FDA Inspection Trends for 503(a) Compounding Pharmacies

Compounding pharmacies should be Food and Drug Administration (“FDA”)-inspection ready and establish a plan to mitigate FDA inspection stress. As we approach the 10-year anniversary of passage of the Drug Quality and Security Act, the FDA appears to have stepped up the number, frequency, and intensity of inspections of state Board of Pharmacy-licensed 503(a) compounding pharmacies.

The FDA has authority to inspect for “insanitary conditions”[1] under the Food Drug & Cosmetic (“FD&C”) Act as well as the Drug Supply Chain Security Act (“DSCSA”). The FDA is often accompanied by the domicile State Board of Pharmacy for the first few days of its inspections, which regularly last several days to multiple weeks. Most states have adopted United States Pharmacopeia (“USP”) 795 (oral) and 797 (sterile product) as their compounding rules. Some states have also adopted USP 800 (hazardous drugs). Instead of applying USP compounding rules which most pharmacies are familiar with, the FDA applies its 2020 Guidance entitled “Insanitary Conditions at Compounding Facilities”. The Guidance has current Good Manufacturing Practices (“cGMP”) components outside of the USP requirements and includes both sterile and non-sterile compounding and the handling of hazardous products to prevent cross-contamination. Additionally, the Guidance encourages 503(a) pharmacies to develop preventative quality controls.

In our experience, it is clear that the FDA is now using the Guidance to inspect pharmacies and issue FDA Form 483 lists of inspectional observations/deviations[2] which must be addressed within 15 days together with a plan for action. Failure to adequately address the deviations can result in an FDA-issued Warning Letter and other enforcement actions such as a request to recall a compounded product. Issuance of a Form 483 may trigger a ‘reciprocal discipline’ reporting requirement to Boards of Pharmacy in certain states.

Inspections are increasingly more likely to occur where the pharmacy compounds “high risk” medications, where there has been a complaint filed, where the pharmacy’s website makes specific claims regarding compounded products, or where a Board of Pharmacy inspection has found issues. FDA inspections are unannounced and require the pharmacy to produce hundreds of documents requested by FDA inspectors on site.[3] Due to the nature of these inspections, they have the propensity to cause major disruptions in patient care and the pharmacy’s business operations. As such, ensuring a pharmacy is ready for an FDA inspection at all times is key.

The regulatory nuances of preparing for an inspection are detailed and complicated. Preparation for an inspection requires a deep understanding of what the FDA requires during an inspection based on the “Insanitary Conditions” and several other FDA Guidance documents[4] which provide the parameters through which the FDA inspects 503(a) pharmacies as well as an assessment of the pharmacy. For example, pursuant to the Active Pharmaceutical Ingredient (“API”) Guidance, the FDA is requiring that API be sourced from FDA-registered manufacturers, not wholesalers. Records must be produced in a timely manner and, during recent inspections, the FDA has extended the inspection duration citing delays in document production. During the inspection, customized reports and large volumes of records are generally requested; these documents are generally subsequently reviewed by the inspectors onsite and then undergo additional review at FDA offices.

The second-level review often prompts requests for additional documents of the pharmacy.  An effective preparation tool is an ‘inspection readiness’ file containing, for example, copies of all professional staff licenses, copies of out of state pharmacy licenses, continuing education training, Policies & Procedures, basis for anticipatory compounding and Quality Assurance documents (e.g. clean room logs or particulate test results).

How Frier Levitt Can Help

If FDA’s 2023 inspection budget reflects this year’s budget for inspecting compounders, it is not a question of ‘if’ a 503(a) pharmacy gets inspected, but when. To formulate a plan for preparation and to properly frame applicable statutes and rules and place the pharmacy in a proper negotiating position, contact Frier Levitt. Our team is well-versed in FDA inspections and can assist with 483 responses and Warning Letters.

 

[1] FD&C Act § 501(a)(2)(A). A compounded drug product is deemed adulterated if it is prepared, packed, or held under insanitary conditions.

[2] An FDA Form 483 highlights any potential regulatory violations found during a routine inspection.

[3] Records are requested pursuant to FD&C Act § 704(a)(4).

[4] FDA Guidance for Industry. Policy on Compounding Using Bulk Drug Substances Under Section 503(a) of the FD&C Act. Jan 2017; FDA Guidance for Industry. Compounded Products that are Essentially Copies of Commercially Available Drug Products Under Section 503(a) of the FD&C Act. Jan 2018.   

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