What is Needed to Implement a Biosecurity Sequence Screening Program?

An effective biosecurity sequence screening program requires specific components, expertise, and training.

At this time, biosecurity sequence screening programs in the U.S. are voluntary. But if a deadly pathogen can be put to nefarious use by a bad actor, companies fulfilling orders for synthesized DNA sequences have a lot at stake and therefore tremendous incentive to verify their customers and ensure they have a legitimate need for any potentially concerning sequences they order. To accomplish this, companies fulfilling orders for DNA sequences require a system that includes the following guidance, components, expertise, and training.

Biosecurity Screening Guidance

The first order of business is to have a framework for the sequence screening program. The U.S. HHS 2010 Screening Framework Guidance was introduced in 2010 and many companies in the U.S. use this framework. It is also the basis for the Harmonized Screening Protocol v 2.0 from the International Gene Synthesis Consortium (IGSC), an industry consortium with global membership representing approximately 80% of commercial gene synthesis capacity. The framework in these guidances delineates clear steps and considerations for sequence screening programs.

Biosecurity Screening Program Components

Whether the guidance is from the HHS or IGSC, the components required are the same. A company filling orders for genetic materials needs to be able to screen customers against watch lists for customer screening, and, at a minimum, needs a way to screen sequences against a reference database to identify any sequences associated with organisms on the watch lists. The major sequence databases like Genbank® provide annotations to assist in follow-up on any flags. 

Biosecurity Screening Expertise

Experts, usually Ph.D.s in the field, are necessary to follow up on flagged items. Their knowledge is required to determine whether a sequence is inherently dangerous under all conditions, dangerous under some conditions, or is a non-pathogenic portion of a pathogenic sequence and therefore not dangerous for its stated use. The amount of time required for the follow-up depends upon the threat level associated with that flag. Those of a less serious nature can generally be resolved by an expert in a matter of minutes. Flags of a more serious nature can require several hours.

Some companies use commercial software like Battelle’s UltraSEQ™ to augment the available expertise. In addition to the annotation provided by the sequence reference databases, UltraSEQ™ uses a proprietary, curated sequence of concern database that provides additional information and analytics that can be used to assess the threat behind a flag. Some of these analytics are in the form of virulence factors, a threat status score, complex pattern identification, and comprehensive reporting and interpretation. This makes it possible for the designated expert to work from the start, with a full set of facts and factors in context, that are specific to the flagged item.

Biosecurity Screening Training

In an effort to reduce the amount of time required to clear a flag, some companies opt to use trained technicians. These technicians generally work with less complex threats and are supervised by a Ph.D. This is effective in many instances, and the use of a product such as UltraSEQ™ can assist technicians in making their determinations. However, for complex threats, expertise in the field is a definite requirement. 

While the specific implementation of each system may vary, all biosecurity screening programs have the need for the same components, expertise, and training.