Draft — pending regulatory review

This page reflects iFlow's current technical scope and the safety posture we believe appropriate for it. It has not yet been signed off by a qualified person under a laboratory quality system. Your laboratory is responsible for assessing iFlow against its own procedures before using it for patient testing.

Pending actions before this banner is removed:

Named regulatory / QA reviewer at Intelliseq confirms each statement below.
Laboratory-side assessment is recorded alongside the site's standard operating procedures.

Intended Use and Limitations¶

Intended purpose¶

iFlow is a software platform for clinical genomics laboratories. It supports the end-to-end handling of sequencing-based clinical tests by:

Registering subjects, samples, and clinical orders.
Orchestrating configured bioinformatics pipelines that produce variant call files (VCFs) from sequencing data.
Presenting variants for human curation with links to external evidence (NCCN, AMP / ASCO / CAP, ACMG, CKB, CIViC, FDA).
Assembling, reviewing, and signing off on clinical reports that can be issued through the laboratory's existing reporting channels.
Retaining an immutable audit trail of every state change, including who performed each action and when.

iFlow is intended to be used within a clinical laboratory that operates under an applicable quality system (for example CLIA in the US, ISO 15189, or national equivalents). All clinical conclusions that reach a patient or clinician must be reviewed and signed off by a qualified professional authorised under that quality system.

Intended users¶

iFlow is intended for trained laboratory personnel in the following roles:

Role	Typical responsibilities
Laboratory technician	Register subjects and samples, upload sequencing files, advance orders through the lab workflow.
Clinical variant scientist or reviewer	Curate variants, record ACMG / AMP evidence, prepare report drafts.
Signing physician or authorised signatory	Approve and sign clinical reports that will be released to the ordering clinician.
Laboratory administrator	Configure projects, labflows, access controls, report templates.

iFlow is not intended for direct use by patients, by the ordering clinician (who receives signed reports through the laboratory's existing channels), or by personnel who have not been trained on the platform and on the laboratory's standard operating procedures.

Intended test context¶

iFlow is designed to support:

Hereditary (germline) testing — panel, exome, or whole genome tests where variant classification follows ACMG / AMP 2015 standards.
Somatic (oncology) testing — tumour profiling tests where variant reporting follows AMP / ASCO / CAP 2017 tier classifications.

It is configurable to other sequencing-based test types, subject to the laboratory providing a suitable pipeline, report template, and clinical review procedure.

Supported inputs¶

Input	Support status	Notes
Reference genome	GRCh38 (required)	GRCh37 / hg19 inputs are not supported by the current pipelines.
Sequencing read formats	FASTQ, BAM	Consumed by configured pipelines running in Compute.
Variant formats	VCF 4.2 or later, bgzipped (`.vcf.gz`) with tabix index (`.tbi`)	Ingested by the VCF service for browsing.
Variant types	SNVs, small InDels	Reliable for short variants. CNV / SV handling depends on pipeline configuration and is out of scope for the default pipelines.
Test modes	`hereditary`, `somatic`	Selected per order; drives template selection and variant handling.

What iFlow does not do¶

iFlow does not make clinical decisions. Variant classifications, ACMG criteria, AMP / ASCO / CAP tier assignments, and the decision to report a given variant are captured by human users. iFlow records their input; it does not generate them.
iFlow does not validate pipelines. Pipeline correctness is the responsibility of the laboratory. iFlow orchestrates pipelines and stores their outputs, but a pipeline that produces wrong VCFs will feed wrong data into the curation step.
iFlow does not guarantee the accuracy of external annotations. Evidence shown in the variant browser (NCCN references, FDA drug labels, CKB entries, CIViC records) is sourced from external providers and may be out of date. The laboratory is responsible for tracking annotation source versions and the date last refreshed.
iFlow does not certify clinical compliance. The platform provides features (immutable signed PDFs, full transition history, identity-bound sign-off, cryptographically-signed user sessions) that are designed to support the laboratory's compliance with CLIA, ISO 15189, or similar standards. Granting compliance is the laboratory's responsibility.

Immutability and audit guarantees¶

iFlow's audit design is central to its clinical safety story. The following guarantees hold for the current release:

Sign-off is atomic. The transition from sign_off to completed writes the signed PDF, records the signatory, advances the order, and commits the transaction in a single operation. Partial sign-offs are not possible.
Signed PDFs are never overwritten. Each signed report is written to a fixed path in the project bucket and is immutable from the moment sign-off commits.
Amendments preserve the original. If a signed report must be corrected, iFlow creates a new signed PDF at a versioned path and marks the prior report amended. Both PDFs remain accessible for audit.
Every transition is recorded. An append-only audit history captures every stage transition across every order's lifetime — the acting user, timestamp, and any operator notes.
Variant classifications are snapshotted. When a variant is added to a report, a snapshot of the variant's fields at that moment is captured and stored alongside the report entry for that variant. Later changes to the global variant catalogue do not alter what a signed report shows.

Limitations¶

iFlow depends on correct configuration and on its users' clinical judgement. Acknowledging that openly, the following limitations apply:

No IVDR / CE-IVD / FDA clearance. iFlow has not been submitted for regulatory clearance as an in vitro diagnostic device. It is supplied as a software platform for use within a laboratory's quality system.
GRCh38 only. The shipped pipelines and report templates target GRCh38. Supporting other builds is a custom engagement.
Retention is policy-driven. Files outside client-resources/ are subject to the project's retention policy. Keep anything that must survive retention — report templates, BED files, gene panels — under client-resources/.
Single identity provider. Authentication and role resolution go through the Intelliseq-operated Zitadel instance. Self-hosting the IdP is not supported in this release.

Safety warnings¶

For laboratory use only

iFlow output must not be used as the sole basis for a clinical decision. A signed report produced by iFlow is the laboratory's document and is subject to the laboratory's release procedures.

Sign-off is the release act

The Approve-and-Sign step is the point at which a report is considered released by the laboratory. Do not release unsigned preview PDFs to clinicians or patients — they are drafts and may change before sign-off.

Report suspected incidents

Any suspected malfunction, incorrect result, unexpected behaviour, or missing safety-critical feature should be reported to the laboratory's iFlow administrator and to Intelliseq support without delay. Continue to use the platform only when the issue has been assessed and, if necessary, mitigated.

Versioning and traceability¶

Every signed PDF records, alongside the signatory:

The iFlow platform version in use at the moment of sign-off.
The report template version.
The analysis pipeline identifier and version used to produce the VCF.
The dates of the external annotation sources that were referenced.

These fields are populated automatically by the rendering layer and appear in the footer of the signed report. Laboratories requiring a stricter change-control regime can pin the template and pipeline versions per project and cut new versions on a controlled cadence.

Change management¶

Changes to pipelines, report templates, or labflow definitions that are in use for live orders should be version-pinned and reviewed under the laboratory's change control procedure. iFlow supports this by:

Allowing labflows to be marked immutable (is_immutable=true), after which a new version must be cut to make further edits.
Storing report templates in a retention-exempt directory (client-resources/report-templates/) so prior versions remain available for audit.

Approvals and responsibilities¶

Responsibility	Who
Validate that iFlow fits the laboratory's quality system	Laboratory director or QA lead
Configure projects, labflows, templates	Laboratory administrator
Validate pipelines end-to-end	Laboratory bioinformatics lead
Sign off individual reports	Authorised signing physician
Maintain and update this documentation	Intelliseq iFlow team

Feedback¶

Report safety concerns, suspected incidents, or scope clarifications to your iFlow administrator and to Intelliseq support. Non-urgent documentation feedback can be sent via the feedback address listed on your organisation's iFlow landing page.