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March 1, 2017

The Fail-Rate of Compounding Pharmacies – Is It Time to Approach a New Paradigm?

Medical vials and SyringeAlthough it may seem like longer, it was just two short months ago that we welcomed in a new year, one full of promise for exciting developments in the contamination control industry. And it’s off to a flying start. Already in February, as we were still reeling from the issues with Tri-Coast Pharmacy(1), came not one but two recalls affecting Synergy Rx Pharmacy for sterility issues due to contamination.(2) And as we dug deeper into the stories, we came to see that once again a single thread united these problems. Let’s look a little closer to examine case commonality.

Back in November of 2016, Tri-Coast Pharmacy Inc., based in Juno Beach, FL, voluntarily recalled all sterile products prepared within a six-month period. This compounding pharmacy specializes in hormone replacement therapies for both men and women and weight loss products. According to its template website, the company, whose mission includes ‘looking for ways to optimize therapy’, maintains an ‘entire staff of pharmacists and technicians [with] extensive training and expertise in extemporaneous compounding.’(3) Let’s make a note of that: extensive training.

According to the FDA recall, Tri-Coast created non-sterile compounds between May and November of 2016 in what could be described by FDA inspectors as a fundamental failure to observe basic SOPs. For instance, in the report,

inspectors cite employees for not changing or disinfecting their gloves sufficiently

, donning their personal protective outerwear improperly – using their bare hands to put on sterile gowns, masks, and even goggles – and allowing formerly sterile equipment to have contact with non-sterile surfaces, by lounging against the wall of the ante room like a gaggle of terminally bored teenagers in a mall. And perhaps most damning of all was the confirmation given by one of the employees that they ‘re-use their sterile gowns for one day while working on different products within the ISO 5 pressure clean room. They stated that when they finish a batch they will hang their sterile gowns in the ante room.’(4)

And if that’s not enough to leave you shaking your head in wonder at these extensively trained technicians, perhaps this will…

The report also made the point that a variety of aseptic injectables – from Methylcobalamin to a product called ‘Calm Me’ – were observed being prepared in a non-sterile way. In a note that most decidedly does not promote calm, the report stated that ‘during the production operations of Methylcobalamin […] your firm’s operator was observed working directly over the open vials containing sterile product within the LAFW Hood therefore blocking movement of first air around the open unit. Also the operator’s sleeve was observed touching the finished product vials which contained sterile product potentially contaminating the batch.’(5)

Excuse me? The sleeve was observed touching sterile vials of a compound destined for injection into the human body? If this does not scream incompetency and egregious failure to adhere to basic cleanroom standard, we are not sure what would.

And then there were the production failures. One observation noted that, in the production of Calm Me, ‘a round, white-like foreign material’ was observed within the amber vial into which the compound was placed. Given that this light-shielded vial should contain nothing but the clear liquid for which it was intended, the presence of this substance was deeply troubling. In addition to these errors, FDA agents also brought to light a failure in the air filtration and pressure systems. For Tri-Coast, the positive pressure in the cleanroom did not ensure adequate air flow within the room – a problem caused by the closing of no fewer than ten return air vents. We understand – mistakes happen and air vents close. But the response of the operators to the FDA’s observations astoundingly amounted to a shrug of the shoulders and the equivalent of a ‘Meh.’

OK, let’s move on. In February 2017, Synergy Rx Pharmacy, based in San Diego, CA, recalled a slew of products – sublingual tablets, dermatology creams, chemical peels, numbing creams, and products containing Human Chorionic Gonadotropin (HCG).(6) And beyond the facial creams, HCG is where it gets interesting. HCG is a tumor marker – in essence a biomarker found in blood, urine, or tissues – and is used to detect a variety of different types of cancer, from choriocarcinoma to islet cell tumors, seminoma, and testicular cancer. A pretty significantly useful compound, and one that absolutely needs to be contamination free. But the contaminated lots – intended but not approved for the weight loss market – were distributed to physicians’ offices in no fewer than four states – California, Arizona, Wisconsin, and Minnesota. Any one of the units, when administered to a patient, could have caused a potentially life-threatening infection.

So what is the common thread that ties together all of these cases? Arguably it is the fundamentally human failure to follow protocol, to adhere strictly to SOPs in an industry where contamination control is on the front line of the fight to protect public health. So is the answer to enhance our SOPs? Is it to invest in additional training for the technicians who – in the case of Tri-Coast – simply remarked that ‘air vents close,’ like that potential failure to maintain cleanroom sterility was just no big deal. Perhaps not.

Perhaps the answer no longer lies solely in ensuring up-to-date training that is rigorously maintained. Maybe it is not sufficient to circulate SOPs widely and work towards their consistent application. Maybe it is not simply a matter of encouraging/obliging/forcing cleanroom technicians to follow protocol strictly to the letter and to uphold excellence in contamination control. Perhaps instead if, despite all of our efforts, cleanroom technicians are continuing to fall short of expectations, focus should be placed on coming up with alternate paths forward.

Production line in pharmaceutical company

And, in the preparation of sterile compounds, a possible avenue is one upon which we have remarked surprisingly often in previous articles: automation. In an intriguing piece published in January 2015, Jerry Fahni – pharmacy expert, infomatics consultant, and technology blogger – surveyed four different robotic systems in an effort to determine their suitability for use in pharmacy/hospital environments. Researching INTELLIFILL I.V. (Baxter), APOTECAchemo (APOTECA), i.v.STATION (Aesynt), and RIVA (IHS) in inpatient batch processing, patient-specific custom production, and inpatient/outpatient chemotherapy units, Fahni uncovered more benefits to the systems than problems. Top of the ‘pro’ list was, of course, safety, with the robots maintaining a very conservative margin for error. Universally, when something didn’t add up, the robots had no qualms about discarding the materials and starting afresh.(7)

Following hot on the heels of safety came the question of long production runs.

Unlike human personnel, automated systems do not take bathroom breaks, step out for lunch, or otherwise disrupt the on-going workflow.

They simply switch on and run with the job until complete. And this can be for several hours, or sometimes longer. Yes, the system must be set up with all of the necessary supplies to run a batch, but once that front-loading is complete it’s just a matter of time before the products are available and ready to use.

And the other notable benefit to the deployment of robots is the potential for dramatic reductions in waste. Take, for instance, the comments of Dr. Kevin Jones of the Primary Medical Children’s Center in Salt Lake City, UT: ‘“There’s lots of wasted medications at a pediatric hospital because we prepare so many customized, weight-based doses that cannot be redirected to other patients.”’(8) And not only does this effect the health of the individual patients, it also has impacts on the environment and the hospital’s fiscal bottom line. When pharmaceuticals are drawn, they must be paid for whether they’re ultimately used in patient care or not – so less wastage of resources must equate to a reduced strain on medical insurance providers.

But there were also downsides. Robots have a very limited formulary, typically creating compounds with less than 20 medications. And they’re oftentimes bulky and slow, requiring substantially more room than a human worker and taking longer to complete any individual task. And then there’s arguably the biggest downside: sticker shock. For hospital administrators trying to balance the books, an expenditure of between $200,000 and more than $1,000,000 per robotic unit may seem spendy. And when you purchase one robot, you’ll quickly come to realize that you need another. The automated systems analyzed, for instance, were of necessity dedicated solely to either hazardous or non-hazardous compounding. But if a facility compounds its pharmaceuticals sufficiently frequently to even consider a robot, it’s likely they’ll need one for one purpose and a second for the other. That said, in the case of Dr. Jones in Salt Lake City the costs of wasted medication dropped from $120,000 to just $45,000 per month, thereby paying for the purchase of the robot within three years.

So is the writing on the wall for the old ways? Could automation be the future of the compounding pharmacy industry? Perhaps. In ‘A Tale of Two IV Robots,’ published in Pharmacy Practice News in 2013, Steve Frandzel examined the impact of RIVA, a robot which had reduced the reported error rate for IV medication to zero.(9) Purchased by Children’s Hospital of Orange County, CA, RIVA was successful in reducing wastage of IV drugs by one-third, closing the time gap between physician prescription and drug delivery to the patient, and enabling a per-dose cost reduction due to a new independence from external providers. Dr. Rita Jew, executive director of pharmacy at the hospital, leveraged the power of the robot to produce more frequent drug batches, and the changes allowed her to redirect fiscal resources from employing compounding pharmacists to hiring additional clinical pharmacists.

Less human interaction with critical care formulations can only be a good thing. Human-borne contamination accounts for the vast majority of pollution that finds its way into contamination-controlled environments and robotic systems step very neatly around that problem. And as they move beyond the early adoption phase, their set-up costs will fall, allowing increasing numbers of facilities to house them on-site. As Bill Churchill, chief of service in the Department of Pharmacy at Boston’s Brigham and Women’s Hospital, notes:

“We are at the dawn of a new age of technology and this is just the first generation of sterile IV compounding robots.

They’ve met my expectation and do exactly as advertised. But I expect in the next several years they will change substantially, with more functionality, more features and more capabilities. I see nothing but growth for IV robotics. One of the key decisions pharmacy leaders face is whether to buy the technology now while it’s still developing.”(10)

And perhaps this purchase is no further away than one more FDA recall…

Would you like to see a wider-scale adoption of robots in compounding pharmacy units? Does the potential for contamination by technicians in traditional compounding pharmacies concern you? We’d love to know your thoughts!

References:

  1. https://www.fda.gov/Safety/Recalls/ucm530154.htm
  2. https://www.fda.gov/Drugs/DrugSafety/DrugRecalls/default.htm
  3. https://tricoastrx.com/about/
  4. https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-afda-orgs/documents/document/ucm531795.pdf
  5. ibid
  6. https://www.fda.gov/Safety/Recalls/ucm542405.htm
  7. http://jerryfahrni.com/2015/01/should-you-purchase-a-robot-to-help-compound-sterile-preparations-in-the-i-v-room/
  8. ibid
  9. http://www.pharmacypracticenews.com/Technology/Article/05-13/A-Tale-of-Two-IV-Robots/23209/ses=ogst
  10. ibid
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