Bioprocess Development – Design For Manufacture

Lab-scale optimization

Do you have a production strain but lack the time and resources to develop a bioprocess? We can do this for you - because developing and optimizing bioprocesses on a laboratory scale is our daily business.

The producer strains we use include:

• filamentous fungi such as Aspergillus niger,
• yeasts such as Pichia pastoris and Kluyveromyces lactis,
• bacteria such as Escherichia coli, Bacillus subtilis and Bacillus licheniformis.

Wild-type and GMO: We use both wild-type strains and genetically modified organisms to develop the production strain.

Knowledge of regulatory requirements: We have extensive knowledge of the regulatory requirements for a pharmaceutical manufacturing process and take these into account when developing a bioprocess.

Starting in milliliter-scale: To accelerate process development, we use a miniaturized cultivation system on a milliliter-scale with process-like conditions and design of experiments (DoE) in the early stages. Further development is carried out in small-scale stirred tank reactors, always keeping scalability in mind.

Validation studies: As we are able to scale down experiments for higher throughput, we can perform process validation studies for your regulatory approval.

Protein purification: We offer a wide range of protein purification options for the purification of target molecules. Various solid-liquid separation (SLS), ultrafiltration (UF) and chromatography methods are available from the milliliter scale to the scale of several hundred liters.

Five reasons why to choose BRAIN Biotech for process development and optimization:

1. Process development from 1ml to 200L fermenters
2. Highly experienced staff with extensive process development knowledge
3. Experience with a wide range of production organisms
4. Upstream and downstream development in close collaboration between the teams involved
5. Full analytical support available

Broad range of Analytes

We offer novel and sophisticated approaches for the discovery of functional biomolecules and cost-effective biobased processes. As the associated workflows require a wide range of techniques at the interface of biology and chemistry, our instrumental analysis covers an equally broad range of relevant analytes.

Elements and molecules: We analyze elements as well as small and large molecules, including intact proteins. In addition, our laboratory covers a wide range of sample preparation techniques such as SPE, SPME, Soxhlet extraction, pre- and post-column derivatization to work in different biological matrices.

Strong instrumental analytical capabilities: When it comes to selecting the best enzyme, monitoring a specific biochemical pathway or the biochemical pathway or the metal-binding capacity of a microbe selected for bio-mining, we can provide strong instrumental analytical capabilities and provide reliable answers. With our state-of-the-art instrumentation and highly experienced staff we accompany research and development projects from their inception - through to the final implementation of quality and stability controlsand stability testing.

We develop analytics wiht project partners

Developing analytical methods for pharmaceutical applications is daily business at BRAIN Biotech. Our Analytics team interacts closely with the respective project partner. We develop HPLC-based process-relevant methods for protein purity control and protein quantification in various formulations and concentration ranges (low single-digit µg/ml to mg/ml range).

Methods validation: We perform a method validation process for all methods to ensure robustness of the data and accompany the technical transfer of the methods to certified and/or GMP laboratories.

Supporting transfer process: Our analytics team provides all necessary documentation such as SOPs to maximise the efficiency of the transfer process.

Services: In addition, we regularly measure routine samples and advise on analytical issues.

Structure elucidation & NMR analysis: Our analytical laboratory interacts closely and works hand-in-hand with all other technology departments. We also maintain a close synergy with our subsidiary Analyticon Discovery to ensure an efficient flow of information, methodology and knowledge between the scientists of both companies. In addition to our own expertise, we therefore have strong internal support in areas such as structural elucidation and NMR analysis. We also collaborate with specialised analytical laboratories to fill the gaps in areas we cannot cover ourselves.

In brief, we cover the following separation and detection methods with our in-house equipment:

• Inductively Coupled Plasma Mass Spectrometry (ICP-MS) with/without microwave based decomposition
• Various high performance liquid chromatography (HPLC) instruments coupled with a diode array detector (DAD) and in addition one of the following:
  - Refractive index (RI) detector
  - Fluorescence detector (FD)
  - Evaporative light scattering detector (ELSD)
  - Single quadrupole mass spectrometry (MS)
  - Ion trap mass spectrometry (MSn)
  - Gas chromatography (GC) coupled to single-quadrupole mass spectrometry (MS) or flame ionisation detector (FID)

Three additional reasons why to choose us for analytics support:

1. Support and technical guidance throughout the scientific project, from planning to method development, process characterization, target quantification or technology transfer.
2. Flexible instrumentation and highly experienced staff to cover almost all analytical questions arising in a research project in-house, from elemental quantification to protein identification.
3. Strong collaboration with our subsidiaries, Analyticon Discovery and industrial partners to generate fast, reliable and customized solutions for research projects.

Scale-up your bioprocess

Bioreactors ranging from 1 L to 200 L are available at BRAIN Biotech's research campus in Zwingenberg for the development and scale-up of bioprocesses. We have a track record of successfully transferring processes to our subsidiary Biocatalysts in Cardiff or to GMP contract manufacturers. We have successfully scaled up several processes from 1L to 40m³.

Three additional reasons why to choose us for process scale-up and tech transfer:

1. Support and technical guidance throughout the development or transfer project: from process development planning and process characterization to technical transfer.
2. Flexible equipment and highly experienced staff to cover almost all issues arising in a development project in-house
3. Strong networking with our subsidiaries, Biocatalysts and WeissBioTech, as well as with our network of CMOs working with the pharmaceutical industry.