Source: http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2016/01/index.html
Timestamp: 2017-09-23 09:14:53
Document Index: 153798951

Matched Legal Cases: ['§ 513', '§ 205', '§ 205', '§ 205', '§ 205', '§ 205', '§ 205']

FDA Law Blog: January 2016
Premarket Sterility Guidance for Devices is the Latest in a Flurry (Blizzard Pun Intended) of Device Guidance Activity for FDA
Before the multiple feet of snow that the DC area recently received, CDRH had been creating its own storm of device guidance documents. One of the most recent ones is the final guidance “Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile,” which was released on January 21, 2016. This guidance is the final version of the draft by the same name, which was issued in December 2008. FDA is holding a webinar to discuss this guidance on February 11th from 2–3:30pm ET. Webinar details can be found on FDA’s website.
This guidance applies to devices that are labeled as sterile through microbial inactivation. It distinguishes established sterilization methods and those that are novel. That is FDA has established a bifurcated universe of “established” versus “novel.” It is unlikely, though, that all 510(k)s will neatly fall into this scheme. This scheme is also different from the original scheme proposed by FDA in the draft guidance with more methods falling under the “established” category than the draft, which proposed a three-tier system of “traditional,” “non-traditional,” and “novel non-traditional.”
Established methods are those for which there is an FDA-recognized standard and are well-accepted, for example dry heat, EO, steam, and radiation. Established methods are also those for which there is no FDA-recognized standard, but there is “published information on development, validation, and routine control available” and/or FDA has previously reviewed and accepted the sterilization method as being acceptable (e.g., through clearance of a 510(k) for a device sterilized with such a method). These established methods include, for example, hydrogen peroxide, ozone, and flexible bag systems.
On the other hand, novel methods are “newly developed methods for which there exists little or no published information, no history of comprehensive FDA evaluation” and no FDA-recognized consensus standard. Novel methods include, among other things, brand new sterilization methods, changes to parameters of established methods, and combinations of established sterilants which FDA has not previously reviewed or cleared. It is worth noting that the guidance states that a method is novel if “parameters of an FDA-cleared sterilizer have been altered.” The guidance does not address how significant the alterations must be in order to be considered novel. As a result, on its face, it appears that any change to an FDA-cleared sterilizer’s parameters would result in a “novel” sterilization method.
The guidance indicates that FDA intends to inspect device manufacturing facilities that employ novel sterilization methods prior to clearing 510(k)s for such devices. The draft guidance also indicated that pre-clearance inspections would be required for novel sterilization methods. The draft guidance also stated that FDA would perform priority post-clearance inspections of device manufacturing facilities utilizing sterilization methods for which there is no FDA-recognized standard, but there is published information on its validation and FDA has previously reviewed and accepted the sterilization method as being acceptable (previously referred to as non-traditional methods, and now encompassed within the definition of “established” methods). The statement regarding post-clearance inspections has been omitted from the final guidance, and it should be noted that it is unclear what FDA meant by a “priority” inspection in this context. It is not to say, however, that FDA will not still consider performing such post-clearance inspections.
With regard to pre-clearance inspections, the guidance does not indicate how FDA will ensure that such an inspection takes place within the Federal Food, Drug, and Cosmetic Act mandated 90 day review time frame for 510(k)s. Nor does the guidance indicate how FDA will handle inspectional findings that result from such pre-clearance inspections, what effect those findings will have on a pending 510(k) or its review timing, or what the inspectional criteria will be. Historically, FDA has not considered QSR compliance as part of making a substantial equivalence determination, and its ability to use QSR compliance in making an initial classification decision is limited by statute. FDC Act § 513(f)(5).
Moreover, the guidance creates a new standard for sterilization information required in 510(k)s, and although the guidance is nonbinding, failure to comply will likely result in a finding of not substantially equivalent. For devices sterilized by established methods, the guidance indicates that the sterilization information from the current 510(k) Refuse to Accept policy (a copy of the current requirements for sterile devices is at the end of this post) and the CDRH premarket coversheet (i.e., the sterilization facility) should be submitted in a 510(k) plus the following information:
A description of the sterilization chamber (e.g., rigid or fixed);
If the sterilization method is not the subject of an FDA-recognized consensus standard, but the sterilizer or sterilization method has been cleared by FDA:
the 510(k) number,
the make and model of the sterilizer, and
whether the proposed sterilization cycle is identical to a cleared cycle or has been altered (note: if it has been altered then it would be considered a novel method under the guidance);
If the method has not been previously cleared by FDA, but there is “published information on development, validation, and routine control available” it should be stated;
The radiation dose, if the device is sterilized by radiation;
If the sterilization method is not the subject of an FDA-recognized consensus standard, “a comprehensive description of the process and the complete validation protocol;” and
A description of not only the packaging, but also how it will “maintain the device’s sterility, and a description of the package test methods, but not package test data.”
For novel methods, the above information must be provided along with the following additional information:
“A comprehensive description of the sterilization process;
The sterilization validation data. The submission should also identify any applicable published scientific literature.” Note: the requirement to provide the sterilization validation data is in direct contradiction of the current version of the 510(k) RTA, which expressly states that “the sterilization validation report is not required.” We think it would be too cute for FDA to say that asking for the data rather than the report was not a contradiction.
The guidance also provides additional information regarding the information needed to support a “non-pyrogenic” claim and the types of devices for which pyrogenicity data should be provided. These sterilization and pyrogenicity requirements have been modified in the final guidance compared to the draft guidance.
The draft guidance also set out detailed steps for how the reviewers should route sterilization information during a 510(k) reviewing, including, requesting inspections and involving the Infection Control Devices Branch (ICDB) in its review of novel sterilization methods. This detailed routing information and references to the ICDB’s involvement have all been omitted from the final guidance. It is possible that the review team will follow the draft process internally, and it was simply omitted from the public-facing final guidance.
Although the guidance is neither binding nor set out in the 510(k) RTA, we expect that FDA will begin enforcing these requirements sooner rather than later, even if not officially. As a result, manufacturers will want to ensure that they are familiar with these new sterilization requirements prior to submitting a 510(k) to FDA.
Posted at 10:37 PM in Medical Devices | Permalink | Comments (0)
By John R. Fleder & Mark I. Schwartz –
We all know that under the so-called “Park Doctrine”, corporate executives can be criminally prosecuted under the FDC Act for violations of that Act even absent any showing that the executives acted with any wrongful intent. A prosecution is possible when violations are committed by an employer even though the executive did not directly participate in the alleged unlawful conduct and did not even know the conduct was occurring. At least since United States v. Park was decided by the United States Supreme Court in 1975, there has been substantial debate about the level of responsibility at a corporation that should subject an individual to a criminal prosecution. The government’s position has been understated but basically consistent since this writer was in the government between 1973 and 1992: Any person, no matter what his/her level of responsibility, is theoretically subject to criminal prosecution under 21 U.S.C. 333(a)(1) because: (1) that person directly committed a prohibited act under 21 U.S.C. 331; (2) the person “caused” a prohibited act to have occurred or aided and abetted in such an act by his/her employer; or (3) the person was in a position of authority to prevent Section 331 violations from occurring.
On January 14, 2016, the United States Court of Appeals for the Eighth Circuit affirmed the convictions of three individuals convicted of selling misbranded synthetic drugs. Charges had been brought under the FDC Act, the Controlled Substances Act and its Analogue Act. The Court affirmed the FDC Act felony convictions of two of the defendants, ruling that the jury instructions given by the District Court were correct in terms of the “knowledge” element required for a conviction under 21 U.S.C. 333(a)(2). Slip Op. at 12-13.
Two other paragraphs of the Court’s Opinion make this ruling particularly noteworthy. The Court of Appeals affirmed the FDC Act misdemeanor convictions of Joseph Gellerman, who worked as a store clerk for the business run by one of the other two defendants. Gellerman was sentenced to three years of probation, a $1000 fine, and 90 days of home electronic monitoring.
Mr. Gellerman did not own the business or run it, although he was the son of the owner. Nor was he a high level executive. Instead, he was what the Court referred to as a “store clerk.” See Slip Op. at 13-14. The Court ruled that the government could hold Gellerman criminally liable as a store clerk under the FDC Act because he sold misbranded drugs. “[T]he government only had to prove beyond a reasonable doubt that Gellerman was responsible for, or aided and abetted in the commission of, delivering misbranded drugs after they had been received in interstate commerce.” The Court further ruled that “[m]isdemeanor liability stems not from ‘corporate hierarchy,’ but from an individual’s role in the sale of misbranded drugs” [citing United States v. Park. 421 U.S. 658 (1975)]. The Court upheld his conviction because government agents had purchased misbranded drugs from him even though “Gellerman had limited responsibilities as a store clerk.”
As precedent, the government’s appellate brief cited only to a 1986 case where a low-level employee, a store clerk, was prosecuted under the FDC Act. The brief also asserted that the language in Park holding what the government calls “responsible parties” to be liable under the FDC Act did not apply in this case because Gellerman personally sold misbranded drugs to customers. In contrast, Gellerman’s brief argued that he lacked responsibility and authority as a clerk, he believed the products he sold were legal, and he received no prior notice that the drugs he sold were misbranded or otherwise illegal.
This case perhaps answers the question regarding who can be criminally prosecuted for personal involvement in FDC Act violations. The answer, according to this Court, appears to be anyone! Although the Supreme Court in Park and an earlier Supreme Court decision had noted that relying on the “good sense of prosecutors” provides some protection to defendants being unfairly targeted, that is hardly a comfort to lower level employees in an FDA-regulated world.
We do not know the reasons why Gellerman was charged and we are not opining about whether this was an appropriate use of prosecutorial discretion. Rather, the notable (and potentially troubling) aspect of the Eighth Circuit’s Opinion is that the legal principle announced in the case appears to be that there is no legal limit on who can be prosecuted. That is an extremely powerful tool to place in the hands of government prosecutors.
This decision presents a number of very sticky issues for corporations, outside corporate counsel, and employees of a corporation. For instance, when the government investigates a corporation for alleged FDC Act violations, government investigators will frequently ask to speak with “lower-level” employees such as the sales force. Can anyone now assure such an employee that he/she will not be prosecuted absent a grant of immunity? Should company counsel represent both the corporation and lower-level company employees in a corporate criminal investigation when it is at least possible that the government may decide to prosecute low level employees for their actions?
Moreover, we have read numerous articles about the “Responsible Corporate Officer” Doctrine in the context of FDC Act prosecutions. It appears that this Court may have misunderstood Park. The Eighth Circuit said that misdemeanor liability does not stem from “corporate hierarchy” under Park, but instead turns on an individual’s role in the violations charged. In fact, Mr. Park’s conviction was based on his position at his company and his legal duty to prevent violations (as opposed to participating in them). In any event, here Gellerman was prosecuted for what he did, rather than any duty imposed on him to prevent others from violating the FDC Act.
As Congress and others debate the propriety of strict liability “no mens rea” prosecutions, the Gellerman prosecution is likely to be used (perhaps improperly) as Exhibit A by people who believe that strict liability prosecutions give the government too much power.
Posted at 06:56 AM in Medical Devices | Permalink | Comments (0)
Posted at 10:10 PM in Hatch-Waxman, Prescription Drugs and Biologics | Permalink | Comments (0)
Posted at 08:13 PM in Enforcement, Foods | Permalink | Comments (0)
Just ahead of a predicted snow storm in the Baltimore-Washington area, CMS yesterday issued a blizzard of 658 pages constituting its final regulation implementing changes to the Medicaid Drug Rebate Program. Although this is a final rule, CMS will be accepting comments on certain provisions relating to the alternative rebate for line extension drugs.
Hyman, Phelps & McNamara, P.C. will be preparing a memo summarizing the rule in the near future. We’ll also be conducting a webinar on the rule in collaboration with KPMG’s government pricing group. The date and other details will be announced on this blog over the next few days.
Posted at 09:44 AM in Government Pricing, Health Care | Permalink | Comments (0)
Posted at 04:15 AM in Foods, Foods and Dietary Supplements | Permalink | Comments (0)
NOP Clarifies What Substances Can Be Used in Post-Harvest Handling of Organic Products
On January 15, 2016, the National Organic Program of USDA's Agricultural Marketing Service (NOP) announced the availability of guidance on substances that may be used in the post-harvest handling of organic products and in facility pest management.
Under the Organic Food Production Act (OFPA), the NOP of the USDA is authorized to establish the National List of Allowed and Prohibited Substances (National List). The National List identifies the synthetic substances that may be used and the nonsynthetic (natural) substances that may not be used in organic crop and livestock production. It also identifies a limited number of non-organic substances (natural as well as synthetic) that may be used in or on processed organic products. The National List is spread over several regulations identifying the allowed and prohibited substances for crop production (7 C.F.R. §§ 205.601; 205.602); livestock production (7 C.F.R. § 205.603; 205.604); and in (or on) processed food products (7 C.F.R. §§ 205.605, 205.606). However, no regulation addresses use in post-harvest handling, i.e., “the act of handling raw agricultural commodities without further processing” (e.g., washing, cleaning, sorting, packing, cooling, storing of raw agricultural products).
Post-harvest handling of raw agricultural products can take place either on a farm or in a handling facility. It was unclear whether substances allowed in handling (listed in section 205.605) could be used in post-harvest handling on the farm, and if nonsynthetics allowed in crop products could be used in post-harvest handling taking place in a handling facility. NOP developed the guidance to resolve this confusion.
Under the NOP guidance, substances that may be used post-harvest on raw agricultural commodities include substances allowed for use in handling in § 205.605 of the National List, without specific use restrictions that would prevent such post-harvest use, and nonsynthetic substances allowed for use in crop production (without restriction in § 205.602 that would prevent such use). Synthetic substances listed in § 205.601 may only be used if they are specifically annotated to permit post-harvest use.
The organic regulations specify what substances may be used in facility pest management. If management practices fail, a nonsynthetic or synthetic substance “consistent with the National List” may be applied. NOP interprets this to mean that “nonsynthetic substances and synthetic substances” identified in the National List as permitted substances “may be used for facility pest management in accordance with any restrictions” and prohibitions. If a substance is listed as permitted in livestock production but prohibited for use in crop production, the use is not consistent with the National List. If all else fails, substances that are not on the National List may be used “provided that there is no contact with organic products or ingredients” and meet certain other requirements.
Appendices to the guidance include a number of examples illustrating the application of the scheme described in the guidance. In addition, NOP published its responses to comments.
Posted at 09:21 PM in Foods, Foods and Dietary Supplements | Permalink | Comments (0)
Posted at 09:46 PM in Hatch-Waxman, Prescription Drugs and Biologics | Permalink | Comments (0)