FDA Inspections of Compounding Pharmacies

FDAThe vast majority of compounding pharmacies that are currently operating within the United States are actually state licensed facilities that are classified as such under section 503A of the the United States Federal Food, Drug, and Cosmetic Act (sometimes referred to as either the FFDCA, FDCA, or FD&C). The FD&C is a group of federal laws that were first enacted by the US Congress in 1938 and granted authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of all foods, drugs and medications, medical devices, plus cosmetics that are sold within the USA. Although initially replacing the previous Pure Food and Drug Act of 1906 after more than one-hundred deaths were caused by a sulfanilamide preparation where diethylene glycol was used to dissolve the drug and make a liquid form (sometimes referred to as the “Elixir Sulfanilamide Disaster”), the FD&C has been amended numerous times, most recently the requirements being added regarding bioterrorism preparations.

What Defines a 503a Compounding Pharmacy?

A 503a pharmacy is allowed to compound drugs that are not FDA-approved, are not subject to the requirement that labeling bear adequate directions for use, and are not subject to CGMP requirements, plus are dispensed to a patient only based on the individual patient’s needs (and thus require a valid Rx or prescription). These pharmacies are primarily under the jurisdiction of their domicile State’s Board of Pharmacy (BoP), or equivalent, and held to that individual State’s rules and statutes regarding compounding. Most States have adopted in part or in full the United States Pharmacopeia (USP) published guidelines (chapters 71, 85, 795, 797, and 1116) as their rules regarding compounding. Additionally, chapter 800 has just recently been published and is now being evaluated by every BoP for possible adoption and incorporation.

Is a Compounding Pharmacy’s Adherence Sufficient?

Most pharmacists believe that adherence to State rules, statutes and all applicable USP guidelines is the extent of their regulatory responsibility. They would be wrong!

The FDA has jurisdiction anywhere drug products are prepared, packed, or held regarding “Insanitary Conditions”, which also includes all 503a pharmacies. The FDA has recently been utilizing this narrow provision to gain entry to all 503a pharmacies, often accompanied by local State BoP inspectors, to “evaluate operating conditions currently being demonstrated” by compounding pharmacies. So far they have “observed” the operations of many dozens of 503a’s every year and the numbers, frequency and pace of these inspections are rapidly escalating and increasing. The FDA inspectors will spend several days reviewing and observing the pharmacy’s compounding operations. However, it’s critical to know that the FDA inspectors will evaluate the pharmacy NOT based on either the individual State rules or the USP guidance, but instead on the far more stringent Current Good Manufacturing Practices (cGMP).

What are the Current Good Manufacturing Practices (cGMP)?

The Current Good Manufacturing Practices (cGMP) are the Food and Drug Administration’s formal rules and regulations that basically cover all of the the design, monitoring, control, and maintenance of manufacturing processes and facilities operating in the US. Note that the actual compliance by the facility is regulated by the FDA and are the exact same regulations that all drug manufacturers must follow. When an actual inspection is completed, any concerns by the inspectors and any observed deviations are listed on the FDA form 483 (Observations) and published on the FDA website. Depending on the nature of the observations, pharmacies are then required to submit a corrective action plan and undergo a follow up inspection, usually in about twelve to eighteen months after the initial inspection had taken place. If the observations initially observed are deemed as “Significant”, or the 503a does not adequately respond and produce a viable plan to address the initial observations that were documented, the FDA has several  options available that may result in a Warning Letter, a drug recall, and / or a Consent Decree for the pharmacy found deficient and in violation. Please note that a Consent Decree is also known commonly as the “Death Penalty” for the pharmacy!

How Do I Get Prepared For an FDA Inspection?

An increased tempo of FDA inspections of compounding (503a) pharmacies over the last three years has made understanding and meeting their expectations vitally important for the continued viability and operation of any compounding pharmacy. All Pharmacy managers and owners of compounding pharmacies, especially those compounding “High Risk” medications and / or shipping into other states, must be aware of the likelihood of an unannounced FDA inspection and what they can do to best “get ready” and be prepared for it.

Preparation by a 503a pharmacy for a potential FDA inspection actually must begin with a complete understanding of how an FDA inspector actually evaluates a compounding pharmacy. A guidance document published by the FDA regarding insanitary conditions in compounding facilities can be found here: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/insanitary-conditions-compounding-facilities-guidance-industry. Another extremely valuable reference is a free newsletter, produced by an HCC affiliated consultant, that documents and evaluates each and every FDA form 483 that’s issued to any 503a or 503b facility. This newsletter analyzes and discusses each observation that the FDA inspector identifies for a particular pharmacy, thus providing the reader with a deeper understanding of what the FDA expectations actually are. The free newsletter can be obtained thru this sign up link:  https://us12.list-manage.com/subscribe?u=a2e4c7b0e4f8a701c196f1671&id=5c73c07d24. After signing up, you will receive all new newsletters generated via an email.

The next step, once the pharmacy manager is familiar with the actual FDA inspection process and the FDA’s expectations, is to conduct a thorough assessment of the situation that currently exists at the pharmacy: including the business’s physical facility, operations, Policy & Procedures, training, and quality management. Remember, the FDA does not use USP guidance as a reference! The FDA uses cGMP as the gold standard. Becoming conversant in cGMP is now critically important to understanding that these practices are more than just “USP On Steroids”, as is frequently stated.

Who Can Help My Compounding Pharmacy Get Prepared for an FDA Inspection?

Healthcare Consultants (HCC) can provide you with experienced pharmacy consultants that have extensive knowledge of both the USP and the cGMP requirements, as well as the FDA inspection actual expectations. From assessing every single 483 that’s ever been issued to both 503a pharmacies and 503b outsourcing facilities, our material expert consultants are keenly aware of the FDA expectations and know the “routine”, plus will help you to be prepared. They will identify the specific areas of risk for compounding pharmacies such as yours, plus assist your managers in both the corrective action planning that’s required and its implementation, thereby lessening the risk of  possible “observations” by FDA inspectors should they “visit” your pharmacy.

Here at HCC, we recommend this “enhanced” survey for all medium to large sterile compounding pharmacies as a means of minimizing the impact of an unexpected FDA inspection. We personally have seen far too many 503a pharmacies caught by surprise when the FDA showed up in their lobby demanding immediate access to the pharmacy.

Healthcare Consultants (HCC) provides compounding (503a) pharmacies and outsourcing (503b) facilities with scalable and client defined comprehensive assessments. Our expert consultants, experienced pharmacists and cGMP experts, can evaluate the business globally or focused on specific areas such as pharmacy operations, regulatory compliance, workflow, facility suitability, inventory management, financial performance, quality assurance, and risk evaluation.

About HealthCare Consultants

From major hospitals and healthcare systems to individual community pharmacies, HCC has been the nationally renowned pharmacy consultant firm of choice for over 30+ years now. We work with businesses of every size – from the corner drug store to national corporations and organizations – with only one goal in mind: to improve your pharmacy’s business operations. We can assist with expert advice in any area of your pharmacy business or practice.

We urge you to contact us today to see how our Pharmacy Consulting services can help you improve your business now, plus be ready for the future. With a full-time staff of in-house Pharmacy Consultant specialists, HCC can answer any questions that you may have in all pharmacy settings. Contact us online or call us today at 800-642-1652 for a free consultation.


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FDA 483 Actions

FDA 483 ActionsAfter discussing the difference between an FDA Form 483 and an FDA Warning Letter, it may perhaps be worthwhile to take a closer look at some of the most recent actions that have occurred (including new FDA 483 Forms and Warning Letters). Although perhaps a couple of months have already passed, but March of 2019 makes a great example for looking at exactly how aggressively the FDA is proceeding with their efforts on these facility inspections.

How Many FDA 483’s and Warning Letters Were Issued in March of this Year?

In just the month of March, the FDA issued a total of eleven (11) 483 Forms (including FMD 145 letters) and one (1) Warning Letter. Let’s take a closer look at some of these examples and take a closer look at what the FDA observers and inspectors are actually concentrating on when they visit a facility.

Please take note that you should probably download each of the 483 forms discussed in the examples below and take a closer look when time permits (we’ve included a link for each individual 483 form for downloading the actual PDF posted on the FDA’s website). In both of the first two examples that we’ll take a look at there are nine (9) observations total, but a closer look reveals that each observation may have numerous additional points “attached” to it that also need to be addressed by the compounding facility.

  1. QuVa Pharma Inc. in Temple, Texas is known for providing 503B outsourcing services and concentrates on compounded drug formulations and medications for obstetrics, OR, anesthesia, general medicine, cardiovascular, ER, and pain management. QuVa received a 483 Form after an observational inspection on March 14th of 2019. Click here to download a full copy from the FDA that you can review, but the operation was listed with a total of nine (9) “observations” on the 483 Form. The majority were based on a lack of procedural documentation and the lack of written Policies and Procedures specific to how they perform their compounding services.
    Two that summed up the observations are definitely worth noting here:
    – “Written procedures are lacking which describe in sufficient detail the receipt, identification, approval, and rejection of components”.
    – “There are no established written methods of cleaning or methods of processing to remove pyrogenic properties”.
  2. ACRx Specialty Pharmacy located in Las Vegas, Nevada performs both sterile and non-sterile compounding of products, specializing in Women’s Health products, Ophthalmology, Thyroid Dysfunction and Weight Loss. ACRx retrieved a 483 Form on 3/20/2019. The 483 listed a total of nine (9) “observations”, and as in the QuVa example above, the majority were based on a lack of procedural documentation and the lack of written Policies and Procedures specific to how they actually perform their compounding services. Click here to download the entire 483 Form that they received.
    Just to point out quickly again what the FDA was concentrating on while observing the operation of the compounding facility, let’s use the exact verbiage from the form:
    – “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established”.
    – “Written procedures for cleaning and maintenance fail to include maintenance and cleaning schedules, description in sufficient detail of methods, equipment and materials used, description in sufficient detail of the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance, instructions for protection of clean equipment from contamination prior to use and parameters relevant to the operation”.
  3. Customceutical Compounding located in Phoenix, Arizona received a 483 Form on March 8th of 2019 (Click here to download the entire 483 Form that they received). Known primarily for the compounding of Injectable Medications, Ophthlamics (eye drops & ointments), Inhalation Solutions and Intrathecals, they had a total of five (5) documented observations noted. Again, the observations centered around the fact that the facility’s “procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not adequate”.
  4. Front Door Pharmacy (DBA Pure Pharmaceuticals) in Houston, Texas received their 483 Form on March 20th this year. (Once again, click here to download the entire 483 Form that they received as a PDF from the FDA website.) Front Door Pharmacy had a “whopping” eleven (11) documented observations that included a lack of documented policies and procedures as noted in the examples discussed above. However, the specificity of some of the observations that were noted make a great example of the level of actual “scrutiny” that the FDA is exhibiting:
    – Personnel engaged in aseptic processing were observed with exposed skin.
    – Personnel touched equipment or other surfaces located outside of the ISO 5 classified aseptic processing area with gloved hands and then engaged in aseptic processing without changing or sanitizing gloves.
    – Equipment and materials or supplies were no disinfected prior to entering the aseptic processing area.

How Do You Prepare For the Inevitable FDA Inspection?

Once again, these are just a few examples of the detailed level of observation and documentation that the FDA is exhibiting. An actual discussion of each noted observation for each 483 Form would take several hours, but we recommend that you actually take a very close look at at least one of these forms that were issued to get an accurate idea of the depth of the the detail involved. Keep in mind that the FDA will thoroughly review the facility’s response and revisit to see whether or not the operation is doing their utmost to be in compliance. Also consider that if the response is found to be lacking, then the next step is the “dreaded” Warning Letter!

The answer is to take action now and be prepared! In other words, take a look now and don’t wait for the inevitable inspection that is certain to come! The FDA strongly recommends that you undertake a comprehensive assessment of your facility’s current operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. As the FDA actually states: “A third-party consultant with relevant sterile drug production expertise should assist you in conducting this comprehensive evaluation”. The FDA also points out very clearly that “It is YOUR responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations”.

Which Third-Party Pharmacy Consulting Firm Can Help Me?

Healthcare Consultants has been known as a national leader in pharmacy consulting for over 30+ years now. Since 1989, our network of experienced pharmacy consultants and in-house specialists have provided expert guidance across all sectors of the pharmacy industry. We work with pharmacies of every size – from the corner drug store to national corporations and organizations – with only one goal in mind: to improve your pharmacy’s business operations.

One of the services that HCC specializes in is the development and customization of both 503A and 503B Policies and Procedures. We have nationally renowned in-house experts and consultants with proven “track records” and successful results in responding to both FDA 483 Forms and Warning Letters.

We urge you to contact us today to see how our Pharmacy Consulting services can fit your needs and help you improve your business now, plus be ready for the future. With a full-time staff of experienced in-house Pharmacy Consulting specialists, HCC can answer any questions that you may have in all Pharmacy settings. Contact us online now or call us today at 800-642-1652 for a free consultation.

 

 


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