Generic Drug Substitution Laws Readings Module 3 Law

Generic Drug Substitution Laws

• Prior to the 1970s, nearly all states had laws preventing pharmacists from dispensing generic drugs instead of brand-name drugs.
• These laws were intended to prevent the substitution of counterfeit drugs.
• Increased generic drug approvals in the late 1960s/early 1970s led to public demand for lower-cost options.
• The Medicaid Maximum Allowable Cost Program (1974) encouraged generic substitution by limiting reimbursement.
• State laws hindered patient access to generics and state Medicaid participation.
• Current state laws allow generic drug substitution under certain conditions.

Types of Drug Product Selection Laws

• State drug product selection laws vary.
• Mandatory substitution states mandate generic substitution unless the prescriber specifies "dispense as written."
• Permissive substitution states allow pharmacists to substitute if the prescriber permits.
• Substitution generally requires prescriber permission, even if the consumer desires it.
• Rules apply when a specific product is prescribed; pharmacists can choose any product in a generic drug class if the prescription is generic.

Labeling of Substituted Generic Drugs

• Labeling a substituted generic drug with the brand name is misbranding under state and federal law.
• This can lead to legal violations like deceptive business practices.
• Agbogun v. State: A pharmacist was found guilty for labeling a generic drug with the brand name Flagyl.

Importance of the Orange Book

• Pharmacists must ensure that a substituted generic drug is bioequivalent to the prescribed product.
• Bioequivalence means similar bioavailability (rate and extent of absorption).
• Initial bioequivalence concerns existed among physicians and pharmacists.
• The FDA published "Approved Drug Products with Therapeutic Equivalence Evaluations" (Orange Book) in 1979.
• The Orange Book is republished annually with updates and is available on the FDA's website.
• It lists FDA-approved drugs as safe and effective.
• The Orange Book helps healthcare professionals determine approval dates, patent/exclusivity expiration, and the existence of generic equivalents.

Therapeutic Equivalence Evaluations

• Approved drugs that are pharmaceutical equivalents (same ingredients, strength, dosage) are rated for therapeutic equivalence.
• Therapeutic equivalence is the expectation of the same clinical effect and safety.
• The FDA assumes that bioequivalent pharmaceutical equivalents are therapeutically equivalent.
• Therapeutic equivalence (Orange Book) is different from therapeutic substitution (substituting different therapeutic agents).
• Pfizer, Inc. v. Shalala : The court favored the FDA's interpretation on if drugs with the same active ingredient but different sustained-release systems could be considered pharmaceutical equivalents.

FDA's Two-Letter Coding System

• The FDA uses a two-letter coding system for therapeutic equivalence.
• First Letter: "A" or "B".
• A-rated: Therapeutically equivalent to a reference drug.
• B-rated: Not therapeutically equivalent (bioequivalence problems, inadequate standards, insufficient data, ongoing review).
• Second letter provides more specific information.

Examples of Orange Book Codes

• AA: Conventional dosage forms with no bioequivalence problems.
• AB: Bioequivalence problems resolved by scientific evidence.
• AN: Bioequivalent solutions and powders for aerosolization.
• AO: Bioequivalent injectable oil solutions.
• AP: Bioequivalent injectable aqueous solutions.
• AT: Bioequivalent topical drug with no known bioequivalence problems.
• BC: Extended-release dosage forms with bioequivalence issues.
• BD: Active ingredients/dosage forms with documented bioequivalence problems.
• BE: Delayed-release oral dosage forms with potential bioequivalence problems.
• BN: Aerosol nebulizer drug delivery systems (unless proven bioequivalent).
• BP: Active ingredients/dosage forms with potential bioequivalence problems.
• BR: Suppositories/enemas for systemic absorption (unless proven bioequivalent).
• BS: Products having drug standard deficiencies.
• BT: Topical drug products with bioequivalence issues.
• BX: Insufficient data to determine therapeutic equivalence.
• B*: No therapeutic equivalence determination will be made until questions are resolved.
• Generic drugs marketed after 1984 (approved under ANDA) should have an A rating due to bioequivalence requirements of the Drug Price Competition and Patent Term Restoration Act (PTRA).
• The number of B-rated products has decreased since 1986.

Implications for Pharmacists

• The Orange Book is essential for generic substitution and drug formulary decisions.
• Pharmacists can generally interchange A-rated pharmaceutically equivalent drugs.
• Interchanging B-rated drugs carries a risk of different clinical effects.

Multiple Reference Drugs and Three-Character Codes

• Multiple pharmaceutically equivalent reference drugs may not be bioequivalent to each other.
• The FDA uses a three-character code (e.g., AB1, AB2, AB3).
• Generic drugs bioequivalent to one reference drug receive the same code.
• Adalat CC (AB1) and Procardia XL (AB2) are not bioequivalent.
• AB1-rated drugs are not considered bioequivalent to AB2-rated drugs.
• Consult the Orange Book before switching pharmaceutically equivalent products.

Switching Pharmaceutically Equivalent Products

• Switching means substituting a pharmaceutically equivalent product for the patient's regular drug.
• Switching B-rated products requires pharmacist professional care and judgment.
• Consult with the physician and counsel the patient about potential risks. Many state laws require this.
• Formularies should be developed with awareness of B-rated drugs or those that might not be bioequivalent.
• Substituting a B-rated drug without assessing clinical risks increases civil liability.
• The Orange Book is a guide, not a mandate, so substituting a B-rated drug does not violate the FDCA, but it may violate state law.

Narrow Therapeutic Index (NTI) Drugs

• NTI drugs have a narrow window between toxic/lethal and effective doses.
• Careful titration and monitoring are needed.
• Examples: carbamazepine, clonidine, levothyroxine, lithium, minoxidil, phenytoin, theophylline, and warfarin.
• Concerns exist that FDA bioequivalence standards (80-125%) may not be precise enough.
• In 2010/2011, new FDA guidelines for NTI drugs narrowed the potency range to 95-105%.
• Exercise professional judgement when switching NTI drugs, inform patients and advise them to report any physiological changes.
• Do not switch B-rated NTI drugs without notifying the prescriber and informing the patient.
• Be aware of state laws restricting NTI product substitution.

Substitution of Biosimilar Biologics

• The Biologics Price Competition and Innovation Act (BPCIA) of 2010 created a regulatory framework for biosimilars (generic biologics).
• Key issue: whether a biosimilar can be substituted for the reference drug or another biosimilar.
• Biosimilars are not pharmaceutically equivalent.
• Biosimilarity: "highly similar" with no clinically meaningful differences in safety, purity, and potency.
• Interchangeable biosimilars must produce the same clinical result without greater risk.
• The FDA assures that interchangeable biologics can be switched back and forth without risk.
• The FDA publishes the "Purple Book" electronically.
• The Purple Book indicates the licensure date and whether a product is biosimilar ("B") or interchangeable ("I").
• If a biosimilar is deemed interchangeable, it can be substituted without prescriber intervention.
• If approved as biosimilar but not interchangeable, it can be specifically prescribed but cannot be substituted.
• Adhere to state laws regarding biosimilar substitution.
• As of July 2017, 35 states had statutes on biosimilar substitution, generally allowing substitution of interchangeable biosimilars with prescriber authorization/non-prohibition and pharmacy notification.

Patient Package Inserts (PPIs)

• Prior to the late 1960's, the FDA paid little attention to manufacturer-provided prescription drug labeling for patients.
• PPIs explain uses, risks, and precautions.
• Manufacturers must instruct pharmacists to distribute PPIs with each oral contraceptive and estrogen-containing drug prescription.
• Failure to do so is misbranding.
• PPI regulations apply to both community and institutional pharmacies.
• Institutions can provide the PPI like an ambulatory patient.
• Institutions can provide the PPI before the first dose and then once every 30 days thereafter.
• Schlieter v. Carlos (1989): Institutions cannot delegate PPI responsibility to the prescribing physician.
• In 1980, the FDA enacted regulations requiring PPIs for all prescription drugs, but this was revoked in 1982.

Consumer Medication Information (CMI)

• The FDA proposed distribution goals and performance standards, leaving it to the private sector to achieve them.
• 1996 legislation established a voluntary private sector process to provide useful written information with new prescriptions (95% goal by 2006).
• A 2001 study found that 89% of patients received written information, but it was useful only about 50% of the time.
• In July 2006, the FDA issued guidance on "Useful Written Consumer Medication Information (CMI)."
• A 2008 study showed 94% of consumers received CMI, but only 71% met minimum usefulness criteria.
• CMI remains unreviewed and unregulated by the FDA.

Medication Guides (MedGuides)

• The FDA mandates MedGuides for drugs posing a "serious and significant concern".
• Requirements apply to outpatients and for both new and refill prescriptions.
• Patient labeling (MedGuide) is required if:
• Labeling could help prevent serious adverse effects.
• The product has serious risks that patients should be aware of to decide whether to use or continue using the product.
• Patient adherence is crucial to the drug's effectiveness.
• Most situations when dispensing a drug to a healthcare professional, a MedGuide is not needed.
• However, exceptions and situations where MedGuides are mandatory include:
• When the patient or their agent requests a MedGuide.
• When the drug is dispensed in an outpatient setting for use without direct supervision.
• The first time a drug is dispensed to a healthcare professional for outpatient administration.
• The first time a drug is dispensed in any outpatient setting after a MedGuide is materially changed.
• When a drug is subject to a REMS that includes specific requirements for reviewing or providing a MedGuide.
• MedGuides must be written in nontechnical language and contain information on uses, contraindications, adverse reactions, proper use, and cautions.
• Manufacturers must obtain FDA approval before distribution and must provide sufficient MedGuides to distributors/dispensers.
• The dispenser must provide the MedGuide to the patient each time the medication is dispensed when required.
• Other written drug information does not replace the MedGuide.
• A 2004 study found that 29% of pharmacists were not familiar with MedGuides.
• The FDA has significantly increased the number of drugs requiring MedGuides; now nearly 800.
• The FDA is working toward a single, easy-to-read document ("patient medication information" or PMI).
• In February 2017, the FDA discussed a proposed rule requiring manufacturers to produce a one-page document highlighting the most important drug information.

Medication Guides and REMS

• The Food and Drug Administration Amendments Act (FDAAA) of 2007 authorized the FDA to require Risk Evaluation and Mitigation Strategies (REMS).
• MedGuides are an important component of REMS.
• The FDA considers every new MedGuide to be part of a REMS, although the agency has the discretion to require a new MedGuide as labeling only, not as part of a REMS.

Drug Information Websites

• The FDA offers "Drug Info Rounds"—training videos for pharmacists.
• The FDA provides its own drug information source at Drugs@FDA for consumers and healthcare professionals.
• A searchable database with information on approved prescription and some OTC drugs, as well as discontinued drugs.

Florida Pharmacy Regulations: Written Prescriptions (Section 456.42)

• Must be legible and understandable by the pharmacist.
• Must include the prescriber's name.
• Must include the drug name and strength.
• Must include the quantity and directions for use.
• Must be dated and signed by the prescriber on the day issued.

Electronically Generated/Transmitted Prescriptions

• Must contain the prescriber's name.
• Must contain the drug name and strength.
• Must contain the quantity in numerical format.
• Must contain the directions for use.
• Must contain the date.
• Must have an electronic signature by the prescriber on the day issued.

Controlled Substance Prescriptions (Chapter 893)

• Must have the quantity in both textual and numerical formats.
• Must be dated in numerical, abbreviated month, or full month format.
• Must be written on a standardized counterfeit-proof prescription pad or electronically prescribed per s. 408.0611.
• Approved vendors must submit monthly reports.

Mandatory Electronic Prescribing

• Practitioners with electronic health records must electronically transmit prescriptions upon license renewal or by July 1, 2021, whichever was earlier.

Exceptions to Mandatory Electronic Prescribing

• The practitioner and dispenser are the same entity.
• Electronic transmission isn't possible under the latest National Council for Prescription Drug Programs SCRIPT Standard.
• The practitioner has a waiver due to economic hardship, technological limitations, or another exceptional circumstance.
• The practitioner determines electronic prescribing would delay treatment and negatively impact the patient.
• The drug is prescribed under a research protocol.
• The FDA requires elements that cannot be included electronically.
• The prescription is for hospice care or a nursing home resident.
• The practitioner or patient wants to compare drug prices among pharmacies (documented in the patient's record).

Electronic Prescribing Restrictions (Section 456.43)

• Electronic prescribing cannot interfere with a patient's right to choose their pharmacy.
• Software cannot use incentives, advertising, or pop-ups to influence prescribing or direct patients to a specific pharmacy.
• "Prescribing decision" refers to the decision to prescribe any medicinal drug, and "point of care" is the time the practitioner prescribes any medicinal drug.
• Formulary information may be displayed if it doesn't hinder pharmacy or drug selection.

Oral Prescriptions and Copies (Rule 64B16-27.103)

• Only a pharmacist or registered pharmacy intern may accept oral prescriptions.
• Only a pharmacist or registered pharmacy intern may prepare a prescription copy or read it for treatment reference.
• A notation must be made on the original prescription with the date given and to whom.

Pharmacy Intern Registration (Section 465.013)

• The department will register individuals certified by the board as:
• Enrolled in an intern program at an accredited pharmacy school/college.
• Graduates of accredited pharmacy schools/colleges who are not yet licensed in Florida.
• The board may refuse to certify or revoke an intern's registration for good cause.

Pharmacy Technician (Section 465.014)

• Duties, tasks, and functions can be delegated to registered pharmacy technicians by a licensed pharmacist that do not fall within the purview of the practice of pharmacy (s. 465.003).
• All actions must be performed under the direct supervision of a licensed pharmacist.
• Supervised technicians may communicate with practitioners regarding refill authorizations.
• Generally, a pharmacist may not supervise more than one technician unless permitted by board guidelines.

Pharmacy Technician Registration Requirements

• File an application with the board, and both remit a registration and a nonrefundable application fee (not exceeding $50 biennially).
• Be at least 17 years old.
• Have completed a board-approved pharmacy technician training program.
• Registered techs before January 1, 2011, with 1500 hours or national certification are exempt from the training program.
• Those whose pharmacy licenses have been denied, suspended, or restricted cannot register as technicians.
• Students in approved training programs can perform technician functions with identification.
• Licensed pharmacy interns can work as registered pharmacy technicians without registration fees.
• Complete 20 hours biennially of approved continuing education, including 4 live hours and 2 hours related to medication error prevention and pharmacy law.
• Techs administering vaccines need certification with at least 6 hours of immunization training and 2 hours of additional continuing education for renewal.
• The board will adopt rules requiring the display of technician registrations publicly.

Registered Pharmacy Technicians Penalties

• Act constituting grounds for discipline under s. 456.072(1) or violations of Chapter 465 can result in penalties.

Delegation to and Supervision of Pharmacy Technicians; Responsibility of Supervising Pharmacist (Rule 64B16-27.4001)

• Pharmacists cannot delegate more tasks than they can personally supervise.
• Registered Pharmacy Technicians (RPT): Duly registered with the board.
• Pharmacy Technicians in Training (PTT): In training, not required to be registered.
• Delegated tasks require direct supervision and compliance with laws.
• The supervising pharmacist determines supervision methods.
• The pharmacist must be readily available, aware of the tasks, and provide assistance.
• Technology can be used to assist in supervision.

Pharmacist Supervision Ratios

• Supervision of more than one technician must enhance service,.
• Generally, the supervision ratio is 1:1.
• Required Documentation:
• Policy and Procedures Manual: Number and utilization of technicians, scope of delegable tasks, qualifications, training, duties, prescription processing, inventory control, record retrieval, delegable/non-delegable tasks, confidentiality, refill/renewal authorization, automated system functions, quality improvement.
• Each technician must acknowledge reviewing the manual.
• Documentation of training in job description, tasks, and policies required.
• Manuals must be onsite and documentation provided within 72 hours.
• 3:1 Ratio: Allowed only for sterile compounding.
• 6:1 Ratio: Allowed when neither pharmacist nor technicians engage in sterile compounding.
• 8:1 Ratio:
• For Non-dispensing pharmacies not engaged in sterile compounding.
• Also allowed in dispensing pharmacies in a physically separate area where medicinal drugs are not dispensed.
• 12:1 Ratio: Allowed for closed-door pharmacies.
• The Prescription Department Manager determines the applicable supervision ratio, and no other person can interfere with this professional judgment.

Pharmacy Technician – Delegable and Non-Delegable Tasks (Rule 64B16-27.420)

• Technicians assist pharmacists but cannot engage in the practice of pharmacy.
• Delegable Tasks: Performed under direction, without independent judgment, and do not require pharmacist judgment.
• Non-Delegable Tasks:
• Cannot receive new non-written prescriptions.
• Cannot interpret prescriptions.
• Cannot conducts final verification of dosage and directions.
• Cannot engage in review.
• Cannot monitor prescription usage.
• Cannot override clinical alerts without pharmacist notification.
• Cannot transfer a prescription.
• Cannot prepare a copy or read a prescription for treatment reference.
• Cannot engage in patient counseling.
• Cannot receive therapy or blood product procedures in a nuclear pharmacy.
• Can not engage in any act requiring a pharmacist's professional judgment.

Application for Pharmacy Intern Registration (Rule 64B16-26.2032)

• Students/graduates of ACPE-accredited programs use form DH-MQA 104.
• Graduates of non-ACPE accredited programs use form DH-MQA 102.
• Applicants must submit proof of enrollment or graduation from an accredited pharmacy school.
• The Board will certify the applicant for registration unless there is good cause for refusal.

Approved Pharmacy Internship Programs (Rule 64B16-26.2033)

• Internship programs by ACPE-accredited schools/colleges.
• Internships required for a PharmD degree from accredited institutions.
• Other approved programs must meet certain requirements, including pharmacy location, preceptor qualifications, and applicant requirements.
• Internship Hours: All hours can be obtained pre-graduation, but hours exceeding 50 per week pre-graduation or 60 per week post-graduation will not be credited.
• Up to 2080 hours of work as a licensed pharmacist in another state can substitute for internship hours, except foreign pharmacy graduates must complete 500 hours of supervised work activity in Florida.
• Governmental and private radiopharmacy internship programs are not approved.

Prescription Labeling (Section 456.0392)

• Prescriptions from practitioners without DEA numbers must include the practitioner's name and professional license number.
• The dispensing pharmacist/practitioner must include the practitioner's name on the container.
• Prescriptions issued by licensed APRNs (s. 464.012) or PAs (Chapter 458 or 459) are presumed valid.

Registration of Nonresident Pharmacies (Section 465.0156)

• Any pharmacy outside Florida shipping drugs into Florida must register with the board.
• Requirements:
• Maintain a valid license in their state of operation.
• Disclose location, names, and titles of principal officers and the prescription department manager within 30 days of changes.
• Comply with information requests and respond to communications about dispensing errors.
• Maintain retrievable records of drugs dispensed to Florida patients.
• Maintain a toll-free telephone service at least 6 days a week, 40 hours per week, for communication with a pharmacist.
• The board can deny, revoke, or suspend registration.
• Unregistered nonresident pharmacies cannot advertise services in Florida.
• This section does not apply to Internet pharmacies under s. 465.0197.
• The registered pharmacy and its prescription department manager must be licensed in their state of location to dispense into Florida.

Nonresident Sterile Compounding Permit (Section 465.0158)

• Required for shipping compounded sterile products.
• Application requirements include proof of registration as an outsourcing facility (if eligible), written attestation of understanding Florida laws, sterile compounding policies, and a current inspection report.
• Restrictions: Permittees cannot ship products that violate home jurisdiction laws or do not meet Florida standards.
• The board can deny, revoke, or suspend permits.

Distribution of Medicinal Drugs Without a Permit (Section 465.0161)

• An Internet pharmacy distributing medicinal drugs to anyone in Florida without being permitted as a pharmacy commits a felony of the second degree.

Florida Drug and Device Permitting Requirements

• Categories of activity, locations inside and outside of Florida, and required permits are detailed.