misbranding vs adulteration Flashcards

Question

What is current good manufacturing practice?

Answer 1

Current good manufacturing practices (CGMP or cGMP) are regulations that establish the minimum requirements for manufacturing drug products for administration to humans or animals. These regulations assure proper design, monitoring, and control of manufacturing processes and facilities. These regulations apply to manufacturers of drug products but not pharmacies unless the pharmacy engages in manufacturing. Manufacturers must be registered with the FDA and generally undergo an inspection process at least once every two years. Inspections are often delayed for companies in specific locations due to the difficulty of obtaining visas and traveling internationally. Current good manufacturing practices help prevent contamination, mix-ups, deviations from protocol, failures, and overall errors to assure drug products meet quality standards. cGMP applies to all facilities manufacturing products for use in the United States. So moving a facility overseas does not exempt you from these requirements. Failure to follow cGMP leads to a product being per se adulterated. Failure to register an establishment where US drug products are made causes it to be both adulterated and misbranded, as we’ll discuss next.

Answer 2

“A drug or device shall be deemed to be misbranded— (a) If its labeling is false or misleading in any particular... (b) If in package form unless it bears a label containing (1) the name and place of business of the manufacturer, packer, or distributor; and (2) an accurate statement of the quantity of the contents in terms of weight, measure, or numerical count… (c) If any word, statement, or other information required…on the label or labeling is not prominently placed thereon with such conspicuousness…and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use. … (e)(1)(A) If it is a drug, unless its label bears, to the exclusion of any other nonproprietary name (except the applicable systematic chemical name or the chemical formula) (i) the established name (as defined in subparagraph (3)) of the drug, if there is such a name; (ii) the established name and quantity or, if determined to be appropriate by the Secretary, the proportion of each active ingredient, including the quantity, kind, and proportion of any alcohol, and also including whether active or not the established name and quantity or if determined to be appropriate by the Secretary, the proportion of any bromides, ether, chloroform, acetanilide, acetophenetidin, amidopyrine, antipyrine, atropine, hyoscine, hyoscyamine, arsenic, digitalis, digitalis glucosides, mercury, ouabain, strophanthin, strychnine, thyroid, or any derivative or preparation of any such substances, contained therein, except that the requirement for stating the quantity of the active ingredients, other than the quantity of those specifically named in this subclause, shall not apply to nonprescription drugs not intended for human use; and (iii) the established name of each inactive ingredient listed in alphabetical order on the outside container of the retail package and, if determined to be appropriate by the Secretary, on the immediate container, as prescribed in regulation promulgated by the Secretary, except that nothing in this subclause shall be deemed to require that any trade secret be divulged, and except that the requirements of this subclause with respect to alphabetical order shall apply only to nonprescription drugs that are not also cosmetics and that this subclause shall not apply to nonprescription drugs not intended for human use. (B) For any prescription drug the established name of such drug or ingredient, as the case may be, on such label (and on any labeling on which a name for such drug or ingredient is used) shall be printed prominently and in type at least half as large as that used thereon for any proprietary name or designation for such drug or ingredient…(3) As used in subparagraph (1), the term “established name “… means (A) the applicable official name… or (B) if there is no such name and such drug…is an article recognized in an official compendium, then the official title thereof in such compendium, or (C) if neither clause (A) nor clause (B) of this subparagraph applies, then the common or usual name… (f) Unless its labeling bears (1) adequate directions for use; and (2) such adequate warnings against use in those pathological conditions or by children where its use may be dangerous to health, or against unsafe dosage or methods or duration of administration or application, in such manner and form, as are necessary for the protection of users, except that where any requirement of clause (1) of this paragraph, as applied to any drug or device, is not necessary for the protection of the public health, the Secretary shall promulgate regulations exempting such drug or device from such requirement… (g) If it purports to be a drug the name of which is recognized in an official compendium, unless it is packaged and labeled as prescribed therein… (h) If it has…to be a drug liable to deterioration, unless it is packaged in such form and manner, and its label bears a statement of such precautions… (i) (1) If it is a drug and its container is so made, formed, or filled as to be misleading; or (2) if it is an imitation of another drug; or (3) if it is offered for sale under the name of another drug. (j) If it is dangerous to health when used in the dosage or manner, or with the frequency or duration prescribed, recommended, or suggested in the labeling thereof. … (m) If it is a color additive the intended use of which is for the purpose of coloring only, unless its packaging and labeling are in conformity with such packaging and labeling requirements.. (n) …unless the manufacturer, packer, or distributor includes in all advertisements and other descriptive printed matter…a true statement of (1) the established name…printed prominently and in type at least half as large as that used for any trade or brand name thereof, (2) the formula showing quantitatively each ingredient of such drug…and (3) such other information in brief summary relating to side effects, contraindications, and effectiveness… … (p) If it is a drug and its packaging or labeling is in violation of an applicable regulation of the Poison Prevention Packaging Act of 1970 … (y)If it is a drug subject to an approved risk evaluation and mitigation strategy…and the responsible person…fails to comply with a requirement of such strategy… … (bb) If the advertising or promotion of a compounded drug is false or misleading in any particular. (cc) If it is a drug and it fails to bear the product identifier as required…”

Answer 3

anything false or misleading on a label and within labeling will cause a product to be misbranded. Recognize this broad statement covers many things, including wrong information on a label or within labeling, missing information on a label or within labeling, or added or unapproved information on a label or in labeling. Recall the definition of labeling; it includes labels, prescribing information, medication guides, and advertisements, to name a few. All labeling must be FDA-approved, so it’s crucial variations don’t occur from approved materials. This is why companies are often cautious about the statements made in advertisements or other items. Similarly, statements made by individuals representing the company can also be problematic because verbal statements that differ from approved information can also be misbranding. That’s why only specific individuals at a drug company, like medical science liaisons (MSLs), can talk about off-label uses, and even then, it’s still carefully curated information.

Answer 4

labels must list the name and place of the manufacturer, packer, or distributor. Without this information, a drug is misbranded.

Answer 5

labels must provide a statement of the quantity of the product in the container. This will vary depending on the product but might list the number of tablets, ounces, weight, or another measure.

Answer 6

this provision is really about preventing someone from hiding information that may need to be seen on a label. This provision highlights that things must be able to be read and understood by “the ordinary individual under customary conditions of purchase and use.”5 This doesn’t tell us who is considered an ordinary individual or what typical conditions are; however, it puts manufacturers and pharmacies on notice in making sure that they do everything possible to make their information clear to most people.

Answer 7

this provision is lengthy and can be confusing, but it’s written in this way to be as complete as possible. It addresses both prescription and non-prescription product labels, which are different. This provision requires the generic name must be on the label, even if the product is branded. It also requires that all active ingredients be listed on the label or in the labeling and inactive ingredients when required. This second part is best demonstrated by OTC drugs, where you see combinations of active ingredients listed and often see inactive ingredients listed. The final thing to notice about this provision is that it notes that the generic name must be in type at least half the size as the brand name on the label. We don’t know if that means half the size measured by a ruler (e.g., 1 inch and ½ inch) or half the font size (e.g., 20-point font and 10-point font). Again, this is about putting people on notice, so information isn’t hidden.

Answer 8

drug labeling must contain adequate directions for use and warnings. Consider that this information is often seen in OTC labeling since the user is a layperson, and information must be more apparent to them. Directions for use, when to discontinue a product, and warnings are prominently placed to ensure the information is accessible to the general population. This information is also provided for prescription drugs but may be less accessible within the prescribing information.

Answer 9

the official compendium lists standards for drugs as noted in adulteration, but these also list how products should be packaged. These provisions must be followed, or the drug is misbranded. The official compendium may provide specific requirements regarding the packaging or storage of a product. Examples include packaging in a glass vial, light-resistant packages, temperature requirements, or specific desiccant requirements. Specific packaging may be required for stability or other issues observed with the drug, so if not followed, the drug may no longer act as we expect.

Answer 10

some drugs deteriorate over time and must be labeled with information about the deterioration and how to recognize the product has deteriorated to prevent use. Some drugs may deteriorate in unique ways, like precipitating, changing color, or producing a smell. These unique things should be noted on the label. All drugs deteriorate over time, and expiration dates are the traditional way things are noted. Any drug missing an expiration date is misbranded since it’s not labeled for deterioration but is also adulterated because we don’t know that it is still good to use.

Answer 11

this is about a product pretending to be something it’s not or making you think it’s something it’s not. Counterfeit products and imitations are pretending to be something they’re not. But misleading containers may be harder to understand. In these cases, the products often use their name and are marketed as the correct product, but the layout of information or the label’s design is such that a normal person would be drawn to certain parts that mislead the reader. This is harder to understand, so I’ve created a fake label based on a real example.

Answer 12

a drug that’s dangerous to health based on its standard recommended dosing is misbranded. This occurs after the drug has undergone the usual clinical trials and received approval. At that time, the drug is used widely across the population, and that’s when unexpected issues occur. While it doesn’t occur often, it has happened previously, notably with the drug Vioxx (rofecoxib).

Answer 13

this one is often confused with adulteration, but this is about a color additive not having information on the label that it is a color additive or not being packaged as required for the color additive.

Answer 14

have you ever wondered why advertisements list so many things, including side effects, active ingredients, generic names, and other things? This is the reason why. The product is misbranded if the manufacturer doesn’t put this information in advertisements. This is part of the labeling, and no one wants a patient to be misled.

Answer 15

we’ll spend time discussing the Poison Prevention Packaging Act, but it requires that drugs meeting specific requirements be packaged in child-resistant packaging. If a drug must be placed in this type of packaging and you haven’t packaged it as required or received an exemption, the product is misbranded.

Answer 16

if the drug requires risk evaluation and mitigation strategies (REMS) and you don’t follow the REMS with dispensing, the drug is misbranded. We’ll discuss the different types of REMS later in this course.

Answer 17

this was mentioned in the last section, but prescription medications must bear the identifier “Rx-Only” or “Prescription Only” on the label. Another option is the statement, “Caution: Federal law prohibits dispensing without a prescription.” Similarly, controlled substances must have a schedule identifier on the label, which we’ll discuss in the course’s controlled substance section. If this is missing, the product is misbranded. The clonazepam bottle label below shows these required product identifiers for prescription drugs and controlled substances and many other requirements noted in this section.

Answer 18

Misbranding can be summarized as issues outside of the product or issues with the words associated with the product (e.g., label, labeling, statements made). While adulteration focuses more on the drug product (strength, purity, quality, manufacturing process), misbranding focuses more on the label and labeling of a drug product.1,2 As noted previously, all labeling is approved as part of the FDA drug approval process, and any deviation from approved labeling on the part of a manufacturer, manufacturer representative, or pharmacy is misbranding.2 I think most of the misbranding provisions listed here are more transparent than the adulteration provisions, though there are more provisions to remember.