7.2 DEA Registration and Forms 222, 106, 41

Why the form number is the exam answer

Quick Answer: Pharmacies and practitioners register on DEA Form 224 and renew on 224a. Schedule I/II acquisition uses single-sheet Form 222 or CSOS; a power of attorney (21 CFR 1305.05) lets named staff sign. Theft or significant loss → written notice to the DEA Field Division within one business day, then Form 106 within 45 days (21 CFR 1301.76(b)). Destruction of registrant stock → Form 41 or a reverse distributor (who issues a 222 for CII). Connecticut’s own CS practitioner registration is a separate credential; it does not replace DEA.

NABP 4.1 still tests whether you grab 222, 106, or 41. Grabbing the wrong form is a scored miss even if you later recite Connecticut’s three-year record rule. Full 222 workflow, invoices, and DSCSA paperwork live in Chapter 15. This section is identity, execution, and which form fires.

Who must hold a DEA registration

21 U.S.C. § 822 and 21 CFR 1301.13 require every person who manufactures, distributes, reverse-distributes, dispenses, imports, exports, or conducts research with controlled substances to obtain a DEA registration for that business activity. For the MPJE bench:

• Retail pharmacy — dispenses to patients. This is the store’s registration, not the staff pharmacist’s personal 224.
• Hospital/clinic — institutional practitioner registration covering the registered location.
• Practitioner — physician, dentist, veterinarian, or other individual practitioner authorized by state law to prescribe, administer, or dispense.
• Mid-level practitioner (MLP) — nurse practitioner, physician assistant, and similar roles if Connecticut law grants CS authority. DEA will not outrun the state license. MLP applications must include the state credential (and a supervisory agreement if Connecticut requires one for that role).
• Teaching institution — a narrower 224 category the exam rarely uses except as a distractor.

New applications for those groups are DEA Form 224. Renewals are DEA Form 224a, generally every three years. Manufacturers, distributors, researchers, importers, and exporters use 225/225a. Narcotic treatment programs use 363/363a. Do not put a community pharmacy on a 225.

21 CFR 1301.12(a) requires a separate registration at each principal place of business or professional practice where controlled substances are manufactured, distributed, or dispensed. A second storefront is a second 224. A practitioner who stores and dispenses at an office needs a registration at that office. Using a home address makes the home a controlled premises subject to inspection.

Connecticut overlays a Controlled Substance Registration for Practitioners (DCP). That state credential is not a DEA number and does not let a Hartford clinic skip Form 224. Who may prescribe in Connecticut, and how the state CS registration interacts with APRNs and PAs, is Chapter 8.

Form 222 and CSOS — how Schedule I and II move

21 CFR Part 1305 requires a DEA Form 222 or its electronic equivalent for each distribution of a Schedule I or II substance (with listed exceptions). CIII–V move on ordinary invoices; they do not ride a 222.

DEA replaced the historic triplicate 222 with a single-sheet form. As of October 30, 2021, triplicate forms are no longer used (21 CFR 1305.20(a)). Unused triplicates go back to DEA Registration in Springfield, Virginia. A 2026 technical amendment cleaned leftover triplicate language; the current process is single-sheet only.

Single-sheet execution (21 CFR 1305.12–1305.13):

• The purchaser prepares the form with a typewriter, computer printer, pen, or indelible pencil; one item per line; no alteration that changes the order.
• The purchaser makes a copy of the original (paper or electronic) for its records, then sends the original to the supplier.
• The supplier ships only to the purchaser and the location printed by DEA on the form, records containers furnished and the ship date on the original, and keeps the original. A supplier not reporting to ARCOS also forwards a copy to DEA at month-end.
• The purchaser records containers received and dates received on its copy.
• An order is valid 60 days from execution; partial shipments are allowed within that window.

CSOS (Controlled Substance Ordering System) is the electronic 222 (21 CFR Part 1305 Subpart C and Part 1311). Digitally signed electronic orders do not need a supporting paper 222. CSOS can order any schedule the registrant is authorized to handle, which is why a buyer may use CSOS for CII and CIII–V in one session. Lost paper 222s and voided electronic orders have their own Part 1305 procedures — Chapter 15.

Power of attorney

Only the registrant (or a person with a valid power of attorney) may execute a 222 or CSOS order. 21 CFR 1305.05 lets the registrant authorize one or more individuals, whether or not they work at the registered location, by executing a POA for each person. Keep the POA with the 222 file for as long as any order the attorney signed must be kept.

Who signs the POA matters. After the 2019 single-sheet rule, and as confirmed by DEA’s March 20, 2026 technical amendment, the POA is executed by the registrant if an individual; a partner if a partnership; or an officer if a corporation or similar entity. The person who merely signed the last Form 224 is not, by that fact alone, authorized to issue or revoke a 222 POA. A staff pharmacist signs 222s only with a current POA — not because “I am the PIC.”

Form 106 — theft and significant loss

21 CFR 1301.76(b) (pharmacies and other practitioners) requires two steps after theft or significant loss of controlled substances:

1. Notify the DEA Field Division Office in writing within one business day of discovery.
2. File a complete and accurate DEA Form 106 through DEA’s Diversion Control secure network (Theft/Loss Reporting Online) within 45 days after discovery.

“Significant” is not a tablet count. The regulation lists factors: quantity relative to the business, the specific substances, whether loss maps to a person or process, a pattern of losses, diversion attractiveness, and local trends. A bottle of 100 oxycodone 30 mg missing from a community safe is significant. A single alprazolam 0.25 mg that fell under a counting tray and was recovered before closing may not be — document the investigation either way. Report even if the drugs are later recovered or the thief is identified. In-transit losses follow the party that contracted the carrier (1301.76(d) for central-fill arrangements).

Connecticut separately requires reporting of loss, theft, or unauthorized destruction discovered on perpetual-CII reconciliation within 72 hours to the Commissioner (CGS § 20-633e(c); § 21a-262). File both. Details of the state report sit with inventories in 7.4 and Chapter 15.

Form 41, reverse distributors, and what not to do

21 CFR Part 1317 is how a registrant disposes of its own controlled-substance inventory (expired, damaged, unwanted). A pharmacy typically:

• Transfers the stock to a DEA-registered reverse distributor. The reverse distributor issues a Form 222 (or CSOS) to the pharmacy for Schedule II. The pharmacy keeps a distribution record for III–V (name, form, strength, quantity, date). The reverse distributor destroys the drugs and documents destruction on DEA Form 41 (21 CFR 1304.21(e)), generally within 30 calendar days of receipt (21 CFR 1317.15(d)).
• Or destroys on-site by a method that renders the substance non-retrievable (21 CFR 1317.90, 1317.95) and records that destruction on Form 41, with two witnesses when DEA’s pharmacist-manual guidance is followed.

Non-recoverable breakage or spillage (a smashed CII vial observed by staff, nothing to send back) is not a Form 106 theft if there was no diversion. DEA’s position is to record it on Form 41 with two witnesses who can testify to the spill. Recoverable spill material still has to be disposed under Part 1317.

Do not flush registrant inventory, toss it in municipal trash, or pour it into the pharmacy’s take-back kiosk. A kiosk is for ultimate-user returns by an authorized collector; it is not the store’s reverse-distribution method. Patient take-back operations are Chapter 11.

Scenario: Saturday shortage, Monday form

A Stamford PIC opens Saturday and the CII safe is short one sealed 100-count bottle of oxycodone 15 mg that was on Friday’s perpetual log. Staff find no spill. The PIC emails the DEA New England Field Division the same business day (Monday, if Saturday is not a DEA business day — count business days), starts the internal count, and files Form 106 through TLR once the investigation supports a complete count — inside 45 days, not “when we have time after Thanksgiving.” The PIC also notifies DCP of the CII loss under Connecticut’s 72-hour rule. Expired hydromorphone still in the safe is not listed on the 106; it is transferred to a reverse distributor on a 222 the reverse distributor issues, and the reverse distributor files Form 41. Using a triplicate 222 “we found in the basement” is invalid.

CT may be stricter; more-restrictive wins.

Official anchors

• DEA registration — Forms 224/224a.
• 21 CFR Part 1305 — 222, CSOS, power of attorney.
• 21 CFR 1305.13 — single-sheet filling procedure.
• 21 CFR 1301.76 — pharmacy theft/loss; Form 106.
• DEA theft/loss reporting.
• 21 CFR Part 1317 — disposal; reverse distributors; Form 41 linkage in 1304.21(e).