The pharmaceutical biologics are the newest class of drugs requiring complex and sensitive handling. Obtained from living organisms, biologics like vaccines and antibodies have a high susceptibility to degradation if exposed to contaminants or environmental changes. Packaging of the drug must, therefore, be air-tight to meet safety and efficacy requirements; thus, there is a need for Container Closure Integrity testing (CCIT). Traditional testing methods are mainly destructive. In that case, biologics safety cannot be ensured. However, the industry is shifting towards non-destructive, deterministic, highly accurate and reliable techniques of testing.
Overview of Biologics Packaging
Biologics are sensitive to temperature, light, and contaminants, hence requiring specialty packaging to ensure shelf-life stability. Glass vials, prefilled syringes, and ampoules are some common formats with individual specifications to produce a sterile barrier. Because biologics are easily affected, the packaging needs to maintain a completely sealed environment.
Why CCI Testing Is Important for Biologics
Biologics have even the slightest impurities reduce the product's effectiveness and make it potentially unsafe. Here's why CCI testing is so important for biologics:
- Ensures Safety and Effectiveness: Biologics degrade very fast when exposed to air or moisture or any contaminants. Appropriate CCI testing ensures that the packaging is sealed.
- Regulatory Compliance: Regulatory agencies like FDA require accurate, numerical CCI testing of biologics' packaging. Noncompliance with these requirements may even lead to recalls and, therefore, harm the reputation of a manufacturer.
- Extended Shelf Life: Biologics are expensive to produce, so obtaining the CCI results in an extended shelf life with less waste and financial losses.
- Minimal Risk to Patient: Strong packaging ensures a patient does not receive a compromised product, therefore ensuring safety for the patient.
Techniques for Ensuring Container Closure Integrity
For biologics, non-destructive and reliable methods of testing are preferred over traditional techniques. Here’s an introduction to two advanced CCI methods widely used in the industry:
1. Helium Leak Detection
Helium Leak Detection (HLD) is a precise method for identifying tiny leaks in sealed systems, using helium as a tracer gas. Helium’s small atomic size and inert, non-flammable nature make it ideal for penetrating leaks, allowing accurate leakage rate measurements. Its benefits include lower weight, cost-effectiveness, and availability in various forms, setting it apart from alternatives like hydrogen.
The technique operates on mass spectrometry principles, where ionized helium ions are accelerated and directed through a magnetic field, ensuring only helium ions reach the detector. This ion current, converted to an electric current, is then displayed as a leak rate. Compared to traditional methods like vacuum bubble and dye tests, helium testing offers highly accurate, quantitative assessments across diverse packaging conditions and lifecycle stages.
With sensitivity levels as low as 1×10-12 l/s, helium leak testing enables unmatched detection of minute leaks, supporting comprehensive package integrity evaluations.
2. MicroCurrent HVLD Technology
It is one of the most advanced non-destructive, non-invasive Container Closure Integrity Testing (CCIT) methods-PTI's MicroCurrent HVLD technology-that produces very effective CCIT in any range of application, whether it be pre-filled syringes, vials, cartridges, ampoules, Blow-Fill-Seal containers, bottles, and pouches. This technology proves to be effective for leak detection of liquid-filled parenteral products. Applications include low-conductivity products, such as sterile WFI and large molecule protein-based products.
In this process, electrode probes scan the sealed container to detect any potential leaks. A variation in current flow helps identify container defects and pinpoint their location. Notably, MicroCurrent HVLD technology operates with approximately 50% lower voltage, exposing both the product and its environment to less than 5% of the voltage used in conventional HVLD methods. This makes it one of the most effective CCI solutions for parenteral and biologic products.
The complexity and sensitivity of biologics have driven the industry toward advanced, non-destructive CCI testing methods. MicroCurrent HVLD and Helium Leak Detection provide the precision, reliability, and non-invasive testing needed to ensure that biologics remain safe, effective, and compliant with regulatory standards. These techniques not only help biologics manufacturers meet regulatory requirements but also support the safe delivery of biologics to patients, ensuring the highest product integrity.