This one hour webinar was originally presented by Visante Senior Consultant Fred Massoomi (PharmD, FASHP) on December 1, 2015.
In his usual, fast-paced and highly informative style, Fred reviewed the incidents and responding regulations that have brought us through an ongoing evolution toward greater safety regarding the complexities associated with compounding pharmaceutically elegant sterile products.
Dr. Massoomi is an internationally recognized expert on implementation strategies for a compliant USP 797 program including proper handling of hazardous drugs based on OSHA and NIOSH recommendations, as well as proper disposal of pharmaceutical waste, Fred humbly never resorts to pointing an accusatory finger, but rather draws from his own experiences and observations in this field. In addition to his work with Visante, he has served as Pharmacy Operations Coordinator for the Nebraska Methodist Health System since 1996.
Tracing Our Evolution Toward Enhanced Safety
The presentation began with a summary of findings from the PEW Trust’s 2014 study on “US illnesses and Deaths Associated with Compounded Medications,” high level findings were discussed. Since 2001 pharmacies have self-reported 25 compounding errors and 1,076 adverse events resulting in 90 deaths. Many of the practices commonly in place during the early years of this study were improved with the publication of the first USP chapter 797 in 2004. In truth, a number of these standards had been in place since 1975, but simply were not being followed.
By 2013, the Drug Quality and Security Act came out as a modification to the Federal Food, Drug and Cosmetic Act granting more authority to the FDA to monitor compounding processes and to recall any unsafe sterile products. The Act also provided more direction for hospitals producing small amounts of compounded agents (§503A) and guidance for organizations producing larger batches of compounded pharmaceuticals (§503B). If an organization is receiving federal dollars for services, further qualifications were set forth with CMS’ Conditions of Participation. Along with standards of accreditation from The Joint Commission on medication management, the preparation of sterile medications was clearly to be taken from patient care floors and relegated as the full responsibility for production and oversight by the pharmacy.
Complexities Associated with Compounding Pharmaceutically Elegant Sterile Products
The data all point to human error as the primary source of microbial contamination in compounding processes. This number one ranking was the same in 1986 as it was in 2001. Dr. Massoomi noted that most sterile compounding processes have an average of 20 steps that must be followed precisely and repeated exactly with every product made to maintain sterility.
This complex set of activities begins with an extensive training of personnel that should last between six and eight weeks. Physical plant metrics must be maintain with exacting attention to room design and set up (secondary engineering controls), the cabinets (primary engineering controls) , as well as the garb worn. From there, the details of monitoring appropriate temperature, humidity, positive air pressure were discussed along with the importance of alarms to indicate when thresholds for each of these elements are exceeded. One area that can be easily overlooked is how housekeeping staff are trained to clean work surfaces, floors, and all discarded materials. In one example given, Fred shared how environmental sampling of devoted equipment showed a HEPA filter had not been changed for a very long time and had a hidden corroded surface that could possibly have been contaminated. This was immediately changed out. He also gave many other examples of often overlooked elements can be casually dismissed, such as the use of sterile gloves and the errant use of syringes for drug storage. Device compatibility assumptions regarding syringes and various open system protocols were discussed and their vulnerabilities exposed. The importance of sterility and stability testing was emphasized, especially when the BUDs exceed those recommended in Chapter 797.
Now, with the rewrite of chapter 797 and anticipated adoption of USP 800 in 2016 (with compliance required by 2018), more emphasis is being placed on hazardous drug compounding and the proper disposal of these elements. This includes standards for protecting healthcare workers as well as patients who are exposed to hazardous, high alert and high risk medications. These areas have become a point of extreme interest and focus for Dr. Massoomi.
Evaluating Available Resources
The presentation continued with a discussion of available resources for healthcare organizations to procure sterile products. These include: in-sourced production by the hospital pharmacy (covered under §503A), ordering from an FDA monitored pharmaceutical manufacturer and use of an outsourced compounding pharmacy (covered by §503B). Those attending the webinar were polled about how they review and approve outsourcers for sterile compounded products in use by their organizations. A number of those attending used all of these options. The results from this informal poll are below.
- 47% relied on recommendations from their GPO
- 59% completed ASHP’s outsourcing tool
- 43% conducted outsourcer site visits
- 43% visited the FDA website to review survey results.
It was agreed by all that if an outsourcer does not appear on the FDA website survey, that would necessarily mean the end of that relationship.
Dr. Massoomi’s experience is that when there were so many news stories about lack of sterility resulting in injury and death, there was a sharp reduction in the use of outsourcers. This trend seems to be reversing as healthcare organizations examine the cost and complexity of compounding these elements within their own facilities.
Several tools for outsourcer assessment were discussed. These included on-site visits, evaluation of quality documents, examination of recall notification and process, and the outsourcer’s ongoing monitoring protocols. ASHP Foundation’s Outsourcing Sterile Products Preparation, Contractor Assessment tool was noted as helpful in this process.
However these products are obtained, it was emphasized that, from a legal standpoint and The Joint Commission perspective, the hospital is responsible for the services provided to its patients. This includes products obtained from an outsourced vendor. To assist healthcare organizations with this responsibility, there is the recent “Guidance for Industry Drug Supply Chain Security Act, new and heavier due diligence from the FDA, additional regulation from CMS and more complex standards from The Joint Commission. There is also new EPA oversight that that came out in late 2015 as 40 CFR Parts 261, 262, 266, 268, and 273 for “Management Standards for Hazardous Waste Pharmaceuticals.”
So, where are we in our evolution towards safety for patients and healthcare workers? Fred Massoomi remains ever hopeful that new and better methods for compounding of sterile products will come to the forefront and that the safe handling and disposal of hazardous wastes will become common practice for all concerned.
By way of concluding the webinar, Fred shared a quote from an article on Risk Management. He stated that perhaps even within our lifetime, this will become a reality.
|“The time is approaching to make hand filling in clean rooms a part of our history, something we used to do.”
(2008 PDA Risk Management in Aseptic Processing Meeting/ Risk Management, cGMP, and the Evolution of Aseptic Processing Technology; PDAJ Pharm Sci and Tech 2009, 63 8-10)