Drug Enforcement Administration Compliance for University and Health System Research Facilities
August 29, 2007
Lack of compliance with federal and state requirements regarding controlled substances can result in strict penalties and damaged reputations for research institutions.Academic and institutional research facilities often use controlled substances while conducting research, including the development and analysis of drug compounds, and animal research. In particular, controlled substances may be used to anesthetize animals during research; as a substrate or other reagent; and generally in clinical, analytical and animal investigations. Research institutions and investigators are subject to federal and state law requirements that mandate proper maintenance, storage, use and disposal of controlled substances.
However, university and health system research facilities are not always aware of the legal requirements concerning controlled substances. Lack of awareness may result from institutional habits that have fostered a focus on research and scientific doctrine, without consideration for legal constraints that may require changed or increased compliance with controlled substances laws. Additionally, some institutions may not be wholly involved with research on a regular basis, leading to a lack of recognition of legal requirements when undertaking research protocols.
This article is intended to alert those using controlled substances of their compliance obligations under federal and state law, identify areas of vulnerability for research institutions and describe a sampling of compliance objectives to which research institutions and investigators must adhere when maintaining, storing, using and disposing of controlled substances for research purposes.
Federal and State Registration Requirements
The Drug Enforcement Administration (DEA) regulates compliance with and diversion of controlled substances pursuant to the Controlled Substances Act. Controlled substances include drugs that are subject to abuse or diversion, such as narcotics, stimulants, depressants, hallucinogens and cannabis. Controlled substances are "scheduled," with those requiring strictest control classified as Schedule I, and those requiring the least control classified as Schedule V. (Some states have introduced additional schedule levels in their regulations. Massachusetts, for example, has an additional Schedule VI, which includes all prescription drugs not in Schedule II-V.) As a result, research facilities should be aware that persons engaged in synthesizing (even temporarily), prescribing, dispensing, distributing, administering, conducting research on or disposing of controlled substances must register with the DEA. In a research setting, this typically means that the principal investigator using controlled substances in a research protocol will be required to submit a registration with the DEA in order to be legally permitted to possess, store and use a particular controlled substance. (Similar to pharmacies, researchers who store and dispense any controlled substance must be registered with the DEA.) Additionally, any research involving Schedule I substances requires additional special controls, which include submission of the research protocol to the DEA along with the required registration application.
Typically, the DEA requires separate registration at each laboratory where the researcher is engaged in the dispensation and administration of controlled substances for research purposes. Registered researchers may conduct only those activities using only those scheduled controlled substances that are authorized by their DEA registration, as set forth on the respective DEA Form 225. DEA Form 225 can be obtained through the internet.
In addition to federal DEA registration requirements, it also is likely that individual state registration is required for possession, distribution and use of controlled substances in a research facility. This may require registration with a local state board of pharmacy or a separate state administrative agency, depending on what state law requires. Typically, states require a separate application for controlled substances, and they may have additional specific requirements, such as an initial on-site inspection.
Authorization to Use Controlled Substances
Although a research facility is subject to DEA and state law enforcement, the DEA often will require a principal investigator or supervisor of research in which controlled substances are used to bear full responsibility on behalf of the research facility for compliance with federal and state laws and regulations. Additionally, research settings often have controlled substances policies and procedures with which the principal investigator will be required to comply, in addition to any federal or state law requirements. To that end, research settings often require that a principal investigator understand all applicable federal and state laws and regulations, and keep all required registrations, certificates, licenses and records in force. Additionally, the DEA requires DEA registrants (and individuals who will handle controlled substances in the course of their laboratory research) to undergo an initial background check.
Laboratory Security
All controlled substances must be kept in a locked cabinet in a research facility. Because of the greater potential for abuse and diversion, Schedule I and Schedule II controlled substances have higher security requirements than drugs in Schedule III-V and are required to be kept under a double lock system in a safe. Schedule I controlled substances are drugs or other substances that have a high potential for abuse, have no currently accepted medical use in treatment in the United States, and lack accepted safety for use under medical supervision. Schedule II controlled substances are drugs or other substances that have a high potential for abuse, have a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions, and may lead to severe psychological or physical dependence.
Access to keys or security devices for locked controlled substances should be limited to authorized personnel only, and not left unattended or otherwise readily available in the laboratory. Although there may be designated persons who will be in charge of keys for the locked controlled substances, the DEA registrant ultimately is responsible for any drug loss or diversion.
Record-Keeping and Inventory Compliance
The DEA requires a chain of custody from the time a controlled substance is received to the time researchers use or dispose of it. Periodic verification of records and re-counting of inventory should be conducted on a regular basis to document inventory. Inventory log books should assess the description and quantity of controlled substances present at all times.
The DEA requires complete and accurate records to be kept by registrants who are storing or using controlled substances in the research laboratory. This requirement applies to all procurement, dispensation and inventories, for a period of at least two years. In cases where state laws have been implemented to provide additional controlled substance requirements that are not inconsistent with federal requirements, those laws may require an even longer time period. Additionally, all Schedule II records must be maintained separate from Schedule III-V records. In the case where a principal investigator terminates a research study or departs from the research setting, all documentation should be maintained by that individual, unless notification is made to the DEA of the name, address and registration number of the establishment maintaining such records.
Purchasing Controlled Substances
Procurement of controlled substances normally is restricted to a designated department or individual in a research setting, in order to identify an accountable entity for purposes of DEA registration. This identification is accomplished by a demonstration of accurate and comprehensive account information, along with an authorized signature, a copy of a current DEA license and the completion of a triplicate order form (DEA Form 222) if the purchase includes any Schedule II controlled substances.
DEA Form 222 must be completed carefully with respect to quantities and dates. No material alteration is permitted when completing DEA Form 222, and in the case of an error, special filing steps must be followed for the voided form. All triplicate copies must be signed by a DEA registrant, and copies should be retained for the designated time period, as required by law.
Disposal and Destruction
The DEA requires that institutions and researchers account for controlled substances and keep records to demonstrate how controlled substances are used. Additionally, disposal of controlled substances must follow standardized procedures and may rely on authorized "reverse distributors" (entities that are registered with the DEA and approved to destroy controlled substances) filing appropriate DEA forms and promptly reporting thefts and diversions. In the case of large quantities, the DEA may require on-site field investigation and completion of required DEA forms prior to destruction of any quantities of controlled substances. Furthermore, state laws may require additional procedures to be in place prior to any such disposal or destruction. For example, a state may require an on-site visit by one of its controlled substances inspectors to meet any state inspection requirements.
Compliance and Enforcement
All research facilities are subject to unannounced DEA or state audits or inspection of controlled substances, as well as records and procedures. Although this varies from state to state, typically a state board of pharmacy governs controlled substances audits or inspections. Some states, however, have created separate drug control divisions for this purpose. Massachusetts, for example, regulates controlled substances registrations under the Massachusetts Department of Public Health. The DEA has the authority to impose criminal sanctions and penalties for violation of the Controlled Substances Act. These may range from monetary penalties up to and including imprisonment, depending on the nature of the offense.
Compliance with Other Laws
In addition to DEA compliance, other federal laws may affect how a controlled substance may be stored and used in a research setting. If applicable, investigators also should confirm that their research protocols are compliant with other laws, such as the Animal Welfare Act in instances where animal research is being conducted; and the Food and Drug Administration (FDA) and National Institutes of Health regulations, for research involving human subjects.
Special Areas of Vulnerability for Research Institutions
There are several areas of particular non-compliance concern at research institutions. These include the following:
-
Orphaned products, which are left behind by departing researchers and no longer under an appropriate registration or traceable to a proper registrant.
-
Visiting researchers who bring their own supply without appropriate location registration.
-
Synthesis of drugs during research and for research purposes without recognition that the drugs are controlled substances and subject to federal and state laws. This includes growth of botanicals in botanical collections.
-
Expired drugs, which frequently are left in a lock up (either in original packaging or diluted for use) and ignored for long periods of time without proper record-keeping.
-
Non-compliant facilities, due to lack of proper storage, proper record-keeping and access controls to controlled substances.
-
Theft or loss of controlled substances that are intended for research use but diverted due to improper storage and poor access controls.
-
Lack of written procedures on how a laboratory should properly manage controlled substances, including inventory, storage, security, use and disposal, among other issues.
-
Researcher screening ensures that individuals who are accessing and using controlled substances in research have no history of drug violations with legal authorities.
Absence of appropriate and stringent controls is an invitation to criminal activity. On several occasions, university research settings have been implicated directly or indirectly because of non-compliance with federal and state drug enforcement laws. Such examples include but are not limited to the following:
-
In 2005, a California university laboratory was described as an illicit drug manufacturing site after a California graduate student was caught synthesizing methamphetamine, "ecstasy" and anesthetic that was thought to be 80 times more potent than morphine. The graduate student was already on probation with legal authorities for prior drug violations.
-
In 2004, a prominent midwestern university was the subject of a multi-agency federal criminal investigation after authorities uncovered the university’s purchase of $13,000 of pre-cursor raw material that can be used to synthesize "ecstasy."
-
In 2001, a well-known southwestern university suspended one of its professors after he was arrested as a suspect in an "ecstasy" ring. The professor allegedly ordered the chemicals and equipment that was to be used at the university for the purpose of manufacturing "ecstasy."
This article has addressed how research institutions and investigators are subject to federal and state law requirements that mandate proper maintenance, storage, use and disposal of controlled substances. Compliance issues that arise are unique and have the propensity to represent significant risk to reputation, as well as monetary and criminal penalties.
Parties intending to possess and use controlled substances in their research setting should have well-defined written policies covering all activities from procurement through use and disposal, conduct training of researchers and periodically audit their internal compliance. Experienced legal counsel should be sought promptly if and when compliance issues arise. Prevention measures also are strongly recommended. Early consultation with experienced legal professionals will help universities and health systems maintain compliance to prevent problems from developing.
