© 2004, William E. Fassett
Revised 2/10/04
i. The FDA web site provides several articles on the History of the FDA and the food and drug laws.
ii. The Pure Food and Drug Act, also known as the Wiley Law, was passed in 1906, as the first comprehensive federal statute to assure purity and truthful labeling for foods and drugs.
iii. Growing problems with modern chemicals, and limits on the applicability of the Wiley Law, led to the passage in 1938 of the FDCA, which has been amended several times since then. A major impetus to the passage of the FDCA was an influential book by Ruth DeForest Lamb, “The American Chamber of Horrors.” A precipitating event was the marketing of “Sulfanilamide Elixir” by the S.E. Massengill Company, which contained diethylene glycol as the solvent – 107 deaths occurred before the FDA could get the product removed from the market.
1. The FDCA improved on the Wiley Law in three ways:
a. Required proof of safety before marketing drugs
b. Required pre-marketing approval of “new drugs” by the FDA.
c. All drugs marketed after 1938 in the US are “new drugs.” Drugs marketed prior to 1938 are not covered by the FDCA, unless changes are made in their formulation or labeling. Examples of these “old drugs” include some dosage forms of phenobarbital and various narcotic drugs. The FDA is developing a proposed Compliance Policy Guide on Marketing Unapproved Drugs that will allow the agency to take a closer look at pre-1938 drugs and possibly remove them from the market, or require manufacturers to bring market only dosage forms that have met FDCA requirements.
iv. Prior to 1951, pharmacists could dispense any drug – except narcotics – without a prescription. As a matter of professional ethics and courtesy, however, most pharmacists required prescriptions for many drugs, although refill procedures were somewhat lax. After 1951, however, the Durham-Humphrey Amendments created a new class of drugs that could not be dispensed without a prescription. These have become called “legend drugs,” because they were required to bear a “legend” on their label: “Caution: Federal Law prohibits dispensing without prescription.”
1. All existing drugs could be sold over the counter (OTC), without prescription.
2. New drugs that could not bear adequate labeling for safe use by the consumer would now be able to be marketed if information was provided to the physician, and these required a prescription.
3. The law allowed for oral prescriptions, and for refills.
v. In 1962, additional amendments, the Kefauver-Harris Amendments, were passed, triggered by problems with thalidomide, a drug which had not actually been marketed in the US, but which caused birth defects (phocomelia) in many babies born in Europe and Canada. The 1962 amendments required:
1. Proof of efficacy (effectiveness) as well as safety prior to marketing.
a. All drugs marketed between 1938 and 1962 had to be reviewed for efficacy, in a long-lasting effort by FDA known as the Drug Efficacy Study Implementation (DESI). Many marketed drugs – especially combination products – were removed from the market by this process (e.g., combinations of meprobamate and conjugated estrogen, combinations of antibiotics with antihistamines).
2. Established regulations called Good Manufacturing Practices (GMPs) requiring significant monitoring of manufacturers’ facilities and processes
3. Moved control of advertising for Rx drugs from the Federal Trade Commission to the FDA
4. Improved procedures and requirements for obtaining informed consent during clinical trials of new drugs.
vi. Other amendments since 1976 have largely affected marketing, patent rights, and promotion of generic drugs. These include:
1. Orphan Drug Act of 1983, extending patent protection and giving tax relief to companies that develop needed drugs without significant market potential. One such drug, however, was AZT (zidovudine).
2. Waxman-Hatch Amendment of 1984, which streamlined processes for approval of generic drugs, and gave extended terms of patents for certain drugs.
3. Prescription Drug Marketing Act of 1987, which controls distribution of legend drug samples, reselling of drugs by hospitals, and requires state licensing of drug wholesalers.
vii. FDAMA. The Food and Drug Administration Modernization Act of 1997 created significant changes in the FDCA, predominantly affecting manufacturers. A major section dealt with pharmacy compounding, but was invalidated by the US Supreme Court in Thompson v. Western States Medical Center, 238 F.3d 1090 (2002)
viii. Rx-to-OTC Switches
1. Most modern new drugs begin their marketed lives as legend drugs. However, after some time on the market, their general safety and usefulness for the lay public may become better known, and manufacturers may seek to have them moved to OTC status. This process is known as an Rx to OTC switch.
i. Preclinical testing, in vitro and in animals.
ii. Filing with the FDA of a Notice of Investigational New Drug (IND)
1. This allows the drug to shipped in interstate commerce for purposes of testing
iii. Clinical testing
1. Phase I – a small number of healthy volunteers to determine pharmacodynamic and pharmacokinetic properties
2. Phase II – a limited number of patients who have the target disease, to determine efficacy and dose-response.
3. Phase III – large-scale clinical trials in patients with the disease. At least two clinical trials must be conducted that are double-blinded and placebo-controlled.
iv. Filing of a New Drug Application (NDA). This filing describes the drug, the results of preclinical and clinical trials, sets forth the proposed labeling, a Risk Management Plan, and describes manufacturing and testing processes. If the NDA is approved, the drug may be marketed.
v. Post-marketing surveillance (also called Phase IV). The manufacturer must maintain records and file annual reports which include summaries of adverse reactions and problems discovered after marketing. Significant problems must be reported promptly, which may lead to revisions in the labeling.
vi. Supplemental NDAs are filed when the manufacturer seeks additional indications or changes in the labeling or production of the drug.
vii. Abbreviated NDAs are filed by manufacturers who wish to market generic versions of approved drugs after patent rights expire. (See drug product selection section.)
viii. New products are classified by the FDA using a rating scheme, which is indicated in information announcing the drug’s approval. A number indicates the chemical type and a letter (P or S) indicates the therapeutic potential. The FDA considers 1P (New Chemical Entity that is a Therapeutic Advance) the most important kind of new drug:
1. Chemical Type (1-6)
a. 1 = New Chemical Entity (NCE), a novel chemical agent
b. 2 = New salt or ester of a previously approved drug
c. 3 = New formulation of previously approved drug(s)
d. 4 = New combination of previously approved drugs
e. 5 = Duplicate of another product
f. 6 = Previously marketed by the same firm
2. Therapeutic Potential (P or S)
a. P = Therapeutic advance
i. No other effective drugs for the indication
ii. More effective or safe than other drugs for the indication
iii. Other important advantages compared to other drugs
b. S = Similar to other drugs on the market for the condition
i. articles used for food or drink for man or other animals,
ii. chewing gum, and
iii. articles used for components of any such article.(21 USC § 321(f))
i. articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and
ii. articles intended for use as a component of any such articles; except that such term shall not include soap. (21 USC § 321(i))
i. recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
ii. intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
iii. intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. (21 USC § 321(h))
1. Class I – Common and simple devices needing to conform to general standards (e.g., tongue depressors, bandages, neck braces)
2. Class II – Devices needing to meet specific performance standards (e.g., thermometers)
3. Class III – Devices that pose risk of injury if not properly used or produced, that require pre-market approval (e.g., defibrillators, pacemakers, IUDs)
ii. Restricted Devices. Some devices require a prescription or order of a prescriber to sell or dispense. These are labeled “Caution: Federal law restricts this device to sale by or on the order of a physician.”
(g) (1)
The term ''drug'' means
(A)
articles recognized in the official United States Pharmacopoeia, official
Homoeopathic Pharmacopoeia of the United States, or official National
Formulary, or any supplement to any of them; and
(B)
articles intended for use in the diagnosis, cure, mitigation, treatment, or
prevention of disease in man or other animals; and
(C)
articles (other than food) intended to affect the structure or any function of
the body of man or other animals; and
(D)
articles intended for use as a component of any article specified in clause
(A), (B), or (C). A food or dietary supplement for which a claim, subject to
sections 343(r)(1)(B)
and 343(r)(3) of
this title or sections 343(r)(1)(B)
and 343(r)(5)(D)
of this title, is made in accordance with the requirements of section 343(r) of this title
is not a drug solely because the label or the labeling contains such a claim. A
food, dietary ingredient, or dietary supplement for which a truthful and not
misleading statement is made in accordance with section 343(r)(6) of this
title is not a drug under clause (C) solely because the label or the labeling
contains such a statement.
i. Any article listed in the official compendium (i.e., the USP/NF) must conform to compendial standards for purity, quality, strength, and appropriate assays.
ii. Drugs must be stored in accordance with USP standards, and any special requirements specified on the manufacturer’s label.
iii. The USP defines the following temperature ranges for storing drugs:
1. Controlled room temperature
2. Cool place
3. Cold place
iv. Pharmacies must maintain their drug storage areas within a controlled range, which requires air conditioning in most areas of the US.
v. Refrigerators or freezers used to store drugs may not be used to store food or non-drug products.
i. The “label” of a drug is the actual label affixed to the bottle or box containing the medication. The “labeling” includes the label, and any other printed or written material accompanying the drug. Labeling also includes statements made by the manufacture or seller in promotional materials, advertisements, or other communications to patients or health professionals.
ii. OTC drugs must bear adequate directions so that lay persons can use the product safely and effectively. If a product cannot be labeled in such a way that the consumer can use it just by reading the label, it will be restricted to sale by prescription.
iii. Specific elements are required by the FDCA on the labels of OTC drugs. The “7-point label” must contain:
1. Name of Product
2. Name and address of manufacturer, packager, distributor
3. Net contents
4. Active ingredients and quantity of certain other ingredients
5. Name of any habit forming drug
6. Cautions and warnings
7. Adequate directions for use
iv. The FDA has recently developed new regulations that have changed the look of OTC drug labels and require the same format for all labels.
i. Covered OTC products include
1. Aspirin
2. Acetaminophen
3. NSAIDs
4. Iron preparations > 250 mg elemental iron per package
5. Diphenhydramine > 66 mg per package
6. Lidocaine and Dibucaine
7. Minoxidil
8. Methyl salicylate
9. Ethylene glycol
10. Methyl alcohol
11. Hydrocarbons and solvents
12. NaOH, KOH
ii. For OTC drugs, each manufacturer must make at least one package size with a CRC. A manufacturer may make one size only that is intended for households without small children. It must bear the caution “This Package for Households without Young Children.”
iii. Washington law requires pharmacists who dispense any of the above-listed OTC drugs on prescription to use a CRC. (RCW 18.64.246 and WAC 246-869-230) These regulations can be read to require CRCs on all prescriptions in which OTC drugs are dispensed, even if the CPSC has not listed the product, but in at least one state court case the judge ruled to the contrary.
i. An indicator of tampering or barrier to entry, that
ii. If breached or missing provides visible evidence of tampering
iii. A label statement must describe the barrier or indicator
i. Pharmacists are allowed to make recommendations to customers about the hazards and benefits of medications, consistent with their knowledge, training, experience, and good judgment.
ii. Specific assurances (“this is perfectly safe for your baby”) may create a warranty of fitness for a particular purchase that can lead to liability to the consumer if the product does not perform as stated or is harmful.
i. Vitamin
ii. Mineral
iii. Herb or other botanical
iv. Amino acid
i. Intended to supplement the diet by increasing total dietary intake, or
ii. A concentrate, extract, metabolite, constituent or combination of the above.
i. Intended for ingestion
ii. Not represented for use as a conventional food or sole item of a meal or diet
iii. Labeled as a dietary supplement
i. Claim benefit related to a classic nutritional deficiency disease (e.g., scurvy, beri-beri)
ii. Describe the role of a nutrient intended to affect the structure or function of the body
iii. Characterize the mechanism of action
iv. Describe general well-being gained from consuming a nutrient
v. Must state that the FDA has not evaluated any labeling claims
i. Sellers may sell or display articles, books, and abstracts of peer-reviewed scientific publications.
1. These must be reprinted in their entirety
2. Must be presented with other publications to present a balanced view
3. Must be physically separate from the product
ii. Sellers may not apply information to the product by sticker, shelf-talker, etc., that would make claims not allowed in labeling
i. The “label” of a legend drug is the actual label affixed to the bottle or box containing the medication. The “labeling” includes the label, and any other printed or written material accompanying the drug. Labeling also includes statements made by the manufacture in promotional materials, advertisements, or other communications to patients or health professionals.
ii.
The FDCA and state law requires the following on the label of
a prescription dispensed by a pharmacist to a patient:
|
Elements required on a prescription label dispensed
to a patient |
||
|
|
FDCA |
RCW 18.64.246 |
|
Name
and address of the pharmacy |
ü |
ü |
|
A
serial number |
ü |
ü |
|
Name
of prescriber |
ü |
ü |
|
Name
of patient, if on the prescription |
ü |
|
|
Name
of patient |
|
ü |
|
Directions
for use, if on the prescription |
ü |
|
|
Complete
directions for use |
|
ü “As directed” prohibited. (WAC 246-875-020(1)(h)) |
|
Date
of filling or refilling |
ü |
ü |
|
Name
and strength of drug |
|
ü* |
|
Quantity
dispensed |
|
ü* |
|
An
expiration date. Often called a “use before” or “discard after” date |
|
ü |
|
The
statement, “Warning: State or Federal law prohibits transfer of this drug to
any person other than the person for whom it was prescribed” |
|
ü |
|
Identity
of pharmacist responsible for dispensing. |
|
ü** |
|
Supplemented
by additional oral or written written information as required by regulation.
Includes auxiliary labels. |
|
ü |
|
* May be omitted if prescriber requests. |
||
i. Oral contraceptive inserts consist of a complete insert and a brief insert. Both must be dispensed to ambulatory patients each time the drug is dispensed. In hospitals, these must be provided to the patient at the first dispensing, and once every 30 days.
ii. Estrogens and progestins also require a single patient information leaflet be dispensed with each prescription and each refill. In hospitals, these must be provided to the patient with first use of the drug, and every 30 days.
i. All states allow physicians, podiatrists, dentists, and veterinarians to prescribe legend and controlled substances. Other practitioners may or may not have prescriptive authority for one or more classes of drugs
ii. Most states honor prescriptions from out of state physicians, podiatrists, dentists, and veterinarians.
1. Washington allows full or partial prescriptive authority to a variety of practitioners. Click here for a table that summarizes prescriptive authority and scope of practice in WA. This table also includes academic and other abbreviations commonly used by professionals who practice in health care settings.
2. Practitioners – out of state prescriptions are acceptable. WA allows the following prescribers who are licensed in any state, or in British Columbia, to issue prescriptions for legend drugs that are valid in WA. (Note: Canadian prescribers cannot issue CSAs.)
a. Physicians (MD) and Osteopathic Physicians (DO)
b. Dentists (DMD, DDS)
c. Podiatrists (PodD, DPM)
d. Veterinarians (DVM)
3. “Mid-level” practitioners – out of state prescriptions are not allowed from these practitioners.
a. Physician’s Assistants (PA, PA-C)
b. Nurse Practitioners (ARNP) (includes Nurse Midwives)
c. Nurse Anesthetists (CRNA)
d. Optometrists (OD)
e. Naturopaths (ND)
f. Midwives (very limited)
g. Pharmacists (R.Ph., Pharm.D.) under collaborative practice agreements
i. Must be prescribed in the context of a bona fide prescriber-patient relationship. Prior to issuing a prescription, for example, the prescriber must have conducted an appropriate examination and maintained proper records, and made a professional judgment.
1. Prescriptions that are “sold” to patients are not valid. For example, Internet prescribing seldom involves a bona fide patient-prescriber encounter. Likewise, prescription “mills” where patients pay to have prescriptions written (often for CSAs) do not produce valid prescriptions that a pharmacist can lawfully dispense.
ii. Must be within the scope and authority of the prescriber. A podiatrist cannot prescribe medications for congestive heart failure, even though ankle edema is a result of CHF. A dentist cannot normally prescribe birth control pills. Likewise, some practitioners, such as optometrists, are not able to prescribe Schedule II drugs in most states. Veterinarians cannot prescribe drugs for humans, and MDs cannot prescribe drugs for cats or dogs. A pharmacist who knows, or should know, that a particular prescription is not within the scope or authority of the issuing prescriber has a corresponding responsibility not to fill the prescription. The pharmacist must be aware, however, of current trends in use of drugs by the various practitioners who normally prescribe for his or her clients. If in doubt, ask the prescriber to fill you in on how they intend the drug to be used, so you can help the client understand its use better.
i. Drugs used for non-medical purposes include stimulants for “recreational use” or androgens for weight training. This could include Ipecac used by persons with eating disorders. Non-legitimate drug use is a greater problem with controlled substances than with legend drugs. Nevertheless, if a pharmacist knows or should know that the drug is being used for a non-medical purpose, he or she is not authorized to dispense the product.
ii. Specific statutory prohibitions exist against prescribing, administering, or dispensing “steroids,” or any form of autotransfusion, for the purpose of manipulating hormones to increase muscle mass, strength, or weight, or to enhance athletic ability unless medically necessary (e.g., runner’s anemia). Steroids include
1. “Anabolic steroids”
2. “Androgens”
3. “Human growth hormone” (RCW 69.41.300-310)
i. RCW 69.41.010(11) defines a “legible prescription” as “capable of being read and understood by the pharmacist filling the prescription or the nurse or other practitioner implementing the medication order.”
ii. RCW 69.14.120 requires prescriptions to be legible.
iii. Pharmacists who fill illegible prescriptions without verifying the prescription are liable for damages caused to their patients.
i. Date written
ii. The patient’s address must be on the prescription or available in patient medication record, a record book, or hospital or clinic record. (WAC 246-869-100(2)(a))
iii. Directions for use. Washington does not allow a prescription for an outpatient prescription to bear “UD” (ut dictum – as directed) instructions. Thus the prescription must contain complete directions. If not, the pharmacist must ascertain the directions from the prescriber.
1. Some products are clearly labeled on the container, such as birth control pills. In these cases, UD should be interpreted to read “as directed on the container.”
2. Some directions are for complicated doses. The prescriber may have given a written schedule to the patient, such as in step-down dosing of prednisone. In such a case, the pharmacist needs to know what those instructions were, to determine compliance. The pharmacist should make a copy of the instructions and attach them to the original prescription, and use them to estimate a days’ supply. The directions would then be interpreted as “Take according to written sheet provided by physician.” If appropriate, a “not to exceed” limit should be specified on the label.
3. Sometimes the patient is given the drug, and told to confirm the dosage with the prescriber, or will take differing doses in accordance with monitoring of therapy, as in treatment with Coumadin®. In such cases, the directions should be interpreted as “take on a [daily] basis per consultation with [physician].” Maximum dosing should be specified if appropriate.
iv. Instructions regarding generic substitution. This is automatic with two-line prescription blanks, but the information needs to be gathered specifically on telephoned orders, and recorded on the face of the prescription by the pharmacist. (RCW 69.41.120).
1. Prescriptions written by generic name (or telephoned by generic name) do not come under the requirements of the substitution law.
v. The pharmacist must place a serial number, the date of dispensing, and the initials of the responsible pharmacist on the face of the prescription. (WAC 246-869-100(2)(c)).
vi. In all cases where product interchange has occurred (see below), the pharmacist must record the identity of the actual drug dispensed on the prescription and in the patient record. (RCW 69.41.120) This is most easily and clearly done by recording the National Drug Code (NDC) of the product dispensed.
i. Must contain the date, time, and telephone number and location of the transmitting FAX machine.
ii. The pharmacist is responsible for assuring that the FAX will be legible for two years (i.e., not printed on thermal paper).
iii. The pharmacist is responsible for verifying that each FAX is valid and shall verify the authenticity of the prescription with the prescriber if there is a question.
iv.
There cannot be an exclusive agreement concerning FAXed orders
between the pharmacy and the prescriber.
(Additional requirements have been established for FAXes of controlled
substances in Schedule II.)
i. The law allows for electronic transmission of prescriptions, (RCW 69.41.055) and permits the Board to adopt specific rules. The law requires the following:
1. Transmission is directly from the prescriber to a pharmacy of the patient’s choice, with no intervening person having access to the information. (This prohibits orders being transmitted through an insurance company.)
2. The Board must approve the systems for sending and receiving the information.
3. The information must include an “explicit opportunity” for prescribers to communicate preferences regarding generic substitution.
4. Confidentiality and security of the information must be assured.
a. The pharmacist in charge (responsible pharmacy manager) shall establish or verify procedures and policies to ensure integrity and confidentiality of the prescription information.
b. All managers, employees, and agents of the pharmacy must read, sign, and comply with the established procedures
5. The pharmacist must exercise professional judgment regarding the accuracy, validity and authenticity of the drug orders transmitted electronically.
ii. The Board publishes a list of approved systems on its website.
i. When a drug is prescribed by its official or “generic” name (e.g., Ibuprofen tablets 800 mg), the prescriber has left it to the pharmacist to determine the particular manufacturer or source of the product, secundum artem (“according to the art” of the apothecary).
ii. When a drug is prescribed by brand name (e.g., Motrin tablets 800 mg), it is understood that the prescriber intends a particular product from a particular manufacturer.
i.
Pharmacist’s Reference Sources
In all states, a prescription written by generic (nonproprietary) name permits
the pharmacist to choose the source of the product, whether it is bioequivalent
to a brand name drug or not.
1.
Orange Book
The “Orange Book” is officially entitled “Approved Drug Products with
Therapeutic Equivalents,” and is published by the FDA. The only products
listed are drugs with NDAs and/or ANDAs. Old drugs (including digitalis,
Phenobarbital, etc.), which were marketed prior to 1938, do not have NDAs and
are not included in the Orange Book. Drugs that are considered therapeutically
equivalent are given an “A” rating; those that are not are rated “B.” A second
letter is appended to indicate the basis for the rating, and all generically
equivalent products are rated “AB.” In every case, the rating of a generic drug
is related to a specific innovator’s product. In some cases, two innovator’s
products have the same chemical ingredient, but are not, themselves,
bioequivalent. This is most often the case with sustained-release preparations
that use different formulations to achieve their release characteristics. For
example, Adalat CC™ and Procardia XL™ each contain nifedipine HCl. However,
they use different formulations, and are not interchangeable as generics.
Procardia XL was marketed first, and is given a three-symbol rating: AB1;
Adalat CC is rated AB2. Generic nifedipine formulations that are
interchangeable with Procardia XL are rated AB1, and those that can be
substituted for Adalat CC are rated AB2.
2.
Positive Formularies
Some states do not allow the pharmacist to substitute any equivalent generic,
but require the pharmacist to choose from drugs on a specific list. This list
is often called a “positive formulary.” Some states specify the Orange Book as
their positive formulary, while others have a special commission that develops
the list. Washington allows the pharmacist to choose from sources in addition
to the Orange Book, so would not be said to use a positive formulary. However, the Orange Book is referred to in WAC 246-899-030(b)
as a “board approved reference for a positive formulary of therapeutically
equivalent products within the limits stated in that publication.” (Revised
2/10/04)
3.
Negative Formularies
A few states have lists of drugs that cannot be substituted. Many of these
lists include so-called “narrow therapeutic index drugs,” such as
levothyroxine, warfarin, digoxin, and furosemide. The drugs placed on these
lists are often placed there as a result of a political process in which
manufacturers and physicians have lobbied to limit generic substitution.
Illinois is an example of a state that uses a negative formulary, and also
requires each pharmacy to develop its own “positive formulary” that is made
available to the public. Washington does not specifically preclude generic
substitution by use of a negative formulary.
ii.
“DAW” instructions and special prescription blanks.
Most states allow prescribers to prevent generic substitution on a
per-prescription basis. Some will allow the prescriber to indicate “Dispense As
Written” or “DAW” in writing on the prescription. Others allow a check-box (þ
DAW). Washington, like several other states, requires a two-line prescription
blank, with one signature line indicating “Substitution Permitted” and the
other indicating “Dispense As Written.” In Washington, manufacturer’s
successfully lobbied to have the DAW line be on the right hand side of the
blank, reasoning that many right-handed physicians would, by force of habit,
preferentially sign that line. Under Washington law, a prescription that is
written by a Washington prescriber is not valid unless it is written on a
two-line prescription blank. In Washington, pharmacists are required to obtain
and record specific instructions regarding substitution when receiving
telephoned prescriptions, and to indicate this on the permanent record (WAC
246-899-020 (a))
1. Dealing
with out-of-state prescriptions.
According to the statute, Washington pharmacists may substitute the generic
product on an out-of-state prescription written by brand name unless “otherwise
instructed by the prescriber through the use of the words ‘dispense as
written’, words of similar meaning, or some other indication.” However, the Board has qualified this requirement in WAC
246-899-050. If the practitioner has not clearly provided instructions
regarding substitution, the pharmacist may substitute a generic only if the
pharmacist has determined substitution is permitted by one of the following
means:
a. The pharmacist has personal knowledge of the rules in the
state of origin; or
b. The pharmacist has obtained authorization from the
prescriber; or
c. The pharmacist obtains current information on the rules in
the other state from
i.
The Washington Board of
Pharmacy
ii.
The Board of Pharmacy in the
other state
iii.
Some other reliable
professional means. [rev. 2/10/04]
iii.
Generic substitution is required in Washington.
Washington does not allow the pharmacist to dispense a brand name if
substitution is permitted except when:
1. The pharmacy does not have a generic product in stock which is, in the pharmacist’s professional judgment, bioequivalent to the drug prescribed; or
2. The patient or the patient’s agent requests the branded product, and the product is not being paid for by public funds.
iv.
Savings must be passed on to purchaser in Washington.
Washington law requires that 60% of savings resulting from generic substitution
be passed on to the consumer. The calculation should be made as follows:
Savings |
= |
Actual Acquisition Cost of Brand Name Drug |
– |
Actual Acquisition Cost of Generic Drug |
|
Maximum Price |
= |
Normal Price of Brand Name Drug |
– |
(Savings ´ 0.6) |
Example: Your pharmacy’s normal cash price for a brand-name drug is $85.00 for 90 tablets. The Average Wholesale Price (AWP) for this product is $83.00 per 100. Your Actual Acquisition Price (AAC) from the wholesaler is AWP less 18% for this drug. Your AAC for the generic equivalent is $41.00 per 100. What is the maximum price you can charge the patient for 90 tablets under WA law?
Savings = ($83 ´ 90/100 ´ 0.82) – ($41 ´ 90/100) = $24.35
Max. Price = $85.00 – ($24.35 ´ 0.6) = $70.39
Margin on brand name drug: $23.75 ¸ $85.00 ´ 100% = 27.9%.
Margin on generic drug: $33.49 ¸ $70.39 ´ 100% = 47.5% (assuming competition will allow you to charge the maximum allowed price).
v. Notice to Public. RCW 69.41.160 requires the following notice to be displayed to the public in every pharmacy: “Under Washington law, an equivalent but less expensive drug may in some cases be substituted for the drug prescribed by your doctor. Such substitution, however, may only be made with the consent of your doctor. Please consult your pharmacist or physician for more information.”
vi. Pharmacists are protected by RCW 69.41.170 from being coerced by employers to dispense a particular generic drug or to substitute a generic drug for another drug.
i. With prior authorization (Washington requires documentation to be available in the pharmacy records – WAC 246-899-030(3) [rev. 2/10/04]
ii. Specific authorization
iii. Via Collaborative Practice Agreement
iv. In accordance with the Therapeutic Interchange Program and Preferred Drug List (WA)
1. The 2003 Legislature passed SB 6088, which creates a Preferred Drug List (PDL) for use in all state-funded drug programs, including Medicaid and the Uniform Medical Plan (UMP) for state employees. The Washington Health Care Authority (HCA) administers the program, which is entitled Rx Washington.
2. The current Preferred Drug List is updated frequently on the Rx Washington web site.
3. The Pharmacy & Therapeutics Committee that determines the PDL is composed of 10 members (4 physicians, 4 pharmacists, 1 PA, 1 ARNP). Currently three of the 10 members are on the WSU faculty: Angelo Ballasiotes, PharmD; Jason Iltz, PharmD; John White, PharmD, PA.
4. A Therapeutic Interchange Program (TIP) is established by the legislation. Currently (2/04) the agencies project that this program will go into effect on May 1, 2004. After that time, pharmacists dispensing prescriptions that are paid for by a state program are authorized and required to perform therapeutic substitution using drugs on the PDL, where a non-preferred drug has been ordered.
a. Eligible prescriptions must be have been written by an “endorsing practitioner.”
i. HCA maintains a database to identify endorsing practitioners
ii. Prescriptions written by non-endorsing practitioners
1. Will be filled at Tier-3 rates for UMP beneficiaries
2. Will be subject to prior authorization for other state plans
3. May be substituted via prior authorization
iii. The endorsing practitioner may indicate “DAW” – the drug will NOT be subject to prior authorization, but will be subject to Tier-3 pricing for UMP recipients.
1. This “DAW” does not relate to generic substitution, which is indicated by a signature on a two-line blank.
iv. A UMP recipient may request DAW, and pay the Tier-3 price, if the drug is covered.
b. Substitutions are to be made from within the same therapeutic class.
c. Refills of certain types of drugs are not subject to substitution
i. Antipsychotics
ii. Antidepressants
iii. Chemotherapy
iv. Antiretroviral
v. Immunosuppressive
d. When a substitution is made, the pharmacist shall notify the prescriber of the specific drug and dose dispensed (can be by FAX, etc.)
5.
A new paragraph is added at the end of RCW 69.41.150:
(3) A pharmacist who substitutes a preferred drug for a nonpreferred drug
pursuant to section 5 of this act assumes no greater liability for substituting
the preferred drug than would be incurred in filling a prescription for the
preferred drug when prescribed by name.
i. For financial reasons (including insurance coverage) the patient doesn’t want to purchase the full amount. A prescription written for levothyroxine 100 mcg, #90, can be filled for any quantity less than 90, e.g., 30 tablets. It may be refilled in quantities of 30 until a total of 90 have been dispensed.
ii. When the patient has not received the drug before and is unsure whether he or she will tolerate it or if it will meet the patient’s needs.
iii. When the pharmacy does not have sufficient medication in stock.
1. Handling of out-of-stock creates problems when third parties (especially government payors) are to be billed for the drug. These parties do not want to pay for unused drug or drug that is not delivered to patients. When partial fills have been made with the expectation that patients will pick up the remainder, and the third party is billed for the full amount due to transaction requirements, the third party will feel defrauded if the patient forgets to pick up the drug. The US government sued a major chain over this issue and the settlement was in the millions of dollars.
a. If possible, 3rd parties should not be billed until the full quantity has been dispensed.
2. The pharmacy cannot legally reuse drugs that have been sold to a patient, even if the patient “abandons” the drug by not returning. Most states, including Washington, have “abandoned property” statutes that require that the abandoned property belong to the state.
3. If the pharmacy wants to deliver or mail the remainder of the product to the patient, that may raise problems of making drugs available to children or others without the knowledge of the patient that the drug was to be mailed.
a. If possible, obtain the patient’s written permission to mail the remainder of the drug to their home in the event that they have not picked up the drug in a certain length of time.
iv. It is a long-standing standard of practice that the pharmacist may dispense more than the amount specified in the prescription when refills have been allowed, and the patient’s interests warrant it. For example, the physician prescribes Lipitor 10 mg, #30, and labels the prescription “Refill PRN.” It is known and obvious that if the patient tolerates the initial prescription, he or she will be continuing to take the drug chronically. If the insurance allows a 90-day supply, the patient will want to obtain the drug in the larger quantities on refills. Using good judgment, the pharmacist may reasonably refill the Lipitor in quantities of 90, without consulting the physician. If no refills were allowed, however, this would not be possible. Generally, controlled substance prescriptions cannot be refilled in larger amounts than specified on the original prescription.
1. Judgment is important. Just because a drug is not a controlled substance does not justify refilling in larger quantities than originally specified. For example, a patient with a history of attempted suicide may be placed on tricyclic antidepressants in quantities of 10 to 30 tablets per refill. Even if additional refills are allowed, the pharmacist must be cognizant of the reality that dispensing 100 tablets at a single time provides the patient with the opportunity of taking a fatal overdose.
i. A prescription written for prednisone 10 mg tablets #50, ½ tablet daily, may be filled with prednisone 5 mg #100, provided the label directions correctly specify one tablet instead of ½ tablet as the dose. The patient must clearly understand what has been done, and it is a good practice to notify the prescriber.
ii. A prescription written for levothyroxine 225 mcg cannot be dispensed as such because no manufacture makes a 225-mcg tablet. The pharmacist may wish to verify the dose to be sure an error was not made, but otherwise has the choice of dispensing the prescription as follows:
1. Levothryoxine 113 mcg, with directions of 2 tablets per dose.
2.
Levothyroxine 200 mcg, 1 tablet per dose, plus
Levothryoxine 25 mcg, 1 tablet per dose, as two separate prescriptions.
In either situation, it is advisable to notify the prescriber what was actually dispensed.
i. May be refilled X times. In this case, the pharmacist may refill the drug up to X times, in the same quantity as the original.
ii. May be refilled through a certain date. In this case the pharmacist may refill the drug as often as needed until the date shown.
iii. May be refilled “PRN.” In Washington, PRN is defined by the Board to indicate authorization for up to one year from the date the prescription was written. No prescription in Washington may be refilled beyond one year from the date written. (WAC 246-869-100(2)(d))
iv. Refills may be authorized by the prescriber after the prescription is written, typically upon a call from the pharmacist. The Board requires pharmacies to treat a refill authorization occurring more than a year after the prescription is written as a new prescription, with a new prescription number.
i. “Copies.” The original of every prescription must be retained in the pharmacy. Sometimes patients will request a “copy” of their prescription for informational purposes. Such copies may be made, but must be clearly labeled as such. (WAC 246-869-100(e)).
1. Prescriptions may be photocopied and provided to the patient or others to whom the patient has authorized, stamped with “COPY”.
2. Pharmacists may hand copy the prescription on the pharmacy’s prescription form, indicating a COPY.
a. It was the practice of pharmacists in past years to include pricing information on the prescription, often in coded fashion. One popular code was called the NARD Code, developed by the National Association of Retail Druggists, now known as NCPA. This code used the word “PHARMOCIST’ where each letter represented the digits, 1-2-3-4-5-6-7-8-9-0, respectively. The letters NA preceded the code and it was followed by RD. For example, “NA-PHM-RD” would indicate a price of $1.25. This practice is uncommon now, in part because of challenges to its use as a means of price fixing among competitors.
3. These copies are not valid for filling, so the pharmacist receiving such a copy must contact the prescriber and obtain a new oral prescription.
ii. Pharmacies are allowed under WAC 246-869-090 to transfer prescriptions, along with available refills, to another pharmacy. It is important for the pharmacist or intern involved in the process to follow the steps listed in the regulation. In Washington, pharmacists or interns may transfer and receive transferred prescriptions.
1. The originating pharmacist (“transferor pharmacist”) must perform the following steps:
a. Record that the prescription has been transferred in the medication record system.
b. Record in the medication record system the
i. Name and address of the pharmacy to which it has been transferred
ii. The name of the pharmacist (or intern) that received the information.
1. Note: a person’s “name” for the purposes of drug and practice laws is the full name that the person normally would use to conduct business. Thus, simply recording the first name of the other pharmacist is not appropriate.
c. In addition, for controlled substances (schedule III, IV, and V), the originating pharmacist must follow the procedures specified in 21 CFR § 1306.25,* which include the following:
i. Locate the original hard copy of the transferred prescription.
ii. Write the word “VOID” on the face of the prescription
iii.
Record the name, address, and DEA number of the pharmacy
receiving the information on the reverse of the original prescription, along
with the name of the pharmacist receiving the information.
*Note: in the July 2003 version of WAC 246-869-090 (2)(e), the citation to the
CFR incorrectly indicates “21 CFR 1300.26” instead of “21 CFR 1300.25”.
2. The receiving pharmacist treats the prescription as an oral prescription, and must perform the following steps:
a. Reduce the prescription to writing on a prescription blank, including patient name, address, doctor’s name and address, and other information required to be on the prescription.
b. Write the word “TRANSFER” on the face of the prescription.
c. Also record the following:
i. The date the prescription was originally written (cannot be refilled for a year after that.)
1. When processing a transferred prescription, it is important to override the current date in the computer, and record the original date written
ii. Number of refills remaining
iii. Date of last refill
iv. The name and address of the transferring pharmacy, and the serial number of the original prescription at that pharmacy
v. The name of the transferring (transferor) pharmacist.
d. For controlled substances, the receiving pharmacist must also record the following:
i. Number of original refills allowed on the prescription
ii. Dates (and locations) of all previous refills
iii. Number of valid refills remaining
iv. DEA number of transferring pharmacy
v. Name, address, serial number and DEA number of pharmacy at which prescription was originally filled (if different from transferring pharmacy).
3. Legend drugs may be transferred, and re-transferred as often as needed until all refills are used. If a patient has had a prescription transferred to another pharmacy, and now wants to have it refilled at the original pharmacy, the original pharmacy must contact the other pharmacy and receive the prescription back as a transferred prescription. At this point, it should be given a new prescription number.
4. According to DEA rules, controlled substances may be transferred on a “one-time” basis, unless the transferring pharmacies share a common electronic database.
5. Pharmacies with a common electronic database may track refills for non-controlled substances at any outlet in this common database, without going through the prescription transfer process. Many chains (e.g., Rite-Aid and Walgreens) have these databases.
i. All prescriptions for ORAL dosage forms of legend drugs in WA must be dispensed in CRCs, except for drug products exempted by the CPSC. Exempted products are listed in 16 USC § 1700.14, and include:
1. Nitroglycerine sublingual tablets
2. Sublingual and chewable isosorbide tablets £ 10 mg
3. NaF £ 110 mg per package (tablets and liquids, must be £ 0.5% elemental fluoride w/w or w/v)
a. Exercise: how many tablets of Chewable Vitamins with Flouride containing 0.5 mg of fluoride ion per tablet may be dispensed in a non-CRC? (Hint: 1 mg F- is contained in 2.21 mg of NaF.)
4. Cholestyramine and colestipol powder
5. Oral cortisteroids
a. Prednisone containing £ 105 mg per package
b. Betamethasone containing £ 12.6 mg per package
c. Methylprednisolone containing £ 84 mg per package
6. Mebendazole £ 600 mg per package
7. K+ supplements £ 50 mEq/dose
8. Erythromycin ethylsuccinate, measured as erythromycin equivalent
a. Granules for suspension and suspensions containing £ 8 g
b. Tablets containing £ 16 g per package
9. Aerosols for inhalation
10. Pancrelipase
11. Hormone products
a. Oral contraceptives in memory aid packages
b. Methylprogesterone acetate tablets
c. Conjugated estrogens in mnemonic packages containing £ 32 mg per package
d. Norethindrone acetate in mnemonic packages containing £ 50 mg per package
e. Hormone Replacement Therapy Products relying solely on one or more estrogens or progestogens for activity.
12. Sacrosidase (sucrase) in glycerol and water.
ii. Pharmacists may dispense legend drugs in non-CRCs if:
1. The patient or the patient’s agent requests. Such a request may be a “blanket” request that all drugs dispensed to the patient be in non-CRCs.
2. The prescriber requests it on the prescription at the time it is written. Prescribers may not issue “blanket” requests, either for all drugs dispensed to a particular patient, or for all of his or her patients.
iii. Under federal law, requests for non-CRC containers may be oral or in writing. Washington incorporates the federal rules into its pharmacy regulations, but requires requests for non-CRC containers be:
1. In writing, by the patient or the patient’s agent, or in writing by the prescriber; and
2.
An indication that a non-CRC has been requested must be made
in the patient medication record system.
The date of the request should be included in the documentation kept in the
pharmacy. At various times, Washington Board of Pharmacy investigators have
insisted that such requests be renewed after some “reasonable” length of time,
such a one year. This is a good practice, but it is NOT required by current
Washington pharmacy regulations.
iv.
Legal liability for use of non-CRCs.
If a pharmacist dispenses a covered drug in a non-CRC, and a child is injured
as a result of gaining access to the drug, the child, his or her guardian, or
the child’s estate (in case the child dies), may file a lawsuit against the
pharmacist for damages. In an Iowa case (Baas v. Hoye,
766 F.2d 1190), the pharmacist was found liable for the death of a child
who ingested Tedral SA (containing theophylline) prescribed for her father that
was dispensed in a non-CRC. The
pharmacy argued that the father had requested a non-CRC on the prescription,
but didn’t have a written record to substantiate this, and the parents claimed
otherwise. Normally, being able to document that the parent or guardian of the
child authorized the use of the non-CRC will serve as a defense against
liability. However, most childhood poisonings from legend drugs now occur as a
result of children obtaining access to grandparents’ drugs. Because
grandparents are not normally the legal guardians of their grandchildren, their
request for non-CRCs may not provide an adequate defense. Pharmacists should
consider including statements covering the following elements in the form used
by patients to request a non-CRC.
1. CRCs are required by law unless specifically requested otherwise by the patient.
2. The purpose of these regulations is to prevent childhood poisoning from prescription drugs.
3. As few as one or two tablets of some drugs may be fatal to young children.
4. The number one source of childhood poisoning by prescription drugs is non-CRC containers stored at a grandparent’s house or in a grandparent’s purse or bag.
5. Over 90% of elderly persons can successfully open non-CRCs if shown how. The pharmacy is willing to provide demonstrations and instructions to the patient on how to open a CRC. There are alternative CRCs that can be used by patients with arthritis or lack of hand strength, and the pharmacy is willing to obtain and provide these at cost to the patient.
6. The patient agrees that it is his or her responsibility to keep medications out of children’s reach, especially when using a non-CRC container.
7. Having read and understood the above, the patient nevertheless requests that non-CRCs be used on his or her prescription, and agrees to indemnify and hold harmless the pharmacy for any injuries that might occur to a child as a result of the patient’s request to use non-CRCs.
i. Wholesaler level
ii. Retail level
iii. Consumer level
i. Class I – there likelihood of injury or death from the use of the product; may include a public warning
ii. Class II – health problems, if any, are expected to be temporary or reversible
iii. Class III – use of the product is NOT likely to cause health problems
iv. Market withdrawal – minor health risk or minor FDA violation