Fermentation for APIs

BOC Sciences reserve strong microbial fermentation capabilities for APIs. We focus on the production and manufacturing of biological and chemical APIs via the fermentation technique. We provide pilot-to-commercial microbial fermentation capabilities, offering full support throughout the products’ life cycle. Our extensive experience and advanced fermentation technique support the development of pharmaceutical APIs.

Introduction

In the pharmaceutical industry, fermentation production of active pharmaceutical ingredients (APIs) commonly includes small molecules such as peptides, oligonucleotides, low molecular weight organic molecules, and biological macromolecules such as protein, DNA, RNA, polysaccharides, lipids and their assemblies. Microbial fermentation could be considered as the preferred solution for the production of APIs. In comparison to the synthetic chemical method, fermentation processes support the production of unique chemical molecules dependent on microorganism systems, such as antibiotics and other secondary metabolites. In addition, organic molecules are often structurally complex, including chiral centers, large stereocyclic rings, or heterocyclic systems that require multi-step synthesis to obtain. In contrast, fermentation is often a way to convert readily available raw materials such as sugars, or other inexpensive substrates into high-value products with high yields that ensure the commercial viability of high-quality products. Thus, microbial fermentation provides a more economical method for chemical APIs.

API fermentation process

API fermentation refers to the process of using microorganisms to produce the active ingredient of a drug by fermentation. This biotechnological approach uses the natural metabolic pathways of bacteria, fungi, or other cells to produce desired compounds that can be used as APIs in drugs. It mainly includes the following steps.

The first step is the careful selection of microbial strains, based on their natural ability to produce the desired compounds or their potential for genetic modification, to be carefully optimized through mutagenesis, genetic engineering techniques and adaptive evolutionary strategies to ensure high yield, high productivity and high stability.

Then it enters the rigorous culture and maintenance stage, using AGAR plate or liquid medium culture under sterile conditions to establish pure strains, laying the foundation for subsequent scale-up production. This process is not only the purification art of microorganisms, but also the precise regulation of their vitality.

This is followed by the critical mass expansion step, which promotes rapid growth of biomass under specific conditions by transferring purified strains to a larger aseptic culture system in preparation for large-scale fermentation.

Entering the core fermentation stage, the selected microorganisms are placed in carefully prepared media to grow and metabolize in a strictly controlled environment. At this time, temperature, pH, oxygen supply and stirring rate need to be precisely adjusted to achieve the maximum output of API, which is a precise combination of technology and science.

During fermentation, with the help of modern sensor technology and automated monitoring system, the key parameters including pH, dissolved oxygen, temperature, biomass and metabolites are continuously monitored and immediately adjusted to optimize fermentation conditions and promote the efficient synthesis of target APIs.

After fermentation, centrifugation, filtration or membrane separation technology is adopted to achieve effective separation of microbial cells from fermentation liquid. For extracellular products, direct recovery; For intracellular products, the API is released by cell lysis technology, which is an example of fine manipulation.

The following purification process, involving advanced extraction, chromatography, crystallization and precipitation techniques, aims to refine the API from the complex mixture to a high purity level, while removing all non-targeted impurities to ensure the excellent quality of the finished product.

In the end, the obtained APIs are subject to rigorous chemical, physical and biological property evaluation, using high-precision detection methods such as spectroscopy, chromatography and biological analysis to verify that they meet the purity, activity and safety requirements of international medical standards.

In this whole chain process, BOC Sciences relies on our deep microbial fermentation technology to continuously optimize the process, not only improve production efficiency and product quality, but also ensure the timeliness and cost effectiveness of API supply, contributing high-value innovative solutions to the global pharmaceutical industry.

Application of Fermentation for APIs

Although microbial fermentation is not a new technology, it supports pharmaceutical companies by providing an optimal economic way to shorten the production period. Moreover, safer and more effective medicines are provided when fermentation technique is combined with current molecular biology technologies or genetic engineering tools. We believe that the continuous growth of molecular biology and synthetic biology technologies will significantly impact novel biosynthetic pathways. Microbial fermentation methods are not only used in the pharmaceutical field but also food, agriculture, biocatalytic enzymes and other fields.

High Potent APIs

BOC Sciences has chemical and fermentation processing suites equipped to handle potent substances. We have facilitated successful delivery in more than 20 HPAPI (Highly potent active pharmaceutical ingredient) projects over the past years and it’s an area where we plan to continue expanding our capabilities.

Our Advantages

• Considerable experience in traditional strain breeding and fermentation production.
• One-stop fermentation, analysis and purification services for targeted small molecules.
• Advanced fermentation process and modern fermentation facilities.
• Expertise in combining synthetic chemistry with fermentation and successfully developed many chiral APIs and intermediates.
• Extensive strain development technologies, include genetic engineering directed breeding, high-throughput screening technique, protoplast fusion, space breeding technology, strains preservation and identification.
• Comprehensive analytical capabilities for molecules characterization.
• Complete strain expression systems cover bacterial systems and eukaryotic systems.
• Large-scale fermentation capability and the downstream process development.
• Cost-effective and high-quality products.

Our Methods

Based on the synthetic biology and synthetic chemistry methods, we offer one-stop fermentation services for various APIs.

Strain development and improvement

• Interspecific protoplast fusion: Recombination of genetic information from rather closely related producer strains
• Gene cloning: Genes may be transferred between unrelated strains which are producers of known substances
• Heterologous gene expression, adaptive laboratory evolution, random mutagenesis, site-directed mutagenesis and more.

High-throughput screening and analytical technologies

• Agar plate-based screening
• Fluorescence-activated cell sorting
• Liquid chromatography-mass spectrometry
• Other characterization methods: GC-MS, NMR, XRD, etc.

Fermentation process optimization

• Process characterization
• Stability development
• Recovery and purification of fermentation products, etc.

Project Workflow

• Customer advisory
• Project discussion, fermentation formulation (customers can provide fermentation strains)
• Strain development and improvement
• Lab-scale fermentation and scale-up fermentation
• Targeted molecules extraction and purification
• Product delivery