Protecting Patients Through Microbiological Controls
Microbiological quality control is fundamental to safe and successful drug development. Designed to protect patients from harmful microorganisms and their toxins, these controls are mandated by global regulators and underpin compliance across sterile and non‑sterile products. Without robust, validated microbiological procedures, drug development programmes can face delays, regulatory findings, and serious patient safety risks.
In this blog, Eve Spirit, Microbiology Lead, discusses why microbiology is fundamental to ensuring quality, safety, and progress at every stage of drug development.
How Does Microbiology Support Drug Development?
Microbiology is foundational to every stage of drug development, from early discovery to final product release. It ensures that medicines are safe, effective, stable, and compliant with global regulatory expectations. Modern pharmaceutical development, especially for sterile products, biologics, vaccines, and antibiotics, cannot function without microbiology.
Why Are Microbiological Quality Controls Essential?
Microbiological quality control systems verify that pharmaceutical products are free from harmful microorganisms, potential pathogens and toxins. These controls are required by global regulatory authorities and are essential to prevent adverse patient outcomes. These controls aim to detect, quantify, identify and prevent microbial contamination in products, raw materials, and manufacturing environments.
Inadequate controls can lead to delays, recalls, out-of-specification occurrences, failed audits, or serious patient risk.
It is therefore crucial that microbiological controls are adequately validated for their intended purpose and followed meticulously to ensure compliance with the current Good Manufacturing Practice (cGMP) guidelines.
What Does Sterility Assurance Mean, and Why Is It Important?
Some drug products are administered intravenously and subcutaneously, bypassing the body’s natural defences, therefore presenting a high risk to the patient, so ensuring sterility is vital. Sterility assurance is the collective system of controls, procedures and validations used to ensure that sterile drug products are free from viable microorganisms, and remain so throughout manufacturing, storage and use. Sterility assurance is a systematic approach, relying on process controls, not just end-product filtration and testing. Sterility testing is a destructive, limited test whereby a small number of samples are tested and therefore cannot assure sterility alone. Instead, sterility is assured through robust, validated processes and depends on:
- Controlled cleanroom environments
- Operator training and qualification
- Aseptic technique and behaviour of operators
- Sterilisation and depyrogenation of materials and components
- Viable and non-viable environmental monitoring
- Aseptic process simulations
- Transfer of materials and strict process control
How Do You Know If Sterilisation Will Be Effective?
Bioburden testing ensures sterilisation is effective; if the bioburden is too high, the sterilisation steps of the manufacture may fail. Reducing the bioburden through contamination control ensures that this is avoided.
Endotoxin testing is testing for pyrogens which are part of the outer membrane of Gram-negative bacteria such as Escherichia coli. Bacterial endotoxins are released by bacteria via multiplication, death and lysis of cells, and can cause an immune response in humans such as fever, inflammation, sepsis, and in severe cases, organ failure and death. They are heat stable and can remain even after sterilisation, therefore must be controlled upstream by depyrogenation of equipment and materials used during manufacture.
How Are Microorganisms Measured in Non-Sterile Drug Products?
Not all drug products are required to be sterile – for example, some are administrated orally, where they pass through the body’s natural microbial defence system. Nonetheless some microorganisms could still have adverse effects via this route of administration. To quantify the microorganisms in a product, we use enumeration testing, known as total aerobic microbial count (TAMC) and total yeast and mould count (TYMC). These are quantitative tests that determine the number of aerobic microorganisms, and the yeasts and moulds present in a sample. We use different types of media that are full of nutrients, and we incubate the samples at ideal temperatures for the growth of the microorganisms. If present, microorganisms are visually countable (in colony forming units) after a determined period of time.
The allowable amount of contamination of non-sterile drug products can vary from product to product, however any microorganisms isolated during testing, even if well below the limit, should be identified to assess whether they are objectionable or not. To assess if a microorganism is objectionable, a microbiologist must consider:
- The type of microorganism and whether it could proliferate in the product
- The intended use of the product
- The route of administration
- The age and health of the recipient
- Any known pathogenicity of the microorganism
- Opportunistic infection potential
- Microorganisms’ ability to degrade the product
How Does Arcinova Carry Out Microbiological Testing?
Our microbiology laboratories and experienced microbiologists are capable of performing several types of testing to cover all the microbiology needs of our customers under one roof.
For non-sterile and sterile drug substances and drug products, a full method development and validation service is offered to support the application of key microbiological techniques.
As method development, validation, and testing can all be performed at one facility, there is no need for time-consuming material and technology transfer activities.
We are equipped to perform microbiological testing such as sterility, endotoxin, bioburden, TAMC/TYMC and presence of specified microorganisms, on radiolabelled, high-potency, and some cytotoxic and controlled substances.
Our microbiologists are not only involved in the testing of the samples for release and stability studies, but they are also an integral part of the manufacturing process, including:
- Ensuring the facilities, equipment, materials, and personnel are monitored using settle plates, contact plates, air samples, finger dabs and swabs
- Performing gowning validation for personnel working in classified cleanroom areas
- Assessing aseptic techniques
- Supporting aseptic process simulations
- Establishing scientifically sound and appropriate specifications such as calculating limits for bacterial endotoxins
Our expert team of microbiologists pride themselves on applying their knowledge and skills to ensure that pharmaceutical drug substances and drug products are safe and meet today’s rigorous quality specifications and regulatory standards.