In biopharmaceutical manufacturing, product safety and quality can be maintained only through effective control of biological contamination. Biological contamination can take place during manufacturing process, can affect the quality of product and can raise many regulatory issues. This is why there is a need for contamination control measures to be adopted by pharmaceutical manufacturers.

With increasing importance of biologicals and products of biotechnology, it is essential to know about how to control contamination risk.

Why Viral and Bacterial Contamination Control Matters

Contamination of biopharmaceutical products is likely to occur due to their manufacturing process that could require the use of living cells, biological starting materials, and complex manufacturing environment.

The possible sources of contamination may include cell substrate, starting material, culture media, equipment, personnel, and manufacturing environment. The implications of contamination may extend from rejecting the batches to delaying the production through conducting extensive investigation.

The implementation of effective contamination control should start prior to the manufacturing process. According to ICH Q5A(R2), the focus on viral safety of biotechnology products produced using human and animal cell lines should be based on a risk-based approach.



Preventing Viral and Bacterial Contamination

Prevention is the primary step to take. There are steps that pharmaceutical manufacturers can take to mitigate contamination risks through controls during manufacture.

Key measures include:

• Qualified cell banks and raw materials: These biological substances need to be properly characterized and tested for possible contamination risks.
• Control Manufacturing environment: This includes facility design, cleaning and sanitization practices, personnel practices and environmental monitoring of the area.
• Material and supplier control: Proper qualification and monitoring of these materials and suppliers needs to be done considering their possible contamination risk.
• Process validation: Establishment of critical process parameters and controls needs to be done to limit the risks of contamination.
• Segregation: Manufacturing process needs to be properly designed in such a way that there will be reduced chances of cross-contamination.
  
  
  

These prevention controls should not be looked at independently; they should be integrated. Risk-based approach in contamination control helps manufacturers determine the sources of contamination and appropriate mitigations.

Detecting Viral and Bacterial Contamination

Prevention alone is insufficient. There is a need for effective viral and bacterial contamination detection in order to address any risks associated with potential contamination before the safety of the product is compromised.

The classic microbiological testing procedures are still relevant for bacterial contaminations, and there could be a number of complementary methods used for viral safety testing depending on the particular product and production process involved (cell culture assays, molecular testing, adventitious agent testing, etc.).

ICH Q5A(R2) acknowledges the developments in viral detection techniques (next generation sequencing [NGS]) along with the fact that testing is an additional tool in addition to the viral clearance during production processes.

What is worth noting is that sometimes testing alone is not enough to determine the presence of virus in the product or manufacturing environment. It is possible to detect even the very low infectious virus levels, which depends on such aspects as sample size and test performance capabilities. Thus, it is necessary to conduct both testing and demonstrate process-based clearance from viruses.



What Are Viral Clearance Strategies?

Viral clearance is the capacity of the manufacturing process to clear or inactivate any viruses that may exist in the process stream.

A proper viral clearance strategy usually employs several controls instead of one particular processing step. These include:

1. Viral inactivation using controlled process conditions for the purpose of inactivating the viruses.
2. Viral removal the use of purification processes that have the capability of removing viruses from the process stream.
3. Process design and control using manufacturing conditions to ensure the process operates under validated parameters.
4. Risk based testing employing suitable analysis tools in supporting the viral safety evaluation.
   
   

FDA guidelines indicate that viral removal and inactivation are critical processing steps of an applicable manufacturing process and must be carried out under validated parameters. FDA also emphasizes the significance of not introducing contamination during upstream processing prior to viral removal or inactivation.

The efficiency of individual viral clearance steps varies according to the type of virus, the product, process conditions and the manufacturing platform. The manufacturer thus has to establish and justify a viral safety strategy suitable for its product and process.

Keeping Pace with Regulatory Expectations

Viral safety requirements continue to change with improvements in biotechnology and scientific analysis. The latest update of ICH Q5A(R2) took effect in Europe starting June 2024 and serves as a new guideline for viral safety assessment of biotechnological products manufactured using human or animal cell lines.

Some of the areas that are included in the updated guideline include continuous manufacturing, innovations in viral testing methods, and platform-based viral clearance.

It becomes more and more necessary for people working in CMC, quality assurance, analytical development, process development, and regulatory affairs to be aware of these changes.



Building Expertise in Viral Clearance and Contamination Control

Contaminations control in any setting can only be achieved if one understands microbiology, bioprocess engineering, analytical techniques, process validation, and what is expected from regulatory bodies. Training for specialist skills would thus come in handy for people working in biotechnology manufacturing industries.

The course "Prevention and Detection of Viral and Bacterial Contamination, Viral Clearance Strategies" offered by GLC Europe will take place from 25th to 29th of January 2027. The course covers scientific and regulatory aspects of preventing and detecting viral and bacterial contamination, as well as developing strategies of viral clearance.

The course targets individuals such as CMC regulatory experts, CMC leaders, cell-line development experts, drug substance process development experts, analytical development experts, quality assurance experts, among others.



Conclusion

The management of viral and bacterial contamination is a vital element in safe and compliant biopharmaceutical manufacturing. Through the incorporation of prevention, the use of sensitive detection techniques, viral inactivation and removal procedures and a science-based and risk-oriented regulation approach, the manufacture of viral-safe products is ensured.

With evolving technology and regulations, continuing education can go a long way in helping the professionals in this industry learn more about the latest approaches and techniques.

Join our upcoming Prevention and Detection of Viral and Bacterial Contamination Masterclass, to learn from experts!

By Shara Najimudeen, Digital Marketing Executive, GLC Europe, Colombo Office, Sri Lanka.