Ensure Outsourcing Quality Control during Shortages

December 2011 - Vol.8 No. 12 - Page #14
Category: Outsourced Compounding Services (503B)

It is an unfortunate sign of the times that a quick scan through just about any news source will yield at least one example of an adverse drug event that was created or exacerbated, at least in part, by the alarming trend of drug shortages in the US marketplace. Stories abound of treatments delayed or cancelled, inferior drug substitutions, and desperate patients scrambling for life-saving medications. The American Hospital Association (AHA), the Institute for Safe Medication Practices (ISMP) and the American Society of Health System Pharmacists (ASHP) all have published data surrounding the impact of these product shortages on patient care, and although no definitive systematic studies are yet available, these sources all point to a wide and deepening problem that seems to have no end in sight. The FDA is reporting that the number of annual drug shortages has tripled from 61 in 2005 to 178 in 2010.1 Their data reveals that the majority of drug shortages (80%) involved sterile injectables, with oncology drugs (28%), antibiotics (13%), and electrolyte/nutrition drugs (11%) rounding out the major therapeutic classes of drugs. As the FDA concludes, “the problem of medical product shortages is complex and stems from economic, legal, regulatory, policy, and clinical decisions that are deeply interconnected.”2

A recent study published in the American Journal of Health-System Pharmacy (AJHP) highlighted the time and cost impacts to health-systems, which are staggering. ASHP member pharmacy directors reported that their pharmacy technicians and pharmacists charged with the procurement of these agents are spending nine and eight hours a week, respectively, dealing with drug shortages. This was translated by the authors into an estimated labor cost of $216 million dollars a year.3

As a practical matter, until the global system is repaired it is obvious that health organizations need to develop approaches and strategies to mitigate the impact of drug shortages within their current drug distribution and supply system to assure the safest and most effective care for patients, as well as protect the bottom line. The expanded use of outsourced compounders is one such strategy.

Expansion of Outsourced Compounding
There simply is no quick or single solution to the complex problem of drug shortages and it is clear that in order to resolve this matter the US response will need to be global, well developed, multi-faceted, long term, and sustainable. The FDA, on its own, cannot address all the public and private sector factors that are contributing to this far-reaching public health emergency. However, there are steps that individual facilities and health systems can take to protect themselves in the event of a shortage. Likewise, for facilities that are currently using outsourced compounders as a supplement to, or in place of, in-house compounding operations, knowing that your service provider is delivering safe and certified sterile products adds significant peace of mind.

Partnering with a contract compounder or outsourcing provider has been an annually growing trend. Earlier this year, Pharmacy Purchasing & Products’ annual State of Pharmacy Compounding Survey (April 2011) demonstrated a growing number of facilities participating in some form of outsourced compounding from a baseline of 56% in 2008 to its current high of 66%. This trend is expected to see marked increases in the outsourcing of OR syringes, oncology drugs, TPN, nerve blocks, and electrolyte solutions;4 some of the exact products that have been most affected by shortages according to the FDA. Given the popularity of this type of service—as demonstrated by the 87% of facilities that rated their outsourced compounder as good (48%) or excellent (39%)5—it is apparent that the outsourced compounding provider marketplace will only continue to expand in the foreseeable future.

Rationale for Outsourcing
The drivers for product procurement from outsourced compounders are not just limited to shortage situations and are as varied as the customers themselves. Among the motivations for outsourcing are the following:

  • The reduction of regulatory burdens caused by operating a cleanroom. For example, outsourcing compounded sterile preparation (CSP) that are required to be compounded from non-sterile active pharmaceutical ingredients so that the overall cleanroom operation stays at medium risk and is not required to comply with high-risk standards.
  • Supplementing an existing CSP program of limited capabilities (ie, limited by number or type of CSPs which can be produced there).
  • The offering of services or dosage forms that are beyond the facility’s current capabilities.
  • A response to reductions in pharmacy staffing levels or other resources.

Whatever the driving force, careful selection of an outsourcing partner is a basic responsibility of the pharmacy receiving and dispensing outsourced CSPs. This regulatory reality cannot be overstated; USP <797> describes these responsibilities within the Responsibility of Compounding Personnel section of the chapter.6 An informed pharmacist must carefully select a vendor to partner with and in which to place the trust of the facility, and by extension, its patients. (See the July 2009 issue of PP&P where we outlined the basics for outsourced compounding vendor selection.7)

Selecting a Quality Vendor
Selecting a suitable outsourcing provider or providers can be a complex process. There are several criteria that need to be determined, as understanding both your own requirements, as well as those of the outsourced provider is paramount. Accordingly, the following criteria should be established and garner careful consideration when performing due diligence on prospective service providers:


  • The provider can show current status as a licensed pharmacy in the state where the business resides
  • The provider is registered with FDA as a drug manufacturer or is otherwise licensed to supply CSPs to your facility
  • Determine whether the provider is required to be licensed within their respective states as a wholesaler/distributor to supply CSPs to your facility
  • When considering a provider located in another state, determine whether the provider is required to hold an out-of-state wholesaler or distributor license (where applicable) to provide CSPs to your state
  • Determine whether an out-of-state provider is required to maintain special pharmacy licenses or sterile compounding licenses for your state

Environmental Standards

  • Ask the provider to present certification that its cleanrooms meet or exceed USP<797>
  • requirements
  • Ensure the provider uses only FDA approved sterile components
  • Ask to review the provider’s standard operating procedures (SOPs) for all production, monitoring, and sanitation processes
  • Service Knowledge and Expertise
  • Determine whether the provider has special credentials or experience that indicates expertise in all aspects of CSP compounding
  • Ensure the provider has robust staff training and competency based education programs in place, including documentation


  • Ask the provider to provide a list and range of client references
  • Determine whether these client references can be contacted and interviewed

Controlled Processes

  • Ensure the provider is following the USP <797> mandate on elements of quality control: “A written description of specific training and performance evaluation program for individuals involved in the use of aseptic techniques for the preparation of sterile products must be developed for each site”8
  • Determine whether the provider’s controlled processes are based upon best practices and have been analyzed using a failure modes and effects analysis methodology. Controlled processes should never be based upon oral history or perceived secundum artem
  • Documentation
  • Carefully review the provider’s current licensure from the FDA, its state board of pharmacy, and the DEA; its liability insurance; and the provider’s current staff licensure to determine if these elements are sufficient for your operation
  • Review the provider’s SOP manual for policies on compounding, cleaning and sanitation, BUD determination, sterility testing (drug and environmental), recalls, and variances processes
  • Review the provider’s training materials and examples of quality reports, including daily cleaning logs, QA testing logs, stability references, and BUD data
  • Finally, request samples of standard reports, service contracts, and any current recalls or incident reports that would be provided to all customers. Carefully review these documents to determine if they adequately meet your specific legal and operational requirements

All Outsourced Compounders Are Not Created Equal
Unfortunately, even armed with data from the comprehensive checklist detailed above, it can be a challenge for pharmacy directors to dedicate the time or resources necessary to visit all vendor candidates under consideration or to perform comprehensive on-site visits and/or quality audits of the outsourcing compounder(s) they ultimately contract with for services. In 2010, LDT Health Solutions conducted an independent Web-based survey of 250 pharmacy directors and IV room managers and found that 85.7% of pharmacy directors had not once visited the contracted outsourced compounders they were receiving CSPs from.9 

Regardless, due to the complex nature of compounding CSPs—particularly large batch CSPs—the ability of a casual observer to detect a true controlled quality process and separate that from the unfamiliar surroundings of a commercial production cleanroom and its processes is at best, unrefined. To separate and objectively evaluate all of the core functions being performed during a brief tour is a daunting task. Consider enlisting the assistance of a qualified consultant to accompany the pharmacy director and/or members of the team on any provider site visit. A capable consultant should be able to acclimate and prepare the director and the team members prior to any site visits and assist in the post-visit critique. Such a service can provide valuable, independent data on the outsourcer’s operations, as well as quality education for the director and leadership team to apply to future endeavors. With this in mind, once the outsourced vendor is selected, it is wise to supplement announced visits with unannounced visits (during regular business hours). This will help ensure that operations viewed during staged visits are representative of true daily compounding operations. 

It is worth noting that independent reviews based upon comprehensive compounder verification tools are available for the larger regional and national outsourcing compounders in order to objectively evaluate these competing providers. These verification reports should be highly detailed and include many more data elements than the average pharmacy team could collect in a single site visit. Such a report should offer a longer and wider view of the following areas of the compounding processes, at minimum:

  • A clear description of the provider’s license status
  • Cleaning and sanitation
  • Environmental monitoring
  • Sterility testing
  • Labeling standards
  • Recall processes
  • Quality assurance programs

These reports can be used to supplement information collected during a director’s site visit or as an initial evaluation metric.

Complete the Due Diligence Process
Outsourcing for CSPs does not release the pharmacy director from responsibility for these products under USP and state board of pharmacy statutes, rules, or regulations regardless of the license status of the outsourced compounder (either as a state licensed pharmacy or FDA registered establishment). Thus, it remains the responsibility of the pharmacy director to review each potential outsourced compounder using a structured inspection visit checklist or comprehensive verification review tool.

Whether actively pursuing an outsourced partner for daily production needs or planning to supplement in-house compounding efforts against critical drug shortages, careful review of all available quality data is essential to an informed decision. Organizations must hold any outsourced compounder to the same or higher levels of accountability for the preparations they purchase as for those they would prepare themselves.10

There are many reasons for partnering with an outsourced CSP provider including supplementing in-house compounding, attempting to reduce regulatory burdens, or managing a drug shortage. Regardless of the reason, contracting with an outsourced compounder—whether theoretical or actual—requires proper due diligence and maintenance review of the selected provider(s) throughout. While your facility may have no perceived need to outsource CSPs, choosing to remain unaware, uneducated, or unprepared for such an interaction will place your pharmacy practice at risk. Therefore, a rational, methodical, and informed search and review of suitable outsourcing compounders to aid your organization during periods of critical need—should they arise—or to supplement current operations must be part of any multidisciplinary risk management plan.

Lou Diorio, RPh, is a principal of LDT Health Solutions, Inc, a quality management consulting company and a graduate of Long Island University’s Schwartz College of Pharmacy, where he is an adjunct professor of pharmacy practice and member of the college’s alumni board of directors. Lou has served as the operations chief of SoluNet, LLC, an FDA registered compounding division of Coram Inc. Before his tenure with SoluNet Lou was the COO of Hebrew Hospital in the Bronx, NY for ten years. Lou has held clinical and management positions in homecare and hospital practice and can be reached at LSDiorio@LDTRx.com.

Dave Thomas, RPh, MBA, is a principal of LDT Health Solutions, Inc. Mr. Thomas previously served as the director of information technology operations for SoluNet, LLC. Mr. Thomas has also served as the manager of implementation and technology development for Baxter Healthcare and as the technology systems manager for Baxter’s COMPASS Group. Before his 15-year tenure with Baxter, Dave held hospital practice and management positions for five years. Dave is a graduate of St. Louis College of Pharmacy and can be reached at DThomas@LDTRx.com.


  1. A Review of FDA’s Approach to Medical Product Shortages. Silver Springs, MD: US Food and Drug Administration; October 31, 2011. (www.fda.gov/DrugShortageReport).
  2. Ibid.
  3. Kaakeh R, Sweet BV, Reilly C, et al. Impact of drug shortages on U.S. health systems. Am J Health Syst Pharm. 2011;68:1811-1819.
  4. 2011 State of Pharmacy Compounding. Pharm Purch Prod. 2011;8(4)Supplement:S30-S31.
  5. Ibid.
  6. USP General Chapter <797>. www.usp.org
  7. Diorio L, Thomas D. Maximizing Outsourcing Options for Compounded Preparations. Pharm Purch Prod. 2009;6(7)Supplement:S6-S9.
  8. USP General Chapter <797>. www.usp.org
  9. 2010 Internal LDT Health Solutions data ©2010 LDTRx.
  10. Sanborn M. Special Report - Outsourcing Compounding Services To Meet USP Chapter <797> Requirements: An Overview. Pharm Pract News. October 2008.
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