Over the last year or two, the Food and Drug Administration’s (FDA) Office of Criminal Investigations (OCI) has grown to play a crucial role in protecting the public health from fraudulent or counterfeit drugs, devices, cosmetics and other FDA regulated products. Increasingly, OCI has also played a large role in several recent high-profile settlements involving off-label marketing or deceptive promotional practices.
Several recent posts on the FDAVoice blog, written by OCI’s director, John Roth, explain the work OCI has done in the past and what the future holds.
OCI consists of numerous federal agents, who have the same type of arrest authority as other federal law enforcement agents, and give “the FDA unique fact-finding tools and provides for strong, industry-wide deterrence.” Conduct that OCI looks out for includes rogue internet pharmacies, purveyors in grey and black market unapproved medicines, and counterfeiters, both in the United States and overseas. Roth explained that OCI focuses its efforts on threats to the public health in four areas:
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investigating criminals who can’t be reached by the rest of FDA, particularly in the area of counterfeit and unapproved medical products;
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moving against public health problems when our ordinary regulatory tools aren’t the best option;
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Seeking criminal penalties against conduct in which the harm to the public is so grievous that a criminal response is appropriate; and
- Investigating lying to the FDA and other behavior that deprives the FDA of its ability to regulate.
OCI has a variety of tools l to accomplish its mission, including
- felony charges under the Federal Food, Drug, and Cosmetic Act,
- misdemeanor prosecutions of responsible corporate officers, and
- prosecutions for fraud, money laundering and obstruction of justice.
Roth’s first post described an undercover operation in which OCI agents were able to arrest Chinese individuals who were making and selling fake or counterfeit weight loss drugs.
In his second post, Roth explained the importance of compliance for FDA-regulated companies, and the impact certain factors can have that OCI considers when considering to bring criminal charges. For example, Roth noted that when lapses in compliance occur, “the criminal remedy is available to gain compliance for that small portion of the industry that fails to respond to ordinary regulatory tools.” Before selecting that remedy, OCI will look to see
- whether the entities have demonstrated a resistance to other regulatory efforts, including requests for voluntary cooperation and FDA formal warning letters or inspection reports, and
- instances in which entities fail to comply with judicial orders.
Roth said that OCI is “particularly sensitive to circumstances in which it appears that the regulated entity engages in fraud or other deceptive conduct, either in relation to the FDA or the public at large.” The OCI Director noted that “[o]ne area of particular OCI focus is the deceptive conduct by those who manufacture and market pharmaceuticals.” He then went on to describe the role OCI played in the Abbott Laboratories Depakote case, as well as the Amgen case regarding Aranesp. These two cases resulted in $1.4 billion in fines against the two firms.
In a third post in early June, Roth noted that in addition to deceptive marketing or promotional practices, some companies conduct “evinces such a complete disregard for the health and safety of the public that a criminal response is necessary.”
For example, the OCI director used two examples of cases which suggested this level of criminality. First, the Synthes case, which involved a bone cement product called Norian XR. The product was cleared by FDA for use in certain instances, but was specifically rejected for the use Synthes wanted: injection into the spine as part of a mixture.
Roth described how Synthes decided to convince doctors to perform the procedure and then publish the results, notwithstanding the risks, rather than get approval for the spinal indication. He noted how the Syntheses executives “plunged forward with a plan to conduct what amounted to an unauthorized clinical trial of the use of Norian to treat vertebral compression fractures of the spine. Equally appalling, the company marketed uses of the product in contravention of a “Black Box” warning — the most serious warning the FDA can require.”
After working on the case, OCI, alongside FDA’s Office of Regulatory Affairs and CDRH, was able to obtain a guilty plea in 2010 by Synthes, along with a maximum fine of $23 million. Additionally, four executives were convicted and sentenced to prison terms up to almost one year.
In addition, Roth reference a similarly tragic case of “reckless conduct” involving ApotheCure, a compounding pharmacy in Dallas that shipped colchicine injectable solution to a medical center in Portland, Oregon. Colchicine is used to prevent gout attacks and relieve the pain of gout attacks when they occur. In 2007, three patients, within hours of receiving the drug, died.
In addition to OCI’s recent activities, FDA has been busy citing companies for various manufacturing violations—some of which have raised concerns about potential Park Doctrine prosecutions. For example, as recently reported by RAPS, FDA sent three (3) Warning Letters to dietary supplement manufacturers Natures Health Options, Body Systems Inc, and Glucorell, Inc. “All three are Florida-based companies, manufacture dietary supplements, and utilize outside third-party contract manufacturers. And, according to FDA’s Warning Letters, all three are deficient in their responsibilities to oversee those same contractors,” RAPS writes.
Interestingly, the Warning Letters noted that while the firm “may contract out certain dietary supplement manufacturing operations, it cannot, by the same token, contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement cGMP requirements,” FDA wrote, citing United States v. Park.
“Thus, a firm that contracts with other firms to conduct certain dietary supplement manufacturing, packaging and labeling operations for it is responsible for ensuring that the product is not adulterated for failure to comply with dietary supplement cGMP requirements, regardless of who actually performs the dietary supplement cGMP operations,” FDA added.
FDA’s clear focus on the Park Doctrine and responsible corporate officer doctrines also comes at a time when the CEO of the Johnson & Johnson subsidiary of Janssen may face criminal charges in South Korea related to the company’s manufacturing problems regarding over-the-counter products such as Tylenol. As reported by FiercePharmaManufacturing, “Authorities seem to be keying in on the fact that the Janssen unit continued to sell Children’s Tylenol after discovering it might contain more than the labeled amounts of acetaminophen, a problem that can lead to liver damage. There were no adverse reactions reported, The Korea Times reports.”
The increased attention at RCO prosecutions also comes as long-time Forest Labs CEO Howard Solomon announced that he will be stepping down from that role on December 31st of this year, with plans to stay as chairman until next year’s annual meeting and as a director for some time after that. Now 86 years old, Solomon has worked at the company for almost 50 years, and he’s been CEO for almost 37 of them.
Solomon was under investigation along with the company when DOJ asserted off-label claims regarding its antidepressant Lexapro, and settled with the government for $313 million. HHS-OIG wanted to exclude Solomon and several other executives, but never went through with the decision—or gave a reason why it backed off. However, just as Solomon was stepping down, DOJ issued a subpoena to the company requesting documents relating to its small-selling lung disorder product, the Tudorza Pressair inhaler, the company said in a filing.
The subpoena, which came from the U.S. Attorney for the Southern District of New York, was noted briefly in the company’s annual 10-k filing with the Securities and Exchange Commission.
Tudorza Pressair is used to treat spasms associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. The product had sales of $23 million for the fiscal year ending March 31. There were no other details of the nature of the investigation in the filing, but this is not the first time Forest has come under scrutiny from U.S. authorities, reported Reuters.
These letters, along with others (discussed below), also reiterate FDA and the U.S. Department of Justice’s new focus on going after manufacturers with cGMP or product quality concerns—particularly in light of the tremendous scrutiny agencies are receiving in the wake of the New England Compounding outbreak. For example, FDA recently sent a warning letter to Boehringer-Ingelheim for various manufacturing deficiencies found at the company’s Rhein, Germany plant, as also reported by RAPS.
Boehringer Ingelheim said in a statement from the head of its quality division that the company was taking the warning letter issues very seriously. Dr. Gerhard Koeller said the company would “invest all our energy to remedy the situation.” He pointed out that aside from the November FDA inspection, the plant had successfully passed 22 inspections by different authorities in the past 5 years.
According to Alexander Gaffney, author of the article, the Warning Letter, “sent 6 May 2013, references a November 2012 inspection at the facility, which manufactures both active pharmaceutical ingredients and finished pharmaceuticals. FDA said its inspectors observed a number of violations of US current good manufacturing practice (CGMP) regulations for both types of products, raising concerns and causing those products to be identified as ‘adulterated.'”
Such increased scrutiny on cGMP also comes at a time when companies are increasingly becoming more risk averse and taking affirmative action to recall products on the market. For example, Sandoz recently initiated a recall of two lots of its cancer drug methotrexate sodium after it said particulate matter was observed in vials of the drug. Such recalls, coupled with cGMP violations or problems have the potential to create additional drug shortages.