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By Matt Martin, PharmD, PCCA Clinical Services Manager
All pharmacists want the medications their patients take to be free from potentially harmful contamination. Using the Food and Drug Administration’s (FDA’s) recently finalized guidance document Insanitary Conditions at Compounding Facilities can help you identify situations that might create the potential for contamination before they become a problem. This is applicable for both nonsterile and sterile compounding. Additionally, a recent interview with an FDA division director provides more insight into how pharmacies can protect patients and minimize risk. I’ll discuss how to use both of these documents as helpful resources below, along with what you can do next to implement some of their insights.
How to Interpret the FDA’S Guidance Document
Within the FDA’s insanitary conditions guidance, there is a boxed statement prior to the introduction that states, “This guidance represents the current thinking of the Food and Drug Administration (FDA or the Agency) on this topic. It does not create any rights for any person and is not binding on FDA or the public.”1 Some have interpreted this to convey that the guidance is not law and therefore doesn’t have high standing among the rules, regulations, guidelines and other expectations created by the federal laws, state laws, boards of pharmacy, USP chapters, certification requirements and other demands on pharmacy practice and compounding. While it is true that the guidance document is not law, section 501(a)(2)(A) of the Food, Drug and Cosmetic Act states that drugs are deemed to be adulterated if they are prepared, packed or held under insanitary conditions that may render them injurious to health.
In creating the guidance document, the FDA is communicating how it interprets and plans to enforce the law, although the document is not an exhaustive list. Therefore, beyond using the guidance as a resource to protect patients by preventing potential contamination of compounded medications, the document also serves as a list of issues to address in your pharmacy practice that would likely lengthen the course of FDA inspections and lead to “observations” on the FDA Form 483 issued for correction after inspection. In more serious cases, the FDA may strongly suggest or request that the pharmacy recall compounded medications if the inspectors observe insanitary conditions.
Clues from an Insider Interview
As the guidance document suggests, the FDA has been focused on identifying insanitary conditions in pharmacies, and they will continue to shine light on this topic. One helpful resource that does this is an interview with Ian Deveau, a division director within the FDA Center for Drug Evaluation and Research’s (CDER’s) Office of Manufacturing Quality that was released the same day as the final guidance. The title of the interview is to the point: “CDER’s Efforts to Help Improve the Quality of Drug Compounding Include an Ongoing Focus on Insanitary Conditions.” There is good news to report as Ian notes that “many compounders have stepped up to address our concerns about practices that could result in compounding drugs that cause patient harm.”2 Beyond this, some of the information included in the interview could be helpful in your pharmacy.
Some Insights These Resources Provide
There is always more to be done in refining and examining practices in all pursuits, and compounding is no different. It is vital for pharmacists to remain vigilant in reviewing facilities, products and practices to prevent or correct insanitary conditions. This goes for both nonsterile and sterile compounding.
A key takeaway in the language of the federal law on this topic is the focus on conditions that may render drugs injurious to health. When reviewing the guidance document or even inspection observations from other pharmacies, you typically are not being shown that the potential contaminant was found in a particular compounded medication, but rather that contamination was present in the compounding area and could find its way into a compounded medication, such as foreign matter in the production area. Alternatively, it may not be contamination in the compounding area, but rather how people work in that environment that increases the probability of contamination, such as putting on personal protective equipment in a way that may cause it to become contaminated. Finally, it may be that the products used in the compounding process create a higher probability of contamination because those products are not of the appropriate quality or have not been appropriately tested or qualified for use with medications, such as using nonsterile disinfecting agents and cleaning pads or wipes in ISO-classified areas.
Additionally, the interview provides some images and examples that the FDA has not prominently featured, including the underside of a table made of wood particle board that would be challenging to clean and could harbor drugs or microbes due to its porous nature. Another image shows a hot plate that is visibly dirty with an unknown substance that could lead to contamination.
“When reviewing the guidance document … you typically are not being shown that the potential contaminant was found in a particular compounded medication, but rather that contamination was present in the compounding area ….”
Another focus of the guidance and inspections is the possibility of cross contamination by “handling bulk drug substances or drug products that are hazardous, sensitizing or highly potent (e.g., hormones) with inadequate controls to prevent cross-contamination.”1 This part of the guidance has led some pharmacies to wonder if the FDA is attempting to enforce USP General Chapter <800>. The FDA has made no public statements regarding their interest in enforcing USP <800>, but it has listed four distinct considerations around cross contamination:
1. “Inadequate dedication, segregation and containment (e.g., a powder-containment hood) of a suite, room or piece of equipment based on risk”
2. “Inadequate cleaning of rooms, work surfaces and equipment (e.g., utensils), including spills”
3. “Inadequate segregation of HVAC systems (as appropriate for the operation)”
4. “Inadequate control over the movement of personnel and materials” 1
As a specific example that would factor into the second consideration above, some pharmacies have used 70% isopropyl alcohol (IPA) to clean surfaces and instruments. While 70% IPA is a useful disinfectant, it is not an appropriate deactivating agent. The FDA would take issue with not using an appropriate deactivating agent to clean with after compounding with hazardous, sensitizing or highly potent drugs.
What You Should Do Now
Pharmacy compounding has no shortage of considerations when going from the initial prescription to ultimately providing the correctly compounded medication to the intended patient. All of the situations that the FDA identifies in the guidance document and interview cover conditions that pharmacy staff should address in their own facilities. Many of these are typically described and monitored as a part of standard operating procedures (SOPs). Writing an SOP specific to monitoring for insanitary conditions — or more commonly, folding the various considerations provided by the guidance document into the appropriate SOPs — can make the prevention or correction of insanitary conditions a common part of daily operation within your compounding facility.
If you are interested in having a better understanding of facility operations and preventing insanitary conditions, you could also consider formal training. We offer two training courses to PCCA members that would be incredibly helpful in this area. For nonsterile compounding, the two-day USP Implementation Training course takes an in-depth look at USP <795> proposed changes, competencies, workflow, packaging, beyond-use dating and practical applications in your lab. It also engages participants in laboratory practicums covering USP <800> requirements. The second day specifically focuses on the pharmacy’s “designated person(s)” as defined in the proposed USP <795> and <800> chapters. It includes facility operations, SOPs, personnel training, adverse event documentation, FDA guidance documents (including the insanitary conditions guidance), learning how to assess competencies in the pharmacy and laboratory practicums.
For sterile compounding, our Sterility Assurance Training course integrates USP General Chapter <797>, FDA guidance documents and federal law along with other relevant guidelines and USP chapters. It also interprets observations from recent FDA inspections and shows how to avoid them. Finally, this training course qualifies attendees to perform the competencies found in the latest USP <797> and examines your practice from the ground up to help you develop systems to protect patients and reduce risk.
If you are a PCCA member with Clinical Services support, our team of clinical compounding pharmacists looks forward to working with you on strategies to avoid insanitary conditions in your operation and ensure that patients are receiving the quality compounded medications they expect and deserve.
Matt Martin, PharmD, is the Clinical Services Manager at PCCA. He joined the PCCA Clinical Services department in September 2014. Matt graduated from Morehead State University with a BS in Chemistry in 2002, and received his PharmD from the University of Kentucky College of Pharmacy in 2006. Prior to joining the PCCA team, Matt worked in pharmacy compounding for more than eight years, and has experience with both sterile and nonsterile preparations.
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