Recent CBER warning letters target unapproved products, BIMO violations

The US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) recently warned two Phoenix, Arizona-based companies and a clinical investigator; the companies were admonished for making unapproved drug claims for their amniotic fluid-based PalinGen products, while the clinical investigator was warned for failing to ensure that a drug was administered according to the clinical investigation plan.

Pinnacle Transplant Technologies and Amnio Technology warning letters

FDA’s warning letters to Pinnacle and Amnio Technology come more than two years after the agency inspected the two firms’ facilities in August 2022. The warning letters concern the companies’ PalinGen products, which are derived from amniotic fluid or amniotic fluid and amniotic membrane. Dawn Holts, director of operations at Amnio Technology, told Focus that Pinnacle is a contract manufacturer for Amnio.

In its letter to Pinnacle, FDA said the firm’s PalinGen products are unapproved new drugs that fail to qualify for exceptions as human cell, tissue, or cellular or tissue-based products (HCT/Ps).

FDA said these products were distributed to third-party distributors, healthcare professionals, and medical facilities around the country. The products were intended for injection and were purported to be sterile.

The agency said that both products were promoted as “intended for use in the cure, treatment, or prevention of diseases or conditions, such as wound healing, and/or are intended to affect the structure or functions of the body.”

FDA also found a number of significant deviations upon further review of the information collected during the inspection. These deficiencies included failing to validate aseptic processes used to mancning its PalinGen products. For example, the media fill simulations did not follow its commercial manufacturing processes for the products. In addition, “critical manufacturing steps were not simulated during the validations.”

The firm was also failed to investigate any unexplained discrepancy and failed to investigate eight sterility failures between July 2020 and February 2022.

A similarly worded warning letter was sent to Amnio Technology after a two-week inspection conducted in August 2022.

FDA said the firm’s amniotic membrane and amniotic fluid product, PalinGen Flow, and the amniotic fluid-derived PalinGen InovōFlo, were distributed to third-party distributors, hospitals, and medical clinics throughout the United States, and are intended to be injected and purportedly sterile.

FDA said the company promotes these products as “intrinsic to the complex wound healing process,” and describes amniotic tissue as a “rich source of various biologically active factors involved in tissue regeneration and wound healing with reported anti-inflammatory, anti-bacterial, re-epithelialization and anti-fibrotic properties.”

The company further promotes amniotic fluid as possessing “anti-inflammatory, anti-microbial and regenerative properties that make it attractive for use in clinical applications.”

FDA said the company also failed to have an approved biologics license application (BLA) or new drug application to make these claims.

FDA also listed a number of “significant [current good manufacturing practice] CGMP deviations,” including failing to validate the manufacturing processes with respect to identity, strength, quality, and purity.

For example, the company failed to demonstrate that the manufacturing process could consistently yield the expected product characteristics. “Your firm distributed approximately [redacted] units” of products of PalinGen Flow and approximately (b)(4) units of PalinGen InovFlo since January 2020 to August 2022. These units were distributed without process validation for these products.”

Both companies were given 15 days to respond to the warning letters.

Namita Goyal cited for BIMO violations

A CBER investigator also found “objectionable conditions” related to Orange, California-based clinical investigator Namita Goyal’s handing of patients participating in study for an investigational amyotrophic lateral sclerosis (ALS) drug, according to a warning letter posted on 22 October.

In one case, a subject was enrolled in the study despite the fact they were not eligible to participate. “The subject failed to meet inclusion criterion #10 for geographic accessibility to the study site. The subject did not reside in the United States prior to and during participation in the study.”

In another case, Cedars-Sinai sent a letter to Goyal in January 2018 stating that a subject had already completed all study activities in another ALS study. Yet this document “was not located in the subject file, and you did not acknowledge the letter until brought to your attention by the FDA investigator.”

Warning letter: Pinnacle, Amnio Technology, Namita Goyal

Recent CBER warning letters target unapproved products, BIMO violations

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