21 CFR Part 212

This glossary term is part of the SG Systems Global regulatory & operations guide library.

Updated January 2026 • 21 CFR Part 212, PET drug cGMP, hot cell workflow, EOS anchoring, decay-corrected activity, radionuclidic identity/purity, dose calibrator controls, sterility pending release, beyond-use time (BUT), radioactive waste logs, audit-ready records • PET & Radiopharmaceutical Manufacturing (cyclotron sites, radiochemistry labs, nuclear pharmacies, hospital PET production)

21 CFR Part 212 is the FDA’s current Good Manufacturing Practice (cGMP) regulation written specifically for positron emission tomography (PET) drugs. Operationally, it is the rule set that turns “we produced a PET tracer” into “we can prove this lot was made under control, met defined quality expectations, was released under documented authority, and is supported by defensible records—despite the reality of short half-life products and compressed timelines.” Part 212 is built for PET reality: time-driven manufacturing, rapid release sequencing, and tight control of identity, strength, quality, and purity while the clock is running.

Part 212 is not “a paperwork regulation.” It is a control model for a fast, high-consequence manufacturing environment. It forces discipline around defined procedures, controlled facilities and equipment, production controls inside hot cell workflows, laboratory controls, and recordkeeping that does not rely on reconstruction. It also forces you to be honest about time: you must define and capture End-of-Synthesis Time (EOS), manage decay-corrected activity and measurement credibility, and enforce Beyond-Use Time (BUT) so time pressure doesn’t become a loophole.

Tell it like it is: most PET operations don’t fail because they lack “a quality manual.” They fail because controls don’t hold under speed. EOS gets captured inconsistently, activity math depends on who is working, instruments are used while out of status, pending sterility is treated as normal release, and waste handling becomes a side log nobody trusts. Part 212 is where that informal model collapses—because the regulation expects the same thing inspectors expect: consistent execution, controlled exceptions, and records that stand on their own.

“If your operating model depends on ‘we’ll sort it out after the run,’ Part 212 is where that model breaks.”

1) What people mean when they cite 21 CFR Part 212

When someone says “we need to comply with Part 212,” they usually mean one of three practical realities:

First: you’re operating under short half-life constraints, and your current controls depend on heroics. Part 212 is where “heroics” becomes a compliance liability because work is fast, access is constrained, and records can’t be reconstructed credibly after the fact.

Second: you’re trying to become inspection-ready. Part 212 is full of “show me” moments: show me controlled hot cell execution, show me the time anchor (EOS), show me activity measurement credibility (dose calibrator checks), show me your identity and purity basis, show me how you handle sterility timing, show me beyond-use time enforcement, show me how you handle waste. If your evidence requires a spreadsheet rescue, you are already losing.

Third: something drifted: yield dropped, impurity signals increased, an instrument was out of status, sterility results created a response event, or you found a time-anchor inconsistency. Under stress, weak systems collapse because they can’t link “what happened” to “who approved it” to “what was shipped” to “what we did about it.”

Tell it like it is: Part 212 forces PET operations to behave like controlled manufacturing—not like a high-speed lab with good intentions.

2) Scope map: what Part 212 actually controls

Part 212 is best understood as a control map that respects PET reality: time is central, activity measurement is central, and hot cell execution is central.

The practical takeaway: Part 212 is not a slower version of Part 211. It is tailored for PET, where speed and radiation constraints demand even tighter operational discipline.

3) Who Part 212 applies to (and why PET reality still requires discipline)

Part 212 applies to PET drug production and related quality operations. The misconception is “PET is special, so rules are softer.” PET is special, but the control expectation is not softer—it’s more explicit about how to remain controlled under time pressure.

Common operating models that still need Part 212-grade control include:

• Cyclotron + radiochemistry facilities: integrated production with time-critical distribution.
• Nuclear pharmacies: dose preparation, labeling, handoffs, and custody controls.
• Hospital PET production: on-site workflow where “clinical urgency” can pressure controls.

Tell it like it is: PET speed is not an excuse. It’s a risk factor that must be engineered out through workflow gates and evidence capture.

4) Quality authority: release posture under short timelines

Part 212 still expects quality authority, even when release decisions are compressed. The key is to design a release posture that is executable:

• define what must be complete before release vs what may be pending under controlled rules,
• document approval authority (who can release, who can approve exceptions),
• enforce holds so “late” never becomes “ship anyway.”

Tell it like it is: if quality can be bypassed because the patient is waiting, you don’t have quality authority—you have wishful thinking.

5) Hot cell execution as the center of gravity

Part 212 is where hot cell execution becomes the manufacturing record. Your Hot Cell Workflow must be stepwise, stateful, and evidence-driven:

• no-skip sequencing,
• controlled transfers and connections,
• intervention governance,
• cleaning and turnaround verification,
• component identity and equipment eligibility gates.

Tell it like it is: if the hot cell workflow is “what people remember,” you don’t have control—you have a high-speed improvisation system.

6) EOS as the time anchor: make time non-negotiable

Time is a quality boundary in PET operations. Part 212 effectiveness depends on a stable time anchor. End-of-Synthesis Time (EOS) should be defined as one unambiguous event and captured as a workflow step.

Tell it like it is: multiple EOS definitions create multiple “truths,” and multiple truths destroy compliance. Fix EOS as one truth, protect it, and use it everywhere.

7) Activity credibility: dose calibrators + decay correction

Part 212 expects activity statements to be credible. That requires two non-negotiable controls:

• measurement system credibility via Dose Calibrator Checks (with enforced lockouts when overdue/failing), and
• governed calculations via Decay-Corrected Activity anchored to defined reference times.

Tell it like it is: decay correction doesn’t fix bad measurement. It only makes bad measurement look precise. That’s why calibrator checks and time anchors must be enforced together.

8) Radionuclidic identity and purity as release-critical controls

PET operations must control what radionuclide is present and what impurities exist. That’s why Part 212 aligns naturally to:

• Radionuclidic Identity Test (prove what it is), and
• Radionuclidic Purity Limit (control what else is present).

Yield and drift signals matter too (see Radiochemical Yield). Tell it like it is: if identity/purity is assumed because “it’s always fine,” you’re waiting for the day it isn’t.

9) Sterility testing and “sterility release pending” governance

PET time constraints create pressure around sterility testing. If your model allows conditional distribution while sterility is pending, it must be governed like a real release state (see Sterility Release Pending):

• explicit prerequisites before pending release,
• approved scope constraints (who can receive pending product),
• unit-level traceability,
• predefined failure response when results fail.

Tell it like it is: pending sterility without a failure playbook is reckless. If you can’t contact every recipient fast, you can’t operate pending release responsibly.

10) Beyond-use time (BUT) gating across handoffs

Part 212 reality is that product moves through handoffs while decaying. Beyond-Use Time must be enforced as a hard gate at release, pick, dispatch, and (where applicable) receipt/use. Warnings are not enough under patient pressure.

Tell it like it is: if the system allows “use it anyway,” people will. BUT must be enforced by hard stops, not polite reminders.

11) Recordkeeping: audit trails, edits, and “no reconstruction” posture

Part 212 recordkeeping must be credible under speed. That means:

• unique user identities and role-based permissions,
• audit trails for any edits with reason-for-change,
• protected time anchors (EOS),
• system-derived calculations (not spreadsheet math),
• fast retrieval for inspection or incident response.

Tell it like it is: if your PET records depend on after-the-fact reconstruction, your evidence is weak by design. Build records as a byproduct of execution.

12) Radioactive waste control as part of the batch story

Waste handling is not separate from manufacturing control. A controlled waste program (see Radioactive Waste Log) proves you controlled containers, locations, decay timing, and disposition—without orphan containers and unlogged moves.

Tell it like it is: waste chaos is a leading indicator of workflow discipline collapse. If waste isn’t controlled, other things aren’t either.

13) Deviations, OOS/OOT, and CAPA under PET speed

Part 212 does not require perfection. It requires control. When something drifts—yield, purity, timing, instrument status—you must capture it as an event, investigate it, and prevent recurrence:

• Deviation Investigation for abnormal execution conditions,
• OOS discipline for failed results,
• OOT posture for drift signals,
• CAPA when recurrence risk is real.

Tell it like it is: “we were late” is not a root cause. PET speed is expected; weak controls under speed are not.

14) Inspection readiness: how Part 212 failures get found

Part 212 failures get found in predictable ways:

• time anchor inconsistency: EOS differs by record or by shift.
• instrument credibility gaps: calibrator checks missing/overdue; measurements still used.
• manual math drift: spreadsheets and edits create inconsistent activity statements.
• pending sterility scope creep: pending becomes normal release; response readiness is weak.
• BUT not enforced: expired doses can still be moved or used.
• waste disorder: unlabeled containers, unlogged moves, weak disposition proof.
• records not retrievable: evidence exists but can’t be produced quickly.

Tell it like it is: inspectors follow the evidence chain. If the chain breaks, you will feel it immediately.

15) Copy/paste Part 212 readiness scorecard

Use this as a practical self-assessment. If you can’t answer these cleanly, your Part 212 posture is fragile.

The goal isn’t “score high.” The goal is to replace reconstruction with workflow-native evidence.

16) Selection pitfalls: how Part 212 compliance gets faked

• EOS as a flexible idea. Multiple definitions create loopholes.
• Calibrator checks as “paperwork.” If out-of-status tools can still be used, control is fake.
• Spreadsheets as system-of-record. Manual math creates ungoverned calculation risk.
• Pending sterility as normal release. Scope creep without response readiness.
• BUT as a warning only. Warnings get ignored under patient pressure.
• Waste as “not QA.” Disorder here signals disorder everywhere.
• Records exist but aren’t retrievable. If you can’t produce them fast, they don’t protect you.

17) How this maps to V5 by SG Systems Global

V5 supports Part 212 outcomes by making PET controls executable: stepwise execution, time anchoring, status-based gating, governed quality events, and fast retrieval. Part 212 compliance is a systems property, not a policy property.

• V5 platform + products:
  V5 Solution Overview,
  Quality Management System (QMS),
  Manufacturing Execution System (MES),
  Warehouse Management System (WMS),
  V5 Connect (API).
• How it supports Part 212 control surfaces:
  MES captures stepwise hot cell execution, readiness gates, and EOS; QMS governs release states, deviations, CAPA, and audit trails; WMS enforces disposition and time-based movement controls; V5 Connect integrates instruments/LIMS/scheduling so status and evidence stay synchronized.

The point isn’t “software equals compliance.” The point is that Part 212 assumes you can create and retrieve defensible evidence as a byproduct of execution. V5 is designed to make that practical.

18) Extended FAQ

Q1. Is Part 212 just “documentation”?
No. Documentation is how you prove control, but Part 212 is fundamentally about whether PET manufacturing is actually controlled under time pressure: hot cell execution, time anchoring, activity credibility, identity/purity, and governed exceptions.

Q2. What’s the most common Part 212 failure pattern?
Time anchor inconsistency (EOS), combined with manual activity math and instrument status gaps. If time and measurement aren’t controlled, records become narratives.

Q3. Does sterility release pending mean “release anyway”?
No. It is a controlled conditional state with prerequisites, constrained scope, unit traceability, and a predefined failure response if sterility later fails.

Q4. What’s the fastest way to test if our Part 212 system is real?
Pick a lot and produce a complete package: hot cell execution record, EOS, dose calibrator status, decay correction inputs/outputs, identity/purity evidence, BUT gating evidence, sterility lifecycle status, distribution/recipient traceability, and waste disposition linkage. If you need spreadsheets to assemble truth, the posture is fragile.

Q5. Why does waste show up in Part 212 conversations?
Because waste handling reflects real control discipline: container identity, movement logging, decay/disposition evidence, and segregation. Disorder in waste management is often a leading indicator of broader workflow drift.

Related Reading
Build Part 212 as a time-and-evidence system: control execution with Hot Cell Workflow, anchor time with EOS, keep activity credible with Dose Calibrator Checks + Decay-Corrected Activity, enforce eligibility with BUT, and keep conditional distribution honest with Sterility Release Pending. Close the loop with disciplined waste control via Radioactive Waste Log.