Articles Posted in Regulation

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On July 29, 2016, President Barack Obama signed S.764 into law. The law amends the Agricultural Marketing Act of 1946 to require that the U.S. Department of Agriculture (“USDA”) establish and oversee a national bioengineered food disclosure standard. Under the law, USDA has two years to promulgate regulations that establish the disclosure standard, as well as any related requirements and procedures that the Agency deems necessary.

Under the law, any disclosure regulations that USDA promulgates shall: (i) prohibit a food from being considered “bioengineered” solely because the animal from which it was derived consumed feed that was bioengineered; (ii) set the amounts of a bioengineered substance that need to be in a food for it to be considered “bioengineered”; (iii) establish a process by which other considerations may be given to whether a food is “bioengineered”; (iv) require that the bioengineered disclosure be a text, symbol, or electronic or digital link (e.g. a QR or Quick Response Code), with the disclosure option to be selected by the food manufacturer; (v) provide alternative reasonable disclosure options for food with small packaging; (vi) for “small food manufacturers,” provide at least one additional year for compliance with the disclosure regulations, as well as the additional option to disclose that the food contains bioengineered material through a phone number or internet website, (provided that they indicate that the number or URL provides access to additional information); and (vii) exclude food served in restaurants or “very small food manufacturers”—to be defined by USDA—from the disclosure requirements.

While the law should ultimately lead to more information on food labeling and enable consumers to make more informed choices about their food, it has also received significant criticism. For example, opponents of the law say that the definition of “bioengineered foods” is unduly narrow.

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Congress passed the Food and Drug Administration Amendments Act of 2007 (“FDAAA”) to give the U.S. Food and Drug Administration (“FDA”) new authority to regulate the safety of marketed drugs. As part of this authority, FDA may require drug companies to propose and implement Risk Evaluation and Mitigation Strategy (“REMS”) for certain drugs whose risk- benefit profiles warrant safety measures beyond professional labeling. FDA may require REMS as part of the approval of a new drug or biologic (brand or generic), or for an approved product when new safety information arises. If FDA determines that a drug has been shown to be effective but is associated with an adverse drug experience, the FDA will require that the REMS have elements to assure safe use (“ETASU”). An example of an ETASU is that health care providers who prescribe the drug have particular training or experience or are specially certified.

The FDA, Federal Trade Commission, and generic drug manufacturers have raised concerns that branded drug manufacturers could be using REMS to impede generic competition. One concern is that branded companies may use REMS distribution restrictions to deny generic companies the drug samples they need to conduct necessary testing and otherwise meet the requirements for generic drug approval. Another concern is that branded drug firm may abuse situations where FDA approval of a generic drug is conditioned on the utilization of a single, shared ETASU by both the generic and branded companies. Essentially, the concern is that branded firms are impeding negotiations of a single, shared ETASU in order to delay generic entry.

To address these concerns, the Senate Judiciary Committee introduced Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act of 2016 on June 14, 2016. The bill—co- sponsored by Senators Grassley (R-IA), Klobuchar (D-MN), Leahy (D-VT), and Lee (R-UT)— permits a generic manufacturer to sue the branded manufacturer if: (1) the branded manufacturer fails to “provide sufficient quantities of [a drug sample] on commercially reasonable, market- based terms”; or (2) branded and generic manufacturers are unable to develop single, shared ETASU after 120 days of initiating a request to develop a shared ETASU. The relief contemplated in the bill is (1) a court order that the brand company provide the drug sample or the brand and generic develop single, shared ETASU or generic firm join a pre-existing ETASU; and (2) monetary award.

handsoap.jpgOn December 17, 2013, the FDA issued a Proposed Rule for consumer antiseptic wash drug products. Prior to this Proposed Rule, the last Tentative Final Monograph (“TFM”) issued for antiseptic active ingredients was in 1994 (59 Fed. Reg. 31,402), which classified 22 active ingredients for over-the-counter (“OTC”) antiseptic handwash use.

The new Proposed Rule affects manufacturers of antibacterial hand soap and hand and body wash products containing OTC antiseptic active ingredients for repeated daily use, to be used with water. Those products do not include hand sanitizers or wipes. Additionally, the Proposed Rule is only to evaluate consumer antibacterial products and not health care setting antibacterial products, which have distinct proposed use settings, target populations, and risks for infection.

The Proposed Rule requires manufacturers of antibacterial soaps and washes to: (1) demonstrate the products are safe for long-term daily use; and (2) demonstrate with clinical data that the products are more effective than plain soap and water in the prevention of illness and the spread of infection. The manufacturers have one year to submit new data demonstrating that safety and effectiveness. If a manufacturer cannot demonstrate those two requirements, then it will have to reformulate the product (remove the antibacterial active ingredient).
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Thumbnail image for 3699948229_d7732f8df0_o.jpgYesterday, FDA issued two new items to help clarify combination products: 1) a Final Rule published in the Federal Register entitled, “Current Good Manufacturing Practice Requirements for Combination Products” and 2) a Draft Guidance entitled, “Guidance for Industry and FDA Staff:
Submissions for Postapproval Modifications to a Combination Product Approved Under a BLA, NDA, or PMA”, also announced in the Federal Register.

The Final Rule is intended to clarify which good manufacturing practice (“CGMP”) requirements apply when drugs, devices, and biological products are combined to create combination products. The Rule also provides a mechanism that FDA describes as “transparent and streamlined regulatory framework” for companies to use when demonstrating compliance with CGMP requirements for “single-entity” and “co-packaged” combination products. “Single-entity” combination products are two or more regulated components, e.g., drug/device, biologic/device, drug/biologic/device, which are physically, chemically, or otherwise combined or mixed and produced as a single-entity. Two or more separate products packaged together in a single package or as a unit and comprised of two or more regulated products is a “co-packaged” combination product. The Final Rules started as a Draft Guidance announced on October 4, 2004 (69 FR 59239), entitled “Current Good Manufacturing Practices for Combination Products.” Based on comments and FDA’s own internal review, FDA decided that “rulemaking was warranted” and issued Proposed Rules on September 23, 2009 (74 FR 48423).

The concept behind the CGMP Rule is simple for parts that are separately manufactured and marketed: each of the constituent parts of a combination product are subject only to the CGMP regulations applicable to that part, e.g., drug, biologic, or device. The two categories of combination products mentioned above, however, “single-entity” and “co-packaged” are slightly different due to the possibility for overlapping CGMP requirements for the different regulated components. Companies have two basic options for these types of products: 1) demonstrate compliance with the specifics of all CGMPs to each of the parts, or 2) demonstrate compliance with the specifics of either the drug CGMPs at 21 C.F.R. Parts 210 and 211 or the quality system (“QS”) regulation at 21 C.F.R. Part 820 rather than both, for drug/devices under certain conditions. For combination products including biologics, the specific regulations are 21 C.F.R. parts 600 through 680, and for product including any human cell, tissue, and cellular tissue-based products, the regulations are 21 C.F.R. Part 1271.
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onlinepharmacy.jpgPurchasing of pharmaceuticals through on-line pharmacies is on the rise and gives rise to many potential problems. Crucially the most important issue is whether the medicinal product is genuine, contains the correct ingredients, and is an approved product in the relevant regulatory jurisdiction. Medicines supplied via on-line links can come from anywhere in the world, and this method of distribution is more open to fraudulent activity.

In Europe, the European Parliament passed Directive 2011/62/EU, which relates to medicinal products for human use, and is in regard to the prevention of the entry into the legal supply chain of falsified medicinal products. The European Commission (“EC”) has put some thought into how on-line pharmaceutical purchases can be made safe and to comply with the Directive. To that end, they have released a Concept Paper for public consultation on the introduction of a “common logo” for websites of legally-operating on-line pharmacies/retailers.

The requirements are that the logo is recognizable throughout the EU and identifies the Member State in which the on-line pharmacy/retailer is established. There is also an obligation for each Member State to set up a dedicated website providing a national list of all legally-operating on-line pharmacies/retailers. The entries in these lists must have a hyperlink to the respective on-line pharmacies/retailer’s website and a reciprocal link from the logo on the on-line pharmacies/retailer’s website back to the national list. The point being that a customer can go to either the national list to find approvable pharmacies and vice versa to the on-line pharmacies/retailer’s website and link back to the national list via the logo thus assuring authenticity.
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generic-drugs.jpgA research letter published online in the Journal of the American Medical Association (“JAMA”) last Tuesday reports findings that pharmaceutical advertisements have a tendency to minimize potential adverse effects when the products they promote become available over-the-counter (“OTC”). The researchers attribute this shift in content to the differences in prescription drug advertising standards, governed by FDA, and those for OTC advertising, governed by the Federal Trade Commission (“FTC”). FDA requires that ads present a “fair balance” of the risks and benefits of a drug, a requirement that is absent from FTC’s “reasonable consumer” standard. Commentators note that the FDA regulations are better equipped to ensure against “active deception.”

The research endeavor, sponsored by CVS Caremark, considered four drugs that transitioned from prescription to OTC status within the last ten years: Claritin® (loratidine), Prilosec® (omeprazole), Xenical®/Alli® (orlistat), and Zyrtec® (cetirizine). It examined 133 total television and print advertising materials from twenty-four months prior to, through six months after, each transition, and found that the percentage of advertisements that referenced side effects plummeted from 70% while prescription only to 11% once available OTC. Conversely, the proportion describing drug benefits jumped from 83% to 97%. The study further reports that OTC advertisements frequently omit the generic names of drugs, “a powerful tool for the patient as a consumer in that it helps tie together scientific information on the drug from different places.” Roughly 50% of the OTC ads mentioned the generic name, while over 95% had when the drugs were available by prescription only.

Written by Rachael P. McClure

Thumbnail image for pediatrics.jpgThe Pediatric Committee (“PDCO”) of the European Medicines Agency (“EMA”) is tasked with identifying the needs for children in a variety of therapeutic areas and aims to encourage the research and development of pediatric medicinal products. The first Inventory, which is now open for discussion and public consultation, covers medicines for cardiovascular diseases. The EMA points out that it will be releasing similar lists for other therapeutic areas for public consultation during 2012 and 2013.

According to the EMA, the Inventory aims to enable:

  • Companies to identify opportunities for business development;
  • The PDCO to judge the need for medicines and studies when assessing draft pediatric investigation plans, waivers and deferrals; and
  • Healthcare professionals and patients to have an information source available to support their decisions as to which medicines.

The Inventory is based on a report on the survey of all pediatric uses of medicinal products in Europe completed by the PDCO in December 2010.
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eyemouthnew.jpgOn July 2, the much heralded new European Pharmacovigilance legislation came into operation. This new piece of legislation is aimed at promoting and protecting public health by strengthening the existing Europe-wide system for monitoring the safety and benefit-risk balance of medicines and provides regulators with a range of new or improved tools to ensure that patients are not exposed to unnecessary risks when taking medicines.

Highlights of the new legislation include:

  • The establishment of a new scientific committee, the Pharmacovigilance Risk Assessment Committee (“PRAC“).
  • A clarification of the roles and responsibilities leading to more robust and rapid European Union (“EU”) decision-making.
  • The engagement of patients and healthcare professionals in the regulatory process.
  • An improved collection of key information on medicines, e.g., through risk-proportionate, mandatory post-authorization safety and efficacy studies.
  • More transparency and better communication.

The first meeting of the new key committee, PRAC, will be on July 19 and 20, 2012. PRAC’s mandate includes, among other things, “All aspects of the risk management of the use of medicinal products including the detection, assessment, minimization and communication relating to the risk of adverse reactions, having due regard to the therapeutic effect of the medicinal product, the design and evaluation of post-authorization safety studies and pharmacovigilance audit”.
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IMG_0148.JPG On May 11, FDA reportedly told attendees of the Consumer Healthcare Product Association’s Regulatory & Scientific Conference in Washington, D.C. to be patient while FDA implements its “new paradigm” for prescription to over-the-counter (“Rx-to-OTC”) switch applications (The Tan Sheet (May 21, 2012). Andrea Leonard-Segal, M.D., Director, Division of Nonprescription Clinical Evaluation, Office of Nonprescription Products, Center for Drug Evaluation and Research, said that FDA’s anticipated, revised Rx-to-OTC regulations will allow for expanded conditions of safe nonprescription use.

Leonard-Segal acknowledged, however, that the process will take time, warning “if you submit [a new drug application] where we don’t have the regulations to support the switch, if you’re ahead of your time compared to the regulations, then I think the project won’t go where you want it to go.” While waiting for FDA to final the regulations, Leonard-Segal suggested that firms make business decisions about initiating switch programs that employ new diagnostic technologies and other measures, according to their internal estimate project timelines. Leonard-Segal, however, sympathized with sponsors that had failed to meet FDA’s current, less flexible regulations that only permit OTC conversions where the Drug Facts label has full comprehension. An example of failed Rx-to-OTC switches cited was statins to lower cholesterol, but other categories of products that may benefit from the new regulations are sleep aids and triptans to treat migraines.

Commenting further, Leonard-Segal said at the Conference: “One of the frustrations of being in the switch business . . . has been watching the regulations interfere with, what in my perspective have been some very interesting and very innovative ideas, but that just can’t move forward because the regulations don’t allow us to go there.” Leonard-Segal further noted that a priority for the new regulations will be to consider how diagnostic devices could work together with OTC drugs, which is currently a complex approval process involving multiple centers and considerations.
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3699948229_d7732f8df0_o.jpgOn April 30, FDA published in the Federal Register final regulations amending the scope of its clinical investigator disqualifications. Now when the Commissioner determines that a clinical investigator is ineligible to receive one kind of test article (drug, device, animal drug), the clinical investigator is also ineligible to conduct any clinical investigation that supports an application for research or marketing for other FDA-regulated products, including foods and tobacco products. FDA amended its regulations “to protect the rights and safety of subjects involved in FDA-regulated investigations, and help[s] to ensure the reliability and integrity of the data used to support the marketing of products regulated by FDA.”

According to FDA, the final rule was based on a recommendation from the General Accounting Office (“GAO”) in September 2009. The GAO Report, Oversight of Clinical Investigators: Action Needed to Improve Timeliness and Enhance Scope of FDA’s Debarment and Disqualification Process for Medical Product Investigators, stated that it was “critical for FDA to take action–and to have the authority to take action–to prevent clinical investigators . . . who engaged in serious misconduct from doing it again, whether in research that involve drugs, biologics, or devices.” FDA is also amending its regulations for informal hearings under 21 C.F.R. Part 16 by changing the scope of certain provisions that were “inadvertently omitted.”

FDA proposed the rule in the Federal Register on April 13, 2011 and received only two comments. FDA, however, managed to convert one of the filed comments to ten points to address in the preamble to the final rule. First, FDA clarified the “repeatedly or deliberately” language in the regulations for when a clinical investigator may be disqualified for repeatedly or deliberately failing to comply with FDA’s applicable clinical investigations regulations or deliberately submitting false information to the sponsor. FDA said “repeatedly” means more than once, which can be more than one time in a single study or in more than one study. “Deliberately” means “willful” conduct or with reckless regard, such as knowingly failing to comply with FDA’s regulations or falsifying data. In another point, FDA clarified that FDA will place no limits on how far back FDA will investigate to find applications or submissions that may have been affected by a disqualified investigator. In yet another point, FDA summarized the notification process for how sponsors become aware of an clinical investigator’s ongoing disqualification process, including redacted letters on FDA’s website. In the final point, FDA indicated how FDA notifies sponsors that clinical investigators have been reinstated–once again, primarily FDA’s website.
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