Response to Regulatory Questions (RTQ)
0.1.0 - ci-build

Response to Regulatory Questions (RTQ), published by HL7 International. This guide is not an authorized publication; it is the continuous build for version 0.1.0 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/rtq-ig/ and changes regularly. See the Directory of published versions

Use Case

This section illustrates how the Regulatory Questionnaire profile enables efficient, automated handling of regulatory questions and responses in regulatory workflows. By structuring questions with CTD mappings, rich text, and clear sender/recipient details, both health authorities and sponsors can triage inquiries, leverage historical data, and generate draft responses—reducing manual effort, accelerating reviews, and improving global regulatory harmonization.

The profile supports end-to-end automation, from question issuance to response submission, integrating with FHIR ready systems and agency review platforms. This aligns with emerging real-time paradigms in global regulatory affairs, where FHIR enables sub-second processing of regulatory information, shrinking timelines from months to days or hours.

Scenario: EMA Type II Variation Review

EMA Type II Variation Review: During review of a shelf-life extension for a biologic drug, the European Medicines Agency (EMA) issues 10 targeted questions on stability data (CTD 3.2.P.8), impurities (3.2.P.5.4), and labeling updates (1.3.1). The questions are sent as a FHIR Questionnaire bundle via secure API, email, or portal upload.

Without Structured Q&A

  • Regulator: Manually drafts the questions in Word/email; inconsistent formatting; no traceability to prior reviews; high redundancy.
  • Sponsor: Manual parsing of PDF/email; 2–3 days to categorize and assign; duplicate effort across submissions.
  • Delays: 4–6 weeks total cycle—exacerbating backlogs, and risk staff burnout.
  • Capacity limits: One team handles 2–3 parallel applications; high question volume increases turnover.

With Structured Q&A (Using This Profile)

Regulator Benefits
  1. Standardized Issuance: Reviewers use structured authoring tools to generate FHIR-compliant questions with CTD codes, rich text, and deadlines (effectivePeriod)—ensuring clarity and consistency.
  2. Automated Tracking: System auto-logs questions by CTD section, agency, and product—enabling real-time dashboards on review workload, aging, and bottlenecks.
  3. Global Benchmarking: Query historical questions across submissions to identify recurring issues (e.g., 70% of stability questions involve timepoint gaps), informing guidance updates and reviewer training.
  4. Faster Decision-Making: Structured responses arrive with pre-linked CTD references, reducing verification time by 60–80%.
  1. Immediate Triage: Upon import, a FHIR-ready system parses item.code for CTD sections, auto-routing questions (e.g., stability queries to CMC folder, labeling to SPL team). AI flags urgency based on effectivePeriod.
  2. Historical Reuse: System queries past QuestionnaireResponses for matching item.linkId or CTD codes (e.g., reusing 80% of prior stability justifications from a similar variation). Flags "asked before" with confidence scores.
  3. Draft Generation: Pre-built templates and knowledge bases suggest responses, pulling from validated CMC data (e.g., auto-populating impurity thresholds from ICH Q3B). Human review takes 1–2 days.
  4. Submission: Export as FHIR QuestionnaireResponse bundled with Task for API delivery (via APIX IG) or export to FHIR compliant XML or JSON for portal/email delivery ensuring traceability.

Joint Outcomes:

  • Effort Reduction: 70–80% less manual work for both parties; drafts ready in hours vs. weeks.
  • Increased Capacity: Regulators process 5–10x more submissions; sponsors handle 8–12 parallel applications.
  • Turnover Mitigation: Predictable, structured workflows reduce burnout, automate administrative tasks, and leave more time for higher value activities.
  • Global Impact: Enables accelerated "wave plans" for multi-market submissions (e.g., EMA + FDA + PMDA), shortening global timelines overall.

KPI Comparison: Current Process vs. FHIR-Enabled Process

The following table quantifies the transformative impact of structured regulatory Q&A for both regulators and sponsors.

KPI Current Process (PDF/Email) With FHIR (Structured Q&A) Improvement
Capacity
Questions triaged per week per analyst		 20–30 100–150 5x
Speed
Time from receipt to first draft		 3–5 days 4–8 hours 90% faster
Throughput
Parallel applications managed per team		 2–3 8–12 4x
Accuracy
% of responses requiring rework		 25–35% 5–10% 70% reduction
Volume
Total questions processed per year		 ~1,000 ~5,000+ 5x scale

KPIs are illustrative based on pilot implementations and industry benchmarks. Actual gains depend on system maturity and AI integration.

Strategic Benefit: Global Question Intelligence

Storing all regulatory questions in a structured, standardized FHIR format creates a powerful, queryable knowledge base across submissions, agencies, and regions.

Predictive Regulatory Intelligence

With structured data:

  • Pattern Detection: Identify recurring question themes (e.g., 65% of EMA stability questions reference ICH Q1A timepoints).
  • Agency Profiling: Predict likely FDA focus areas based on EMA precedents.
  • Risk Forecasting: Flag high-risk CTD sections (e.g., 3.2.P.5.4 impurities) for preemptive data strengthening.
  • Global Benchmarking: Compare question volume, response times, and complexity across markets to optimize submission strategy.

Example: A sponsor analyzes 500+ structured questions from EMA, FDA, and PMDA over 3 years and discovers that extended shelf-life claims trigger stability questions in 92% of cases. They proactively include additional timepoint data in future submissions, reducing follow-up questions by 60%.

This global question repository transforms reactive compliance into proactive regulatory strategy, enabling:

  • Faster first-round approvals
  • Reduced amendment cycles
  • Data-driven submission planning

Broader Applications

  • CMC Review Cycles: Streamline quality queries during IND/NDA reviews; auto-link to CTD modules for contextual responses.
  • Global Harmonization: Use CTD mappings for cross-agency questions (ICH-aligned), supporting parallel filings.
  • Vendor Integration: Contract manufacturers (CMOs) receive targeted PQI questions, responding via linked QuestionnaireResponse for seamless supply chain.

​For technical details, see the Questionnaire Profile and APIX IG for API submission.

References:
Anderson, M., Algorri, J.F., Abernathy, M. (2023). Real-time algorithmic exchange and processing of pharmaceutical quality data and information. International Journal of Pharmaceutics, 648, 123342. DOI: 10.1016/j.ijpharm.2023.123342