1. OTC: INTRODUCTION AND DEFINITIONS

2. Over-the-counter (OTC) medications are defined as safe and effective drugs available to use by the general public without a doctor’s prescription (FDA). They play an increasingly vital role in our healthcare system and are the most prevalent means of treating the majority of common health problems in the United States. There are over 80 therapeutic categories of OTC drugs which can be grouped in 12 broad therapeutic classes.

3. Durham-Humphrey Amendment of 1951
In the US, the term OTC drugs was legalized in 1951 via Durham-Humphrey Amendment.
The law distinguished between legend (prescription) drugs and over-the-counter (OTC) (nonprescription) drugs
It also authorized:
verbal prescriptions
prescription refills
For information only; not required material

5. The benefits of over-the-counter availability include:
Direct, rapid access to effective medicines
Wide availability
Decreased healthcare system utilization (fewer physician visits, lower healthcare system costs)
Allowing individuals to be in charge of their own health

6. Risks associated with OTC use
Incorrect self-diagnosis delaying diagnosis and treatment of serious illnesses (delay in seeking advice from a healthcare professional)
Increased risk of drug-drug interactions.
Increased risk of adverse events when not used appropriately.
Potential for misuse and abuse

7. Important Definitions.
Misuse: An unintentional improper or incorrect use of a substance by deviating from the prescriber’s directions for reasons other than the pursuit of a psychotropic or euphoric effect. Intentional misuse: An exposure resulting from the intentional improper or incorrect use of a substance for reasons other than the pursuit of a psychotropic or euphoric effect. Abuse: An exposure resulting from the intentional improper or incorrect use of a substance where the individual was likely attempting to achieve a euphoric or psychotropic effect. The term abuse also applies to intentional or purposeful use of a drug for an indication NOT approved by the Prescriber for a perceived benefit that the patient desires.

8. Therapeutic (Medication) error: An unintentional Preventable deviation from a proper therapeutic regimen that results in the wrong dose, incorrect route of administration, administration to the wrong person, or administration of the wrong substance. Medication vs Drug (homework) Dependence Vs Addiction. (homework)

9. FDA defines drugs as follows:
A drug is a substance that exerts an action on the structure or function of the body by chemical action or metabolism and is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. A new drug is defined as one that is not generally recognized as safe and effective for the indications proposed.

10. A herb is a plant or part of a plant used for its flavor, scent, or potential therapeutic properties. Includes flowers, leaves, bark, fruit, seeds, stems, and roots.

11. Dietary Supplements (including Herbal Ingredients): A dietary supplement is a product taken by mouth that contains a "dietary ingredient" intended to supplement the diet. Permitted ingredients of dietary supplements include vitamins, minerals, herbs or other botanicals, and amino acids. Cosmetics: Cosmetics are “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body... for cleansing, beautifying, promoting attractiveness, or altering the appearance."

12. Dietary Supplement Health and Education Act (DSHEA) of 1994
Provided definitions and guidelines on diet supplements
manufacturers are not required to prove safety, efficacy, or standardization to the FDA as they are with prescription and nonprescription drugs
The FDA may only review “false claims” advertisements and monitor safety of diet supplements

13. Adulteration
(1) If it consists in whole or in part of any filthy, putrid, or decomposed substance.
(2) If it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health.
(3) If it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice (CGMP)
(4) If it bears or contains, for purposes of coloring only, a color additive which is unsafe.
These are current definitions; they are required.

14. Misbranding
Occurs when the labeling or advertising is misleading. The term ''label'' means a display of written, printed, or graphic matter upon the immediate container of any article. The term ''immediate container'' does not include package liners. The term ''labeling'' means all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article

15. Generally If a drug is mislabeled—
It is Misbranded
If drug not manufactured according to CGMPs
It is adulterated
If Drug does not conform to compendial standards and is labeled “USP”
Drugs can be both misbranded and adulterated at the same time

16. Interesting Facts!
FDA does not use the term “OTC medications,”. The official term is OTC drugs. Female individuals are more likely to use OTC medications. In a 2002 survey, 87% of women reported the use of an OTC pain medication in the past year compared to 80% of men. A study conducted in 2011 confirmed that OTC medications are American’s most popular treatment choice for common ailments such as headache, heartburn, allergies, and colds.

18. Poison Prevention Packaging Act of 1970
Passed to prevent accidental childhood poisonings from prescription and nonprescription products
Enforced by the Consumer Product Safety Commission
Requires most over-the-counter (OTC) and legend drugs be packaged in child-resistant containers
cannot be opened by 80% of children under five
can be opened by 90% of adults
Older patients may request a non-child-resistant container; other exceptions are provided for by law
Definition of Child-Resistant Package is required

19. Evaluation of OTC Drugs
Over-the-counter (OTC) drugs play an increasingly vital role in most health care systems. As with prescription drugs, FDA Center of Drug Evaluation and Research (CDER) oversees OTC drugs to ensure that they are properly labeled and that their benefits outweigh their risks. 

20. Characteristics of Eligibility for OTC Approval
OTC drugs generally have these characteristics:(They have to meet ALL of the characteristics to be eligible for OTC approval).
Their benefits outweigh their risks
The potential for misuse and abuse is low
Consumer can use them for self-diagnosed conditions
They can be adequately labeled
Health practitioners are not needed for the safe and Effective use of the product
Please provide examples for each characteristic: (i.e. narcotics would never be eligible for OTC approval since the potential for misuse and abuse will never be low)

21. Orange Book
The FDA publishes a list of all approved drugs called, Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the "Orange Book" because of its orange cover. It lists marketed drug products that are considered by the FDA to be safe and effective and provides information on therapeutic equivalence evaluations for approved multisource prescription drug products monthly.
The Orange Book rates drugs based on their therapeutic equivalence. For a product to be considered therapeutically equivalent, it must be both pharmaceutically equivalent (i.e., the same dose, dosage form, strength), and bioequivalent (i.e., the rate and extent of its absorption is not significantly different than the rate and extent of absorption of the drug with which it is to be interchanged).

22. What does FDA do with regard to OTC drugs?
Review OTC products for safety and effectiveness
Responsible for establishment of regulations of OTC drugs labeling
Responsible for the reclassifying process of OTC drugs from prescription status

23. Drug Reclassification:
Classes of drugs limited to Rx:
Certain habit-forming drugs listed by name;
Drugs not safe for use except under the supervision of a licensed practitioner because of toxicity or other potential for harmful effect, the method of use etc;
Drugs limited to prescription under an NDA

24. Drug Reclassification: Rx OTC
Reclassification Criteria:
The indication(s) for which the drug to be used on an OTC basis should be similar to those on Rx and must permit easy diagnosis and monitoring by the patient.
A favourable adverse-event and drug interaction profiles, relatively low toxicity and a low potential for abuse.
The drug should not have properties that make it impractical for OTC use, e.g. narrow therapeutic index.

25. Labeling & Packaging Issues

26. The need for NEW labeling?
“switch” from Rx OTC: the need for more sophisticated self-diagnostic and self-monitoring evaluation;
The older population is increasing in the USA
The new format helps pharmacists to readily find information on the label and point it to the patient
This new labeling format will use terms that are more familiar to consumers. E.g. ‘uses’ instead of ‘indications’
And it will no longer use the terms precautions or contraindications. Lay terms will be used, instead of medical jargon (e.g. lung instead of pulmonary)

27. OTC “Drug Facts” box
From May 2002: Most OTC medicines manufactured after this date carried the new Drug Facts label.
However, certain products e.g. sunscreens were not required until 2006
Many manufacturers voluntarily used the new OTC label before the effective date
Before simplifying the OTC label, The FDA conducted extensive research on how consumers use OTC drug labels. One major problem has been the readability of OTC drug labels, especially for older Americans, who purchase almost 30 percent of the nonprescription drugs sold in the US.
The FDA also found that consumers thought words like “indications”, “precautions” and “contraindications” were too technical and confusing.
The FDA established an implementation plan, dependent on the monograph and the approval status of the product, most OTC labels must use the Drug Facts format by 2006;
An OTC product that lacks the labeling after its required implementation plan date may be considered misbranded and subject to the same enforcement approach that FDA can take with other misbranded drugs: issuance of a warning letter, product seizures and injunctions

33. The new Drug Facts labeling requirements do not apply to dietary supplements, which are regulated as food products, and are labeled with a Supplement Facts panel.

35. The Tylenol Cyanide crisis!
In 1982, Johnson and Johnson experienced a major crisis when it discovered that numerous bottles of its Extra-Strength Tylenol capsules had been laced with cyanide. By the end of this major crisis, seven people had passed away from the use of the laced Extra-Strength Tylenol!
In response to the September 1982 cyanide poisonings in Chicago, the Food and Drug Administration (FDA) has issued tamper-resistant packaging requirements for all over-the-counter (OTC) drug products and certain cosmetic products, excluding dermatologics (products applied to the skin), dentifrices and insulin.

36. Tamper-evident Packaging
The FDA defines a tamper-resistant package as:
“one having an indicator or barrier to entry which, if breached or missing, can reasonably be expected to provide visible evidence to consumers that tampering has occurred”
Tamper-resistant packaging may involve immediate container/closure systems or secondary container carton systems.
The OTC drug products that are covered by these regulations include oral, nasal, otic, ophthalmic, rectal, and vaginal drug products.
Cosmetic products covered include liquid oral hygiene products (mouthwash), and vaginal products.

37. Tamper-evident Packaging
OTC drug products must have one or more barriers to entry that, if breached or missing from package, provide consumers with evidence that tampering may have occurred
Packages must have unique designs or characteristics that can not be duplicated
A statement that alerts consumers to this tamper-evident feature

38. e.g.
“ For your protection, this bottle has an imprinted seal around the neck”
You should encourage patients to look for tamper-evident features and if missing or breached to return the product to the pharmacy or store.
It is not acceptable to have the tamper-resistant labeling solely on package inserts and
all tamper-resistant features must be referenced in the labeling statement.
If the tamper-evident system is an outer container, the inner container must bear a statement that it should be in the outer container at the time of purchase.

39. Tamper-evident Packaging
The agency stresses that “tamper-proof” OR “tamper resistant” packaging is not possible.
A labeling statement suggesting that the package is tamper-proof, as contrasted with tamper-resistant will be considered false and misleading.

40. Tamper-evident Packaging Examples
Examples of acceptable packaging include but are not limited to:
Film Wrappers-The film is wrapped around the entire product and must be cut or torn to open the package.
Blister or strip packs-The individual compartment must be torn or broken to obtain the product.
Bubble packs-The product and container is sealed in plastic and mounted in or on a display card. The plastic must be torn or broken to remove the package

41. Tamper-evident Packaging Examples
Heat Shrink bands or wrappers-The bands, applied at the juncture of the cap and the container, must be torn or broken to open the package. Cellulose wet shrink seals are not considered an effective tamper-resistant mechanism.
Foil, paper or plastic pouches-The product is enclosed in an individual pouch that must be torn or broken to obtain the product.

42. Tamper-evident Packaging Examples
Bottle seals-Paper, foil or thermal plastic is sealed to the mouth of a container under the cap. The seal must be torn or broken to remove the product. Bottle seals applied with a pressure sensitive adhesive are no longer considered an effective tamper-resistant mechanism.
Breakable caps-The container is sealed by a plastic or metal cap that either breaks away completely when removed from the container or leaves part of the cap attached to the container. The cap must be broken to open the container.

43. Tamper-evident Packaging Examples
Sealed tubes-The mouth of a tube is sealed and the seal must be punctured to obtain the product.
Aerosol containers -Aerosol containers are inherently tamper-resistant.
All Metal and Composite Cans-The container cannot be pulled apart without visible evidence of entry.
Note: Barriers made from readily obtainable material such as plain tape, saran wrap, aluminum foil, etc. must be printed to distinguish themselves from a substitute available from a retail product. Vitamins are currently excluded from tamper-resistant requirements because of their classification by the FDA as a food.
Saran polyvinylidene chloride or Saran resins and films (called PVDC) have been wrapping products for more than 50 years. Saran works by polymerizing vinylide chloride with monomers such as acrylic esters and unsaturated carboxyl groups, forming long chains of vinylide chloride. The copolymerization results in a film with molecules bound so tightly together that very little gas or water can get through. The result is a barrier against oxygen, moisture, chemicals and heat-qualities used to protect food, consumer and industrial products. PVDC is resistant to oxygen, water, acids, bases, and solvents.

44. OTC Drug Labelling Comprehensibility Readability Comprehensiveness
During the design of the label, special effort should be directed to ensure adequate comprehensibility, readability and comprehensiveness

45. Comprehensibility:
FDA regulations require that OTC drug labelling contain terms likely to be read and understood by the average consumer
Counselling consumers on how to interpret product labels properly
Labels on OTC drug containers and packaging should provide detailed information, so that consumers can properly select and use the drugs. The message should not be constrained by the size of the container or package.
To standardize labelling information for the average consumer is challenging: significant percentage of the population are “below average” in its ability to read, comprehend, discern and act properly on label information.I.e. 20% of the US adult population functionally illiterate (e.g. reading is below fifth grade level, expressing difficulty in reading and accurately comprehending a food package label or restaurant menu)

46. Readability:
Provision of essential information in the same order and area
Uniformity in print size, pictograms, icons, colours, numbering, margins etc.
Special populations: a threshold print size of 4.5, has been suggested as minimum, while not optimal.
Readability= how easy it is to read the text.
To increase the readability of the drug labelling:
Essential information should be provided in the same order and in the same area of every drug label.
Uniformity in the print size, pictograms, icons, colour, type size, type spacing, margins, paragraphs, upper vs. lower case lettering, bulleting, numbering and language simplification.
Special populations with impaired vision. E.g. a 45 year old needs 50% more light than a 20 year old and a 75 year old needs three times as much light as a 20 year old. We cannot control light! But we can compensate for low light and poor visual acuity by using large print for the most critical messages.

47. Limitations of package labelling:
A package label can never address the infinite management issues associated with drug use,particularly in the comorbidity or polypharmacy. Thus, package labelling should acknowledge and encourage dialogue with health professionals (pharmacist, doctor).
“ If you still have any questions about this product, talk to your doctor, pharmacist, or other health-care professional”

48. Expiration Date Labeling
Expiration Date: is the date beyond which the product should not be used because the stability, potency, strength, or quality may have been affected over time
FDA regulations govern how this date is determined and tested
Most OTC products are required to include an expiration date on the labeling

49. e.g. topical drugs, skin protectants, lotions, and astringents
OTC drug products that do not have a dosage limit and are stable for at least 3 years are exempt from the requirement to include the expiration date on the label
e.g. topical drugs, skin protectants, lotions, and astringents
Labels must also include any special storage conditions or requirements for the product
Pharmacist should remind patients to check their OTC product labels periodically for expiration date

50. “Can I use it if expired?”!!
“Can I use it if expired?”
Safety: Rarely does a safety issue arise
Effectiveness: You should advise patients that the product probably has lost some of its ability to work as effectively as possible of the particular symptom or medical problem and it should be discarded

51. Marketing Issues Product Line Extensions
Nonprescription Drug Advertising (HOME WORK+ quiz)

52. Product Line Extensions
Reasons for product line extensions:
To capitalize on the loyalty created by consumer recognition and trust of a brand name
New doses, formulations, combinations of ingredients or even a totally different therapeutic entity (e.g. device) of a brand name product that has been originally marketed as single ingredient at a specific dose to treat specific symptom
Such extensions can create consumer confusion and inappropriate selection and use
Pharmacists must be familiar with the range of products within a brand name to recommend safely and correctly and to counsel patients on these products
Some product line extensions that carry the original brand name as prefix retain the active ingredient of the original product, but strengths may vary (e.g. Nytol and Nytol-one-a-night)
Some manufacturers may continue to use the brand name as the prefix but use none of the active ingredients of the original product and attach a suffix for differentiation (e.g. cold & flu, Extra, non-drowsy, sinus, Day/Night, and Plus)