Definitions and Standards for Drug Wholesale and Pharmacy Distributors

PURPOSE: This rule provides standards for the proper storage, maintenance, labeling and distribution of drugs by drug wholesale and pharmacy distributors, and further defines methods of inspections and quality assurance used by the Board of Pharmacy to ensure the public’s safety in these areas. For purposes of this rule, the term drug distributor will be used to define all entities that are licensed under section 338.330, RSMo and are subject to this rule. (1) Drug distributors must maintain standards of practice that will ensure that only drugs of appropriate quality will be distributed to practitioners for further compounding and dispensing to the public. These standards shall be subject to periodic reviews through the board’s inspection process. (A) This process will include on-site inspections for drug distributors who are located in this state and may include border states or by requesting information on licensure and inspections conducted by other states or the federal government through the board office. (B) For purposes of this rule, the term drug distributor, when used, defines anyone engaged in any activity as defined in section 338.330, RSMo. (2) No drug distributor license will be issued unless the facility is under the direct supervision of a manager-in-charge. (A) The board shall consider the same factors in reviewing the qualifications of someone who is appointed as a manager-in-charge as those outlined in 20 CSR 22205.020(8)(A)1. (B) A person must also have appropriate education, experience, or both, before assuming the duties of manager-in-charge. Appropriate education for purposes of this section is defined as education in the areas of work environment, standards of operation and knowledge of laws concerning drug distributor compliance and requirements. 1. Minimum requirements for education/experience may be attained separately or in combination to total two (2) years. 2. Experience within a drug wholesale or pharmacy distributor facility or in any education endeavor beyond a certificate of graduation from an accredited high school or its equivalent may be utilized in meeting these minimum requirements. (C) Any individual that is considered a manager or supervisor within a facility but is not the manager-in-charge of the facility must meet the minimum education/experience requirements as set forth in this rule for a total of one (1) year. (D) The licensee shall require all other persons employed in any prescription drug wholesale distribution activity to have education, training and experience, or any combination, sufficient for that person to perform the assigned functions in a manner as to provide assurance that the drug product quality, safety and security at all times will be maintained as required by law. (E) Drug distributor operations must be conducted at all times under the supervision of a properly designated manager-in-charge. The manager-in-charge must be actively involved and aware of the actual daily operations of the drug distributor operation. The manager-in-charge must be physically present at the drug distributor operation during normal business hours, except for time periods when absent due to illness, scheduled vacation or other authorized absence; and be aware of, and knowledgeable about, all polices and procedures pertaining to the operations of the drug distributor operation. When the person who is manager-in-charge resigns or is terminated from the position, the holder of the license shall immediately notify the board office of the resignation or termination of the manager-in-charge and by notarized affidavit give the name of the new manager-in-charge. (3) Minimum standards of practice for drug distributors shall include the following: (A) The facility must be of a suitable size and construction to facilitate cleaning, maintenance and proper operations; (B) The temperature of the facility where drugs are stored must be maintained thermostatically within temperature requirements as provided for by the manufacturer or the latest edition of the United States Pharmacopeia (USP). Appropriate manual, electromechanical, or electronic temperature and humidity recording equipment, devices, logs, or all of these, shall be utilized to document proper storage of prescription drugs; (C) Appropriate housekeeping, sanitation, lighting, ventilation and humidity of all areas where drugs are stored must be maintained. 1. All aisles and walkways must be free and clear of debris, dirt or filth. 2. Dust shall be kept at low levels through adequate ventilation, cleaning procedures, or both. 3. All shelves and storage areas shall be kept free of debris, dirt, dust and filth. 4. Full cases of drug products shall be raised above floor level and placed on a pallet or similar device. 5. Upon receipt of legend drugs, each outside shipping container shall be visually examined for identity and to prevent the acceptance of contaminated prescription drugs or prescription drugs that are otherwise unfit for distribution. This examination shall be adequate to reveal container damage that would suggest possible contamination or other damage to the contents. 6. Each outgoing shipment shall be carefully inspected for identity of the prescription drug products and to ensure that there is no delivery of prescription drugs that have been damaged in storage or held under improper conditions. 7. Drugs stored in a facility or being processed for distribution must be physically separated at all times from articles, supplies or other drugs that are outdated, distressed, misbranded or adulterated. An area separate from drug storage must be used to store quarantined, nonusable substances or accumulated waste/garbage. Any prescription drugs whose immediate or sealed outer or sealed secondary containers have been opened or used shall be identified as such and shall be quarantined and physically separated from other prescription drugs until they are either destroyed or returned to the supplier. If a drug is received or further distributed, either directly or through a secondary broker (paper) transaction, that is wholly or in part found to be counterfeit, a report which includes the name of the drug, quantity and lot number(s) must be forwarded to the Board of Pharmacy within seven (7) days of gaining knowledge of the transaction. Any recall of a product that is initiated by the Food and Drug Administration (FDA) or by a vendor licensed with the state of Missouri shall not be subject to the reporting requirement. 8. Flammable articles must be stored separately and away from drug products held for later wholesale distribution. 9. Drugs which may be held for later distribution that are labeled for veterinary use must be stored separately from those drugs that are to be distributed for human use. 10. Procedures must be in place to prevent, control and alleviate infestation by insects, rodents, birds or vermin of any kind. Animals, except for service animals as defined by the Americans with Disabilities Act (ADA), are not allowed in the drug storage areas. 11. Appropriate sewage disposal and a hot and cold water supply must be available. 12. The outside perimeter of the premises shall be well-lighted. 13. All facilities shall be equipped with an alarm system to detect entry after hours. 14. All facilities shall be equipped with a security system that will provide suitable protection against theft and diversion. When appropriate, the security system shall provide protection against theft or diversion that is facilitated or hidden by tampering with computers or electronic records; (D) The drug distributor license issued to the facility must be displayed in a public area; (E) Adequate refrigeration must be available to ensure enough storage space for drugs requiring refrigeration or freezing and under temperatures adequate to maintain the drug products as recommended by the manufacturer, the latest edition of the USP, or both; (F) The labeling of drug products held for wholesale distribution must conform to requirements as set forth by the manufacturer, FDA, the USP and section 338.059.2, RSMo; (G) If the conditions under which a prescription drug has been returned cast doubt on the drug’s safety, identity, strength, quality or purity, then the drug shall be destroyed or returned to the supplier, unless examination, testing or other investigation proves that the drug meets appropriate standards of safety, identity, strength, quality and purity. In determining whether the conditions under which a drug has been returned cast doubt on the drug’s safety, identity, strength, quality or purity, the drug distributor shall consider, among other things, the conditions under which the drug has been held, stored or shipped before or during its return and the condition of the drug and its container, carton or labeling, as a result of storage or shipping; (H) Drugs held for wholesale distribution must be stored in a secure area where only authorized personnel have access to them. Sufficient locking mechanisms must be in place and a list of personnel who possess keys or passes which allow them to have independent access to any part of a facility which stores drugs held for later distribution or where any controlled substances are stored must be maintained. Records on all past employees who have had access to drug storage or processing areas must be maintained for a period of three (3) years; (I) Wholesale drug and pharmacy distributors shall establish and maintain inventories and records of all transactions regarding the receipt and distribution or other disposition of prescription drugs. These records shall include the following information: 1. The source of the drugs, including the name and principal address of the seller or transferor and the address of the location from which the drugs were shipped; 2. The identity and quantity of the drugs received and distributed or disposed of; and 3. The dates of receipt and distribution or other disposition of the drugs; (J) Inventories and records shall be made available for inspection and photocopying by authorized federal, state or local law enforcement agency officials for a period of three (3) years following disposition of the drugs; (K) Records described in this section that are kept at the inspection site or that can be immediately retrieved by computer or other electronic means shall be readily available for authorized inspection during the retention period. Records kept at a central location apart from the inspection site and not electronically retrievable shall be made available for inspection within two (2) working days of a request by the board or its representatives; (L) Record requirements as described in this rule shall be followed for appropriate accountability and disposition for all outdated, damaged, deteriorated, misbranded or adulterated prescription drugs; (M) Wholesale drug and pharmacy distributors shall establish, maintain and adhere to written policies and procedures, which shall be followed for the receipt, security, storage, inventory and distribution of prescription drugs, including policies and procedures for identifying, recording and reporting losses or thefts and for correcting all errors and inaccuracies in inventories. Drug distributors shall include in their written policies and procedures the following: 1. A procedure where the oldest approved stock of a prescription drug product is distributed first. The procedure may permit deviation from this requirement if the deviation is temporary and appropriate; 2. A procedure to be followed for handling recalls and withdrawals of prescription drugs. This procedure shall be adequate to deal with recalls and withdrawals due to any— A. Action initiated at the request of the FDA or other federal, state, or local law enforcement or other government agency, including the Board of Pharmacy; B. Voluntary action by the manufacturer to remove defective or potentially defective drugs from the market; or C. Action undertaken to promote public health and safety by replacing existing merchandise with an improved product or new package design; 3. A procedure to ensure that drug distributors prepare for, protect against and handle any crisis that affects the security or operation of any facility in the event of strike, fire, flood or other natural disaster, or other situations of local, state or national emergency; 4. A procedure for reporting counterfeit or suspected counterfeit drugs or devices or counterfeiting or suspected counterfeiting activities to the board; 5. A procedure for the mandatory reporting to the board and any other appropriate federal or state agency of all shortages of prescription drugs and devices where it is known or suspected that diversion or theft is occurring; 6. A procedure for investigating discrepancies involving counterfeit, suspect of being counterfeit, contraband, or suspect of being contraband in the inventory and reporting such discrepancies within seven (7) business days to the board and any other appropriate federal or state agency shall be maintained by each drug distributor; 7. A procedure for reporting criminal or suspected criminal activities involving the inventory of drug(s) and device(s) to the board within the seven (7) business days; and 8. A procedure to ensure that any outdated prescription drugs shall be segregated from other drugs and either returned to the manufacturer or destroyed. This procedure shall provide for written documentation of the disposition of outdated prescription drugs. This documentation shall be maintained for three (3) years after disposition of the outdated drugs. (N) Drug distributors will be responsible for security procedures for the delivery of drugs from the wholesale facility to the destination site of all drug shipments; and (O) No drug distributor license shall be issued to any location, regardless of zoning, that is a residence or that shares an address and/or physical space with a business not related to the distribution of prescription drugs or drug-related devices, or not licensed and regulated by the state of Missouri. (4) In addition to standards listed in this rule for drug distributors, drug repackagers must observe federal standards for— (A) Packaging; (B) Record keeping; (C) Expiration dating; (D) Plant facilities; (E) Equipment; (F) Personnel; (G) Production and control procedures; (H) Containers; (I) Testing; and (J) Federal registration requirements. (5) Agents or employees of licensed or registered drug distributors may have legend drugs in their custody if they are acting in the usual course of business or employment and their names and addresses and the addresses of all sites where drugs are stored have been provided to the board. (A) Storage and transport of drugs by agents or employees of drug distributors must be maintained in accordance with manufacturer or USP guidelines and must be free of contamination, deterioration or adulteration. (B) Drug distributors shall report to the board any agents or employees that are registered pursuant to this section of this rule for any convictions for violations of state or federal drug laws. (6) Drug distributors shall establish and maintain lists of officers, directors, managers and other persons in charge of wholesale drug distribution, storage and handling, including a description of their duties and a summary of their qualifications. (7) Drug distributors shall be subject to the provisions of any applicable federal, state or local laws or regulations that relate to prescription drug product salvaging or reprocessing, including Parts 207, 210 and 211 of the Federal Food, Drug and Cosmetic Act. (8) The executive director of the board, at his/her discretion, may grant exemptions to compliance with portions of section (3) of this rule when such exemptions are not contrary to federal drug distributor laws and the exemption is limited to a specific request. Any exemption requests by a licensed drug distributor must be submitted in writing. Any exemptions that are granted as outlined in this section will be provided in writing. (9) As used in section 338.330(3), RSMo, the term “drug related device” shall be defined as an article that is not considered a prescription drug under federal law, but which meets the definition of a device as provided in 21 U.S.C. 321(h) and 21 U.S.C. 360j(e). AUTHORITY: sections 338.333, 338.343 and 338.350, RSMo 2000.* This rule originally filed as 4 CSR 220-5.030. Original rule filed Feb. 4, 1991, effective June 10, 1991. Amended: Filed Jan. 27, 1995, effective Sept. 30, 1995. Amended: Filed March 15, 2000, effective Sept. 30, 2000. Amended: Filed Nov. 1, 2000, effective June 30, 2001. Amended: Filed May 13, 2005, effective Oct. 30, 2005. Moved to 20 CSR 2220-5.030, effective Aug. 28, 2006. Amended: Filed Aug. 21, 2006, effective April 30, 2007. Amended: Filed Feb. 6, 2008, effective Aug. 30, 2008. *Original authority: 338.333, RSMo 1989; 338.343, RSMo 1989, amended 1993; and 338.350, RSMo 1989, amended 1993, 1995.