Learning Objectives. What is a Compounding Pharmacist? Disclosure

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1 PHARMACY COMPOUNDING: Update on Trends & Regulations Michael Roberge, RPh Certified Compounding Pharmacist Owner, Compounded Solutions in Pharmacy LLC Monroe, CT Learning Objectives Define pharmacy compounding and its role within a pharmacy practice Discuss basic components involved in quality pharmacy compounding Explain compliance issues with the current regulatory requirements for compounding List resources available for pharmacists with regards to helping a patient with compounded products Disclosure Michael Roberge R.Ph Owner Compounded Solutions in Pharmacy, LLC Monroe, CT (203) or 877-Rx NEEDS What is a Compounding Pharmacist? Specially trained pharmacist Problem solver preparing customized medications to help meet unique physician and patient needs. Ultimate goal - help the patient & MD achieve optimal therapeutic outcome. PERSONALIZED MEDICINE Michael Roberge, RPh Improve Therapeutic Outcomes by solving problems: Medication not commercially available (discontinued or backordered) Customization of active ingredient(s) /strength(s) Dosage Form Alterations Palatability: flavoring Convenience : combinations Reduction of adverse side effects : suppositories, transdermals Avoidance of dyes, preservatives, specific inactives Combinations or Sustained-Release therapies to improve compliance 1

2 Compounding As defined in the NABP Model State Pharmacy Act: The preparation, mixing, assembling, packaging, or labeling of a drug or device (i) as a result of a practitioner s prescription drug order or initiative based on the Practitioner / Patient / Pharmacist relationship in the course of professional practice, or (ii) for the purpose of or as an incident to research, teaching, or chemical analysis, and not for resale or dispensing. Compounding also includes the preparation of drugs or devices in anticipation of prescription drug orders based on routine, observed patterns. Manufacturing As defined in the NABP Model State Pharmacy Act: The production, preparation, conversion, or processing of a drug or device Any packaging or repackaging of the substance(s) or labeling or relabeling of its container Promotion and marketing of such Drugs or Devices. Preparation and promotion of commercially available products from bulk compounds for resale by the pharmacies, practitioners, or other persons. COMPOUNDING OUTSOURCING MANUFACTURING Making the formula match the patient s needs Administer the drug to the sight of action in the most effective dosage form available Patient s needs in mind or for specific in-office procedure Regulated by the state Shipping out of CT limited to 5% Out sourcing - Large volume compounding dispensed without patient specific data Shipped across state borders Regulated by the FDA under 503B No specific patient in mind when drug is produced Has prescribers matching patients to the product available Economic considerations limit choices in drug dosages and dosage forms Regulated by the FDA Quality & Safety in Connecticut Compounding Pharmacies State of Connecticut CONTINUES to Enforce USP 797 Guidelines for Sterile Compounding & USP 795 for Non-Sterile Compounding (not all states enforce USP Guidelines) State of CT Inspection State Inspection criteria same as retail pharmacies Plus 795/797 inspector Post NECC, CT added inspectors to focus on sterile compounding. Typically a minimum of 2 full days with 2 inspectors going through all the required documentation. State is also inspecting Hospital Pharmacies for 795/797 compliance Expect same standard to be applied to any pharmacy that compounds at any level. Compounding Pharmacist knowledge base responsibility Trained & proficient in compounding CE s pertinent to compounding Knowledge of: 795,797,1151,1160,1163,1176,1191,1265 & all applicable state & federal laws NIOSH 2

3 General Principals Personnel training is well documented Proper storage of quality ingredients from reliable sources OSHA labeling & MSDS available Equipment maintained & used properly Environment maintained to protect personnel & prevent cross-contamination Limited personnel access to compounding area Processes are clear and reproducible All aspects are well documented Procedures & records exists for researching & correcting problems Process Criteria Preparation suitability Formulation records (master & specific) Ingredient verified via CofA, MSDS, FDA Proper environment for each formula Equipment clean & operational BUD established Proper hygiene & garb Critical processes & final product verified by pharmacist Packaging & labeling comply with law & includes this is a compounded preparation Facility & Equipment Dedicate space for compounding Temp & Humidity monitored and recorded Nothing on the floor Equipment cleaned & maintained regularly Everything is documented Ingredient Selection & Storage USP, NF, FCC whenever possible Manufactured in FDA-registered facilities Adhere to mfg expiration dates (if no exp date, assign date < 3 yrs from receipt) Not on Do Not Compound list for humans All ingredients properly stored and labeled 795 Compounding Categories SIMPLE: USP monograph Peer-reviewed journal Reconstitution of commercially available product per mfg directions MODERATE: Special calculations or procedures Stability data unavailable COMPLEX Special training, equipment & procedures Personnel Training Anyone involved in process needs proper training Read USP795 Understand process requirements Training documented and reviewed annually 3

4 USP 795 Stability & BUD Assigned conservatively based on drug-specific & general stability data as well as supportive literature Refer to manufacturer s literature when available Without manufacturer s literature or supportive data: NonAqueous: earliest API exp. or 6 months max Aqueous Oral: 14 days max Aqueous Topical/Mucosal or SemiSolids: 30 day max USP 797 GUIDELINES HIGH LIGHTS 1. Must be prepared by licensed pharmacists certified in aseptic compounding 2. Air & Surface Sampling Required 3. Room Certifications 4. QA testing 5. Beyond Use Dating 797 Personnel Requirements Properly trained to perform & document duties aseptic hand cleaning & garbing achieve & maintain sterility within ISO 5 environment select, measure & manipulate ingredients handle sterile products aseptically Low Risk CSP s Transfer, measure & mix of <3 commercially manufactured sterile products < 2 entries into any sterile container BUD without documented stability/sterility testing: 48 hrs (rm temp), 14 days (fridge), or 45 days (frozen) If product compounded in ISO5 equipment which is NOT located within ISO7 environment, product must be administered within 12 hrs Annual media tests completed & documented Medium Risk CSP s Multiple sterile ingredients combined for multiple patients or single patient on multiple occasions. Extended time to complete (dissolution or mixing) BUD without documented stability/sterility testing: 30 hrs (rm temp), 9 days (fridge), or 45 days (frozen) Annual Media Tests completed and documented High Risk CSP s Non-sterile ingredient(s) Use of equipment or ingredients that have been exposed to environment worse than ISO5 BUD without documented stability/sterility testing: 24 hrs (rm temp), 3 days (fridge), or 45 days (frozen) Sterility testing for autoclaved CSP s not required for batches < 25 units Sterility by filtration must be performed using 0.22 micron filter in an ISO5 environment or better. Semi-Annual Media Tests completed and documented 4

5 Special Conditions Immediate-Use CSP s Hazardous Drug CSP s Radiopharmaceutical CSP s Allergen Extract CSP s Sterilization Verification of testing & monitoring of personnel & environment API determined to be stable under chosen method Glass & metal devices dry heat sterilized Filter integrity tested after use Autoclaving at 121 degrees, 15 psi, for minutes Dry-heat sterilization reserved for special cases Environmental Quality ISO 5 workspace within ISO 7 buffer area with > water column pos pressure to ante-room ISO 8 ante-room for garbing, storage and prep with > water column pos pressure to unclassified areas ACPH (air changes per hour) > 30 Constructed of approved materials (non-porous) Environmental Sampling Environmental recertification (q 6 mo), facility or equip servicing, and/or issue response Nonviable: tests performance of system Pressure Differential: Meter installed to measure positive pressure between classified areas. Readings monitored and recorded daily Viable: Surface sampling with contact plates & volumetric air sampling > every 6 months Environmental Maintenance ISO 5 area: each shift, each batch, after spill or suspected contamination, after 30 minutes of ongoing compounding. ISO 7 & ISO 8 work surfaces cleaned daily (counters & easily cleanable work surfaces) Floors: Daily Walls, Ceilings, storage shelves: Monthly CONNECTICUT REGULATION CHANGE EFFECTIVE 7/1/14 STATE OF CT MANUFACTURING LICENSE REQUIRED TO DISPENSE COMPOUNDED MEDICATIONS TO MEDICAL FACILITIES/OFFICES PHARMACY REQUIRED TO CREATE & MAINTAIN A SEPARATE FILING SYSTEM FOR MEDICATIONS DISPENSED TO MEDICAL FACILITIES/OFFICES LIMITED TO A TWO WEEK SUPPLY 5

6 Double Blinded Research Phase I Clinicals Clinical Trials FDA COMPOUNDING QUALITY ACT Outsourcing Facilities or 503B exempt from labeling requirements CGMP requirements interstate commerce allowed large volume batches allowed Pharmacies producing drugs for clinical studies under an IND must adhere to the requirements in the IND and are subject to all requirements and regulations applicable to INDs * * Commonly Compounded Non-Sterile Medications Bio-Identical Hormones (Bi-Est, Tri-Est, Progesterone, Testosterone, DHEA, etc) Transdermal Creams (NSAIDS, Corticosteroids, Anxiolytics, etc) Mupirocin Nasal Spray Nail Fungus Solutions (Fluconazole, Itraconazole, Zinc, etc) Pain Gels -ketamine -gabapentin -cyclobenzaprine -amitriptyline -baclofen Salicylic Acid 70% Ointment Commonly Compounded Sterile Medications Injections TriMix or Triple P Intrathecal pain meds Bladder Irrigations Gentamicin DMSO/Lidocaine Ophthalmics PF Combinations Commonly Ordered Office-Use Medications Tetracaine solution or gel (Pontocaine) Cantharidin Solutions Salicylic Acid 70% Ointment Dexamethasone Injections Benzocaine/Lidocaine/Tetracaine Gels 1. Pharmaceutical compounding includes preparation of drug dosage forms for all of the following except: 1. Animals 2. Resale by physicians 3. Clinical research 4. In anticipation of routine ordering patterns 6

7 2. Which condition is considered a basic required component of quality compounding? 1. Well documented personnel training 2. Reproducible process 3. Certificate of Analysis for all ingredients 4. All of the above 3. Which of the following is not a requirement for ingredient selection in compounding? 1. MSDS available 2. FDA-registered source for manufacturer 3. Documentation of storage conditions 4. NDC number recognized by patient s insurance company 4. Which ingredient is not on the NIOSH Hazardous chemicals list? 1. Salicylic Acid 2. Chlorambucil 3. Progesterone 4. Warfarin Sodium 5. Which of the following is an acceptable sterilization method for an aqueous suspension? 1. Filtration through 0.22 micron sterile filter 2. Autoclaving at 121 degrees Celsius & 15 psi for minutes 3. Dry Heat sterilization at 250 degrees Celsius for 30 minutes 4. Autoclaving at 100 degrees Celsius & 20 psi for 15 minutes Questions??? For more information Michael Roberge (203) mike@compoundedsolutions.com 7