The Common Mechanism aims to give every provider of synthetic DNA and RNA access to synthesis screening through free, open-source, globally-available tools.

The tools are designed to help providers screen orders efficiently, securely, and in compliance with global biosecurity standards. These tools include a software package designed as a global baseline for sequence screening; practical resources for customer screening; and supports technical resources to strengthen synthesis screening. The Common Mechanism tools are hosted in Switzerland, developed by an international consortium, and incorporate biosecurity standards from every continent.

Industry leaders have recognized for nearly 20 years that some sequences, such as those that can reconstruct pathogen genomes, should only be sent to trusted customers. Doing this requires screening orders to recognize potentially risky sequences (sequence screening) and screening customers’ identity and intended use for orders (customer screening).

Synthesis screening remains voluntary, inconsistent, and globally fragmented; it is easy to find companies or intermediaries that do not screen, but new standards, tools and regulations have changed incentives around screening. Synthesis screening has long been necessary to comply with export control regulations in over 50 countries, bur is now recommended by national-level guidance in multiple countries, leading AI developers, ISO standards, and the WHO.

IBBIS works to increase the share of synthesis orders for which sequences and customers are screened and support international standards that are inclusive and rigorous. Several IBBIS projects address this challenge, including our work on the Common Mechanism, Global DNA Synthesis Map, and Screening Standards.

The Common Mechanism is part of an emerging ecosystem of nucleic acid screening tools. DNA synthesis providers building their own screening tools often rely on BLAST searches that are vulnerable to evasion strategies and fail to keep pace with evolving taxonomy and policy requirements, and IBBIS collaborates with other tool developers to increase the fraction of global orders that are screened according to best practices. The core differences between the Common Mechanism and other tools in the ecosystem are:

• Free, open-source software and databases. The commec software package, and its associated databases are fully public and open-source.
• No data transfer. Intellectual property embedded in customer sequences can make providers reluctant to outsource screening to third-party services. The commec software is designed to be installed locally by individual providers, lowering barriers to access while protecting customer data.
• Globally accessible, internationally designed. The software was designed by an international technical consortium and incorporates screening standards from every continent.
• Customer screening. We also offer methods for verifying customer legitimacy, developed with a focus on serving international customers.

The commec sequence screening package is free to use, designed to avoid false positives, and provides decision support to reduce the amount of time needed to review flagged orders. It runs locally, with no data transferred from users to IBBIS. It is more robust against screening evasion attempts (including AI-generated sequences) than basic BLAST-based approaches and meets or exceeds industry-standard performance benchmarks.

The Common Mechanism is developed and maintained by IBBIS, the International Biosecurity and Biosafety Initiative for Science. From 2021-2023, the software and databases were developed by a team of technical consultants working with the Nuclear Threat Initiative. In 2024, IBBIS was launched and became the home of the project. Major milestones in the development of the Common Mechanism include:

• January 2020: the Common Mechanism was proposed by an international working group jointly convened by the Nuclear Threat Initiative (NTI) and the World Economic Forum (WEF), which also called for an international entity that will house the mechanism, promote its adoption, and work to establish global norms for nucleic acid synthesis screening.
• 2020-2023: advised an international technical consortium, the Common Mechanism software and databases were developed by a team led by Dr. Nicole Wheeler of the University of Birmingham, and including contributions from Brittany Rife Magalis of the University of Louisville and Jennifer Lu of the Center for Computational Biology at Johns Hopkins University.
• February 2024: IBBIS is launched, acting as a long-term home for the Technical Consortium and Common Mechanism, among other initiatives to advance biosecurity.
• May 2024: public launch of the first open-source version of the Common Mechanism software.

The Common Mechanism continues to be developed by an IBBIS team.

The Common Mechanism is developed and maintained by the International Biosecurity and Biosafety Initiative for Science. IBBIS is an independent Swiss foundation that received launch funding from Founder's Pledge, a philanthropic organization with nonprofit registration in Germany, the UK, and the USA. IBBIS receives no funding from government or industry sources.

The Common Mechanism screens nucleotide sequences of 50 base pairs or more through the following screening steps:

1. Biorisk search: Sensitively identify well-established sequences of concern, such as toxins and virulence factors. (This is done using a fast HMM-based search against sequence profiles curated from annotations of regulated pathogens and toxins.)
2. Taxonomy Search: Query large protein and DNA databases to retrieve the organism the genome most closely matched to the query sequence, then cross-referencing that match with a variety of control lists, including those from India, China, and South Africa.
3. Low-concern search: Clear earlier flags based on matches to common or conserved sequences. This database includes protein sequences found in thousands of bacterial species, RNA sequences that participate in processes essential for life, and sequences submitted to the iGEM parts registry with no associated safety flags.

These steps, and how they lead to decisions to flag a sequence, are shown below:

No, anyone is welcome to use the Common Mechanism. The commec package has been primarily used by DNA synthesis providers, including non-traditional providers such as DNA data storage companies and biofoundries. Other users include AI tool developers, curators of sequence databases, sequencing-as-a-service providers, and academic researchers. Please reach out if you have feature requests that would allow the Common Mechanism to better serve your needs!

The Common Mechanism is designed to screen DNA and RNA sequences. There are some limitations:

• Sequences below 50bp cannot be screened, and screening performance is best with sequences over 150bp.
• Protein sequences cannot be screened directly, though translations of the input DNA sequences are screened as part of the process.
• The system does not have any specialized functionality for screening oligo orders.
• Sequences containing ambiguity codons may not be scored correctly by every step in the pipeline.

IBBIS is working on reducing these limitations.

When running the software in fast mode, a single run typically takes only a few seconds. However, when performing a full search using NCBI databases, it may take several minutes to generate the final output files, depending on your machine's computational power.

Yes; you can submit multiple sequences at once to the software by combining them into a single FASTA input. Depending on the computing environment where screening is conducted, it may sometimes be faster to split sequences into several batches and screen each in parallel.

Yes, the Common Mechanism is designed with integration capabilities in mind. It includes a "fast mode" that is specifically designed to enable our sensitive biorisk detection to be incorporated into other pipelines that may use different approaches for flagging sequences of concern through taxonomic measures. Since the Common Mechanism is available as a Python package and can be run on Linux systems, it can be readily incorporated into standard bioinformatics pipelines. The software’s modular design allows for flexible implementation, where users can utilize specific components of the Common Mechanism that best complement their existing workflows.

The Common Mechanism sequence screening was developed with a dual emphasis on reducing ambiguities and flagging a baseline level of sequences of concern, making it a useful tool for benchtop synthesis devices. The decision support tool is able to provide a fully automated “flag” or “pass” decision for each order; benchtop devices could then be configured to refuse to synthesize sequences that are flagged during screening. Legitimate users of those sequences would need to order them from another commercial provider or provide an authentication key that allows them to synthesize specific sequences of concern.

Yes, the software is open-source, and you can inspect the code and databases online.

Installing the Common Mechanism sequence screening software requires a computing environment which can run shell scripts and Python with adequate storage space for the databases used (~1 Gb for the curated biorisk and benign databases, ~600 Gb for the standard protein and nucleotide databases used for similarity search, which will already be installed in many bioinformatics computing environments). It is also possible to install and run the program with Biocontainer (Docker image). Since the release of this document, the software has only been extensively tested in Linux computing environments, although trials in Windows and MacOS demonstrated its capacity to run in these operating systems as well. We expect to make available an API for testing small numbers of sequences in the near future.

No. The Common Mechanism is designed to be locally installed by synthesis providers, keeping all customer information in-house and ensuring that your data is protected. The output files generated by the software are stored locally and are not sent to IBBIS or any third party.

The initial “biorisk” database used by the Common Mechanism draws only from existing, publicly available databases of sequences known to be associated with toxicity or pathogenicity. This list is further limited to only those sequences that are found in regulated, listed pathogens and toxins, such as those on export control lists. This limited biorisk database allows the Common Mechanism to flag sequences that are well established, transparently sourced, and represent some level of international consensus. As such, sharing the initial databases does not present a security concern.

No, IBBIS does not request or collect any personal information from users during installation. The only metrics we have access to is the number of downloads the software has via Bioconda.

A flagged sequence means that the order contains a sequence of concern (SOC) matching proteins or organisms known to pose biosecurity risks and that are regulated by national control lists. If you are a synthesis provider, do not ship a flagged sequence until you are confident that the customer has a legitimate intended use for it. Recommendations on screening customers are provided by the IBBIS SOC Order Form, and accompanying decision guidance.

The Common Mechanism was designed to adhere to the most comprehensive DNA screening guidelines currently available: the Framework for Nucleic Acid Synthesis Screening of the United States, the UK screening guidance on synthetic nucleic acids for users and providers, the Harmonized Screening Protocol of the International Gene Synthesis Consortium and ISO 20688-2:2024.

Database updates are released when there are major updates to our source databases, in response to vulnerability disclosures, and when definitions of biological risk change. Historically, we have released database updates at least once per year. We are planning to transition to a quarterly maintenance update schedule to provide more frequent improvements and ensure the screening remains aligned with rapidly evolving biosecurity requirements. Users will be notified of available updates through our GitHub repository and communications channels.

For general inquiries, please get in touch with IBBIS at info@ibbis.bio. Our technical staff and consultants are available to support users of the sequence screening software and will guide you through the installation process; feel free to contact us if you are interested in using it.

If you experience a bug during installation or when using the software, you can open an issue on GitHub and our team will address it as soon as possible.

Although unlikely, if a known benign sequence is flagged or if a sequence with a previously identified risk is not, please contact us at screening@ibbis.bio and explain the situation.

While the Common Mechanism provides robust DNA synthesis screening capabilities, the software currently has a few limitations users should be aware of:

• Processing speed: When running comprehensive searches using NCBI databases, the software may require significant processing time depending on your computational resources.

• Database size requirements: The software depends on large reference databases (~600 GB for standard protein and nucleotide databases), which may present storage challenges for some users.

• Oligonucleotide handling: The system does not currently have specialized functionality for screening oligo orders.

• Scope: The Common Mechanism is focused solely on sequence screening and does not provide customer screening capabilities. For guidance on customer screening, please refer to our customer legitimacy verification guidelines.

IBBIS is constantly working on reducing these limitations, which should gradually disappear as new updates are released.

When citing the Common Mechanism in academic publications or presentations, please use the following reference:

April 2024. Overcoming Challenges to Developing a Common Global Baseline for Nucleic Acid Synthesis Screening.Nicole Wheeler, Sarah R. Carter, Tessa Alexanian, Christopher Isaac, Piers Millett, Jaime Yassif. Applied Biosafety. Available online (archive).

Yes. Users of the Common Mechanism may display our logo or wordmark in presentations, talks, documents, or papers when explaining how they used it. Please use the commec wordmark when specifically referencing the sequence screening software. Depending on layout, you may wish to use the compressed logo (also available for light backgrounds) or the horizontal wordmark (also available for light backgrounds):