Laws and regulations

Federal requirements for handling and disposal of pharmaceutical substances and waste

The Resource Conservation and Recovery Act (RCRA), enacted in 1976, is the principal Federal law in the U.S. governing the disposal of solid waste and hazardous waste. This includes generating, transporting, treating, storing, and disposing of hazardous waste. RCRA also set forth a framework for the management of non-hazardous solid wastes. Hazardous waste is any substance determined as such by EPA, CDC, or FDA, or has properties such as corrosiveness, flammability, releases toxic gases, is a carcinogen, causes reproductive harm, or is poisonous, e.g., acids, alcohol, anti-neoplastic drugs, warfarin, benzene, etc.

Hazardous pharmaceutical waste should never be flushed down the toilet or poured into drains due to the risk of environmental contamination. Waste is gathered in color-coded bins for disposal. Proper PPE should be used while disposing of any pharmaceutical waste.

Table showing color coding for waste disposal

Hazardous drugs need to be prepared using proper personal protective equipment and engineering controls. The risk of exposure to hazardous drugs through inhalation or direct skin contact is present during preparation and handling activities like transferring, reconstituting, or mixing drugs, labeling, setting up IV lines, etc. Sharps, like needles, should be disposed of in specially marked, leak and puncture-proof containers. Hazardous drugs should be stored separately from non-hazardous drugs, clearly labeled as hazardous, and in an area with limited access.

The Occupational Safety and Health Administration (OSHA) ensures safe and healthful working conditions by setting and enforcing standards. It was created in 1970 under the Occupational Safety and Health Act.

Federal requirements for controlled substance prescriptions

The Controlled Substances Act (CSA) classifies all substances that were regulated under existing federal law into one of five schedules. This placement is based on the substance’s medical use, potential for abuse, and safety or dependence liability. Controlled substances are classified into Schedules I to V, which can be reviewed in the DEA Drug Schedules Section.

Some important things to consider involving the processing and dispensing of controlled substances in the pharmacy are as follows:

1. All prescribers need a DEA number to write a prescription for controlled substances. Under federal law, a prescription for a controlled substance may only be issued by a physician, dentist, veterinarian, or mid-level practitioner.
2. Verbal orders cannot be made for Schedule II medications except in an emergency situation. The prescription should be checked for completeness and accuracy.
3. Schedule II medications cannot be refilled. Instead, they need a new prescription for every fill.
4. Schedule III and IV cannot be refilled after six months or five times, whichever is earlier.
5. Schedule V medications may be written for up to 1 year, although many states limit this to 6 months.
6. Government-issued photo IDs are required to pick up controlled prescriptions.
7. Transfer of Schedules I and II requires filing DEA Form 222 and must be to an authorized DEA registrant.
8. Transfers for Schedules III through V drugs are limited; only one transfer is allowed per day unless the two pharmacies share a real-time database. Any remaining refills must be processed at the pharmacy to which they were transferred.
9. In the event of a significant loss of controlled substances, pharmacies must notify the DEA in writing through Form 106 within a business day.

Controlled substance prescribing, partial fills, and DEA compliance

Although refills are not permitted for Schedule II drugs, prescribers are authorized to issue three separate prescriptions, each for 30-day supply. Prescribers will enter a “do not fill until” date on such prescriptions. The pharmacist cannot legally fill a prescription before the specified “do not fill until” date. For example, if the “do not fill until date” is 10/15/2025, then the earliest date the prescription may be filled is 10/15/2025. The common practice for spacing sequential prescriptions is 30 days.

Partial fills for controlled substances: According to Federal regulations, partial fills for controlled substances are allowed if the pharmacy does not have enough stock and must be fulfilled within 72 hours of the partial fill; otherwise, a new prescription is required. In case a prescriber or patient requests, the remaining fill can be completed within 30 days, except for emergency prescriptions. Such refills should be properly documented. If State laws are more stringent, then they should be followed.

Partial fills for Schedules III-V drugs are permitted up to 6 months from the date the prescription was issued. The total dispensed quantity must not exceed the total prescribed quantity.

Transferring prescriptions for Schedule II controlled substances between pharmacies: An electronic prescription for a Schedule II substance may be transferred once to another pharmacy for the purpose of initial fill only, upon patient request, along with any authorized refills included with the original prescription.

Transferring prescriptions for Schedules III-V controlled substances between pharmacies: Transferring a prescription for a controlled substance between Schedules III-V between pharmacies is allowed only once. If the pharmacies share a real-time, online database, then they can transfer up to the maximum refills on the prescription. The transfer must be communicated directly between the two licensed pharmacists. The invalidated prescription is marked “VOID”.

Record-keeping of controlled substances: Records for controlled substances, whether paper or electronic, must be maintained for a minimum of two years. Schedule II records should be kept separately from Schedules III through V.

Inventory requirements for controlled substances: Inventory is taken at pre-determined intervals, as follows:

• Initial inventory - A complete and accurate record of any controlled substance should be taken on the first date that the pharmacy dispenses the controlled substance.
• Biennial inventory - A new inventory for all stocks of controlled substances on hand should be taken at least every two years.

Table showing important DEA forms for use in a pharmacy

The Comprehensive Addiction and Recovery Act (CARA): The CARA Act was passed in 2016 to control the opioid crisis by funding prevention, treatment, recovery, naloxone training, promoting prescription drug monitoring programs, and supporting patients and families. The CARA Act permits pharmacists to partially fill prescriptions for Schedule II medications. It also supports pharmacists in providing naloxone access in order to treat opioid overdose. CARA also provided more avenues for safe medication disposal by expanding drug take-back programs.

Federal requirements for receiving and storing controlled substances

Each commercial container of a controlled substance shall have a prominent print on the label, the symbol designating the schedule in which such controlled substance is listed. All controlled substances must be stored securely in a steel safe or vault, with limited access by authorized individuals only.

Federal requirements for restricted drug programs

Certain medications can cause serious adverse effects in special populations or conditions, e.g., Isotretinoin, which is used for acne, may cause severe birth defects in the growing fetus. Federal programs like REMS and the Combat Methamphetamine Epidemic Act were enacted to protect vulnerable populations from this risk.

The Combat Methamphetamine Epidemic Act (CMEA) passed in 2005 established retail sales and purchase transaction limits in grams for scheduled, listed chemical products, which include pseudoephedrine. Ephedrine, pseudoephedrine, and phenylpropanolamine are precursor chemicals used in the illicit manufacture of methamphetamine or amphetamine. They are common ingredients in cold and allergy medications. The CMEA sets a daily limit of 3.6 grams and a 30-day limit of 9 grams per purchaser. Pseudoephedrine (common brand name Sudafed) should be kept behind the counter or in a locked cabinet. It should not be sold without a photo identification. Buyer name, address, signature, date, and time of sale must be entered. A logbook of pseudoephedrine sales needs to be maintained.

The Ryan Haight Online Pharmacy Consumer Protection Act of 2008 (Ryan Haight Act) amended the CSA by adding various provisions to prevent the illegal distribution and dispensing of controlled substances through the Internet. The Act mandated that a practitioner must conduct at least one in-person medical evaluation of the patient prior to prescribing a controlled substance via the Internet.

The Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program under which the U.S. Food and Drug Administration (FDA) monitors certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Some common medications with a REMS program include isotretinoin, clozapine, and thalidomide. As part of REMS, prescribers, pharmacists, and patients are mandated to fulfill specific requirements to gain medication access. Such actions include training, providing evidence of safe use conditions like negative pregnancy tests, obtaining recent liver function test results, or enrolling in patient registries.

FDA recall requirements

A recall is a voluntary method of removing or correcting products that violate FDA laws. Recalls may be initiated for safety reasons, contamination, mislabeling, etc.

Recalls are classified as follows:

Class I: Recalls for products that could cause severe injury or death

Class II: Recalls for products that might cause significant injury or temporary illness

Class III: Recalls for products that are unlikely to cause injury or illness but violate FDA regulations

The FDA states that all recalled products are in its weekly enforcement report. It works with the manufacturer to improvise a recall strategy to ensure that all recalled products are safely destroyed and that corrective action has been taken to prevent any future safety issues. In 2023, over-the-counter eye drops commonly sold in many retail pharmacies were recalled due to microbial contamination.