Chapter 1.1-13.edited.docx

Federal Food, Drug, and Cosmetic Act (FDCA), Poison Prevention Packaging Act (PPPA), and Other Miscellaneous Federal Laws Scanned with CamScanner CHAPTER ONE Federal Food, Drug, and Cosmetic Act (FDCA), Poison Prevention Packaging Act (PPPA), and Other Miscellaneous Federal Laws Federal Food, Dru...

Federal Food, Drug, and Cosmetic Act (FDCA), Poison Prevention Packaging Act (PPPA), and Other Miscellaneous Federal Laws Scanned with CamScanner CHAPTER ONE Federal Food, Drug, and Cosmetic Act (FDCA), Poison Prevention Packaging Act (PPPA), and Other Miscellaneous Federal Laws Federal Food, Drug, and Cosmetic Act (FDCA) and Major Amendments Food, Drug, and Cosmetic Act of 1938 Following deaths caused by sulfanilamide elixir in 1937, Congress passed the first legislation that required new drugs to be proven safe prior to marketing. Established the FDA and is the primary federal law dealing with food, drug, cosmetic, and medical device safety today (with many amendments). Durham-HumphreyAmendments of 1951 Established two classes of drugs: prescription and over-the-counter (OTC). STUDY TIP: You are expected to know those pharmaceutical products that require a prescription. It is particularly important to know that certain products in the same drug class may be either prescription or nonprescription, depending on the product or its strength. For example, some insulin products are nonprescription; however, certain other insulin products, such as Lantus° and Humalog°, are prescription-only products. Other examples—ibuprofen 400 mg, ó00 mg, and 800 mg—require a prescription, while ibuprofen 200 mg does not. 2. Authorized verbal prescriptions and prescription refills. Kefauver-Harris Amendments of 1962 Required new drugs be proven safe and effective for their claimed use. Increased safety requirements for drugs and established Good Manufacturing Practices (GMPs) for manufacturing of drugs. Gave FDA jurisdiction over prescription drug advertising. PrescriptionDrug Marketing Act of 1987 (PDMA) Bans the reimportation of prescription drugs and insulin products produced in the United States (except by the manufacturer). — 31 Copyright O 2023 Gary Cacciatore Scanned with CamScanner Note: This prohibition is on the reimportation of drugs produced in the United States and then exported. This is different than the importation of drugs manufactured in another country. Importation of drugs is generally prohibited; however, the Medicine Equity and Drug Safety (MSDS) Act of 2000 and the Medicare Prescription Drug Improvement and Modernization Act of 2003 both have provisions that allow the importation of drugs under specific conditions. On September 24, 2020, the FDA finalized regulations that permit states or Indian tribes (and, in certain circumstances, in conjunction with wholesalers and pharmacies) to serve as Sponsors to import drugs from Canada with detailed requirements. A few states (but not Texas) have passed laws to allow drug importation from Canada, but as of the date of this hook's publication, no state plan has been approved by IDA or implemented. Bans the sale, trade, or purchase of prescription drug samples. STUDY TIP: TSBP rules on samples are consistent with federal law and prohibit most pharmacies from Selling, purchasing, trading, or possessing prescription drug samples. The only exception is for pharmacies that are owned by a charitable organization or by a city, state, or county government and that are part of a healthcare entity providing care to indigent or low-income patients at no or reduced cost. Such samples may only be provided at no charge to patients. Mandates the storage, handling, and recordkeeping requirements for prescription drug samples. Prohibits, with certain exceptions, the resale of prescription drugs purchased by hospitals or healthcare facilities. Note: There are some exceptions to 4. above, but this law is intended to prevent the diversion of drugs due to price differences because hospitals generally receive lower prices for drugs than community pharmacies. The Drug Quality and Security Act (DQSA) of 2013—These amendments to the FDCA addressed two primary topics: large-scale compounding by pharmacies and the establishment of a framework for a uniform track and trace system for prescription drugs throughout the supply chain. Drug Compounding Quality Act (DCQA). Maintains regulation of traditional compounding with states under Section 503A but establishes Section 503B 32 Copyright@ 2023 G Scanned with CamScanner in the FDCA that allows facilities that are compounding sterile pharmaceuticals that are not based on patient-specific prescriptions to register with the FDA as an “Outsourcing Facility.” Outsourcing facilities that meet the Act's requirements are exempt from the new drug provi5ions (FDCA Section 505), adequate directions for use (FDCA Section 502(I)(1)), and drug track and trace provisions (FDCA Section 582). Outsourcing facilities, often referred to as 503B facili ties, are permitted to compound sterile products without receiving patient-specific prescriptions or medication orders. They are primarily regulated by the FDA and are subject to the FDA's current Good Manufacturing Practices (cGMPs). Compounding pharmacies that are not registered with the FDA as an “outsourcing facility” are often referred to as 503A facilities or 503A pharmacies and may only compound products pursuant to an individual prescription or medication order. They are permitted to do limited anticipatory compounding, are primarily regulated by the states, and are subject to USP Chapter 797 quality standards for sterile compounding. Outsourcing facilities must: f1) Have a licensed pharmacist who provides direct oversight for the drugs compounded; Register as an outsourcing facility. The FDA website provides a list of the names of each outsourcing facility along with the state where the facility is located, whether the facility compounds from bulk drug substances, and whether drugs compounded from bulk are sterile or nonsterile; Report to the Secretary of HHS upon registering, and every six months thereafter, the drugs sold in the previous six months; Be inspected by the FDA according to a risk-based inspection schedule and pay annual fees to support it; Report serious adverse event experiences within 15 days and conduct a follow-up investigation and reporting similar to current drug manufacturers; and 33 CO yright O 2023 Gary Cacciatore Scanned with CamScanner (6) Label products with a statement identifying them as a compounded drug and other specified information about the drug. Outsourcing facilities may not compound a drug product that includes a bulk drug substance unless: (I) The bulk drug substance appears on a list identifying bulk drug substances for which there is a clinical need (the 503B bulks list) or (2) The drug product compounded from such bulk drug substance appears on the FDA's drug shortage list at the time of compounding, distribution, and dispensing. Note: Bulk drug substances must be accompanied by a valid certificate of analysis and must have been manufactured by an establishment registered with the FDA. In addition, if an applicable United States Pharmacopeia (USP) or National Formulary monograph exists, bulk drug substances must comply with the monograph. IDA issued an Interim Policy on Compounding Using Bulk Drug Sub-stances under Section S03B of FDCA, which is in place while IDA develops the 503B bulks list. The guidance describes conditions under which the agency does not intend to take action against outsourcing facilities that compound drug products from bulk drug substances that cannot otherwise be used in compounding under Section 503B. See the compounding section of the FDA's website for more information. Interstate distribution of compounded drugs from a 503A pharmacy. (I) Section 503A also limits interstate distribution of compounded drugs to 5% unless the compounder is located in a state that has entered into a memorandum of understanding (MOU) with the FDA addressing inordinate amounts of compounded drugs in interstate commerce and providing for appropriate investigation of complaints by a state. (2) In states that have entered into an MOU with the FDA, a pharmacy is considered to have distributed an inordinate amount of compounded drug products in interstate commerce if the number of prescription 34 Copyright B 2023 Gary Cacciatore Scanned with CamScanner orders for compounded human drug products that the pharmacy distributed interstate during any calendar year is greater than 50% of the sum of: the number of prescription orders for com- pounded human drug products that the pharmacy sent out of(or caused to be sent out of) the facility in which the drug products were compounded during that same calendar year; plus the number of prescription orders for com- pounded human drug products that were dispensed (e.g., picked up by a patient) at the pharmacy during that same calendar year. Note: All of the compounded drugs must still be prepared based on an individually identified patient. Details on how these calculations are made can be found on the compounding page of IDA’s website. In states that have not entered into an MOU with the FDA, a pharmacy may not distribute (or cause to be distributed) compounded drug products out of the state in which they are compounded in quantities that exceed 5% of the total prescription orders dis- pensed or distributed by such pharmacy. (4) The FDA made a standard MOU available for states to sign in October 2020 that set forth obligations of states, including investigating complaints of adverse drug experiences and product quality issues for compounded products, identifying and investigating pharmacies distributing inordinate amounts of compounded drug products interstate, and required information sharing with the FDA. The deadline for states to sign the MOU was extended until Octo- ber 22, 2022, but a lawsuit filed by some compounding pharmacies has caused the FDA to withdraw the October 2020 MOU. FDA will now develop an MOU through the rulemaking process. Note. IDA hO5 issued several additional guidance documents to implement the Compounding Quality Act that are beyond the scope of this review guide. Detailed information may be found on the FDA's 35 Copyright O 2023 Gary Cacciatore Scanned with CamScanner Drug Supply Chain Security Act (DSCSA) (Track and Trace). Provides for a uniform national framework for an electronic track and trace system for prescription drugs as they move through the supply chain and sets national standards for states to license drug wholesaler-distributors. Applies to prescription drugs for human use in finished dosage form, but certain products are exempted, including blood and blood components, radioactive drugs, imaging drugs, certain intravenous products for fluid replacement, dialysis solutions, medical gases, compounded drugs, medical convenience kits containing drugs, certain combination products, sterile water, and products for irrigation. Manufacturers are required to provide “Transaction Data” for each product sold. Wholesalers are required to receive transaction data upon purchase and subsequently provide transaction data to the buyer (pharmacies or other wholesalers), and pharmacies are required to receive transaction data and pass this information along if they further distribute the product. “Transaction Data” includes Transaction Information, Transaction History, and a Transaction Statement. (I) Transaction Information includes the product's name, strength, and dosage form; NDC num- ber; container size and number of containers; date of transaction; and name and address of the person from whom ownership is being transferred and to whom ownership is being transferred. A unique product identifier or serialized numerical identifier (SNI) will also be required that identifies an individual bottle or unit of sale. Transaction History is a paper or electronic statement that includes prior transaction information for each prior transaction back to the manufacturer. Transaction Statement is a paper or electronic statement by the seller that the seller is authorized (licensed), received the product from an authorized (licensed) person, received the transaction information and transaction history from the prior owner if required, did not knowingly ship a suspect or illegitimate product, has systems and processes to comply 36 Copyright O 2023 Gary Cacciatore Scanned with CamScanner with verification requirements, and did not knowingly provide false transaction information. STUDY TIP: Transaction data must be maintained for 6 years by each supply chain partner. Pharmacies may only receive drugs with product identifiers. Pharmacies are not yet required to authenticate (scan) those product identifiers. Note: A product identifier is a standardized graphic with three elements: the product's standardized numerical identifier {SNI), which comprises the NOffOfl‹2I Drug Code plus a unique alphanumeric serial number; a lot number; and an expiration date. Product identifiers must be in human- and machine-readable formats. Pharmacies must investigate and properly handle suspect and illegitimate products. Suspect products are products that one has reason to believe are potentially counterfeit, diverted, stolen, subject of a fraudulent transaction, intentionally adulterated, or appear otherwise unfit for distribution such that they would result in serious adverse health consequences or death to humans. Illegitimate products are products for which credible evidence shows that the product is counterfeit, diverted, stolen, subject of a fraudulent transaction, intentionally adulterated, or appears otherwise unfit for distribution such that it would result in serious adverse health consequences or death to humans. 13) Pharmacies must investigate any suspect or illegitimate product. As part of the investigation, a pharmacy must verify the product identifier of at least 3 products or 10% of the suspect product, whichever is greater, or all of the packages if there are fewer than 3. Pharmacies must also verify any illegitimate product in response to a notification of an illegitimate product from the FDA or a trading partner. Note: This requirement was scheduled to go into effect on November 27, 2020, but IDA hOS delayed enforcement until November 27, 2023. 37 Copyright O 2023 Gary Cacciatore Scanned with CamScanner If a product is illegitimate, pharmacies must notify the FDA using Form FDA 3911 and notify trading partners within 24 hours. Pharmacies should also work with the manufacturer to prevent illegitimate products from reaching patients. Pharmacies that are “distributing” (distributing is defined as providing a drug to anyone other than the consumer/patient, as compared to dispensing, which is providing a drug to the patient/consumer) must have a wholesale distribution license and must pass DSCSA transaction data with that distribution. The only exceptions to having a distribution license and passing transaction data are as follows: (1} When the distribution is between two entities that are affiliated or under common ownership; When a dispenser is providing product to another dispenser on a patient-specific basis; When a dispenser is distributing under emergency medical reasons; or When a dispenser is distributing “minimal quantities” to a licensed practitioner for office use. The DSCSA also requires the FDA to establish national standards for the licensure of wholesale drug distributors and third-party logistics providers. A third-party logistics provider or 3PL is an entity that provides or coordinates warehousing or other logistics services of a product in interstate commerce on behalf of a manufacturer, wholesale distributor, or dispenser of a product but does not take ownership of the product, nor have a responsibility to direct the sale or disposition of the product. FDA issued a proposed rule for these licensure standards on February 4, 2022, with enforcement to begin two years following the finalization of the rule. Note: The FDA has issued more than 25 guidance documents on the DSCSA that are beyond the scope of this book but can be found on the EDA's DSCSA web page. Prohibited Acts Under the FOCA Nearly all violations of the FDCA cause the products to be adulterated and/or misbranded. It is important to understand the difference between these two concepts. Although drug manufacturers are more 38 Copyright O 2023 Gary Cacciatore Scanned with CamScanner likely to violate the FDCA, actions taken by pharmacists (e.g., a dispensing error) could also cause a product to be adulterated or misbranded. It is likely these are the types of situations that may be covered on the MPJE. Adulteration—A drug is adulterated if: It contains any filthy, putrid, or decomposed substance. It has been prepared or held under unsanitary conditions where it may have been contaminated. The methods of manufacture do not conform to current Good Manufacturing Practices (cGMPs). It has been manufactured, processed, packed, or held in any factory, warehouse, or establishment, and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection or refuses to permit entry or inspection. The container is composed of any poisonous or deleterious substance which may contaminate the drug. It contains an unsafe color additive. It purports to be a drug in an official compendium, and its strength differs from or its quality or purity falls below the compendium standard unless the difference is clearly stated on the label. Note: This means if the product claims to meet USP standards but its strength or quality does not meet those standards, it is adulterated. It is not in a compendium, and its strength differs from or its quality falls below what it represents (i.e., what is on its label). It is mixed or packed with any substance that reduces its strength or quality, or the drug has been substituted in whole or in part. STUDY TIP: If a product's strength differs from what is represented on its label, it could be both misbranded and adulterated. Misbranding—A drug is misbranded if: The labeling is false or misleading in any particular way. It is a prescription drug, and the manufacturer's label fails to contain the following information: The name and address of the manufacturer, packer, or distributor. Brand and/or generic name of the drug or drug product. 39 Copyright 0 2023 Gary Cacciatore Scanned with CamScanner The net quantity (weight, quantity, or dosage units). The weight of active ingredient per dosage unit. The federal legend, “Rx only.” If not taken orally, the specific routes of administration (e.g., for IM injection). Special storage instructions if appropriate. Manufacturer's control number (lot number). Expiration date. Adequate information for use (package insert and medication guide or patient package insert if required). This includes other information required (e.g., certain products, including opioids and benzodiazepines, require “black boxed warnings” to alert healthcare professionals about essential information regarding the product). STUDY TIP: These labeling requirements are for the manufacturer's container. When a pharmacist dispenses a drug to a patient pursuant to a valid prescription, the label does not have to contain all these elements except requirements for patient package inserts and medication guides. State prescription drug labeling requirements would dictate what is required on the label. It is an OTC drug and fails to contain the following: A principal display panel, including a statement of the identity of the product. The name and address of the manufacturer, packer, or distributor. Net quantity of contents. Cautions and warnings are needed to protect user. Adequate directions for safe and effective use (for layperson). Note: OTC products must have adequate directions for safe and effective use, while prescription products must have adequate information for use {i.e., the package insert). Content and format of OTC product labeling in “Drug Facts” panel format including: Active Ingredients. Purpose. Use(s)—indications. Warnings. 40 Copyright 0 2023 Gary Cacciatore - Scanned with CamScanner Directions. (b) Other Information. l7) Inactive Ingredients (in alphabetical order). (8) Questions? (optional) followed by telephone number. STUDY TIP: Pharmacists don't usually concern themselves with these labeling requirements as it is expected that manufacturers will label their products appropriately, but you should know the labeling requirements for OTC drugs. It is a drug liable to deterioration unless it is packaged or labeled accordingly. The container is made, formed, or filled so as to be misleading. The drug is an exact imitation of another drug or offered for sale under the name of another drug. It is dangerous to health when used in the dosage or manner suggested in the labeling. It is packaged or labeled in violation of the Poison Prevention Packaging Act. STUDY TIP: The FDCA specifically states that a drug that is not packaged in a child-resistant container (if required) is misbranded. This may not be as obvious because it is about the packaging and not the label or labeling. Adulteration and Misbranding as Applied to Pharmacies Dispensing a prescription without authorization causes the drug to be misbranded even if it is labeled correctly by the pharmacist. This is because a prescription drug prod uct is only exempt from the manufacturer's labeling requirements in B.2. above when it is dispensed pursuant to a valid prescription. STUDY TIP: There are a number of drug products that are currently approved and sold for both prescription and OTC use. For example, Prilosec and Prilo sec OTC contain the same active ingredient (omeprazole), but the indications for the prescription product require a diagnosis (e.g., GERD) and supervision by a doctor, while the OTC version is indicated for heartburn. Readers should be aware of the common medications that may be sold both as a prescription and OTC and that their labeling and indications will not be the same. Pharmacists must also have a prescription in order to dispense the prescription product, or the product will be misbranded. 41 Copyright B 2023 Gary Cacciatore Scanned with CamScanner Misfilling a prescription with the wrong drug, strength, or directions for use will always cause the drug to be misbranded. s. If a misfilled prescription involves the wrong strength of the drug prescribed, it would also be adulterated. This is because the definition of adulteration includes when the strength differs from, or quality falls below that which it represents. If a drug is subject to a Risk Evaluation and Mitigation Strategy (REMS) and it is prescribed or dispensed without meeting the requirements of the REMS, it is misbranded because the REMS program is part of the official labeling of the drug. The advertising or promotion of a compounded drug that is false or misleading would be misbranding. An expired drug product in a manufacturer's bottle is adulterated because, after the expiration date, the strength cannot be assured. If a prescription is filled using an expired product, it may also be misbranded if the pharmacist places a beyond-use date that is after the expiration date of the drug. If a pharmacist counts a medication on a tray that has residue from another medication, the product would be adulterated. If a pharmacist stores inventory in a room or refrigera tor where the temperature is not adequately controlled, the products would be adulterated. If a pharmacist stores a specific product incorrectly, such as stocking a medication on a pharmacy shelf instead of in the refrigerator as required, this will lead to the product being adulterated. If a pharmacist fails to dispense a medication in a child-resistant container when required, this would be misbranding. STUDY TIP: You are more likely to encounter questions related to adulteration and misbranding based on scenarios in a pharmacy. 42 Copyright O 2023 Gary Cacciatore Scanned with CamScanner