FDA warns HIV test distributors, supplement firm, and OTC drugmaker

The US Food and Drug Administration (FDA) has cited several companies for marketing human immunodeficiency virus (HIV) serological diagnostic dried blood spot (DBS) card self-collection kits without a marketing authorization. It also cited a nutritional supplement company for conducting an unauthorized clinical trial, and a drugmaker for failing to comply with current good manufacturing practices (CGMP).

Lack of marketing authorization

On 20 January, FDA published several warning letters, including four warning letters to HIV diagnostic kit-makers in the US and online. Inspectors sent almost identical warning letters to Genovate.com, Genetrace.com, ProDx Health and Germaphobix for marketing the kits without authorization from FDA.

"FDA has not authorized your firm’s HIV DBS card self-collection kit for any use, including for use in HIV serological diagnostic testing," said the agency in their warning letters.

Florida-based Germaphobix responded to FDA's concerns and argued that since it was only a distributor of the HIV dried blood spot test kits that it said are considered LDTs, it did not require a marketing authorization and did not come under the agency's regulatory oversight. FDA, however, wrote back to the company that the HIV DBS card self-collection kits are not considered LDTs and their distribution is illegal.

"As noted above, your firm’s HIV DBS card self-collection kit has not received FDA marketing authorization for any use and to date, your firm has not submitted any premarket submission to FDA seeking authorization to market this kit," the agency added.

More broadly, FDA said the companies failed to meet legal requirements to prove safety and efficacy.

"Without appropriate testing, data review, and marketing authorization, there is a lack of assurance of the safety and effectiveness of your HIV DBS card self-collection kit," said FDA. "Self-collection raises several issues of importance, including, for example, whether the user can safely and properly collect the specimen, if the sample has been properly shipped, and if there is adequate stability of the specimen given the time lapse between collection and testing and the potential impact of shipping conditions.

"We also note that there is an FDA-approved over-the-counter HIV test that can help meet the needs of individuals who wish to test themselves at home or who are unable to access other testing options," the agency added.

Lack of IND authorization

FDA also issued a warning letter to California-based Prodrome Sciences for conducting a clinical trial of ProdromeNeuro Oil (Omega-3 Plasmalogens) without an investigational new drug (IND) approval. The company argued that it was studying the safety and tolerability of the product but since it was a nutritional supplement, it did not fall under FDA's oversight.

"Additionally, during the inspection you stated that the investigational product, ProdromeNeuro Oil, is a blend of naturally occurring alkylglycerols composed of docosahexaenoic acid (DHA) [22:6], docosapentaenoic acid (DPA) [22:5], and eicosapentaenoic acid (EPA) [20:5] fatty acids," said FDA. "You further stated that these dietary alkylglycerols are found naturally in shark liver oil, which makes ProdromeNeuro™ Oil a dietary supplement that does not require an IND."

FDA, however, said that whether the product is a naturally occurring nutritional supplement does not factor into the equation. Instead, inspectors said whether a product is a drug under its regulatory oversight depends on the intent of the clinical investigation.

"Based on the study design of Protocol Pro-040-Plasm-01, the investigational product, ProdromeNeuro Oil, as used in the clinical investigation, was a drug as defined in section 201(g)(1) of the FD&C Act, because ProdromeNeuro™ Oil was studied for use in the treatment of mild to moderate dementia," said FDA. "Thus, before initiating the clinical investigation of ProdromeNeuro Oil conducted under Protocol Pro-040-Plasm-01, under 21 CFR 312.40, Prodrome Sciences was required to submit an IND to FDA and to have an IND in effect.

"FDA’s records indicate that Prodrome Sciences failed to submit an IND before conducting Protocol Pro-040-Plasm-01, in which 29 human subjects were enrolled and received investigational drug between July 2020 and March 2021," the agency added.

Prodrome told FDA that it had hired a consultant to aid it in remediating its regulatory requirements and ensure FDA compliance. The agency acknowledged the company's plans to take corrective and preventive actions but said it was inadequate because it did not provide detailed information on how it plans to address similar future violations.

"For example, your response does not include sufficient details on how Prodrome Sciences, as a sponsor, will determine whether IND regulations apply to future clinical investigations of products regulated by FDA, as required under 21 CFR part 312.2(a)," said FDA. "Additionally, your corrective and preventive action plan does not include sufficient details about developing and implementing procedures to comply with IND regulations, if Prodrome Sciences should decide in the future to initiate another clinical investigation for which an IND is required.

"As a sponsor, you are responsible to comply with IND requirements, including submitting and having in effect an IND before initiating a clinical investigation; and it is Prodrome Sciences’ responsibility, as a sponsor, to be aware of and to follow all applicable FDA regulations," the agency added. "Prodrome Sciences’ failure to submit, and to have in effect, an IND before initiating Protocol Pro-040-Plasm-01 with an investigational drug raises significant concerns about the safety and welfare of enrolled subjects, and raises concerns about the validity and integrity of the data collected during the conduct of this clinical investigation."

Lack of CGMP compliance

In another warning letter, FDA cited St. Louis-based over-the-counter (OTC) drugmaker Integrity Partners Group for CGMP violations. More specifically, inspectors said the company failed to adequately test and ensure the final drug product conformed to final specifications.

While Integrity said they would develop adequate test methods to analyze their products or use a contract testing laboratory to revise their product release standard operating procedures (SOPs) and ensure final products conformed to specifications, FDA said the response was inadequate because they still haven't developed the test protocols. Inspectors also noted that the company failed to conduct adequate tests to ensure the raw materials used in their final products met specifications.

"In your response, you state that you will develop a test method and/or use a contract testing laboratory to test incoming [redacted] for [redacted] and incoming high risk drug components, including but not limited to, [redacted] for [redacted]," said FDA. "Your response is inadequate because you do not provide adequate details that ensure identity testing for raw materials will meet all [United States Pharmacopeia (USP)] monograph requirements."

Integrity was also cited for failing to use adequate procedures to clean and maintain its manufacturing equipment, and for lacking process and system validations. The agency said its quality systems were inadequate and recommended it get help from a CGMP consultant to address its shortcomings.

"Drugs must be manufactured in conformance with CGMP," said FDA. "FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers.

"FDA regards contractors as extensions of the manufacturer," the agency added. "You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners."

Warning letters

FDA warns HIV test distributors, supplement firm, and OTC drugmaker

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