Written Directives in Nuclear Medicine

A written directive is the dated, signed order an authorized user must complete before certain radiopharmaceutical therapies and higher-activity I-131 administrations — and it is the single most important control preventing a misadministration. Under 10 CFR 35.40, it specifies the patient, the radionuclide or drug, the activity, the route, and the treatment site; under 10 CFR 35.41, the licensee must have verification procedures that ensure each administration actually matches that directive. ^{1, 2}

Written directives are deceptively simple — a form, a signature, a date — but they are the legal and clinical backbone of safe therapeutic nuclear medicine. Get them right and most medical events never happen. Get them wrong, late, or unverified, and a reportable medical event becomes far more likely. This guide explains exactly when a directive is required, what it must contain, the emergency oral-directive rule, the verification procedures, and how directives connect to medical-event reporting. DRPS supports this work through its radiation safety officer and radioactive material license support services. ^{1, 2, 3}

Introduction

The written directive exists because therapeutic nuclear medicine delivers biologically significant radiation doses, and an error in patient, drug, activity, route, or site can cause real harm. ^{1, 3} Unlike a diagnostic FDG scan, where a modest dosing variance changes little, a therapeutic I-131 or Lu-177 administration that goes to the wrong patient or at the wrong activity is a serious adverse event. The Nuclear Regulatory Commission (NRC) — and Agreement States through equivalent rules — therefore require a formal, signed order before these administrations, plus procedures to verify the order is followed. ^{1, 2}

The framework is built from two linked sections of 10 CFR Part 35:

• § 35.40 — Written directives: what the order is, when it is required, what it must contain, and the rules for oral directives and revisions. ¹
• § 35.41 — Procedures for administrations requiring a written directive: the verification system that gives high confidence each administration matches the directive. ²

Together they form a prospective control (the order) and a checking control (the verification), and a deviation between administration and directive is precisely what defines most medical events under § 35.3045. ⁴ This topic is closely tied to medical event reporting under 10 CFR 35.3045 and to patient release after radiopharmaceutical therapy.

Topic Explanation

When a written directive is required

A written directive is required before the administration in the situations summarized below. Diagnostic imaging studies for which a directive is not required — most Tc-99m, F-18, and low-activity diagnostic procedures — are explicitly outside this requirement. ¹

The 1.11 MBq (30 µCi) I-131 sodium iodide threshold is important: it sits well below diagnostic thyroid-uptake activities in some contexts, so any I-131 sodium iodide administration above that small threshold — diagnostic or therapeutic — pulls in the written-directive requirement. ¹ For the therapy radionuclides themselves, see our coverage of RPT shielding for Lu-177, Ra-223, and Ac-225.

What a written directive must contain

The directive must include the patient's (or human research subject's) name plus the procedure-specific information. For unsealed byproduct material, that means the radioactive drug, the dosage (activity), and the route of administration; for I-131 sodium iodide above the threshold, the dosage; for sealed-source treatments, the radionuclide, treatment site, dose, and source/fraction details. Critically, it must be dated and signed by an authorized user before administration. ¹

A written revision to an existing directive is permitted, but the revision itself must also be dated and signed by an authorized user before the relevant dosage, dose, or next fraction is administered. ¹

The oral directive rule

The regulation accommodates emergencies. If, because of the emergent nature of the patient's condition, a delay to produce a written directive would jeopardize the patient's health, an oral directive is acceptable. Two conditions then apply: the information in the oral directive must be documented in writing in the patient's record as soon as possible, and a written directive must be prepared within 48 hours of the oral directive. ¹ This is a narrow allowance for genuine emergencies, not a routine workaround.

Key Technical Principles

Verification under § 35.41 — the checking control

Section 35.40 creates the order; § 35.41 makes sure the order is actually followed. It requires the licensee to develop, implement, and maintain written procedures that provide high confidence that the patient's identity is verified and that each administration is in accordance with the treatment plan, if applicable, and the written directive. ²

In practice, a defensible § 35.41 procedure addresses:

• Patient identity verified by more than one method (for example, name plus date of birth or a second independent identifier) before administration. ²
• Matching the administration to the written directive: correct radionuclide or drug, correct activity, correct route, and correct site. ²
• Independent check of the prepared activity against the directive before administration, typically using a calibrated dose calibrator. (See our guide to dose calibrator quality control.)
• Documentation that the verification occurred, retained as a record. ^{2, 5}

Worked example — does a dosing variance become a medical event?

Section 35.3045 defines a medical event partly by how far the delivered dose departs from the written directive. One core criterion combines a 20% difference from the prescribed dose and exceedance of dose thresholds. Consider a prescribed therapeutic dosage and an administered dosage that differ:

Suppose the written directive prescribes 5550 MBq (150 mCi) of I-131 but 4070 MBq (110 mCi) is administered:

Because 26.7% exceeds the 20% criterion, this administration would be evaluated as a potential medical event — reportable if the associated dose also exceeds the regulatory thresholds. ⁴ Those thresholds are: a dose differing from the prescribed dose by more than 0.05 Sv (5 rem) effective dose equivalent, 0.5 Sv (50 rem) to an organ or tissue, or 0.5 Sv (50 rem) shallow-dose-equivalent to the skin. ⁴ The unit relationship behind the I-131 threshold is worth stating explicitly:

The point of the worked example is not the arithmetic — it is that the written directive is the reference against which every administration is judged. If the directive is wrong, late, ambiguous, or unsigned, the entire downstream safety and reporting framework is built on sand. ^{1, 4}

Recordkeeping

A copy of each written directive must be retained as a record (in accordance with 10 CFR 35.2040), and records of the § 35.41 verification procedures must be maintained and available for inspection. ^{1, 5} These records are routinely examined during NRC or Agreement-State inspections, so completeness and legibility matter as much as the clinical content.

Clinical Impact

Written directives are where radiation safety and patient safety meet, and where most preventable therapy errors are caught — or missed. ^{3, 4} The clinical consequences fall into three groups.

Preventing the wrong-patient and wrong-dose event. The leading categories of nuclear medicine medical events involve administration to the wrong individual or a dose that deviates substantially from what was intended. A complete written directive plus a robust two-identifier verification under § 35.41 is the direct control against both. ^{2, 4}

Therapy program credibility. For programs offering I-131 thyroid therapy, Lu-177 and Y-90 radiopharmaceutical therapy, and similar treatments, the written-directive process is a core part of the quality system that referring physicians, accreditors, and regulators expect to see functioning. Weaknesses here surface quickly in inspections. See preparing for an NRC inspection.

Clear lines of responsibility. Only an authorized user can sign the directive, which anchors clinical accountability. The radiation safety officer and technologists implement the verification procedures, but the AU owns the order. This separation — order versus verification — is itself a safety feature, because it builds an independent check into the workflow. ^{1, 2}

Practical Optimization Tips

Make the written-directive process reliable

• Use a standardized form that prompts for every required element (name, radionuclide/drug, activity, route, site, date, AU signature) so nothing is omitted. ¹
• Sign before administration, every time. A directive signed after the fact does not meet § 35.40; build the signature into the pre-administration timeout. ¹
• Two-identifier patient verification at the point of administration, documented. ²
• Independent activity check against the directive using a calibrated dose calibrator before administration. ²
• Define the emergency path so staff know exactly how to document an oral directive and convert it to a written directive within 48 hours. ¹
• Audit directives periodically as part of the radiation safety program and the annual program review. (See building an ALARA program.)

Common pitfalls to avoid

• Missing or late signature. The most common deficiency; the AU signature must precede administration. ¹
• Incomplete content. Omitting route, site, or activity undermines the directive's purpose and the § 35.41 check. ¹
• No documented verification. Section 35.41 requires procedures and evidence they were followed. ²
• Treating oral directives as routine. The oral-directive allowance is for emergencies only and still requires a written directive within 48 hours. ¹
• Revisions without a new signature. A revised directive must be separately dated and signed before the next dose or fraction. ¹
• Assuming diagnostic studies are covered or not covered correctly. Confirm the I-131 sodium iodide threshold; small activities can still trigger the requirement. ¹

Regulatory Considerations

Written directives are a federal requirement under 10 CFR Part 35, administered directly by the NRC in non-Agreement jurisdictions and by Agreement States under compatible rules. ^{1, 2, 6} The relevant framework:

• 10 CFR 35.40 — Written directives: content, timing, oral-directive rule, and revisions. ¹
• 10 CFR 35.41 — Procedures for administrations requiring a written directive: the verification system. ²
• 10 CFR 35.3045 — Report and notification of a medical event: defines the reportable deviations from the written directive, including the 20% criterion and the 0.05 Sv / 0.5 Sv dose thresholds. ⁴
• 10 CFR 35.2040 — Records of written directives: retention requirement. ⁵
• 10 CFR Part 20 — Standards for Protection Against Radiation: the dose-limit framework underlying the medical-event dose thresholds. ⁷
• NRC NUREG-1556, Volume 9 — program-specific guidance for medical-use licenses, which describes NRC expectations for the written-directive and verification procedures a licensee should have in place. ³

Of the jurisdictions DRPS serves, Florida, Maryland, Virginia, California, Nevada, Pennsylvania, New York, and New Jersey are NRC Agreement States that administer equivalent medical-use rules, while Washington DC and Delaware are regulated directly by the NRC for byproduct material. A licensee must verify which authority issues its license and confirm any state-specific wording, but the substance of the written-directive and verification requirements is compatible across jurisdictions. ⁶ DRPS provides radioactive material license support, radiation safety officer services, and program audits to keep these procedures defensible.

Frequently Asked Questions (FAQs)

What is a written directive in nuclear medicine?

A written directive is an order that must be dated and signed by an authorized user before certain administrations of byproduct material — such as I-131 sodium iodide above 1.11 MBq (30 microcuries) and any therapeutic dosage of unsealed radiopharmaceutical. It specifies the patient, radionuclide or drug, activity, route, and treatment site, and is required by 10 CFR 35.40.

When is a written directive required under 10 CFR 35.40?

A written directive is required before administering I-131 sodium iodide greater than 1.11 MBq (30 microcuries), any therapeutic dosage of unsealed byproduct material, any manual brachytherapy or implant, gamma stereotactic radiosurgery, and teletherapy. Diagnostic imaging dosages generally do not require a written directive.

What must a written directive contain?

It must contain the patient or human research subject's name and, depending on the procedure, the dosage of the radioactive drug, the radionuclide, the route of administration, the treatment site, and — for sealed-source treatments — the dose, the source, and the number of fractions or treatment details, all dated and signed by an authorized user before administration.

What is the oral directive rule?

If a delay to produce a written directive would jeopardize the patient's health because of an emergent condition, an oral directive is acceptable. The oral directive's information must be documented in writing in the patient's record as soon as possible, and a written directive must be prepared within 48 hours of the oral directive.

What does 10 CFR 35.41 require?

Section 35.41 requires licensees to develop, implement, and maintain written procedures to provide high confidence that each administration is in accordance with the written directive. The procedures must verify the patient's identity by more than one method and check that the administration matches the treatment plan and the written directive.

How do written directives prevent medical events?

A medical event under 10 CFR 35.3045 generally involves an administration that differs from the written directive — wrong patient, wrong radionuclide or drug, wrong route, wrong site, or a dose that differs by more than 20 percent and exceeds the dose thresholds. A correct, verified written directive is the primary control that prevents these deviations.

Who can sign a written directive?

Only an authorized user (AU) named on the radioactive material license for the relevant use can date and sign a written directive. The authorized user is responsible for the order; the radiation safety officer and staff implement the verification procedures, but the AU's signature is what authorizes the administration.

Key Takeaways

• A written directive is a dated, signed order from an authorized user required before therapeutic administrations and I-131 sodium iodide above 1.11 MBq (30 µCi). ¹
• It must be complete: patient name, radionuclide/drug, activity, route, site, with the AU signature before administration. ¹
• The oral-directive allowance is emergency-only and still requires a written directive within 48 hours. ¹
• Section 35.41 is the verification backbone: two-identifier patient checks and confirmation that the administration matches the directive. ²
• Deviations define medical events: wrong patient, drug, route, site, or a >20% dose difference exceeding the 0.05 Sv / 0.5 Sv thresholds under § 35.3045. ⁴
• Records matter: retain directives and verification records for inspection. ^{1, 5}

Conclusion

The written directive is small in size and large in consequence. It is the prospective control that fixes, in writing and under an authorized user's signature, exactly what is to be administered to exactly which patient — and § 35.41 is the verification system that makes sure reality matches that order. When both work, the wrong-patient and wrong-dose events that dominate nuclear medicine medical-event statistics are stopped before they reach the patient. ^{1, 2, 4}

For a radiation safety program, the written-directive process deserves the same rigor as shielding or dosimetry: a standardized form, signatures captured before administration, two-identifier verification, an independent activity check, a clear emergency path, complete records, and periodic audit. These are not bureaucratic formalities — they are the difference between a near-miss caught at the bedside and a reportable medical event. ^{2, 3}

How DRPS Can Help

Diagnostic Radiation Physics Services helps nuclear medicine and radiopharmaceutical-therapy programs build defensible written-directive and verification procedures. Our support includes radioactive material license support, radiation safety officer consulting, procedure development aligned with 10 CFR 35.40 and 35.41, medical-event-prevention audits, and inspection readiness reviews.

DRPS serves facilities across our service locations, including Florida, Maryland, Virginia, Washington DC, California, Nevada, New York, Pennsylvania, New Jersey, and Delaware. A strong written-directive process is not about paperwork — it is about making the safe administration the default one.

Related Resources

• Medical event reporting under 10 CFR 35.3045
• Patient release after radiopharmaceutical therapy
• The radiation safety officer's role
• Preparing for an NRC inspection
• NRC radioactive material license guide
• Building an ALARA program
• Radioactive material license support
• Radiation Safety Officer consulting

References

1. U.S. Nuclear Regulatory Commission. 10 CFR 35.40: Written directives. ecfr.gov
2. U.S. Nuclear Regulatory Commission. 10 CFR 35.41: Procedures for administrations requiring a written directive. ecfr.gov
3. U.S. Nuclear Regulatory Commission. NUREG-1556, Volume 9, Revision 3: Consolidated Guidance About Materials Licenses — Program-Specific Guidance About Medical Use Licenses. nrc.gov
4. U.S. Nuclear Regulatory Commission. 10 CFR 35.3045: Report and notification of a medical event. ecfr.gov
5. U.S. Nuclear Regulatory Commission. 10 CFR 35.2040: Records of written directives. ecfr.gov
6. U.S. Nuclear Regulatory Commission. Agreement State Program. nrc.gov
7. U.S. Nuclear Regulatory Commission. 10 CFR Part 20: Standards for Protection Against Radiation. ecfr.gov