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The Oregon Administrative Rules contain OARs filed through November 15, 2014
 
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BOARD OF PHARMACY

 

DIVISION 45

STERILE AND NON-STERILE COMPOUNDING

855-045-0200

Application

(1) These rules (OAR 855-045-0200 to 855-045-0270) apply to any person, including any business entity, located in Oregon that engages in the practice of compounding drugs, or any person, including any business entity, located in any other state that compounds drugs for the use of patients located in Oregon. Compounding of radiopharmaceuticals is specifically exempted from these rules where these rules are in conflict with the rules or guidelines established by the Nuclear Regulatory Commission, the Radiation Protection Services of the Oregon Department of Human Services or any other applicable agency. Any person located outside Oregon that compounds drugs for the use of patients located in Oregon is expected to follow the compounding rules of their home state or these rules, whichever are more stringent.

(2) These rules apply to sterile and non-sterile compounding of medications that are prepared for a specific patient and that are prescribed or ordered subject to a valid practitioner - patient relationship.

(3) Whilst the Board does not insist on rigid application of, or adherence to, all the guidelines of the current edition of the United States Pharmacopeia Chapters 795 (USP 795) and 797 (USP 797), it expects pharmacists engaging in compounding to adhere to those guidelines that apply to their practice setting and in all situations to comply with the spirit of USP 795 and USP 797.

(4) Any compounding activity that is not pursuant to a valid prescription or an order to prepare for administration and for a specific patient is considered to be manufacturing, and any person engaged in manufacturing must be registered in accordance with OAR 855-060-0001, with the following exceptions:

(a) Compounding by a pharmacy located in Oregon for a practitioner or dispenser located in Oregon that is covered by a Shared Pharmacy Services agreement as defined in OAR 855-006-0005;

(b) Compounding in anticipation of a prescription drug order or an order to prepare for administration, based on a routine, regularly observed pattern;

(c) Notwithstanding any other provisions of this rule, the preparation of a patient specific product utilizing all non-sterile commercial components, as defined in these rules as Category 1 compounding, is not considered compounding under these rules provided that:

(A) Preparation of these products is an infrequent occurrence;

(B) Quantity of product prepared does not exceed the requirements of a single prescription except that small quantities can be prepared upon request for in-office use by licensed practitioners.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: BP 2-2008, f. & cert. ef. 2-20-08

855-045-0210

Definitions

As used in this division of administrative rules:

(1) "Airborne Particulate Cleanliness Classification" means the level of cleanliness defined by the maximum allowable number of particles per cubic meter of air as specified in the International Organization of Standardization (ISO) Classification Air Cleanliness (ISO 14644-1). The levels used in these rules are:

(a) ISO Class 5 is an atmospheric environment that contains less than 3,520 particles 0.5 microns in diameter per cubic meter of air.

(b) ISO Class 7 is an atmospheric environment that contains less than 352,000 particles 0.5 microns in diameter per cubic meter of air.

(c) ISO Class 8 is an atmospheric environment that contains less than 3,520,000 particles 0.5 microns in diameter per cubic meter of air.

(2) "Beyond Use Date" (BUD) means the date after which the preparation may not be dispensed or administered to a patient. BUD has the same meaning as "Expiration Date".

(3) "Biological Safety Cabinet" (BSC) means a ventilated cabinet with an inward airflow for personnel protection, a downward, High Efficiency Particulate Arresting (HEPA) filtered, laminar airflow for product protection, and a HEPA filtered exhaust system for environmental protection.

(4) Categories of compounding: In these rules, compounding is defined as:

(a) Category 1: Nonsterile -- Simple: Generally, the mixing of two or more commercial products. In these rules, this is not considered to be compounding.

(b) Category 2: Nonsterile -- Complex: Generally, compounding with bulk drug substances or when calculations are required.

(c) Category 3: Sterile -- Risk Level 1: Low-Risk, as defined in OAR 855-045-0250.

(d) Category 4: Sterile -- Risk Level II: Medium-Risk, as defined in OAR 855-045-0250.

(e) Category 5: Sterile -- Risk Level III: High-Risk, as defined in OAR 855-045-0250.

(5) "Compounding Aseptic Isolator" (CAI) means a glove box isolator with a microbially retentive HEPA air filter that maintains an aseptic compounding environment within the isolator throughout the compounding and material transfer process.

(6) "Compounded Sterile Preparation" (CSP) means:

(a) A preparation prepared according to the manufacturer's labeled instructions and other manipulations when preparing sterile products that expose the original contents to potential contamination, and includes all preparations compounded in IV rooms; or

(b) A preparation containing nonsterile ingredients, or employing nonsterile components and devices, that must be sterilized before administration; or

(c) Biologics, diagnostics, drugs, nutrients, and radiopharmaceuticals that possess either of the above two characteristics, and which include, but are not limited to, baths and soaks for live organs and tissues, implants, inhalations, injections, powders for injections, irrigations, metered sprays, and ophthalmic and otic preparations.

(7) "Compounding pharmacy" means any pharmacy where sterile or non-sterile compounding occurs on a regular basis.

(8) "Parenteral Admixture" means a sterile preparation that is the combination of one or more sterile products with an appropriate admixture vehicle.

(9) "Laminar Airflow Hood" (LAF) means a workspace where the work surface is subjected to a constant, HEPA filtered airflow that is directed towards the user.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: BP 2-2008, f. & cert. ef. 2-20-08

855-045-0220

Personnel

(1) Personnel who prepare compounded pharmaceuticals, both sterile and non-sterile, shall be provided with appropriate training before they begin to prepare such products including for CSPs, training in the theoretical principles and practical skills of aseptic manipulations.

(2) The pharmacist in charge (PIC) shall establish pharmacy Policies and Procedures that contain protocols in accordance with the guidelines in USP 797, for the initial training and testing of all personnel and for annual retesting in aseptic manipulative skills for those personnel involved in low and medium risk compounding.

(3) Personnel involved in high-risk compounding must be retested in aseptic manipulative skills at least semi-annually.

(4) The PIC shall ensure that training protocols are followed and records are kept for the training of all new personnel and for all continuing education and periodic testing that is completed.

(5) The PIC is responsible for the procedures and the overall operation of all activities within the pharmacy and must:

(a) Ensure all pharmacy personnel involved in preparing compounded products are trained and have demonstrated skills commensurate with the complexity of the procedures they are performing;

(b) Establish a procedure for verification by a pharmacist of the preparation of each completed compounded product. This verification shall be accomplished by a review of each compounded product that includes but is not limited to:

(A) Ensuring that the drug, dose and dosage form ordered are appropriate for the patient;

(B) Verifying that the correct drugs and components were selected;

(C) Confirming that the calculation and quantity of each drug and component is correct;

(D) Verifying the label is correct and where appropriate contains all the information specified in OAR 855-041-0065 and these rules.

(c) Document verification by the pharmacist responsible for the review.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: BP 2-2008, f. & cert. ef. 2-20-08; BP 3-2011, f. & cert. ef. 4-18-11

855-045-0230

General Requirements

A person licensed to practice pharmacy by the Oregon Board of Pharmacy who is working in a compounding pharmacy, including a pharmacy that only prepares sterile parenteral products, has the duty to exercise that degree of care, skill, diligence and professional judgment that is used by ordinarily competent, careful pharmacists in the same or similar circumstances in the community of the pharmacist or a similar community.

(1) A pharmacist engaged in compounding shall:

(a) Conform to all relevant federal laws and rules;

(b) Dispense a compounded product only subject to a valid prescription except as provided in OAR 855-045-0200(4), and only when, in their professional judgment, it results from a valid prescriber-patient relationship;

(c) Compound only products that are not commercially available except as allowed in OAR 855-045-0240(2), and, except that with the prior approval of the Board, a commercial product that is temporarily in short supply or otherwise unavailable, may be compounded subject to OAR 855-045-0200(4)(c);

(d) Maintain all records in accordance with OAR 855-045-0270;

(e) Perform final product verification.

(2) The pharmacist-in-charge of a compounding pharmacy including a pharmacy that only prepares sterile parenteral products shall ensure that policies and procedures for that pharmacy are reviewed not less than annually, are available for all staff to refer to, and are complied with by all staff. The policies and procedures for a compounding pharmacy shall include but are not limited to, the following:

(a) An organized index;

(b) Product formula information;

(c) Specifications for a compounding log book in compliance with OAR 855-045-0270;

(d) Conditions and surveillance of the compounding environment;

(e) Compounding procedures including requirements for use of gowns, shoe covers or dedicated shoes, hair covers, gloves and masks;

(f) Cleaning and equipment maintenance procedures;

(g) QA plan and documentation;

(h) Shipping and delivery procedures;

(I) Product labeling;

(j) Procedures for final product verification by the pharmacist;

(k) Compounded product quality procedures including procedures for establishing BUD;

(l) Training requirements for all staff;

(m) Safety procedures and training for personnel handling hazardous materials including:

(A) Use of personal protective equipment;

(B) Availability of Manufacturers' Safety Data Sheets;

(C) Emergency procedures related to spills, fire, or exposure to hazardous materials.

(n) Requirements for availability of reference materials.

(3) Pharmacies that compound sterile products including parenteral products shall, when appropriate, also include in their policies and procedures:

(a) Establishment of BUD;

(b) End Product Testing;

(c) Random sampling of both the environment and CSPs.

(4) The pharmacist-in-charge of a compounding pharmacy shall ensure that a quality assurance plan is written for that pharmacy and that:

(a) It includes record keeping requirements for cleaning, testing and calibration of all equipment and devices;

(b) Pharmacies that compound sterile products shall additionally include:

(A) Schedules and protocols for End Product Testing. Pharmacies mixing High Risk Level CSPs or extending Beyond Use Dating (BUD), must establish an End Product Testing schedule that includes random sampling. End Product Testing of a mixing process must show an acceptable sampling of the total preparations prepared annually;

(B) Protocols for establishing BUDs. BUDs may not exceed those in USP 797 guidelines unless a quality assurance program is established that verifies End Product Testing beyond the dating established by USP 797. Records to verify sterility and pyrogenicity must be maintained and available for review for three years.

(5) Bulk chemicals require a certificate of analysis.

(6) The labeling of bulk chemical containers shall contain:

(a) The date obtained;

(b) The BUD, which shall be established as specified in the pharmacy policies and procedures but not more than five years after opening unless additional testing is conducted to extend that BUD by not more than one year.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: BP 2-2008, f. & cert. ef. 2-20-08

855-045-0240

Sterile Parenteral Products

(1) In addition to complying with all the other rules in this chapter of rules that are appropriate to their practice setting, pharmacists compounding sterile parenteral products must comply with the following specific rules.

(a) Establish, maintain and enforce written policies and procedures associated with the pharmacy's preparation and dispensing of parenteral products. Policies and procedures shall be available for inspection at the pharmacy. These policies and procedures shall include all requirements of OAR 855-045-0230 as appropriate to the practice setting and:

(A) Requirements for compounding, labeling and storage of the products;

(B) Requirements for administration of parenteral therapy;

(C) Requirements for storage and maintenance of equipment and supplies.

(b) Labeling: In addition to regular labeling requirements, the label shall include:

(A) Rate of infusion, as appropriate;

(B) Beyond Use Date;

(C) Storage requirements or special conditions, if applicable;

(D) Name, quantity and concentration of all ingredients contained in the products, including primary solution;

(E) Initials of the pharmacist who verified the accuracy of the completed product.

(c) Patient Care Services: Counseling shall be available to the patient or patient's agent concerning proper use of parenterals and related supplies furnished by the pharmacy.

(2) In addition to complying with all the requirements in section (1) of this rule, licensed pharmacy personnel preparing parenteral admixtures as defined in OAR 855-045-0210 may:

(a) Prepare multiple source commercially available premixed parenteral admixtures;

(b) Prepare single source premix parenteral admixtures if the individual components of the premixed parenteral solution are commercially available;

(c) Reassign a parenteral admixture to another patient if the admixture does not exceed the documented BUD for that admixture, and the parenteral admixture that was prepared and dispensed for a patient specific order, and has been stored at all times under the control of a person trained and knowledgeable in the storage and administration of drugs;

(d) In the case of a patient specific parenteral admixture, the pharmacist does not need to comply with the worksheet and log requirements in these rules provided that a quality assurance process is in place to address drug recalls, and appropriate safeguards are in place.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: PB 5-1987, f. & ef. 5-1-87; PB 12-1989, f. & cert. ef. 8-11-89; BP 7-2005, f. 12-14-05, cert. ef. 12-15-05; Renumbered from 855-041-0063, BP 2-2008, f. & cert. ef. 2-20-08; BP 3-2011, f. & cert. ef. 4-18-11

855-045-0250

Definitions of Risk Levels for Sterile Preparations

The three risk levels of CSPs recognized by USP 797 are based on the probability of contamination by microbial, chemical or physical agents. Low-Risk and Medium-Risk Level CSPs are determined by the potential for microbial contamination during preparation, and High-Risk Level CSPs by the potential for not being properly sterilized before administration to patients. These risk levels are defined, and products must be prepared and managed as follows:

(1) Low Risk Conditions:

(a) CSPs prepared using aseptic manipulation within an air quality environment that is equal to or better than ISO Class 5, using only sterile ingredients, products, components and devices;

(b) No more than three commercially manufactured sterile products and entries into one container of sterile product during preparation;

(c) Manipulations limited to:

(A) Aseptically opening ampoules;

(B) Penetrating sterile stoppers on vials with sterile needles and syringes;

(C) Transferring sterile liquids in sterile syringes to sterile administration devices, package containers of other sterile products, and sterile containers for storage and dispensing.

(d) In the absence of sterility testing, preparations must be properly stored prior to administration as follows:

(A) BUD less than or equal to 48 hours at controlled room temperature;

(B) BUD up to14 days: under refrigeration;

(C) BUD up to 45 days: in solid frozen state at -20 °C.

(2) Medium Risk Conditions:

(a) CSPs compounded aseptically under Low-Risk Conditions but with the addition of one or more of the following conditions:

(A) Multiple individual or small doses of sterile products are combined or pooled to prepare a CSP that will be administered either to multiple patients or to one patient on multiple occasions;

(B) The compounding process includes complex aseptic manipulations other than single-volume transfer;

(C) The compounding process requires unusually long duration, such as that required to complete dissolution or homogenous mixing.

(b) In the absence of sterility testing, preparations must be properly stored prior to administration as follows:

(A) BUD less than or equal to 30 hours: at controlled room temperature;

(B) BUD up to 9 days: under refrigeration;

(C) BUD up to 45 days: in solid frozen state at -20 °C.

(3) High Risk Conditions:

(a) CSPs compounded from non-sterile ingredients, including products manufactured for other routes of administration, or a non-sterile device is employed before terminal sterilization;

(b) Exposure to an air quality environment that does not meet ISO 5 or better conditions for more than one hour for any of the following:

(A) Sterile contents of commercially manufactured products;

(B) CSPs that lack effective antimicrobial preservatives;

(C) Sterile surfaces of devices and containers for the preparation, transfer, sterilization and packaging of CSPs.

(c) Prior to terminal sterilization:

(A) Nonsterile procedures including weighing and mixing occur in an air quality environment that does not meet ISO 7 or better conditions;

(B) Compounding personnel are improperly gloved or garbed;

(C) Water-containing preparations are stored for more than 6 hours.

(d) In the absence of sterility testing:

(A) A preparation must be properly stored prior to administration as follows:

(i) For a BUD not to exceed 24 hours, at controlled room temperature;

(ii) For a BUD up to three days, under refrigeration;

(iii) For a BUD up to 45 days, in solid frozen state at -20 °C.

(B) All nonsterile devices must be rinsed thoroughly with sterile, pyrogen-free water then thoroughly drained or dried immediately before use;

(C) Terminal sterilization is required as follows:

(i) CSP solutions passed through a filter with a nominal porosity not larger than 1.2 micron preceding or during filling into their final containers to remove particulate matter;

(ii) Sterilization of high-risk level CSPs by filtration must be performed with a sterile 0.22 micron porosity filter entirely within an air quality environment better than or equal to ISO 5.

(4) Immediate-use:

(a) A compounded preparation intended for immediate use may be prepared in an air quality environment that does not meet ISO 5 or better conditions and a preparer is not required to wear gloves or gown, provided that it is prepared using aseptic manipulation, only sterile ingredients, products, components and devices are used, and it meets all of the following conditions:

(A) No more than three sterile ingredients, products, components and devices are used;

(B) Only simple manipulation techniques employed;

(C) The preparer completes the preparation without interruption and with no direct contact contamination;

(D) Administration must begin within one hour of preparation;

(E) If prepared by someone other than the person who will administer the drug, labeling must include patient name, name and quantity of ingredients, name of person who prepared it, and exact one hour BUD.

(b) Provided that such preparations do not involve the use of hazardous materials, they are classified as "Low Risk".

(5) "Same-day-use": In this rule, the term "Same-day-use" means that the administration of the preparation shall commence within 24 hours from the time of preparation. A same-day-use product that is prepared using aseptic manipulation in a controlled environment with ISO 5 or better class air quality conditions, using only sterile, ingredients, products, components and devices, may be classified as Low or Medium risk provided that it meets all the following conditions:

(A) Only simple manipulation techniques employed;

(B) The environment meets or exceeds the following conditions:

(i) The mixing cabinet is located in an area that restricts airflow to prevent drafts and reduce particle counts;

(ii) There is a partitioned area around the mixing cabinet to create a buffer zone, which must be at least the width of the hood in front of the mixing cabinet;

(iii) The buffer zone must be clearly identified to prevent cardboard or outer packing material intruding into the buffer zone and to prevent any intrusion during the compounding process;

(iv) The environment is cleaned daily.

(C) The preparer completes the preparation without interruption and with no direct contact contamination;

(D) Batch preparation will not exceed eight CSPs;

(E) Administration of the preparation must begin within twenty-four hours of preparation;

(F) The preparer must use gloves, shoe covers or dedicated shoes, hair covers, gown and mask.

(6) Single-dose vial.

(a) The BUD shall be no greater than one hour from time of initial entry if accessed in an environment worse than ISO 5;

(b) The BUD may be up to 24 hours from time of initial entry if appropriately stored and accessed only in an environment better than or equal to ISO 5;

(c) Medications in a single dose ampoule may not be reused.

(7) Multi-dose vial. The BUD may be up to one month or the manufacturer's assigned BUD whichever is shorter, from time of initial entry, in accordance with the pharmacy policies and procedures.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: BP 2-2008, f. & cert. ef. 2-20-08

855-045-0260

Pharmacies and Equipment

Minimum standards for pharmacies and equipment are dependent on the risk level of the products being prepared.

(1) Pharmacies and equipment for the preparation of immediate-use CSPs shall be in accordance with OAR 855-045-0250(4).

(2) Effective January 1, 2009, for preparation of low-risk level CSPs, an ISO 5 certified or better Biological Safety Cabinet (BSC), or a Compounding Aseptic Isolator (CAI), or a Laminar Airflow Hood (LAF) shall be used.

(3) Effective January 1, 2009, for preparation of medium-risk level CSPs, an ISO 5 certified or better BSC, CAI or LAF shall be used. BSCs and LAFs shall be placed in an ISO 7 certified or better buffer room or area. This buffer room or area shall be connected to an ISO 8 certified or better anteroom or area. These areas must have positive airflow unless used to prepare hazardous drugs. CAIs may be placed in an area away from traffic and in a room with ISO 8 certified or better environment, or in accordance with the manufacturer's specifications.

(4) Effective January 1, 2009, for preparation of high-risk level CSPs, an ISO 5 certified or better BSC, CAI, or LAF shall be used. BSCs and LAFs shall be placed in an ISO 7 certified or better buffer room or area. This buffer room or area shall be connected to an ISO 8 certified or better anteroom or area. Unless used to prepare hazardous drugs, the buffer room or zone shall have a positive air pressure of 0.02 to 0.05-inch water column and may not contain a sink or drain. Surfaces and essential furniture in buffer rooms and zones and anterooms shall be nonporous, smooth, nonshedding, impermeable, cleanable and resistant to disinfectants. CAIs may be placed in an area away from traffic and in a room with ISO 8 certified or better environment, or in accordance with the manufacturer's specifications.

(5) Hazardous drugs must be prepared in compliance with state and federal regulations.

(6) Radiopharmaceuticals must be prepared in accordance with OAR 855-042-0005 through 0025.

(7) Pharmacy policies and procedures must include protocols for cleaning and monitoring that include:

(a) A cleaning policy that requires the cleaning of all work surfaces in ISO 7 and 8 areas to be performed at least daily. Floors in ISO 7 and 8 areas cleaned at least daily. Surfaces that are used to prepare CSPs must be cleaned either with a high-level disinfectant or with a medium-level disinfectant that is alternated regularly with another medium-level disinfectant. Empty shelving, walls and ceilings in anterooms and buffer rooms will be cleaned at least monthly with appropriate disinfectant solution;

(b) All ISO classified areas will be checked and certified by a qualified individual no less than every 6 months and whenever the LAF, BSC, or CAI is relocated or the physical structure of the buffer room or anteroom has been altered;

(c) Maintenance, and documentation of maintenance, of all equipment in accordance with manufacturer's specifications.

(8) The Board may waive any requirement of this rule if, in the Board's judgment, a waiver will further public health or safety. A waiver granted under this section shall only be effective when issued in writing.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: BP 2-2008, f. & cert. ef. 2-20-08

855-045-0270

Records

(1) Except for products prepared subject to OAR 855-045-0200(4)(c), all appropriate compounding logs, formula worksheets and documentation of the preparation, verification, dispensing or transfer of all compounded products must be stored in an organized manner, retained for a minimum of three years and be available for inspection by the Board.

(2) The formula worksheets for compounding pharmacies, excluding those for patient specific IV admixture products, must include but are not limited to the following:

(a) Drug name and strength;

(b) Quantity prepared;

(c) Date prepared;

(d) Pharmacy unique lot number;

(e) Manufacturers' lot numbers and expiration dates of all ingredients used to prepare compounded product;

(f) Beyond Use Date;

(g) Name of verifying pharmacist;

(h) Names of all technicians involved in the process;

(I) Copy of the label used for the compounded product;

(j) Mixing instructions;

(k) Physical evidence of the proper weight of each dry chemical or drug used;

(l) Pharmacist verification that the correct formula and the correct weights or volumes of chemical or drugs were used;

(m) Certification of completion of any additional testing, including endotoxin, required by the pharmacy's policies and procedures;

(n) Any other information required by the pharmacy's policies and procedures.

(3) Record of maintenance and certifications for all equipment must be retained for a minimum of three years and be available for inspection by the Board.

Stat. Auth.: ORS 689.205
Stats Implemented: ORS 689.155
Hist.: BP 2-2008, f. & cert. ef. 2-20-08

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