# Biosynthetic steroids (fermentation & biocatalytic API)

Corticosteroid and reproductive-hormone APIs made by mycobacterial fermentation of phytosterol into AD/ADD/9-OHAD precursors, then biocatalytic and semi-synthetic finishing — a globally-offshored manufacturing tier anchored by Olon, Farmabios and Gadea in Europe, Tianjin Tianyao in China, Symbiotec in India and Asymchem's biocatalysis CDMO.

Source: https://en.bioecon.ru/technology/biosynthetic-steroids/
Updated: 2026-08-18



## Overview and value chain

Markers: [EC: Directive 2001/83/EC + EDQM CEP / FDA DMF | OECD: Bio-pharma | Regulator: FDA (USA), EMA (European Union), NMPA (China)]

Biosynthetic steroids are corticosteroid and reproductive-hormone active pharmaceutical ingredients (APIs) produced by microbial fermentation of phytosterol feedstocks into steroid precursors (androstadienedione/AD, androstadienediol/ADD, 9-hydroxyandrostenedione/9-OHAD), followed by biocatalytic and semi-synthetic finishing into cortisone, hydrocortisone, budesonide, testosterone and progesterone. The manufacture has largely moved offshore from the US to Europe, China and India. Olon partners with Ajinomoto Bio-Pharma Services on cGMP biopharmaceutical manufacturing; Farmabios markets a corticosteroid API list; Gadea Pharma supplies sterile corticoid APIs such as budesonide; Tianjin Tianyao is a leading Chinese corticosteroid API producer; Symbiotec Pharmalab is a vertically integrated steroid-API specialist (IPO 2026); and Asymchem is a biocatalysis CDMO whose enzyme-catalysed routes serve steroid synthesis.

The key directions of biosynthetic steroids are:
1. **Phytosterol biotransformation (Phytosterol Biotransformation):** mycobacterial (Mycobacterium) sidechain cleavage of soya/wood-derived phytosterols into AD, ADD and 9-OHAD steroid precursors — the upstream of every biosynthetic steroid.
2. **Corticosteroid API manufacture (Corticosteroid API):** cortisone, hydrocortisone, budesonide, prednisolone and other adrenal corticoids — Olon, Farmabios, Gadea Pharma, Tianjin Tianyao, Symbiotec.
3. **Androgen and reproductive-hormone API (Reproductive Steroid):** testosterone, progesterone, norgestrel and their precursors for replacement therapy and contraception.
4. **Biocatalytic CDMO (Biocatalysis):** enzyme-catalysed regio- and stereo-selective steroid transformations (17α-hydroxylation, Δ1-dehydrogenation) — Asymchem and CDMO peers.

### Sectoral value chain

```
[soya / wood phytosterol] ──> [mycobacterial fermentation → AD/ADD/9-OHAD] ──> [biocatalytic + semi-synthetic finishing]
                                              │
                                     (GMP crystallisation, CEP/DMF)
                                              │
                                              ▼
[formulation-grade API] <─── [cortisone / testosterone / budesonide] <─────┘
```

### Value chain levels

| Level | Description | Key inputs/outputs |
|:---|:---|:---|
| **Phytosterol Feedstock** | soya/wood sterol extraction (β-sitosterol, stigmasterol, campesterol) | **In:** soya/wood oil.<br>**Out:** phytosterol. |
| **Fermentation / Biotransformation** | mycobacterial sidechain cleavage to AD, ADD, 9-OHAD | **In:** phytosterol, mycobacterium.<br>**Out:** steroid precursor. |
| **Biocatalytic & Semi-synthetic Finishing** | enzyme-catalysed hydroxylation/dehydrogenation and chemical steps to final steroid | **In:** precursor, enzymes.<br>**Out:** steroid API. |
| **API Purification & GMP** | crystallisation, impurity control, CEP/DMF filing | **In:** crude API.<br>**Out:** GMP API. |
| **Formulation-grade Supply** | shipment to oral, sterile, topical formulators | **In:** API, dossier.<br>**Out:** formulated drug. |
| **Supply Security & PV** | pharmacopeial compliance, supply-chain resilience, pharmacovigilance | **In:** field data.<br>**Out:** quality, supply. |

Cross-cutting technologies of the sector:
- **Mycobacterial phytosterol degradation (Phytosterol Biotransformation):** mycobacteria selectively cleave the phytosterol sidechain to yield AD/ADD/9-OHAD, the universal precursors that replaced chemical synthesis from diosgenin.
- **Biocatalytic stereochemistry (Biocatalysis):** enzyme-catalysed 17α-hydroxylation, Δ1-dehydrogenation and 11β-hydroxylation introduce the stereochemistry required for corticoid activity, with higher selectivity than chemical routes.
- **Sterile and high-potency API CMC (API CMC):** sterile corticoid APIs (Gadea) and high-potency corticosteroid GMP require dedicated particle and containment engineering.

---

## US

The US is the largest consumer of steroid APIs but no longer a major producer: steroid-API manufacture has largely offshored to Europe, China and India, leaving the US tier as buyer/formulator.

### offshored manufacture, FDA DMF, supply security
- **Offshored API tier:** US pharmaceutical companies source corticosteroid and reproductive-hormone APIs from European (Olon, Farmabios, Gadea), Chinese (Tianjin Tianyao) and Indian (Symbiotec) manufacturers under FDA Drug Master Files, with limited US-based fermentation capacity.
- **FDA DMF framework:** steroid APIs enter the US supply chain under FDA Drug Master Files and cGMP inspection, with corticosteroid products reviewed as generics and branded drugs under NDA/ANDA.
- **Supply security:** concentrated offshore steroid-API production has made supply security a recurring US policy concern, especially for hospital-critical corticosteroids.

---

## CN

China is the world's largest steroid-API producer, with Tianjin Tianyao a leading corticosteroid manufacturer and Asymchem a global biocatalysis CDMO.

### Tianjin Tianyao, Asymchem, NMPA
- **Tianjin Tianyao (天津天药药业):** a leading Chinese corticosteroid API producer, manufacturing hydrocortisone, prednisolone and related adrenal-cortical APIs from phytosterol biotransformation for global supply.
- **Asymchem (凯莱英):** a biocatalysis CDMO whose enzyme-catalysed routes serve steroid and broader API synthesis, supporting the biocatalytic shift from traditional chemical semi-synthesis.
- **Domestic cluster:** China's phytosterol-fermentation cluster (including the Zhejiang Xianju region) is the world's largest steroid-API manufacturing base, exporting cortisone and reproductive-hormone APIs globally.
- **NMPA framework:** steroid APIs are produced and exported under NMPA cGMP inspection, with API dossiers filed for FDA/EDQM and other regulators.

---

## EU

Europe hosts three specialist steroid-API manufacturers — Olon, Farmabios and Gadea Pharma — plus the EDQM Certification procedure.

### Olon, Farmabios, Gadea, EDQM
- **Olon (Italy):** a biopharmaceutical CDMO that in October 2025 announced a partnership with Ajinomoto Bio-Pharma Services, strengthening European cGMP fermentation and API capacity for steroid and other complex APIs.
- **Farmabios (Italy):** markets a portfolio of corticosteroid APIs, with a long-standing position in adrenal-cortical and reproductive-hormone manufacturing.
- **Gadea Pharma (Spain):** supplies sterile corticosteroid APIs such as budesonide (oral and respiratory) for inhalation and other sterile applications, under the Minakem group.
- **EDQM CEP framework:** steroid APIs enter the EU supply chain under European Directorate for the Quality of Medicines (EDQM) Certificates of Suitability (CEP) and central EU medicines regulation under Directive 2001/83/EC.

---

## Leading companies and research institutes

| Company / Institute | Country | Key products / platforms | Tech features | Status 2026 |
|:---|:---|:---|:---|:---|
| **Olon** | 🇮🇹 Italy | *Steroid API / CDMO* | Fermentation, Aji Bio partnership | commercial |
| **Farmabios** | 🇮🇹 Italy | *Corticosteroid API portfolio* | Adrenal-cortical, reproductive | commercial |
| **Gadea Pharma** | 🇪🇸 Spain | *Budesonide sterile corticoid API* | Sterile corticoid, Minakem group | commercial |
| **Tianjin Tianyao** | 🇨🇳 China | *Hydrocortisone, prednisolone API* | Phytosterol biotransformation (CN leader) | commercial |
| **Symbiotec Pharmalab** | 🇮🇳 India | *Vertically integrated steroid API* | Steroid-API specialist, IPO 2026 | commercial |
| **Asymchem** | 🇨🇳 China | *Biocatalysis CDMO* | Enzyme-catalysed steroid synthesis | commercial |

---

## Tech stack and innovations

The stack pairs mycobacterial phytosterol fermentation with enzyme-catalysed stereochemical finishing and GMP sterile API crystallisation, replacing older diosgenin-based chemical synthesis.

1. **Phytosterol biotransformation (Phytosterol Biotransformation):**
   - Mycobacteria selectively cleave the aliphatic sidechain of β-sitosterol/stigmasterol to yield androstadienedione (AD), androstadienediol (ADD) and 9-hydroxyandrostenedione (9-OHAD) — the universal steroid precursors that anchor the entire biosynthetic-steroid industry.
2. **Corticosteroid API manufacture (Corticosteroid API):**
   - Olon, Farmabios, Gadea, Tianjin Tianyao and Symbiotec convert AD/ADD/9-OHAD precursors into hydrocortisone, prednisolone, budesonide and other corticoids via regioselective hydroxylation, with Gadea specialising in sterile inhalation APIs.
3. **Biocatalytic CDMO (Biocatalysis):**
   - Asymchem and CDMO peers apply enzyme-catalysed 17α-hydroxylation, Δ1-dehydrogenation and 11β-hydroxylation to introduce corticoid stereochemistry with higher selectivity and lower waste than chemical routes.
4. **Sterile and high-potency API CMC (API CMC):**
   - Sterile corticoid APIs (Gadea budesonide) and high-potency corticosteroid GMP require dedicated crystallisation, particle and containment engineering under EDQM CEP and FDA DMF dossiers.

---

## Value chains and production pipelines

### Industrial pipeline of a biosynthetic steroid API (EDQM CEP / FDA DMF)

```
┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Phytosterol feedstock  │ ───> │ 2. Fermentation /         │
└───────────────────────────┘      │    biotransformation      │
                                   └───────────────────────────┘
                                                   │
                                                   ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. API purification &     │ <─── │ 3. Biocatalytic &         │
│    GMP                    │      │    semi-synthetic finishing│
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Formulation-grade      │ ───> │ 6. Supply security & PV   │
│    supply                 │      │                           │
└───────────────────────────┘      └───────────────────────────┘
```

#### Stage 1: Phytosterol feedstock
Phytosterols (β-sitosterol, stigmasterol, campesterol) are extracted from soya or wood-derived tall-oil sterol streams and purified as the carbon feedstock for steroid fermentation.

#### Stage 2: Fermentation and biotransformation
Mycobacterial fermentation selectively cleaves the phytosterol sidechain, producing androstadienedione (AD), androstadienediol (ADD) and 9-hydroxyandrostenedione (9-OHAD) precursors at multi-thousand-tonne scale (Tianjin Tianyao and the Chinese cluster lead globally).

#### Stage 3: Biocatalytic and semi-synthetic finishing
Enzyme-catalysed hydroxylations and dehydrogenations (Asymchem) plus targeted chemical steps convert the precursors into hydrocortisone, prednisolone, budesonide, testosterone and progesterone with high regio- and stereo-selectivity.

#### Stage 4: API purification and GMP
The steroid API is crystallised, impurity-profiled and released under cGMP, with EDQM Certificate of Suitability (CEP) and FDA Drug Master File (DMF) dossiers supporting global supply.

#### Stage 5: Formulation-grade supply
The GMP API is shipped to oral, sterile-inhalation, topical and injectable formulators in Europe, the US and globally, under pharmacopeial (Ph.Eur., USP) specification.

#### Stage 6: Supply security and pharmacovigilance
Concentrated offshore production makes supply-chain resilience and cGMP re-inspection continuous concerns, and post-market pharmacovigilance tracks steroid-product safety across the large generics and branded portfolio.