Biosafety

In vivo biosafety assays are required at various stages during the manufacture of biopharmaceuticals as defined by international regulatory guidelines. We have a portfolio of regulatory compliant in vivo assays with the animal phase conducted in our GLP accredited animal accommodation.

In vivo adventitious agent assays screen for viral contaminants not known to cause any cytopathic or other discernible effects in cell culture systems. The test article is inoculated into a range of animal species which increases the probability of virus detection. A combination of embryonated eggs, adult mice and suckling mice are generally used with guinea pigs, rabbits and other species included if appropriate. The animals are observed over a period for signs of ill health. These assays detect the presence of viral contaminants but do not identify the nature of the contaminant. Any positive results require further investigation.

Oncogenicity studies assess the capacity of cell substrates to immortalize normal cells and endow them with the ability to form tumours in an animal model. Oncogenic activity from cell substrates could be due to either the cell substrate DNA or an oncogenic agent present in the cells. Typically, cell lysates are injected into immunocompromised mice or hamsters which are monitored for signs of tumour formation.

Custom studies can also be established. Please contact us to discuss your specific requirements.

The sterility of cell lines, media, in-process material and final biopharmaceutical products must be demonstrated during the manufacture of biopharmaceuticals. We conduct sterility testing in our GMP compliant facility in compliance with pharmacopeial standards.

Testing is carried out by the Direct Inoculation Method and the test article is added directly to growth media and incubated. The assay duration is typically 14 days but can take up to a maximum of 21 days depending on the sample type.

Prior to conducting a sterility assay, a qualification assay is carried out to test for any bacteriostatic or antimicrobial substances in the test article. This is undertaken at the start of a production or process run and would not require to be performed again unless there have been changes in the production process.

Please contact us to discuss sample volumes required for different sample types.

Cell cultures used in the manufacture of biopharmaceuticals must be tested for Mycoplasma contamination. Mycoplasma contamination does not produce turbidity but can have adverse effects on cell line characteristics/growth rates and virus production. Certain Mycoplasma species are also classed as human pathogens, therefore their presence in a manufacturing process is of serious concern.
We conduct Mycoplasma testing of client test articles in our GMP facility in compliance with pharmacopeial standards.

Our portfolio of tests includes a combined assay which meets the requirements of both European Pharmacopoeia Section 2.6.7 and the United States Pharmacopoeia <63> Monograph.

Prior to conducting a mycoplasma assay a mycoplasmastasis assay is carried out. This is a qualification test to examine the test article for product-specific inhibitors that can interfere with the growth of Mycoplasma. Normally this test would be required only once for any given product provided there is no change in the manufacturing process.

International regulatory guidelines vary slightly in their recommended Mycoplasma detection methods. Variations of the following assays are used, all with multiple positive controls:

• Mammalian cell culture – The sample is incubated with monkey kidney cells which are then fixed, stained with a DNA-binding fluorochrome (Hoechst Stain), and evaluated microscopically by epifluorescence for the presence of Mycoplasma.
• Broth and agar assays – Broth flasks are inoculated with the test article and are incubated aerobically. Samples from the broth flasks are sub-cultured onto agar plates.
• Plate agar assays – The sample is inoculated directly onto agar plates.

In the above assays, agar plates are incubated under appropriate microaerophilic, anaerobic and/or aerobic conditions depending on the regulatory guidance being followed. Plates are examined for Mycoplasma 14 days post-inoculation.

Pharmacopoeial guidelines suggest that manufacturers should consider testing cell banks, virus seeds and production batches for the presence of Mycobacterial contamination. The protocol involves using three media types (two solid media and one liquid medium) and incubating for 56 days as defined by the EP 2.6.2 Monograph.

A sample of the test article is also challenged with a positive control strain of Mycobacterium tuberculosis to ensure there are no inhibitory substances present which would inhibit the recovery of Mycobacterium species.

We offer a regulatory compliant assay for the detection of a wide range of Mycobacterium species. The assay can be customised to include additional media, alternative control species and increased incubation times if requested. Mycobacteria testing is conducted in our GMP compliant facility.

The Bioburden test allows quantitative enumeration of mesophilic bacteria and fungi that may grow under aerobic conditions. The test is designed primarily to determine whether a substance or preparation complies with an established specification for microbiological quality.The methods are not applicable to products containing viable micro-organisms as active ingredients.

Our Bioburden tests are conducted in our GMP facility in compliance with European Pharmacopeia Section 2.6.12.

We offer custom antiserum production in Conventional, Gnotobiotic or Specific Pathogen Free environments. We work with a range of animal species including rabbits, sheep, goats and rodents.

Our service offering includes antiserum production against hazardous pathogens (up to Containment Level 3). We also produce neutralising antisera for live virus vaccines and gene therapy vector testing. We use welfare friendly adjuvants which have been optimised to maximise antibody titres.

Antisera are produced in our GLP facility to defined quality standards. The procedures used in the production process are audited by our independent Quality Assurance team.

Animal Facilities

Moredun’s extensive, GLP-accredited, high containment facility provides the optimal, controlled environmental conditions required for in vivo biosafety studies.

The unit is staffed by highly trained individuals, including experienced veterinarians, who provide animal care and maintenance.

Laboratory Facilities

Our GLP accredited laboratories include a cell culture laboratory and all associated auxiliary areas including hot and cold rooms, storage areas and washrooms.

Our sterility suite comprises two class D rooms with Grade A integrated QUBE isolators. In each of our sterility and mycoplasma testing suites one room is dedicated to test articles with a separate room for positive controls. All critical equipment is validated to GMP standards.