Biomay

• Host / vector development
• Current Good Manufacturing Practice (cGMP) cell banking (master and working cell banks)
• Technology transfer and scale-up
• Process development and optimisation
• cGMP manufacturing of active pharmaceutical ingredients (API) / drug substance (plasmid DNA, mRNA, recombinant proteins)
• cGMP manual aseptic filling (drug product)
• Quality control with well-established / validated assays
• In-house Qualified Person (QP) release
• Validation (assay / process / cleaning)
• Storage and stability testing
• Regulatory support such as Investigational Medicinal Product Dossier (IMPD) / Investigational New Drug (IND) applications

Plasmid DNA manufacturing

Biomay manufactures GMP-grade plasmid DNA (pDNA) for third party clients. As a plasmid CDMO, Biomay addresses clients requiring batch sizes ranging from 100mg to 20g.

Biomay´s plasmid DNA technology features:

• High-yield E. coli hosts
• High-cell density cultivation
• Optimised culture media (no antibiotics or animal compounds)
• Scalable alkaline lysis
• High-performance downstream process (mainly single-use systems)
• Highly homogenous pDNA (more than 90% supercoiled)

Biomay offers these quality levels for plasmid manufacturing:

• Full GMP/cGMP for drug substances and critical start materials
• High-quality for DNA transcription templates and pre-clinical materials
• Research and development (R&D) for research purposes

GMP facility and manufacturing capacities

Biomay`s GMP facility consists of the following areas:

• Cleanroom class D (upstream / midstream processing)
• Cleanroom class C (downstream processing)
• Cleanroom class A/B (unidirectional airflow units for aseptic filling)
• Airlocks for personnel and material flow
• State-of-the-art heat ventilation and air conditioning (HVAC)
• Preparation, service and storage areas
• Quality control laboratories

Processing equipment and techniques

The complete processing chain for microbial biopharmaceuticals is established. Biomay caters to:

Upstream

• Rotary shakers
• Bioreactors: 5l / 25l / 45l
• Fed-batch fermentation / high cell density cultivation

Midstream:

• Batch or continuous flow centrifuges
• High-pressure homogenisers
• Alkaline cell lysis
• Protein refolding

Downstream (purification):

• Process chromatographies (pilot-scale, up to ~20g drug substance / batch)
• Chromatographic techniques: capillary electrochromatography (CEC), anion-exchange chromatography (AEC), hydrophobic interaction chromatography (HIC), immobilised metal affinity chromatography (IMAC) and affinity chromatography (AC)
• Filtration techniques such as depth, ultrafiltration (UF) / depth filter (DF)

Enzymatic processing of DNA:

• Linearization of plasmid DNA
• In-vitro transcription (IVT) of mRNA

Filling and finishing (partially with subcontracting partners):

• Aseptic 0.2µm filtration
• Manual aseptic filling / class A

Analytical services and quality control

Analytical testing and in-process controls conforming with United States Pharmacopoeia (USP) / European Pharmacopoeia (PhEur) standards are offered. Assay development, validation and stability testing can be performed. Biomay employs a certified QP for internal drug product release.

Established analytical methods:

• Electrophoresis: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot, Agarose gel electrophoresis (AGE)
• High-performance liquid chromatography (HPLC), including reversed-phase (RP), ion-exchange chromatography (IEC), and size-exclusion chromatography (SEC) varieties
• Spectroscopies: ultraviolet (UV), optical density (OD) 600, mass spectrometry (MS), circular dichroism (CD) and dynamic light scattering (DSC)
• Immunochemical: Enzyme-linked immunosorbent assay (ELISA), (product-specific, host cell protein, host cell DNA)
• Microbiological: bioburden, viability, phenotypic identification, plasmid retention, bacteriophages
• Other methods: peptide / restriction mapping, DNA / protein sequencing, amino acid composition, endotoxins, total organic carbon (TOC).