Flourish Integrative Pharmacy, LLC of Oklahoma City, OK was issued a 483 on 12/19/2018. Three Observations were recorded by a single CSO who was on site for four days and who typed the entity as a Producer of Non-Sterile Drugs. The Observations cited water purity (“Your firm does not perform testing (analytical or microbiological) to show the water at least minimum meets the specifications for Purified Water, USP.”), stability testing (“your firm does not have a written stability testing program to determine Beyond Use Dates (BUD)”) and potency testing (“Specifically, your firm does not conduct routine testing for potency for all drug products produced by your firm.”)
Downing Labs, LLC of Dallas, TX was issued a 483 on 11/19/2018. Four Observations were recorded by two investigators who were on site for sixteen days and who typed the entity as a Producer of Sterile Drugs. The Observations cited included equipment disinfection, surfaces or equipment that is difficult to clean, stability testing, and facility designed or operated in a way that permits poor flow of materials (specifically, that the technician left sterile equipment wrappers and sterile wipers present in the ISO 5 throughout production).
Michigan Medicine of Ann Arbor, MI was issued a 483 on 12/14/2018. This is the same entity (same FEI, same street address) as referred to previously on CIRoA in a 483 (6/29/2016) and a Warning Letter (9/28/2017) as “University of Michigan.” (this creates a confusing duplicate header) Five Observations were recorded by a single investigator who was on site for four days and who typed the entity as a Producer of Sterile and Non-Sterile Drug Products.
I have been predicting that eventually FDA may turn its “lidless gaze” toward hospital pharmacies, especially large “central compounding facilities.” This particular 483 is NOTevidence of my prediction. I believe this was simply a revisit of a previously inspected entity that received an earlier Warning Letter. I’ve pointed out that once your entity’s street address is in FDA’s database, there’s a very high likelihood they’ll be back, but if they’ve issued a Warning Letter, the chances of a revisit are nearly 100%
FDA has rarely visited inpatient pharmacies, but the Observations they made in this 483 offer remarkable lessons for the day they begin to do so. The Observations cited included:
- Materials or supplies were not disinfected prior to entering the aseptic processing areas), The specifics for this Observation included (a) product labels that came off the printer in the unclassified area, touched the floor and were transferred into the ISO 7 without sanitization and (b) A Sharpie pen being used in the ISO 5 that was sanitized before entering the hood, but was opened inside the hood and the pen tip was exposed to the ISO 5 environment.
- Personnel moved rapidly in the vicinity of instruments, which disrupted the airflow and increased the risk of bringing lesser quality air into the ISO 5 classified aseptic processing area. Specifics cited “fast hand movements” inside the hood and items “tossed” into the hood “so forcefully that many items slid across the hood work surface and hit the laminar airflow grate.”
- Personnel engaged in aseptic processing were observed with exposed hands, exposed wrists, exposed legs, exposed hair and exposed mouth. Specifics included a technician with “exposed forehead skin” observed with his/her head inside the ISO 5 while processing and “resting” the “elbow of their non-sterile gown and have their sleeve touch the work surface.”
- Your facility was designed and/or operated in a way that permits poor flow of materials.
- The use of sporicidal agents in the cleanrooms and ISO 5 classified aseptic processing area was inadequate. I almost fell off my chair when I read this citation of specifics: “Your firm uses a (b)(4) non-sterile smoke to conduct smoke studies in the ISO 5 hoods. After performing the smoke study, the ISO 5 hood is not disinfected with a sporicidal agent.” NON-STERILE SMOKE?! A huge percentage of 483s issued to pharmacies cite our inadequate smoke studies and I’ve railed before that the average CETA certifier has no idea how to give us a smoke study that FDA would deem “adequate,” but I asked myself, “Does industry actually have a way to STERILIZE SMOKE?!” So, I reached out to my cGMP expert mentor, Rick Van Doel of Performance Validation with that question. We chatted and he said nobody he knows of uses sterile smoke. He speculated that the point of the Observation was apparently that the Investigator suspects that the organization didn’t/doesn’t perform a “deep clean” after completing the smoke study and before resuming productionwhich industry does and documents 100% of the time. (see 21 CFR 42(c)(10)(vi))
As my hospital friends read and absorb these details, I think they know that:
- fast hand movements,
- writing inside ISO 5 areas with Sharpie pens,
- printing labels in unclassified areas and transferring them to ISO 7 areas without disinfection,
- using non-sterile garb,
- having exposed skin inside the ISO 5,
- having personnel leaning into the ISO 5;
- having personnel rest their elbows on the work surface of the ISO 5
…are all commonplace practices even in the best hospital pharmacies.
Why Michigan? Michigan is prestigious and sophisticated; it’s on the cutting edge of pharmacy progress and has been for as long as we remember. Why should this shining example suffer the indignity of having common practices (that most of us have traditionally deemed acceptable) posted on a federal website?
We pharmacists love rules. We love black-and-white, concrete, always-never rules. Don’t give us unbridled latitude to establish my own processes and then force us to defend them with evidence, just tell us what to do and we’ll DO IT! Why won’t FDA just give us the RULES? Why won’t they tell us what to do?
USP standards are concrete, but GMP is abstract. USP presumes to tell us what we “should” or “must” do and seems happy to preempt our professional judgment. By contrast, GMP does not presume to know what we make or how we make it. USP standards are carved on stone tablets every few years, but GMP embraces improvements and is constantly evolving. GMP places the focus on the processes, materials, and environments that WE decided to put in place after which an FDA investigator comes in to contrast our decisions with the broad requirements of 21 CFR 211 et seq. If we can defend what we’re doing with credible scientific evidence, we can do it.
Pharmacy World is new to 483s, but a 483 is not a “Scarlet Letter.” A 483 is simply the result of a highly trained investigator poring over and digging into the finest details of our SOPs, our receipts and records, our training and competency demonstrations, observing and questioning our personnel and – under the close daily guidance of FDA Center leadership – providing us with a list of issues that might represent failure to follow federal regulation. And by that I do mean actualfederal regulation, NOT the USP COMPOUNDING CHAPTERS.
We complain that FDA won’t tell us what to do, but 483s and Warning Letters represent FDA telling us what NOT to do. 483s and Warning Letters are as close as we can get to understanding what FDA expects. We can wait for them to show up or we could begin to incorporate the lessons of other entities’ 483s into our processes right away. A smart person learns from his/her mistakes – a wise person learns from the mistakes of others. Let’s all get WISE!
Barclay, Luke, Pillai Specialty Pharmacy, PLLC of Las Vegas, NV was issued a 483 on 12/14/2018. Eleven Observations were recorded by a single investigator who was on site for eight days and who typed the entity as a Producer of Sterile and Non-Sterile Drugs. The Observations are too detailed to recount, but include inadequate smoke study and media challenge, inadequate environmental monitoring, lack of HEPA filtration over the area to which sterile product (pellets) was exposed, introduction of non-sterile wipes and mop heads into ISO 5, exposed skin in ISO 5, equipment and utensils not maintained to precent contamination, no written stability testing program, failure to perform sterility and endotoxin testing, etc.
Leiter’s Enterprises, Inc. of San Jose, CA (503B) was issued a 483 on 12/19/2018. Three Observations were recorded by a single investigator who was on site for six days and who typed the entity as an Outsourcing Facility. The Observations appear to be easily correctable. They were cited for a deficiency in their quality unit, but the specification was that there are no time frames established in SOP to ensure alarms are reviewed in a timely manner and quality unit is not required to ensure alarms are handled appropriately. They were cited for staff lacking the training required, but the specification was that operators were not given enough rest and the underlying processes are not adequate. They were cited for failing to routinely clean the wheels of chairs and rolling carts in the ISO 7. All three issues strike me as simple tweaks to SOPs and some easy retraining, so if I were in charge of QA there, I would be pleased with myself.
Brookfield Medical/Surgical Supply, Inc. (503B) was issued a 483 on 12/21/2018. Eight Observations were recorded by two investigators who were on site for six days and who typed the entity as an Outsourcing Facility. I’m not going to cover all eight Observations, but a few of them caught my eye:
- The firm does not have scientific justification for not monitoring environmental conditions throughout manufacturing operations within the ISO 5 Laminar Flow Hood
- The firm failed to conduct a disinfectant efficacy study to determine the effectiveness of the cleaning agents utilized by the firm on the surfaces of the facility and equipment used in the manufacturing process of the firm’s sterile drug products.
- The has failed to collect retain samples for any of the finished drug products (Triamcinolone Acetonide, Methylprednisolone Acetate and Betamethasone Sodium Phosphate) that have been manufactured since the began operations in 2015.
- You compound drugs that are essentially a copy of one or more approved drugs within the meaning of sections 503B(a)(5) and 503B(d)(2).
Not quite as smooth as Leiter’s 483, but fairly easy to address.
Medcraft, LLC (503B) – received an FMD-145 Letter on January 30, 2019 in reference to its inspection that took place from May 14, 2018 to July 27, 2018 by FDA.
The Wellness Center Pharmacy, Inc. (DBA Designer Drugs) of Chattanooga, TNreceived both an FMD-145 Letter and an SBoP Referral Letter on February 6, 2019 in reference to its inspection that took place from December 12 to December 22, 2017.
Diplomat Pharmacy Inc. (DBA Diplomat Specialty Pharmacy) of Flint, MI was issued an FMD-145 Letter on February 11, 2019 to close an inspection that took place from October 31, 2017 to November 17, 2017. FDA apparently intended to post an SBoP Referral Letter on 3/7/2019, but inadvertently posted a duplicate copy of the FMD-145. I’m sure they’ll correct it when they perceive their error. I believe that an SBoP Referral Letter has probably been generated.
CIRoA was updated on both 3/7/2019 and 3/8/2019 and all of the edits were either “catch-ups” to actions that had already been posted on FOIA or nearly simultaneous with the new actions from FOIA above. Here are the entries:
3/7/2019 CIRoA Edits
- Barclay Luke & Pillai Specialty Pharmacy PLLC (dba Meta Pharmacy Services), Las Vegas, NV – 483 Issued 12/14/2018 (PDF – 1.5MB)
- Bella Pharmaceuticals, Inc. – Warning Letter (02/11/2019)
- Denver Solutions, LLC (dba Leiter’s Health), Englewood, CO – FMD-145 Letter Issued 10/18/2018 (PDF – 54KB)
- Diplomat Pharmacy, Inc. (dba Diplomat Specialty Pharmacy), Flint, MI – FMD-145 Letter Issued 02/11/2019 (PDF – 70KB)
- Exela Pharma Sciences, LLC, Lenoir, NC – FMD-145 Letter Issued 11/29/2018
- Geneva Woods Pharmacy, Anchorage, AK – 483 Issued 12/07/2018 (PDF – 1MB)
- Good Health Inc., (dba Premier Pharmacy Services), Baldwin Park, CA – 483 Issued 11/29/2018
- Hiers Enterprises, LLC, (dba Northwest Compounding Pharmacy), Roseburg, OR -483 Issued 11/14/2018
- Med Shop Total Care, Inc., Longview, TX – 483 Issued 11/01/2018
- Michigan Medicine, Ann Arbor, MI – 483 Issued 12/14/2018 [Unfortunately, CIRoA made a separate (duplicate) header for Michigan Medicine in addition to the heading called “University of Michigan” which already existed.]
- United Pharmacy, LLC, West Palm Beach, FL – Warning Letter (02/11/2019)
3/8/2019 CIRoA Edits
- Brookfield Medical/Surgical Supply, Inc., Brookfield, CT – 483 Issued 12/21/2018
- Diplomat Pharmacy, Inc. (dba Diplomat Specialty Pharmacy), Flint, MI – State Referral Letter Issued 02/11/2019 [*Note – same mislabeled document as mentioned above in FOIA section – not really SBoP Letter, but duplicate of the FMD-145]
- Diplomat Pharmacy, Inc. (dba Diplomat Specialty Pharmacy), Flint, MI – FMD-145 Letter Issued 02/11/2019
- Duren’s Health Mart Pharmacy, Waynesboro, TN – 483 Issued 11/14/2018
- Flourish Integrative Pharmacy, LLC, Oklahoma City, OK – 483 Issued 12/19/2018
- Leiter’s Compounding, 17 Great Oaks Blvd., San Jose, CA – 483 Issued 12/19/2018
- Medcraft LLC, Mounds, OK – FMD-145 Letter Issued 01/30/2019
- The Wellness Center Pharmacy, Inc., (dba Designer Drugs), Chattanooga, TN – Referral Letter to the Tennessee Board of Pharmacy and an FMD-145 Letter both issued on 02/06/2019
- Thrifty White Drug #762, Minneapolis, MN – 483 Issued 09/21/2018
- Tiberius, Inc., dba Custom Scripts Pharmacy, Wesley Chapel, FL – FMD-145 Letter Issued 05/08/2018
- Vitalab Pharmacy, Incorporated (dba Vasco Pharmacy), Phoenix, AZ – Warning Letter (01/10/2019)
There were nine edits to the ROFs webpage, the most notable of which were the reappearance of Exela Pharma Sciences and Pharmaceutic Labs. There were seven additional changes since my last newsletter:
- Brookfield Medical/Surgical Supply, Inc., Brookfield, CT had its “Date of most Recent Registration” field updated from 12/19/2017 to 2/14/2019;
- Complete Pharmacy and Medical Solutions, LLC, Miami Lakes, FL had its “Date of Most Recent Registration” field updated from 12/28/2017 to 2/13/2019;
- Medcraft LLC, Mounds, OK had its “Other Action, if Any, Based on Last Inspection Field” updated from “Open” to “FMD-145 Issued 1/30/2019”;
- Maitland Labs of Central Florida, Orlando, FL had its Date of INITIAL Registration updated from 3/23/2018 to 2/14/2019. Since that would seem impossible, I suspect FDA intended to update “Date of Most Recent Registration,” but inadvertently updated the “Initial” field instead;
- Molecular PharmaGroup, New Providence, NJ had its “Date of Most Recent Registration” field updated from 5/8/2018 to 2/16/2019;
- RAM Pharma, Inc. Idaho Falls, ID had its “Other Action, if Any, Based on Last Inspection Field” updated from “Warning Letter – 11/1/2017” to “Warning Letter – 10/27/2017”. This appears to have been an error correction.
- RC Outsourcing, LLC, Lowellville, OH had its “Date of Most Recent Registration” field updated from 11/27/2018 to 2/28/2019
There were no compounding-related WLs since my most recent newsletter.
Most of my “other news” today will be of a personal note, but I have to tell you about the latest from Bernie Sanders if you have not already seen it. Bernie has taken on Catalyst Pharmaceuticals regarding their $375,000-per-year agent, Firdapse. Bernie is pressuring FDA to allow compounding pharmacists ample latitude relative to the regulatory interpretation of “essentially a copy.” Senator Bernie’s attitude is the antithesis of the Endo vasopressin law suit. I urge you to click on the Reuters coverage of Bernie’s activities and Catalyst Pharmaceutical’s defense of the annual cost of Firdapse.
On my personal notes:
- Cantrell Drug Company
- The reason I was able to attend last year’s 503B Listening Session at FDA’s White Oak Headquarters was that my friends at Cantrell Drug Company in Little Rock, AR were attempting to resume operations after their Consent Decree and were not able to send anyone from their leadership. I asked for the use of one of their two invitation slots, and, on the stipulation that I would keep my mouth shut and say nothing that could set them back further, they agreed.
- I benefited by quantum leaps for having attended that session because I was able to observe the regulators and the regulated “in their natural habitat,” and form many strong impressions. I will always be grateful to Dell McCarley for being given that opportunity.
- Cantrell is the first and only compounding organization to get FDA’s approval to resume operations after a Consent Decree, but when they resumed production by offering just one single product that was in shortage, the sales were not enough to turn the corner on their situation.They have retained a brokerage firm to handle their sale and they shared their brochure with me. I asked if they would like me to put it in my newsletter to broaden awareness and they agreed, so here is a hyperlink: Cantrell Investment Summary
- CBI Compounding Pharmacy Compliance
- On June 19 and 20, I plan to be attending the CBI Compounding Pharmacy Compliance program in Silver Spring, MD. I am slated to be speaking there on June 20 and my topic is entitled, “A Review of 483s and Warning Letters — Effective Response Strategies.” The Early Registration Fee is $1,099 until April 12, then it goes up to the standard rate of $1,399. If you decide to attend at the last minute, the onsite rate is $1,499.
- Speakers there will include Mike Koch (CAPS), Lisa Ashworth (Children’s Healthcare System of Texas and Member of USP Compounding Committee), Karla Palmer (Hyman, Phelps & McNamara, P.C. *-her analysis of Endo’s lawsuit against FDA was hyperlinked in my last newsletter), Seth DePasquale (Podcast Guru-pharmacyinspections.com), Eric Tosh (IACP Board Chair), Ed Zatta (RXQ), Pat Stephens (Medi-Fare), Matt Martin (PCCA) and many others.
- I have included a voucher you can use to obtain a $500 discount from the standard rate if you register by April 12. I believe this should drop your registration price down to $899 if you enter the discount code of FXJ884 at the appropriate prompt.
- I hope you decide to come! Some senior FDA person or persons may be speaking as well, so if you’re trying to stay under the radar, pack your “funny-nose-mustache-and-glasses” disguise. If you decide to attend based on this newsletter, I would appreciate a quick e-mail letting me know – something like “See you at CBI.”
- Time for me to “Commercialize my Enterprise”
- This “newsletter” started as something I needed to do purely for myself because the FDA actions against pharmacies were being published faster than I could keep up. The CIRoA and ROFs webpages are arranged alphabetically and I couldn’t tell the new actions from the old ones, so I turned it into an evolving Microsoft Access database. Since then, I can simply run a query of the “before” table versus “after” table to see what actions were “new.”
- I shared the new FDA actions with a couple of my close thought-partners, but word of mouth quickly grew the recipient list to more names than I could see on my screen, so I moved it over to MailChimp. MailChimp is a delightful tool and is utterly free until you hit 2,000 recipients or 12,000 e-mails/month. I work closely with many organizations that are rivals to one another and MailChimp has the huge advantage over my initial method that nobody can see who else is receiving it or what their e-mail addresses are.
- I was on the phone recently with a trusted partner/mentor who has been urging me for over a year to (1) improve the look and feel of this newsletter and (2) charge for it. I will NEVER charge for the core data elements of THIS newsletter, because I want the pharmacy owners and managers to know what the FDA is posting. I will continue to distribute the FREE newsletter to let you know:
- What companies got a Warning Letter, Untitled Letter, Compounding Risk Alert, relegated to Regulatory Meeting Status, performed a recall, etc.
- What companies got a 483, with boilerplate details including:
- How many FDA staff showed up
- The category of FDA staff listed on the 483. (Field Investigator, Consumer Safety Officer, Microbiologist, FDA Center Employee, etc.)
- How many days they were on site whenever I can discern it (keep in mind the final day is always the “closeout” when they present the entity with its finalized 483)
- How the FDA staff typed (categorized) the entity
- How many Observations were recorded
- a hyperlink to each 483 on FDA.gov so you can read the details yourself.
- What will be moving to a PAID format:
- I have often delved deeply into the snippet of 21 CFR 211 to which each 483 Observation refers and I often add my editorial opinions regarding the meaning, seriousness, impact and/or difficulty to remedy. I will probably continue to include highlights of that in the FREE newsletter, but most of that will soon move over to a PAID newsletter that I will be evolving as soon as I can.
- From the beginning, I have included a summary of all recent updates and edits to the webpage entitled “Registered Outsourcing Facilities,” but eventually these summaries will also move over to a PAID newsletter aimed at the Outsourcing Industry.
- I have hopes for other new newsletters aimed at particular segments in compounding, including for Legal Firms and Government Regulators.
- I intend to make the PAID newsletters very affordable, but if you really want or need the paid version and simply can’t afford it, write or call and I’ll probably put you on the list at no charge or we’ll negotiate a lower amount.
- Promotion or Advertising or Products/Services
- My Rolodex has been expanding rapidly over the past few months with key suppliers, providers, and vendors to the pharmaceutical manufacturing sector. Some of them have inquired about advertising on my FREE newsletter.
- To date, I have not accepted a dollar from any person or any company for any mention here, but I’ve thought it through, and I believe I may do so in the near future. If I decide to do so, it will be transparent. If I get compensated to mention or if I have any vested interest in a product, I will state explicitly that in the newsletter.
- A proviso to any potential advertisers or anyone who might want to send out a promotional message via this FREE newsletter – I intend to put out the unvarnished truth about your product from my perspective. If I think you’re exceptionally good at something, I’ll be happy to say so, but if your competitor / rival is better at something I will probably say that also. We will negotiate that as we review the claims you want to make.
- For the last few years, I’ve only taken on clients and projects that intrigue me and hold the promise that I’m going to learn something or gain some meaningful insight. Some clients have been bewildered by the fact that I don’t try to leverage an exciting and productive “first visit” into a bigger ongoing project or even decline offers for ongoing work. I simply don’t have time to settle down into the weeds of project management because it would cut sharply into my learning time.
- I’m determined to shift the long-term engagement/project management aspect of my activities to something very much more disciplined and reiterative. I’ve been experimenting with leveraging Subject Matter Experts other than myself to meet client needs and it’s working very well. You get the SME and you get my ongoing oversight. Matching my expert friends with clients in need can become a Win for me, a Win for my SME friends, and a Win for the client. That’s direction I want to go.
- Lots of other topics to cover later, but I want to get this out before the business day is over. As always, call or write if you want to discuss or debate any part of today’s newsletter.