Pharmaceutical & Medical Device Regulatory Update, Vol. III, Issue 7

Top News

FDA Announces November Hearing on Off-Label Communications

On November 9 and 10, 2016, FDA will host a public hearing to obtain feedback on the Agency's regulation of communications by manufacturers, packers, distributors, and their representatives about FDA-regulated medical products, particularly communications regarding unapproved uses of approved and cleared medical products. The request for public viewpoints follows litigation regarding FDA's oversight of these communications, and a recent move by industry groups endorsing the truthful and nonmisleading communication of medical information to health care professionals and payers. FDA is seeking feedback from a broad group of stakeholders, including health care professionals and professional societies, patients and their caregivers, patient advocates, representatives from regulated industry, health care organizations, payors and insurers, academic institutions, public interest groups, and the general public. To help facilitate stakeholder feedback, FDA provided questions in the notice published earlier this month. A transcript will be available following the hearing. Comments will be accepted after the public hearing until January 9, 2017.

FDA Issues Final Rule on OTC Consumer Antiseptic Washes

In the September 6, 2016, Federal Register, FDA issued a final rule establishing that certain active ingredients used in over-the-counter ("OTC") consumer antiseptic products intended for use with water are not generally recognized as safe and effective and are misbranded. FDA is issuing this final rule—which finalizes the proposed rule published in the December 17, 2013, Federal Register and amends the 1994 tentative final monograph for OTC antiseptic drug products published in the June 17, 1994, Federal Register—after considering the recommendations of the Nonprescription Drugs Advisory Committee, public comments on the Agency's notices of proposed rulemaking, and all data and information on OTC consumer antiseptic wash products that have come to the Agency's attention. The final rule is part of the ongoing review of OTC drug products conducted by FDA and covers only OTC consumer antiseptic washes that are intended for use as either a hand wash or a body wash; the rule does not cover health care antiseptics, consumer antiseptic rubs, first aid antiseptics, or antiseptics used by the food industry. The rule is effective September 6, 2017.

FDA Revises Requirements for Establishment Registration and Drug Listing

In the August 31, 2016, Federal Register, FDA announced it is amending the regulations governing drug establishment registration and drug listing. The amendments reorganize, modify, and clarify current regulations concerning who must register establishments and list human drugs, human drugs that are also biological products, and animal drugs. The final rule, which pertains to finished drug products and to active pharmaceutical ingredients, alone or together with one or more other ingredients, requires electronic submission of registration and listing information unless waived in certain circumstances. The final rule also describes how and when owners or operators of establishments at which drugs are manufactured or processed must register their establishments and list the drugs they manufacture or process. In addition, the rule makes changes to the National Drug Code system and supports: (i) implementation of the electronic prescribing provisions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 and (ii) availability of current drug labeling information through DailyMed, a computerized repository of drug information maintained by the National Library of Medicine. The rule is effective November 29, 2016.

Draft Guidances on Deciding When to Submit a 501(k) for a Change to an Existing Device

FDA recently issued two draft guidance documents to help clarify when a change in a legally marketed medical device requires a manufacturer to submit a premarket notification, or 510(k), to FDA. The first document, "Deciding When to Submit a 510(k) for a Change to an Existing Device," addresses non-software changes and, when finalized, will supersede guidance issued in 1997. The second document, "Deciding When to Submit a 510(k) for a Software Change to an Existing Device," focuses on software changes to devices, including adaptive, corrective, and perfective software modifications. Both guidance documents include guiding principles and points for manufacturers to consider when analyzing to what extent a change may affect a device's safety and effectiveness and determining whether FDA notification is required. For more information, see FDA's press release announcing the updated recommendations. Comments on both guidances are due November 7, 2016.

Draft Guidance Issued for IRB Written Procedures

The Department of Health and Human Services ("HHS") Office for Human Research Protections ("OHRP") and FDA recently released draft guidance for the written procedures of Institutional Review Boards ("IRBs"), which is intended to assist IRBs and institutional officials responsible for review and oversight of human subject research. The draft guidance, when finalized, will supersede FDA's 1998 "Appendix H: A Self-Evaluation Checklist for IRBs" and OHRP's 2011 "Guidance on Written IRB Procedures." The issuance of joint draft guidance reflects OHRP's and FDA's ongoing efforts to harmonize the agencies' regulatory requirements and guidance for human subject research.

The draft guidance strongly encourages IRBs to focus on specific operational details and to provide written procedures sufficient for investigators and regulators to understand precisely how the IRB is managing and satisfying its regulatory obligations. The agencies noted an observation that the written procedures of some IRBs simply reiterate the regulations, providing insufficient detail about the actual operations of the IRB. To prompt a critical assessment of IRB operations and organizational structure, the majority of the draft guidance is presented as a checklist identifying the agencies' regulatory requirements and recommendations for IRB written procedures. While HHS and FDA regulations require IRBs to have written procedures for certain functions (45 C.F.R. § 46.103(b)(4) and (5), 21 C.F.R. § 56.108(a) and (b)), such as the initial and continuing review of research and ensuring prompt reporting to the IRB of proposed changes in research activity, the agencies encourage IRBs to consider developing written procedures not required by the regulations, such as procedures for activities required by the regulations but for which written procedures are not required. For example, the checklist includes recommendations for written procedures regarding IRB membership and managing conflicts of interest of IRB members. The goal, according to OHRP and FDA, is for IRB written procedures to be sufficiently detailed to ensure that IRB members and administrative staff are carrying out their duties consistently and effectively, and that the rights and welfare of human subjects are protected.

FDA Issues UDI Form and Content Guidance

At the end of July 2016, FDA announced the availability of a draft guidance titled "Unique Device Identification System: Form and Content of the Unique Device Identifier (UDI)," which clarifies the requirements for unique device identifiers on medical devices, as established in 2013 with publication of the UDI System final rule. The guidance document further defines the two forms of UDI labeling (plain-text and automatic identification and data capture, "AIDC") and clarifies how UDI information should be ordered and presented on device packaging. According to the guidance, plain-text UDIs should be legible interpretations of the data characters encoded in the AIDC form of the full UDI and should be located near the AIDC form of the UDI on devices. Such plain-text versions of UDIs should include device and production information, as well as data delimiters—a defined set of characters that identifies specific data elements within the UDI. The AIDC form of the UDI should be in a format that can be read by a bar code scanner or similar AIDC technology, and the guidance encourages scanning of UDIs whenever possible to minimize errors and allow for "rapid and accurate data acquisition, recording, and retrieval." The guidance document declines to recommend how labelers should disclose the presence of AIDC technology that is not evident upon visual examination, giving flexibility and discretion to labelers. Comments on the draft guidance are due September 26, 2016.

FDA Announces Pilot of Intercenter Consult Request Process for Combination Products

Last month, FDA announced the beginning of its intercenter consult request process that will be piloted across the Agency through 2017. The pilot, which is part of FDA's larger efforts to improve and streamline the review of combination products (i.e., products that combine drugs, devices, and/or biological products), will: (i) establish timelines, specific to center and submission type, for identifying products as combination products and issuing and completing consults needed to support the review; (ii) develop a tiered consult approach that streamlines interactions across centers; (iii) define clear roles and responsibilities for the centers and offices involved; and (iv) create a standard, semi-automated, user-friendly intercenter consult request form that is managed electronically to ensure that users always have the most updated version and that all forms are tracked through a single system. The pilot began on August 1, 2016, and will proceed in three phases. FDA plans to collect data throughout the program to evaluate its success and refine processes, procedures, and training for subsequent phases as needed.

FDA Publishes User Fee Rates for FY2017

Between July 27 and August 1, 2016, FDA announced the fiscal year 2017 ("FY2017") user fee raters for generic drugs, animal drugs, animal generic drugs, biosimilars, prescription drugs, medical devices, and human drug compounding outsourcing facilities. Click here to view a chart summarizing the fees and the percent change over the previous year. The fee rates are effective October 1, 2016, and will remain in effect through September 30, 2017.

Other News

FDA Approves Third Biosimilar Product

FDA Announces Pre-Request for Designation Process

PhRMA and BIO Announce Endorsement of Principles on Responsible Sharing of Truthful and Non-Misleading Information About Medicines with Health Care Professionals and Payers

CMS Hosts Special Open Door Forum on Revisions to Open Payments (request for comments, meeting presentation, and meeting transcript)

FDA Exempts General Wellness, Low-Risk Devices from Regulations in Final Guidance

EMA Announces New Chapter in Guidelines on Good Pharmacovigilance Practices, "Product- or Population-Specific Considerations II: Biological Medicinal Products"

Regulatory Updates

Balancing Premarket and Postmarket Data Collection: CDRH Completes Retrospective Review of PMAs Approved Before 2010 and Seeks Feedback on Results

In the August 8, 2016, Federal Register, the Center for Devices and Radiological Health ("CDRH") announced that—as a part of its 2014-15 Strategic Priority to "Strike the Right Balance Between Premarket and Postmarket Data Collection"—the Center completed its goal of retrospectively reviewing 100 percent of all Premarket Approval ("PMA") product codes ("procodes") with active PMAs that were approved before 2010 to assess whether premarket data collection could be shifted to the postmarket setting or reduced through reliance on postmarket controls and whether reclassification could be appropriate based on the Agency's updated understanding of the relevant technologies. The results of CDRH's review are available online, which are additive to results previously reported in April 2015. While CDRH continues to consider comments on the April 2015 results, it seeks comments on the additional procodes identified as candidates for reclassification, a reduction in premarket data collection through reliance on postmarket controls, or a shift in data collection from premarket to postmarket. FDA is prioritizing the identified procodes according to public health impact and Center resources. Firms that are developing a device in an affected category should seek feedback on their data collection plan through a presubmission or contact the appropriate review branch to obtain additional information. Comments are due October 7, 2016.

FDA Reopens Comment Period for User-Fee Program for OTC Drugs

In the August 8, 2016, Federal Register, FDA announced it is reopening the comment period for the potential development of a user-fee program for nonprescription, or OTC, monograph drugs. FDA initially requested comments and announced a public meeting in the May 11, 2016, Federal Register. The public meeting was held on June 10, 2016, and meeting materials, including a transcript, are available here. FDA recently held a webinar (on September 6, 2016) as a follow-up to the June 2016 public meeting and to provide updates on FDA-industry discussions that began in July 2016 (meeting minutes for those discussions can be found here). Additional information is available here. Comments are due October 6, 2016.

FDA Proposes Revising Regulations for Good Laboratory Practice for Nonclinical Laboratory Studies

In the August 24, 2016, Federal Register, FDA proposed amending its regulations for good laboratory practice ("GLP") for nonclinical (often referred to as preclinical) laboratory studies to require a complete quality system approach, referred to as a GLP Quality System, when safety and toxicity studies support or are intended to support applications or submissions for products regulated by FDA. As proposed, the GLP Quality System includes additional responsibilities for testing facility management and new responsibilities for maintaining Standard Operation Procedures ("SOPs"). FDA also proposes revising the definition of "testing facility" to reflect current practices, making it applicable to all nonclinical laboratory studies, regardless of whether they are conducted at a single facility or at multiple sites. It is FDA's expectation that a GLP Quality System will provide the appropriate framework for building quality into a nonclinical laboratory study and will result in more reliable data for FDA to consider when making regulatory decisions. Comments are due November 22, 2016.

FDA Proposes Expanding Scope of Clinical Investigator Disqualification in Regulations for New Animal Drugs for Investigational Use

In the August 24, 2016, Federal Register, FDA proposed expanding the scope of clinical investigator disqualification in its regulations for new animal drugs for investigational use to include ineligibility to conduct nonclinical laboratory studies. Currently, when the Commissioner of Food and Drugs ("Commissioner") determines that an investigator is ineligible to receive a new animal drug for investigational use, the investigator also is ineligible to conduct any clinical investigation that supports an application for a research or marketing permit for products regulated by FDA. Under FDA's proposal, when the Commissioner determines that an investigator is ineligible to receive a new animal drug for investigational use, the investigator also will be ineligible to conduct any nonclinical study intended to support an application for a research or marketing permit for a new animal drug. With this proposal, FDA intends to help ensure adequate protection of animal research subjects and the quality and integrity of data submitted to FDA. Comments are due November 22, 2016.

FDA to Host Public Conference on Key Aspects of Drug and Device Regulations

In the August 30, 2016, Federal Register, FDA announced it will sponsor a two-day conference titled "FDA Small Business and Industry Assistance Regulatory Education for Industry Fall Conference." The conference is designed for small manufacturers of drugs and/or medical devices who want to learn about FDA's approach to regulating drugs and devices, but anyone involved in the pharmaceutical and/or device industry may attend. Center for Drug Evaluation and Research topics for discussion include manufacturing process validation, interactions with FDA, emerging technology and inspection for new drug applications, and biologic license applications. CDRH topics for discussion include de novo, design controls, and complaints. The meeting will be available via webcast, but there will not be a transcript available following the meeting. The public conference will be held September 27 and 28, 2016.

FDA Issued the Following Draft and Final Guidance Documents:

Draft Guidance for Industry and FDA Staff: Unique Device Identification System: Form and Content of the Unique Device Identifier (UDI), July 26, 2016, Federal Register. Comments are due September 26, 2016.

Draft Guidance for Institutions and IRBs: Institutional Review Board (IRB) Written Procedures, August 2, 2016, Federal Register. Comments are due October 3, 2016.

Draft Guidance for Industry and FDA Staff: Deciding When to Submit a 510(k) for a Change to an Existing Device, August 8, 2016, Federal Register. Comments are due November 7, 2016.

Draft Guidance for Industry and FDA Staff: Deciding When to Submit a 510(k) for a Software Change to an Existing Device, August 8, 2016, Federal Register. Comments are due November 7, 2016.

Guidance for Industry and FDA Staff: Adaptive Designs for Medical Device Clinical Studies, July 27, 2016, Federal Register.

Draft Guidance for Industry and FDA Staff: Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, July 27, 2016, Federal Register. Comments are due October 25, 2016.

Guidance for Industry and FDA Staff: General Wellness: Policy for Low Risk Devices, July 29, 2016, Federal Register.

Guidance for Industry: Determining Donor Eligibility for Autologous Donors of Blood and Blood Components Intended Solely for Autologous Use-Compliance Policy, August 2, 2016, Federal Register.

Draft Guidance for Industry and FDA Staff: Medical X-Ray Imaging Devices Conformance with IEC Standards, August 3, 2016, Federal Register. Comments are due November 1, 2016.

Draft Guidance for Industry: Insanitary Conditions at Compounding Facilities, August 4, 2016, Federal Register. Comments are due October 3, 2016.

Draft Guidance for Industry: Ulcerative Colitis: Clinical Trial Endpoints, August 8, 2016, Federal Register. Comments are due October 7, 2016.

Guidance for Industry and FDA Staff: Premarket Notification (510(k)) Submissions for Electrosurgical Devices for General Surgery, August 15, 2016, Federal Register.

Guidance for Industry and FDA Staff: Premarket Notification (510(k)) Submissions for Bipolar Electrosurgical Vessel Sealers for General Surgery, August 15, 2016, Federal Register.

Guidance for Industry: Use of Nucleic Acid Tests to Reduce the Risk of Transmission of Hepatitis B Virus from Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products, August 17, 2016, Federal Register.

Draft Guidance for Industry: Regulatory Classification of Pharmaceutical Co-Crystals, August 17, 2016, Federal Register. Comments are due October 17, 2016.

Draft Guidance for Industry: Bioequivalence Recommendations for Fidaxomicin, August 24, 2016, Federal Register. Comments are due October 24, 2016.

Guidance for Industry, FDA Staff, and Other Stakeholders: Patient Preference Information—Voluntary Submission, Review in Premarket Approval Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and Inclusion in Decision Summaries and Device Labeling, August 24, 2016, Federal Register.

Guidance for Industry and FDA Staff: Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications, August 24, 2016.

Guidance for Industry: Abbreviated New Drug Application Submissions—Refuse to Receive for Lack of Justification of Impurity Limits, August 25, 2016, Federal Register.

Guidance for Industry: Microbiology Data for Systemic Antibacterial Drugs—Development, Analysis, and Presentation, August 26, 2016, Federal Register.

Guidance for Industry and FDA Staff: Enforcement Policy on National Health Related Item Code and National Drug Code Numbers Assigned to Devices, August 30, 2016, Federal Register.

Draft Guidance for Industry: Bioequivalence Recommendations for Risperidone, August 30, 2016, Federal Register. Comments are due October 31, 2016.

Guidance for Industry: Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components, August 31, 2016, Federal Register.

Guidance for Industry and FDA Staff: Guidance for the Submission of 510(k)s for Solid State X‑ray Imaging Devices, September 1, 2016.

Draft Guidance for Industry: ICH S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies—Questions and Answers, September 8, 2016, Federal Register. Comments are due December 7, 2016.

Draft Guidance for Industry: E17 General Principles for Planning and Design of Multi-Regional Clinical Trials, September 9, 2016, Federal Register. Comments are due November 8, 2016.

Draft Guidance for Industry, FDA Staff, and Third Party Review Organizations: 510(k) Third Party Review Program, September 12, 2016, Federal Register. Comments are due November 14, 2016.

EU Regulatory Notices

EU and US eHealth IT Roadmap

The European Commission's Directorate General for Communications Networks, Content and Technology ("DG CONNECT") and the United States Department of Health and Human Services ("HHS"), after consulting with stakeholders, have updated the roadmap for their Memorandum of Understanding ("MoU") on eHealth/Health information technologies. In spring 2013, DG CONNECT and HHS published a first roadmap of MoU actions, focusing on two priority areas (work streams): (i) standards development to foster transnational interoperability of electronic health information and communication technology and (ii) workforce skills to develop and expand the Health IT workforce in Europe and the United States. At the end of 2015, it was agreed to add a third priority area, "Transatlantic eHealth/Health IT Innovation Ecosystems," which aims at encouraging innovation in the eHealth/Health IT industry. One of its key elements will be to strive to identify key EU and U.S. stakeholders and enlist their support for greater collaboration between companies and ecosystems located in each jurisdiction. The foreseen activities for this new work stream are outlined in the annex to the roadmap and will start in fall/autumn 2016.

New EMA Guidelines on Good Pharmacovigilance Practices

The European Medicines Agency ("EMA") has adopted a new chapter to its guidelines on good pharmacovigilance practices ("EU-GVP"), titled "Product- or Population-Specific Considerations II: Biological Medicinal Products." Good pharmacovigilance practices are a set of measures designed to ensure the robustness of the system of safety monitoring. The new chapter provides guidance on how to better monitor and manage the safety of biological medicines with a view to optimizing the safe and effective use of these products in Europe. The guidance seeks to support those responsible for monitoring these medicines by:

• Highlighting specific issues and challenges for the pharmacovigilance of biological medicines, e.g., in relation to variability of the active substance or traceability of products;
• Providing recommendations on how to address these specificities and challenges; and
• Outlining the roles and responsibilities of the various actors.

The GVP guidance was effective on August 16, 2016.

EMA Workshop on Genetically Modified T-Cells

EMA's Committee for Advanced Therapies ("CAT") is organizing a workshop on November 15 and 16, 2016, to discuss scientific and regulatory challenges of immunotherapy medicines based on genetically modified T-cells (white blood cells that normally fight off viruses and bacteria). The open workshop aims to facilitate dialogue between the CAT and medicine developers from industry and academia on:

• Current scientific developments;
• Regulatory requirements for product manufacture and testing; and
• Non-clinical studies and clinical development.

The workshop program is available online, and the event will be broadcast live. People interested in participating are invited to register using the form available on the website.

French ANSM Issues Guidance on Pilot Phase Clinical Trials

In anticipation of the new clinical trials regulation (Regulation No. 536/2014 dated April 16, 2014) that will repeal the current clinical trials directive (Directive 2001/20/EC), the French National Drug and Health Product Authority ("ANSM"), in conjunction with the 39 existing Ethics Committees ("EC"), is offering sponsors the opportunity to participate in a "pilot phase" in order to anticipate the next stages in the organization and coordinate assessments carried out by voluntary ECs and the ANSM, respectively. The purpose of the pilot phase is to ensure that France is ready when the European Regulation comes into force.

On August 11, 2016, ANSM published a "Practical Information Guide for Applicants" regarding clinical drug trials submitted within the pilot phase. According to the ANSM guide, a sponsor may either apply the regular current French procedure or choose to participate, on a voluntary basis, in the experimental Pilot Phase proposed by the ANSM, which is described in the Guide. Although the EU portal, which will be the single entry point for submitting clinical trials applications in the EU, is not effective yet, the ANSM attempts to simulate the new procedure by: (i) requiring a parallel, simultaneous submission of the application to the ANSM and the competent French EC; (ii) coordinating the assessment period and dialogue between the ANSM and the ECs, since the current procedure provides for separate applications to both bodies; and (iii) complying with the schedule and deadlines provided by the European Regulation.

UK's MHRA Launches FakeMeds Campaign with Warning on Diet Pills

On August 17, 2016, the UK's Medicines and Healthcare products Regulatory Agency ("MHRA") launched FakeMeds campaign aimed at young adults warning of the dangers of buying diet pills online. MHRA seized more than 240,000 doses of unlicensed slimming pills in 2015 and closed down more than 2,000 unauthorized online retailers. Research carried out by MHRA in 2016 showed that although shoppers believe themselves to be "internet savvy," 79 percent of the public are unaware of the issue of fake medical products. The campaign provides practical information on how to recognize legitimate online retailers of medicines and medical devices.

UK's MHRA Issues Guidance on Health Apps

On August 25, 2016, MHRA issued updated guidance to help identify the health apps that are medical devices and make sure they comply with regulations and are acceptably safe. The guidance is presented as a step-by-step interactive PDF. Aimed at both users and developers, app users can use this guidance to check if their health app is a medical device, and what to look for to make sure the app is safe and works; software and app developers can use the guidance to identify if their product is a medical device. The guidance serves as an aid to developers in navigating the regulatory system so they are aware what procedures they need to have in place to get a CE mark and what their reporting responsibilities are when things change or go wrong.

New EMA Guidance on Data Integrity

EMA has released new good manufacturing practice ("GMP") guidance aimed at ensuring the integrity of data generated in the process of testing, manufacturing, packaging, distributing, and monitoring medicines. The advice applies to both paper-based and electronic systems. It specifically addresses:

• Assessment of risks to data integrity in the collection, processing, and storage of data;
• Risk management measures at various stages of the "data lifecycle";
• Design and control of both electronic and paper-based documentation systems; and
• Measures to ensure data integrity for activities contracted out to another company.

European Commission Publishes Revised Medical Device Guidance on Stand-Alone Software

The European Commission has published a revised version of its Guidelines on Qualification and Classification of Stand-Alone Software ("MEDDEV 2.1/6"), which replaces the earlier 2012 version. The changes are limited, with the key change being in the definitions section. The guidance now contains a definition of "software": a "set of instructions that processes input data and creates output data." The guidance also introduces definitions of "input data" and "output data." The new definition of software is used in the new question in decision node 1 in the Medical Devices Directive flow chart ("Is the product a software according to the definition of this document?"). The new MEDDEV version also clarifies that "the criteria specified in this document apply also to mobile applications"; however, it was hoped that the Commission would use this opportunity to provide additional guidance on mobile applications that fall within the classification of medical devices.

EMA Publishes Report on Adaptive Pathways Pilot Project

EMA has published a final report on the experience gained during its pilot project on adaptive pathways, a product development concept for medicines that address patients' unmet medical needs. In March 2014, EMA launched the pilot project to explore the practical implications of the adaptive pathways concept with medicines already under development. It is not a new route of marketing authorization; it makes use of existing regulatory tools. Under this approach, the medicine is first authorized in a small patient population that is likely to benefit most from the medicine. Then, additional evidence is gathered over time, resulting in progressive licensing adaptations to extend or restrict the previously authorized indications of the medicine. During the pilot, EMA received 62 applications, 18 of which were selected for in-depth, face-to-face meetings with the participation of other stakeholders. At the end of the pilot, six of these applications had progressed to receive formal parallel advice by EMA and health technology assessment bodies and one to benefit from simple scientific advice.

Proposals to Revise Guidance on First-in-Human Clinical Trials

EMA, in cooperation with the European Commission and the Member States of the EU, is proposing changes to current guidance on first-in-human clinical trials with the aim of improving strategies to identify and mitigate risks to trial participants. These changes are outlined in a new concept paper that has been released for public consultation. The release of the concept paper is part of a review of the EMA guideline published in 2007 that provides advice on first-in-human clinical trials, in particular on the data needed to enable their appropriate design and allow the initiation of treatment in trial participants. This review identified those parts of the current guideline that need to be amended to take into account the evolution of practices in the conduct of these studies since the guideline was first published. The review also takes into account the lessons learned from the fatal incident that took place during a Phase I first-in-human clinical trial in Rennes, France, in January 2016. Comments on the proposals should be sent to FIH-rev@ema.europa.eu until September 30, 2016.

EMA Consults on Modeling and Simulation in the Development and Regulatory Review of Medicines

EMA has published a draft guideline to support and guide the use of innovative modeling and simulation approaches that are currently being used during the development of medicines. The draft guideline focuses on the use of physiologically based pharmacokinetic ("PBPK") modeling. Using specialized software platforms, these models aim to simulate the concentration of a medicine in the body over time. They are increasingly used by medicine developers for various purposes such as predicting the interaction between medicines in the body or helping to define the initial dose of a medicine in pediatric and first-in-human trials. The draft guideline clarifies how these models can support decision-making in the context of a marketing authorization application. Comments on the draft guideline should be sent to pkwpsecretariat@ema.europa.eu by January 31, 2017.

EMA Consults on Development of Medicines to Treat Tuberculosis

EMA has launched a public consultation on revised guidance on the development of new medicines to treat tuberculosis. The guidance is an addendum to EMA's guideline on the evaluation of medicines to treat bacterial infections. EMA will host a workshop in November 2016 to discuss stakeholders' comments on the revised guidance. Stakeholders can send their comments to the Agency until January 31, 2017.

EMA Updates Organizational Structure

EMA has announced some organizational adjustments and strategic amendments of its corporate management structure that are aimed at creating a leaner, more streamlined architecture and improved administrative support. The main changes include:

• Reduction of the number of divisions dealing with human medicines from four to three, with one division responsible for support to medicines developers; one for the evaluation of medicines, bringing scientific and procedure management under one umbrella; and one for the oversight of medicines, including pharmacovigilance and inspection;
• Creation of a new function dedicated to strengthening the collaboration between EMA and the national competent authorities by overseeing the implementation of the joint network strategy to 2020, promoting innovation in regulatory science across the European regulatory system for medicines, and addressing the increasing complexity of the committees' activities coordination; and
• Streamlining the division dealing with administration and corporate management through separate entities for strategic planning, budgeting and monitoring, finance and procurement, and support to staff and delegates.

It is not anticipated that interactions between stakeholders and the Agency will be affected by these changes.

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