Making A Move To The Hamptons

luxury home for sale

Live Like A Celebrity And Move To The Hamptons

Given that it is such a brief travel from New York or even New Jersey, the unbelievable amount of natural beauty that exists here in East Hampton is extremely astonishing. If you haven’t been here, there are these long stretches of blue Coast lines that are flowing with golden sands. In addition, the natural landscapes that exist, there are also plenty of city parks that unite to form one of the most relaxing and breathtaking destinations along the upper East Coast. If you live near here and you have money, then you know about the Hamptons! There are mega movie stars and musicians that own beautiful property here, which as a result has attracted fantastic restaurants and dining establishments for those that like the finer things in life. There are posh boutiques popping up all over town, and despite its prevalence, however, East Hampton has worked tirelessly to keep its village-like charm, something you will quickly if you visit on vacation or decide to move to the Hamptons. There are few moving companies we trust in New York and New Jersey to move families into the Hamptons, but the team at Bluebell Moving And Storage has proven time and time again that they are the East Coasts premier moving agency for the upper class on the East Coast

As A New Resident Prepare To Shop And Surf The Hamptons

Due to its astonishing landscape, perfect location, and natural abundance of awesomeness, East Hampton has a lot of activities for you to get into once you move to the Hamptons. Main Beach is the biggest attraction for a lot of East Hampton locals and visitors. Believe it or not, it is among some of the best-ranked shorelines in the country, but it is more than just a place to relax on the beach and soak in some sun rays. Main Beach hosts many of the college’s water sports competitions, there is surfing, biking, paddle boarding, body surfing, and boogie boarding. Those of you that prefer spending money on fashion, you will love what Main Street has to offer, with its fashionable posh boutiques, they cater to the upper class that has money to spend on the nicer things in life. If that is not you, don’t bother moving here because poor people don’t fit in.

Embrace The Lavish Culture Of The Hamptons

If you can tear yourself away from the shore, the city of East Hampton has lots of family-friendly attractions to check out during the day and in the evenings. One of the true gems of Long Island is LongHouse Reserve. The beautifully maintained garden stretches 16 acres across the Hamptons and is filled with amazing eye-catching stone sculptures. The Pollock-Krasner House (once home to the artists Jackson Pollock and Lee Krasner) is just another location that civilization aficionados will not want to miss out on checking out, true history at it’s finest. Folks of all ages will love the fascinating tour, and children will love making their very own Pollock-style drip paintings. Living in the Hamptons offers so many great things to enjoy, and those are just a few. Becoming culturally aware of art and the area will be necessary if you are going to fit in here.

If You Are Lucky Enough To Buy Shorefront Property

If you are lucky enough to buy shorefront property you better soak it up! Most families that buy into this luxury area don’t give up their property that easy. move to the hamptons - family home in east hamptonHouses and land are passed down through the generations over the years and children and grandchildren are often left with vacation homes they rather not sell. The experience living on the shore is unforgettable. Even though the months of June through August are the nicest, September is also a fantastic time to enjoy some good sun and good times. If you are not a sun worshiper, late spring is also an amazing time of year. Temperatures are somewhat milder, but East Hampton nonetheless retains its magical, village-like vibe. For those that want to move to the Hamptson this vibe is priceless, for visitors making a vacation of the Hamptons, they often times do not want to leave!

If You Make The Move To The Hamptons Enjoy The Parks

When you move here you may find that there is an overwhelming amount of things to do at first. Moving in, unpacking, finding your way around and all that fun stuff. But after you get settled, you need to check out the Hampton Parks. East Hampton is home to no less than 8 country parks and two county parks, with Cedar Point County Park being the most popular destination among local residents and out of town visitors. It encompasses over 600 acres of coastal beauty and is famous for its magnificent views of Gardiner’s Bay. There is an abundance of things to do such as fishing, hiking, biking, and playing in the park. Additionally, It plays host to a rich ecosystem of wildlife together with everything from deer to ducks. There are also designated dog areas for the dog lovers of the Hamptons. The rich love their poodles and purse dogs, there is no shortage of those dogs here in our parks. Locals take pride in their parks and we ask that if you move to the Hamptons that you bring your dog out to enjoy the natural beauty with you that you clean up after your animal if they poop in the park grass.

READ: New Jersey Proposes New Limits……

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Why You Need Orthodontic Insurance Coverage

Why You Need Orthodontic Insurance Coverage

Insurance insures help patients when they want financial aid to obtain the needed service and have a difficulty. Such policies are used by them as a threat coverage tool, and one main policy folks take, is orthodontic insurance if they have been aware about their oral health. Correcting abnormalities and dental issues like misaligned or damaged teeth can improve grin and an individual’s facial features. Sadly, the prices can bite difficult in the lack of quality insurance. Dental treatment from Sky Orthodontist Oklahoma City changes among individuals so, the adolescents; therefore, many parents are under pressure in the adolescents who need to wear good looking braces.

Things become a lot simpler as the cover protects all processes and gear when you’ve got insurance insuring an orthodontist’s treatment. Check whether the policy contains coverage of treatment if you’ve got an existing dental insurance. Should it not have, then contemplate purchasing a supplementary form especially for this to cover your treatment prices. It’ll save you big time if you’ve got family members that want braces or treatment.

Just like your dental or insurance coverage that is routine, you’ll need to pay a monthly or annual premium. More than a few companies pay as much as fifty percent of the overall care expenses. So, if treatment is required by some of your nearest and dearest at once, your financial weight can ease significantly.

A bulk of the expenses come from the price of gear used in the restoration procedure like other additional dental products, braces, and retainers. The price of dental x rays, allowances that are needed, and monthly visits influence the amount being spent on treatment making it higher as opposed to dental care services that are routine. Averagely, the supplier to cater up to a specific quantity of dental care per year after which the maximum annual sum for all the dental prices become your company was just wanted by the typical dental cover.

In several cases, such processes are seen by individuals as being just decorative thus resulting in just several insurance companies providing cover for such a treatment services.

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Is It Necessary To See A Dentist Frequently?

Is It Necessary To See A Dentist Frequently?

The prevention of periodontal disease, cavities, and bad breath is reached with oral direction techniques which are powerful and affordable, easy to perform on a daily basis. A professional should be consulted or more often depending on significant care attempts and dental demands. Dentist OKC offers complete oral health care services to patients to help in the care of a cavity grin that is free. Personal wellness techniques and advanced oral technology are supplied according to individual conditions.

The oral evaluation can discover changes and tooth issues in tissues indicative of major ailments including cancers and diabetes. Some of the most significant measures that people can take to maintain the healthy state of teeth would be to see with the dental offices frequently. A routine checkup contains the detection of tartar, plaque and cavities in charge of gum disease and tooth decay. The formation of a failure and bacteria can improve discoloration, oral deterioration and decay. A failure to correct oral issues including little cavities may lead to important destruction of tissue and enamel including tooth loss and acute pain.

A dentist will counsel patients on easy and affordable suggestions for health care care that is individual to grow strong teeth and gums. This can be a simple and affordable method shield the state of oral tissues and to prevent cavities. Specialized tools are integrated at the practice to supply a professional clean and accomplish places that cannot be reached with flossing and brushing. It shields against spots and decay that undermine the healthy state of pearly whites. A dental practice provides complete oral care helping in treating gum and tooth ailments. Meeting an oral professional often and following day-to-day hygiene measures can best protect and improve the state of your grin.

It is important to get it assessed time to time and to take good care of your dental health and stay healthy. Google “oral health”  if you want to learn more about the oral health.

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Things To Look For In An Attorney Before Hiring Them

Things To Look For In An Attorney Before Hiring Them

Permit me to start by saying that do it yourself has its limitations. Certainly, contracts can be drafted by you by yourself, it is possible to survive discussions that are grotesque with your company customers, a married dispute can be settled by you but you should get an attorney when the demand to come to court appears. Expenses will be incurred, professional fees must be paid and the normally drawn-out procedure must be born. The prices of solving a difficulty are much greater in relation to the prices of preventing the issue. However, hiring a Sugar Land criminal defense attorney can eliminate the complexity, who knows what needs to be done.

When locating a lawyer so, search for a “competent” attorney. Before you start to share your innermost secrets together it’s absolutely ethical to require a lawyer permit. Generally though, their certifications would hang. He may be a professional in any among the following types of law: taxation law, labor law, civil law, international law, litigation, or criminal law. These are the important types. Therefore, you may learn of an immigration lawyer or a litigation attorney. Note however, that attorneys’ specialties are “obtained” through expertise, not only because they believe they have been excellent at it.

This can be one facet of being a lawyer where a youthful, inexperienced attorney can in fact get ahead of a seasoned one. Young attorneys usually are sympathetic, encouraging and lively. They have a tendency to treat their customers like their infants. They take care of every small detail, even the ones that are unimportant. But this just is paying customers desire to be treated. Customers often believe that they’re getting their money’s worth with the type of focus they can be becoming.

The personal qualities to try to find in an attorney depend significantly on the type of customer you might be. Should you be the no nonsense sort, you may choose to hire an old attorney who is about to retire. These kinds of attorney are interested in what you will need to say. Occasionally, they’re not thinking about what they must say. But their expertise is impeccable. The credibility of an attorney may be viewed in several circumstances. It can be built on charm coupled with referrals from previous satisfied customers. To be sure, no attorney can get customers if he’s not trustworthy and believable.

So at this point you have a credible, skilled and competent attorney having the individual qualities you try to find. Another matter to contemplate is whether that attorney can be acquired to attend to your own issue. Your attorney will say he is capable, willing and happy to help you. He said the identical thing to last week, and several others this morning, and the week. The point is, an attorney can only just do so much. He can not all be attending hearings all. He’d likely resort to rescheduling or cancelling hearings and assemblies that are significant to make ends meet. If your preferred attorney has a law firm, there will surely be other attorneys who can attend in case he is unavailable to you personally. You’ll find this satisfactory but not until your case continues to be reassigned to another from one hand.

The representation starts when you meet with your customer. This, nevertheless, isn’t what defines professionalism. So don’t be misled by the attorney-appear alone. It’d be amazing if your attorney can pull it away with the professionalism that is authentic and the attorney appearance though.

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Comment on FDA’s Notice of Intent to Consider the Appropriate Classification of Hyaluronic Acid Intra-articular Products Intended for the Treatment of Pain in Osteoarthritis of the Knee Based on Scientific Evidence

By Jeffrey K. Shapiro & Jeffrey N. Gibbs

On December 18, 2018, FDA published in the Federal Register a new docket entitled, “Notice of Intent to Consider the Appropriate Classification of Hyaluronic Acid Intra-articular Products Intended for the Treatment of Pain in Osteoarthritis of the Knee Based on Scientific Evidence.

This document is quite unusual, to say the least. Without fanfare, FDA has suddenly announced that products regulated as Class III devices for 23 years “may” actually be drugs. FDA invites holders of device approvals to seek a classification decision the next time they want to make a change to the product.

Let’s back up and start at the beginning: Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 321(h)) a device “does not achieve its primary intended purposes through chemical action within or on the body,” among other things. HA is introduced to the synovial fluid of the affected knee joint via injection, with the intention of treating pain.

Since 1995, FDA has classified these injectable products as devices. The basis for classifying HA as a device has been FDA’s conclusion that this product achieves pain reduction in an osteoarthritic knee via mechanical or physical actions at the joint (e.g., shock absorption). The first premarket application (PMA) was filed in 1995 and approved in 1997 (P950027). Since that time, there have been 198 separate approvals of either PMAs or PMA supplements (mostly the latter). The most recent one was 12 days ago, on December 6, 2018 (P080020 S031).

Now, FDA has suddenly issued a notice suggesting a new scientific theory that would necessarily require classifying these products as drugs. FDA’s summary of the notice (p. 1) states:

The Food and Drug Administration (FDA) is announcing our intent to consider the appropriate classification of hyaluronic acid (HA) intra-articular products intended for the treatment of pain in osteoarthritis (OA) of the knee. Although HA products intended for this use have been regulated as devices (Procode MOZ; acid, hyaluronic, intra-articular), the current published scientific literature supports that HA achieves its primary intended purpose of treatment of pain in OA of the knee through chemical action within the body [which would require classification as a drug]. Because HA for this use may not meet the definition of a device, sponsors of HA products who intend to submit a premarket approval application (PMA) or a supplement to a PMA for a change in indications for use, formulation, or route of administration are encouraged to obtain an informal or formal classification and jurisdiction determination through a Pre‑Request for Designation (Pre-RFD) or Request for Designation (RFD), respectively, from FDA prior to submission. If a sponsor believes their product meets the device definition, they may provide relevant evidence in the Pre-RFD or RFD.

As a procedural matter, this approach does not seem sensible. If FDA believes that new science requires the agency to re‑classify HA injectables for the knee as drugs, then it would make more sense to announce the concern, conduct a public proceeding to gather all the appropriate information and views, and make a class‑wide decision, with clear guidance on the transition and implementation of the decision. The sudden change without public input will deprive FDA of receiving broad feedback.

Instead, FDA has expressed doubt about the classification of all these products but only “encourages” PMA holders to seek classification decisions via the Pre‑RFD or RFD processes, and only if they are making a change to their product. This approach seems likely to result in inconsistency and expense, with little clarity. Will these RFD reviews really have pre‑determined outcomes, based on the notice? Nothing in the notice suggests that the science FDA is citing would apply to some HA products but not others. If so, why bother with case‑by‑case decision making at all? Why not take a class‑wide approach, and solicit comments?

Practical questions come to mind. If a PMA‑holder complies with the Quality System Regulation (QSR) for device manufacturing, would they be required to revamp their operations to comply with the Good Manufacturing Practice (GMP) regulation for drug manufacturing? That could be expensive and time‑consuming. How long would they have? Would companies submit Medical Device Reports (MDRs) for one version and Adverse Event Reports (AERs) for a product with new labeling deemed a drug? It is more than a little strange that the notice does not try to anticipate and answer the obvious practical questions that PMA‑holders will immediately ask.

Under the FD&C Act, a Pre‑RFD/RFD request is voluntary. It will be interesting to see whether the Pre‑RFD/RFD process will remain truly voluntary or if the Center for Devices and Radiological Health (CDRH) will refuse to process new PMAs and PMA supplements for HA products unless the applicant first obtains a Pre‑RFD/RFD decision. If CDRH does continue to process PMAs and PMA supplements for HA products, it would probably be advisable for PMA holders to simply skip submitting a Pre‑RFD/RFD request, since there is only a downside, which is reclassification as a drug.

Finally, if new science may necessitate upsetting long‑settled industry regulatory expectations, can we now expect that devices now inappropriately regulated as drugs will be moved to their rightful domain as well? If this type of notice can be issued announcing an intent to consider reclassifying devices as drugs, then perhaps we will see additional notices in the coming years, announcing an intent to consider reclassifying drugs as devices. Over the years, we have expressed our concerns about the product jurisdictional process (for example, here). This notice only reinforces our concerns.

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Farm Bill Resolves Issue of Added Sugar Declaration for Single Ingredient Foods

Farm Bill Resolves Issue of Added Sugar Declaration for Single Ingredient Foods

By Riëtte van Laack

As we previously reported, one of the main components of FDA’s 2016 final rule to update the Nutrition Facts is the mandatory requirement for a declaration and a daily value (DV) for “added sugar” for both sugars added to processed foods as well as foods “packaged as such,” including a bag of table sugar, jar of honey or container of maple syrup.  The requirement to declare added sugars on foods “packaged as such” created confusion.  Industry, particularly honey and maple syrup manufacturers, objected to the requirement and argued that the declaration of added sugars was misleading.  Thus far, FDA had not come up with an acceptable solution to this issue.  A draft guidance allowing a disclaimer yielded many comments and FDA withdrew the draft guidance.  FDA indicated it would act swiftly and promised a final guidance addressing this issue early in 2019.

Well industry need no longer wait for FDA.  The issue has been resolved by Congress.  Under section 12516 of the Agriculture Improvement Act of 2018, also referred to as the Farm Bill of 2018,

[t]he food labeling requirements under section 403(q) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 343(q)) shall not require that the nutrition facts label of any single-ingredient sugar, honey, agave, or syrup, including maple syrup, that is packaged and offered for sale as a single-ingredient food bear the declaration “Includes X g Added Sugars.”

In other words, single ingredient foods are exempt from the added sugar declaration.  It seems a common-sense solution.

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National Academies of Sciences Releases Report on Science of Patient Input, Citing Input from HP&M’s James Valentine

National Academies of Sciences Releases Report on Science of Patient Input, Citing Input from HP&M’s James Valentine

By Hyman, Phelps & McNamara, P.C.

On December 13, 2018, the National Academies of Sciences, Engineering, and Medicine released the proceedings of a May 2018 expert workshop entitled “Advancing the Science of Patient Input in Medical Product R&D: Towards a Research Agenda.  The workshop, hosted by the Academies’ Forum on Drug Discovery, Development, and Translation focused on approaches to:

  1. Understanding the experience of patients with a disease or a medical condition;
  2. Gaining insights on patient perspectives and preferences regarding the benefits and risks of treatments; and
  3. Considering way that patient input could further continuous improvement of clinical trial development.

Experts across a range of backgrounds, including HP&M’s James Valentine, were convened at the workshop to discuss their experiences with collecting, analyzing, and applying patient input so that those approaches could be applied more broadly across medical product development.  In addition, experts in the development of patient reported outcomes (PROs) were invited to explore lessons learned from that field.  Ultimately, the goal was to explore early and clinical R&D applications for soliciting patient input that can help inform medical product decision-making.

The report documents contributions by speakers and participants alike in a 9-page summary.  Here are some noteworthy excerpts:

  • Theresa Mullin (FDA Center for Drug Evaluation and Research): “It is important to understand what aspects of disease burden and treatment matter most to patients and their families and how to measure them, [and] what aspects of clinical trials can be better tailored to meet the needs and interests of potential clinical trial participants…”
  • Mats Hansson (Uppsala University): “…there is no consensus on the definition and role of patient preferences or on how to conduct patient preference studies []. The literature review identified 32 patient preference exploration and elicitation methods that researchers have used when developing medical products and devices.”
  • Kathryn O’Callaghan (FDA Center for Devices and Radiological Health): discussing how CDRH now used patient preference information (PPI) to assess risk tolerance in a case involving at-home renal devices, “[o]ne finding was that patients expressed a range or a heterogeneity of preferences showing the importance of not oversimplifying with assumptions that they all want the same thing. Another key finding was that a substantial portion of patients was willing to accept risk levels associated with at-home, self-care HHD. Considering the results of this study, FDA cleared a change in the indications for use to remove the care partner requirement.”
  • Lynn Hagger (AstraZeneca): discussing an onsite study simulation involving 18 clinical trial participants, “[a]fter consulting with the mock trial participants, AstraZeneca made 21 changes to its clinical trial protocol… The changes AstraZeneca made increased recruitment and retention in two subsequent trials and produced a net savings of $1.1 million.”
  • Ron Bartek (Friedreich’s Ataxia Research Alliance): “beginning discussions with trial sponsors as soon as they have a therapeutic candidate and before designing their protocols could be beneficial. Trial sponsors could use patient generated natural history data to identify the optimal population for a particular therapeutic candidate and to define their inclusion and exclusion criteria, as well as primary and secondary endpoints…”

HP&M’s Valentine Recommends Qualitative Methods to Solicit Patient Experiences in Clinical Trials

The National Academies of Sciences report includes a suggestion made by HP&M’s James Valentine at the workshop to incorporate patient questionnaires or other qualitative techniques (e.g., patient interviews) to help sponsors and regulators assess the success of clinical trials.  This is an approach that may be particularly useful in rare disease clinical trials, which face methodological challenges of small, heterogeneous patient populations and a lack of validated, disease-specific outcome measures.  Questions can be developed to capture changes that patients experienced during the trial, which may not be of things formally captured by trial endpoints.  When reported in the patients’ own words, this patient experience data can add context to the clinical meaningfulness of clinical trial results.

Valentine, in partnership with a CRO and industry collaborator, has a forthcoming manuscript that will provide a methodologic overview for such an approach – so stay tuned!

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New Data Integrity Guidance Imposes Significant Burdens, Yet FDA Claims It Does Not Regulate by Guidance

New Data Integrity Guidance Imposes Significant Burdens, Yet FDA Claims It Does Not Regulate by Guidance

By Douglas B. Farquhar & Mark I. Schwartz

FDA issued its final Guidance on Data Integrity on December 12.  The federal government has sworn off regulating by guidance (see blogpost here about Brand memo).  In fact, at the Food and Drug Law Institute (FDLI) Enforcement and Litigation Conference that was occurring simultaneously with release of the guidance,FDA Chief Counsel Stacy Kline Amin repeated the principle that the government does not regulate by guidance, and cited the “Brand Memo” as authority.  Despite those assurances, it would be hard to argue that the data integrity guidance does not represent an attempt to regulate by guidance.

To begin with, the guidance cites as support for its propositions (you guessed it!) ten other FDA Guidances; some of them are cited multiple times.  Perhaps more importantly, the final guidance, which governs manufacturing of finished dosage form drugs and by extension Active Pharmaceutical Ingredients (the guidance said that it is “consistent with CGMP for active pharmaceutical ingredients”), imposes onerous regulatory burdens.  In particular, one section jumps out at the authors of this article.

Written in Question and Answer Format, Question 8 of the final guidance asks, “How often should audit trails be reviewed?”  (Audit trails are records showing when and how electronic manufacturing and testing data were created, whether data have been altered or deleted, and other important information.)  The answer is startling.  Answer 8 states that “[i]f the review frequency for the data is specified in CGMP regulations, adhere to that frequency for the audit trail review.  For example, 211.188(b) requires review after each significant step in manufacture, processing, packing, or holding, and 211.22 requires data review before batch release.  In these cases, you would apply the same review frequency for the audit trail”.  In other words, in these instances, the audit trails must be reviewed for each batch before the batch can be released for distribution, despite there being no regulatory authority for this requirement.

This is a significant regulatory burden: in addition to reviewing entries on either the electronic or paper batch records to ensure all proper manufacturing steps have been performed, critical manufacturing checks have been reviewed and confirmed by a second individual, ingredients have been properly weighed and added, labels are accurate, all printed labels have been accounted for, and finished product meets required specifications (all of which are long-standing and well-understood requirements), Quality Control reviewers will now be compelled to review records maintained on electronic recording equipment (such as weight scales, laboratory testing and analysis equipment including High Performance Liquid Chromatographic equipment, and meters establishing density or acidity of finished product or in-process samples) for every batch.  This is a requirement that hardly springs naturally from the relevant regulations, 21 C.F.R. §§ 211.88(b) and 211.22.

Even more curiously, the apparent requirement that audit trail data integrity be reviewed for every batch before the batch can be released appears to be more stringent than the answer to the same question in the draft of this guidance that was issued only a couple of years ago.  We previously blogged about the draft guidance here and here.  That draft guidance answered the same question (although it was Question 7) as follows: “FDA recommends that audit trails that capture changes to critical data be reviewed with each record and before final approval of the record.”  So, in the draft guidance it was a mere “recommendation,” and now it appears to be a requirement (“adhere to that frequency for the audit trail review” instead of “FDA recommends that you adhere to that frequency for audit trail review”).

What has changed?  Certainly not the Federal Food, Drug, and Cosmetic Act in this regard. Not the regulations at 21 C.F.R. Part 211 on this issue.  This seems like more regulation by guidance to us.  And, although the guidance states (as do all guidance) that it does not establish legally enforceable responsibilities unless specific regulatory or statutory requirements are cited (note that none of the regulations FDA cites to make any reference, express or implied, to audit trail review), woe to the quality unit that even dares to claim that audit trail review is consistent with cGMP if done under another standard.

Nor is this the only example of regulation by guidance in the document.  Question 15 asks: “Can an internal tip or information regarding a quality issue, such as potential data falsification, be handled informally outside of the documented CGMP quality system?”

FDA’s response to this question is: “No. Regardless of intent or how or from whom the information was received, suspected or known falsification or alteration of records required under parts 210, 211, and 212 must be fully investigated under the CGMP quality system to determine the effect of the event on patient safety, product quality, and data reliability; to determine the root cause; and to ensure the necessary corrective actions are taken (see §§ 211.22(a), 211.125(c), 211.192, 211.198, 211.204, and 212.100).”

Yet none of these regulatory provisions actually require that firms investigate an internal tip or information regarding a quality issue within the cGMP quality system.

Another example is question 1(a), in which the agency asks “what is data integrity?” The answer states that “[f]or the purposes of this guidance, data integrity refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA).”  Under footnote 5, the agency’s stated support for the proposition that ALL data for drug manufacturing should be “contemporaneously recorded” is the regulatory requirements at 21 CFR 211.100(b) and 21 CFR 211.160(a), which granted, do provide that documentation take place “…at the time of performance…”.

However, these regulatory provisions are very narrowly tailored and refer specifically to, in the first instance, production and process control functions and, in the second instance, laboratory controls.  The agency does not cite to any additional regulatory authority for the general notion enunciated in the answer to question 1(a) that ALL data must be contemporaneously recorded.

Later in the document, in response to question 1(c) the guidance states: “CGMP-compliant record-keeping practices prevent data from being lost or obscured and ensure that activities are documented at the time of performance (see §§ 211.68, 211.100, 211.160(a), 211.188, and 211.194)” [Emphasis added], and yet none of these additional regulatory citations speak to the requirement that all data must be contemporaneously recorded.

Another example is the requirement that ALL data generated and recorded in all drug facilities be “attributable” (meaning ascribed to a particular individual in the facility) as described by answer 1(a) and footnote 5.  Yet, again the regulatory citations for this requirement are sorely lacking.  Of the ones cited in the guidance (§§ 211.101(d), 211.122, 211.186, 211.188(b)(11), and 212.50(c)(10)) only the last three regulatory provisions speak directly to the “attribution” issue, and again they are very narrowly tailored and only speak to, in the first instance, master production and control records, in the second instance, batch production and control records and, in the third instance, Positron Emission Tomography drug production and process control records!

We could go on and on but suffice it to say that the guidance on data integrity is replete with instances of regulation by guidance.  We had hoped that an administration that claims to be concerned about over-regulation would make sure to prevent this, whether it is the result of notice and comment rulemaking, or the result of the more pernicious “regulation by guidance.”

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Comments on FDA’s Proposed Rule Governing the De Novo Classification Process

Comments on FDA’s Proposed Rule Governing the De Novo Classification Process

By Jeffrey K. Shapiro & Allyson B. Mullen

On December 4, 2018, FDA issued a proposed rule that would govern the de novo classification process.  After a comment period, it may be re‑issued as a final rule to take affect 90 days after publication.   While we agree with FDA’s goal of creating greater consistency and predictability in the de novo process, the proposed rule appears in some respects to unduly increase the burden on applicants.  In this regard, the proposed rule would make the de novo process look more like review of a premarket approval (PMA) application than a 510(k) submission.  It is also not clear if FDA has statutory authority to implement certain features of the proposed rule.

As a reminder, de novo classification allows the placement of novel device types into Class I and Class II, rather than burdening them with the Class III, PMA approval process that applies by statutory default to all new device types.  After a new device type is classified in Class I or Class II via de novo classification, similar devices within the same generic type can proceed to market based upon 510(k) clearance.

Most of FDA’s classification regulations were adopted for devices on the market in the 1970s and 1980s.  As time has passed, more novel device types have been developed.  The de novo process is an important way to expand the classification regulations to incorporate new Class I and Class II device types.

Until recently, there was little written guidance from FDA as to how de novo reviews would be conducted.  In recent years, FDA has issued several guidance documents on various aspects of the de novo program (for example: here, here and here).  A regulation would harden “recommendations” in a guidance document into “requirements” that must be followed.  A regulation gives both industry and FDA less flexibility, but it also gives greater certainty about the rules of the road.

In general, the proposed rule is consistent with FDA’s current administrative practice in processing de novo submissions.  The proposed rule appears structurally similar to the 510(k) regulation (21 C.F.R. Part 807, Subpart E) and the PMA regulation (21 C.F.R. Part 814), in setting forth requirements for (i) the format and content of a de novo submission, (ii) the procedures governing FDA’s review, and (iii) grounds for denial.

The proposed content requirements are nearly the same as those FDA proposed in its draft guidance, Acceptance Review for De Novo Classification Requests (Nov. 2017) (see our blog post here).  But, there are several additions that will likely increase the burden on applicants.  For example, de novo sponsors will be required to submit:

  • a bibliography of all published and unpublished reports on the device and any other information relevant to a device’s safety or effectiveness;
  • samples of the device and its components, if requested by FDA; and
  • advertisements for the device.

These requirements are elements of a PMA application, not the 510(k) submission.  21 C.F.R. § 814.20(b)(8)‑(10).  With regard to advertisements, in particular, the PMA regulation is limited to “advertising that constitutes labeling under section 201(m) of the act.”  Id., § 814.20(b)(10).  In contrast, this proposal is broader.  It is not clear what the justification is, since FDA does not have authority to over the advertising of devices classified into Class I or II.  Perhaps they would justify this request based on the need to determine the intended use.  See id., § 801.4 (defining intended use to include labeling and advertising).

Unlike the 510(k) regulations, and more like the PMA regulations, the proposed de novo rule specifies the types of information required in a submission, including various types of non‑clinical data.  Compare 21 C.F.R. § 807.92(b)(1) with id. § 814.20(b)(6)(i).  This specification will at least provide greater certainty about what is required.  One potential omission is acknowledgement of the types of tests done for in vitro diagnostic devices, which have been a significant percentage of de novo clearances.

The procedure for review of submissions in the proposed rule generally follows FDA’s current administrative approach.  Interestingly, the proposed regulation states that a de novo request can be refused for filing if “the requester has not responded to, or has failed to provide a rationale for not responding to, deficiencies identified by FDA in previous submissions for the same device.”  In the preamble to the proposed rule, FDA states that a de novo can be refused for filing if a requester has not provided “a complete response” to such deficiencies.

The completeness of a response is, of course, in the eye of the beholder.  We hope that FDA will clarify in the final rule that a submission will be accepted if there is a response to prior deficiencies, with evaluation of the completeness and adequacy of the response occurring during the review on the merits.  This issue is of particular concern in light of problems in the 510(k) Refuse‑to‑Accept (RTA) process in the early days of its implementation, in which substantive questions were improperly raised.

The proposal sets forth 11 grounds on which the Agency may deny a de novo request.  In the PMA context, the grounds for denial are set forth in the Federal Food, Drug, and Cosmetic Act (FDCA) and are mirrored in the implementing regulation.  In the 510(k) context, the statute defines “substantial equivalence” and the implementing regulation provides that failure to establish substantial equivalence in accordance with this definition is grounds for denial.  In the de novo context, the statute authorizes only two potential grounds for denial:  (i) existence of a predicate device that provides a reasonable basis for a substantial equivalence review; or (ii) a determination by FDA that “the device submitted is not of low‑moderate risk or that general controls would be inadequate to control the risks and special controls to mitigate the risks cannot be developed.”  It seems potentially unauthorized for the implementing regulation to exceed the FDCA by specifying, as it does, nine additional grounds for denial.

Currently, FDA promptly posts letters granting de novo authorization in its de novo database.  Unfortunately, FDA takes considerably longer to post decision summaries, and it has taken months (and sometimes years) before new classification regulations are published in the Federal Register.  For example, the classification regulation for 23andMe’s DEN140044 was published nearly three years after the de novo classification was granted.

More recently, FDA has been posting decision summaries more promptly in the de novo database.  FDA should add a provision to the proposed rule establishing a definite timeline for posting both decision summaries and issuing Federal Register notices.  FDA publishes 510(k) Summaries (and decision summaries for 510(k)s for IVDs) within 30 days of clearance.  That would be a reasonable timeline for publishing the results of de novo classification decisions.

We found it interesting that the proposed rule states that FDA will decide a de novo request within 120 days.  That deadline is already in the statute, so FDA had to adopt the same timeline in the proposed rule.  In actuality, though, FDA routinely misses this deadline.  In the MDUFA IV Commitment Letter, FDA publicly agreed only to approve/deny 50% of de novo requests within 150 days (i.e., 30 days beyond the statutory deadline), with the other 50% presumably being decided somewhere north of 150 days.  In conjunction with the proposed rule, FDA should request appropriate funding from Congress to staff the de novo program to meet the 120‑day statutory requirement.  All parties would benefit.

Possibly the most controversial feature of the proposed rule is that it would give FDA authority to inspect submitter’s manufacturing facilities and clinical trial sites.  Here is the proposed regulatory provision (§ 860.256(c)):

(c) Prior to granting or declining a De Novo request, FDA may inspect relevant facilities to help determine:

(1) That clinical or nonclinical data were collected in a manner that ensures that the data accurately represents the benefits and risks of the device; or

(2) That implementation of Quality System Regulation (part 820 of this chapter) requirements, in addition to other general controls and any specified special controls, provide adequate assurance that critical and/or novel manufacturing processes produce devices that meet specifications necessary to ensure reasonable assurance of safety and effectiveness.

Start with manufacturing inspections:  In the 510(k) context, the FDCA expressly forbids FDA from conducting inspections for Quality System Regulation (QSR) compliance, unless “there is a substantial likelihood that the failure to comply with such regulations will potentially present a serious risk to human health.”  FDCA § 513(f)(5).  FDA has declared that it may conduct preclearance inspections for a few device types, e.g., infusion pumps.  Most device types do not meet this standard and preclearance manufacturing inspections are rare.

In the PMA context, the statute permits FDA to withhold approval if manufacturing facilities do not conform to QSR requirements.  FDCA § 515(d)(2)(C)).  The implementing regulation expressly authorizes conditioning approval on a successful manufacturing inspection.  21 C.F.R. § 814.44(e)(1)(iii).  As a matter of administrative practice, FDA routinely performs QSR inspections prior to granting PMA approval.

As to de novo classification, the FDCA is silent on whether preclearance inspections are authorized.  Yet, in the proposed rule, FDA grants itself authority to conduct manufacturing inspections when deciding de novo classification requests.  Perhaps recognizing this legal weakness, FDA’s proposal is not a straight‑up right to inspect for QSR compliance.  Rather, FDA purports to authorize itself to inspect whether the applicant’s “implementation” of the QSR “in addition to other . . . controls” (whatever that means) will “provide adequate assurance that critical and/or novel manufacturing processes” will “produce devices that meet specifications necessary to ensure reasonable safety and effectiveness” (proposed § 860.256(c)).

The actual meaning of this convoluted language is anybody’s guess.  It seems like a questionable effort to tie QSR compliance to device classification.  There is no support in the FDCA for doing so.  On the contrary, the statutory provision that authorizes all the various classification proceedings (FDCA § 513) does not authorize manufacturing inspections, with an express limited exception in the 510(k) context (discussed above).  In practice, none of the classification regulations promulgated in the 1970s and 1980s were associated with manufacturing inspections.  Since a de novo review is in fact the promulgation of a new classification regulation, it would seem that likewise a manufacturing inspection is not authorized for de novo review.  Certainly, there is no express statement anywhere in § 513 that FDA may conduct manufacturing inspections in conjunction with de novo classification proceedings (in contrast to the express authorization in § 515 in connection with PMA approval).

Apart from the uncertain statutory grounds, this process of inspecting de novo applicants for QSR compliance would create an undue burden on a first comer.  After a de novo is granted, subsequent applicants will proceed through the 510(k) process (for non-exempt devices).  As noted above, FDA is expressly prohibited from inspecting 510(k) applicants for QSR compliance, unless there is a serious risk to health.  Therefore, these second comers will have a lower bar to clearance than the de novo applicant, creating an unevenly applied regulatory scheme.

The proposed rule is on more solid ground with clinical study site inspections.  FDA has authority to inspect data and information related to investigational devices, including the results of clinical studies evaluating such devices.  E.g., 21 C.F.R. § 812.145.  The statutory authority underlying that regulation is not open to question.

One wonders also how practical is will be for FDA to routinely conduct clinical and/or manufacturing inspections in a 120‑day time frame for de novo review?  It would be resource‑intensive to complete inspections in this time frame, possibly detracting from the ability to conduct routine inspections or causing FDA to frequently miss the deadline for completing de novo reviews.  With regard to manufacturing, there will also be a substantial burden on companies that have developed novel device types.  These firms are frequently start‑ups that have not completed building out their manufacturing facilities and procedures.  It might be better to conduct an early inspection once they are engaged in actual commercial distribution.

As to clinical data, although we do not question FDA’s authority or even the need in some cases to conduct inspections, we are already aware of two past de novo requests for which FDA has inspected clinical data and the review time significantly exceeded the 120-day statutory decision deadline.  It is not clear how routine clinical inspections would work as a practical matter or whether FDA envisions such inspections taking place only if there are “for cause” concerns about the integrity or validity of the clinical data.  This point at least needs to be clarified.

Overall, in our view, the proposed rule is a good idea to bring greater certainty to the de novo process.  If the proposed rule is finalized as‑is, though, it will materially increase the burden on applicants seeking de novo marketing authorization for a low‑risk novel device.  That potential impact is concerning, especially in light of FDA’s recent statements about an intent to increase utilization of the de novo pathway.

Those in industry who would be subject to the proposed rule may wish to submit comments on the legalities and burdens associated with the proposed rule.  Comments are due by March 7, 2019.

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The FTC and FDA May Face New Hurdles in Injunction Actions

The FTC and FDA May Face New Hurdles in Injunction Actions

By John R. Fleder & Jennifer M. Thomas

On December 11, 2018, the authors of this blog post attended the oral argument in Federal Trade Commission v. Shire ViroPharma, Inc., No. 18-1807 (3d Cir. filed Apr. 12, 2018).  We have previously blogged about the case here, here, and here. In a nutshell, Shire examines the FTC’s statutory authority to bring suit in federal court seeking injunctive and equitable relief where the alleged statutory violations at issue have long since ceased. Section 13(b) of the Federal Trade Commission Act (“FTC Act”) (15 U.S.C. § 53(b)) gives the FTC authority to file a case only when the FTC has reason to believe that a defendant “is violating” or “is about to violate” the FTC Act.

Although it is often hard to predict the outcome of an appeal after hearing the questions and comments of the three-judge court, in this case the Court’s questions and comments suggested that odds are leaning heavily against the FTC winning.  If the FTC does lose, the question will then be how severe an effect the Court’s ruling will have on other FTC enforcement cases. And this is not the only recent court case that poses significant litigation concerns for the FTC.  Two other recent court rulings suggest that courts are revisiting the FTC’s authority to seek equitable relief (including restitution and disgorgement) under the FTC Act § 13(b).  These rulings also may raise an issue that our firm opined on fifteen years ago, namely whether FDA has the authority to seek equitable remedies when it pursues injunctive relief in court.

What Will an FTC Loss in Shire Mean for FTC Act Enforcement?

The questions presented to the Third Circuit panel (Smith, J., McKee, J., and Fisher, J.) in Shire centered on what legal standard the FTC must meet in order to adequately allege reason to believe that a defendant “is violating, or is about to violate” the FTC Act under Section 13(b), and whether the FTC met its burden in this case. The judges’ questioning at oral argument strongly suggested that the answer to the latter question will be “no.” The answer to the former question is less clear.

The FTC’s primary argument in Shire is that the “about to violate” language must be analogized to the standard applied for injunctive relief under other statutes, which would only require the FTC to adequately plead that an alleged violation was reasonably likely to recur. The FTC cited the Third Circuit case of SEC v. Bonastia, 614 F.2d 908 (3d Cir. 1980) for the factors used to determine likelihood of recurrence – factors that do not include a temporal element. The panel appeared to reject the FTC’s proposed standard, with at least Judges Smith and McKee indicating their belief that some temporal consideration must be involved in a determination of whether someone is “about to violate” the law. Chief Judge Smith, in particular, emphasized that the plain language “about to” seems to reflect a degree of imminence.

The Third Circuit Court’s emphasis on the relatively extreme facts of the Shire case – a five-year delay between the alleged violative conduct and initiation of the FTC’s suit, and no allegations of future circumstances in which Shire could be expected to repeat the alleged misconduct – suggest that the court could simply hold that the FTC had failed to adequately plead even a reasonable likelihood of recurrence and leave the matter there. However, the FTC’s position that the “likelihood of recurrence” includes no explicit consideration of timing may make it difficult for the Court to rule under that standard without altering it to include a temporal factor.

Assuming that the Court does rule against the FTC with respect to the applicable legal standard under Section 13(b), of course the Commission may seek rehearing or rehearing en banc, and may ultimately seek Supreme Court review. Moreover, a loss in the Third Circuit would still permit the FTC to seek a different result in any state other than New Jersey, Pennsylvania, and Delaware (in those three states, the FTC will have to follow an adverse Third Circuit ruling unless and until it is overturned by the Supreme Court).

Still, an ultimate loss for the FTC on this issue, particularly if the Court’s reasoning is adopted by courts outside the Third Circuit, would likely result in a longer process to resolve many FTC Act violations. As Shire’s counsel pointed out at oral argument, the FTC clearly has authority to bring an administrative action for violations of the FTC Act without any statutorily imposed temporal limitation (See 15 U.S.C. § 45(b); 16 C.F.R. Part 3). However, the Commission cannot obtain consumer redress through an administrative proceeding. To obtain recompense for consumers in consumer protection cases, the FTC would have to bring and successfully complete an administrative case, overcome a court challenge to a final order, and then file and win a court case seeking equitable relief pursuant to 15 U.S.C. § 57b. Even that process is inapplicable in “competition” cases such as Shire, because 15 U.S.C. § 57b is focused on consumer protection cases. This means that, practically speaking, in a case of harm to consumers where the FTC cannot make a showing of “imminent” future violation, the FTC may well be unable to provide relief to affected consumers.

The delay associated with pursuing an administrative cease and desist order is one of the reasons that the FTC has filed hundreds if not thousands of cases where the FTC bypasses the administrative process and goes straight to court seeking an injunction.  In consumer protection cases, the FTC seeks relief such as restitution and disgorgement of profits in most such cases.  In many cases, the FTC also seeks and obtains “emergency” relief such as a total freeze of the defendants’ assets. All of this authority would be in jeopardy if the FTC cannot seek and obtain such relief at all, or only after a long administrative process and later court case.

Of course, even if the FTC loses this case, it can collaborate with other government agencies with consumer protection and antitrust authorities, including the U.S. Department of Justice and State Attorneys General. Such coordination takes additional time, as well as the balancing of agency investigative and enforcement resources. Additionally, the FTC would lose its independence to bring these actions without needing to go through another federal or state agency — the FTC has been fiercely fighting to obtain and retain independent litigating authority for almost fifty years.

Does Shire Affect the FTC’s (and FDA’s) Pursuit of Equitable Remedies?

In Shire, the FTC’s brief argued in the alternative that even if the FTC had not adequately alleged a likelihood of recurring violations, the FTC should nevertheless be permitted to go forward with its claim for restitution to consumers who presumably overpaid for one of Shire/ViroPharma’s drugs.  Shire’s brief countered that the FTC failed to adequately plead the statutory prerequisites to bring suit under Section 13(b), thus, the Commission had no right to alternatively seek monetary relief. Shire also noted the Supreme Court’s 2017 ruling in Kokesh v. SEC, 137 S. Ct. 1635, that cast doubt upon agencies’ authority to seek equitable remedies not expressly referenced by the applicable statute.

This week’s oral argument did not address the question of alternative equitable remedies.  Thus, it is quite possible that the Court will simply rule that the entire case must be dismissed because it was brought too late, without reaching the question of whether the FTC has the right under Section 13(b) to seek restitution and other equitable relief such as disgorgement of profits.

However, in many respects, the issue of the FTC’s right to obtain equitable remedies in a Section 13(b) suit is of greater importance to the FTC than the standard for determining whether the FTC has satisfactorily alleged that it has reason to believe that the defendant is about to violate the FTC Act.  That issue is largely a timing question, and the FTC usually brings suit much closer to the violative events than it did in Shire.  In contrast, if the courts definitively rule that the FTC has no authority to seek equitable relief in Section 13(b) cases, that result would severely damage most of the FTC’s consumer protection 13(b) cases, where the Commission typically seeks such remedies.

The question is one of statutory interpretation:  Does Section 13(b) authorize the FTC to seek all forms of equitable relief assuming the court has power to grant any relief at all?  The statute itself specifically authorizes a court to issue a temporary restraining order, a preliminary injunction, or a permanent injunction, but is silent on other forms of equitable relief.  Although the FTC has been successful in arguing to many courts that once a court has jurisdiction over a case seeking injunctive relief, that court has the authority to award equitable relief such as asset freezes, the payment of restitution, and/or the payment of disgorgement of profits, this previously established authority is now being reexamined by the courts.

Aside from the Third Circuit in Shire, other courts have recently looked at the FTC Act and questioned the FTC’s authority to seek and obtain equitable relief not expressly referenced by Section 13(b). FTC v. Hornbeam Special Situations, an October 2018 decision in the Northern District of Georgia, is a similar case we have blogged about.  More recent is the December 3, 2018 Ninth Circuit ruling in FTC v. AMG Capital Mgmt., LLC.  There, the court ruled in favor of the FTC’s pursuit of equitable remedies: The court conceded that defendant’s argument regarding the FTC’s lack of statutory authority “has some force but it is foreclosed by our precedent.”  However, one Ninth Circuit judge (O’Scannlain) also filed a concurring opinion arguing that the Ninth Circuit’s earlier rulings authorizing the FTC to obtain equitable remedies under Section 13(b), while binding, were “no longer tenable.”  Judge O’Scannlain’s opinion suggested that the Ninth Circuit should hear the case en banc to reconsider its precedent on the issue.  He specifically noted that a separate provision of the FTC Act (15 U.S.C. § 57b), applicable in different circumstances, expressly authorizes alternative equitable relief in certain consumer protection cases, while Section 13(b) is tellingly silent on those remedies. Although the ultimate disposition of the AMG Capital case is not yet clear, Judge O’Scannlain’s concurring opinion should give the FTC reason to worry.

In light of the developing case law, FDA may also need to be more circumspect in seeking equitable relief when it (through the Department of Justice) files an injunction action under 21 U.S.C. § 332.  That provision authorizes courts to “restrain violations” of the Federal Food, Drug, and Cosmetic Act, but is silent on the court awarding equitable relief as part of the injunction.  The issue of FDA’s authority to seek restitution or disgorgement in a Section 332 action was hotly debated fifteen years ago, when our firm argued in a law review article that FDA lacks this authority.  See Jeffrey N. Gibbs and John R. Fleder, Can FDA Seek Restitution or Disgorgement?, 58(2) Food & Drug L.J. 129 (2003).  FDA disagreed, and in several subsequent court rulings FDA’s position was adopted.  See United States v. Kaminski, 501 F.3d 655, 670 (6th Cir. 2007); United States v. Rx Depot, Inc., 438 F.3d 1052, 1063 (10th Cir. 2006); United States v. Lane Labs-USA, Inc., 427 F.3d 219, 236 (3d Cir. 2005).  FDA has also successfully received such equitable relief via consent decrees.  See, e.g., FDA: Michigan Heart-Lung Bypass Machine Manufacturer (disgorgement of $35 million, E.D. Mich. 2011, link); Bristol-Myers Squibb to Pay More than $515 Million to Resolve Allegations of Illegal Drug Marketing and Pricing (disgorgement of over $25 million, D. Mass. 2007, link). Nevertheless, FDA’s authority to obtain equitable remedies in an injunction suit may now be in as much in jeopardy as the authority of the FTC.

We will continue to monitor this area of developing case law, and keep readers informed.

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Failure to File Adverse Event Reports Results in Criminal Pleas for Medical Device Company and Quality Manager

Failure to File Adverse Event Reports Results in Criminal Pleas for Medical Device Company and Quality Manager

By Anne K. Walsh

Duodenoscopes are flexible, lighted tubes that are threaded through the body into the top of the small intestine (duodenum) and allow doctors to see potential problems in the pancreas and bile ducts. Because duodenoscopes are reusable devices, they must be reprocessed (cleaned) after each use to ensure that tissue or fluid from one patient is not transferred when used on a subsequent patient.

For several years, FDA has been concerned about the reprocessing of duodenoscopes. In 2015, FDA required all manufacturers who make and sell duodenoscopes in the United States to conduct postmarket studies to allow FDA to better understand how duodenoscopes are reprocessed in real-world settings; in March of this year, FDA issued Warning Letters to all U.S. duodenoscope manufacturers for failing to meet their postmarket surveillance study requirements; and just this week, FDA provided interim results of the reprocessing studies and its recommendations.

Despite all this scrutiny, or maybe because it was already on the government’s radar, one of the manufacturers, Olympus Medical Systems Corporation, and its former quality manager were targeted for their failure to file reports related to known adverse events associated with its duodenoscopes. FDA requires medical device manufacturers to submit Medical Device Reports (MDRs) under 21 C.F.R. Part 803 for an event when they “become aware of that reasonably suggests that one of their marketed devices”:

(i) May have caused or contributed to a death or serious injury, or

(ii) Has malfunctioned and that the device or a similar device marketed by the manufacturer [or importer] would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.

A failure to submit an MDR renders a medical device “misbranded,” and the FDC Act prohibits the introduction of a misbranded medical device into interstate commerce.

On December 10, 2018, Olympus agreed to plead guilty to three misdemeanor counts of introducing misbranded duodenoscopes into interstate commerce. The plea agreement contains a stipulation of facts describing Olympus’ receipt of information requiring submission of an initial or supplemental MDR, and requires the company to distribute to its U.S. customers a notice about the plea agreement. The company also is required to undertake certain compliance measures specific to MDR processes, akin to those contained in FDA civil consent decrees:

  • Retain an independent MDR expert to inspect and review the company’s policies and procedures;
  • Have the MDR expert conduct periodic reviews of the company’s continued compliance with MDR requirements;
  • Report to FDA and DOJ periodically for 3 years; and
  • Require the President and Board of Directors to periodically review MDR compliance measures and provide certifications to FDA and DOJ regarding those reviews.

The global settlement was authorized by DOJ’s Assistant Attorney General Joseph Hunt, which permitted the lead prosecutor from the U.S. Attorney’s Office in New Jersey to bind “the United States Attorney’s Offices for each of the other 93 judicial districts of the United States,” a provision that assures the company that another aggressive prosecutor will not bring follow-on charges against the company.

Hisao Yabe, the former Division Manager for the Quality Assurance and Environment Division, agreed to plead guilty to one count for the same conduct. He stipulated that he was aware of the obligation to file and supplement MDRs, and that he failed to make such submissions even when required. Interestingly, the stipulation notes that he considered whether to submit a supplemental MDR in 2013, but did not file it until 2015. In reviewing the underlying Information, it appears Yabe was in the process of evaluating whether the information it received in 2013 required reporting (e.g., whether the methodology and conclusions of the information were appropriate), and agreed that if a supplemental MDR was required, the company should file it. It is unclear, however, why the company waited until 2015 and what ultimately motivated the filing decision at that time. One can only speculate that the coincident timing of FDA scrutiny resulted in the MDR filing, which three years later, now forms the basis for the criminal charge.

In addition to the mandatory compliance measures, the company agreed to pay an $80 million criminal fine (which was 2.5 times the profit earned from the duodenoscopes sold during the time period), and a $5 million forfeiture. Yabe faces up to a year in prison and a $100,000 fine; he will be sentenced in March 2019.

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Freedom of Information…Unless Agencies Decide Otherwise?

Freedom of Information…Unless Agencies Decide Otherwise?

By Sara W. Koblitz

On Friday, the Yale Law School Media Freedom and Information Access law clinic filed a complaint against FDA, HHS, and NIH alleging violations of the Administrative Procedure Act based on Section 801 of the FDA Amendment Act (FDAAA), which requires results reporting of clinical trials to the defendant agencies. Filed on behalf of a journalism professor and reporter, Charles Seife, and a physician, the President of the Center for Science in the Public Interest, and former FDA official, Peter Lurie, the suit alleges that defendants acted arbitrarily and capriciously in their interpretation of FDAAA 801 to apply only to trials completed after January 18, 2017 and in their application of FDAAA 801 by failing to issue statutorily-required notices of noncompliance and post them on ClinicalTrials.gov.

As we explained when the final rule implementing FDAAA 801 was published in October 2016, FDAAA 801 requires the submission and posting of registration and results information of applicable clinical trials, including both approved, licensed or cleared products and unapproved, unlicensed, or uncleared products. If the product has not been approved, licensed or cleared at the time of a trial completion, basic results information must be reported within 30 days of approval. The final rule added a de facto exemption for clinical trials of unapproved products with a primary completion date before the rule’s effective date; as such, products with a primary completion date prior to January 18, 2017 were exempted from the reporting requirement. The rule also required the agency defendants to maintain a registry and results data bank, which they did via the ClinicalTrials.gov website, along with public notices of violations of these reporting requirements.

Plaintiffs raise the argument that the de facto reporting exemption for studies with a primary completion date prior to January 18, 2017 exceeds the statutory authority set forth in FDAAA 801. Without basic results information, Plaintiffs argue that their efforts to characterize the integrity of clinical trial enterprise and complete research into evidence development and dissemination are harmed by this arbitrary and capricious interpretation.

Additionally, plaintiffs allege that the agency defendants have failed to comply with their congressionally-mandated obligation to issue and publicly post notices of FDAAA violations. Despite public knowledge of widespread noncompliance with the statute, defendants have not issued a single public notice of noncompliance on ClincialTrials.gov, as required by statute. Nor have defendants implemented a public search function for notices of noncompliance on ClincialTrials.gov, as required by statute. Plaintiffs allege that this failure to comply with the FDAAA 801 requirements “constitutes agency action unlawfully withheld and/or unreasonably delayed, in violation of 5 U.S.C. § 709(a).” Plaintiffs cite, amongst other studies, AllTrials data stating that that only 60.8% of applicable clinical trials with completion dates on or after the FDAAA Final Rule effective date, January 18, 2017, have publicly reported results on ClinicalTrials.gov.

Plaintiffs request that the U.S. District Court for the Southern District of New York (SDNY) strike down portions of the final rule exempting studies with primary completion dates prior to January 18, 2017 from mandatory reporting obligations. Further, Plaintiffs ask that SDNY compel defendants to issue noncompliance notices and provide them in an easily-searchable database on ClinicalTrials.gov.

To the best of our knowledge, this is the first litigation arising from FDAAA 801. It’s an interesting tactic, reminiscent of suits brought under FOIA to require agencies and officials to enforce the law (i.e., the FOIA project, EPIC). Because of the strong statutory language with respect to notice of violations in 42 U.S.C. § 282(j)(5)(E)(i)–(ii), plaintiffs do have a persuasive argument that, in this instance, Congress explicitly intended to curtail agency enforcement discretion, and perhaps it will survive a motion to dismiss. But given the extent of Chevron deference and an agency’s discretion to enforce, there is a good possibility that this case will be dismissed.

Nevertheless, the case highlights the lack of transparency in the federal government. While this action is obviously limited to only the three relevant agencies, the overarching issues surrounding transparency seem to be par for the course across all of government right now. FDAAA was clearly passed to provide transparency for the purposes of research integrity, scientific progress, and prevent duplication of unsafe and unsuccessful trials.

Yet here we are, 11 years later, plaintiffs still need to sue to get access to information statutorily-mandated clinical trial information disclosed to the public.

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FDA Takes First Step on Path to Monograph for Antiseptics for Food Handlers

FDA Takes First Step on Path to Monograph for Antiseptics for Food Handlers

By Riëtte van Laack & Deborah L. Livornese

On Dec. 6, FDA announced that it is formally seeking data, comments and information related to the assessment of safety and effectiveness of food handler antiseptic drug products (rubs and washes) for over-the-counter (OTC) use. Although this is a positive development, judging from the questions FDA poses, it is only the first step in what likely will be a long journey.

As detailed in the Federal Register notice, the road to this notice has been long. Since 1994, industry repeatedly has called for regulation of antiseptics for food handlers as a separate category of antiseptics under the monograph.

As readers of this blog know, antiseptic washes and rubs for use by consumers and in health care have been subject to review, and monographs for these products have been finalized. On every occasion, industry has submitted comments requesting that FDA treat food handler products separately. FDA recognizes that a separate category for this type of product is warranted. However, the Agency seems uncertain about a significant number of issues. In the notice, FDA discusses several issues for consideration, including:

  • The broad spectrum of uses. Food handling occurs in commercial settings from farm to table, including where food is grown, harvested, manufactured, packed, held, transported, prepared, served and consumed.
  • The variety of conditions. Not all food handler conditions are the same and they pose different challenges to effectiveness. For example, in some situations, hands are heavily soiled with organic matter such as grease and dirt.
  • The length of contact time. The Model Food Code, which addresses the safety at retail and food service establishments, specifies that a cleaning regime should last at least 20 sec. using a cleaning compound in a hand washing sink. In contrast, in vivo testing for health care antiseptics requires 30 sec. contact.
  • Causes of food borne illnesses include viruses and parasites. In fact, according to the CDC, only 51 percent of foodborne disease outbreaks are ascribed to bacteria. This raises the question whether food handler antiseptics should be tested for effectiveness against viruses and possibly parasites as well. FDA has resisted allowing viral claims for other OTC antiseptics.
  • The potential risk of indirect exposure to antiseptics by consumers due to transfer from the hands from food handlers to food raises questions also.

FDA has established a docket to obtain data, information and comments related to the assessment of the safety and effectiveness of food handler antiseptics. Questions range from determination of eligibility, current conditions of use, and safety and effectiveness criteria and evaluation.

Particularly, the eligibility of active ingredients for the OTC Drug Review may become a hurdle. A product is eligible for the OTC Drug Review if its conditions of use existed in the OTC drug marketplace on or before May 11, 1972, or if drug products with the same conditions of use have been marketed for a material time and extent such that they meet the requirements for eligibility under FDA’s time and extent application (TEA) regulation. FDA indicates that it anticipates that few if any products are eligible based on marketing before May 11, 1972. Thus, evidence of marketing for a material time and extent will be needed. Because no call for data or information about food handler antiseptics then on the market was issued in the 1970s at the inception of the OTC drug review, it may be nearly impossible to identify what products are eligible. Perhaps OTC monograph review will allow FDA and the industry to sidestep this thorny issue.

Comments must be submitted by Feb. 5, 2019.

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The Other Shoe Drops on ev3

The Other Shoe Drops on ev3

By Jennifer M. Thomas & Anne K. Walsh

Hard to believe that just two years ago, ev3, Inc. scored a resounding victory after the First Circuit affirmed the dismissal of a qui tam action against it (we reported it here). This week, DOJ announced that the same company has agreed to a criminal plea on what, at first blush, appears to be the same basic set of facts. The plea includes a misdemeanor count for violation of the Federal Food, Drug, and Cosmetic Act (FDC Act), and payment of $11.9 million in criminal penalties along with a $6 million forfeiture.

The original action involved a qui tam whistleblower who alleged the company was liable under the False Claims Act for misrepresentations it made to FDA when seeking approval of the Onyx liquid embolization device. The government declined to intervene in the case, but the relator pressed his arguments through four amendments to his complaint.

According to the relator, during the approval process for Onyx, ev3 agreed to a very narrow indication for Onyx, and also represented that it would provide significant training to physicians on the proper on-label use of Onyx. Indeed, the approved product labeling restricted its use to “physicians with neurointerventional training and a thorough knowledge of the pathology to be treated, angiographic techniques, and super-selective embolization.” ev3 allegedly also concealed safety issues with the Onyx product from FDA. The relator argued that if FDA had known ev3 had no intention to restrict its marketing to the on-label indication, or adequately train physicians, and if FDA had known about safety issues with the Onyx product, it would not have approved the product (i.e., that the company had fraudulently induced FDA to approve the drug).

The First Circuit rejected the relator’s theory using strong language: “The FDA’s failure actually to withdraw its approval of Onyx in the face of D’Agostino’s allegations precludes D’Agostino from resting his claims on a contention that the FDA’s approval was fraudulently obtained.” In the absence of such official agency action by FDA, the court held that it was impossible to determine that FDA would not have approved the Onyx device without the alleged fraudulent representations. The court also concluded that the relator could not demonstrate materiality where CMS had continued to reimburse for Onyx, stating that “[t]he fact that CMS has not denied reimbursement for Onyx in the wake of D’Agostino’s allegations casts serious doubt on the materiality.”

The December 4 criminal plea, however, demonstrates that the government did take serious issue with ev3’s marketing of its Onyx product, although not necessarily because it evinced the alleged fraud posited by the relator in his FCA claim. The criminal information does not explicitly discuss the company’s communications with FDA during the approval process for the device, but does refer to post-marketing statements by FDA that made clear the company needed additional data to support an expanded indication for Onyx – statements that the company apparently disregarded. Thus, the pleading seems to describe a straightforward off-label promotion violation rather than any “fraudulent inducement” of FDA approval in the first instance.

In sum, while the relator may have “lost,” the government still won. This case showcases the power of the government based on the plethora of statutes at its disposal. It is likely the government saw the flaws in the qui tam case early on (thus choosing to decline the matter) but sought to prosecute the company’s activity and chose the more straightforward FDC Act violation as its tool. Defendants can still appreciate the strong language in the First Circuit opinion, but that may be of little solace to ev3 considering the ultimate end of its story.

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