9. Federal Compounding & Biosimilar Regulation (February 7) - Tagged-1.pdf

Federal Compounding & Biosimilar Regulation February 7, 2024 Exam Monday, February 12 at 10:40AM SDS start time is 10:00 (location TBA) Q&A sessions (recorded) Friday, February 9 at 4:00 in zoom classroom https://olemiss.zoom.us/j/91006519197 Sunday, February 11 at 4:00 in zoom classroom https://ole...

Federal Compounding & Biosimilar Regulation February 7, 2024 Exam Monday, February 12 at 10:40AM SDS start time is 10:00 (location TBA) Q&A sessions (recorded) Friday, February 9 at 4:00 in zoom classroom https://olemiss.zoom.us/j/91006519197 Sunday, February 11 at 4:00 in zoom classroom https://olemiss.zoom.us/j/91006519197 Individual office hours before and after exam available at https://calendly.com/erinholmes Or email Dr. Holmes at [email protected] Exam covers material from January 10-February 7 Formats: MC/TF/fill in the blank Approximately 80 questions expected Detailed logistical instructions coming Friday 2 In the news… 3 Learning Objectives Describe how pharmacy compounding is regulated Describe the Drug Quality and Security Act Describe 503A and 503B designations List USP compounding regulations Describe the USP Describe USP 795 regulations (nonsterile) Describe USP 797 regulations (sterile) Describe USP 800 regulations (hazardous) Describe Safety Data Sheets (SDS) Describe the Biologic Price Competition and Innovation (BPCI) Act Define biosimilar terms Describe the Purple Book Describe state substitution laws 4 Describe how pharmacy compounding is regulated Traditional pharmacy compounding (like you might do in your independent or chain pharmacy) is considered a practice of pharmacy regulated by state boards of pharmacy. We will discuss Mississippi regulations later this semester Traditional pharmacy compounding (like you might do in your independent or chain pharmacy) is not pharmaceutical manufacturing and is therefore is not regulated by the FDA. The regulation of compounding has a complicated and controversial history 5 Describe how pharmacy compounding is regulated Pharmacy Compounding (Regulated by State Boards of Pharmacy) Medication is not commercially available Pharmaceutical Manufacturing (Regulated by the FDA) Medication is commercially available Made for individual patients Made in mass production Cannot be sold in bulk for resale Can be sold in bulk for resale Cannot advertise specific drugs Can advertise specific drugs (DTCA) 6 Describe the Drug Quality and Security Act In October 2012, the United States faced the most serious outbreak associated with contaminated compounded drugs in recent history. A pharmacy in Massachusetts (New England Compounding Center – NECC) shipped compounded drugs that were contaminated with a fungus throughout the country, and these drugs were injected into patients’ spines and joints. More than 750 people in 20 states developed fungal infections, and 64 people died. Approximately 14,000 patients received injections from the lots of contaminated drug product. 7 Describe the Drug Quality and Security Act The Drug Quality and Security Act (H.R. 3204) is a law that amended the Federal Food, Drug, and Cosmetic Act to grant the Food and Drug Administration more authority to regulate and monitor the manufacturing of compounded drugs. The bill was written in response to the New England Compounding Center meningitis outbreak that took place in 2012, which killed 64 people. The bill was signed by President Obama on November 27, 2013. Created 503A and 503B designations An Amendment of the FDCA 8 Describe 503A and 503B designations 503A facilities are referred to by the FDA as a traditional compounding pharmacy that compounds in accordance to patient specific prescriptions and is required by the state boards of pharmacy to comply with USP and guidelines. (traditional compounding) 503B facilities are referred to by the FDA as an outsourcing facility that may produce large batches with or without prescriptions to be sold to healthcare facilities as office use only or shipping out of state and is regulated by the FDA. (more like manufacturing) A prime difference between 503B and 503A facilities, and a major component of CGMP, is the requirement for every process to be validated in a 503B facility. Helpful reference (not on exam in this class): http://www.wellsrx.com/503a-vs-503b-compounding-pharmacies/ Just FYI (503B facilities list): https://www.fda.gov/drugs/human-drug-compounding/registered-outsourcing-facilities 9 List USP compounding regulations USP 795 (Nonsterile) USP 797 (Sterile) USP 800 (Hazardous) State boards of pharmacy enforce these! 10 Describe the USP (United States Pharmacopeia) USP is a non-profit organization Sets standards for all drugs (prescription and OTC Drugs) and compounding The FDCA designates the USP–NF as official compendia for drugs marketed in the United States. A drug product on the US market must conform to the standards in USP–NF to avoid possible charges of adulteration and misbranding. USP does not do law enforcement FDA and state boards of pharmacy enforce USP standards (795, 797, 800) Adulterated drugs do not meet USP standards for strength, quality, or purity ALL USP COMPOUNDING GUIDELINES WERE REVISED NOVEMBER 2023 Christianson E. MPJE master. 2019 https://www.uspnf.com/ 11 Describe USP 795 Regulations (nonsterile) Compounding categories SIMPLE Example: Amoxicillin suspension Adding water and mixing According to manufacturer recommendations for Beyond Use Date (BUD) and stability data MODERATE Example: Mixing two creams Stability isn’t known or studied Beyond use date uncertain due to lack of data COMPLEX Example: Creating transdermal dosage form Involves special training, equipment, facilities, procedures Probably won’t see in community pharmacy Christianson E. MPJE master. 2019 12 Describe USP 795 Regulations (nonsterile) Requirements Staff competency/training Potable water Designated area Cleanliness Plumbing Disposal containers Lighting Heat/cooling Formula records Recalls Patient complaints Designated expert BOP rules/regulations Storage Documentation Christianson E. MPJE master. 2019 13 Describe USP 795 Regulations (nonsterile) Beyond Use Dates (BUDS) Nonaqueous compounds 6 months or earliest expiration date of any ingredient Water-containing oral compounds (refrigerated) 14 days or earliest expiration date of any ingredient Water-containing topical and semisolid compounds 30 days or earliest expiration date of any ingredient 14 Christianson E. MPJE master. 2019 Describe USP 797 Regulations (sterile) Beyond Use Dates (BUDS) – KNOW THESE Beyond Use Dates, commonly referred to as BUDs, are the assigned dates or timeframes after which a compounded sterile preparation (CSP) should not be used. BUDs are determined based on potential for microbial contamination, chemical degradation, or loss of potency, ensuring the compounds administered to patients are both safe and effective USP 797 BUDs are established using a risk-based approach that looks at a combination of factors, including the sterility assurance level (SAL) of the compounding process, storage conditions, and the specific ingredients used in the preparation. It’s important to remember that BUDs are NOT the same as expiration dates. The BUD is the date beyond which a sterile preparation, such as amoxicillin powder mixed with sterile water, must be discarded. The amoxicillin powder itself may have a longer expiration date, but that does not factor into the BUD. 15 CriticalPoint, LLC Describe USP 797 Regulations (sterile) Beyond Use Dates (BUDS) – KNOW THESE Factors that determine CSP Category Primarily based on environment/conditions of where the CSP is compounded Level of garbing Environmental testing and monitoring Frequency of application of a sporicidal Based on BUD assignment 16 Describe USP 797 Regulations (sterile) Personnel & Training Written testing Routine review/training Policies for testing/training Media fill tests 17 Christianson E. MPJE master. 2019 Describe USP 797 Regulations (sterile) Clean Room/Environment/Hood 18 Christianson E. MPJE master. 2019 Describe USP 797 Regulations (sterile) Clean Room/Environment/Hood Ante Area  ISO class 8 Cleanroom  ISO class 7 Work Area (hood)  ISO class 5 Positive pressure (air flows out) for non-hazardous Everything smooth (walls, floors, ceilings, fixtures) Materials should not break down from cleaning agents HEPA Filter removes 99.97% of all particles 0.3 microns or larger Laminar Flow hood - air blows towards you, clean if shut off, generally left on Chemo hood (hazardous) - vertical air flow Don’t place items in front of each other to disrupt air flow 19 Christianson E. MPJE master. 2019 Describe USP 797 Regulations (sterile) Clean Room/Environment/Hood Gowning No lab coats/makeup/jewelry Wash hands to elbows Hair and shoe covers – can be reused Appropriately fitting coveralls/coats – can be reused in same shift Gloves/masks put on in cleanroom Only what is necessary should be in hood (no pens, paper, etc.) Buffer area should not have sink or drain 20 Christianson E. MPJE master. 2019 Describe USP 797 Regulations (sterile) Requirements Need a spelled out quality assurance program Cleaning process spelled out in policies and procedures Cleaning should be done at beginning of each shift at a minimum Hoods should be cleaned from cleanest to dirtiest Ceiling  back  sides  bar/devices  main surface Go from back to front, do not touch HEPA filter Use isopropyl alcohol 70% 21 Christianson E. MPJE master. 2019 Describe USP 800 Regulations (hazardous) Hazardous Drugs Goal is to protect healthcare workers from exposure to hazardous drugs: Carcinogenic Teratogenic Reproductive toxicity Organ toxicity at low doses Genotoxicity Novel agents similar to the above 22 Christianson E. MPJE master. 2019 Describe USP 800 Regulations (hazardous) Personal Protective Equipment (PPE) Goal is to protect healthcare workers from exposure to hazardous drugs: For administration of all chemo, 2 pairs of chemo gloves must be worn For injectable chemo, chemo gowns must also be worn For compounding, all equipment must be removed when leaving compounding area Cannot reuse gowns when leaving compounding area Hazardous vs. nonhazardous compounding equipment must be separate 23 Christianson E. MPJE master. 2019 Describe Safety Data Sheets (SDS) Communicates the hazards of dangerous drugs and chemicals to anyone who compounds, stores, transports, or cleans these items Also called Material Safety Data Sheet (MSDS). Provided by manufacturer/supplier/importer. Administered by Occupational Safety and Health Administration (OSHA) Sections: Identification: Identifier, contact, recommendations, restrictions, PPE Hazards Identification: Damages caused, warning labels needed First-aid measures: Emergency procedures to follow if exposed Accidental release measures: Drug spill cleanup procedures; HAZMAT needed? Handling and storage: Handling and storage procedures 24 Describe Safety Data Sheets (SDS) OSHA requires an SDS binder readily available in pharmacies, hospitals, nursing homes, and other business where hazardous medications are stored Any exposure to hazardous drugs must be reported to your supervisor and documented Document must be kept on file for 30 years 25 Biosimilar : Biologic Generic : Brand Sort of…. 26 Describe the Biologic Price Competition and Innovation (BPCI) Act Congress, through the Biologics Price Competition and Innovation Act (BPCI Act) of 2009, created an abbreviated licensure pathway for biological products that are demonstrated to be biosimilar to or interchangeable with an FDA-approved biological product. This pathway was established as a way to provide more treatment options, increase access to lifesaving medications, and potentially lower health care costs through competition. 27 https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars Describe the Biologic Price Competition and Innovation (BPCI) Act Allows for the approval of biosimilars Subtitle of the Affordable Care Act The FDA determines therapeutic equivalence Grants 12 years marketing exclusivity to the reference product The first interchangeable biological product receives up to one year of exclusivity over subsequent follow-on biologics 28 Define biosimilar terms A biosimilar is a biological product that is highly similar to the reference product notwithstanding minor differences in clinically inactive components, and has no clinically meaningful differences in terms of safety, purity and potency (safety and effectiveness) from the reference product. A reference product is a biological product approved by the FDA under the Public Health Service Act based on a full complement of product-specific data, including nonclinical and clinical data. Generic biologic is not appropriate terminology because it implies an exact copy of the originator’s product, which currently is impossible because of limitations in technology. 29 Define biosimilar terms An interchangeable product is a biosimilar product that meets additional requirements outlined by the Biologics Price Competition and Innovation Act. As part of fulfilling these additional requirements, information is needed to show that an interchangeable product is expected to produce the same clinical result as the reference product in any given patient. An interchangeable product may be substituted for the reference product by the pharmacist without the involvement of the prescriber. https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable- Define biosimilar terms On March 6, 2015, the FDA approved the first biosimilar drug for distribution in the United States. The drug approved was ZARXIO (filgrastim-sndz) a medication used to prevent infections in cancer patients receiving chemotherapy. Neutrophil enhancer. ZARXIO is approved for all indications included in the reference product’s NEUPOGEN (filgrastim) label. 31 But ZARXIO is NOT INTERCHANGEABLE Describe the Purple Book 32 https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/purple-book-lists-licensed-biological-products-reference-product-exclusivity-and-biosimilarity-or Describe state substitution laws An issue at the state level involves defining the requirements in which pharmacists would be permitted to substitute an interchangeable for the prescribed reference drug, because a state’s current generic substitution laws likely do not include biosimilars. The ACA provides that if the FDA determines that a biosimilar is interchangeable, then it may be substituted for the reference product without the intervention of the prescriber. The state laws enacted to date generally permit substitution, provided the prescriber has either authorized or not prohibited substitution, and that the prescriber is notified of the substitution. 33