Key considerations and options for sample collection in process sampling

Process monitoring and control of critical process parameters are required to ensure product quality. The most common methods for process monitoring are linked to sampling.

Sampling is the selection of a representative segment of a population to make conclusions about the entire population. In bioprocess manufacturing, sampling is essential at every stage of the process for control of process parameters, to assess drug product quality and to ensure success and safety of the manufacturing workflow.

There are many options that exist for process sampling. However, not all are appropriate for delivering the desired benefits or fully complying with regulatory requirements. This blog offers insight into the various methods and collection options in sampling, as well as how each fit based on assay type and process stage.

Sampling collection methods

1. Needle and septum

   The methods for extracting samples have progressed over time. The use of a needle and septum was one of the earliest methods of sample collection. This method requires a side stream from the process and is constrained by safety concerns and elevated risk of contamination. Another disadvantage is that only one sample can be taken at a time, and the side stream pipe must be purged, cleaned and given a Steam-in-Place (SIP) before another sample can be collected.

2. Valves and bottle assemblies

   Bottle assemblies are block and bleed valves that are assembled to a bottle and autoclaved prior to being installed on a side stream pipe. Because there is no needle involved, operator safety has improved. The drawback is that only one sampling event from a side stream pipe may be performed at a time, necessitating a SIP between sampling events.

3. SIP Valves

   This method uses the same type of bottle assembly but replaces the side stream pipe, resulting in less product loss. You are, however, limited to a single sample and must use a SIP between sampling occurrences.

4. Hybrid ASD equipment

   The hybrid method utilizes a reusable component and single-use elements and can take multiple samples at multiple times using the same device. Hybrid ASDs (aseptic sampling device) are the first aseptic sampling devices and represent one of the largest steps forward in present-day sampling.

5. Turnkey sampling devices

   A turnkey single-use ASD is a self-contained device with a method for aseptically removing fluid from a vessel. External contaminants are not introduced to the process vessel or to the sample itself because it is a closed system.

   There is no longer a need to SIP between sample events because there are multiple independent sampling pathways, making collection rapid and easy.

   ASDs have reduced bioprocess contamination risks significantly. However, depending on testing, facility and storage needs, some ASD container types are more effective than others.

Assays and process stages

Outlined below are the various assays performed and the process stage that the sample is taken.

Sample collection by sample analysis

There are two categories or applications that assays fall into: microbiological and process monitoring. Regardless of classification, they must be aseptic to the vessel from where they were taken.

Process monitoring comprises various methods and technical processes used to evaluate the manufacturing process. During process monitoring, samples do not need to be sterile during the actual assay and can be brought into any of the available collection containers.

Microbiological assays are used during production and determine the potency of a compound by establishing the amount needed to produce effects on test organisms.

Microbiologic samples carry the additional burden of having to maintain the stability of the sample. Stability is part of a quality target product profile (QTPP) and an understanding of how critical quality attributes (CQAs) of drug substances and products are influenced under specific conditions of temperature, relative humidity (RH), light, storage, pH, and other factors.

Therefore, samples must be taken into a closed system using a bag, bottleor tube to maintain their integrity.

Types of collection vessels

Outlined below are examples of various containers or vessels that are used to store samples.

		Microbiological	Process Monitoring
Bag Assemblies		✔	✔
Tubes		✔	✔
Bottle Assemblies		✔	✔
Syringes			✔
Syringe with Needleless Injection Site			✔

Sterility, bioburden and retention sampling

There are many options for sterility, bioburden and retention sampling. There are numerous factors that will influence which container is best for a bioprocess.

• Footprint – in many circumstances, the container you choose is determined by the size of your footprint and available storage. Bags may be a preferable option if you have a limited amount of room. Bottles are bulky and take up a lot of space, whereas bags are thin and take up much less.
• Storage conditions - temperature and storage guidelines will also play a factor in your decision. If you need to store samples at ultra-cold (-40ºC to -80ºC) or cryogenic (-50ºC to -196ºC) conditions, specialized containers will need to be used.
• Volume control – if volume control is critical to reducing product loss, bags are a poor choice. There is no volume demarcation on bags, whereas tubes and bottles are more appropriate as they have accurate volume markings.

pH and gas analysis sampling

In pH and gas analysis sampling, syringes are a great option. Syringes are constructed of thick and rigid plastic. While all plastics allow some degree of gas transmission, the rate of transmission is much slower as compared to thin-walled plastic bags. The slower the rate of gas transmission, the more accurate the gas or pH analysis will be. Syringes are inexpensive and can be manifolded in conjunction with a luer-activated valve to increase the capacity of a single line.

Conclusion

Regulatory authorities require process sampling throughout the manufacturing process, at the start and end of key manufacturing milestones. The implementation of a robust sampling plan results in compliance with regulations and better process and sampling management.

As part of Qosina’s portfolio of components for the development and manufacture of single-use systems, we offer a wide variety for process sampling applications including, needleless injection sites, syringes, check valves, luer fittings, bags, luer-activated valves, sterile disconnects, vials and tubes and luer caps.

References

• Sampling in an Aseptic Process, Risk and Regulatory Compliance, Somasundaram G, Merck KGaA
• Best Practices for Aseptic Sampling from Stainless Process Equipment, Bobbi Allen, Sartorius Stedim Biotech, 2022