Reference materials & certified reference strains

Reference materials and certified reference strains are the calibrated living standards of the bioeconomy: authenticated, publicly accessible microbial cultures and biological reagents against which identity, potency and purity are measured. The American Type Culture Collection (ATCC), founded in 1925 and holding more than 100,000 strains, now authenticates 3,938 reference genomes through its open genome portal; the Leibniz Institute DSMZ in Braunschweig maintains around 75,000 bacteria, fungi, yeasts and cell lines; and the UK’s NIBSC holds roughly nine in ten of the WHO International Standards that calibrate the potency of vaccines, insulin and cytokines worldwide. These biological resource centres (BRCs) operate under ISO 17034 reference-material-producer accreditation and the OECD BRC guidelines, and most are designated Budapest Treaty authorities for patent deposit of micro-organisms. Their output is the invisible substrate of reproducible biotechnology: a sterility test, an antimicrobial-susceptibility panel or a CAR-T potency assay is only as trustworthy as the reference strain it runs against.

The key directions of reference materials and certified reference strains are:

1. Authenticated type strains (Type-Strain Authentication): the nomenclatural type cultures that define a microbial species, deposited and cryopreserved under the International Code of Nomenclature of Prokaryotes (ATCC, DSMZ, NCTC).
2. WHO biological reference materials (WHO Reference Materials): International Standards and reference reagents that calibrate biological potency — NIBSC holds the majority of the WHO biological standards for biologics, from insulin to monoclonal antibodies.
3. Patent and biodiversity deposit (Patent Deposit): Budapest Treaty designated authorities (ATCC, DSMZ, CCTCC, MTCC) hold micro-organisms cited in patents, satisfying disclosure without revealing trade secrets.
4. Genome-authenticated reference reagents (Genome-Authenticated Reagents): reference strains whose whole genome is sequenced and published, closing the gap between classical culture and modern genomics (ATCC Genome Portal, NCTC 3000).

Sectoral value chain#

[isolation & taxonomy] ──> [authentication & genome sequencing] ──> [cryopreservation] ──> [QC & accreditation]
                                             │
                                  (ISO 17034 / OECD BRC)
                                             │
                                             ▼
[distribution to labs] <─── [catalogue & deposit] <─────┘

Value chain levels#

Cross-cutting technologies of the sector:

• Whole-genome authentication (Whole-Genome Authentication): long-read sequencing of type strains to fix the reference genome (ATCC Genome Portal, NCTC 3000 project).
• Vapour-phase cryopreservation (Vapour-Phase Cryopreservation): master/working banks at -150 °C below the liquid nitrogen line for long-term genetic stability.
• ISO 17034 reference-material production (ISO 17034 RM Production): accredited workflow producing certified reference materials with documented metrological traceability.

The reference-material stack rests on metrological authentication, stable preservation and open data, each hardened by a century of culture-collection practice.

1. Whole-genome authentication (Whole-Genome Authentication):
   • long-read sequencing fixes the reference genome of each type strain, replacing 16S-only identification.
   • case: the ATCC Genome Portal publishes 3,938 authenticated reference genomes; NCTC 3000 sequences historical strains.
2. Vapour-phase cryopreservation (Vapour-Phase Cryopreservation):
   • master and working cell banks are held at about -150 °C in the vapour phase above liquid nitrogen to maximise genetic stability over decades.
   • viability, purity and identity are re-verified on retrieval against the release specifications.
3. Metrological traceability (Metrological Traceability):
   • ISO 17034 accreditation requires documented traceability and uncertainty for each certified reference material, mirroring ISO Guide 34 and the OECD BRC guidelines.
   • WHO International Standards from NIBSC assign International Units (IU) that harmonise biologics potency across manufacturers and regulators.