Can a facility rely on the manufacturer's or pharmacy's stated activity?

For a unit dosage, yes, through decay correction. The regulation permits determining the dosage by a decay correction based on the activity or activity concentration determined by a manufacturer or preparer licensed under 10 CFR 32.72, an Agreement State equivalent, or a PET drug producer licensed under 10 CFR 30.32(j). Many facilities still verify activity by direct measurement as a quality practice.

Dosage Determination Under 10 CFR 35.63

Q: What does 10 CFR 35.63 require?

It requires a licensee to determine and record the activity of each unsealed byproduct-material dosage before it is administered for medical use. For a unit dosage, the activity must be determined either by direct measurement of radioactivity or by a decay correction based on the activity determined by a licensed manufacturer, preparer, or PET drug producer. Unless the authorized user directs otherwise, a dosage may not be used if it falls outside the prescribed range or differs from the prescribed dosage by more than 20 percent.

Q: What records does the dosage determination require?

Under 10 CFR 35.2063 the record must include the patient or human research subject's name or identification number, the prescribed dosage and the determined dosage (or a notation that the total activity is less than 1.1 MBq, 30 microcuries), the date and time of the determination, and the name of the individual who determined it. These records must be kept for 3 years.

Q: What instrument is used to measure the dosage?

A dose calibrator, which is a sealed ionization chamber. Under 10 CFR 35.60 the licensee must possess and use instrumentation to measure activity before administration and must calibrate it in accordance with nationally recognized standards or the manufacturer's instructions, keeping calibration records under 10 CFR 35.2060.

Q: How does 35.63 relate to medical event reporting?

A dosage that is administered well outside the prescribed value can become a reportable medical event under 10 CFR 35.3045 when it also meets that rule's dose or activity thresholds. Correct dosage determination under 35.63 is a primary control that prevents medical events, especially for therapy administrations governed by a written directive.

10 CFR 35.63 requires a licensee to determine and record the activity of every unsealed byproduct-material dosage before it is administered — and, unless the authorized user directs otherwise, not to use a dosage that falls outside the prescribed range or differs from the prescribed dosage by more than 20 percent.¹ For a unit dosage, the activity is determined either by direct measurement in a calibrated dose calibrator or by decay correction from a licensed preparer or PET drug producer.¹

It is one of the shortest sections in Part 35, but it is where dose-calibrator quality control, recordkeeping, written directives, and medical-event avoidance all converge. Getting it right is a routine but non-negotiable part of every nuclear medicine program.¹²³

Introduction

Dosage determination is the last quantitative checkpoint between the radiopharmacy and the patient. Every unsealed radiopharmaceutical dosage — a diagnostic Tc-99m study, an F-18 FDG PET injection, an I-131 therapy capsule — must have its activity determined and recorded before administration, and that determined value must agree with what the authorized user prescribed.¹

The rule is deceptively simple, and that is exactly why it is a recurring inspection finding. Compliance depends on a chain of supporting requirements: a dose calibrator that is possessed, used, and calibrated under 10 CFR 35.60; records that meet the specific content requirements of 10 CFR 35.2063; and a workflow that flags any dosage falling outside the 20 percent agreement window before it reaches the patient.¹²³⁴

This article explains what 35.63 requires, the two permitted methods of determining a unit dosage, the arithmetic of decay correction and the 20 percent rule, the instrumentation and recordkeeping that support it, the clinical and safety impact, practical compliance tips, and the broader regulatory context — including its relationship to written directives and medical event reporting.¹²³⁵

Topic Explanation

What 35.63 actually says

Section 35.63 requires the licensee to "determine and record the activity of each dosage before medical use."¹ For a unit dosage — a single patient dose prepared and supplied by a pharmacy or producer — the activity must be determined by one of two permitted methods:¹

Direct measurement of radioactivity, using instrumentation the licensee possesses and uses under 10 CFR 35.60; or
A decay correction based on the activity or activity concentration determined by a manufacturer or preparer licensed under 10 CFR 32.72 (or Agreement State equivalent), an NRC or Agreement State licensee operating under an RDRC-approved or FDA-accepted IND protocol, or a PET drug producer licensed under 10 CFR 30.32(j).¹

For dosages the licensee prepares itself from bulk material or a generator eluate and kit, the activity is determined by direct measurement.¹ In all cases, the key acceptance criterion is the same: unless the authorized user directs otherwise, the licensee may not use a dosage if it does not fall within the prescribed dosage range, or if it differs from the prescribed dosage by more than 20 percent.¹

Unit dosage versus licensee-prepared dosage

The distinction matters because it determines which method is available:

A unit dosage arrives pre-measured from a licensed nuclear pharmacy or PET producer, with a stated activity at a stated calibration time. The licensee may decay-correct that stated activity to the administration time, or measure it directly. Direct measurement is common practice as an independent check.¹
A licensee-prepared dosage — drawn and compounded on site (for example, from a Tc-99m generator and a cold kit) — must be measured directly in the dose calibrator, because there is no upstream licensed determination to decay-correct from.¹

This ties dosage determination directly to compounding practice; unsealed radiopharmaceutical preparation is also governed by USP General Chapter <825>. See our detailed discussion of USP <825> radiopharmaceutical compounding.

The instrument: the dose calibrator

Direct measurement is performed in a dose calibrator — a sealed, pressurized ionization chamber that reads activity in becquerels or curies for a selected radionuclide. Under 10 CFR 35.60, a licensee must possess and use such instrumentation to measure activity before administration and must calibrate it in accordance with nationally recognized standards or the manufacturer's instructions, retaining calibration records under 10 CFR 35.2060.²⁶ A dose calibrator whose accuracy, constancy, linearity, or geometry is not verified undermines every 35.63 determination that depends on it — which is why routine dose-calibrator QC is inseparable from dosage-determination compliance.⁷ For the QC program itself, see our dose calibrator quality control guide.

Key Technical Principles

Decay correction

When a unit dosage is calibrated by the pharmacy for a future time, or measured earlier than administration, the activity must be corrected for radioactive decay. Activity decays exponentially:

A (t) = A_{0} e^{- λ t}, λ = \frac{ln 2}{T _{1/2}}

where $A_{0}$ is the activity at the reference (calibration) time, $λ$ is the decay constant, and $t$ is the elapsed time.

Worked example (Tc-99m unit dosage). A pharmacy supplies a Tc-99m dosage calibrated to 925 MBq (25 mCi) at 07:00. Administration is scheduled for 10:00 — an elapsed time of 3 hours. Tc-99m has a physical half-life of 6.01 hours, so:

λ = \frac{ln 2}{6.01 h} = 0.1153 h^{- 1}

A (3 h) = 925 MBq \times e^{- 0.1153 \times 3} = 925 \times e^{- 0.346} = 925 \times 0.707 \approx 654 MBq (17.7 mCi)

The decay-corrected activity of 654 MBq is the "determined dosage" recorded and compared with the prescription at administration time.¹

The 20 percent agreement rule

The acceptance test compares the determined dosage $A_{d e t}$ with the prescribed dosage $A_{p r esc}$ :

Percent difference = \frac{∣ A _{d e t} - A _{p r esc} ∣}{A _{p r esc}} \times 100%

Worked example. Suppose the authorized user prescribed 740 MBq (20 mCi) and the determined dosage at administration is 654 MBq. Then:

\frac{∣654 - 740∣}{740} \times 100% = \frac{86}{740} \times 100% \approx 11.6%

Because 11.6% is within 20%, the dosage may be administered.¹ Had the determined dosage been, say, 560 MBq, the difference would be $\frac{180}{740} \approx 24%$ — outside the window — and the dosage could not be used unless the authorized user specifically directed its use (or a prescribed range covered it). The 20 percent rule is a guardrail, not a target; well-run programs aim for much tighter agreement and investigate any dosage approaching the limit.

The recordkeeping floor and the 1.1 MBq notation

Every determination generates a record under 10 CFR 35.2063 that must contain: the patient's or human research subject's name or identification number; the prescribed dosage and the determined dosage (or a notation that the total activity is less than 1.1 MBq / 30 µCi); the date and time of the determination; and the name of the individual who made it. These records are retained for 3 years.³ The comparison of unit systems below summarizes the key numeric anchors.

Quantity	SI value	Conventional value
Dosage agreement window	±20% of prescription	±20% of prescription
Recordkeeping activity floor	1.1 MBq	30 µCi
Dosage-determination record retention	3 years	3 years
Dose-calibrator calibration record retention	Per 35.2060 (life of instrument use)	Per 35.2060
Tc-99m physical half-life (example)	6.01 h	6.01 h

Clinical Impact

Dosage determination is a patient-safety control disguised as a paperwork step. For diagnostic studies, an incorrect activity degrades image quality — too little activity yields a noisy, non-diagnostic study; too much delivers unnecessary dose without benefit. For therapy, the stakes are higher: the administered activity directly determines the absorbed dose to the target and to normal tissue, so an out-of-tolerance therapy dosage can mean under-treatment or excess toxicity.¹⁵

Therapy administrations tie 35.63 to the written directive. For unsealed therapy such as I-131 sodium iodide above regulatory thresholds and for radiopharmaceutical therapies like Lu-177 agents, an authorized user must sign a written directive, and the administered activity must match that directive within the applicable tolerance. A dosage determination that is not reconciled against the written directive is a common root cause of therapy medical events.¹⁵ For the directive framework, see our post on written directives in nuclear medicine.

The link to medical event reporting is direct. When an administration differs from what was intended by more than the dose or activity thresholds in 10 CFR 35.3045, it becomes a reportable medical event. Sound dosage determination — measuring, checking against the prescription and, for therapy, the written directive, and stopping when a value is out of tolerance — is the primary barrier that keeps a mis-measurement from becoming a reported event.⁵ Our overview of medical event reporting under 35.3045 covers that downstream requirement in detail.

Practical Optimization Tips

Build the 20 percent check into the workflow

Make the agreement test an explicit, documented step, not an assumption:¹³

Record the prescribed dosage (or range) from the authorized user before measurement.
Record the determined dosage (measured or decay-corrected) at administration time.
Compute and document the percent difference, and define a hard stop if it exceeds 20% without authorized-user direction.
For therapy, reconcile against the written directive as a separate, named check.

Keep the dose calibrator trustworthy

Because direct measurement depends entirely on the instrument, the dose-calibrator QC program is part of 35.63 compliance:⁶⁷

Constancy (daily), accuracy (at installation and annually), linearity (at installation and periodically), and geometry (at installation) checks.
Use the correct radionuclide setting and appropriate geometry (volume, container) for each measurement.
Retain calibration and QC records under 10 CFR 35.2060.

Standardize the decay-correction method

For unit dosages, standardize whether the program decay-corrects the pharmacy value, measures directly, or does both. Document the half-life and reference time used, and use consistent clocks between the pharmacy calibration time and the administration time so the elapsed interval is correct.¹

Audit records against the 35.2063 content list

Periodically pull dosage-determination records and confirm each contains all required elements — patient identifier, prescribed and determined dosages (or the <1.1 MBq notation), date and time, and the name of the individual. Missing fields are among the most frequent, and most avoidable, inspection findings.³⁸

Regulatory Considerations

Dosage determination sits inside the NRC (or Agreement State) medical-use framework and connects to several adjacent Part 35 requirements.

10 CFR 35.63 — the core requirement to determine and record each dosage before use, with the direct-measurement/decay-correction methods and the 20 percent agreement rule.¹
10 CFR 35.60 — possession, use, and calibration of instruments used to measure activity of unsealed byproduct material; the dose calibrator must be calibrated to nationally recognized standards or manufacturer instructions.²
10 CFR 35.2063 and 35.2060 — records of dosage determinations (3-year retention) and of instrument calibrations.³⁶
10 CFR 32.72 and 30.32(j) — the licensing basis for the manufacturers, preparers, and PET drug producers whose determined activities may be used for decay correction.¹
USP General Chapter <825> — standards for preparation, compounding, dispensing, and repackaging of radiopharmaceuticals, which govern the dosages being measured.⁹
NRC NUREG-1556, Volume 9 — consolidated program-specific guidance for medical-use licenses, including expectations for dosage determination and instrumentation.¹⁰
Jurisdiction and service areas. Byproduct-material medical use is regulated by the NRC or an Agreement State. DRPS serves Florida, Maryland, Virginia, Washington DC, California, Nevada, Pennsylvania, New York, New Jersey, and Delaware; most are Agreement States, while Washington DC and Delaware are direct-NRC for radioactive material. Always confirm requirements with the authority having jurisdiction.

Consistent, documented dosage determination — backed by a calibrated dose calibrator and complete records — is exactly the kind of routine control that inspectors expect to see functioning without gaps.⁸¹⁰

Frequently Asked Questions (FAQs)

What does 10 CFR 35.63 require?

It requires the licensee to determine and record the activity of each unsealed dosage before medical use. For a unit dosage, activity is determined by direct measurement or by decay correction from a licensed preparer or PET producer, and — unless the authorized user directs otherwise — a dosage may not be used if it is outside the prescribed range or differs from the prescription by more than 20 percent.¹

Does the 20 percent rule apply to diagnostic and therapeutic dosages?

Yes. Section 35.63 applies to both diagnostic and therapeutic unsealed administrations; the determined dosage must agree with the prescription within 20 percent (or fall within a prescribed range) unless the authorized user directs otherwise.¹

Can a facility rely on the pharmacy's stated activity?

For a unit dosage, yes — through decay correction based on the activity determined by a 10 CFR 32.72 licensed preparer, an Agreement State equivalent, or a 10 CFR 30.32(j) PET producer. Many facilities also measure directly as an independent quality check.¹

What records does the dosage determination require?

Under 10 CFR 35.2063: the patient/subject identifier, the prescribed and determined dosages (or a notation that total activity is under 1.1 MBq / 30 µCi), the date and time of the determination, and the name of the individual who determined it — retained for 3 years.³

What instrument is used to measure the dosage?

A dose calibrator (a sealed ionization chamber). Under 10 CFR 35.60 it must be possessed and used to measure activity before administration and calibrated to nationally recognized standards or manufacturer instructions, with records kept under 10 CFR 35.2060.²⁶

How does 35.63 relate to medical event reporting?

Correct dosage determination is a primary barrier against medical events. An administration differing from the intended value by more than the thresholds in 10 CFR 35.3045 becomes reportable, so the 35.63 check — especially reconciled against a therapy written directive — prevents mis-measurements from becoming reported events.⁵

Key Takeaways

10 CFR 35.63 requires determining and recording the activity of every unsealed dosage before administration.¹
A unit dosage may be determined by direct measurement or by decay correction from a licensed preparer or PET producer; licensee-prepared dosages are measured directly.¹
Unless the authorized user directs otherwise, a dosage outside the prescribed range or differing from the prescription by more than 20 percent may not be used.¹
Direct measurement depends on a dose calibrator possessed, used, and calibrated under 10 CFR 35.60, making dose-calibrator QC part of compliance.²⁷
Records under 10 CFR 35.2063 must contain the patient identifier, prescribed and determined dosages (or a <1.1 MBq notation), date/time, and the determiner's name, kept for 3 years.³
Dosage determination is a patient-safety control that, reconciled against the written directive, prevents therapy medical events under 10 CFR 35.3045.⁵

Conclusion

Section 35.63 reads as a one-paragraph administrative step, but it anchors a chain of quality and safety controls: a calibrated dose calibrator, a correct decay correction, an explicit 20 percent agreement check, complete records, and — for therapy — reconciliation against the written directive. Programs that treat dosage determination as a deliberate, documented workflow rather than a rote sign-off protect their patients, keep their dose-calibrator QC honest, and stay clear of the medical-event thresholds that make a mis-measurement a reportable event.¹³⁵

How DRPS Can Help

Diagnostic Radiation Physics Services (DRPS) supports nuclear medicine and PET/CT programs across Florida, Maryland, Virginia, Washington DC, California, Nevada, Pennsylvania, New York, New Jersey, and Delaware with radioactive material license support, radiation safety officer services, dose-calibrator QC program design, dosage-determination workflow and recordkeeping audits, and inspection readiness — all delivered by board-certified medical physicists.

A dependable dosage-determination program is not just an inspection item. It is the last quantitative check that keeps the activity a patient receives equal to the activity the authorized user intended.

Related Resources

References

U.S. Nuclear Regulatory Commission. 10 CFR 35.63, Determination of dosages of unsealed byproduct material for medical use. ecfr.gov
U.S. Nuclear Regulatory Commission. 10 CFR 35.60, Possession, use, and calibration of instruments used to measure the activity of unsealed byproduct material. ecfr.gov
U.S. Nuclear Regulatory Commission. 10 CFR 35.2063, Records of dosages of unsealed byproduct material for medical use. ecfr.gov
U.S. Nuclear Regulatory Commission. 10 CFR Part 35, Medical Use of Byproduct Material. nrc.gov
U.S. Nuclear Regulatory Commission. 10 CFR 35.3045, Report and notification of a medical event. ecfr.gov
U.S. Nuclear Regulatory Commission. 10 CFR 35.2060, Records of calibrations of instruments used to measure the activity of unsealed byproduct material. ecfr.gov
Zanzonico P. Routine quality control of clinical nuclear medicine instrumentation: a brief review. J Nucl Med. 2008;49(7):1114-1131. doi:10.2967/jnumed.107.050203. pubmed.ncbi.nlm.nih.gov
U.S. Nuclear Regulatory Commission. Frequently Asked Questions About Licensing Medical Uses of Byproduct Material Under Revised 10 CFR Part 35. nrc.gov
United States Pharmacopeia. General Chapter <825>, Radiopharmaceuticals — Preparation, Compounding, Dispensing, and Repackaging. usp.org
U.S. Nuclear Regulatory Commission. Consolidated Guidance About Materials Licenses: Program-Specific Guidance About Medical Use Licenses. NUREG-1556, Volume 9, Revision 3. nrc.gov