Brand Substitution of Drugs

Brand Substitution of Drugs

• Brand name drugs possess a registered trademark.
• Generic drugs must be equivalent to brand name drugs.

Prescriber Authority and Requirements for Brand Name Dispensing

• Prescribers can mandate that a brand name drug be dispensed.
• Pharmacists are required to substitute a brand name prescription with a less expensive generic equivalent unless requested otherwise by the purchaser or physician.
• Florida Administrative Code 465.025 covers state regulations derived from the legislature.
• Rules from the Board of Pharmacy support the actions of the legislature.
• The legislature relies on the Board of Pharmacy's expertise due to limited pharmacist representation.
• The substituted drug must:
  • Be distributed by a US-based entity.
  • Be subject to legal processes in the US.
  • Be listed in the formulary of generic and brand name products.
• Substitution is unnecessary if the prescriber writes "medically necessary" on the prescription.
• Verbal instructions to make a prescription "medically necessary" also mandates dispensing the brand name drug.

Pharmacist's Responsibilities Regarding Substitution

• Pharmacists must inform patients of the price difference between brand name and generic drugs.
• Patients have the right to refuse the generic substitution.
• Pharmacists must pass on the full savings realized through generic substitution to the consumer.

Negative Drug Formulary

• The Board of Pharmacy and Board of Medicine establish a negative formulary listing generic products with clinically significant biological or therapeutic inequivalence.
• Substitution of drugs on the negative formulary poses a threat to patients.
• Florida is one of the few states with a negative formulary.
• Every community pharmacy must display a sign (at least one inch high in block letters) stating: "CONSULT YOUR PHARMACIST CONCERNING THE AVAILABILITY OF A LESS EXPENSIVE GENERICALLY EQUIVALENT DRUG AND THE REQUIREMENTS OF FLORIDA LAW."
• The Board of Pharmacy and Board of Medicine can remove generic drugs from the formulary if every commercially marketed equivalent is "A rated" or a reference listed drug per the FDA's Orange Book.
• The original negative formulary had 12 medications; the current has six.
• Current medications on the negative formulary:
  • Digitoxin
  • Conjugated estrogens
  • Dicumarol
  • Chlorpromazine (solid dosage forms only)
  • Theophylline (controlled release forms only)
  • Pancrelipase (oral dosage forms only)
• Medications removed from the negative drug formulary:
  • Digoxin
  • Phenytoin
  • Levothyroxine
  • Warfarin

Substitution of Interchangeable Biosimilar Products

• "Biological product," "biosimilar," and "interchangeable" have the same meaning as defined in statute 351 of the Public Health Service Act
• Biological products may only be substituted if deemed biosimilar and interchangeable by the FDA.
• The person presenting the prescription must be notified of any biosimilar substitution.
• Records of biosimilar substitutions are kept for two years.
• Class II institutional pharmacies (hospitals, home health) comply with notification by entering the substitution in the institution's written medical record system.
• The board maintains a public website with a current list of biological products determined by the FDA to be biosimilar and interchangeable.

Positive Drug Formulary

• The positive drug formulary is under rule 64B16-27.520.
• Each community pharmacy must have a positive formulary of generic and brand name products.
• Medicines must be obtained from manufacturers/distributors with an approved NDA or ANDA issued by the FDA.

Duty of the Pharmacist to Inform

• Pharmacists must inform the person presenting a prescription of the retail price difference and their right to refuse substitution, when substituting a generic for a brand name drug.
• This information should be shared appropriately, using professional discretion.
• Technicians or cashiers can offer generic substitution

Expiration Dates

• Manufacturers, repackagers, or distributors must display the expiration date on drug containers and packages.
• Community pharmacies dispensing outpatient drugs must display the expiration date on the outside of the container or in other written form delivered to the purchaser.
• The expiration date should be the manufacturer's provided date or an earlier "beyond use" date (up to one year after dispensing).
• Most pharmacy computer systems use the one-year beyond use date.
• Pharmacists must provide expiration date information and proper use/storage instructions upon request.

Filling of Certain Prescriptions (Transfers)

• Pharmacists can fill/refill valid prescriptions on file in Florida or another state if transferred.
• Before dispensing a transferred prescription, the pharmacist must:
  • Advise the patient that the prescription at the other store must be canceled.
  • Determine the prescription is valid.
  • Notify the pharmacy where the prescription is on file that it must be canceled.
  • Record the prescription order, the transferring pharmacy's name, Rx number, drug name, original amount dispensed, dispensing date, and remaining refills.
• Upon receiving a transfer request, the pharmacist must:
  • Transfer the required information accurately.
  • Record the requesting pharmacy, pharmacist, and date of request.
  • Cancel the prescription on file.
• If a transferred prescription is not dispensed in a reasonable time, the transferring pharmacy must be re-notified to revalidate the canceled prescription.
• For out-of-state transfers, the Florida pharmacist must verify the transferring entity is a licensed pharmacist or pharmacy in that state.
• Transfers can only be done between pharmacists.
• Electronic transfers are permitted regardless of the transferor or transferee pharmacy's business hours.
• Transfer of prescriptions for Schedule III, IV, and V controlled substances is permissible, subject to requirements and federal law.

Centralized Prescription Filling

• Florida-licensed pharmacies may perform centralized prescription filling for another pharmacy with the same owner or a written contract.
• Each pharmacy performing centralized filling must maintain a policy and procedure manual including:
  • Compliance with federal and state laws, rules, and regulations.
  • Maintaining records to identify the dispensing pharmacist and patient counseling.
  • Tracking the prescription through each stage.
  • Identifying on the label all pharmacies involved.
  • Securing patient information confidentiality.
  • Implementing a quality assurance program.
• Filling, delivery, and return through centralized filling are not considered a transferred prescription.

Common Database

• Dispensing by a licensed pharmacist of a prescription in a common database constitutes a transfer, provided:
  • All pharmacies involved are under common ownership and use a common database.
  • All pharmacies and pharmacists are properly licensed.
  • The common database maintains a record of all pharmacists involved.
• The common database owner must maintain a policy and procedure manual including:
  • Best practices for complying with laws and regulations.
  • Procedures for maintaining records, oversight, tracking, identifying pharmacists, and responding to board requests.
  • Security for patient information confidentiality and integrity.
  • A quality assurance program.

Exceptions

• The chapter does not prohibit the sale of home remedies or preparations commonly known as patents or proprietary preparations when sold only in original or unbroken packages.
• The chapter does not prevent businesses from selling sundries, patents, or proprietary preparations.
• The chapter does not apply to manufacturers or agents under chapter 499 solely manufacturing/distributing dialysate drugs/devices for renal dialysis if:
  • The drugs/devices are approved/cleared by the FDA.
  • They are delivered in the original sealed packaging.
  • Delivery is after a physician's order for a patient with chronic kidney failure, their designee, a healthcare practitioner, or an institution.

Emergency Prescription Refill

• Pharmacists may dispense a one-time emergency refill of up to a 72-hour supply if unable to readily obtain authorization from the prescriber.
• For insulin, a one-time emergency refill of one vial may be dispensed.
• If the governor issues a state of emergency, pharmacists may dispense up to a 30-day supply in affected areas, excluding Schedule II controlled substances.
• The medication must be essential for life maintenance or chronic therapy.
• The pharmacist must use professional judgment that therapy interruption could cause undesirable health consequences.
• The dispensing pharmacist creates a written order with all required information and signs it.
• The dispensing pharmacist must notify the prescriber of the emergency dispensing within a reasonable time.

Categories of Pharmacy Permits

Big Picture: Five Permits Applying to Drug Manufacturers

• Five permits apply to drug manufacturers:
  • Prescription Drug Manufacturing Permit (Florida Based)
  • Non-Resident Prescription Drug Manufacturer Permit
  • Over the Counter (OTC) Drug Manufacturer Permit
  • Device Manufacturer Permit
  • Cosmetic Manufacturer Permit

Prescription Drug Manufacturing Permit (Florida Based)

• Required for manufacturers with corporate headquarters in Florida.
• A company owning the patent but contracting out manufacturing is still considered the manufacturer.
• A virtual permit is available if the manufacturer does not take physical possession of the drug.
• Issued by the Board of Pharmacy/Department of Health.
• Required to manufacture and distribute prescription drugs.
• Manufacturers must maintain adequate records.
• Virtual permit holders are exempt from building security and storage requirements, but must comply with temperature, security, and storage requirements to preserve potency.
• Manufacturers must comply with all state and federal regulations.
• Blood banks manufacturing prescription drugs used only in blood donation and processing are exempt.

Non-Resident Prescription Drug Manufacturer Permit

• Applies to manufacturers with corporate headquarters not in Florida distributing prescription drugs in Florida.
• A virtual permit is available for non-resident manufacturers not taking possession of the drug.
• Virtual permit holders are exempt from securities and storage rules.
• A person only distributing must have the out-of-state prescription drug wholesale distributor permit or the third-party logistics provider permit.
• Non-resident manufacturers must be licensed in their state/country of origin.
• Non-resident manufacturers importing drugs into Florida must provide the Department of Health with a list identifying each drug and FDA approval documentation.

Over the Counter (OTC) Drug Manufacturer Permit

• Required for OTC drug manufacturers domiciled in Florida.
• No out-of-state version of this permit.
• Required for making or repackaging OTC drugs in Florida.
• OTC drug manufacturers cannot possess or purchase prescription drugs.
• Pharmacies are exempt when operating under Florida pharmacy practice standards.
• OTC drug manufacturers must comply with all state and federal good manufacturing practices.

Device Manufacturer Permit

• Required for Florida companies making medical devices.
• Exempt if the device is made pursuant to a practitioner's order for a specific patient or if the manufacturer is already registered with the FDA.
• Manufacturers/repackagers of medical devices in Florida must comply with all state and federal good manufacturing practices.

Cosmetic Manufacturer Permit

• Required for manufacturers making or repackaging cosmetics in Florida.
• Exempt if only adding/changing the label without opening the sealed container.

If Not Manufacturing But Distributing (Wholesaling)

• A prescription drug wholesale distributor permit is required if only distributing.
• A distributor broker permit can be obtained if no physical possession is taken.
• An out-of-state prescription drug wholesale distributor permit is required for distributing into Florida from outside the state.
• Three other distributor permits exist:
  • Retail pharmacy drug wholesale distributor permit
  • Veterinary prescription drug wholesale distributor permit
  • Complimentary prescription drug distributor permit

Prescription Drug Wholesale Distributor Permit

• Required for anyone who wholesale distributes prescription drugs in Florida.
• An out-of-state version is required for entities located outside Florida.

Distributor Broker Permit

• The Department of Health issues this permit to anyone who wholesale distributes prescription drugs but does not take physical possession.

Out-of-State Prescription Drug Wholesale Distributor Permit

• Required for anyone who wholesales/distributes prescription drugs from out of Florida into Florida.
• The distributor must have a license/permit in their state of residence, or be licensed as a wholesale distributor as required by the Food Drug and Cosmetic Act (FDCA) if the state of origin does not require a permit.
• This permit is not required for intra-company sales/transfers of prescription drugs operating under the same business name.

Retail Pharmacy Drug Wholesale Distributor Permit

• Allows retail pharmacies within limits to wholesale distribute drugs.
• If equal to or greater than 30% of annual sales are distributed to other entities, the standard prescription drug wholesale distributor permit is required.
• If under 30% of annual sales are distributed to other pharmacies or hospitals, this permit can be obtained.
• Transfer of drugs must be between two retail pharmacies, to a modified class two institutional pharmacy, or to a healthcare practitioner licensed in Florida and authorized to dispense or prescribe prescription drugs.
• Sales records of prescription drugs wholesale distributed must be maintained separately from other records.

Restricted Prescription Drug Distributor Permit

• Required in Florida for anyone who distributes a prescription drug not considered wholesale distribution.
• Applies to receiving or distributing a drug in Florida for processing its return or destruction.
• This is permissible if the distributor is not the person initiating the return, the wholesale supplier, or the manufacturer.
• A blood establishment in Florida that collects blood and blood components only from volunteer donors, or pursuant to an authorized practitioner's order for medical treatment or therapy, may operate under this permit.
• The entity receiving a prescription drug under this permit must be licensed as a closed pharmacy or provide healthcare services at that establishment.
• This permit covers prescription drugs for bleeding or clotting disorders or anemia, blood protection collection containers approved under the FDCA, blood derivative drugs or recombinant or synthetic blood derivatives, prescription drugs identified in Florida Department of Health rules essential to blood establishment services and federally authorized for their distribution, and drugs necessary to collect blood or components from volunteer donors for blood establishment personnel to perform therapeutic procedures under physician supervision and to manage reactions of blood donors or patients.
• Such drugs may be purchased and possessed without a healthcare clinic establishment permit under this restricted permit for blood establishments.
• Holders of this permit must observe Florida rules for wholesale distributors.
• This permit is not required for distribution between commonly owned pharmacies operating in a freestanding end-stage renal dialysis clinic for immediate emergency medical needs of specifically identified patients.
• A prescription drug repackager permit is not required for a restricted prescription drug distributor permit holder that is a healthcare entity to repackage prescription drugs in Florida for its own use or distribution to hospitals or other healthcare entities for their own use, provided certain conditions are met, including notifying the Department of Health 30 days prior, the distributed drug being under common control with the receiving entities, repackaging following GMPs, and proper labeling.
• Common control is defined as the power to direct management and policies through ownership, voting rights, contract, or otherwise.

Veterinary Prescription Drug Wholesale Distributor Permit

• Required for anybody distributing veterinary prescription drugs in Florida.
• Those also distributing prescription drugs subject to the federal FDCA need a prescription drug wholesale distributor permit, an out-of-state prescription drug wholesale distributor permit, or a limited prescription drug veterinary wholesale distributor permit instead.
• Holders must comply with the rules for wholesale distributors as specified under Chapter 499 of Florida Statutes.

Limited Prescription Drug Veterinary Wholesale Distributor Permit

• This permit allows the distribution of veterinary prescription drugs in Florida only under specific conditions.
• The permit allows wholesaling to licensed veterinarians practicing full-time, those regularly and lawfully instructing veterinary medicine, those regularly and lawfully engaged in law enforcement activities, for use in research not involving clinical use, or for use in chemical analysis or physical testing for instruction in law enforcement, research, or testing.
• No more than 30% of total annual drug sales can be prescription drugs approved for human use; otherwise, a different permit is required.
• The permit holder cannot distribute prescription drugs subject to 503B of the federal FDCA to anyone authorized to sell, distribute, purchase, trade, or use these drugs on or for humans.
• An applicant for a new or renewal of this permit must submit a bond of at least $20,000.
• The holder must maintain a license or permit to wholesale distribute prescription drugs in their state of residence (if outside Florida).
• They must comply with all Florida building storage and record rules for wholesale distributors.
• They may not return to inventory for wholesale distribution any drug subject to 503B of the federal FDCA that has been returned by a veterinarian.

Complimentary Prescription Drug Distributor Permit

• This permit is for the distribution of free samples that drug representatives give to physician practices.

Repackagers

• A Florida prescription drug repackager permit is needed for repackaging prescription drugs in Florida.
• A non-resident version is needed for non-resident companies repackaging prescription drugs.

Florida Prescription Drug Repackager Permit

• Required for anybody in Florida that repackages a prescription drug.
• You may distribute prescription drugs repackaged at that establishment.
• You must comply with all the rules that apply to a prescription drug manufacturer, and all state and federal good manufacturing practices (GMPs).

Non-Resident Prescription Drug Repackager Permit

• Required if you are located outside of Florida but within the United States or its territories (not foreign countries) and you repackage and distribute prescription drugs into Florida.
• You must comply with all the rules that apply to a manufacturer.
• You must have the DOH permit and comply with all state and federal GMPs.
• You must be registered as a drug establishment with the US Food and Drug Administration.

Transporters and Shippers

• Two versions of permits exist for transporters and shippers:
  • Third-Party Logistics Provider Permit
  • Freight Forwarder Permit

Freight Forwarder Permit

• A freight forwarder is a business entity that takes control of all the shipping when multiple transport modes (air, train, truck) are used for the same shipment.
• Required for anybody that distributes a prescription drug as a freight forwarder, unless that person is a common carrier like the US Postal Service.
• The permit holder must comply with the storage, handling, and record-keeping requirements that wholesale distributors do.
• They must also provide the source of the prescription drugs with a validated airway bill of lading or other appropriate documentation to evidence exportation of the product.
• Recipients of shipments should ensure the deliverer has either a freight forwarder permit or a third-party logistics provider permit.

Third Party Logistics Provider Permit

• Required for any person that contracts with a prescription drug wholesale distributor or manufacturer to provide warehousing, distribution, or other logistics for them.
• This applies to those who do not take title to the drug or have responsibility to direct the sale or disposition of the drug; their role is limited to storing and transporting.
• A third-party logistics provider outside Florida must be licensed in the state or territory from which the drug is distributed.
• If a logistics provider license is not required in the shipping state, they must be licensed as a logistics provider by the Federal FDCA.
• They must also comply with Florida storage and record rules.

Retail Veterinary Establishment Permit

• Required for a retail veterinary establishment that doesn't also have a pharmacy permit and sells veterinary prescription drugs to the public.
• The sale of a veterinary prescription drug must be based on a valid written order from a Florida-licensed veterinarian with a valid client-veterinarian relationship with the buyer's animal.
• The establishment cannot sell an excess of the amount or go beyond the date specified on the written order.
• The order cannot be valid for more than a year.
• A veterinary prescription drug retail store may not purchase, sell, trade, or possess human prescription drugs or any controlled substances.
• They must sell veterinary prescription drugs in the original sealed manufacturer's container with all labeling intact and legible.
• They must comply with all of the wholesale distribution requirements.
• Prescription drugs sold under a practitioner's order may not be returned into the retailer's inventory.

Healthcare Clinic Establishment Permit

• Required for the purchase of a prescription drug by a place of business at one physical location that provides healthcare or veterinary services by a Florida-licensed healthcare practitioner or veterinarian.
• The permit must designate a qualifying practitioner who is responsible for complying with all legal and regulatory requirements related to the purchase, record-keeping, storage, and handling of prescription drugs.
• The designated practitioner's name, establishment address, and license number must be used on all distribution documents for prescription drugs purchased or returned by the clinic.
• The establishment must notify the department within 10 days after the appointment or any change of the designated practitioner.
• The establishment must employ a qualifying practitioner at each establishment.
• This permit is not a pharmacy permit.
• A healthcare clinic establishment that meets the criteria of a modified class two institutional pharmacy does not apply for a permit under this section.
• This paragraph does not apply to the purchase of a prescription drug by a licensed practitioner under their own license.
• A non-resident prescription drug manufacturer permit is not required for a manufacturer to distribute a prescription drug active pharmaceutical ingredient that it manufactures to a prescription drug manufacturer permitted in Florida for research and not for resale or human clinical use (other than lawful clinical trials and bio studies authorized by federal law). The receiving manufacturer must maintain records of FDA registration, out-of-state license, and the latest FDA inspection report. The active ingredient's label must prominently display "Caution: Research and Development Only. Not for Manufacturing, Compounding, or Resale," and the recipient must maintain records detailing the specific clinical trials or bio studies.
• This permit is also not required to distribute a prescription drug active ingredient received under an approved and valid new drug application (NDA), abbreviated new drug application (ANDA), new animal drug application (NADA), or therapeutic biologic application, provided the application is active and the ingredient or finished dosage form has not been withdrawn for public health reasons.
• Any distributor claiming exemption from this permitting requirement must maintain a license, permit, or registration for wholesale distribution in their state of origin or a federal wholesale distributor license if their state doesn't require one.
• A permit under this part is not required to distribute non-repackaged prescription drugs from a US establishment to a Florida establishment permitted as a prescription drug manufacturer under this part for research and development or to a holder of a letter of exemption from the department under Chapter 499 for research, teaching, or testing. The label of such active ingredients must state "Caution: Research, Teaching, or Testing Only. Not for Manufacturing, Compounding, or Resale".
• Persons receiving prescription drugs and claiming exemption from this permit must maintain records of the FDA establishment registration number, the resident state or federal license/permit/registration authorizing distribution, and a copy of the most recent inspection report for all distributors and establishments from whom they purchase or receive drugs.
• Those claiming exemption who distribute within or into Florida must make all records related to any prescription drugs distributed under this subsection available to the Department of Health within 48 hours, regardless of where the records are stored.
• A person purchasing and receiving a prescription drug from someone claiming exemption must report to the Department of Health in writing within 14 days after receiving any product that is misbranded or adulterated or fails to meet minimum standards in official compendia or state/federal GMPs for identity, purity, potency, or sterility, regardless of the product's subsequent handling.