PROPOSED RULEMAKING
STATE BOARD OF PHARMACY
[ 49 PA. CODE CH. 27 ]
Compounding
[47 Pa.B. 1509]
[Saturday, March 11, 2017]The State Board of Pharmacy (Board) proposes to amend §§ 27.1 and 27.12 (relating to definitions; and practice of pharmacy and delegation of duties), and add §§ 27.601—27.624 to read as set forth in Annex A.
Effective Date
This proposed rulemaking will be effective upon final-form publication in the Pennsylvania Bulletin.
Statutory Authority
This rulemaking is proposed under the authority of sections 4(j) and 6(k)(1) and (9) of the Pharmacy Act (act) (63 P.S. §§ 390-4(j) and 390-6(k)(1) and (9)).
Background and Need for the Amendment
Since at least 2010, the Board has been considering promulgating regulations setting standards for the compounding of drug products by pharmacists. In October 2012, National headlines reported a meningitis outbreak of epidemic proportions. The cause was quickly identified as contaminated compounded injectable medications made by a commercial compounding pharmacy in Massachusetts. Since that time, representatives of the Board have met with interested parties and stakeholders, including representatives from the United States Food and Drug Administration (FDA). Through careful review and input from stakeholders, the Board now proposes to update its regulations to incorporate developments and improvements in the profession's safe, sterile practices and procedures for the compounding of pharmaceutical products for patients.
Description of Proposed Amendments
Definitions of ''FDA'' and ''USP'' are proposed to be added to § 27.1.
Section 27.12 is proposed to be amended to permit a pharmacy technician to assist the pharmacist in the compounding of drug products.
Description of Proposed Provisions on Compounding
Proposed § 27.601 (relating to compounding of preparations) would require that all compounding shall be done in accordance with the current version of the United States Pharmacopeia (USP), specifically chapters governing compounding, which is consistent with Federal law. At the present time, Chapters 795 and 797, regarding pharmaceutical compounding—nonsterile preparations and pharmaceutical compounding—sterile preparations, are the most relevant. There are other chapters of the USP that are relevant and are subject to change. For this reason, the Board refers to the current version of the USP chapters governing compounding. The FDA requires that compounded drug products conform with USP standards in accordance with section 503a of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.A. § 353a), regarding pharmacy compounding. Compounded drugs that do not conform to the USP chapters on compounding may be deemed adulterated or misbranded, which would make them commercially unavailable for consumption. On November 27, 2013, the Federal Drug Quality and Security Act (DQSA) (Pub.L. No. 113-54) was enacted. Title I of the DQSA enacted the Compounding Quality Act, which included important provisions regarding the FDA's oversight of compounding of human drugs, and enhanced communication with state boards of pharmacy. In June 2016, the FDA issued a guidance document, ''Pharmacy Compounding of Human Drug Products under Section 503a of the Federal Food, Drug, and Cosmetic Act—Guidance,'' that is intended to explain how the FDA will interpret section 503a of the Federal Food, Drug and Cosmetic Act while it engages in the rulemaking process. It is available for review on the FDA's web site at http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm469119.pdf. Because the FDA requires that pharmacies follow the USP chapters on compounding, the Board proposes to likewise require compounding by pharmacies in this Commonwealth to comply with the USP.
Proposed § 27.602 (relating to compounding commercially available product) would permit compounding of drug products that are commercially available in the marketplace if the compounded product is changed to produce for a patient a significant medical difference, as authorized by the prescriber, between the compounded drug and the comparable commercially available drug product, or if use of the compounded product is in the best interest of the patient. An example of a significant medical difference would include the removal of a dye to which the patient is allergic.
Proposed § 27.603 (relating to bulk drug substances) addresses the use of bulk drug substances for compounding drugs, including the required registration and certification of analysis of these substances.
Proposed § 27.604 (relating to dispensing compounded drugs) addresses dispensing a compounded drug and the circumstances under which compounding is permitted prior to the pharmacist's receipt of a valid prescription for a particular patient, based on that patient's prescription history. Bulk compounding shall comply with proposed § 27.603 and § 27.623 (relating to production record for drugs compounded in bulk quantities).
Proposed § 27.605 (relating to resale of compounded drug products) would prohibit the wholesale distribution of compounded drug products to other pharmacies, commercial entities or prescribers except in certain circumstances relating to medical practitioners. Pharmacists may only compound nonprescription over-the-counter products for sale pursuant to a prescription and shall comply with FDA labeling requirements and restrictions.
Proposed § 27.606 (relating to compounding prohibited) would prohibit compounding of certain FDA-identified drugs and restricts the compounding of certain commercially available products beyond that otherwise permitted under § 27.602.
Proposed § 27.607 (relating to pharmacist responsibilities) would set forth the pharmacist's responsibilities regarding compounding practice.
Proposed § 27.608 (relating to protective apparel) would specify the clothing required to be worn by pharmacy personnel engaged in compounding and, in certain circumstances involving sterile pharmaceuticals, additional gowning components required by the USP.
Proposed § 27.609 (relating to drug compounding facility requirements) would set forth the requirements regarding facility conditions to minimize the possibility of contamination or decomposition.
Proposed § 27.610 (relating to equipment) would require that the equipment used in compounding of drug products must comply with the USP chapters on equipment.
Proposed § 27.611 (relating to equipment maintenance) addresses the cleaning and sanitizing of the equipment and utensils used for compounding prior to their use to prevent contamination of the drug product.
Proposed § 27.612 (relating to specialized equipment) would provide for measures including the use of dedicated equipment or the meticulous cleaning of contaminated equipment prior to its return to inventory to prevent cross-contamination.
Proposed § 27.613 (relating to use of automated equipment) would require the routine inspection and calibration of equipment used in compounding and the maintenance of the related documentation of these tasks.
Proposed § 27.614 (relating to control of containers and closures) would require drug product containers and closures to meet the requirements of the USP chapters regarding drug product containers and closures.
Proposed § 27.615 (relating to storage) would require that components, bulk drug substances and other materials used in compounding drug products shall be stored in accordance with the USP storage requirements. It also describes the requirement that the composition of the drugs, containers or closures permit the appropriate handling and storage, the cleaning of the work area and the rotating of those items to ensure that the oldest stock of each is utilized first.
Proposed § 27.616 (relating to drug compounding controls) expressly assigns the responsibility of accountability for quality control to the compounding pharmacist.
Proposed § 27.617(a) (relating to standard operating procedures required) would require the establishment of standard operating procedures implementing the applicable USP chapters to ensure the safety, identity, strength, quality and purity of the finished product. Subsection (b) requires standard operating procedures that are designed to prevent microbiological contamination of purportedly sterile compounded drug products. Subsection (c) requires standard operating procedures regarding the tests or examinations to be conducted designed to ensure the reasonable uniformity and integrity of compounded drug products.
Proposed § 27.618 (relating to accuracy) provides additional quantity and quality control procedures regarding weights, measures, subdivision and container labels.
Proposed § 27.619 (relating to production record) specifies the necessary contents and retention of production records for each drug product compounded for an individual patient, as to be distinguished from the production records for each batch of drug product compounded, as required under proposed § 27.623.
Proposed § 27.620 (relating to label information required) itemizes the specific information required on the label affixed to the dispensing container, or on the container itself, of a compounded drug product dispensed by a pharmacy pursuant to a prescription or drug order.
Proposed § 27.621 (relating to compounding records) provides that records required by this chapter shall be retained as original records and shall be readily available at the pharmacy for inspection and photocopying by authorized authorities for at least 2 years following the date of the record. Prescriptions for products compounded at the pharmacy shall be maintained on file at the pharmacy as required under § 27.18(b) (relating to standards of practice).
Proposed § 27.622 (relating to master formula record) specifies the necessary contents of the master formula record for each drug product compounded in bulk quantity.
Proposed § 27.623 specifies the necessary contents and retention of production records for each batch of drug product compounded.
Proposed § 27.624 (relating to label information) itemizes the specific information to be recorded on the label affixed to the container of each batch of drug product compounded.
Fiscal Impact
This proposed rulemaking would have little fiscal impact on the Commonwealth, its political subdivisions or the public. A pharmacy that elects to engage in compounding pharmaceuticals may incur a cost regarding compliance with the standards in this proposed rulemaking. However, as the Board is unable to determine at this time how many pharmacies engage in compounding or may elect to do so at some future date, it is impossible to estimate the fiscal impact on the regulated community.
Paperwork Requirements
This proposed rulemaking would impose additional paperwork requirements on the regulated community. Pharmacies that engage in compounding of pharmaceuticals will have to keep records on file as required by the regulations. The Board will need to alter its inspection forms to capture information relating to compounding, but no other paperwork requirements would be imposed on the Commonwealth.
Sunset Date
The Board continuously monitors the effectiveness of its regulations. Therefore, a sunset date has not been assigned.
Regulatory Review
Under section 5(a) of the Regulatory Review Act (71 P.S. § 745.5(a)), on March 1, 2017, the Board submitted a copy of this proposed rulemaking and a copy of a Regulatory Analysis Form to the Independent Regulatory Review Commission (IRRC) and to the Chairpersons of the Senate Consumer Protection and Professional Licensure Committee and the House Professional Licensure Committee. A copy of this material is available to the public upon request.
Under section 5(g) of the Regulatory Review Act, IRRC may convey comments, recommendations or objections to the proposed rulemaking within 30 days of the close of the public comment period. The comments, recommendations or objections must specify the regulatory review criteria in section 5.2 of the Regulatory Review Act (71 P.S. § 745.5b) which have not been met. The Regulatory Review Act specifies detailed procedures for review prior to final publication of the rulemaking by the Board, the General Assembly and the Governor.
Public Comment
Interested persons are invited to submit written comments, suggestions or objections regarding this proposed rulemaking to the Board Counsel, State Board of Pharmacy, P.O. Box 69523, Harrisburg, PA 17106-9523, RA-STRegulatoryCounsel@pa.gov within 30 days following publication of this proposed rulemaking. Reference No. 16A-5419 (Compounding) when submitting comments.
JANET GETZEY HART, RPh,
ChairpersonFiscal Note: 16A-5419. No fiscal impact; additional inspection costs would be absorbed by the Board and licensing fees would be adjusted accordingly; (8) recommends adoption.
Annex A
TITLE 49. PROFESSIONAL AND VOCATIONAL STANDARDS
PART I. DEPARTMENT OF STATE
Subpart A. PROFESSIONAL AND OCCUPATIONAL AFFAIRS
CHAPTER 27. STATE BOARD OF PHARMACY
GENERAL PROVISIONS § 27.1. Definitions.
The following words and terms, when used in this chapter, have the following meanings, unless the context clearly indicates otherwise:
* * * * * Drug order—
(i) An oral or written order issued by a medical practitioner which is either written on or entered by computer into the medical record of a patient in an institution for the dispensing of a drug or device for administration to the patient.
(ii) The term does not include an order for a drug for a patient in an institution which the patient will self-administer which will be considered a prescription.
FDA—The United States Food and Drug Administration, a division of the United States Department of Health and Human Services.
FDLE—Federal Drug Law Examination.
* * * * * Satellite pharmacy—
(i) A pharmacy in an institution which provides specialized services for the patients of the institution and which is dependent upon the centrally located pharmacy for administrative control, staffing and drug procurement.
(ii) The term does not include a pharmacy serving the public on the premises of the institution nor does it include a pharmacy located off premises from the centrally located pharmacy of the institution regardless of whether the pharmacy is owned by the same person or entity which owns the institution.
USP—United States Pharmacopeia—A compendium of drug information published by the United States Pharmacopeial Convention.
STANDARDS § 27.12. Practice of pharmacy and delegation of duties.
* * * * * (d) Pharmacy technicians.
(1) A pharmacy technician may work only under the direct, immediate, personal supervision of a pharmacist in accordance with subsection (b)(2).
(2) The following are examples of the types of activities which a pharmacy technician may perform:
* * * * * (vi) Enter prescription, drug order or patient information in a patient profile.
(vii) Assist the pharmacist in the compounding of drug products.
(3) A pharmacy technician may not:
* * * * * (Editor's Note: Sections 27.601—27.624 are new and printed in regular type to enhance readability.)
COMPOUNDING § 27.601. Compounding of preparations.
The compounding of sterile and nonsterile preparations shall be done in accordance with the current version of the USP chapters governing compounding.
§ 27.602. Compounding commercially available product.
Based on the existence of a pharmacist/patient/prescriber relationship and the presentation of a valid prescription or drug order, pharmacists may compound, for an individual patient, drug products that are commercially available in the marketplace if one of the following conditions is met:
(1) The compounded preparation is changed to produce for that patient a significant medical difference, as authorized by the prescriber, between the compounded drug and the comparable commercially available drug product. An example of ''significant medical difference'' includes the removal of a dye for a medical reason such as an allergic reaction.
(2) Use of the compounded preparation is in the best interest of the patient.
§ 27.603. Bulk drug substances.
Bulk drug substances to be used in compounding drugs must meet one of the following:
(1) When a monograph exists, bulk drug substances must comply with the applicable USP or National Formulary monograph and the USP chapters on pharmaceutical compounding.
(2) If not subject to a monograph, bulk drug substances must meet one of the following:
(i) The bulk drug substances are ingredients of drugs that the FDA has approved.
(ii) The bulk drug substances appear on the FDA list of approved bulk drug substances not subject to a monograph.
(iii) Peer-reviewed medical literature supports and, in the professional judgment of the pharmacist and prescriber, demonstrates the safety and effectiveness of the bulk drug substances.
§ 27.604. Dispensing compounded drugs.
A compounded drug shall only be dispensed pursuant to a prescription or drug order by the prescriber for a specific patient. Pharmacists may compound drugs in anticipation of receiving a valid prescription based on a history of receiving valid prescriptions generated solely within an established practitioner/patient/pharmacist relationship. Bulk compounding shall comply with §§ 27.603 and 27.623 (relating to bulk drug substances; and production record for drugs compounded in bulk quantities).
§ 27.605. Resale of compounded drug products.
(a) The wholesale distribution of compounded drug products to other pharmacies, commercial entities or prescribers is considered manufacturing and is prohibited, except for distribution to a medical practitioner to administer to an individual patient if the medical practitioner has an administrative system whereby the product can be tracked through the medical practitioner to the individual patient.
(b) Pharmacists may compound for sale over-the-counter products in which all components are nonprescription. The products may be compounded only pursuant to a prescription and shall comply with FDA labeling requirements and restrictions in 21 CFR Part 201 (relating to labeling).
§ 27.606. Compounding prohibited.
Pharmacists may not compound any of the following:
(1) Drugs that have been identified by the FDA as withdrawn or removed from the market because the drugs were found to be unsafe or ineffective as set forth in 21 CFR 216.24 (relating to drug products withdrawn or removed from the market for reasons of safety or effectiveness).
(2) Drugs that are essentially copies of a commercially available drug product, except as provided in § 27.602 (relating to compounding commercially available product).
(3) Drugs that have been identified by the FDA in the Federal Food, Drug, and Cosmetic Act (21 U.S.C.A. §§ 301—399h) or the Code of Federal Regulations as products which may not be compounded.
§ 27.607. Pharmacist responsibilities.
(a) As in the dispensing of prescription drugs, the pharmacist has the responsibility for all of the following:
(1) Inspection and approval or rejection of all components, bulk drug substances, drug product containers, closures, in-process materials and labeling.
(2) Preparation and review of all compounding records to assure that errors have not occurred in the compounding process.
(3) Proper maintenance, cleanliness and use of all facilities and equipment used in compounding practice.
(b) If errors have occurred, the pharmacist is responsible for conducting a full investigation, and creating and maintaining a record of the investigation which must include conclusions and corrective action.
§ 27.608. Protective apparel.
Pharmacy personnel engaged in the compounding of drugs shall wear clean clothing appropriate to the operation being performed. Protective apparel, such as a coat or jacket, apron, or hand or arm coverings, shall be worn as necessary to protect drug products from contamination. For a sterile compounding operation involving one or more aseptic manipulations, sterile gowning components are necessary as required by the USP chapter on sterile compounding.
§ 27.609. Drug compounding facility requirements.
Pharmacies engaged in compounding shall provide all of the following:
(1) A specifically designated area for the orderly placement of equipment and materials to be used to compound medications and to prevent mix-ups or contamination among components, containers, labels, in-process materials and finished drug products.
(2) Washing facilities, easily accessible to the compounding area of the pharmacy, including a sink with hot and cold running water, soap or detergent, and air driers or single use towels.
(3) Lighting, heating, ventilation and air conditioning to prevent contamination or decomposition of components in compliance with the USP provisions regarding facility requirements.
§ 27.610. Equipment.
Equipment used in the compounding of drug products must comply with the USP chapters on equipment.
§ 27.611. Equipment maintenance.
Equipment and utensils used for compounding shall be cleaned and sanitized in accordance with the USP chapters on equipment maintenance prior to use to prevent contamination that would alter the safety, identity, strength, quality or purity of the drug product beyond that desired.
§ 27.612. Specialized equipment.
If drug products with special precautions to prevent contamination are involved in a compounding operation, appropriate measures, including either the dedication of equipment for the operations or the meticulous cleaning of contaminated equipment prior to its return to inventory, shall be utilized to prevent cross-contamination.
§ 27.613. Use of automated equipment.
Automatic, mechanical or electronic equipment, or other types of equipment or related systems, may be used in the compounding of drug products. If this equipment is used, it shall be inspected and calibrated in accordance with the manufacturer's recommendations to ensure proper performance. Documentation of inspection and calibration shall be kept on file for 2 years from the date of inspection and calibration.
§ 27.614. Control of containers and closures.
Drug product containers and closures must meet the requirements of the USP chapters regarding drug product containers and closures.
§ 27.615. Storage.
(a) Components, bulk drug substances and other materials used in the compounding of drug products shall be stored in accordance with the USP storage requirements.
(b) Components, bulk drug substances, drug product containers, closures, and bagged or boxed parts of drug product containers and closures used in the compounding of drug products must allow for all of the following:
(1) Handling and storage in a manner to prevent contamination and to permit inspection.
(2) Cleaning of the work area, including floors.
(3) Rotating of components, bulk drug substances, drug product containers and closures for use in compounding of drug products to ensure of use of oldest stock first.
§ 27.616. Drug compounding controls.
Accountability for quality control is the responsibility of the compounding pharmacist.
§ 27.617. Standard operating procedures required.
(a) The pharmacist shall establish and implement standard operating procedures for the compounding of drug products in accordance with applicable USP chapters to ensure the safety, identity, strength, quality and purity of the finished product. These procedures must include maintaining a listing of the bulk drug substances and components, their amounts in weight or volume, the order of bulk drug substance and component addition, and a description of the compounding processes. Equipment, utensils and the container closure system relevant to the sterility and stability of the intended use of the compounded drug product must be listed.
(b) The pharmacist shall establish standard operating procedures in accordance with applicable USP chapters that are designed to prevent microbiological contamination of compounded drug products purported to be sterile, including validation of any sterilization process.
(c) To ensure the reasonable uniformity and integrity of compounded drug products, the pharmacist shall establish standard operating procedures that describe the tests or examinations to be conducted on the product being compounded. Control procedures must include all of the following, as appropriate:
(1) Capsule weight variation.
(2) Adequacy of mixing to ensure uniformity and homogeneity.
(3) Clarity, completeness or pH of solutions.
§ 27.618. Accuracy.
(a) Components and bulk drug substances used in the compounding of drug products shall be accurately weighed, measured or subdivided as appropriate. These operations shall be verified at each stage of the process to ensure that each weight or measure is correct as stated in the compounding procedures.
(b) If a component or bulk drug substance is removed from the original container and stored in another container, the new container must be identified with all of the following:
(1) Name.
(2) Lot number.
(3) Manufacturer's name.
(4) Beyond-use date.
§ 27.619. Production record.
The pharmacist shall prepare and keep a production record for a minimum of 2 years for each drug product compounded. The record must include all of the following information:
(1) Production date.
(2) List of ingredients and quantity of each ingredient used.
(3) Initials or other identifier of the person or persons involved in the compounding.
(4) Initials or other identifier of the pharmacist verifying the final compounded product.
(5) Internal control or prescription number and, if the prescription is filled using a product compounded in bulk, the internal control number assigned to the batch and recorded in the batch production record in accordance with § 27.623 (relating to production record for drugs compounded in bulk quantities).
§ 27.620. Label information required.
The label affixed to or on the dispensing container of a compounded drug product dispensed by a pharmacy pursuant to a prescription or drug order must bear the information as required in § 27.18(d) (relating to standards of practice) and all of the following:
(1) The name of the compounded drug, the strength, dosage form and quantity of the drug dispensed.
(2) Beyond-use date.
§ 27.621. Compounding records.
Compounding records required by this chapter shall be retained as the original records and shall be readily available at the pharmacy for inspection and photocopying by agents of the Board or other authorized authorities for at least 2 years following the date of the record. Prescriptions for all products compounded at the pharmacy shall be maintained on file at the pharmacy as required under § 27.18(b) (relating to standards of practice).
BULK COMPOUNDING § 27.622. Master formula record.
A pharmacist may compound drugs in bulk quantities for subsequent prescription labeling and dispensing in accordance with § 27.604 (relating to dispensing compounded drugs). For each drug product compounded in bulk quantity, a master formula record shall be prepared containing all of the following information:
(1) Name, strength and dosage form of the drug product compounded.
(2) All components and an accurate statement of the weight or measure of each component.
(3) Equipment needed to prepare the drug product.
(4) Mixing instructions.
(5) Beyond-use date.
(6) Container, closures and packaging materials used in dispensing.
(7) Storage requirements.
(8) Labels and labeling with appropriate beyond-use date and instructions for storage and use.
(9) Quality control procedures to include identification of the person or persons performing and directly supervising or checking each significant step in the compounding.
(10) Other factors pertinent to the replication of the drug product as compounded.
§ 27.623. Production record for drugs compounded in bulk quantities.
For each batch of drug product compounded, a production record shall be prepared and maintained containing all of the following information:
(1) The information from the master formula record.
(2) Records of each step in the compounding process including all of the following:
(i) Documentation of the name and strength of the compounded drug product.
(ii) Formulation record reference for the drug product.
(iii) Sources and lot numbers of the components.
(iv) Total number of dosage units compounded.
(v) Name of the person who prepared the drug product.
(vi) Name of the pharmacist who approved the drug product.
(vii) Date of preparation.
(viii) Prescription number or assigned internal identification number.
(ix) The results of quality control procedures as described in the pharmacy's continuous quality improvement program.
(3) Beyond-use date.
(4) Internal control number.
(5) Total yield.
§ 27.624. Label information.
For each batch of drug product compounded, labels containing all of the following information shall be prepared and affixed to each container:
(1) Drug product name or formula.
(2) Dosage form.
(3) Strength.
(4) Quantity per container.
(5) Internal control number.
(6) Beyond-use date.
[Pa.B. Doc. No. 17-427. Filed for public inspection March 10, 2017, 9:00 a.m.]
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