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 injury 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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You Don’t Have to Be Old to Be Mature – FDA Likes “Mature” Quality Organizations, and Offers Tips

You Don’t Have to Be Old to Be Mature – FDA Likes “Mature” Quality Organizations, and Offers Tips

By Douglas B. Farquhar

At the cGMP conference sponsored by pharmaconference.com earlier this month, FDA’s compliance wing encouraged pharmaceutical companies to ensure that they demonstrate “quality maturity,” and offered specifics about what FDA wants to see.  Like my grandmother used to say this time of year about the best corn to make corn pudding, there is a difference between “old” and “mature.”  You don’t have to be old, to be mature.  The quality organization recipe FDA is promoting applies equally to startups and to established manufacturers and sponsors of medical products.  FDA’s advice on mature quality systems also applies equally to medical device companies and to pharmaceutical companies.

Preliminarily (a word I doubt my grandmother used very often), we should note that FDA’s advice on these points is not incorporated in binding statute or regulations, or even in published guidance documents.  Nonetheless, by following the advice offered by FDA on these issues, regulated industry can more likely avoid adverse findings during regulatory inspections, and find pathways to remediation that FDA will more likely accept, after adverse inspections.

Several FDA speakers at the conference (agenda here) discussed the importance of having mature quality systems, but the most specific advice was offered in a PowerPoint delivered by Theresa Mullin, FDA’s Associate Director for Strategic Initiatives for the Center for Drug Evaluation and Research and entitled “Update from FDA CDER.”

Summarizing the Quality Metrics Research Final Report by the University of St. Gallen in Switzerland, Morrison described the appropriate steps to ensure “quality maturity” as follows (emphasis is added):

  1. Optimized set-up and cleaning procedures are documented as best practice process and rolled out throughout the whole plant.
  2. A large percentage of equipment on the shop floor is currently under statistical process control.
  3. For root cause analysis, the firm has standardized tools to get a deeper understanding of the influencing factors for problems.
  4. Goals and objectives of the manufacturing unit are closely linked and consistent with corporate objectives and the site has a clear focus.
  5. Manufacturers have joint improvement programs with suppliers to increase performance.
  6. All potential bottleneck machines are identified and supplied with additional spare parts.
  7. For product and process transfers between different units or sites, standardized procedures exist that ensure a fast, stable and complied [probably should read “compliant” instead of “complied”] knowledge transfer.
  8. Charts showing the current performance status such as current scrap rates and current up times are posted on the shop floor and visible for everyone.
  9. The firm regularly surveys customers’ requirements.
  10. The firm ranks its suppliers and conducts supplier qualifications and audits.

Critically, a mature quality system should not be stagnant, nor should advice about the maturity of the quality system be considered in isolation.  FDA wants industry to produce and report quality metrics, as discussed in prior blogposts (here, here, and here).  Moreover, FDA encourages industry to aim for continuous improvement in manufacturing, laboratory, and quality systems.

So, back to corn pudding recipes.  What my grandmother meant by “mature” was that corn that had stayed a long time on the stalk might be past its prime, if eaten on the cob, but was the best to use to make corn pudding.  She didn’t recommend corn that had been picked days ago (“old” corn).  As to whether the best corn pudding is made just with eggs, or with eggs and flour, that is a whole ’nother controversy (here).

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Petition to Allow Generic Label Approval for Labels on Products from Exotic Species that Received Voluntary Inspection

Petition to Allow Generic Label Approval for Labels on Products from Exotic Species that Received Voluntary Inspection

By Riëtte van Laack

As we previously reported, in 2013, the Food Safety and Inspection Service (FSIS) of the USDA updated its regulations to expand the type of labels that can be generically approved, i.e., are not subject to FSIS pre-market review and approval.  Under the revised regulations, only labels that include so-called special claims are subject to pre-market review and approval. FSIS took this action in an effort to reduce the time for approval of labels that do not qualify for generic approval and to free up agency resources for more targeted review of materials that are potentially false or misleading.  Unfortunately, the time for label approval has increased again; in June 2019, FSIS reported that it is experiencing a 20+ business delay in label approval.

One of the categories of labels that remain subject to pre-market review are labels for products derived from so-called exotic species, including bison, water buffalo, cattalo, deer, and elk.  Exotic species are not subject to mandatory inspection because they are non-amenable species.  Under 9 C.F.R. Part 352, FSIS provides a voluntary inspection and certification service for wholesomeness relating to the slaughter and processing of exotic animals and the application of a triangular shaped mark of inspection.  Even if the label for a product derived from these exotic species does not contain special claims, the label is subject to premarket review and approval by FSIS.  Compared to companies marketing products from amenable species, the requirement for label review and approval puts companies marketing products derived from exotic species at a significant disadvantage because they will need to wait 3 weeks or more for approval of a “generic” label whereas there is no waiting time for a similar product derived from an amenable species.

Frustrated by the resulting delay in label review and approval, the National Bison Association petitioned FSIS to amend the regulation for generic label approval to allow generically approved labels for product generated at an establishment receiving voluntary inspection under 9 C.F.R. Part 352.  Concerned with the time involved in notice-and-comment rule making, the NBA asks that FSIS amend the regulation via a direct rule without notice and comment.

FSIS’ regulations permit interested persons to submit comments on petitions filed with the Agency within 60 days of the posting date of the petition.  Thus, comments should be submitted by Sept. 30, 2019.

Just recently, the North American Meat Institute (NAMI) submitted comments in support of allowing generic approval for labels for products from exotic species as the “proposed change would benefit all FSIS regulated entities because reducing the number of label submissions for exotic species will likely result in a quicker turnaround generally for labels requiring submission.”  NAMI did not endorse the amendment via a direct rule, however.

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“Wine-ing” about FDA Involvement in Regulating Alcohol Labels

“Wine-ing” about FDA Involvement in Regulating Alcohol Labels

By Anne K. Walsh

This case caught our eye for a few reasons, none of which directly relates to the business activities of most of our blog readers but may relate to their happy-hours activities.  As most know, FDA regulates foods, including beverages, but Congress delegated most of the authority to regulate alcoholic beverages to other federal agencies.  Nevertheless, FDA is more involved than you would think – recent litigation illuminates the close relationship FDA holds with those regulatory agencies.

In a cleverly drafted opinion from Judge Boasberg (D.D.C.), in which the court pours alcohol humor throughout (e.g., “Whichever way the Court tilts the wineglass, Bellion’s vintage is wanting,” “Not so fast, Plaintiffs say – the Court’s methodology is corked.”), the question was whether the plaintiffs could make certain health claims on labels of its vodka products.  Plaintiffs, Bellion Spirits and Chigurupati Technologies, were manufacturers of vodka infused with a proprietary compound called NTX.  Plaintiffs sought to advertise their vodka as having benefits associated with NTX, claiming that NTX could help protect against, or reduce, damage to DNA caused by the alcohol.

The Alcohol and Tobacco Tax and Trade Bureau (TTB), an agency under the Department of Treasury, requires mandatory pre-approval for any health claims made on alcohol beverage labels.  Bellion petitioned TTB for approval of these health claims, and TTB determined that the claims were unsubstantiated and misleading and denied Bellion’s petition.  TTB explained that the claims lacked substantiation and that they were misleading as to the “serious health consequences of both moderate and heavy levels of consumption of alcohol beverages containing NTX.”   The claims also implied that drinking the beverages would reduce the risk of damage to the liver and to the brain.  In short, TTB rejected the idea that NTX-infused vodka was less harmful to a person’s DNA than other vodka.

Bellion submitted to TTB several animal and in vitro studies purportedly supporting the health claims.  TTB, in turn, forwarded the full petition along with these studies to FDA for its scientific and medical review of whether the data provided adequate substantiation for the proposed claims.  Bellion sued TTB, claiming the government had overstepped its authority by involving FDA in its review of the claims and arguing the restrictions infringed on Bellion’s First and Fifth Amendment rights. The court patiently addressed each of Bellion’s constitutional and APA arguments, which are far too detailed for this blog post, and affirmed TTB’s conclusion that any claims about salutary health effects are misleading, and thus not subject to First Amendment protection.

It may not ever be clear without a FOIA request or congressional inquiry how often FDA is consulted by TTB for its scientific expertise.  In this case, FDA’s involvement was significant: FDA reviewed the scientific and medical evidence submitted by Bellion, which included 112 articles or studies; and assessed whether the data adequately substantiated the proposed claims.  FDA and TTB took over a year to respond to plaintiffs’ petition.  It would be interesting how many competing priorities of FDA were deprioritized or postponed for this project.

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First Warning Letter for Failure to Develop Foreign Supplier Verification Program

First Warning Letter for Failure to Develop Foreign Supplier Verification Program

By Riëtte van Laack

On August 13, 2019, FDA announced that it has issued the first Warning Letter (WL) for a violation of the requirements for a Foreign Supplier Verification Program (FSVP).  This is a good reminder for importers that they must have a FSVP for each food for which they are the FSVP importer.

The Food Safety Modernization Act (FSMA) provided FDA with a new tool to enhance FDA’s oversight of foreign food facilities and farms.  Under the FSVP requirements, a U.S.-based FSVP importer must conduct a range of activities to ensure that food from foreign suppliers is produced in compliance with applicable U.S. food safety provisions.  The first FSVP compliance date was May 30, 2017.   By now, most importers of human foods are past the compliance date and all FSVP importers of food, unless exempted, must have developed a FSVP.

The FSVP regulations for the first time assigned importers of food (including dietary supplements) the responsibility to ensure that the products they bring into the United States are held to the same safety standards as domestically produced food.  FDA recognized that this was a new concept to a lot of importers which previously may not have had any dealings with FDA.  FDA indicated that it would apply the same approach as it had done previously with the introduction of other new FSMA regulations, i.e., educate while regulating to create a culture of compliance but take swift action when it becomes aware of food safety problems that pose an imminent public health risk.

The first WL concerning the FSVP was issued to Brodt Zenatti Holdings LLC in Jupiter, Florida.  The Company imported tahini which, in May 2019, had been implicated in a Salmonella outbreak.  After identifying the importer, FDA conducted an FSVP inspection.  According to the WL, FDA found that the importer did not develop an FSVP for the imported tahini as required.  As with everything imported, the consequences of a violation of the applicable regulations may have serious consequences.  As mentioned in the WL, if it fails to take the appropriate corrective actions, FDA may place the Company on the newly created import alert 99-41 resulting in all foods that the Company imports being detained without physical examination.  (The tahini contaminated with Salmonella already is subject to DWPE under import alert 99-19).

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HP&M is Pleased to Welcome Suchira Ghosh to the Firm

HP&M is Pleased to Welcome Suchira Ghosh to the Firm

Hyman, Phelps & McNamara P.C. (“HP&M”) is pleased to announce that Suchira Ghosh has joined the firm as Counsel.  Suchira comes to HP&M with more than 10 years of FDA and Hatch-Waxman legal experience, as well as several years of experience working as a process engineer in R&D at a global pharmaceutical company.  Most recently Suchira was Counsel at Axinn LLP where she helped develop the firm’s FDA practice and worked as a patent litigator.

As part of the Hatch-Waxman practice at HP&M, Suchira will continue to provide counseling and litigation services to pharmaceutical companies on the Hatch-Waxman Act, the BPCIA, and the Orphan Drug Act.  Suchira has extensive experience with coordinating IP and regulatory strategy for her clients, including advising them on exclusivity, forfeiture, and labeling issues.  She also counsels drug sponsors on approval requirements, lifecycle strategies, post-marketing requirements, and REMS issues, and frequently represents clients before FDA via citizen petitions, formal dispute resolution, and comments to rulemaking and guidance.  In addition to her work with drug sponsors, Suchira provides regulatory counseling to medical device and HCT/P manufacturers.

Suchira has been recognized as a “Rising Star” in Life Sciences, and she frequently presents and comments on emerging issues in FDA law.  She graduated from the University of Michigan Law School and received her B.S. in Chemical Engineering from Columbia University.  Prior to law school, she worked at Schering-Plough where she was responsible for developing and scaling up the manufacturing processes for new sterile drugs.

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Note to Pharma: Stop With the Dancing! (And Get Off My Lawn)

Note to Pharma: Stop With the Dancing! (And Get Off My Lawn)

By Dara Katcher Levy

After reading OPDP’s latest enforcement letter, we had déjà vu all over again and were transported back to 2016 when we blogged that OPDP was Not Dead Yet.  At that time, OPDP had posted two enforcement letters on the same day relating to TV ads and alleging misleading risk presentations.  Both letters cited to individuals dancing during the major statement.  Fast forward almost 3 years and OPDP’s fourth letter of 2019 asserts the following:

Additionally, the presentation of certain risk information in the “major statement” of risks through audio and SUPERs is undermined by the simultaneous presentation of fast-paced visuals that feature choreographed dancing to instrumental background music and multiple scene changes. . .  As a result, it is difficult for consumers to adequately process and comprehend the risk information, resulting in a misleading impression of the drug’s risks.

The language is almost identical to the language used in one of OPDP’s 2016 Letters:

The TV ad communicates the “major statement” of serious risks through the audio and onscreen SUPERS. At the same time, the TV ad presents fast-paced visuals that feature a man continuously dancing to music from the song “Let’s Groove” throughout multiple scene changes . . .   As a result, it is difficult for consumers to adequately process and comprehend the risk information. The overall effect undermines the communication of the important risk information and thereby misleadingly minimizes the risks associated with the use of Toujeo.

Putting OPDP’s apparent disdain for dancing aside, allegations of misleading risk presentations in TV ads due to distractions are not new.   It is consistent with previous enforcement letters (see, e.g., here) as well as FDA research on consumer comprehension of risk.   And, in fairness, OPDP’s latest letter did not simply allege that dancing was the issue – OPDP cited omissions and other mechanisms for minimizing risk in this 30 second commercial.

So, what are the key takeaways here (the tl; dr if you will): The subject of OPDP’s latest letter ticks off at least two boxes from previously stated enforcement priorities – the ad was a far-reaching campaign (DTC TV) and was the subject of a complaint (brought to FDA’s attention through the “Bad Ad” program).  Other enforcement priorities for OPDP are drugs new to the market; drugs that have serious risks; and drugs cited for past violations.

One need only look at OPDP’s research page to see the emphasis put on consumer comprehension and understand that DTC is a high enforcement priority.  Given the number of studies specific to TV ads, industry should holistically consider visuals, audio and timing (both overall length of the commercial as well as narration cadence) and how these play into consumer comprehension.

And then there’s another key takeaway – don’t include dancing in TV ads for drugs.  While not a specifically stated enforcement priority, it doesn’t seem to go well.

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Is Promoting a 361 HCT/P for Its Clinical Effects Compatible with a Homologous Intended Use?

Is Promoting a 361 HCT/P for Its Clinical Effects Compatible with a Homologous Intended Use?

By Jeffrey K. Shapiro

The Food and Drug Administration (FDA) regulates human cell, tissue, and cellular and tissue-based products, or HCT/Ps, under a unique regulatory regime set forth in 21 C.F.R. Part 1271 (Part 1271).   An HCT/P that meets certain requirements is eligible for regulation as a “361 HCT/P.”  This term is a shorthand way to designate a product that is regulated solely under section 361 of the Public Health Service Act (PHSA) and Part 1271, both of which are aimed at preventing the transmission of communicable disease.  Such a product is not subject to additional regulation by FDA as a device, drug, or biologic under the Food, Drug, and Cosmetic Act (FDCA).

This discussion will focus on the requirement that a 361 HCT/P be labeled and advertised only for homologous use.  We will look first at the basic regulatory definition and guidance.  Then, we will ask the specific question of whether advertising the clinical effects (performance characteristics) of an HCT/P 361 is compatible with meeting the homologous use requirement.

Homologous Use

The regulation defines homologous use to mean “the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor.”  In determining whether a product is “intended” for homologous use, FDA considers only “the labeling, advertising, or other indications of the manufacturer’s objective intent.”  21 C.F.R. § 1271.10(a)(2).

In the preamble to the regulation, FDA clarified that homologous use does not require use of tissue in its native anatomic location:  “a use of a structural tissue may be homologous even when it does not occur in the same location as it occurred in the donor.  For example, the use of bone for repair, replacement, or reconstruction anywhere in the skeleton of the recipient (including the vertebral column) would be considered homologous use.”  66 Fed. Reg. 5447, 5457 (Jan. 19, 2001).

In addition, as a general matter, FDA indicated that the homologous use test merely would be a coarse screen for unproven uses:  “We intend to interpret ‘nonhomologous’ narrowly. Examples of uses that would be considered nonhomologous include:  The use of dermis as a replacement for dura mater . . .  and the use of cartilage in the bladder.”  Id.   And:  “For example, promotion of an HCT/P for an unproven therapeutic use, such as curing cancer, would clearly make it inappropriate to regulate the HCT/P [as a 361 HCT/P].”  Id.  Instead, an HCT/P intended for an unproven therapeutic use would be regulated under both Part 1271 (to prevent disease transmission) and the Federal Food, Drug, and Cosmetic Act as a drug, device or biologic.  These preamble statements are legally entitled to great weight in interpreting and applying the regulation.

In a recent guidance, FDA elaborated on the concept of the “same basic function or functions” of an HCT/P:

The basic function of an HCT/P is what it does from a biological/physiological point of view, or is capable of doing when in its native state.  By “basic” we mean the function or functions that are commonly attributed to the HCT/P as it exists in the donor.  Basic functions are well understood; it should not be necessary to perform laboratory, pre-clinical, or clinical studies to demonstrate a basic function or functions for the purpose of applying the HCT/P regulatory framework.

FDA, Guidance for Industry, Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use, 16 (Dec. 2017) (footnotes omitted) (2017 Guidance).

FDA adds:  “Also, clinical effects of the HCT/P in the recipient that are not basic function or functions of the HCT/P in the donor would generally not be considered basic function or functions of the HCT/P for the purpose of applying the definition of homologous use.”  Id. at 16‑17.

As an example, FDA cites different uses of amniotic membrane.  The basic functions of amniotic membrane “include serving as a selective barrier for the movement of nutrients between the external and in utero environment, protecting the fetus from the surrounding maternal environment, and serving as a covering to enclose the fetus and retain fluid in utero.”  Id. at 18.  Accordingly, FDA concludes that when “an amniotic membrane product is used for wound healing and/or to reduce scarring and inflammation,” this intended use “is not homologous use because wound healing and reduction of scarring and inflammation are not basic functions of amniotic membrane.”  Id. at 18.  In contrast, amniotic fluid as a covering is homologous.  For instance:

amniotic membrane product is applied to the surface of the eye to cover or offer protection from the surrounding environment in ocular repair and reconstruction procedures.  This is homologous use because serving as a covering and offering protection from the surrounding environment are basic functions of amniotic membrane.  [Id.]

Clinical Effects

This sounds like a fair distinction – an amniotic membrane intended as a wound cover in the recipient is essentially performing its native covering function.  On the other hand, the same amniotic membrane when “intended” to reduce scarring or inflammation is likely not performing the same function as it did in utero.

But what exactly does it mean for the amniotic membrane to be “intended” to reduce scarring or inflammation?  Is it not possible for an amniotic membrane to be intended as wound cover (a homologous use) and, as such, have the clinical effect of reducing scarring and inflammation compared to other wound covers?

There are at least two ways one could establish this proposition.  One way is to claim that the biological/physiological composition of amniotic tissue (e.g., presence of cytokines) is such that it is likely to have anti‑scarring and anti‑inflammatory effects in a skin wound.  This approach may be what FDA implicitly meant to convey in the example above.  It is not homologous because, says FDA, preventing scars or inflammation is not a well understood biological/physiological function of native amniotic membrane.  On this view, it is an unproven functional claim.

A second way to establish the proposition is to conduct a well‑controlled randomized clinical trial to substantiate it.  Imagine a clinical trial showing that an amniotic membrane used as a skin wound cover provides a 10% statistically significant reduction in scarring as compared to a synthetic wound cover.

The question is whether presenting this study in labeling or advertising would generate a new, non‑homologous “intended use.”  This question has important ramifications.  Increasingly, manufacturers seek to study 361 HCT/Ps and quantify their clinical effects.  These studies help advance the science of medicine and benefit patients.  Such studies, however, may never be undertaken if the results cannot be disseminated without exposing a 361 HCT/P to regulation as a drug, device or biologic under the FDCA or PHSA.

As discussed above, the concept of homologous use does not derive from the treatment intent of an HCT/P.  Rather, it is based upon the biological or physiological functioning of an HCT/P.  For instance, if an HCT/P is being used to perform a covering function, the definition of homologous use is satisfied, regardless of where the covering is applied.  That is why FDA agrees that homologous use is not dependent upon an HCT/P being used in the same location as the native tissue.  It also why FDA correctly asserts (as quoted above) that clinical effects in a recipient are not to be considered in determining homologous use.

This principle logically cut both ways.  If clinical effects in the recipient cannot contribute to a determination that an intended use is homologous, then providing information about such clinical effects cannot contribute to a determination that an intended use is non‑homologous.  The homologous use test is not a general inquiry into the objectively intended therapeutic effects of an HCT/P.  Rather, it is a limited inquiry into the biological or physiological functioning that is objectively claimed for the HCT/P.  If this limited intent meets the requirement of homologous use, the inquiry should be over.  Claims as to clinical effects, of course, require adequate substantiation and must be presented in a truthful and non‑misleading manner.  But they are not properly part of a homologous use analysis.

To return to the amniotic membrane example, a white paper describing the results of a study comparing the two types of wound coverings (amniotic membrane and synthetic) is not relevant to whether the amniotic membrane covering is intended for homologous use.  That is because the study results are based upon observed clinical effects in the recipient; they do not address the putative biological or physiological function involved, which is the basis of a homologous intended use determination.  On the other hand, if the white paper also discusses the role of native cytokines in the amniotic membrane in inhibiting scar formation as an explanation for the study results, that would properly be considered in determining whether the intended use is homologous.  If FDA finds that native cytokines in the donor are not commonly understand to prevent scarring, then it could find that the amniotic membrane has a non‑homologous intended use.

None of this is to say that FDA has accepted this approach.  Frankly, the discussion around homologous use has not proceeded in these terms.  Yet, the framing here seems implicit in the logic of FDA’s regulatory definitions and guidance.  It would certainly be helpful to have more explicit guidance from FDA, because this confusion around homologous use may inhibit sponsors from initiating valuable clinical studies of 361 HCT/Ps.  Any clarity FDA could provide around its position on this issue would be very welcome.

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CMS Proposes Regulations to Expand Sunshine Reporting

CMS Proposes Regulations to Expand Sunshine Reporting

By Alan M. Kirschenbaum

Among the provisions contained in CMS’ proposed Physician Fee Schedule revisions for 2020, which appeared in today’s Federal Register, were proposed changes to the Open Payments program (sometimes called the Physician Payment Sunshine Law).  See 84 Fed. Reg. 40482, 40713-16 (Aug. 14, 2019).  Some of the proposals implement an expansion of the Open Payments program enacted in October 2018 as part of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act), which we reported on here.  CMS proposes additional changes as well.  Here are the highlights:

  • New covered recipients: To implement the SUPPORT Act amendments, CMS proposes to add to the current covered recipients (physicians and teaching hospitals) the following new covered recipients (with a definition for each):  physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives.
  • New “nature of payment” categories: Three new types of payment categories are proposed to be added:  (1) debt forgiveness; (2) long-term loans of covered devices or medical supplies (as distinct from the current category of short-term loans of 90 days or less); and (3) acquisitions, comprising buyout payments to covered recipients in an acquisition of a company in which a covered recipient has an ownership interest.
  • DIs for devices: Currently, applicable manufacturers are not required to report device identifiers (DIs) or other numerical identifiers of specific devices to which a payment or other transfer of value relates.  CMS now proposes that the DI of a device, if any, must be reported.  See 21 C.F.R. § 801.20 et seq. (FDA requirements for unique device identifiers).
  • Consolidation of continuing education program nature of payment categories: There are currently two nature of payment categories for direct compensation for serving as faculty or speaker – one for accredited/certified medical education programs and another for unaccredited/noncertified programs.  These would be consolidated into one category for medical education programs generally.

The new requirements would go into effect for payments and other transfers of value made in CY 2021, which will be reported in March 2022.  Comments on the proposed changes will be accepted until September 27, 2019.

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Illinois Law Requiring Sesame Labeling to Spark a National Trend?

Illinois Law Requiring Sesame Labeling to Spark a National Trend?

By Riëtte van Laack

The Food Allergen Labeling Consumer Protection Act (FACLPA) amended the FDC Act to require that foods containing a “major food allergen,” defined as milk, eggs, fish, shellfish, tree nuts, peanuts, wheat, and soybeans, must declare the food source of the allergen using its common or usual name on food labels.  There appears to be increasing evidence that sesame allergies may be a growing concern.  In fact, a recent study published in JAMA Network Open suggests that more American children and adults have an allergy to sesame than previously thought.  Based on results of a survey, investigators concluded that more than 1.5 million children and adults in the United States (i.e., 0.49% of the population) report a current sesame allergy.

As a result of the growing concern regarding sesame as a food allergen, there have been several calls for action by FDA to require disclosure when sesame is present in a food.  Last year, FDA issued a request for information “to learn more about the prevalence and severity of sesame allergies in the US.”  Comments were due December 31, 2018. (More than 4800 comments were submitted to the docket).  However, FDA has yet to take further action and, based on the most recent semi-annual agenda, FDA does not have any immediate plans to develop a regulation.

Seemingly tired of waiting, the State of Illinois amended its state Food, Drug and Cosmetic Act to include a provision that a packaged food not for immediate consumption is misbranded if it contains sesame, unless the food bears labeling stating that fact.  Apparently, the hope is that this state requirement will “spark a national trend.”  However, in light of the FALCPA preempting state laws (meaning that state governmental agencies may not adopt labeling requirements that differ from the federal requirements), the validity of the Illinois law is open to question.  Thus, the law might prove to have little effect, other than drawing renewed attention to the issue of sesame allergies.

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Dust Yourself Off and Try Again: GAO Report On ANDA Approval Shows that Multiple Review Cycles Are Still Often Necessary

Dust Yourself Off and Try Again: GAO Report On ANDA Approval Shows that Multiple Review Cycles Are Still Often Necessary

By Sara W. Koblitz

Over the last few years, FDA has clearly prioritized efficient generic development (see, for example, the Drug Competition Action Plan).  While FDA hosted public meetings, published MAPP revisions, and compiled lists of off-patent/off-exclusivity drugs, Congress reauthorized the Generic Drug User Fee Act in 2017 and included a provision requiring GAO to study issues regarding approval of a generic drug applications in the first review cycle.  Further, as part of GDUFA II, FDA committed make changes in an effort to minimize the number of review cycles necessary for applicants to attain approval.    This month, the GAO released its report commenting on both the first review cycle statistics and FDA’s efforts to minimize review cycles thus far.

The GAO Report looked at generic drug approvals between FY 2015 and 2017 – before implementation of the GDUFA II commitments – as well as documentation from the first review cycle for 35 applications from FY 2017 and 2018.  GAO identified several factors that may impact approval in the first cycle, including the sufficiency of the application, deficiencies in drug quality, the type of drug reviewed, and the application’s priority status.  Ultimately, GAO made two recommendations: FDA should improve consistency in communication between reviewers and sponsors, and FDA should assess the effect of brand-name labeling changes on approval of generic drugs.

Given the timeframe of the approvals reviewed, the Report tells us little about FDA’s success in achieving its GDUFA II commitment with respect to first cycle reviews.  The Report also relies on a small sample size of detailed application review (35) and interviewees (15).  But the Report is nonetheless enlightening.  Notably, of the 2030 generic drug applications reviewed by FDA from FY 2015 through 2017, only 12 percent (or approximately 244) applications were approved in a first review cycle.  That means that 1786 ANDAs went through subsequent review cycles to obtain approval, potentially delaying approval for years.  On average, from 2013 through 2017, it took three review cycles for ANDAs to attain approval.

Some of the GAO’s findings were neither surprising nor attributable to FDA:  some applications, particularly those of unsophisticated sponsors, simply were not sufficient.  Either the application was not complete or the applicants did not fully understand and fulfill application requirements, directly impacting the likelihood of receiving approval during the first review cycle.  Applications that FDA initially Refused to Receive were slightly less likely to be approved in the first review cycle.  All of this makes sense if one assumes that the RTRs and insufficient applications were filed by relatively inexperienced filers.  An inexperienced filer is more likely to get tripped up than a sponsor that has been through the process before.  Additionally, drug complexity factored into likelihood of approval during the review cycle.  Again, this makes sense: route of administration, formulation, combination drugs, complex APIs, and like factors impact the sufficiency and complexity of the data needed for approval.   Drug quality deficiencies, like the drug manufacturing facilities, were also responsible for large share of failure to attain approval during the first review cycle.

Interestingly, the GAO also noted that the type of Priority Review designation a product receives may be correlated with first cycle failures.  According to the GAO analysis, rates of approval in the first cycle were lower for first generics than for applications with no priority designation.  Meanwhile, first-cycle approval rates for other types of priority designations (i.e. drug shortages or public health emergencies) were higher than for applications with no priority designation.  The GAO report hypothesized that rushing to submit applications to get first generic status may result in lower quality applications.

The Report does highlight some of the changes that FDA has adopted since 2013 to enhance communication with applicants and improve reviewer consistency.  FDA has issued 993 new and revised product-specific guidance documents since 2013, in addition to other regulatory guidance to facilitate approval and reduce deficiencies.  378 of the product-specific guidances have been focused on complex drugs.  At the GAO’s suggestion, FDA now publicly announces its plans for issuing new and revised product-specific guidances.  Additionally, FDA now encourages reviewers to communicate with applicants about issues and issue discipline review letters at the mid-point of the review cycle rather than at the end of the cycle to provide applicants with an opportunity to address issues before issuing a Complete Response Letter.  FDA has also taken steps to enhance consistency from FDA reviewers, including review templates and adopting common phrases for communicating deficiencies.

The GAO Report notes that, even with FDA’s enhancements, inconsistency among generic drug application reviewers persists.  These inconsistencies may play a big role in approval during the first review cycle because reviewers may provide substantively different assessments of similar generic applications.  Some reviewers provide suggestions on how to remedy a deficiency while others do not even specify what further information may be required.  This inconsistency could mean the difference between addressing deficiencies in a timely manner during the first review cycle and a Complete Response Letter.  As such, inconsistency in reviewer communication is a major focus of the GAO’s recommendations to FDA.

Further, based on interviews, the Report posits that brand-name drug labeling changes occurring mid-cycle may impact first review cycle approvals.  Because the generic sponsor must change the labeling to match the Reference Listed Drug, such a change midway through the review cycle may require the ANDA sponsor to revise its labeling.  FDA thought that gamesmanship in labeling changes to delay generic competition would be challenging to coordinate but acknowledged that such a scenario was a possibility.  However, because the Office of Generic Drugs does not coordinate on timing of approval of brand-name drug label changes with the Office of New Drugs, the Agency could not speak to this directly.  As such, GAO recommended that FDA assess the extent to which brand-name label changes impact first review cycle approval of generic drugs.

On the whole, the Report was not too critical of FDA considering the statistics.  With a paltry 12 percent of ANDAs approved in the first review cycle, one would think that GAO would have a myriad of recommendations.  But it didn’t, which may indicate that FDA’s changes are helping ANDA review trend in the right direction.  But for now, as FDA further implements these changes to meets its GDUFA II goals, those ANDA sponsors who don’t attain that elusive first review cycle approval must continue to try.  In the words of the late Aaliyah: If at first you don’t succeed (first you don’t succeed), dust yourself off, and try again.

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