2.1 Drug Enforcement Administration (DEA)

The DEA is a federal agency under the U.S. Department of Justice responsible for enforcing the Controlled Substances Act (CSA). It regulates the manufacturing, distribution, prescribing, and dispensing of controlled substances (Schedules I–V) to prevent diversion and abuse. Pharmacists must comply with DEA registration requirements, maintain controlled substance inventories, follow proper storage and recordkeeping, and report thefts or losses. For example, a community pharmacist dispensing oxycodone (Schedule II) must verify the prescriber’s DEA registration number, document dispensing records accurately, and ensure secure storage to remain compliant with federal law.

The Drug Enforcement Administration was established on July 1, 1973,[3] by Reorganization Plan No. 2 of 1973, signed by President Richard Nixon on July 28. It proposed the creation of a single federal agency to enforce the federal drug laws as well as consolidate and coordinate the government drug control activities. Congress accepted the proposal, as they were concerned with the growing availability of drugs. As a result, the Bureau of Narcotics and Dangerous Drugs  (BNDD), the Office of Drug Abuse Law Enforcement (ODALE); approximately 600 Special Agents of the Bureau of Customs, Customs Agency Service, and other federal offices merged to create the DEA.

The DEA is the primary federal agency charged with implementing and enforcing the Controlled Substances Act (CSA), which is Title II of a larger Federal Act called the Comprehensive Drug Abuse Prevention and Control Act of 1970. The DEA is responsible for drugs listed in the CSA's five drug Schedules, categories that rank drugs by their potential for harm, and whether they have a medical use. The CSA seeks to ensure legitimate access to controlled pharmaceuticals, while preventing illicit use of controlled drugs.

2.2 The Federal Controlled Substances Act (CSA)

The CSA (Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970, 21 U.S.C. §§ 801–971) regulates the manufacture, distribution, and dispensing of controlled substances to prevent abuse and diversion. It classifies drugs into schedules, sets recordkeeping, labeling, and security requirements, and provides penalties for violations.

Example: A pharmacist must comply with CSA requirements when dispensing oxycodone (Schedule II), maintaining accurate records, and storing it securely to prevent diversion.

Pharmacist’s Manual

The DEA publishes the Pharmacist’s Manual, which provides guidance for pharmacists on CSA compliance, dispensing requirements, recordkeeping, and security standards. It is an essential reference for understanding federal obligations.

Example: A pharmacist consulting the manual confirms that refills of Schedule III–V drugs are limited to five within six months.

CSA Definitions

The CSA defines terms such as “controlled substance,” “dispense,” “practitioner,” and “pharmacy” to clarify regulatory responsibilities (21 U.S.C. §802).

Example: “Dispense” includes the pharmacist’s final act of delivering a medication pursuant to a prescription; counting tablets alone does not constitute dispensing.

Protecting Patient Access to Emergency Medications Act of 2017

This act amended federal law to allow certain practitioners and pharmacies to dispense controlled substances in emergencies without a prescription under defined conditions.

Example: A pharmacist may dispense emergency doses of an opioid antagonist to a first responder in an overdose scenario.

Application of the CSA to Dispensing

To apply for a controlled substance registration, one must complete the appropriate application forms, provide necessary documentation, and pay any applicable fees.

Pharmacists must dispense controlled substances according to CSA rules, including valid prescriptions, recordkeeping, labeling, and security measures (21 CFR Part 1306).

Example: Dispensing a Schedule II opioid requires a written or electronic prescription signed by a DEA-registered prescriber; no refills are allowed.

Required Information for Labels of Controlled Substances

DEA requires controlled substance labels to include the pharmacy name, address, prescription number, patient name, drug name/strength, directions, and warning statements (21 CFR §1306.22).

Example: A pharmacist labels hydrocodone with patient info, dosage instructions, and “Caution: Federal law prohibits the transfer of this drug to any person other than the patient prescribed.”

United States Postal Service Mailing Requirements for Controlled Substances

Controlled substances may be mailed following DEA and USPS regulations, including secure packaging, labeling, and authorized sender/receiver verification (21 CFR §1317).

Example: A mail-order pharmacy ships a Schedule III in a sealed, labeled envelope using traceable shipping methods.

2.3 Controlled Substance Schedules

The CSA classifies drugs into five schedules (I–V) based on medical use, abuse potential, and dependence risk (21 U.S.C. §812).

Example: Fentanyl is Schedule II; its high abuse potential and accepted medical use dictate strict handling and prescribing rules.

Schedule I Controlled Substances

Schedule I substances have no accepted medical use and high abuse potential. They are illegal to prescribe or dispense in the U.S. (e.g., heroin, LSD).

Example: A pharmacist may not dispense Schedule I substances; only DEA-licensed research facilities can handle them.

Schedule II Controlled Substances

Schedule II drugs have accepted medical use but high abuse potential, no refills permitted, and strict documentation (e.g., oxycodone, morphine).

Example: A patient receives a written prescription for morphine; the pharmacist files it and dispenses only the exact quantity.

Schedule III Controlled Substances

Schedule III drugs have moderate abuse potential and accepted medical use. Refills limited to five within six months (e.g., hydrocodone combination products).

Example: A patient may refill a hydrocodone-acetaminophen prescription up to five times in six months.

Schedule IV Controlled Substances

Schedule IV drugs have lower abuse potential; prescriptions may be refilled up to five times in six months (e.g., alprazolam).

Example: A pharmacist verifies prescription refills and documents each dispensing of alprazolam.

Schedule V Controlled Substances

Schedule V drugs have the lowest abuse potential, often available OTC in some states (e.g., cough syrups with codeine).

Example: A pharmacist may dispense a Schedule V cough syrup without a new prescription under state law limits.

Rescheduling

The DEA can add, remove, or transfer drugs between schedules based on abuse, safety, and medical use evidence (21 U.S.C. §811).

Example: In 2014, hydrocodone combination products were moved from Schedule III to II, tightening dispensing and prescribing rules.

Registration

Pharmacies, prescribers, and manufacturers must register with the DEA to handle controlled substances (21 U.S.C. §822).

Example: A community pharmacy completes DEA Form 224 to legally dispense controlled drugs.

To register a new pharmacy with the DEA, one must complete the application process, which includes submitting the required forms and ensuring compliance with controlled substance regulations.

Steps for DEA Registration

• Determine Eligibility: Ensure that your pharmacy meets the necessary requirements to register with the DEA. This includes having a valid state pharmacy license and complying with federal and state laws regarding controlled substances.
• Complete the Application: One can apply for a new DEA registration online or via a paper application. The application form is available on the DEA's official website. For online applications, visit the DEA Diversion Control Division's registration page.
• Submit Required Information: The application will require details such as the pharmacy's name, address, and the type of services provided. Ensure that all information is accurate and complete to avoid delays in processing.
• Pay the Registration Fee: There is a fee associated with the registration process, which varies depending on the type of registration (e.g., retail pharmacy, hospital, etc.). Make sure to check the current fee structure on the DEA website.

• Await Processing: After submission, the DEA will process your application. One may receive electronic notifications regarding the status of your application. Ensure that the email address associated with your registration is current and active.

• Receive Your DEA Registration: Once approved, you will receive your DEA registration certificate, which allows your pharmacy to handle controlled substances legally.

Important Considerations

• Separate Registrations: Each pharmacy location must have its own DEA registration. If you plan to operate multiple locations, you will need to register each one separately.

• Compliance: Ensure ongoing compliance with DEA regulations, including proper record keeping and reporting of controlled substances. or more detailed information and to access the application form, visit the DEA's official registration page. This will guide you through the necessary steps to successfully register your new pharmacy with the DEA.

New Pharmacy Registrations

New pharmacies apply to the DEA using Form 224, demonstrating compliance with security, recordkeeping, and personnel requirements.

Example: A new retail pharmacy receives DEA approval before ordering Schedule II opioids.

DEA Form 224 is an application for registration under the Controlled Substances Act. It is primarily used by pharmacies and other entities to apply for a new registration with the DEA to dispense controlled substances. This form is essential for any pharmacy before beginning operations involving controlled substances.

Persons Required to Be Registered

Pharmacists, prescribers, manufacturers, distributors, researchers, and certain institutional staff must hold DEA registration to handle controlled substances.

Example: A hospital pharmacist managing Schedule II medications must be registered with the DEA.

Separate Registration for Separate Locations

DEA regulations require distinct registrations for each physical site handling-controlled substances.

Example: A pharmacy chain operating multiple stores must register each location separately.

On-Line Pharmacies

Internet pharmacies must comply with DEA regulations and maintain verification and reporting for controlled substances dispensed online.

Example: A telepharmacy verifies prescriber credentials before shipping Schedule III medications.

DEA Number

The DEA issues a unique number to registered practitioners and pharmacies for controlled substance prescribing and dispensing verification.

DEA numbers should be verified using the following procedure:

• Be sure it has 2 letters and 7 numbers (e.g., AA1234567)
• Add the first, third and fifth digits and record as SUM 1
• Add the second, fourth and sixth digits. Multiply the results by 2. Record as SUM 2
• Add SUM 1 and SUM 2 to obtain SUM 3
• The seventh digit will be the second digit of SUM3 for validation. If not, the DEA number is not valid.

Example: Pharmacists verify a prescriber’s DEA number before filling a Schedule II prescription.

Renewal of Pharmacy Registration

DEA registrations must be renewed every three years using Form 224a. Failure to renew results in termination of registration.

Example: A pharmacy renews its DEA registration online before expiration to continue dispensing controlled substances legally

Prescriptions

A prescription is a lawful order from a practitioner for a patient-specific medication. Prescriptions for controlled substances must comply with DEA regulations, state law, and professional standards. Proper documentation, validity, and patient-specific instructions ensure safe and legal dispensing.

Example: A physician writes a prescription for hydrocodone with patient information, directions, and DEA number.

Required Information for Prescriptions

DEA rules (21 CFR §1306.05) require the practitioner’s name, address, DEA number, patient’s name/address, drug name, strength, quantity, directions, and date of issuance.

Example: A pharmacist rejects a prescription missing the DEA number for a Schedule II opioid.

Persons Entitled to Issue Prescriptions

Only practitioners authorized by law (physicians, dentists, nurse practitioners, physician assistants) with a valid DEA registration may issue controlled substance prescriptions (21 U.S.C. §829).

Example: A dentist prescribes a Schedule III analgesic after a tooth extraction.

Purpose of Issue; Corresponding Responsibility

Controlled substance prescriptions must be issued for a legitimate medical purpose. Pharmacists share corresponding responsibility to verify validity (21 CFR §1306.04).

Example: A pharmacist questions an unusually high opioid dose and contacts the prescriber before dispensing.

Verification of Practitioner Registration by DEA Number

Pharmacists must verify the DEA number to confirm the prescriber is registered for the appropriate drug schedule.

Example: Checking DEA number AB1234567 for a Schedule II prescription before dispensing oxycodone. Is this legitimate?

Manner of Issuance

Prescriptions may be issued written, oral, electronic, or faxed following CSA rules.

Example: A physician faxes a Schedule II narcotic for hospice care to a pharmacy.

Specific Prescription Requirements for Schedule II Controlled Substances

Schedule II prescriptions must be written or electronic, signed by the prescriber, include no refills, and provide all required patient/prescriber info (21 CFR §1306.12).

Example: A patient receives a 30-day supply of morphine, no refills permitted; pharmacist logs prescription.

Specific Prescription Requirements for Schedules III, IV, and V Controlled Substances

These may be oral, written, or electronic and may be refilled up to five times in six months (21 CFR §1306.13).

Example: A patient receives a Schedule III hydrocodone combination product prescription with refills authorized.

Selected Exceptions Under the Controlled Substances Act

• Exceptions for Schedule II Facsimile Prescriptions - Faxed Schedule II prescriptions are allowed in hospice, LTCF, or for compounded sterile products. Example: Faxed oxycodone prescription sent from a hospice physician to a pharmacy.
• Emergency Dispensing - Schedule II drugs may be dispensed on oral emergency prescriptions with limited quantity, followed by a written prescription within seven days (21 CFR §1306.11). Example: Patient in severe pain receives an emergency phone-order for morphine.
• Electronic Prescription - Electronic prescribing is permitted if DEA-compliant software is used. Example: A physician sends a secure e-prescription for hydrocodone.

Faxed Schedule II prescriptions are allowed in hospice, LTCF, or for compounded sterile products. 

Example: Faxed oxycodone prescription sent from a hospice physician to a pharmacy.

Emergency Dispensing

Schedule II drugs may be dispensed on oral emergency prescriptions with limited quantity, followed by a written prescription within seven days (21 CFR §1306.11).

Example: Patient in severe pain receives an emergency phone-order for morphine.

Electronic Prescriptions

Electronic prescribing is permitted if DEA-compliant software is used.

Example: A physician sends a secure e-prescription for hydrocodone.

Nonprescription Dispensing

Schedule V substances may be dispensed OTC under state rules (21 U.S.C. §829).

Example: Cough syrup with codeine dispensed without a prescription to an adult with ID and log entry.

Ordering Schedules I and II Controlled Substances on DEA Form 222 is required for each order of Schedule I/II drugs (21 CFR §1305.03).

Example: A pharmacy orders morphine tablets using Form 222.

Tracking Receipt on DEA Form 222

Pharmacies must document receipt and reconcile order forms.

Example: Received morphine shipment is logged with date, quantity, and supplier.

Transfers

Controlled substances can only be transferred to DEA-registered entities.

Example: A hospital transfers excess Schedule III meds to another registered pharmacy.

Supplier Acceptance of DEA Form 222

Suppliers review accuracy before filling orders; incomplete forms are rejected.

Example: Wrong quantity on Form 222 requires correction.

Cancellation and Voiding an Official Order Form

Forms can be canceled by the purchaser or supplier and documented.

Example: Pharmacy voids Form 222 after order duplication.

Lost or Stolen Order Forms

Loss must be reported to the DEA immediately (21 CFR §1311).

Example: Missing Form 222 triggers DEA notification and investigation.

• All entities that prepare, handle, or distribute controlled substances must register with the DEA using DEA Form 224. The form is available online at https://www.deadiversion.usdoj.gov/drugreg/reg_apps/224/224_instruct.htm
• A purchaser must make a copy of the original DEA Form 222 for their records and submit the original to the supplier
• The form must include the name and address of the supplier, as well as the name and address of the purchaser
• When transferring controlled substances between laboratories, the receiving party must also have a DEA Form 222
• The DEA Form 106 is used to report the theft or loss of controlled substances. 
  Here are the key points:
• It must be completed electronically via the Theft/Loss Reporting Online (TLR) system
• Registrants must provide the National Drug Code numbers for the substances involved
• All forms must be submitted electronically; paper copies are no longer accepted
• Any person or facility registered with the DEA that experiences loss or theft of controlled substances is required to complete this form
• Refer to the DEA website for more detailed instructions.
• Title 21 Code of Federal Regulations; PART 1317 — DISPOSAL sets forth the rules for the delivery, collection, and destruction of damaged, expired, returned, recalled, unused, or otherwise unwanted controlled substances that are lawfully possessed by registrants (subpart A) and non-registrants (subpart B).
• Promptly destroy that controlled substance in accordance with https://www.ecfr.gov/current/title-21/chapter-II/part-1317/subpart-C using an on-site method of destruction;
• Promptly deliver the controlled substance to a reverse distributor's registered location by common or contract carrier pick-up or by reverse distributor pick-up at the registrant's registered location;
• DEA Form 41 shall include the names and signatures of the two employees who witnessed the destruction. 21 C.F.R. § 1317.95(d)

Ordering Schedules III-V Controlled Substances

No Form 222 needed; standard invoices and records suffice (21 CFR §1304).

Example: Ordering acetaminophen with codeine tablets through normal purchasing channels.

Electronic Ordering - Controlled Substance Ordering System (CSOS)

DEA-authorized electronic orders replace paper forms for Schedule I-II drugs.

The DEA Electronic Ordering System (CSOS) allows for secure electronic transmission of controlled substance orders without the need for the traditional paper DEA Form 222.

Benefits: CSOS reduces ordering errors, allows for more line items on a

single order, and speed up transactions, leading to cost savings.

Process: Users must enroll with the DEA to obtain a CSOS digital certificate, which is required for electronic orders.

Example: A pharmacy submits CSOS order for oxycodone via secure software.

Inventory: Initial Inventory

Pharmacies must take exact counts of all controlled substances on opening day.

Example: New pharmacy counts and logs all Schedule II–V drugs.

Biennial Inventory

Every two years, pharmacies must take a complete inventory (21 CFR §1304.11).

Example: Inventory includes Schedule II, III, IV, V drugs, with exact counts for Schedule II.

Newly Scheduled Controlled Substance Inventory

Substances newly classified as controlled must be inventoried on the effective date.

Example: Newly scheduled hydrocodone products are added to pharmacy inventory on Day 1 of scheduling.

Required Records

DEA regulations (21 CFR §1304.03) mandate that pharmacies maintain records of controlled substances’ receipt, dispensing, and inventory. These include invoices, DEA Form 222, prescriptions, and inventory logs.

Example: A pharmacist maintains paper/electronic records of all Schedule II-V drugs, ensuring compliance for DEA inspection.

Prescription Records

Prescriptions must be retained for two years (21 CFR §1304.04). Schedule II prescriptions require separate files; III–V may be kept together.

Example: Schedule II oxycodone prescriptions are filed separately, while hydrocodone combination prescriptions (Schedule III) are in a second file.

Electronic Prescriptions

Electronic prescriptions for controlled substances must be DEA-compliant, encrypted, and stored securely (21 CFR §1311).

Example: A pharmacy securely archives electronic Schedule II prescriptions for later reference and auditing.

Offsite Records

Pharmacies may store older records offsite with prior DEA notification; they must be retrievable within two business days (21 CFR §1311).

Example: A pharmacy stores prescriptions older than two years in an offsite secure facility.

Separate Records

Schedule II records must be kept separate from other prescriptions. Schedule III–V can be separate or centrally stored under specific rules (21 CFR §1304.04).

Example: Controlled substance prescriptions are filed by schedule for easy DEA inspection.

Records of Receipt and Dispersal

Pharmacies must document all controlled substance purchases and dispensing, including invoices and DEA Form 222 for Schedule I-II drugs (21 CFR §1304).

Example: When receiving morphine, the pharmacist logs quantity, supplier, and date; dispensed doses are recorded daily.

Security Requirements

Controlled substances must be stored in secure, locked cabinets or dispersed throughout non-controlled stock (21 CFR §1301.71).

Example: Schedule II narcotics are stored in a locked cabinet accessible only to authorized personnel.

Diversion Prevention

Pharmacies must implement policies and procedures to prevent theft or misuse (21 CFR §1301.71).

Example: Restricted access areas, background checks, and inventory reconciliation help prevent diversion of opioids.

The Prescription Drug Marketing Act of 1987 (PDMA)

PDMA regulates drug distribution, requiring proper labeling, pedigree, and prohibiting resale of samples to ensure safety and authenticity (21 U.S.C. §353).

Example: A pharmacy refuses to purchase discounted samples from an unlicensed wholesaler.

Employee Screening

DEA requires pharmacies to screen employees handling controlled substances for criminal history or substance abuse risk.

Example: A pharmacy conducts background checks and drug screening for all new pharmacy technicians.

Controlled Substance Theft or Significant Loss

The DEA mandates reporting theft or significant loss of controlled substances within one business day using DEA Form 106 (21 CFR §1301.76).

Example: A pharmacy discovers missing fentanyl patches and immediately files Form 106.

Controlled Substance Registrant Protection Act (CSRPA)

CSRPA (18 U.S.C. §670) provides federal penalties for robbery, burglary, or theft from pharmacies handling controlled substances.

Example: Armed robbery targeting oxycodone is prosecuted under federal law.

The Prescription Drug Marketing Act (PDMA) was signed into law on April 22, 1988, as a response to growing concerns about the safety of prescription drugs in the United States. The act aims to protect consumers by establishing safeguards in the drug distribution system and preventing the introduction of counterfeit, adulterated, misbranded, subpotent, or expired drugs into the market.

Key Provisions

• Reimportation Restrictions: The PDMA prohibits the reimportation of prescription drugs produced in the U.S., except for emergency medical care.

• Drug Samples: The act restricts the sale, purchase, or trade of prescription drug samples and requires that samples be distributed only to licensed practitioners upon written request.

• Authorized Distributors: Manufacturers must maintain a list of authorized distributors of record, and unauthorized distributors must inform their wholesale customers of all previous sales of the product before selling it to them.

• Civil and Criminal Penalties: The act establishes penalties for violations, ensuring compliance with its provisions.

• Consumer Protection: The PDMA aims to protect consumers from the risks associated with counterfeit and substandard drugs by ensuring that only safe and effective medications are available in the market.

Breakage and Spillage

Breakage or spillage of controlled substances must be documented and destroyed under DEA supervision; losses are reported if significant (21 CFR §1307.21).

Example: A spilled morphine solution is recorded and destroyed with two witnesses present, and minor losses logged internally.

Transfer or Disposal of Controlled Substances

Pharmacies must follow DEA rules when transferring or disposing of controlled substances, including use of Form 222 for Schedule I-II drugs and DEA-approved reverse distributors (21 CFR §1317).

Example: Expired oxycodone tablets are sent to a DEA-registered reverse distributor for destruction.

Methamphetamine Control

Methamphetamine precursors (pseudoephedrine, ephedrine) are regulated under the Combat Methamphetamine Epidemic Act (21 U.S.C. §§ 830–831). Pharmacies must limit sales, maintain logs, and verify purchaser ID.

Example: A pharmacy logs pseudoephedrine purchases and restricts sale to 3.6 g per day per federal law.

The Combat Methamphetamine Epidemic Act of 2005 (CMEA) is a federal law aimed at regulating the sale of pseudo-ephedrine and other precursor chemicals used in the illicit production of methamphetamine.

Purpose of the Act

The CMEA was enacted to combat the growing problem of methamphetamine production and abuse in the United States. It regulates the sale of over-the counter medications containing pseudoephedrine, a common ingredient in cold and allergy medications that can be used to manufacture methamphetamine.

Key Provisions

• Sales Restrictions: The act limits the amount of pseudoephedrine that an individual can purchase to 3.6 grams per day and 9 grams per month. This is to prevent individuals from buying large quantities for illicit use.

• Behind-the-Counter Sales: Products containing pseudoephedrine must be kept behind the counter or in locked cabinets, making them less accessible to potential abusers.

• Identification Requirements: Customers must present a valid photoID when purchasing these products, and retailers are required to maintain a log of sales for at least two years.

• Employee Training: Retailers must train employees on how to recognize suspicious transactions and comply with the law’s requirements.

• Reporting Suspicious Transactions: Retailers are required to report any suspicious purchases to law enforcement, which helps in monitoring potential illegal activities related to methamphetamine production.

Employee Screening

DEA requires pharmacies to screen employees handling controlled substances for criminal history or substance abuse risk.

Example: A pharmacy conducts background checks and drug screening for all new pharmacy technicians.

The DEA employee screening procedures are outlined in 21 CFR § 1301.90.

Key points include:

• Employers must inquire about felonies and misdemeanors within the past five years and any current charges for criminal offenses.

• Questions about drug use (narcotics, amphetamines, barbiturates) in the past three years are also part of the screening process.

• Employers must obtain written authorization to check court and law enforcement records for potential charges or convictions.

• The screening process is essential for assessing the likelihood of an employee committing a drug security breach.

• Controlled Substance Theft or Significant Loss

The DEA mandates reporting theft or significant loss of controlled substances within one business day using DEA Form 106 (21 CFR §1301.76).

Example: A pharmacy discovers missing fentanyl patches and immediately files Form 106.

Test Your Knowledge:

Question 1: Which action is required of a pharmacist under the Controlled Substances Act (CSA) when dispensing a Schedule II medication?

A. Allowing up to five refills within six months
B. Accepting an oral prescription without follow-up documentation
C. Verifying the prescriber’s DEA registration and dispensing with no refills
D. Filing the prescription with Schedule III–V records

Correct Answer:
C. Verifying the prescriber’s DEA registration and dispensing with no refills


Question 2: Which DEA form must a pharmacy use to report theft or significant loss of controlled substances?

A. DEA Form 222
B. DEA Form 224
C. DEA Form 106
D. DEA Form 224a

Correct Answer:
C. DEA Form 106