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Focus on Regulation

EMA updates guidance concerning medicinal products intended exclusively for non-EU countries

The European Medicines Agency (“EMA”) has updated its guidance (Guidance) regarding procedural advice for medicinal products intended exclusively for markets outside the European Union (“EU”). The Guidance addresses several questions which applicants requesting a scientific opinion as provided in Article 58 of Regulation (EC) No 726/2004 (“Article 58”, the “EMA Regulation”) may have. Article 58 of the EMA Regulation provides that EMA, in co-operation with the Word Health Organisation (WHO), may provide a scientific opinion concerning certain medicinal products for human use. These medicinal products are intended exclusively for markets outside the EU in which population is largely low and middle income.

The Guidance also provides information regarding issues that are commonly discussed during pre-submission meetings related to requests for scientific opinions. Pre-submission meetings provide applicants with the opportunity to obtain regulatory and procedural advice regarding their application in accordance with Article 58 of EMA Regulation. Accordingly, EMA explicitly encourages the establishment of pre-submission meetings with the applicants concerning the evaluation of medicinal products that are intended for non-EU markets.

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Smallsat companies form trade association to address issues facing the smallsat community

At the annual Smallsat conference in Logan, Utah, the Commercial Smallsat Spectrum Management Association (CSSMA) held its first meeting since legally forming earlier this month. A number of well-known smallsat operators and other companies have joined the organization, which seeks to advance a number of goals common to the smallsat community. These goals include creating conditions for a transparent and expedited spectrum coordination process for shared spectrum and advocating CSSMA views on spectrum management and other policy matters affecting the smallsat community.

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Unburden Yourself: FDA Requests Comments on Ways to Implement President Trump’s Regulatory Reform Executive Orders

Earlier this year, in an effort to alleviate unnecessary regulatory burdens, President Trump issued two executive orders, Executive Order 13771, Reducing Regulatory and Controlling Regulatory Costs and Executive Order 13777, Enforcing the Regulatory Reform Agenda. On September 8, 2017, FDA published several notices in the Federal Register, to implement these orders, soliciting comments from the public on ways to modify the agency’s current regulations, while still meeting both the Agency’s public health mission and statutory obligations. Questions FDA hopes the public will consider include:

  • Have advancements and innovations in science or changes in the law resulted in outdated or unnecessary regulations?
  • Are regulations duplicative of FDA or other agency requirements or voluntary or consensus standards from third party organizations?
  • Do regulated entities find compliance with any regulations particularly difficult, and if so, how?
  • Do any regulations require an unnecessary amount of recordkeeping and reporting?
  • Can goals be achieved through less costly means, while still protecting public health?
  • How should FDA prioritize regulations for reform?

FDA has indicated that comments may address considerations beyond the list of questions provided, but that all comments should be as specific as possible, include supporting data or information, and be submitted in the format provided for in the notice.

Yesterday, Deputy Commissioner Anna Abram posted a statement explaining the purpose of the exercise. She stated that “science will remain FDA’s North Star when it comes to our role in devising regulatory policy.” She identified several possible areas of focus, including regulations that “may not adequately reflect advances in science, technology or changes in industry practice.” She also highlighted, as an example, “places where FDA’s rules concerning new drugs are being used in ways that may create obstacles to the timely entry of generic competition.”

Comments are due by December 7, 2017. The agency published seven virtually identical notices—one for each Center and one general notice. The Federal Register Notice for the Center for Drug Evaluation and Research can be accessed here, and the one for the Center for Biologics Evaluation and Research is here.

If you have any questions about these notices or are considering submitting comments, please contact one of the authors of this alert or the Hogan Lovells attorney with whom you regularly work.

UK MHRA Publishes Guide to the New EU Medical Device and IVD Regulations

The UK Medicines and Healthcare products Regulatory Agency (“MHRA”) has published an interactive guide to assist companies with understanding the requirements of the new EU Medical Device Regulation (“MDR”) and In Vitro Diagnostic Medical Device Regulation (“IVDR”).

The MDR and IVDR entered into force on 25 May 2017. Most of the requirements under the MDR will apply from 26 May 2020 and under the IVDR from 26 May 2022. During the transition period, devices can comply with the requirements under either the current EU medical device directives (MDD) or the new Regulations, but not a hybrid of both. After the transition period, devices placed on the market in the EU must comply with the new MDR/IVDR, unless they benefit from the extended CE certificate provisions which allow CE certificates issued within the transition period under the MDD to remain valid for up to four years (MDR) or two years (IVDR) from the date of issue (subject to certain conditions, for example, the certifying notified body must be designated under the new Regulations).

The guide includes:

  • an overview of the transition periods for the application of the new Regulations;
  • examples of the new classification categories of medical devices and in vitro diagnostic devices in the Regulations, as well as of previously unregulated “products without an intended medical purpose” (such as non-corrective contact lenses and brain stimulation equipment), which will be regulated under the MDR;
  • a summary of the classes of devices for which a conformity assessment by a notified body will be required under the Regulations;
  • an overview of the steps that manufacturers must take in order to comply with the MDR/IVDR before placing their device on the market, including assigning a unique device identification (“UDI-DI”) number and entering information in the Eudamed databank;
  • a summary of the obligations that apply to different operators in the medical device supply chain, depending on whether they are a manufacturer, importer, distributor or authorised representative; and
  • an overview of the new, more rigorous post-market surveillance requirements.

The full guidance is available here: https://www.gov.uk/guidance/medical-devices-eu-regulations-for-mdr-and-ivdr.

EMA released reflexion paper clarifying information related to the selection of starting materials

The European Medicines Agency (“EMA”) has released a reflexion paper on the requirements for selection and justification of starting materials for the manufacture of chemical active substances. The reflexion paper provides clarification with respect to Section 5 of ICH guideline Q11 on Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities). This Section 5 provides the information that should be submitted in marketing authorisation applications to justify the selection of starting materials.

EMA’s reflexion paper aims to expand some of the points of Section 5 of ICH Q11 in order to harmonise opinions between assessors and clarify the requirements for applicants. EMA also recognises that the information submitted by applicants or Active Substance Master File (ASMF) holders to justify the selection of starting materials is often insufficient to allow adequate assessment of suitability. According to EMA, the description of the manufacturing process should be sufficiently detailed to demonstrate that the process and its associated control strategy will consistently provide active substance of satisfactory quality. 

The reflexion paper recalls that, in relation to synthetic drug substances, a sufficient number of chemical transformation steps, as defined in the glossary of ICH Q11 need to be included so that the generation, fate and control of impurities can be understood. According to EMA, short synthetic routes will not normally be accepted. The detailed description of the manufacturing process should cover all the synthetic steps critical to the quality of the active substance.

The reflexion paper defines a “critical step” as one where the process conditions, test requirements or other relevant parameters must be controlled within pre-determined limits to ensure that the active substance meets its specification.

In addition, the reflexion paper underlines that the term “significant structural fragment” is frequently misinterpreted by applicants as meaning structural proximity to the active substance. However, EMA explains, that the phrase applies to materials which contribute to the final molecular structure of the active substance, as opposed to reagents, catalysts, or solvents.

EMA’s reflexion paper also provides explanatory notes on the content of information of starting materials that applicants should submit as well as explanatory notes on the content of justification of starting materials.

EMA highlights that this reflexion paper is not intended as a revision of ICH Q11.

 

FDA Seizes Stem Cell Therapy—A First of Many?

On August 25, 2017, U.S. Marshals Service, at the request of FDA, seized five vials of ACAM20000—a smallpox vaccine containing live vaccinia virus (cow pox), which is reserved for people at high risk of contracting the disease—that were discovered during an FDA inspection at StemImmune Inc., a San Diego, California company that purports to specialize in “immune-oncology.”  Each of the vials originally contained 100 doses of the vaccine, and although one vial was partially used, four of the vials were intact.

According to the government’s Complaint for Forfeiture, the vaccine was combined with stem cells to create an unapproved treatment for late-stage cancers.  The government alleges that the stem cell/ACAM2000 combination contained ACAM2000 at several times the approved dose and was administered intravenously to potentially immune-compromised cancer patients, despite express warnings in ACAM2000’s FDA-approved labeling that the vaccine not be administered intravenously and not be used in individuals with severe immune deficiency.  In addition to potential harm to individuals who received the unapproved treatment, the complaint states that the use of live vaccine created a risk that the vaccinia virus could be transmitted to people in close contact with those individuals.

In an announcement of the seizure action, FDA Commissioner, Dr. Scott Gottlieb, took a strong stance against establishments such as StemImmune as “unscrupulous clinics” making “audacious but ultimately hollow claims” in order to take advantage of vulnerable patients.  Dr. Gottlieb stated that FDA would pursue both regulatory and criminal enforcement against such companies.

Not long ago FDA took a similarly strong enforcement posture against illegal drug-compounding operations—which has resulted in numerous enforcement actions and continues to be a focus of FDA inspectional resources and compliance activities to this day.  So the question is—are more enforcement actions coming in the near future against therapeutic stem cell operations that are not in compliance with FDA requirements?

Awaiting a monumental decision by the President

As expected, Secretary of the Interior Ryan Zinke on Thursday delivered his draft report to the President regarding the fate of certain national monuments, as directed by Executive Order No. 13792. Specifically, the President required that Secretary Zinke undertake an unprecedented review of all national monuments of more than 100,000 acres, which had been established under authority of the Antiquities Act since 1976. The Antiquities Act was enacted in 1906, and provides that a President may designate a national monument on federally-owned lands to protect historic landmarks and historic and pre-historic structures and objects of historic or scientific interest. The President was inspired to re-evaluate these actions of his predecessors by politicians in western States, notably including Utah, who had long objected to the establishment of national monuments on federally-owned public lands in their states. Continue Reading

FDA, EU Regulators Agree to Share Unredacted Inspection Reports and Other Confidential Information

The U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the European Commission – DG Sante (DG Sante), signed a new confidentiality commitment which expands the scope of the current confidentiality arrangements that apply to the cooperative law enforcement activities conducted by the regulators.  The new confidentiality commitment allows the regulators to share commercially confidential information, trade secret information, personal data and other non-public information relating to drug inspections and investigations.  This commitment furthers ongoing implementation of the EU and FDA agreement on mutual recognition of inspections of drug manufacturers announced earlier this year (discussed in our prior post), and strengthens the EU and US relationship by promising to maintain the confidentiality of exchanged non-public information.

A complete exchange of such information, including unredacted inspection reports, was not possible under previous confidentiality agreements among the regulators.  The FDA, the EMA and DG Sante provided reciprocal warranties concerning the confidentiality of the information exchanged under the new arrangement.  In particular, the EMA and DG Sante are entitled to share the information provided by the FDA with the EU Member States’ authorities only if these authorities and the FDA have concluded an arrangement convening the exchange of the same information.  The commitment could lead to decisions based on findings from inspections conducted within the other regulator’s borders.  This coordination effort allows regulators to reallocate resources to focus on drug inspections with potentially higher public health risks outside of the U.S. and EU, which is consistent with the increasing focus on inspections in China, India, and Asia more broadly.

USTR Requests Input on Impact of Trade Agreements on Government Procurement

On August 21, 2017, the Department of Commerce (Commerce) and the Office of the United States Trade Representative (USTR) issued a request for public comment on the impact of government procurement provisions of U.S. trade agreements on U.S. manufacturers and suppliers.  Prompted by President Trump’s “Buy American and Hire American” Executive Order (E.O.), the request seeks to understand how domestic preference laws affect participation of U.S. manufacturers and suppliers in the Federal procurement process.  Noting the significance of reciprocity in the global trading arena, the request also asks for industry input concerning the “costs and benefits” of trade agreements, and related laws, from those U.S. manufacturers and suppliers competing in foreign government procurement markets.  Comments are due by September 18, 2017. Continue Reading

EC issues a new guidance concerning the safety features for Falsified Medicines

The European Commission has published a guidance concerning “Safety Features for medicinal products for human use” (Guidance). The Guidance is in the form of a “Questions and Answers” document. It is intended to facilitate the implementation of the EU Falsified Medicines legislation.

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