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Pharmacy Compounding and Ohio Law

Objectives After completing this lesson, the pharmacist will be able to: 1. Differentiate between five different types of compounding. 2. Describe legal requirements for preparing non-sterile Compounded Drugs for Administration to Patients by Prescribers. 3. Describe legal requirements for preparing sterile Compounded Drugs for Administration to Patients by Prescribers. 4. Discuss limits of preparing batches of compounded drugs. 5. Discuss using a prescribers location as a pick-up-station.

Introduction The matter of regulating compounding pharmacies (or compounding by pharmacies) and manufacturers recently gained renewed attention when an operation in Massachusetts allegedly prepared and distributed corticosteroids that were administered to patients who subsequently developed serious fungal infections. Some of these patients died. According to reports from the Centers for Disease Control and Prevention, the New England Compounding Center and its sister company (Ameridose) were involved in the production and eventual recall of methylprednisolone acetate (MPA) and other products in September 2012. Centers for Disease Control and Prevention. CDC responds to multistate outbreak of fungal meningitis and other infections. http://m.cdc.gov/en/HealthSafetyTopics/DiseasesConditions/Meningitis/currentsituation Accessed November 10, 2012. The methylprednisolone was particularly prone to sterility concerns because it was produced without antimicrobial preservatives, a common practice for medications injected into the fluid of the central nervous system.

The law regulating compounding includes a series of state and federal regulatory schemes.

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Compounding Defined Ohio state law defines compounding in ORC 4729.01(C) as one or more of five activities. Compounding means the preparation, mixing, assembling, packaging, and labeling of one or more drugs in any of the following circumstances: Pursuant to a prescription issued by a licensed health professional authorized to prescribe drugs; [ORC 4729.01(C) (1)] Pursuant to the modification of a prescription made in accordance with a consult agreement; [ORC 4729.01(C) (2)] As an incident to research, teaching activities, or chemical analysis; [ORC 4729.01(C) (3)] In anticipation of orders for drugs pursuant to prescriptions, based on routine, regularly observed dispensing patterns; [ORC 4729.01(C) (4)] Pursuant to a request made by a licensed health professional authorized to prescribe drugs for a drug that is to be used by the professional for the purpose of direct administration to patients in the course of the professionals practice, if all of the following apply: [ORC 4729.01(C) (5)] (a) At the time the request is made, the drug is not commercially available regardless of the reason that the drug is not available, including the absence of a manufacturer for the drug or the lack of a readily available supply of the drug from a manufacturer. (b) A limited quantity of the drug is compounded and provided to the professional. (c) The drug is compounded and provided to the professional as an occasional exception to the normal practice of dispensing drugs pursuant to patient-specific prescriptions.

Type of Compounding Traditional Prescription Consult agreement Research Batch Prescriber for Direct Administration
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ORC Section Defined ORC 4729.01(C) (1) ORC 4729.01(C) (2) ORC 4729.01(C) (3) ORC 4729.01(C) (4) ORC 4729.01(C) (5)

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Compounded Drugs for Administration to Patients by Prescribers OAC 4729-9-25 In addition to complying with ORC 4729.01 (C) (5) as discussed above, compounded drugs must also comply with OAC 4729-5-25 and OAC 4729-9-25. The Board does not want to see pharmacies compounding drugs for administration to patients by prescribers as a major type of routine compounding practice. The pharmacy is limited to five percent (5%) of total compounding sales, within a twelve (12) month period. See OAC 4729-9-25 (A) (1).

Which compounded drugs may be provided by a pharmacy to the prescriber? The pharmacy shall only provide those compounded drugs that are not commercially available to a prescriber which are needed: See OAC 4729-9-25 (A) (2). To treat an emergency situation; See OAC 4729-9-25 (A) (2) (a). For an unanticipated procedure for which a time delay would negatively affect a patient outcome; See OAC 4729-9-25 (A) (2) (b). For diagnostic purposes. See OAC 4729-9-25 (A) (2) (c).

Board rules also limit the pharmacy to supplying an amount which will last the prescriber only seventy-two (72) hours about three days. See OAC 4729-9-25 (B). The prescriber also may not have on hand more than a supply that will last the prescriber seventy-two (72) hours. The rule seems to place the burden on the prescriber for determining the amount that will last the prescriber for seventy-two (72) hours, since the rule reads that the amount shall be determined by previous administration patters provided by a prescriber to the pharmacist. See OAC 47299-25 (B). Indeed, it would be difficult if not impossible for a pharmacist alone to know or accurately estimate this amount.

The seventy-two (72) hour supply limitation does not apply to the following supplied to a prescriber, meaning the following two categories of compounded preparations may be provided even if the supply may last more than seventy-two (72) hours: Small amounts sixty (60) grams or sixty (60) milliliters of non-sterile topical preparations. See OAC 4729-9-25 (B) (1). Non-sterile preparations intended to treat individuals in the event of an emergency. See OAC 4729-9-25 (B) (2).
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Pharmacies may not sell a compounded drug to another pharmacy or wholesaler. See OAC 4729-9-25 (C). Sale and sell include delivery, transfer, barter, exchange, or gift, or offer therefor, and each such transaction made by any person, whether as principal proprietor, agent, or employee. ORC 4729.01 (J). A prescriber may only administer compounded drugs directly to patients of the prescriber. Prescribers are not permitted to do any of the four acts: OAC 4729-925 (D) Dispense a compounded drug to a patient administration is allowed. See OAC 4729-925 (D) (1) Sell a compounded drug to another prescriber. See OAC 4729-9-25 (D) (2) Sell a compounded drug to a pharmacy. See OAC 4729-9-25 (D) (3) Return a compounded drug to the supplying pharmacy. See OAC 4729-9-25 (D) (4)

For compounded drugs provided to prescribers for patients, beyond-use dates are required. See OAC 4729-9-25 (E). For non-sterile compounded drugs, testing pursuant to acceptable practice standards is required. Two types of standards are provided: published peer reviewed pharmaceutical literature that have been critically reviewed by unbiased independent experts. See OAC 4729-9-25 (E) (1) current edition of an official compendium, such as the United States Pharmacopoeia (USP) or National Formulary (NF). See OAC 4729-9-25 (E) (1) Beyond-use dates for sterile compounded drugs must be determined by the compounding pharmacy through one of the two following types of standards: drug product testing pursuant to acceptable practice standards. See OAC 4729-9-25 (E) (2) United States Pharmacopoeia (USP) or National Formulary (NF) standards. OAC 47299-25 (E) (2) The standards account for level of risk of contamination by antimicrobials. The United States Pharmacopoeia (USP) or National Formulary (NF) standards are further refined to include low, medium, and high risk level compounded drug preparations as follows: Low Risk - beyond use date of not more than forty-eight (48) hours when stored at controlled room temperature at twenty to twenty-five degrees Celsius, or fourteen (14)
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days when refrigerated at two to eight degrees Celsius, or forty-five days in solid frozen state at minus twenty-five to minus ten degrees Celsius. See OAC 4729-9-25 (E) (2) (a). An example of low risk preparations includes using sterile syringes with sterile needles to conduct single sterile dose transfers from the manufacturers original packaging such as bottles, bags and vials in an ISO Class 5 cleanroom. An ISO class 5 cleanroom contains at most 105 (or 100,000) particles per cubic meter. See OAC 4729-19-01 (A) (2). To give perspective, the ambient air outside in a typical urban environment contains 35,000,000 particles per cubic meter. Medium Risk - beyond use date of not more than thirty (30) hours when stored at controlled room temperature at twenty to twenty-five degrees Celsius, or nine (9) days when refrigerated at two to eight degrees Celsius, or forty-five days in solid frozen state at minus twenty-five to minus ten degrees Celsius. See OAC 4729-9-25 (E) (2) (b). An example of medium risk preparations includes preparation of Total Parenteral Nutrition (TPN) solutions using automated or manual compounders. High Risk - beyond use date of not more than twenty-four (24) hours when stored at controlled room temperature at twenty to twenty-five degrees Celsius, or three (3) days when refrigerated at two to eight degrees Celsius, or forty-five days in solid frozen state at minus twenty-five to minus ten degrees Celsius. See OAC 4729-9-25 (E) (2) (c). An example of high risk preparations includes dissolving non-sterile bulk drug powders for solution preparation that will be terminally sterilized. Labeling a Compound Drug for Administration by Prescriber OAC 4729-9-25 (F) (1-10) The labeling of a compounded drug preparation must contain the following: (1) The statement For direct patient administration only displayed prominently; (2) The statement Not for resale displayed prominently; (3) Proper storage conditions; (4) Beyond use dates pursuant to OAC 4729-9-25 (E); (5) The name(s) of the active and inactive ingredients; (6) The amount or percentage of active drug ingredients; (7) The quantity of compounded drug provided; (8) The route of administration;
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(9) The pharmacy name, address, and telephone number; (10) The pharmacy control number assigned to the compounded drug preparation.

For a container that is too small, it is permissible for the labeling to omit the quantity of drug provided [OAC 4729-9-25 (F) (7)] and the notation for direct patient administration only [OAC 4729-9-25 (F) (1)]. In all cases, a complete label meeting the requirements of paragraph (F) of this rule must be applied to the outside container in which such compounded preparation is supplied. OAC 4729-9-25 (G).

The sale of a compounded drug preparation to a prescriber is considered a wholesale sale as defined in section 4729.01 of the Revised Code. OAC 4729-9-25 (H). A pharmacy is required to follow record keeping requirements for wholesale sales. See OAC 4729-9-16 (H). The types of records include: source of the drugs, including the name and principle address of the seller or transferor, and the address of the location from which the drugs were shipped. OAC 4729-9-16 (H) (1) (a) identity and quantity of the drugs received and distributed or disposed of. OAC 4729-916 (H) (1) (b) dates of receipt and distribution of the drugs. OAC 4729-9-16 (H) (1) (c) system of records and procedures which prevent the sale or other distribution of dangerous drugs to any person not authorized by division (B) of section 4729.51 of the Revised Code. OAC 4729-9-16 (H) (1) (d) These records must be retained for at least three years. OAC 4729-9-16 (H) (2)

Drugs Compounded in a Pharmacy for Dispensing to Patients OAC 4729-9-21 Most community pharmacists are primarily concerned with compounding relatively small amounts of non-sterile preparations, for specific patients, having a prescription from a physician. These are typically oral or topical preparations provided directly to patients, not physicians.

For all compounded prescriptions, the pharmacist must: Inspect and approve the compounding process. OAC 4729-9-21 (C) (1)
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Perform the final check of the finished product. OAC 4729-9-21 (C) (2) Maintain all compounding records. OAC 4729-9-21 (D) (1) Ensure the proper maintenance, cleanliness, and use of equipment. OAC 4729-9-21 (D) (2)

Personnel engaged in the compounding of drugs need to wear clean appropriate clothing for protection and to prevent contamination. See OAC 4729-9-21 (E). The prescription must be compounded and dispensed only pursuant to a specific order for an individual patient issued by a prescriber. A limited quantity may be compounded in anticipation of prescription drug orders based on routine, regularly observed prescribing patterns. See OAC 4729-9-21 (F). Containers for compounded prescriptions dispensed must be labeled in the same matter as any other prescription medication dispensed. See OAC 4729-9-21 (G) and OAC 4729-5-16 [labeling of drugs dispensed on prescription].

The pharmacist may need a substantial amount of chemicals and time to prepare a batch of some compounded medications. Likewise, the equipment and compounding process involved may dictate that compounding small quantities are simply impractical. For example, if a pharmacist wants to prepare medicated suppositories, a melt-able solid medium must be heated and melted in a receptacle. Active ingredients must be obtained, weighed, and added to the melted medium. The melted mixture must be poured into a suppository mold and allowed to cool. The cooled product must be removed from the mold. The mold and other equipment must be cleaned and stored. All this takes time. Suppose the mold may be adapted to form no less than one hundred (100) units at a time. Does the pharmacist have to postpone compounding activities until one or more prescriptions are in hand for exactly one hundred suppositories and then compound only exactly one hundred suppositories?

Fortunately, the answer is no. A limited quantity may be compounded in anticipation of prescription drug orders based on routine, regularly observed prescribing patterns. See OAC 4729-9-21 (F). If a batch is made, the portion dispensed to patients and the stored portion must be labeled. See OAC 4729-9-21 (H). Labels for the stored medication must contain at least the following information:
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The name, strength, and quantity of each drug used in the compounded prescription. OAC 4729-9-21 (H) (1)

The identification of the repackager by name or by the final seven digits of its terminal distributor of dangerous drugs license number. OAC 4729-9-21 (H) (2)

Pharmacy control number. OAC 4729-9-21 (H) (3) The pharmacys expiration date or beyond use date. OAC 4729-9-21 (H) (4)

Using a Prescribers Location as a Pick-Up-Station See OAC 4729-5-10 Suppose the pharmacist wants to compound a drug for a patient that is not going to be picked up at the pharmacy. It is also not going to be administered to a patient by the prescriber. Can it be delivered to a prescribers office and picked up by a patient there? Yes. See OAC 4729-5-10. To offer this service, a request form (available on the Board website at http://pharmacy.ohio.gov/) must be completed and approved by the Board. Basically, there are five requirements for such a pick-up station: The site is appropriately licensed pursuant to Chapter 4729 of the Revised Code. See OAC 4729-5-10 (B) (1). The receipt, storage, control, and distribution of prescriptions or drugs are in the full and actual charge of a health care professional licensed pursuant to Ohio Revised Code Chapter 4715 [dentist], 4723 [nurse], 4729 [pharmacist], 4730 [physician assistant], 4731 [physician], or 4741 [veterinarian]. See OAC 4729-5-10 (B) (2). An appropriate recordkeeping system is in place that will provide accountability for proper receipt, delivery, and return of all prescription medications. See OAC 4729-5-10 (B) (3). There is a documented method in place to ensure compliance with rule 4729-5-22 of the Administrative Code. See OAC 4729-5-10 (B) (4). The state board of pharmacy has approved the site for such activity due to clear and convincing evidence that delivery of prescription medication directly to the patient would result in: o Danger to public health or safety, [See OAC 4729-5-10 (B) (5) (a)] or o Danger to the patient without increased involvement by a health care professional in the patients drug therapy. [See OAC 4729-5-10 (B) (5) (b)]
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CPE Quiz Questions credit will be provided with correct responses to at least seven questions: 1. The labeling of compounded drugs sold to physician for administration to a patient of the physician must contain name of patient. a) true b) false

2. Compounding a drug in batches can be done in anticipation of prescriptions: a) Based on routine prescribing patterns b) Based on regularly observed patterns c) Based on buying patterns d) Both A and B are correct 3. Compounding a drug in a pharmacy for administration to a patient by a prescriber is permitted when: a) The drug is commercially available b) The drug is provided as a principal source of income for the pharmacy c) A supply of the drug is not readily available from a manufacturer d) The drug is provided directly to the patient 4. Compounding a drug in a pharmacy for administration to a patient by a prescriber is permitted when the compounded drug is to be used: a) To treat an emergency situation. b) For an unanticipated procedure for which a time delay would negatively affect a patient outcome. c) For diagnostic purposes. d) All of the above

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5. Compounding a drug in a pharmacy for administration to a patient by a prescriber may be supplied in an amount that will last more than seventy-two (72) hours when: a) No more than sixty (60) grams of a non-sterile topical preparation is supplied to the prescriber. b) No more than sixty (60) milliliters of a non-sterile topical preparation is supplied to the prescriber. c) A non-sterile preparation intended to treat individuals in the event of an emergency is supplied to the prescriber. d) All of the above

6. When labeling a compound drug for administration to a patient by a prescriber in a container that is too small to bear a complete label, the label must still include all but: a) the statement, for direct patient administration only b) the statement, not for resale c) the route of administration d) the pharmacy name

7. A pharmacy is required to follow record keeping requirements for wholesale sales, including sales of a compounded drug preparation to a prescriber, including all except: a) source of the drugs b) collection of sales taxes and amounts c) identity and quantity of the drugs received and distributed or disposed of d) dates of receipt and distribution of the drugs

8. When acting as a wholesaler, a pharmacy is required to retain records for sales of a compounded drug preparation to a prescriber for five years. a) True b) False

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9. For all compounded prescriptions, the pharmacist must do all of the following except: a) Inspect and approve the compounding process b) Personally perform every step in the compounding process c) Maintain all compounding records d) Ensure the proper maintenance, cleanliness, and use of equipment

10. For a limited quantity of drug compounded in anticipation of receiving a prescription, when a batch is made, the stored portion must be labeled with all but the following: a) The name, strength, and quantity of each drug used in the compounded prescription. b) The initials of the pharmacist. c) Pharmacy control number. d) The pharmacys expiration date or beyond use date.

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Lesson number 036-368-13-001-H03 Answer Sheet: Expires April 18, 2015 Approved for one contact hour of Ohio Jurisprudence by the Ohio State Board of Pharmacy

Pharmacy Compounding and Ohio Law

Answer Sheet circle the one best answer Question Answer 1 True False 2 A B C D 3 A B C D 4 A B C D 5 A B C D Question 6 7 8 9 Answer A B C A B C True False A B C A B C

D D D D

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