Pre-filled Syringes: A comprehensive overview

Pre-filled syringes (PFS) are single-dose, pre-loaded syringes are widely used across various therapeutic areas, including vaccines, biologics, and anticoagulants. They have become a preferred method for delivering injectable medications due to their convenience, safety, and precision. In this article, we will explore the reasons behind the growing use of pre-filled syringes, key manufacturers in the industry, the design and approval process for combination products involving PFS, and the design verification and validation stages required to meet regulatory standards.

Why Are Pre-Filled Syringes Used?

1. Patient Convenience: Pre-filled syringes are designed for easy handling, reducing the number of preparation steps compared to traditional vials. This is particularly important for patients who self-administer medications, such as those using biologics for chronic conditions like rheumatoid arthritis or diabetes.
2. Accuracy and Dosage Precision: Pre-filled syringes ensure that the correct dose is pre-measured, reducing the risk of dosing errors. This is especially critical for high-potency biologics, where small deviations can affect efficacy or safety.
3. Enhanced Safety: By eliminating the need for drawing up medication from vials, pre-filled syringes reduce the risk of contamination, needle-stick injuries, and medication exposure for healthcare providers. Many PFS are also equipped with safety features like needle guards.
4. Faster Administration: In emergency situations, PFS enable quicker administration, which can be life-saving for conditions requiring rapid intervention.
5. Self-Administration: Pre-filled syringes are also safe and accurate for self-administration reducing the cost and increasing the ease and accessibility for administration.

Key Manufacturers of Pre-Filled Syringes

Several leading manufacturers dominate the global pre-filled syringe market, producing PFS for pharmaceutical companies and healthcare providers. Some of the key players include:

West Pharmaceutical Services: West provides pre-filled syringe systems with integrated safety and drug compatibility solutions. Their offerings are commonly used for biologics and vaccines.

BD (Becton, Dickinson and Company): A global leader in medical technology, BD offers a range of pre-filled syringes for vaccines, biologics, and therapeutic injectables. Their systems include advanced features such as passive needle guards and glass syringes with minimal drug interactions.

Gerresheimer: Specializing in glass and plastic packaging for drugs, Gerresheimer produces high-quality pre-filled syringes that are used for injectable solutions and suspensions, particularly for biologics.

SCHOTT Pharma: A global leader in glass manufacturing, SCHOTT produces pre-filled syringes with a focus on minimizing chemical interactions and ensuring drug stability.

Nipro Pharma Packaging: Known for its glass syringe technology, Nipro supplies pre-filled syringes to the pharmaceutical industry, focusing on minimizing extractables and leachables.

Design and development of PFS

Prefilled syringes must follow the design process for medical devices as described. Refer to our article on design and development of combination products for injectable therapeutics.

The design and development process for pre-filled syringes involves several key stages to ensure safety, efficacy, and regulatory compliance. Here’s an outline of the main steps:

1. Defining User Needs and Requirements

• The process begins with identifying user needs, including the specific drug formulation, target patients, and the healthcare setting. This includes considering how the syringe will be used, whether in clinical settings or by patients for self-administration.
• Key factors like dosage accuracy, ease of use, safety features (e.g., needle shields or auto-retracting needles), and drug stability must be specified.

You can download our template for the pre-filled syringes. It would give you a jumpstart for defining your user needs. However, that would need to be customized for your specific therapeutics. If you need assistance for modifying that, contact us.

2. Design Process

2.1. Material Selection

• The syringe materials, typically glass or high-grade plastic, must be compatible with the drug to ensure no chemical reactions, degradation, or contamination.
• Careful consideration is given to selecting components that maintain drug stability over time, minimize extractables and leachables, and ensure sterility.

2.2. Prototyping

• Initial designs are created and prototyped, which include both functional and ergonomic aspects. Prototypes are evaluated for ease of handling, delivery mechanism performance, and patient comfort.
• Several iterations are typically required to refine the syringe design, especially for handling by patients with limited dexterity or in emergency situations.

2.3. Risk Assessment and Mitigation

• A thorough risk assessment is performed using tools like Failure Modes and Effects Analysis (FMEA) or ISO 14971 to identify potential risks associated with drug delivery, contamination, needle-stick injuries, or user errors.
• Risk mitigation strategies are implemented, including safety features like needle shields and tamper-evident packaging.

3. Design Verification

• Verification ensures that the design meets all specified requirements. This involves physical testing, such as ensuring the syringe accurately delivers the correct dose, verifying its sterility, and confirming material compatibility with the drug.
• Environmental testing is also performed to ensure the syringe performs under various conditions (temperature, humidity, etc.).
• There are a list of key tests that needs to be completed for prefilled syringes. You can refer to this article for a comprehensive list of testing that needs to be completed with your drug product. However, keep in mind that these experiments need to be adjusted for your own drug product.

4. Design Validation

• Validation ensures that the pre-filled syringe meets the intended use under real-world conditions. This stage often includes human factors testing, especially for self-administration, to confirm that users can operate the syringe safely and effectively.
• It also involves stability testing of the drug in the syringe over time and clinical trials if necessary.

5. Regulatory Approvals

• For pre-filled syringes classified as combination products, regulatory submission involves documentation of the design, testing, and manufacturing processes.
• The design history file (DHF), risk management files, and testing results must be submitted to regulatory bodies like the FDA or EMA for approval, which may involve either a 510(k) or PMA (Pre-Market Approval) pathway depending on the complexity.

6. Manufacturing Scale-Up

• Once the design is validated and approved, the manufacturing process is scaled up. This includes ensuring that manufacturing facilities comply with good manufacturing practices (GMP) and that processes are in place for consistent quality control and sterility maintenance.
• Assembly processes such as filling, sealing, and packaging are automated to ensure high volume production with stringent quality standards.

7. Post-Market Surveillance

• After market launch, the performance of the pre-filled syringe is continually monitored through post-market surveillance. This involves tracking adverse events, user feedback, and conducting periodic reviews to ensure the product maintains safety and efficacy.