ASTM Packaging Standards: Biotechnology and Pharmaceutical Packaging

Part 5: Challenges in the Biotechnology and Pharmaceutical Packaging Industry

The biotech and pharma sector deals with products that are often high value, highly sensitive, and sometimes hazardous. Vaccines, drugs, lab reagents, or diagnostic samples must be kept within strict temperature ranges, and protected from contamination.

Many pharma products are sterile liquids or lyophilized powders in vials, where maintaining container closure integrity (CCI) is directly tied to product safety. A small leak in a vaccine vial could let in microbes or reduce efficacy. Think of the Cold Chain Problem where temperature control is a huge challenge. Shipping a sensitive biologic might require refrigerated or frozen packaging with insulation and refrigerants, where packaging must be tested to ensure it can hold the temperature for the required duration.

Biotech samples, like DNA kits or blood samples, often fall under regulations for transport of hazardous materials (UN/IATA guidelines), meaning the packaging must prevent any leakage even if the package is dropped or mishandled. Additionally, many pharmaceutical packages need to be child-resistant yet accessible to the elderly, adding complexity to closure design.

Long-term stability is another factor. A drug could sit in its package for years. Therefore, aging studies are needed to confirm the packaging and closure will remain intact over time.

ASTM Standards and Solutions for Biotechnology and Pharmaceutical Packaging

Pharmaceutical packaging heavily utilizes ASTM leak and seal integrity standards for validation. Container Closure Integrity Testing (CCIT) is a regulatory requirement for sterile drug products. ASTM F2338 (vacuum decay) has become a go-to method here because of its sensitivity and non-destructive nature. Companies will test batches of sealed vials or syringes with vacuum decay to ensure no microleaks that could admit contaminants.

Another common CCIT method is dye ingress, which is essentially the inverse of F1929. Vials are immersed in dyed solution under vacuum to see if dye enters. ASTM has guidelines but often USP <1207> procedures are followed.

ASTM F2391 helium leak testing is used for critical applications, such as verifying the integrity of sealed drug delivery devices or implantable device packaging, as helium testing can quantify leak rates to very fine levels.

ASTM F88 seal strength is important for pouches containing sterile devices or diagnostic strips, it ensures the pouch seals won’t crack open during distribution, maintaining sterility. In fact, a pharma device combination product, like a pre-filled syringe in a pouch, would be subject to seal strength tests (F88), leak tests (F1929 or F2338), and distribution tests (D4169) as part of its validation.

For shipments sensitive to temperature, standards like ASTM D3103, Thermal Insulation Performance of Distribution Packages provide a way to measure how well a package with insulation and cold packs maintains the internal temperature.

A biotech company shipping clinical trial samples might perform ASTM D3103 testing in an environmental chamber to certify that their packaging can keep contents between 2 to 8 Degrees Celsius for 48 hours in summer and winter profiles. They also often follow ISTA 7E, which is not an ASTM but a related standard for thermal shipping, as part of a comprehensive test plan.

On the distribution side, ASTM D4169 or the specialized ASTM D7386 (for single parcel delivery) are used to simulate FedEx/UPS shipment of diagnostic kits or biologic medicines. D7386, for example, is tailored to parcel delivery drops and vibrations, which is very relevant as many specialty pharmacies now ship medications direct to patients. Drop tests (D5276) are critical when validating the packaging of blood vials or specimen containers. Regulations require that infectious substance packaging survives drops of 1.2 meters without leakage.

To comply, companies will use D5276 and even ASTM D4991, a vacuum leak test for the assembled sample transport package, to ensure a triple-packaged specimen kit is leak-tight after a drop. Altitude testing (D6653) is applied for biologic vials shipped via air to ensure they don’t leak or pop due to pressure changes, especially if they are filled near sea level and then go in a low-pressure cargo hold.

Accelerated aging (ASTM F1980) protocols are extensively used to validate long-term stability of pharmaceutical packaging. A vaccine vial kit with a specific stopper and seal, will undergo accelerated aging at elevated temperature and humidity per F1980, and then be tested for CCI (F2338) and seal strength to confirm that after 3 years equivalent aging the package still passes integrity tests. This gives confidence that the drug will remain sterile and effective until its expiration date.

Solutions and Best Practices Biotechnology and Pharmaceutical Packaging

The pharma industry often incorporates ASTM standards into their quality by design process for packaging. That includes designing closures that have redundant sealing features, and testing them via multiple methods, as in both vacuum decay and helium tests on prototype packages to ensure leak-tightness. They also often use statistical sampling plans to perform routine leak tests on production lots, per ASTM standards, to catch any drift in sealing performance.

For cold chain, best practices involve qualifying the shipping container, the box, insulation, and coolant, in summer and winter profiles using ASTM/ISTA thermal tests and also doing real-world test shipments with data loggers.

Packaging engineers in biotech and pharma industries maintain meticulous documentation of all ASTM standard test results to present to regulatory agencies. These test reports demonstrate compliance with USP and FDA expectations that packaging will protect the product’s potency and sterility. A key compliance consideration here is that many ASTM tests for pharma are recognized consensus standards by FDA. This means that using ASTM methods can expedite approvals because regulators are familiar with and trust these methods. Hence, for any new drug packaging, aligning test plans with ASTM standards for seals, leaks, distribution, etc., is a de facto requirement in the development process.