NRC 10 CFR 35.1000: Emerging Medical Uses

Introduction

New radioactive therapies arrive faster than the regulations written for them. When a modality does not fit the established medical-use subparts — not an imaging agent, not a conventional unsealed therapy, not a hand-placed sealed source, not a remote afterloader — the NRC still has a way to license it safely. That pathway is 10 CFR 35.1000, Subpart K, the home for "other medical uses of byproduct material." ¹

Section 35.1000 is how yttrium-90 and holmium-166 microspheres, intravascular brachytherapy, and other emerging modalities were brought into clinical use before dedicated rules existed. Rather than a fixed checklist, it is a framework: the NRC publishes use-specific radiation safety and training criteria, and each facility must earn written approval through a license amendment before the first patient is treated. ^{1, 2, 5}

This article explains what 35.1000 is, why certain therapies land there instead of in the standard subparts, how a facility gets authorized, and what the radiation safety officer (RSO) and medical physicist must build into the application. DRPS supports facilities through this process as part of its radioactive material license support, radiation safety officer consulting, and medical physics consulting services across Florida, Maryland, Virginia, Washington DC, California, Nevada, Pennsylvania, New York, New Jersey, and Delaware.

Topic Explanation

What 35.1000 actually says

Section 35.1000 permits a licensee to use byproduct material for a medical use that is not specifically addressed in the other subparts of Part 35, provided the licensee has submitted the required application information and received written approval from the Commission in a license or license amendment, and uses the material under the conditions the Commission considers necessary. ¹

The key words are not specifically addressed and written approval. Part 35 is organized by modality:

• Subpart D — unsealed material for uptake, dilution, and excretion (diagnostic).
• Subpart E (§35.200) — unsealed material for imaging and localization.
• Subpart E (§35.300) — unsealed material requiring a written directive (therapies such as I-131, Lu-177 DOTATATE, Lu-177 PSMA, and Ra-223).
• Subpart F (§35.400) — manual brachytherapy with sealed sources.
• Subpart H (§35.600) — remote afterloaders, teletherapy, and gamma stereotactic units.

When a new use does not fit any of these, Subpart K (§35.1000) is the catch-all. It is not a loophole; it is a deliberate mechanism that lets the NRC apply tailored safety conditions to a use it has not yet written a dedicated rule for. ^{1, 2} For the broader licensing picture, see the NRC radioactive material license guide and NRC medical license amendments.

Where 35.1000 sits among the subparts

The distinction is substantive. A Lu-177 DOTATATE program is licensed under §35.300 as an unsealed radiopharmaceutical therapy; a yttrium-90 microsphere program for the same facility is licensed under §35.1000, because microspheres are a different kind of source presenting different hazards. ^{1, 3}

Key Technical Principles

Why microspheres need their own pathway

Yttrium-90 microspheres are the archetypal 35.1000 use. They are millions of tiny glass or resin particles, each carrying Y-90, delivered through a catheter into the hepatic arterial supply so that they lodge in the tumor microvasculature. That is neither a hand-placed sealed source (Subpart F) nor a freely distributed unsealed radiopharmaceutical (Subpart E). Their small size, large number, and intra-arterial route call for radiation safety considerations beyond manual brachytherapy, which is exactly why the NRC placed them in Subpart K with device-specific guidance. ^{2, 5}

Practical consequences flow from this classification. For example, routine sealed-source leak testing is not required for Y-90 microspheres, because the criteria of 35.67 make leak testing impractical given the particles' size and number — a condition spelled out in the licensing guidance rather than left to the general sealed-source rules. ^{2, 11}

The physics the license has to account for

Y-90 is a pure beta emitter with a high maximum energy and a soft-tissue range on the order of a centimeter, which is why microsphere therapy delivers an intense, locally confined absorbed dose to the liver target. The planned absorbed dose is tied directly to the administered activity and the treated mass. For glass microspheres, the manufacturer's dose model assumes complete local absorption and uniform distribution: ⁷

The constant follows from Y-90's physics — a mean beta energy of about 0.9367 MeV and a physical half-life of 64.1 hours — so that complete decay of 1 GBq uniformly distributed in 1 kg of tissue deposits roughly 50 Gy:

Worked example. Delivering 3 GBq of glass microspheres to a 1500 g liver target region gives a planned absorbed dose of:

A licensee's program has to be built around getting that activity-and-mass calculation right, documenting it, and handling the material safely — which is what the 35.1000 radiation safety conditions are designed to ensure. ^{2, 7, 10} For the shielding and contamination side of emerging therapies, see RPT shielding for Lu-177, Ra-223, and Ac-225.

The approval pathway

A facility cannot simply start a 35.1000 use. The sequence is: ^{1, 2, 4}

1. Identify the use and its guidance. Find the NRC's use-specific 35.1000 licensing guidance (for example, the guidance for yttrium-90 microsphere devices).
2. Prepare the amendment under 10 CFR 35.12. Submit the application for a license amendment with the radiation safety program, procedures, and training and experience documentation.
3. Address radiation safety conditions. Handling, surveys, contamination and spill response, waste, emergency procedures, and device-specific requirements.
4. Receive written NRC approval. Use may begin only after the NRC issues the amended license with its specific conditions.

Clinical Impact

For the facility, 35.1000 is the difference between legally offering an emerging therapy and not. A hospital that wants to start yttrium-90 radioembolization, add a new microsphere product, or bring on an emerging alpha- or beta-emitting device cannot do so under its existing authorizations; it needs the 35.1000 amendment first. Treating a patient before the amendment is in place is a licensing violation, not a paperwork technicality.

The classification also shapes day-to-day operations:

• Authorized users are credentialed under the use-specific training and experience criteria, often including manufacturer device training, rather than a generic subpart.
• Procedures must be written from device guidance, because there is frequently no established department template for a newer modality.
• Records and written directives follow the Part 35 framework, so the medical physicist's dosimetry and documentation are integral to a defensible program.

Because these therapies are high-dose and locally intense, the safety stakes are real: the program has to ensure the right activity reaches the right target, that staff and the public are protected during delivery and recovery, and that the facility can defend the administration during inspection. For how these pieces fit into broader medical-use recordkeeping, see NRC Part 35 recordkeeping requirements and written directives in nuclear medicine.

Practical Optimization Tips

1. Start from the use-specific guidance

Every 35.1000 use has its own NRC licensing guidance that states the radiation safety program elements and training and experience criteria. Build the amendment from that document rather than from a generic Part 35 template. ^{2, 5}

2. Map the training and experience early

Confirm which individuals will be authorized users and whether they meet the use-specific criteria, including any manufacturer device training. Gaps in training and experience are a common reason amendments stall. ^{2, 6}

3. Write device-specific procedures

Handling, administration, surveys, contamination and spill response, and waste procedures should reflect the actual device and workflow — a catheter-delivered microsphere therapy is not a vial-and-syringe unsealed therapy.

4. Coordinate the amendment as a team

The RSO, authorized user, authorized medical physicist, and often the manufacturer all contribute. Assign ownership of each application section and track the submission.

5. Verify the regulating authority

Because 35.1000 is Compatibility Category D, confirm whether the NRC or your Agreement State issues your license, and follow that authority's version of the requirements. ²

6. Keep dosimetry and records defensible

Tie the planned activity-and-mass calculation, written directive, and administration records together so the treatment can be reconstructed and defended during inspection. ^{1, 10}

Common pitfalls to avoid

• Assuming an existing authorization covers a new modality. A §35.300 or §35.400 license does not authorize a §35.1000 use.
• Treating before the amendment is issued. Written NRC approval must precede the first administration.
• Copying another therapy's procedures. Microsphere and intravascular brachytherapy workflows differ from conventional therapies.
• Overlooking Agreement State differences. Category D means the state's approach may differ from the NRC's.
• Under-documenting training. Missing device-specific training records are a frequent deficiency.

Regulatory Considerations

A 35.1000 program must align the use-specific guidance with the rest of the Part 35 and Part 20 framework. The emerging use does not get a pass on the fundamentals: occupational and public dose limits, surveys, waste, and recordkeeping still apply. ^{1, 9}

Key frameworks to reference:

• 10 CFR Part 35, Subpart K (§35.1000) — the authority for other medical uses and the requirement for written NRC approval. ¹
• 10 CFR 35.12 — the application and amendment process a facility uses to request the authorization. ³
• NUREG-1556, Volume 9, Revision 3 — the NRC's consolidated program-specific guidance for medical-use licenses, the backdrop for any amendment. ⁴
• NRC use-specific 35.1000 licensing guidance — the operative radiation safety and training criteria for each approved use, such as yttrium-90 microsphere devices. ^{2, 5}
• 10 CFR Part 20 — the underlying standards for protection against radiation that set dose limits and survey expectations. ⁹

Jurisdiction note: byproduct material for medical use is regulated by the NRC or the equivalent Agreement State program. Of the states DRPS serves, Florida, Maryland, Virginia, California, Nevada, Pennsylvania, New York, and New Jersey are NRC Agreement States that administer their own medical-use rules, while Washington, DC and Delaware are regulated directly by the NRC. Because 35.1000 is Compatibility Category D, Agreement State requirements for emerging uses may differ, so confirm your authority before submitting. ^{2, 9} Connect the amendment work to radioactive material license support and RSO program guidance.

Frequently Asked Questions (FAQs)

What is 10 CFR 35.1000?

Section 35.1000 is the part of NRC's medical-use rule (Subpart K) that covers "other medical uses of byproduct material or radiation from byproduct material" — uses that are not specifically addressed in the standard subparts for imaging, unsealed therapy, manual brachytherapy, or remote afterloaders. A licensee may use material for such a use only after receiving written approval from the NRC in a license or license amendment, under the radiation safety conditions the Commission sets.

Why do Y-90 microspheres fall under 35.1000 instead of the brachytherapy subpart?

Yttrium-90 microspheres have properties that go beyond manual brachytherapy under Subpart F: they are delivered as large numbers of tiny particles through the hepatic arterial system rather than as discrete sealed sources placed and retrieved by hand. Because their size, number, and route of administration require radiation safety measures beyond Subpart F, the NRC licenses them under 35.1000 with device-specific guidance.

How does a facility get authorized for a 35.1000 use?

The facility submits a license amendment request under 10 CFR 35.12, addressing the radiation safety program and the training and experience criteria in the NRC's use-specific 35.1000 licensing guidance. The use cannot begin until the NRC issues the written approval in the amended license. The RSO, authorized user, and medical physicist typically prepare the procedures, training records, and device-specific documentation together.

What training and experience do authorized users need for a 35.1000 use?

Training and experience for a 35.1000 use are defined in the NRC's use-specific licensing guidance rather than by a single Part 35 subpart. For device-based uses such as Y-90 microspheres, this generally includes the broad classroom and laboratory training in radiation safety plus manufacturer-provided, device-specific training on the particular product and delivery system. The exact criteria are specified in the guidance for each use.

Do Agreement States follow 35.1000?

Section 35.1000 is assigned NRC Compatibility Category D, which means Agreement States are not required to adopt it verbatim. In practice, Agreement States administer their own medical-use programs and typically develop equivalent approaches for emerging uses. A facility must confirm whether the NRC or its Agreement State regulates its license and follow that authority's requirements.

Is a written directive required for 35.1000 therapies?

For therapeutic 35.1000 uses such as microsphere brachytherapy, the license conditions and NRC guidance apply written-directive and patient-specific documentation requirements consistent with the rest of Part 35. The authorized user prescribes the treatment, and the medical physicist supports the dosimetry and the records that make the administration defensible.

What is the RSO's role in adding a 35.1000 use?

The radiation safety officer coordinates the license amendment, builds the use-specific radiation safety procedures (handling, surveys, spill and contamination response, waste, and emergency plans), ensures authorized-user and staff training is documented, and maintains the records the NRC expects. Because these are newer modalities, the RSO and medical physicist often develop procedures from device guidance rather than from an established department template.

Key Takeaways

• 35.1000 is the catch-all for other medical uses. Subpart K covers modalities the standard Part 35 subparts do not address.
• Written NRC approval comes first. A license amendment under 10 CFR 35.12 must be issued before the first administration.
• Classification is substantive. Y-90 microspheres are licensed under 35.1000, not the brachytherapy subpart, because of their size, number, and route.
• Training and experience are use-specific. Authorized-user criteria come from the NRC's per-use guidance, often including manufacturer device training.
• Agreement States may differ. Section 35.1000 is Compatibility Category D, so confirm your regulator and its requirements.
• The fundamentals still apply. Part 20 dose limits, surveys, waste, written directives, and recordkeeping all carry over to emerging uses.

Conclusion

Section 35.1000 is the NRC's answer to a permanent problem: medicine innovates faster than rulemaking. Rather than freeze out new therapies or wait years for dedicated regulations, Subpart K lets the NRC license emerging uses case by case, with safety conditions tailored to each modality and written approval required before any patient is treated.

For the facility, that makes 35.1000 a gateway rather than an obstacle — but only for programs that do the work: start from the use-specific guidance, meet the training and experience criteria, write device-specific procedures, and secure the amendment before treating. The RSO and medical physicist are central to getting there, turning device guidance into a defensible radiation safety program that lets the facility offer the newest therapies safely and legally.

How DRPS Can Help

Diagnostic Radiation Physics Services helps facilities add emerging therapies to their licenses the right way. For 35.1000 uses, this includes radioactive material license support and amendment preparation, radiation safety procedure development, training and experience review, RSO program guidance, and medical physics consulting aligned with NRC and Agreement State requirements.

DRPS supports facilities across our service locations, including Florida, Maryland, Virginia, Washington DC, California, Nevada, New York, Pennsylvania, New Jersey, and Delaware. A well-prepared amendment is what turns an emerging therapy into a service your patients can actually receive.

Related Resources

• The NRC radioactive material license guide
• NRC medical license amendments
• NRC Part 35 recordkeeping requirements
• Written directives in nuclear medicine
• RPT shielding for Lu-177, Ra-223, and Ac-225
• Qualified medical physicist credentials and standards
• Radioactive material license support
• Radiation Safety Officer consulting

References

1. U.S. Nuclear Regulatory Commission. 10 CFR Part 35, Subpart K, §35.1000: Other Medical Uses of Byproduct Material or Radiation From Byproduct Material. ecfr.gov
2. U.S. Nuclear Regulatory Commission. Medical Uses Licensed Under 10 CFR 35.1000 (Emerging Technologies) — Licensing Guidance. nrc.gov
3. U.S. Nuclear Regulatory Commission. 10 CFR 35.12: Application for License, Amendment, or Renewal. ecfr.gov
4. U.S. Nuclear Regulatory Commission. NUREG-1556, Volume 9, Revision 3: Consolidated Guidance About Materials Licenses — Program-Specific Guidance About Medical Use Licenses. 2019. nrc.gov
5. U.S. Nuclear Regulatory Commission. Licensing Guidance for Yttrium-90 Microsphere Brachytherapy Sources and Devices. nrc.gov
6. U.S. Nuclear Regulatory Commission. 10 CFR 35.190, 35.290, 35.390 and related training and experience provisions. ecfr.gov
7. Boston Scientific. TheraSphere Yttrium-90 Glass Microspheres Instructions for Use (absorbed dose calculation). bostonscientific.com
8. International Commission on Radiological Protection. ICRP Publication 140: Radiological Protection in Therapy with Radiopharmaceuticals. Annals of the ICRP. 2019;48(1). icrp.org
9. U.S. Nuclear Regulatory Commission. 10 CFR Part 20: Standards for Protection Against Radiation. ecfr.gov
10. Kao YH. Rapid predictive dosimetry for radioembolization. Asia Oceania Journal of Nuclear Medicine & Biology. 2024;12(1):35-36. doi:10.22038/AOJNMB.2023.74023.1514. PubMed
11. U.S. Nuclear Regulatory Commission. 10 CFR 35.67: Requirements for Possession of Sealed Sources and Brachytherapy Sources (leak testing). ecfr.gov