Tag: prescription drugs

Physicians Face Regulatory Exposure for Prescribing COVID-19 Drugs Cited by President Trump

Physicians and medical professionals throughout the world are facing and attempting to treat one of the most serious and deadly viruses that has affected the world in our lifetime. Medical professionals are on the front lines and in a position, despite their best efforts to protect themselves, to contract the disease. Medical professionals do not only fear for their own lives but also for the lives of their family members if they unintentionally bring this disease home.

In light of safety concerns for their family members, over the past few weeks, there have been reports claiming physicians throughout Ohio have prescribed chloroquine and hydroxychloroquine, frequently cited by President Donald Trump, to family members and friends. In some reported instances, prescriptions were issued even when such individuals did not exhibit signs or symptoms of the coronavirus.

In order to preserve the stockpile of medications for patients, on March 22, 2020, the Ohio Board of Pharmacy issued an emergency rule (OAC 4729-5-30.2) that prohibits a pharmacist from filling prescriptions for chloroquine or hydroxychloroquine without a valid COVID-19 diagnosis and positive test result.

On March 30, 2020, the Ohio Attorney General’s Office issued the following statement, which highlighted the Pharmacy Board’s new emergency rule and advised physicians to self-report to the State Medical Board of Ohio if they prescribed these medications improperly:

“It has come to my attention that physicians may be abusing their privilege to prescribe medications by writing prescriptions for chloroquine and hydroxychloroquine for themselves, their friends and their families without any legitimate medical need for the medication. As Attorney General, I am very concerned with these reports and will work vigorously with Ohio’s regulatory boards and agencies to address any illegal or prohibited conduct. I encourage anyone who has written a prescription of this type improperly to self-report to their respective regulatory authority.”

The State Medical Board of Ohio is also on record stating that it takes allegations of inappropriate prescribing very seriously, and that it will be actively investigating complaints as they come in and working with the Ohio Attorney General on any necessary enforcement actions for bad prescribing.[i]

In addition to state regulators, the U.S. Attorney’s Office for the Northern and Southern Districts of Ohio have set up a COVID-19 Task Force. One of its responsibilities is to investigate and criminally prosecute physicians who have egregiously prescribed chloroquine and hydroxychloroquine to themselves, family members, or friends without a legitimate medical purpose. The Task Force is comprised of representatives of the United States Attorney’s Office, Ohio Attorney General’s Office, State Medical Board, and the Pharmacy Board.[ii]

Physicians who recently prescribed chloroquine and hydroxychloroquine and who are considering whether they should self-report to the Medical Board should first contact experienced legal counsel to determine the implications of a possible self-report, including the potentiality of license discipline and/or criminal charges.

[i] See:  https://clt945532.bmeurl.co/A27E486

[ii] See: https://www.dispatch.com/news/20200324/feds-yost-will-prosecute-doctors-who-abuse-power-with-personal-coronavirus-prescriptions

© 2020 Dinsmore & Shohl LLP. All rights reserved.

For more COVID-19 developments, see the dedicated National Law Review Coronavirus News page.

COVID-19 Update: Patent Rights in the COVID-19 Pandemic: How will Industries and Governments Respond?

As the world scrambles to address an ever-expanding wave of COVID-19 infections, new and urgent needs for medical supplies, diagnostics and treatments arise.  Shortages of such supplies are plaguing hospitals and care-givers, while doctors and nurses put their lives at risk in their desperate efforts to save COVID-19 patients.  Many of these vital supplies, however, are protected by valuable patent rights.  The essence behind patents rights is to exclude others from making, using, or selling a patented invention, except by authorization of the patent holder in carefully negotiated license agreements to ensure proper compensation for the efforts and costs invested in developing the patented invention.1  On the other hand, the U.S. government has rights to forcibly license a patented invention during times of need, in particular when there is a threat to public safety.2  Will the government resort to use of these available, yet rarely used, compulsory licensing provisions?  How patent owners are responding to the current COVID-19 pandemic is revealing that benevolence may, in some cases, have a place in commercial business without the government needing to exercise its compulsory licensing rights.

In the face of the COVID-19 pandemic, several large companies have come forward with offers to manufacture medical supplies such as masks and respirators.  Manufacturers, such as the auto makers General Motors, Ford and Tesla, are offering to repurpose production lines to help manufacture and increase the supply of ventilators and other much needed medical equipment.3  Fashion and cosmetic companies, such as Louis Vuitton, L’Oréal and Coty, are also pitching in and offering to re-allocate their resources to produce hand sanitizers, while fashion designers, like Christian Siriano and Brandon Maxwell, are offering to mobilize their teams to produce masks and hospital gowns.4  Even the beer company giant, ABInBev will use its facilities to manufacture and distribute hand sanitizer.5

On the patent front, the drug manufacturer AbbVie has taken a bold public health stance by suspending enforcement of its global patent rights on all formulations of the HIV medication, Kaletra (Aluvia) while the drug is being evaluated as a candidate to treat COVID-19 in several clinical trials.  AbbVie’s bold stance would allow generic versions of Kaletra to be made by others without fear of repercussion based on patent infringement.  This would allow countries to purchase generic versions of Kaletra, if it is found effective in treating COVID-19, and would help alleviate possible drug supply shortages.  AbbVie is the first drug-maker to take such a strong public health stance amid the COVID-19 pandemic.  However, whether AbbVie’s decision to suspend its patent rights to Kaletra is an act of pure benevolence, mounting public pressures, or because at least one clinical trial  already suggested Kaletra may not be effective in treating COVID-19, AbbVie’s strong public health stance is at the very least a comforting thought and may hopefully sway other drug-makers, like Gilead Sciences Inc. (“Gilead”), to do the same.

On the other end is the drug-maker Gilead who recently halted emergency access to its COVID-19 candidate drug, Remdesivir, except for pregnant women and children with severe symptoms.6  In suspending access to Remdesivir, Gilead issued a company statement7 on March 22, 2020 citing “overwhelming demand” and “exponential increase” in requests which “flooded [its] emergency treatment access system.”  However, Gilead’s restrictions to Remdesivir come on the heels of it being granted “orphan” drug status8 by the U.S. Food and Drug Administration (“FDA”) on February 23, 2020 and on the heels of a Chinese drug-maker, BrightGene Bio-Medical Technology (“BrightGene”),9 filing for patent protection in China for a combination drug therapy to treat COVID-19 using the active ingredients of Remdesivir.  The 1983 Orphan Drug Act10 allows a seven-year market exclusivity period for pharmaceutical companies developing treatments for a “rare disease” and also provides tax credits.  Gilead’s strategic move to obtain orphan drug status for Remdesivir blocks generic drug manufacturers from supplying the drug and thus further limiting access.

Remdesivir has been previously used to treat the Ebola virus, Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), but these infections did not cause a sustained global crisis to earn Gilead a sizable or continued financial revenue stream and other more successful experimental therapies existed.11  If Remdesivir is found to be effective for combating COVID-19, a patent protecting such a use may stand to earn a high and continued stream of global revenue for the patent owner.  As new combination drug patents or method patents for new uses of known drugs may be separately patentable, repurposing Remdesivir as a combination drug patent or for treating COVID-19 may prove to be a blockbuster hit for its patent owner.  Thus, while Gilead has cited overwhelming demand as the reason to restrict access to Remdesivir, one can’t help but wonder whether patent rights and the associated commercial revenue are Gilead’s underlying concern.

Gilead is not the only patent holder invoking a protectionist stance and seemingly attempting to profit from the global pandemic through the patent system’s exclusionary principle.  Labrador Diagnostics LLC (“Labrador”)—a company backed by its major investor SoftBank and who bought patents from a failed blood-testing start-up called Theranos—recently filed a patent infringement lawsuit against BioFire Diagnostics (“BioFire”), a health start-up who launched three COVID-19 tests.12  Labrador also requested an injunction demanding BioFire to stop using the technology covered by the Theranos patents.13  However, since filing the lawsuit and seemingly after public backlash, Labrador issued a press release14 stating it would allow third parties to use its Theranos patents to develop COVID-19 tests with a royalty-free license, but that it is continuing its lawsuit against BioFire for activities over the past six years not related to COVID-19 testing.

Similarly, in Italy, a patent holder of a special respirator valve used in respiratory machines allegedly threatened a patent infringement lawsuit against two engineers who volunteered to use their 3-D printing technology to manufacture the patented valves for a hospital in Brescia, Italy without obtaining permission or a license from the patent holder.15  However, in a follow-up statement, both the patent holder and the two engineers stopped short of calling the communications a threat, and instead characterized them as merely a refusal of the patent holder to assist or collaborate with the engineers.16

While some patent owners are choosing to suspend their global patent rights and others are taking a more protectionist stance, the U.S. government also has the right to take action by forcing patent owners to grant compulsory licenses when there is a threat to public safety.  A compulsory license refers to the government’s authority to grant permission to a party seeking use of another’s patented invention without the consent of the patent owner, and is provided broadly by 28 U.S.C. § 1498.  Several multilateral international agreements also address compulsory patent licenses.17  Other U.S. laws also allow for compulsory licenses in certain circumstances.  For example, march-in rights is a provision of the Bayh-Dole Act of 1980 and is codified in 35 U.S.C. § 203.  March-in rights allow the federal government the right to grant patent licenses to other parties or take licenses for themselves if the patented invention was researched and developed with the help of federally funded dollars.18

March-in rights may be a perfectly poised vehicle for increasing access to COVID-19 related therapeutic drugs and vaccines.  To fight the global pandemic, the Biomedical Advanced Research and Development Authority (“BARDA”), a division of the U.S. Department of Health and Human Services (“HHS”), has partnered with several drug manufacturers, including Johnson & Johnson, Sanofi and Regeneron Pharmaceuticals, to fund the development of treatments and vaccines for COVID-19.19  However, some members of Congress have expressed concern as to the affordability and access should such drugs be found safe and effective, especially since federal funds are being provided.

No U.S. federal agency has ever exercised its power to march-in and license patent rights to others.  For example, advocacy groups have long petitioned the National Institute of Health (“NIH”) to exercise march-in rights for HIV/AIDS related drugs, but have been rejected by the NIH contending that high drug prices are an insufficient reason to break a patent.  However, in the face of a global pandemic, “health or safety needs” may provide a strong basis for the exercise of march-in rights and grant of a compulsory license if more patent owners, like Gilead, take a protectionist patent stance.  On the other hand, if more companies like AbbVie take a more socially conscious approach, there may not be need for government intervention in terms of compulsory patent licenses.  Nevertheless, the availability of this measure may at least provide some comfort and may motivate companies to voluntary suspend their patent rights during this global public health emergency in order to avoid government march-in, or maybe as a pure act of benevolence showing that social responsibility has a place in commercial business.

1   See 35 U.S.C. § § 154, 271.

2   See, e.g., 28 U.S.C. § 1498(a), 35 U.S.C. § 203.

3   See https://www.usatoday.com/story/money/cars/2020/03/22/coronavirus-ventilator-shortage-gm-tesla-covid-19/2895190001/.

4   See https://wwd.com/fashion-news/fashion-scoops/fashion-designers-make-masks-hospital-gown-hand-sanitizer-to-fight-coronavirus-1203545006/.

5   See http://longisland.news12.com/story/41926769/anheuserbusch-to-make-hand-sanitizer-in-response-to-coronavirus-pandemic.

6   See Id.

7  https://www.gilead.com/purpose/advancing-global-health/covid-19/emergency-access-to-remdesivir-outside-of-clinical-trials.

8   See https://www.ibtimes.com/coronavirus-treatment-gileads-potential-covid-19-treatment-labeled-orphan-drug-could-2945353.

9   See https://time.com/5782633/covid-19-drug-remdesivir-china/.

10 Orphan Drug Act of 1983. Pub L. No. 97–414, 96 Stat. 2049.

11 See https://www.statnews.com/2020/03/16/remdesivir-surges-ahead-against-coronavirus/.

12 See https://www.theverge.com/2020/3/18/21185006/softbank-theranos-coronavirus-covid-lawsuit-patent-testing; see also, https://www.businessinsider.com/theranos-patents-fortress-labrador-diagnostics-lawsuit-biofire-coronavirus-tests-2020-3.

13 See Id.

14 See https://www.businesswire.com/news/home/20200316005955/en/.

15 See https://www.law360.com/articles/1255547/3d-printing-as-indirect-patent-infringement-amid-covid-19.

16 See https://www.theverge.com/2020/3/17/21184308/coronavirus-italy-medical-3d-print-valves-treatments.

17 See Convention of Paris for the Protection of Industrial Property, 13 I.S.T. 25 (1962), Art. 5(A)(2) (“Paris Convention”); See Agreement on Trade-Related Aspects of Intellectual Property Rights, April 15, 1994, Art. 31. (“TRIPS Agreement”).

18 See 35 U.S.C. § 203.

19 See https://crsreports.congress.gov/product/pdf/LSB/LSB10422.

© Copyright 2020 Cadwalader, Wickersham & Taft LLP

Compliance Risk Alert: Opioid Warning Letters issued by the U.S. Department of Justice Target Prescribers

U.S. Attorney’s Offices (“USAOs”) across the country are issuing warning letters to physicians and other prescribers (collectively, “Prescribers”) cautioning them about their opioid prescribing practices (the “Warning Letters”). In just the last week, the USAO for the Eastern District of Wisconsin sent warning letters to over 180 prescribers identified by Drug Enforcement Administration (“DEA”) data as prescribing opioids at relatively high levels. The Food and Drug Administration and the Federal Trade Commission have also been issuing their own warning letters to opioid marketers and distributors over the past several months, evidencing a concerted effort to combat the opioid epidemic on a number of fronts through various federal enforcement and regulatory efforts.

The Warning Letters appear to be based entirely on review and analysis of DEA’s data with no other investigation into the patients who received opioid prescriptions or their medical conditions. Importantly, each of these USAOs has recognized explicitly that the prescribers have not necessarily broken any laws and that the prescriptions may all be medically appropriate. Nevertheless, any warning from an office wielding criminal enforcement authority should never be taken lightly, particularly when related to an issue – opioid overprescribing – that remains a top Department of Justice and U.S. government enforcement priority. While the Warning Letters themselves are issued without meaningful investigation, they may often signal that additional investigatory or enforcement action is forthcoming. In some cases, for instance, prescribers may be visited unannounced and in-person by DEA diversion investigators, special agents, or other law enforcement officers.

Prescribers who have already received a Warning Letter should contact legal counsel to assist in taking measures to assess their degree of risk and preparing for potential further government inquiry. Contacting legal counsel early and preserving privilege could be key to prevent an informal inquiry from becoming a protracted criminal investigation. Experienced counsel can help focus the government’s inquiry, provide the information in a manner that is responsive to the government’s request while also providing relevant context, and limit disruption to the provider’s practice. In collaboration with their counsel, contacted Prescribers should consider:

  • An audit of medical records related to patients who have received opioid prescriptions to confirm their propriety in light of medical documentation;
  • Correction and supplementation of any deficient records, consistent with government requirements for medical documentation to support such prescriptions; and
  • Implementing any required process improvements to mitigate future risk.

Prescribers who prescribe opioids as part of their practices but who have not received a Warning Letter should consider taking prophylactic measures in response to this increased government scrutiny, as should their employers and partners. For instance, Prescribers – and those who employ or contract with prescribers – should consider:

  • Reviewing prescribing patterns against local and national benchmarks;
  • Reviewing a sample of documentation related to opioid prescription decisions to ensure that it sufficiently supports medical necessity and provides additional training on documentation practices as needed;
  • Reviewing and implementing the most current standards of care related to opioid prescribing and patient monitoring, including recommendations issued by the Centers for Disease Control and Prevention’s Guideline for Prescribing Opioids for Chronic Pain; and
  • In larger practices, implementing or updating, as necessary, policies and procedures related to opioid prescribing.
Copyright © 2019, Sheppard Mullin Richter & Hampton LLP.
This post was written by Erica J. Kraus, Michael W. Paddock, David L. Douglass, Danielle Vrabie and A. Joseph Jay, III of Sheppard Mullin Richter & Hampton LLP.
Read more health care compliance news on the National Law Review’s Health Care Type of Law page.

DEA Proposed Rule Would Limit Drug Manufacturer’s Annual Opioid Production

In yet another development on the fight to address the opioid epidemic, U.S. Attorney General Jeff Sessions announced on Tuesday, April 17th that the U.S. Drug Enforcement Administration (“DEA”) will issue a Notice of Proposed Rulemaking (“NPRM”) amending the controlled substance quota requirements in 21 C.F.R. Part 1303. The Proposed Rule was published in the Federal Register yesterday and seeks to limit manufacturers’ annual production of opioids in certain circumstances to “strengthen controls over diversion of controlled substances” and to “make other improvements in the quota management regulatory system for the production, manufacturing, and procurement of controlled substances.”[1]

Under the proposed rule, the DEA will consider the extent to which a drug is diverted for abuse when setting annual controlled substance production limits. If the DEA determines that a particular controlled substance or a particular company’s drugs are continuously diverted for misuse, the DEA would have the authority to reduce the allowable production amount for a given year. The objective is that the imposition of such limitations will “encourage vigilance on the part of opioid manufacturers” and incentivize them to take responsibility for how their drugs are used.

The proposed changes to 21 C.F.R. Part 1303 are fairly broad, but could lead to big changes in opioid manufacture if implemented. We have summarized the relevant changes below.

Section 1303.11: Aggregate Production Quotas

Section 1303.11 currently allows the DEA Administrator to use discretion in determining the quota of schedule I and II controlled substances for a given calendar year by weighing five factors, including total net disposal and net disposal trends, inventories and inventory trends, demand, and other factors that the DEA Administrator deems relevant. Now, the proposed rule seeks to add two additional factors to this list, including consideration of the extent to which a controlled substance is diverted, and consideration of U.S. Food and Drug Administration, Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and state data on legitimate and illegitimate controlled substance use. Notably, the proposed rule allows states to object to proposed, potentially excessive aggregate production quota and allows for a hearing when necessary to resolve an issue of material fact raised by a state’s objection.

Section 1303.12 and 1303.22: Procurement Quotas and Procedure for Applying for Individual Manufacturing Quotas

Sections 1303.12 and 13030.22 currently require controlled substance manufactures and individual manufacturing quota applicants to provide the DEA with its intended opioid purpose, the quantity desired, and the actual quantities used during the current and preceding two calendar years. The DEA Administrator uses this information to issue procurement quotas through 21 C.F.R. § 1303.12 and individual manufacturing quotas through 21 C.F.R. § 1303.22. The proposed rule’s amendments would explicitly state that the DEA Administrator may require additional information from both manufacturers and individual manufacturing quota applicants to help detect or prevent diversion. Such information may include customer identities and the amounts of the controlled substances sold to each customer. As noted, the DEA Administrator already can and does request additional information of this nature from current quota applicants. The proposed rule would only provide the DEA Administrator with express regulatory authority to require such information if needed.

Section 1303.13: Adjustments of Aggregate Production Quotas

Section 1303.13 allows the DEA administrator to increase or reduce the aggregate production quotas for basic classes of controlled substances at any time. The proposed rule would allow the DEA Administrator to weigh a controlled substance’s diversion potential, require transmission of adjustment notices and final adjustment orders to a state’s attorney general, and provide a hearing if necessary to resolve material factual issues raise by a state’s objection to a proposed, potentially excessive adjusted quota.

Section 1303.23: Procedures for Fixing Individual Manufacturing Quotas

The proposed rule seeks to amend Section 1303.23 to deem the extent and risk of diversion of controlled substances as relevant factors in the DEA Administrator’s decision to fix individual manufacturing quotas. According to the proposed rule, the DEA has always considered “all available information” in fixing and adjusting the aggregate production quota, or fixing an individual manufacturing quota for a controlled substance. As such, while the proposed rule’s amendment may require manufacturers to provide the DEA with additional information for consideration, it is not expected to have any adverse economic impact or consequences.

Section 1303.32: Purpose of Hearing 

Section 1303.32 currently grants the DEA Administrator to hold a hearing for the purpose of receiving factual evidence regarding issues related to a manufacturer’s aggregate production quota. The proposed rule would amend this section to conform to the amendments to sections 1303.11 and 1303.13 discussed herein, allowing the DEA Administrator to explicitly hold a hearing if he/she deems a hearing to be necessary under sections 1303.11(c) or 1303.13(c) based on a state’s objection to a proposed aggregate production quota.

Industry stakeholders will have an opportunity to submit comments for consideration by the DEA by May 4, 2018.

[1] DEA, NPRM 21 C.F.R. Part 1303 (Apr. 17, 2018).

 

©2018 Epstein Becker & Green, P.C. All rights reserved.

New Board of Pharmacy Regulations Significantly Narrow the Sole Proprietor Exemption and Impose New Compounding Standards

New regulations from the Ohio State Board of Pharmacy now require any prescriber who will possess, have custody or control of, or distribute dangerous drugs that are compounded or used for the purpose of compounding to be licensed as a Terminal Distributor of Dangerous Drugs (TDDD). This new requirement is particularly noteworthy for physicians, dentists, and others who have previously operated under the “sole proprietor” exemption from licensure as a TDDD. That exemption has been widely used in Ohio and has traditionally permitted practitioners who 1) operate as sole proprietor, sole shareholder of a corporation or professional association, or sole member of a limited liability company; and 2) are the sole authorized prescribers in the practice to be exempt from the TDDD licensure requirements. These new regulations narrow this exemption by now requiring that all prescribers who “compound” or use “compounded” drugs become licensed as a TDDD, even if those prescribers had previously qualified under the “sole proprietor” exemption.

The scope of what constitutes “compounding” is broad – likely broader than what is commonly believed. Ohio law defines “compounding” as the preparation, mixing, assembling, packaging, and labeling of one or more drugs and also includes the reconstitution of drugs in accordance with the manufacturer’s instructions.1 Under the new regulations, any “compounding” activity, possession, or administration of a compounded drug requires TDDD licensure, even by a previously exempt “sole proprietor.”

Additionally, these same new regulations impose new standards for compounding sterile products, non-sterile products, and hazardous drugs and more stringent rules governing purchase of compounded drugs from in-state pharmacies, out-of-state pharmacies, and outsourcing facilities.2 These regulations were imposed in order to bring Ohio into compliance with the 2013 Drug Quality and Security Act, a federal law passed in response to the deadly outbreak of fungal meningitis in 2012 that was linked to the New England Compounding Center.

Article By Eric J. Plinke, Sarah C. Persinger, PharmD, RPh & Daniel S. Zinsmaster

© 2016 Dinsmore & Shohl LLP. All rights reserved.

1 Hazardous Drug Compounding by Prescribers
2 http://codes.ohio.gov/oac/4729-16

Behind the Curtain: Shkreli was NOT the Big Story on the Hill Today

Congress’s complex relationship with prescription drugs was on display today in the House of Representatives.  In the House Committee on Oversight and Government Reform (OGR), Martin Shkreli pleaded the 5th at a hearing investigating drug pricing.  Meanwhile, the Energy and Commerce Committee (E&C) held a hearing regarding implementation of biosimilars.  While all the attention will be on the former, the latter was more important, especially for participants in the biosimilar space.

First, the OGR Committee was a media show built around the flamboyant Shkreli.  Shkreli took the 5th when given the opportunity to testify and later tweeted – after being excused from the hearing for refusing to answer any of the Members questions – that the Committee Members were ‘imbeciles’.  The tone of the hearing was very aggressive towards drug pricing and what were described as unsavory business practices. Members were also critical of the FDA generic drug programs.  However, Member interest in strengthening the program to bring competition to the marketplace was clear. Dr. Janet Woodcock, Director of the Center for Drug Evaluation and Research at the FDA,  stated that funds collected as a result of the Generic Drug User Free Amendments (GDUFA) helped expedite the review process and that by October there will be a 10-month review process on all new applications. The Senate HELP Committee held a hearing last week on reauthorization of GDUFA, which will expire next year, and this bipartisan interest, coupled with the prescription drug cost crisis, could lead to increased resources for the FDA review process. Beyond some public shaming of specific drug companies, there was little suggestion of substantive action on drug pricing.

Second, the E&C Committee was less about drug pricing, but more so about the ability of manufacturers to get new biosimilar products to the market. Notably, Committee Members on BOTH sides of the aisle were critical of CMS for trying to price biosimilars more like generic drugs and categorize different products under a single billing code.  They said the CMS ruling undermines the intent of the Biologics Price Competition and Innovation Act of 2010 (BPCIA) by removing incentives for a robust marketplace. Biologics make up a $200 billion market, so the consequences of policy decisions are significant. Members were also critical of delays in approving more biosimilars and issuing guidance on product labeling. Rep. Frank Pallone (D-NJ) asked if additional appropriations would address these problems, to which Dr. Woodcock replied that she’s more concerned the FDA will be unprepared for a rapid expansion of the biosimilar market.

While 2016 may be devoted to campaigning against drug prices, the Committees responsible for the regulatory regimes for drugs are still very focused on preserving the ability of manufacturers to successfully bring drugs to the market.  That is a much bigger deal than the plethora of Martin Shkreli smirks you will be subjected to in the media.

Article By Rodney L. Whitlock of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

©1994-2016 Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. All Rights Reserved.

FDA Flunks Mylan’s India Facilities, Finds cGMP Violations

When we open our medicine cabinet, we take for granted that the drugs we find there are safe and properly labeled. Many physicians privately worry, however, about the safety and efficacy of prescription drugs.

About 85% of the prescription drugs sold in the United States are manufactured offshore. Many of those offshore drugs are made by generic companies, foreign contract manufacturing companies and sometimes, offshore facilities owned by the so-called “big pharma” manufacturers themselves. Wherever manufactured, drugs distributed in the United States must meet certain current good manufacturing practices or cGMP standards.

Recently the Food and Drug Administration (FDA) began ramping up inspections of offshore manufacturing facilities and the results are shocking. Although cGMP violations have been found worldwide, experts are particularly worried about drugs made in China and India.

Earlier this month the FDA cited three facilities in Bangalore, India that manufacture drugs for Mylan. Headquartered in the U.K., Mylan is the second largest generic and specialty pharmaceutical company in the world. With approximately 30,000 employees worldwide and revenues of $7.72 billion (USD), Mylan certainly qualifies as big pharma.

The FDA says it inspected three of Mylan’s Indian plants between August of 2014 and February of this year. It found “significant” cGMP violations at all three facilities.

Worse, the FDA says that in all three instances Mylan’s response to the three inspections lacked “sufficient corrective actions.”

cGMP standards are in place throughout the manufacturing process to insure the potency and quality of the finished pharmaceuticals. The FDA wants to insure that there are no contaminants in the finished product as well as insuring the finished product is neither stronger nor weaker than advertised.

As a result of the inspections, the FDA concluded a likelihood that the finished drugs from all three plants were adulterated. Those findings are certainly bad news for consumers. It’s also bad for physicians as well. It’s hard for doctors to get dosages correct or monitor for side effects if a drug has inconsistent potency or the presence of contaminants.

In the case of Mylan’s Bangalore, India facilities, the violations were numerous and included:

  • gloves and sterile gowns for use in aseptic environments had holes and tears

  • personal sanitation violations

  • clean room violations

  • discolored injection vials

  • lots with failed assays or contaminants

At least one of the facilities had similar violations dating back to a 2013 inspection.

Overall, the FDA noted, “These items found at three different sites, together with other deficiencies found by our investigators, raise questions about the ability of your current corporate quality system to achieve overall compliance with CGMP. Furthermore, several violations are recurrent and long-standing.”

The FDA declared that continued noncompliance could result in drugs from these facilities being blocked from importation and distribution within the United States.

Mylan has had previous problems with U.S. regulators. In 2000 Mylan paid a $147 million fine to settle charges that the company raised the price of generic lorazepam by 2,6000% and generic clorazepate by 3,200%. The FTC had charged that the company raised the price of lorazepam, the generic equivalent of the brand name antianxiety medication Ativan, from $7 per bottle to $190. Although Mylan agreed to the payment of the fine, it denied any wrongdoing.

Only the FDA can punish drug companies for cGMP violations but if there is proof of an adulterated product entering the commerce stream, the federal False Claims Act can come into play. That law allows private individuals to file a lawsuit against a wrongdoer and receive a percentage of whatever is recovered by the government. Last year the Justice Department paid $635 million in whistleblower awards under the False Claims Act.

Whistleblowers in cGMP cases have received tens of millions of dollars. Dinesh Thakur, a former Ranbaxy executive, received $48 million for information about adulterated generic drugs.

To qualify for a whistleblower award, one must possess inside, “original source” information about a cGMP violation resulting in an adulterated drug or under / over potency medication being approved for sale by Medicaid, Medicare or Tricare. (Most drugs are approved.)

While we believe that contaminated drugs are relatively rare, industry sources tell us that potency issues are rampant. That means the drugs in your medicine cabinet may have little or no active ingredients.

Article By Brian Mahany of Mahany Law

© Copyright 2015 Mahany Law

Making Use of Social Media: FDA Releases Two Draft Guidelines on the Use of Social Media Platforms by Drug and Device Manufacturers

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The Food and Drug Administration (FDA) has released two long-awaited draft guidance documents for the drug and device industries revolving around the use of social media platforms by drug and device manufacturers — Internet/Social Media Platforms: Correcting Independent Third Party Misinformation About Prescription Drugs and Medical Devices (“Guidance on Correcting Third Party Misinterpretation”), and Internet/Social Media Platforms with Character Space Limitations – Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices (“Guidance on Presenting Risk/Benefit Information”).

As the titles suggest, the purpose of the documents is to clarify how social media may be utilized by drug and medical device companies for the voluntary correction of misinformation provided by independent third parties, as well as for presenting promotional messaging regarding risk/benefit information of products. But while the guidelines provide helpful clarification regarding how such platforms may be utilized, they each also raise considerations that companies should take heed of before beginning to use these outlets, and should be factored into a company’s social media guidelines.

Internet/Social Media Platforms: Correcting Independent Third Party Misinformation About Prescription Drugs and Medical Devices

As an initial matter, the Guidance on Correcting Third Party Misinterpretation (“Draft Guidance #1”) establishes two points: first, Draft Guidance #1 only applies to misinformation posted to Internet-based platforms by an independent third party, therefore excluding content provided by the company itself, its employees and agents. Second, Draft Guidance #1 establishes that the exception to a company’s obligation to respond to or correct misinformation only applies to information that is “truly independent,” for example posted by an independent third party to an unaffiliated platform or a platform providing content that is not controlled by the company.

However, Draft Guidance #1 does not completely exclude company-operated sites. In stark contrast with the company’s obligation to correct content when that content is “owned, controlled, created …influenced or affirmatively adopted or endorsed by, or on behalf of, the firm,” where such corrections are obligatory and also carry advertising and labeling regulatory requirements, Draft Guidance #1 does not hold companies responsible for correcting misinformation where a company owns or operates an online platform that allows for user-generated content (chat room, etc.) over which a company does notexert control. However, Draft Guidance #1 cautions that such a site should contain an “overarching and conspicuous statement that the firm did not create or control the [user-generated content].”

If a company chooses to voluntarily respond to truly independent misinformation, Draft Guidance #1 sets parameters on the process for taking correction action, which should either be by (i) providing appropriate truthful corrective information or (ii) providing “a reputable source for correct information, such as the firm’s contact information. In either approach, in order to constitute “appropriate corrective information” a firm’s communication should denote the affiliation of the corrective post with the company, and be:

  • relevant and responsive to the misinformation;
  • limited and tailored to the misinformation;
  • non-promotional in nature, tone, and presentation;
  • accurate;
  • consistent with the FDA-required labeling for the product;
  • supported by sufficient evidence; and
  • posted either in conjunction with or reference the misinformation.

In acknowledgement of the vast nature of the Internet and certain forums and the reality that it may be impractical for a company to attempt to correct all misinformation about its products that may appear, Draft Guidance #1 stipulates that companies do not need to address all incorrect information that may be posted regarding a particular drug or device, even if a company elects to correct a selective portion. When addressing any misinformation, therefore, Draft Guidance #1 recommends that a company create a figurative box around the particular misinformation and portion of the forum it intends to correct, and then revise all the incorrect information within that defined boundary, which should include also correcting positive misinformation or exaggerations. Following corrective action, while Draft Guidance #1 does not hold companies responsible for monitoring the communication, it does recommend that companies keep records that include (i) the date, location, and content of the misinformation; (ii) when the wrongful information was discovered; and (iii) a description of the corrective information provided, including the date it was furnished.

Finally, Draft Guidance #1 suggests that the FDA does not intend to object if a firm voluntarily corrects misinformation and the voluntarily provided corrective information does not satisfy otherwise applicable regulatory labeling or advertising requirements, so long as the corrective information is not non-truthful, misleading, or in a manner other than recommended by Draft Guidance #1. However, companies should take heed that any corrective action that goes beyond merely providing accurate information that is specifically tailored to the misinformation it is addressing (i.e., including slogans or promotional information) must comply with applicable regulatory requirements related to labeling or advertising.

While helpful for establishing clearly both the parameters for correctly responding to misinformation as well as for clearly limiting a company’s obligation to respond to any or all misinformation posted by an independent third party, the Guidance on Correcting Third Party Misinterpretation also reminds companies to take caution when doing so to ensure that their responses are narrowly tailored enough to fall under the purview of the guidance and outside regulatory requirements. That caution includes carefully considering where misinformation clearly constitutes “truly independent” information. Companies should be mindful of the reality that “truly independent” is not a concept that is well defined, and should thus be cautious before asserting that certain misinformation may fall under the purview of Draft Guidance #1 as the FDA advances a broad interpretation of when a company is responsible for taking corrective action.

Internet/Social Media Platforms with Character Space Limitations — Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices

Prepared by the Office of Prescription Drug Promotion, the second guidance issued by the FDA last week, the Guidance on Presenting Risk/Benefit Information (“Draft Guidance #2”), addresses the parameters around presenting benefits and risks information on Internet and social media platforms with character spacing limitations, such as microblogs (e.g., Twitter) and online paid search (e.g., “sponsored links” on search engines such as Google). Draft Guidance #2 clearly establishes that, as a threshold matter, the character restrictions do not eliminate the company’s responsibility to ensure its promotional messaging complies with all applicable regulations related to advertising and labeling, and cautions that such forms of media may not be appropriate for promotion of certain products, such as those with complex indications or risk profiles.

For companies that choose to make product benefit claims on character-space-limited communication sites, while each may reasonably use common abbreviations (including scientific and medical abbreviations), punctuation marks, and other symbols to comply with space constraints, Draft Guidance #2 presents a broad set of rules that must be satisfied by each communication relating to both risk and benefit information.

Benefit Information

  • Benefit information should be accurate, non-misleading, and reveal material facts within each individual message or tweet.
  • Benefit information should be included with risk information in the same message. Do not spread benefit and risk information across multiple messages or tweets.

Risk Information

  • Risk information should be included with benefit information in the same message. Do not spread risk and benefit information across multiple messages or tweets.
  • Risk information should be “comparable in scope” to the benefit information, and should, at minimum, include the most serious risks, e.g., those included in a boxed warning or known to be life-threatening, among others, associated with the product. To determine whether risk information is “comparable in scope” to the benefit information, the FDA weighs (i) whether the risk information “qualifies any representations made about the product,” and (ii) whether the risk information is presented with a “prominence and readability comparable to the benefit claims about the product.” While risk disclosures may be concise when paired with benefit information, a hyperlink to a complete, and exclusive, discussion of risks should be included and appropriately titled and not promotional in nature.
  • Both the proprietary and established (generic) name for the product should be included within the character-space limited communication and on each landing page associated with each hyperlink in that initial communication. Draft Guidance #2 recommends that the landing page be devoted exclusively to the communication of risk information about the product and not to the promotional home page. Such landing page should also prominently display quantitative ingredient and dosing information for prescription drugs.

In light of the restrictions set forth by Draft Guidance #2, while companies should feel comfortable taking advantage of current social media platforms including those with character restrictions, they should also ensure that the parties responsible for drafting any such posts are aware of the parameters placed on such communications. A hypothetical example provided by Draft Guidance #2 exemplifies some of the potential disadvantages of such messaging:

NoFocus (rememberine HCl) for mild to moderate memory loss-May cause seizures in patients with a seizure disorder www.nofocus.com/risk

While the message complies with each of Draft Guidance #2’s directives, the balancing of risk and benefit information in a space restricted communication may have the unintended result of highlighting risk over benefit. Additionally, from a practical standpoint, the space constraints may prevent the inclusion of all necessary information. If a company cannot conclude that “adequate” benefit and risk information (along with other required disclosure) may be communicated in the same message or tweet — particularly at 140 characters — Draft Guidance #2 recommends that the company reconsider whether the use of the particular platform is the appropriate forum for the dissemination of such messaging before making use of such forums, once again in particular for drugs with complex indications or high risk profiles.

As a general conclusion, while the Guidance on Presenting Risk/Benefit Information is self-admittedly limited in scope, and does not address “promotion via product websites, webpages on social networking platforms (e.g., [Facebook, Twitter, YouTube]), and online web banners,” it undeniably provides helpful direction for drug and device companies’ use of social media sites for promotional messaging where communications are restricted to a limited number of characters, as well as highlighting how the FDA may intend to regulate such use. Companies should pay careful attention to the restrictions while taking advantage of the opportunities these social media platforms offer, and should take care to ensure to instill clear policies that comply with Draft Guidance #2 that are available to, and understood by, individuals tasked with producing and monitoring social media content for the company.

The FDA will be accepting comments on both Draft Guidance #1 and Draft Guidance #2 until September 16, 2014.

Article By:

Cynthia J. Larose
Christine M. Wahr
Of:
Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.