There’s Clean…and then there’s ‘Cleanroom Clean.’

Sterile SatPax

When it comes to cleanroom and controlled-environment news, the stories we read in the press can often be dramatic. Last week, we reviewed a dire situation with ebola where sub-standard gowns, gloves, and glove liners were jeopardizing the lives of medical personnel by allowing bodily fluids to permeate through to the wearer’s skin in a phenomenon known as ‘strike-through.’ And in previous articles we have also examined the role of cleanliness and excellent SOPs in the food processing industry – specifically cases of food-borne illnesses at a seafood processing plant. At Berkshire Corp, we believe it’s crucial to bring you these, and other, stories so that we can shine a spotlight on the very public dangers of not pursuing excellence in contamination-control protocols.

…the very public dangers of not pursuing excellence in contamination-control protocols.

But it is not just the egregious and overtly shocking stories that gain our attention. And this week, we’ll show you why.

Positioning itself as ‘among the most successful and professionally distinguished pharmacies in the state of California and in the Western United States,’ Hartley Medical, a compounding pharmacy based in Long Beach, California, boasts a 30-year tradition of providing pharmaceutical products for the treatment of ‘malignant and non-malignant pain and movement disorders.’(1) The pharmacy specializes in the production of intrathecal medications which, by definition, must be of the highest quality and completely sterile. Why? Because these preparations are introduced directly into the subarachnoid cavity of the brain or into the spinal canal of a patient via a catheter or a pump. Examples of these drugs include pethidine (an anesthetic and opioid analgesic), baclofen (delivered via a pump for spastic cerebral palsy patients), and methotrexate (a chemotherapy drug.) Intrathecal drugs are unusual insofar as they must be administered in this direct way to avoid the blood-brain barrier and, in contrast with drugs given orally, these medications must be absolutely pure and cannot contain preservatives or other inactive ingredients that could be present in injectable preparations.

So it should go without saying that the production of these compounds must conform to the highest possible standards.

According to its own website, Hartley Medical espouses five key ideals: purity, science, safety, service, and compassion. And even a casual surfing of its multitude of articles and blog entries does give a sense of confidence and reassurance in the quality of its products and the integrity of its employees. The site gives the appearance of a highly professional organization with a real dedication to patient well-being. Which is why we were shocked and surprised to discover that Hartley Medical was issued a warning letter from the Federal Drug Administration (FDA) last month regarding a 2015 inspection of the facilities.

While not as dire as previous stories we’ve covered, the situation at Hartley Medical is dangerous nonetheless. In the warning letter, the FDA noted that the pharmacy “did not use a sporicidal agent or sterile wipes, and used non-sterile sanitizers as part of [their] disinfection program for the aseptic processing areas. Therefore, [the] products may be produced in an environment that poses a significant contamination risk.” Again, these are compounds that are introduced to patients directly into the spinal canal or into the brain – a point we must bear in mind during this discussion. While acknowledging that many corrective actions had been taken by Hartley Medical, their use of inappropriate cleaning materials and inadequate SOPs persisted as a cause for FDA concern as it presented a clear violation of the Federal Food, Drug, and Cosmetic Act (FDCA).

And their failures also gave us cause for reflection.

According to the complaint, Hartley Medical’s SOPs did not “establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions.”(2) The equipment referenced in this area included a Laminar Air Flow Workbench which is a relatively common piece of cleanroom equipment and, although not difficult to clean, does require careful consideration. This basis of the FDA complaint was two-fold: the company’s SOPs lacked guidance on the contact time required for effective cleaning with sporicidal agents; and the company was using inappropriate cleaning products – non-sterile wipers instead of sterile ones.

The first of these issues is easy to remediate and requires only an SOP update and some staff training. And to this point, we have produced a training video on cleaning Laminar Air Flow Workbenches which we encourage Hartley Medical to review. It is freely available here. But even with the best SOPs in place, it is imperative that the correct production consumables are used in the manufacturing process. It appears that Hartley Medical was remiss in not using sporicidal agents and validated sterile wipes, relying instead on non-sterile wipes even within their aseptic environment. And again, in the spirit of wishing to assist companies within our industry, we would like to point to some useful resources. If the difference between sterile and non-sterile wipes is unclear, we have an informative reference guide that presents a complete overview of validated procedures, sterility assurance levels, good manufacturing processes, and more. This technical brief is free to download from our website and gets to the heart of how our wipers meet manufacturing and documentation standards and what the concept of sterility means within a contamination-controlled environment.

In the case of Hartley Medical, we note that the FDA complaint does acknowledge the company’s attempts at remediation and corrective action. The pharmacy voluntarily recalled several batches of products and sent multiple responses to the FDA Form 483 indicating how it proposed to come back into compliance. But it also notes that Hartley Medical may wish to consult with a third-party with relevant experience in sterile manufacturing to ensure that the mistakes of the past are not repeated.

consult with a third-party with relevant experience in sterile manufacturing to ensure that the mistakes of the past are not repeated.

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