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Jo Ann Gibbs, PharmD, BCPS Director of Pharmacy Byrd Regional Hospital
Jo Ann Gibbs, PharmD, BCPS Director of Pharmacy
Byrd Regional Hospital
The Participant will be able to discuss: 1. Discuss the current facts surrounding the
compounding deficiencies found at NECC that led to patient deaths from fungal meningitis after receiving one of their products.
2. Discuss the Emergency Rule from the Board of Pharmacy regarding compounding and how it affects your practice.
3. Apply appropriate Beyond Use Dating to your products.
4. Identify weakness in the compounding environment or process.
The Participant will be able to discuss:
1. Discuss the current facts surrounding the compounding deficiencies found at NECC that led to patient deaths from fungal meningitis after receiving one of their products.
2. Discuss the Emergency Rule from the Board of Pharmacy regarding compounding and how it affects your practice.
3. Apply appropriate Beyond Use Dating to your products.
4. Assist the Pharmacist in charge of quality controls to identify weakness in the compounding environment or process.
A. Minimal Caution, Moderate Caution, Maximum Caution
B. Retail, Hospital, Professional
C. Low Risk, Medium Risk, High Risk
1. Compounding Risk Level, type of storage, and chemical/physical drug stability data.
2. Data from a reference such as Lawrence A. Trissel’s Handbook on Injectable Drugs.
3. Data found in the drug package insert only.
Consider possible sources of contamination, propose a theory, devise and complete an action plan, do follow-up testing and a report of results.
Consider it a testing error and wait for the next regular scheduled maintenance.
Discard results and reschedule testing from another vendor.
To be considered a valuable part of the quality control team.
Do not need to be part of the discussion surrounding out of range quality control results.
Need to be trained in quality control before they are consulted.
Need to be terminated and replaced when an out of range quality control measure is found.
A written environmental control monitoring plan.
A written training plan for compounding personnel.
A written plan for personnel competency testing and results of the testing performed.
An action plan for out of range quality control activities.
All of the above.
http://www.cdc.gov/hai/outbreaks/meningitis-map-large_2013-02-04.html
http://www.cdc.gov/hai/outbreaks/meningitis-map-large_2013-02-04.html
http://www.fda.gov/Drugs/DrugSafety/FungalMeningitis/default.htm
10-15-2012] As a result of FDA, CDC, and state health departments' ongoing investigation of contamination at the New England Compounding Center's (NECC) Framingham, Massachusetts facility, on October 4, the FDA advised providers to not use any NECC products. On October 6, NECC announced a recall of all its products.
Also as a result of the ongoing investigation of NECC, a patient with possible meningitis potentially associated with epidural injection of an additional NECC product, triamcinolone acetonide, has been identified through active surveillance and reported to FDA. Triamcinolone acetonide is a type of steroid injectable product made by NECC. The cases of meningitis identified to date have been associated with methylprednisolone acetate, another similar steroid injectable product.
1. All products were recalled and NECC was essentially put out of business. Key pharmacist leaders lost their pharmacy license to practice in many if not all of the states where they were licensed.
2. Identification of issues was facilitated by active surveillance and reported to FDA.
MedWatch Program
https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
FDA Inspection Dates: 10/1, 10/4-5, 10/15, & 10/26
On 10/2/2012
83 of 321 vials of methylprednisolone acetate (PF) 80mg/mL from lot #08102012@51(shipped to customers between 8/17/12-9/25/12 per firm distribution data), a sterile injectable drug, to contain what appeared to be greenish black foreign matter.
17 of the 321 vials from the same bin were observed to contain what appeared to be white filamentous material.
Formula worksheets state the raw materials are sterile, but the Pharmacy Director stated the firm uses non sterile active pharmaceutical ingredients and raw materials, with the exception of sterile water for injection, to formulate injectable suspensions. ◦ Labeling of the API and additional raw materials did not
indicate they were sterile.
◦ The firm provided to documentation to support that the steam autoclave cycle used to sterilize suspension formulated using non-sterile ingredients is effective.
Environmental Monitoring Program yielded isolates of bacteria and mold within Clean Room 1 and Clean Room 2, used for production of sterile drug products.
Firm personnel stated that the firm shuts off the air conditioning from 8:00 PM to 5:30 AM nightly in the Clean Room.
NECC distributed large batches of compounded sterile products directly to facilities apparently for general use rather than requiring a prescription for an individual patient. • Records show that NECC had lists of potential patient names but did not have patient-specific prescriptions from an authorized practitioner when compounding and dispensing medication, as required by state law. • Manufacturing and distributing sterile products in bulk was not allowed under the terms of its state pharmacy license. If NECC was appropriately licensed as a manufacturer with the FDA the company would have been subject to additional levels of scrutiny. • NECC did not conduct patient-specific medication history and drug utilization reviews as required by regulations.
Final sterilization of product did not follow proper standards for autoclaving (sterilization through high pressure steam) pursuant to United States Pharmacopeia Standard 797 (USP 797) and NECC’s own Standard Operating Procedures: Examination of NECC records indicated a systemic failure to keep products in the autoclave for the required minimum 20-minute sterilization period necessary to ensure product sterility.
NECC did not conduct proper validation of autoclaves pursuant to USP 797:
NECC failed to test their autoclaves to ensure proper function.
Visible black particulate matter was seen in several recalled sealed vials of methylprednisolone acetate from Lot 08102012@51.
Powder hoods, intended to protect pharmacists from inhaling substances during medication preparation, within the sterile compounding area were not thoroughly cleaned pursuant to USP 797.
Residual powder was visually observed within the hood during inspection. This contamination may subsequently lead to contamination of compounded medications.
Condition of “Tacky” mats, which are used to trap dirt, dust, and other potential contaminants from shoes prior to clean room entry, violated the USP 797.
Mats were visibly soiled with assorted debris. A leaking boiler adjacent to the requisite clean room created an environment susceptible to contaminant growth:
A pool of water was visually observed around the boiler and adjacent walls, creating an unsanitary condition; the culture results of this potential contaminant are still pending.
NECC did not ensure equipment was used and maintained properly.
They could not provide a written follow-up for out of range quality controls.
They did not identify microbial growth from samples or provide written investigation into their source.
NECC did not follow USP 797 guidelines concerning testing of batches prior to shipping product.
CHANGE YOUR TACKY MATS WHEN THEY ARE VISIBLY SOILED.
The FDA is making plans and asking for more power from Congress to regulate Compounding Pharmacies.
Congress has 2 pieces of legislation proposed.
The various State Boards of Pharmacy are passing rules.
The NABP is proposing to survey and investigate Compounding Pharmacies as a third party and provide information to State Boards of Pharmacy for registered pharmacies located out of state.
Where is the point that a compounding pharmacy is no longer compounding and has moved to manufacturing?
Where does state jurisdiction end and federal jurisdiction begin?
ASHP is concerned about the necessary practice of anticipatory compounding—the preparation not for specific patients but on known usage trends. Decisions concerning this practice could have a major impact on hospital pharmacies preparing OR room products, epidural and PCA preparations, and oxytocin solutions for L&D.
Current practice allows pharmacies to compound an unlimited amount of product for general use.
The emergency rule allows only 10% of a compounded products to be made without a patient specific prescription (even when intended for prescriber use). At least 90% of compounded product from any pharmacy must prepared in response to a patient specific prescription order
Assigned by considering compounding environment risk, physical/chemical stability, and storage.
Storage Temperatures
Immediate Use Segregated Compounding Area
Low Risk Preparations
Medium Risk Preparations
High Risk Preparations
Controlled Room Temperatures 20 to 25 C (68 to 77 F)
1 hour
12 hours
48 hours
30 hours
24 hours
Controlled Cold Temperatures 2 to 8 C (36 to 46 F)
N/A
12 hours
14 days
9 days
3 days
Controlled Frozen Temperatures -30 to -10 C (-13 to 14 F)
N/A
N/A
45 days
45 days
45 days
Choose your staff wisely.
Only the brightest candidate with great attention to detail should be given IV training.
Include Quality Monitoring and Environmental Monitoring in their training.
Foster an attitude of safety and teamwork with your IV compounding staff.
Weed out poor performers fast.
Do a face to face coaching conversation with your staff regularly—daily, weekly, monthly.
Ask questions such as: Do you have the tools to do their jobs? Do you see any problems I need to address? Are our environmental controls working properly?
Praise them for something they did!! I really appreciate your attention to detail when you clean your area.
A. Minimal, Moderate, Maximum
B. Retail, Hospital, Professional
C. Low Risk, Medium Risk, High Risk
Consider possible sources of contamination, propose a theory, devise and complete an action plan, do follow-up testing and a report of results.
Consider it a testing error and wait for the next regular scheduled maintenance.
Discard results and reschedule testing from another vendor.
To be considered a valuable part of the quality control team.
Do not need to be part of the discussion surrounding out of range quality control results.
Need to be trained in quality control before they are consulted.
Need to be terminated and replaced when an out of range quality control measure is found.
1. Compounding Risk Level, type of storage, and chemical/physical drug stability data.
2. Data from a reference such as Trissel’s Handbook for Injectable Drugs.
3. Data found in the drug package insert only.
A written environmental control monitoring plan.
A written training plan for compounding personnel.
A written plan for personnel competency testing and results of the testing performed.
An action plan for out of range quality control activities.
All of the above.
Compounding Pharmacies will experience regulatory changes in the near future.
We need to work with our professional organizations, Board of Pharmacy, and Legislators to help shape the discussion. It is better to be proactive so as a profession we are driving the bus and not being run over by the bus.
We MUST develop a culture of SAFETY FIRST!!! Looking at the number of patients who have been sickened or died because of this process breakdown should make us realize WE MUST TAKE ACTION.
Questions????
