Big Trouble in Little Pharma

In a previous post on Science-Based Medicine, I described the Florida Department of Health‘s sanction of Mark Geier for the unlicensed practice of pharmacy, David Geier’s establishment of DAP Pharmaceuticals LLC, and the 2019 inspection of DAP by the FDA—events that occurred after Mark Geier’s license to practice medicine was suspended by the Maryland Board of Physicians, and after David Geier was charged with the unlicensed practice of medicine. At the time I wrote my post, many questions were left unanswered, since all I had to go on was the FDA’s 483 report, which cited only general categories of concern followed by a brief description of the investigators’ findings.

I have since obtained the long-form Establishment Inspection Report (EIR) from FDA’s first and only visit to DAP between its formation in 2011 and its dissolution in 2021. The EIR provides a complete account of the inspection, inspectors’ interactions with management, and the real-time responses of its Manager, Patrick E. Riley of West Palm Beach, Florida, and its President, David A. Geier of Jupiter, Florida. DAP’s written response, prepared with the assistance of a compliance consultant, describes the actions taken by Mr. Riley and Mr. Geier to cure the deficiencies noted in the 483 report. The significance of these documents is enhanced by Mr. Geier’s recent appointment by HHS Secretary Robert F. Kennedy, Jr. to lead a study of possible associations between vaccines and autism.

Filling In the Blanks

The EIR describes an unannounced “surveillance inspection of a non-sterile, prescription active pharmaceutical ingredient (API) repacker.” According to statute, “repacking” is “taking a finished drug product or unfinished drug from the container in which it was placed in commercial distribution and placing it into a different container without manipulating, changing, or affecting the composition or formulation of the drug.” According to the EIR, the only API handled by DAP Pharmaceuticals was leuprolide acetate; as a repacker, DAP presumably measured out powdered leuprolide acetate into smaller containers for distribution to customers.

Since we are told that DAP handled only leuprolide acetate, and since further references to the API are redacted, I have assumed that redacted entries referring to the API refer to leuprolide acetate. Given that leuprolide is an injected drug, I have assumed that redacted entries referring to method of administration refer to injection. And given that manufacturers of leuprolide acetate salts recommend that it be stored at -10 to -25°C, I have assumed that redacted references to proper storage temperature refer to that range.

A Knock and a Phone Call

The report begins with the arrival of FDA investigators Jennifer Huntington and Vivin George at the DAP’s Lake Park, Florida facility. Although the office was closed, a sign on the door identified the owner and manager as Patrick E. Riley. After the investigators called the contact number provided, Mr. Riley arrived in short order and ushered them into DAP’s offices. DAP did not keep standard business hours.

Mr. Riley told the investigators that DAP was established in 2013 and began operations in 2014. He identified the owners of DAP as David Geier, Mark Geier, and himself, and stated that each were one-third owner of the firm. Mr. Riley was present throughout the inspection, whereas David Geier only appeared via teleconference, and Mark Geier not at all.

A Singular Product & Customer

Mr. Riley claimed that DAP only served a wholesale market and did not distribute leuprolide acetate out of the state of Florida; they were therefore exempt from regulations pertaining to interstate commerce. Throughout the report, investigators refer to “customer” in the singular, implying that the firm had only one customer who was a resident of Florida. (The customer was not identified.) Records provided to the investigators indicated that the most recent batch of leuprolide had been produced and distributed in September 2016, three years prior to the inspection.

The report noted that “the intended use for this API was to produce a sterile [redacted].” The ±40-character redaction is long enough to encompass the phrase “solution for injection by syringe,” the customary means of administering prepared leuprolide acetate. Presumably, DAP’s singular customer was a compounding pharmacist, because only a compounding pharmacist would be trained and legally authorized to convert leuprolide API, a powder, into a sterile solution for injection.

The Silent Partner

According to the report, “Mr. Riley stated that he and Mr. David Geier held equal responsibilities in the day-to-day operations of the firm,” and that “both could receive and release API and repackage and release [leuprolide acetate] for distribution.” Although Mark Geier was identified as one-third owner, Mr. Riley stated that he was not actively involved in the day-to-day activities of the firm.”

Although Mr. Riley informed the investigators that DAP was established in 2013, the firm was actually registered with the Florida Division of Corporations (FDOC) in 2011, with Patrick Riley designated as Registered Agent and David Geier as Owner/Manager. The name of the third owner, Mark Geier, appears nowhere on the registration or any of DAP’s subsequent FDOC filings.

Certificate of Slack Manufacturing Practice

Mr. Riley produced certificates of completion in cGMP training for both himself and David Geier but admitted that neither had received any additional training since December 2012. (Online cGMP courses can be had for as little as $200, and take less than a day to complete.) DAP maintained no documentation of training on the firm’s procedures. Although they had prepared a few Standard Operating Procedures, Mr. Riley confirmed that both he and David Geier were out of compliance with their own Quality Control Unit Responsibilities due to their failure to participate in further cGMP and SOP training. They also failed to document changes in product labeling.

DAP’s records comported with Mr. Riley’s assertion that the firm had not distributed repackaged leuprolide since 2016. Mr. Riley stated that he was not sure whether DAP would continue to engage in that business since there was unspecified “difficulty with the finished product.” There is no further explanation of the nature of those difficulties, or whether “difficult” production batches were destroyed or distributed to their singular Florida customer.

Failure & Ignorance

In their investigation of DAP’s quality control systems, investigators determined that Mr. Riley and Mr. Geier had:

When asked whether he performed Annual Product Reviews (APRs), Mr. Riley stated that he did not even know what they were. And neither, apparently, did David Geier, for there were no APRs to be found.

Inside the Labóratóry

The DAP facility consisted of a 480 square feet, two room suite with an office space and a separate, unclassified production room containing an ISO 5 BSC (biosafety cabinet) vertical laminar flow hood, a refrigerator/freezer, a scale, and a HEPA filter.

The freezer contained a bottle of leuprolide acetate dated February 2019; the investigator noted that the temperature of the freezer was higher than that required for safe storage of the API. Although the identity of the supplier of the leuprolide acetate was redacted from the report, a number of firms sell the same product. Millipore Sigma recommends that leuprolide acetate be stored at -10 to -25°C.

Calibration of the scale was not properly documented; although Mr. Riley stated that a third party performed the calibration, the only record consisted of statements from the vendor. The last internally documented calibration occurred in 2014, the year Mr. Riley stated that DAP went into operations, and five years before the inspection.

BSC hood certifications were performed annually by a third party; however, National Sanitation Foundation (NSF)/American National Standards Institute (ANSI) standards call for certifying BSC hoods for pharmacy usage every six months. Additionally, the hood was located in an unclassified, nonsterile room, and was unplugged between uses, contrary to ISO 5 standards.

Not Sterile? Not a Problem!

When DAP’s lack of sterile working conditions was called to his attention, Mr. Riley responded that an ISO 5 environment was not required for repacking the firm’s non-sterile API. The investigator pointed out that while this may be the case, DAP was preparing leuprolide for a specific use. Although that use was redacted, it is reasonable to speculate that the missing word was “injection.”

The inspector then asked Mr. Riley whether DAP “tested for microbial contamination or bacterial endotoxins after repacking and prior to distribution.” Mr. Riley responded no. Both Mr. Riley (in person) and David Geier (by teleconference) stated that “the customer should [redacted] the drug substance prior to [redacted].” Whatever actions purchasers were advised to take to ameliorate the potential for microbial contamination is left to the imagination. The investigator emphasized the importance of controlling microorganisms and bacterial endotoxins throughout the repackaging process especially since bacterial endotoxins could not be removed by the means recommended by Mr. Riley and Mr. Geier. Mr. Geier then set forth his rationale for his lack of concern for maintaining sterile conditions:

Mr. Geier reiterated that the [leuprolide acetate] they repackage is not labeled as a sterile product and believed they were not responsible for testing for microbial contamination nor bacterial endotoxins.

Maybe Clean, Maybe Not

Mr. Riley’s and Mr. Geier’s cleaning procedures entailed spraying with a cleaning agent (the name of which was redacted), and wiping the space down with a mop prior to repacking. The BSC hood would be turned on, then repacking items were placed into it. Amber jars, caps and spatulas would be rinsed and left to dry.

In spite of several requests by the investigators, Mr. Riley was unable to provide internal studies that he claimed demonstrated the effectiveness of the firm’s cleaning agents. When reminded of this request, David Geier stated that:

he believed the firm was exempt from controlling for microorganisms as the [leuprolide acetate] they repackaged was not labeled as sterile or for sterile use.

When the investigator reminded Patrick Riley and David Geier that they were “responsible for ensuring the control of microorganisms whether or not the drug was sterile,” and reminded them of “the importance of controlling microorganisms and bacterial endotoxins throughout the repacking process especially since bacterial endotoxins are not removed by [their cleaning agent] and the intended use for this drug substance was for [presumably injection],” neither had anything to say.

Trust, but Don’t Bother to Verify

Mr. Riley confirmed to the investigators that neither he nor David Geier performed in-house testing upon receipt of API, and did not send samples to a laboratory for testing; rather, they relied solely on the supplier’s COA. The leuprolide, as delivered, was non-sterile, although the COA indicated that each lot “was tested for bacterial endotoxins.” The inspector noted that DAP had not defined the drug substance specifications; that is, DAP had established no procedures to ensure that the API they received was actually leuprolide, and that it was safe for human consumption.

When asked whether the amber jars and lids used for storage of repackaged leuprolide were sterile, Mr. Riley stated that they were not. The firm had no procedures governing the receipt, specification, examination and release of these packaging materials, and performed no sampling and examination of the jars and lids prior to use. Masks, sleeves, caps and gloves used during the repacking process were also not sterile.

Too Warm a Room

When asked by the inspector how they stored the leuprolide after thawing, Mr. Riley stated that it was maintained at room temperature, and that the repacking process took place at room temperature. Once thawed, leuprolide must be kept beneath 25°C/77°F to guarantee stability; however, the firm maintained no logs indicating the temperature at which either thawed or repackaged leuprolide was stored. In fact, DAP did not maintain master batch and packaging records.

As they did with thawed leuprolide, DAP maintained repackaged leuprolide at room temperature, and did not create batch and packaging records for individual lots of repackaged leuprolide. No record was kept of the time either frozen API or repacked leuprolide was kept out of proper storage conditions. DAP relied solely on the manufacturer’s retest date to determine an expiration date for their repacked leuprolide; however, they performed no independent stability testing to justify an expiration date for leuprolide stored at a higher temperature than that recommended by the manufacturer.

Lax Labeling

DAP had also established no procedures for the printing, review and release of labeling, or for documenting changes in labeling. When asked for a representative label for each batch of repackaged leuprolide, Mr. Riley first printed them out, then admitted that the firm maintained no relevant logs and kept no representative hard-copy labels for each batch. Neither had DAP established any procedure for assigning lot numbers.

The Close-Out Meeting

On September 11, 2019, after the inspection was complete, the inspectors convened a close-out meeting with DAP’s management; Patrick Riley attended in person and David Geier by videoconference. The inspectors presented the pair with FDA’s 483 report listing eight objectionable conditions and gave Mr. Riley and Mr. Geier an opportunity to respond.

1. Failure of your quality unit to ensure that there is stability data to support retest or expiry dates and storage conditions of the API.
2. Failure to test the identity of each batch of incoming production material or appropriately qualify suppliers to rely upon their Certificate of Analysis.
3. Failure to prepare and use production and control records for each API batch.
4. Failure to establish written procedures describing the receipt, specifications, examination, and release of packaging and labeling materials.
5. Failure to provide the manufacturer’s Certificate of Analysis with shipments of repackaged API to your customer.
6. Failure to have a quality unit that is independent of production and fulfills quality assurance (QA) and quality control (QC) duties.
7. Failure to establish a procedure for the training of employees and to ensure training is regularly conducted by qualified individuals and covers, at a minimum, the particular operations that each employee performs and cGMP as they relate to the employee’s functions.
8. Failure to ensure that your cleaning and sanitization methods for equipment used in the repackaging of API are effective.

No Comment

With respect to inspectors’ concerns about DAP’s product labeling procedures, David Geier suggested changing their label to instruct the user to store the repackaged leuprolide at the proper temperature. The inspector responded that freeze/thaw studies would still need to be conducted in order to demonstrate that the thawing process had no effect on its quality or shelf-life. Although Mr. Geier insisted that DAP already had a quality agreement with their supplier, he could not provide any documentation.

When the inspectors expressed their concern about DAP’s lack of production and control records, written packaging, labeling and employee training procedures; their failure to provide Certificates of Analysis with their finished product; and their lack of an independent quality control unit independent of production, neither Patrick Riley nor David Geier asked any questions or offered any comment.

What, Me Worry About Endotoxins?

It was only when the inspectors came to “Observation 8,” noting that DAP had failed to ensure the effectiveness of their cleaning and sanitization methods for equipment used in the repackaging of API, that David Geier rose to justify his and Mr. Riley’s relaxed housekeeping, stating:

he felt the firm was exempt from having to ensure microbes are removed from the environment since the firm repackages a non-sterile drug.

The inspector responded that “although the API was non-sterile, the firm was responsible for ensuring microbial contamination is minimized during production especially since [leuprolide acetate] is intended for use as a sterile drug product.” Neither Mr. Riley nor Mr. Geier had anything to say; Mr. Riley simply stated that they would respond in writing to FDA’s Office of Pharmaceutical Quality Operations within fifteen days.

At the end of the close-out meeting, the investigators notified Mr. Riley that the EIR would be reviewed by other FDA staff in order to determine whether official action should be taken; they reminded him of “his responsibility to assure full compliance to all applicable laws and regulations”; and they warned him that “failure to implement appropriate corrections could result in regulatory actions such as an untitled letter, warning letter, regulatory meeting, seizure, or injunction.”

Too Little Too Late

Immediately after the inspection, Mr. Geier and Mr. Riley engaged FDA Compliance Group, LLC to assist them in preparing their response. In a September 25, 2019, letter to FDA, they reasserted that they repacked their last batch of leuprolide in 2016, three years prior to the inspection:

No drug products have been marketed, manufactured, repackaged, sold or distributed by DAP Pharmaceuticals, LLC since September of 2016 … There is no planned production or existing orders for the repacked [leuprolide] or any other drug products. There is no active website, sales or marketing of a drug product on going at this time. Any of our products that were sold in September 2016 or before September 2016 have reached their expiration date and would not be used by any of our customers since they are expired. Since we have not marketed, manufactured, repackaged, sold or distributed any product since September 2016, we will fully implement and train to all proposed FD-483 corrections should we decide to market, manufacture, sell or distribute any of our products in the future.

Mr. Geier and Mr. Riley assured FDA that since the inspection, they had developed or modified Standard Operating Procedures relating to each category of noncompliance:

• product stability, processing time and freezer temperatures;
• supplier qualification;
• master packaging and labeling records;
• receipt and inspection of packaging materials;
• production of certificates of analysis for repacked leuprolide;
• independence of production and QA functions;
• employee training;
• and last but not least, cleaning and sanitization of production equipment to prevent microbial contamination.

In every instance, Mr. Geier and Mr. Riley stated that the procedures described “will be fully implemented and training completed, should we decide to market, manufacture or distribute any product in the future.”

They offered no explanation as to why these Standard Operating Procedures were not in place prior to the commencement of DAP’s operations.

DAP Pharmaceuticals LLC was dissolved in March 2021.

A Sordid Enterprise

It is profoundly disturbing (not to mention ironic) to discover that the son of and co-author with a doctor who routinely offered sworn, ostensibly “expert” testimony that the DPT vaccine contained unacceptable levels of endotoxins that resulted in a client’s irreversible neurological damage, would argue that he need not control for microorganisms at his leuprolide repacking facility because the API was labeled non-sterile, even though the finished product was presumably destined for injection into autistic children.

One of the earliest articles co-authored by David Geier with Mark Geier, The True Story of Pertussis Vaccination: A Sordid Legacy? (2002) proclaimed:

Endotoxin is a highly toxic substance. Doctors and scientists take great care to ensure its absence from most medicines, intravenous tubing, syringes, and other medical instruments before using them.

In at least a half dozen papers published between 2002 and 2004, both Mark and David Geier alleged that endotoxins in pertussis, influenza and MMR vaccines had given rise to countless instances of disability and death. In a review article written after they were retained by VICP petitioners’ attorneys to develop scientific evidence implicating thimerosal as a cause of autism, Mark and David Geier speculated that “increased endotoxins levels… may also increase Hg intoxication in the brain.”

However, it would seem from the DAP Pharmaceuticals EIR that endotoxins were only a concern for Messrs. Geier, Geier and Riley when they might potentially be found in someone else’s product.

Missing Information

Given that their task was to inspect DAP’s physical plant and production processes rather than to ascertain its principals’ backgrounds and credentials, the investigators were probably unaware that in 2012, Dr. Mark Geier’s license to practice medicine in that state was revoked following the Maryland Board of Physicians’ finding that he had endangered autistic children in his care through the indiscriminate administration of leuprolide, often in dosages far exceeding those approved by the FDA for the treatment of central precocious puberty. It is also likely that the FDA investigators were unaware that in 2013, the same year that Mr. Riley claimed that DAP was established, co-owner Mark Geier was charged with the unlicensed practice of pharmacy by the Florida Department of Health (DOH).

As noted in my previous article about DAP, Florida Board of Pharmacy records indicate that neither Patrick Riley nor David Geier hold a license to practice pharmacy in that state; additionally, Florida DOH charges against Mark Geier note that Hal Goldman, the Tamarac, Florida pharmacist who allowed Dr. Geier to compound leuprolide at his establishment and was later disciplined for doing so, stated that he himself did not know how to compound.

The Supporting Cast

Mark Geier’s alleged non-involvement in the operations of the firm strains credulity, given his professional investment in the “Lupron protocol,” his purported accumulation of hundreds of autistic patients prior to the suspension of his license to practice medicine in Maryland in 2011, and his determination to continue promoting the “Lupron protocol” as evidenced by his decision to illegally compound the drug for distribution to “J.Y.,” “G.D.,” and “D.C.”.

Following the revocation of his license in 2012, many of his patients were ostensibly transferred to the care of his ASD Centers, LLC colleagues John L. Young of Bethesda, Maryland and Palm Beach Gardens, Florida, who continued to prescribe leuprolide injections to autistic patients entirely at Mark Geier’s direction, and was ultimately disciplined by the state of Maryland for doing so. Other “Lupron protocol” subjects were patients of other associates of the Geiers, four of whom testified in support of Mark Geier during his revocation hearing. These included:

• Pediatrician Mary Norfleet Megson of Richmond, Virginia (who at Autism One 2005 reportedly parroted as fact the Geiers’ baseless hypothesis that lowering autistic children’s testosterone with leuprolide enables “sheaths” of mercury to be “pulled out” through chelation);
• Psychiatrist Georgia Davis of Springfield, Illinois (who, like Dr. Young, consulted extensively with Mark Geier by teleconference during patient examinations, interpretation of tests, and dosage determinations, and whose initials corresponded to those of a recipient of Dr. Geier’s illegally compounded leuprolide);
• Radiologist David Clayman of Tamarac, Florida (who was the designated registered agent for ASD Centers, LLC in Florida and another likely recipient of Dr. Geier’s illegally compounded leuprolide); and
• Pediatrician Jerry Kartzinel of Jackson, Tennessee and Clermont, Florida (whose Orlando-based Kartzinel Wellness Center is listed by Healthgrades as a pharmacy, and whose “particularly unpersuasive” testimony in the Maryland Board of Physicians proceedings against Mark Geier included opinions that “a physical examination of patients is highly overrated,” and that a physician need only “bide by his eye” and “get a gestalt” without the need to document those impressions in a patients’ medical record).

Although each of these doctors claimed expertise on the “efficacy and safety of Lupron for treatment of autistic children,” none possessed any expertise in the field of endocrinology.

Expertise & Disingenuity

There is little reason for physicians to prescribe or pharmacies to distribute leuprolide acetate manufactured in a manner unapproved by the FDA when FDA-approved preparations are readily available for intramuscular or subcutaneous injection by people who truly have a need for it. There is little reason for a pediatrician, psychiatrist, radiologist, or any other non-endocrinologist to begin treating any child with leuprolide without consulting an endocrinologist. There has never been any reason to administer leuprolide to autistic children not experiencing precocious puberty.

The only people to have recommended it for the treatment of autism are Mark Geier, David Geier, and their similarly unqualified colleagues. Although leuprolide may have helped to lessen aggression in some autistic children, I am aware of no evidence that any board-certified endocrinologist has ever condoned the use of leuprolide as a short-acting psychopharmaceutical; indeed, a 2009 consensus statement by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology on the use of gonadotropin-releasing hormone analogs [GnRHa] in children notes that although Mark and David Geier had posited “that GnRHa may benefit behavioral symptoms in children with autism, the consensus is that there is no current evidence for GnRHa therapy for this indication.” A 2019 follow-up review offered greater detail:

GnRHa treatment cannot be recommended for autism as there is no validated evidence of efficacy. A single article reported that GnRHa usage in both prepubertal and pubertal children with autism improved behavioral symptoms (e.g., reduced aggressiveness and inappropriate sexual behavior) in the short term. Attempts to replicate these data have not been successful. There is no evidence of any longstanding improvement in patients’ inappropriate behavior or use of such therapy in children with autism. Although GnRH agonists have been used to treat patients with developmental problems (i.e., males who masturbate in public and females unable to care for themselves during menstruation), preventing pubertal progression can be seen, at best, as a temporary measure.

Attempted End Run

It is likely that adverse publicity surrounding the “Lupron protocol” and Mark Geier’s license revocation alerted insurance companies to his and his colleagues’ misdiagnoses of autistic children with “precocious puberty,” “testicular hyperfunction,” “hyperandrogenism” and other convenient, coverage-enabling medical fictions, and made it more difficult for parents to obtain the drug, and to obtain insurance reimbursement for it.

The end of Mark Geier’s career as a practicing physician, the fading of his career as an expert witness, and both Mark and David Geier’s inability to extract income from either the VICP program or petitioners’ attorneys, offered an incentive to find new sources of income. Any desire on the part of Mark Geier’s former patients’ parents or his leuprolide-slinging colleagues to continue their off-label treatment of autistic children with leuprolide offered an incentive to find new sources of injectable leuprolide.

Unanswered Questions

The identity of DAP’s singular customer was not disclosed in the Establishment Inspection Report, and at this point in history could only be revealed by Patrick Riley, David Geier, the customer himself or herself, and any physicians or parents who might have ordered injectable leuprolide directly from that individual.

The Establishment Inspection Report also does not indicate the supplier of the leuprolide API, the API’s wholesale price, or the price of the repackaged API. DAP’s irregular hours and infrequent operation notwithstanding, the acquisition of office space and investment in production equipment suggests that DAP Pharmaceuticals was a profitable operation.

The parents who were persuaded to believe that leuprolide could have a long-term positive impact on their autistic children’s development, that it could make mercury easier to remove from the body, that it could make a child “fall off the spectrum,” or “make the autism virtually disappear,” were tragically, even criminally misled, both by the late Dr. Mark Geier, and by his uncredentialed son.

The Ultimate Target

David Geier is neither a physician, nor the aspiring scientist that he appeared to be when, fresh out of college, he began co-authoring articles and attending Congressional hearings with his father, where they broadcast their identical convictions regarding the supposed dangers of vaccines. A decade later, after serving as co-investigator in a prolonged, scientifically unsupportable, profoundly unethical pharmaceutical experiment on disabled children, and after a lengthy investigation by the Maryland Board of Physicians of his father’s practice and his role in it, he was charged with practicing medicine without a license.

After the Geier family relocated to Florida, he and his father co-founded a firm for the express purpose of continuing their human subjects research at the expense of autistic children’s welfare and their parents’ bank accounts, all in support of their grandiose, factually-deficient belief that they had discovered both the cause and the cure for autism.

The leuprolide acetate salts repacked by the principals of DAP Pharmaceuticals were doubtless destined for injection into the bodies of autistic children. Any endotoxins that found their way into the product thanks to David Geier, Patrick Riley and Mark Geier’s sloppy manufacturing practices were doubtless destined for injection into the bodies of autistic children.

The man hired by HHS Secretary Robert F. Kennedy Jr. to validate his pre-existing conviction that autism is a consequence of vaccine injury, but who expressed no concern about the potential for microbial contamination in his own product, will doubtless bring the same twisted sense of ethics to bear on this new research project that he brought to his past promotion of “the Lupron protocol” and his more recent misadventure in the world of Little Pharma.