Sterility testing is one shared crucial component of medical device industry and pharmaceutical biotechnology. Guaranteeing sterility in all such products is not only important for patient safety but also for the purpose of regulatory compliance.
With the evolution in industry, sterility testing methodologies have seen a significant improvement owing to the betterment in technology. Moreover, with the passing time there is also an increase in regulatory scrutiny leading to a more a betterment in sterility testing protocols.
An Understanding of the Sterility Testing
Sterility testing is a measure specifically designed to identify the presence of disease causing microorganisms on sterile products.
This is mostly performed on:
- Ophthalmic solutions
- Injectable items
- Tissue grafts
- Medical devices that are implantable
Sterility testing is a need by the regulatory agencies such as the European Medicines Agency (EMA), World Health Organisation (WHO) and the U.S. Food and Drug Administration (FDA).
These tests are crucial as they approve the manufacturing processes along with the aseptic conditions in an attempt to prevent microbial contamination.
The Objectives of Sterility Testing
Some of the significant objectives of sterility testing have been mentioned below:
1- By confirming the sterility of products, patient safety is guaranteed.
2- Authenticate the manufacturing processes for aseptic conditions.
3- To comply with the regulatory standards such as the EP, JP guidelines and USP <71>.
Hurdles in Sterility Testing
- False Negatives: There is a high probability for the false negatives to occur if the testing methodologies are unable to detect pathogens. This may happen due to the insufficient sample volumes or detection techniques that are simply inefficient.
- False Positives: This is one major concern too. False positives mostly occur because of contamination during the process of sample handling.
- Destruction of the Sample: Sterility testing, although extremely important, requires destruction of some of the product. This is one drawback as it may be hefty for bio pharmaceuticals that are of high-value.
The Traditional Sterility Testing Protocols and Their Limitations
1- Membrane Filtration Method
This technique is very frequently used for products that are aqueous, oil-based or alcoholic. Products with this consistency are able to pass through the filter.
This technique involves:
- Passing the product through a 0.45 micrometer membrane.
- Transferring the filter membrane in to a culture medium.
- Incubating the membrane under the right conditions, i.e. (A period of 14 days at 20-25 degrees and 30-35 degrees).
2- The Direct Inoculation Method
In this technique, the product is inoculated into two categories of media such as:
- Soybean Casein Digest Medium (SCDM)
This is mostly used for the purpose of fungal and aerobic bacterium. - Fluid Thioglycollate Medium (FTM)
This is used for the aerobic and anaerobic bacteria.
The above mentioned product-media combination is then incubated for a period of 14 days.
Limitations of Traditional Sterility Testing Techniques
- Labor-Intensive Methods
These methods require highly skilled personnel along with stringent aseptic handling. - Lengthy Turnaround Time
The results coming out of these techniques take up to 14 days. - An Inability to differentiate between Non-Cultivable (VBNC) Microorganisms
Certain microorganisms do not grow with in the standard culture medium.
Innovations in Sterility Testing
The industry has seen advancements with in the sterility testing protocols that mainly aim to enhance sensitivity, reliability along with efficiency.
- Rapid Sterility Testing Methods
These methods are able to provide accurate and reliable results with in a matter of days and sometimes even hours. They cut down the turnaround time when compared to the regular or standard methods.
Some of the key technologies are listed below:
- ATP Bioluminescence
Adenosine triphosphate or ATP is a biomarker for living cells. This fact is brought into use in this technique as it detects microbial contamination measuring the ATP levels.
One major benefit of this technique is its high sensitivity and immediate results, with in a matter of hours.
- Automated Microbial Detection Systems
Systems such as BacT/ALERT tend to minimize human intervention. This causes a significant fall in chances of contamination. Automated systems in the form of robotic arms are able to handle all the steps of the process.
Trends in the Sterility Testing Industry
1- An increased use of automation
Automation has lately become the standard in sterility testing. These systems tend to improve efficiency therefore decreasing operator fatigue and consequently lowering chances of errors.
2- A transition towards Real-Time Release Testing (RTRT)
The prominent regulatory industries such as FDA are promoting a transition towards RTRT. It is able to release products much faster without posing a threat to safety.
3- Adoption of advanced data management systems
Use of digital tools like Laboratory Information Management Systems (LMS) and blockchain ultimately enables secure yet efficient data management.
4- Eco-friendly Practices
Some of the sustainable practices involve decreasing practice such as one-time plastic use. Moreover, energy-efficient equipment is also gaining hype in this regard.
