Pharmacy Federal Rules and Regulations

Issues of Concern

The FDA was founded as a consequence of Theodore Roosevelt’s Pure Food and Drug Act (1906), which prohibited misbranding, defined as misleading and fraudulent labeling of foods and drugs. It is important to note that the Supreme Court ruled that this Act does not prohibit false therapeutic statements, only misleading ones.[2] 

The Food, Drug, and Cosmetic Act (1938) replaced the legislation mentioned above. Significant differences include increased strictness of safety, criminalization of false therapeutic claims, the requirement for distributors to list ingredients, indications, and warnings; extension to cosmetics and therapeutic devices; and authorizing inspections at factories. It also lowered the reimbursement rate for durable medical equipment.[3][4] This legislature presently serves as the primary basis of the Administration, with a myriad of amendments listed below.

The Durham-Humphrey Amendment divided drugs into two classes: prescription (Rx) and over the counter (OTC). The FDA has the authority of categorization. Prescription medications are drugs that have the potential to create poor habits or be harmful if used without the supervision of a professional. Previously manufacturers were allowed to determine drugs’ categories. In scenarios where manufacturers disagree with the assigned class, they may choose to submit a supplemental application, petition, or go through a review process. Prescription medications are required to have a federal label on it. The amendment allowed the filling of prescription medications over the phone.[5]  

The Kefauver-Harris Amendment was passed due to ex-post-facto discovery of Thalidomide teratogenicity, which led to the birth of 10,000 children with severe deformities. The amendment provides the modern framework for pharmaceuticals approval, which include the following:

1. Discovery and pre-clinical trials
2. Proposal for clinical trials through the investigational new drug application
3. Phase 1 trials: An observation of harmful effects in a sample of 20 to 100 healthy individuals
4. Phase 2 trials: An analytical study to assess the therapeutic claim of the drug in a sample of 100 to 500 patients fitting the intended indications
5. Phase 3 trials: A larger analytical study similar to phase 2 with a larger sample size of 1000 to 5000 patients
6. A general period where drug sponsors and the FDA meet before submitting the new drug application (NDA)
7. Submission of the NDA
8. A 6 month to a 2-year period where the FDA appraises the research of the drug sponsor
9. Approval or non-approval of the drug by the FDA
10. Phase 4 trials where drug sponsors perform post-marketing studies.[6]

While manufacturers and research companies may pick the trade name, the assignment of non-proprietary names is by the United States Adopted Names (USAN) Council. Other associations, including the American Medical Association (AMA), the American Pharmacists Association (APhA), and the United States Pharmacopeial Convention, have a co-sponsoring role. Names are unofficial until published on the Federal Register.[7] 

The Medical Devices Amendment Act differentiated medical devices from pharmaceuticals as instruments that do not cause chemical reactions. It classified devices based on risk to patients into three classes and provided proportional strictness of guidelines on approval before the distribution based on said risk. The FDA must receive reports from manufacturers on adverse events. The FDA has the authority to ban devices from markets if deemed appropriate.[8] 

The Comprehensive Drug Abuse Prevention and Control Act was passed under Nixon’s term as part of his war on drugs. This law created the Drug Enforcement Administration (DEA) and regulated drug classification, procurement, distribution, prescription, and registration. Drugs are classified based on indications and potential abuse summarized in Table I.

Table I: Controlled Substances Classification, Distribution, and Examples

Prescription of Schedule II drugs must be written or electronic unless it is directly dispensed by a professional to the user, or in emergency situations. It is not allowed to have corrections; in scenarios with improper information, a new prescription must be issued. Prescription for Schedules III - V drugs may be oral written, or electronic. Transfer of Schedules I and II require the filing of DEA Form 222 and must be to an authorized DEA registrant. Current guidance encourages the use of the Controlled Substances Ordering System (CSOS), an electronic equivalent, which increases the accuracy, turnaround, and inventory management ability. Transfer 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 it was transferred. Upon the transfer, the word VOID must be written in cases where the prescription was on paper, and information about the other pharmacy, including the facility DEA number and receiving pharmacist name, must be recorded. Voiding in the system should also be checked. Destruction of any Schedules of controlled substances requires the filing of DEA Form 41.

In the event of a significant loss of controlled substances, pharmacies must notify the DEA in writing through Form 106 within a business day. It is noteworthy that the level of “significance” is not specified. While all theft must be reported, missing substances due to a damaged or lost product would not require the procedure.[9] 

The Omnibus Reconciliation Act improved pharmacy-patient interaction and outcomes through more thorough assessments prior to medication prescription with the intent to decrease costs. Algorithms detect potential drug problems including but not limited to therapeutic duplication, possible drug interactions, contraindications, improper dose or duration, and allergies. However, it allows pharmacists to exercise the final decision. Each state must also have local standards on patient counseling about medications. It also increased the quality of the database by encouraging pharmacists to obtain, record, and maintain information on Medicaid patients to improve health outcomes. It, therefore, established a minimum standard of care for all facilities seeking Medicare financing. It is important to note that though the Act’s primary target was Medicaid patients, the same standards also apply to non-Medicaid patients.[10] 

The Medicare Modernization Act massively changed the Medicare system since its inception. It provides an opt-in insurance system where the government helps fund prescription costs in situations where the cost is high, or patients are struggling economically. For high-cost prescriptions, annual reviews of prescribed medications take place to find ways to reduce costs, minimize potential drug interactions, and screen for other potential issues. Patients who part take in the program can save in a tax-free savings account. Though voluntary, healthy people who decide not to opt-in may be penalized.[11] 

In addition to the FDA, other regulatory bodies have oversight over pharmacy.

The Poison Prevention Packaging Act of 1970 under the Consumer Product Safety Commission requires the use of child-resistant packaging for household substances and special packages for medications. For patients with difficulty opening said packages, requests for non-child-resistant packages are possible. Other exemptions include emergency medications.[12] 

Congress passed the prescription drug marketing act to ensure the quality of medications of American consumers, specifically against adulterations, counterfeiting, misbranding, sub-potency, and expiration. It prevents the reimportation of drugs by anyone barring the manufacturers once exported; this resulted from the discovery of diversion markets of pharmaceuticals. It also enhanced the rigor in sales and distribution of pharmaceuticals: wholesale retailers must attain special licenses; samples are only available upon requests by a licensed prescriber.

Clinical Significance

Health professionals require a controlled substance registration through the Drug Enforcement Administration (DEA) and will be assigned a number. It is important to note that because pharmaceutical representatives’ roles do not cover prescription or administration of drugs, they do not require a DEA number.[9] They must be aware of different laws in order to ensure they follow best clinical practice and adhere to guidelines. Failure to do so may result in adverse consequences to the patient, the public, and oneself.[13]