Kerry Maloney, Esq., General Counsel, and

1. What Every Pennsylvania Pharmacy Needs to Know about State Board of Pharmacy Compounding Regulations Kerry Maloney, Esq., General Counsel, and Gayle A Cotchen, RPh MBA PharmD, Acute Care Institutional Member Both are employees of the Pennsylvania State Board of Pharmacy.

2. Disclaimer • This presentation should not be construed as legal advice or as an advisory opinion from the Board.  To the extent any of the information may appear to conflict with the Pharmacy Act or other statutes, or the Board’s regulations, the statutes and regulations will be controlling.  The State Board of Pharmacy members, its counsel, and its staff are not permitted to provide legal advice or advisory opinions, including interpretations of the law or regulations or indications of how the Board might vote in any particular case.  Applicants and licensees are encouraged to seek private counsel for legal advice.

3. Disclosure • The presenter for this activity has been required to disclose all relationships with any proprietary entity producing health care goods or services, with the exemption of non-profit or government organizations and non-health care related companies. • No significant financial relationships with commercial entities were disclosed by any of the speakers.

4. Learning Objectives • At the end of this presentation, CE participants will be able to: • List 2 of the topics addressed in Section 503A of the Food Drug and Cosmetic Act • Describe 4 of the topics addressed in USP chapters governing compounding • List 3 of the RPh responsibilities addressed in the compounding regulations

5. Background: Compounding crisis involving New England Compounding Center • 2012 NECC fungal meningitis outbreak killed 64 and caused infections in 793 patients1 • 2017 Glenn Chin, NECC supervisory pharmacist, convicted by a federal jury of 77 counts, including racketeering, racketeering conspiracy, mail fraud and introduction of misbranded drugs into interstate commerce with the intent to defraud and mislead • 2018 Glenn Chin sentenced to 8 years in prison, 2 years supervised release, forfeiture and restitution 1 FDA Office of Criminal Investigations website

6. Compounding crisis involving NECC (continued) • Improperly sterilized preservative-free methylprednisolone acetate • Failed to verify sterilization process • Improperly tested it to ensure sterility • Directed shipping of drugs prior to sterility test results • Directed staff to mislabel drugs to conceal this • Directed compounding with expired ingredients, including chemo that had expired several yrs prior • Prioritized drug production over cleaning • Directed forging cleaning logs • Routinely ignored mold & bacteria found inside clean rooms • Utilized tech with Board-revoked license, concealed this from regulators

7. Compounding Regulations • Following the New England Compounding Center case in 2012, the board drafted compounding regulations with input from stakeholders • “The compounding of sterile and non-sterile preparations shall be done in accordance with 503A of the Federal Food, Drug and Cosmetic Act (FDCA) and the current version of the United States Pharmacopeia (USP) chapters...”  • Proposed regulations submitted by the board in 2017 came back from the Independent Regulatory Review Commission with comments • With input from stakeholders, the Board revised drafted compounding regulations

8. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.12 Standards – examples of activities which a pharmacy technician may perform • (vii) Assist the pharmacist in the compounding of drug products New Sections • 27.601 shall compound in accordance with 503A of FDCA and the current version of USP chapters governing compounding

9. Test your Knowledge • What are some topics in the compounding regulations that are addressed in FDCA Section 503A?

10. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with 503A of Food Drug and Cosmetic Act… • Drug product is compounded for an identified individual patient based on the receipt of a valid Rx order or a notation, approved by the prescriber, on the Rx order that a compounded product is necessary for the identified patient… • In limited quantities before receipt of a valid Rx order for such individual patient; and • Based on a history of the RPh receiving valid Rx orders for the compounding of the drug product…

11. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with 503A of Food Drug and Cosmetic Act… • Compounds the drug product using bulk drug substances: • that are accompanied by valid certificates of analysis (COAs)… • that comply with the standards of an applicable USP/NF monograph, if a monograph exists… • Such as monographs for phenolated calamine topical suspension, strong iodine tincture, ipecac oral solution, paregoric, progesterone compounded vaginal inserts, tacrolimus compounded oral suspension, and ivermectin compounded oral solution, veterinary

12. Test your Knowledge • What are some topics in the compounding regulations that are addressed in USP chapters governing compounding?

13. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with… the current version of USP chapters governing compounding, such as: • USP <7> labeling • USP <659> packaging and storage requirements • USP <795> compounding nonsterile products • USP <797> compounding sterile products • USP <800> handling hazardous drugs in healthcare settings “(e.g., pharmacies, hospitals & other healthcare institutions, pt treatment clinics, physicians’ practice facilities, veterinarians’ offices)”

14. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with… the current version of USP chapters governing compounding, such as: • USP <7> labeling (revised effective 5/1/19) • Differentiates between beyond use date (BUD), expiration dates; compounded preparation’s label must bear a BUD…see <795> and <797> • Provide names and strengths of both the active moiety and specific salt form (when applicable) in the labeling • Labeling should indicate that “this is a compounded preparation.”

15. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with… the current version of USP chapters governing compounding, such as: • USP <659> packaging and storage requirements (revised effective 5/1/19) • Defines tight container, well-closed container, associated components, dry place, refrigerator, controlled room temperature

16. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with… the current version of USP chapters governing compounding, such as: • USP <795> compounding nonsterile products • Hand hygiene/clothing appropriate to type of compounding • Appropriate temperature and humidity monitoring • Assigning beyond use dates • Written standard operating procedures (SOPs) • Employees involved in compounding shall read this chapter; document training, annual evaluation

17. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with… the current version of USP chapters governing compounding, such as: • USP <797> compounding sterile products • Topics addressed in <795> plus • Garbing (such as gown, gloves, mask, hair covers) • Facility design and environmental controls (such as hoods, airflow, particle counts, air sampling) • Minimum frequencies of cleaning/disinfecting • Review of ingredient labeling and COAs • Documented training and competency evaluation

18. Adding compounding regulations to Chapter 27. State Board of Pharmacy • 27.601 shall compound in accordance with… current version of USP chapters, such as: • USP <800> handling hazardous drugs in healthcare settings • List of HDs that entity handles; containment • Handling: receipt, storage, compounding, etc • Environmental wipe sampling • PPE (gloves; gown; head/hair/shoe/sleeve covers; eye/face protection, respiratory protection) • Policies/procedures to ensure worker safety; SOPs • Documented training and competency assessment • Deactivate, decontaminate, clean, disinfect areas

19. Adding compounding regulations to Chapter 27. State Board of Pharmacy New Section • 27.602 prohibited compounding (withdrawn/removed unless IRB approved, essentially copies of commercially available product, FDA identified as products that may not be compounded) • Per FDCA Section 503A, “essentially a copy of a commercially available drug product” does not include a drug product in which there is a change, made for an identified patient, which produces for that patient a significant difference, as determined by the prescriber…

20. Test your Knowledge • What RPh responsibilities will compounding regulations address?

21. Adding compounding regulations (cont.) More New Sections • 27.603 a. RPh responsible for • Inspecting & approving or rejecting components, API, containers, closures, materials and labeling • Preparing and reviewing records to assure no errors occurred in compounding process • Proper maintenance, cleanliness and use of compounding facilities and equipment used, as required by USP • 27.603 b. If errors, RPh responsible for investigation, creating & maintaining investigation record to include conclusions, corrective actions

22. Adding compounding regulations (cont.) More New Sections • 27.604 RPh responsible for accountability for quality control • 27.605 Label on compounded drug product must bear information required in 27.18(d) and in USP. • 27.606 Compounding records retained and readily available at pharmacy for > 2 years; Rx’s on file as required in 27.18(b)

23. Compounding Regulations—Answers to Test your knowledge slides • What are some topics in the compounding regulations addressed in FDCA Section 503A? Compounding _________________ • In limited quantities based on drug product Rx history • For an identified individual patient • Based on receipt of Rx or notation • Using bulk drugs accompanied by COAs • Three of the above • All of the above

24. Compounding Regulations—Answers to Test your knowledge slides • What are some topics in the compounding regulations addressed in USP chapters governing compounding? • Wearing PPE to safeguard staff handling hazardous drugs • Cleaning/disinfecting the compounding area • Reviewing ingredient labeling and COAs • Documenting training and competency assessment • Three of the above • All of the above

25. Compounding Regulations—Answers to Test your knowledge slides • What are some RPh responsibilities are addressed in the compounding regulations? • Inspecting/approving/rejecting components • Prioritizing drug production over cleaning • Creating & maintaining records of error investigation • Proper maintenance, cleanliness, and use of facilities • Three of the above • All of the above

26. Compounding Regulations • Public comment period of at least 30 days; closed April 10, 2017 • Statutory Period is two years from close of public comment period; so, final had to be to Independent Regulatory Review Commission (IRRC) no later than April 10, 2019 • IRRC acts at its public meeting • With Attorney General approval, regulations published as final in PA bulletin

27. Pennsylvania Board of Pharmacy Contact Information • Phone: 717-783-7156 • Email: st-pharmacy@pa.gov • Board Website: http://www.dos.pa.gov/pharm