FDA Warning Letter Breakdown: Inside a 503B Compounder's Quality System Problems
A May 5 letter pulls back the curtain on how an outsourcing facility’s quality system unraveled—from unqualified API suppliers to glass in injectable vials.
This breakdown is available for paid subscribers. Only paid subscribers get regular full access to our breakdowns and other analyses. If you’re not already a paid subscriber, you can upgrade here. Want to stay out of our warning letter breakdowns? Contact us to access our global network of 3,250+ consultants and 250+ former FDA employees. We run audits, mock inspections, and remediation for 17 of the top 25 life science firms.
Today’s warning letter breakdown is tailored for our 503B compounding audience—a niche group, but one we’re seeing more of as FDA oversight intensifies. That said, every drug manufacturing team will find value here: the violations highlight broader GMP breakdowns that are all too common.
On May 5, 2025, the FDA’s CDER issued a warning letter to a 503B-registered outsourcing facility based in Nebraska. The facility initially registered under §503B in 2020, renewed its registration in December 2024, and underwent a 16-day inspection from September 3 to 18, 2024. Form FDA 483 observations were issued on the final day, with an amended version following on September 26.
By the end of that same month, the company was already recalling a large lot of high-dose ascorbic acid injection due to the presence of glass particles. Despite submitting two written responses—one in October 2024, another in January 2025—the FDA deemed the corrective actions “inadequate.” The resulting warning letter reads like a play-by-play of what happens when §503B expectations aren’t met.
Below, we’ve outlined the key violations along with practical, actionable takeaways you can apply immediately.
If you’re a 503B, make sure to catch our recent conversation with Jesse Gillikan on CGMP compliance:
503B rules broken before the audit even begins
The letter opens with two lapses that nullified the exemptions the facility thought it enjoyed.
First, investigators discovered that one bulk active ingredient came from a supplier not listed in the FDA’s registration database. That single oversight means every drug containing that substance must meet full NDA/ANDA, labeling, and DSCSA pedigree rules. Second, container labels for products such as Glutathione 200 mg/mL and Ascorbic Acid 500 mg/mL lacked both the MedWatch phone/URL and basic dosage directions, violating §503B(a)(10).
Taken together, these omissions turned otherwise legitimate compounded drugs into unapproved, misbranded products the moment they crossed state lines.
Ask yourself:
Do we run a live comparison between our Approved Supplier List and FDA’s registration feed so an unregistered API source automatically blocks a purchase order?
Could any container labeling reach production without mandatory MedWatch language or dosage instructions?
Insanitary conditions: the ISO 5 work zone that only looked compliant
Inside the laminar-flow hood, inspectors observed operators reaching in beyond their elbows, despite microbial contamination action limits for personnel monitoring of the elbows exceeding acceptable levels. The FDA noted that the correct limit should be <1 CFU for critical surfaces.
Media-fill runs were not performed under the most challenging or stressful conditions. The FDA noted that protocols were in draft form with undefined "worst-case" scenarios, and updated media fills would need to include simulation of challenging conditions such as stuck syringes and interventions to remove syringes.
Smoke studies to demonstrate unidirectional airflow were inadequate due to positioning issues with the smoke source in relation to items within the ISO-5 space. The FDA specifically noted concerns about whether ISO-7 air was entering the ISO-5 space during certain operator movements
These three missteps—the liberal gowning limit, the easy-mode media fill, and the cosmetic smoke study—unsurprisingly left investigators unconvinced that sterile product was ever produced under a validated state of control.
Ask yourself:
Are our gown-plate limits harmonized with USP <1116>, and do we automatically fail any operator who exceeds them?
Does every media-fill protocol spell out specific worst-case events—line jam, maximum run time, full shift—rather than just the phrase “worst case”?
Could we stream a recent smoke study that shows airflow recovery while operators perform real manipulations, not staged poses?
CGMP cracks that widened into system-level failures
Once the inspection moved beyond the hood, investigators found what reads like a domino row of CGMP deficiencies.
Investigations (21 CFR 211.192) — Glass particulates triggered a recall, yet the investigation failed to expand to other potentially affected vial lots. The FDA noted that the firm did not conduct a thorough investigation to include evaluation of other vial lots involved in production or identify a root cause for the glass contamination.
Process validation (211.100(a)) — Only one product had a partial validation run; the rest of the portfolio was in commercial production with no evidence of reproducibility.
Personnel training (211.25(a)) — Operators who passed visual-inspection qualification still missed major defects during routine fills—pointing to a test that teaches the answers, not the skill.
Environmental monitoring (211.42(c)(10)(iv)) — The SOP treated gown plates as “environmental” samples and buried alert/action limits inside a multi-use form.
Equipment cleaning (211.67) — New sterile wipes and dedicated brushes were introduced before validating whether they remove drug residues.
Aseptic process control (211.113(b)) — Media fills, growth-promotion testing, and smoke studies were all “in draft” four months after the Form 483.
Each of these findings is cited verbatim in the warning letter, underscoring how an unvalidated change, an incomplete investigation, or a missing SOP attachment can render an entire quality system suspect.
We see this all the time in our 483/warning letter response work as well as our own audits and mock inspections at client sites: singular quality system problems are treated like errant strings hanging from a ball of yarn. As soon as an auditor or investigator sees one, they pull it to see if the whole ball unwinds.
Ask yourself:
When foreign matter appears, do we automatically extend the investigation to every lot sharing that vial, stopper, or operator for the past year?
Can we pull up a dashboard that shows PPQ status for every SKU, and block shipment until a PPQ report is approved?
Do our inspector qualification programs include routine blind-defect challenges, and are the outcomes of retraining documented?
Is “revised SOP” in our CAPA database always accompanied by the final, signed procedure, not a draft?
Have we run cleaning-validation studies on worst-case residues for every tank, line, and utensil in service?
CAPA as fiction: when “implemented” really means “planned”
Nearly a third of the warning letter dissects unfulfilled corrective-action promises.