.

Polymer Vials Gaining Share

Glass Type I borosilicate vials currently command roughly 70–75% of the regional volume, but polymer vials (COP/COC) are expanding at a faster rate, with a projected CAGR of 9–12% through 2035, as cell and gene therapy developers seek break-resistant, low-protein-binding containers. Polymer vials (COP/COC) account for approximately 35–45% of value in key markets, reflecting strong demand from cell and gene therapy developers and CDMOs that prioritize break resistance and low extractable profiles.

Emerging Technologies

The industry is seeing rapid innovation in CGT packaging, including:

Fit-for-purpose platforms specifically designed for cell and gene therapy production
Therapeutic containers for closed filling and retrieval
Simplified closed production with sterile connectors
Reduced failure rates to meet FDA specifications

Conclusion: Partnering for CGT Packaging Excellence

Primary packaging for gene and cell therapies represents one of the most demanding challenges in pharmaceutical packaging. The unique sensitivity of living cells and viral vectors demands nothing less than excellence in material selection, container design, manufacturing quality, and supply chain management.

At Vialab Pharmaceutical Packaging Co., Ltd. , we understand that gene and cell therapies are not just products—they are hope for patients with previously untreatable conditions. From Type I borosilicate glass vials with advanced surface treatments to cyclic olefin polymer vials optimized for cryogenic storage, from sterile ready-to-use containers to aluminum caps with tamper-evident features, we engineer every component to meet the exacting standards that advanced therapies demand.

Our advanced production lines and cleanroom facilities ensure consistent quality, integrity, and compliance—from development through commercial supply. With ISO and GMP-compliant quality systems, rigorous container closure integrity testing, and deep expertise in extractables and leachables evaluation, Vialab is your trusted partner for gene and cell therapy packaging solutions.

The cell and gene therapy market is projected to reach unprecedented heights in the coming decade. As this remarkable class of therapeutics continues to transform patient care, the packaging that protects them must evolve in parallel. At Vialab, we are committed to delivering the safety, reliability, and innovation that gene and cell therapies—and the patients who depend on them—deserve.