Pharmacy Laws and Regulations

Pre-clinical testing

Animals. Relatove safety. Therapeutic potential

Phase I

~20-100 healthy volunteers or peop;e with the disease. Safety. Side effects. Pharmacokinetics & p-harmacodynamics

Phase II

~100-300 people with the disease. Efficacy and safety. Find optimum dose or dose range

Phase III

~300-3,000 people with the disease. Efficacy compared to placebo or standard-of-care. Adverse events

Phase IV

Post-marketing surveillance. Long-term efficacy and safety. High-risk patient monitoring. Other populations and new uses

Investigational New Drug (IND)

What approval represents the FDA’s permission to begin Phase I?

New Drug Application (NDA) for drugs, Biologics License Application (BLA) for biologics

If Phase III studies show promising results, what is the next step?

Supplemental New Drug Application (sNDA) or Supplemental Biologics License Application (sBLA)

To change a ;avel, add a new indication, add a new dosage or strength of a drug or change drug manufacturing processes, what must a company submit?

Boxed warnings, indications and usage, dosage and administration, dosage forms and strengths, contraindications, warnings and precautions, adverse reactions, use in specific populations (including pregnancy, nursing, pediatrics, and geriatrics), drug abuse and dependence, overdosage, description, clinical pharmacology, toxicology, clinical studies, references, how supplied/storage and handling, patient counseling information

What must labeling include?

OTC monograph

How can OTC drugs be marketed without FDA pre-approval or an NDA?

OTC Monograph Order Request (OMOR)

What can a manufacturer do if they wish to add or change an OTC mongraph?

Abbreviated New Drug Application (ANDA) or 505 (b) (2) application

Two abbreviated applications for generic drug approval

Same active ingredient, route of administration, dosage form and strength as the branded drug. It must also be bioequivalent to the branded drug

ANDA generic drug requirements

Unlike a generic approved by ANDA, 505 (b) (2) drugs can be marketed in a different strength or formulation than the previously approved product

Difference between ANDA and 505 (b) (2) generic drugs

Unapproved drugs

Have an NDC number but will not be listed in the FDA’s Approved Drug Products with Therapeutic equivalence Evaluations (the Orange Book)

MedWatch

Interacts with the FDA’s Adverese Event Reporting System (FAERS), a database containing adverse event and medicaiton error reports submitted to the FDA. Designed to identify adverse events not found in clinical trials (part of Phase IV: post-marketing surveillance)

Healthcare professionals, patients and consumers

Who can submit reports to MedWatch?

The manufacturer or the FDA

Who can initiate a drug recall?

180 days prior

When should manufacturers notify the FDA about withdrawing an approved drug from sale?

The FDA

Who regulates prescription drug advertising?

The Federal Trade Commission (FTC)

Who regulates OTC drug advertising?

The name of the drug (brand and generic), at least one FDA-approved use for the drug and the most significant risks of the drug

The FDA requires an advertisement to contain three items

Pure food and drug act of 1906 (the Wiley act)

Ingredients must meet standards (USP-NF) and label cannot be false or misleading

Food, drug and cosmetic act of 1938 (FDCA)

Drug must be safe and FDA-approved, defined adulteration and misbranding

Durham-Humphrey act of 1951

Distinction made between OTC and prescription (legend) drugs, with different labeling requirements

Kefauver-Harris act of 1962

Drugs must be safe and effective, serious side effects must be reported

Controlled substances act of 1970 (CSA)

Classified drugs into 5 “schedules” and created a closed system to reduce drug diversion

Poison prevention packaging act of 1970 (PPPA)

Drugs and certain household substances must have child-resistant (C-R) packaging

Drug listing act of 1972

OTC and Rx drugs must be registered with the FDA and have a national drug code (NDC)

Federal anti-tampering act of 1982

Required tamper-resistant features on OTC drugs (with a few exceptions)

Orphan drug act of 1983

Incentives provided to manufacturers to develop treatments for rare diseases

Hatch-Waxman act (drug price competition and patent term restoration act) of 1984

Streamlined generic approvals (ANDA) and granted patent exclusivity for branded drugs

Prescription drug marleting act of 1987 (PDMA)

Curbed “diversion/gray” market by limiting reimportation & resale of discounted drugs

Omnibus budget reconciliation act of 1990 (OBRA 90)

Required prospective DUR by pharmacist and counseling for Medicaid beneficiaries

Dietary supplement health and education act of 1994 (DSHEA)

Supplements must be safe and cannot claim to prevetn, treat, or cure a disease

FDA modernization act of 1997 (FDAMA)

Legend shortened to “Rx only” and updated regulations for fast track approvals

The drug addiction treatment act of 2000 (DATA 2000)

Qualified physicians may prescribe/dispense schedule II, IV or V opioid use disorder treatments in office setting

FDA amendments act of 2007 (FDAAA)

Enhanced drug safety through REMS program

Biologics price competition and innovation act of 2009

Created an abbreviated approval pathway for biosimilars (info in Purple Book)

Affordable care act of 2010 (ACA)

Aimed at increasing access to care, reducing cost and improving quality through collaboration and accountability

Drug quality and security act of 2013 (DQSA)

Compounding Quality Act - increased oversight if compounding by FDA

Drug Supply Chain Security Act - all transactions in supply chain must be documented

Pregnancy and lactation laveling final rule 2014 (PLLR)

Categories A, B, C, D and X no longer used

The comprehensive addiciton and recovery act of 2016 (CARA)

Allowed partial fills of schedule II drugs, NPs and PAs can treat opioid dependence