Regulatory News

The latest regulatory news, consultation documents, and adopted guidelines and legislation, mainly from the European Commission, the European Medicines Agency and the Food and Drug Administration.

Providing regulatory submissions in electronic and non-electronic format
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Providing Regulatory Submissions in Electronic and Non-Electronic Format—Promotional Labeling and Advertising Materials for Human Prescription Drugs.”

This guidance pertains to submissions of promotional materials for human prescription drugs (drugs) to the Food and Drug Administration (FDA or Agency) made by manufacturers, packers, and distributors (firms), whether the applicant or an entity acting on behalf of the applicant. Specifically, this guidance pertains to submissions made to the Office of Prescription Drug Promotion (OPDP) in the Center for Drug Evaluation and Research (CDER) and the Advertising and Promotional Labeling Branch (APLB) in the Center for Biologics Evaluation and Research (CBER). This guidance also explains certain aspects of electronic submission of promotional materials in module 1 of the electronic common technical document (eCTD), using version 3.3 or higher of the us-regional-backbone file. More information is available on the FDA’s website.

Benefit-risk assessment framework for opioid analgesic drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework.”

The purpose of this guidance is to describe the benefit-risk framework the Agency uses in evaluating applications for opioid analgesic drugs. This guidance summarizes the information that should be included in a new drug application (NDA) for an opioid analgesic drug to facilitate the Agency’s benefit-risk assessment. More information is available on the Federal Register’s website.

Consultation Deadline: 20th August, 2019

Content and format of ANDA submissions
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “ANDA Submissions — Content and Format.”

This guidance is intended to assist applicants in preparing abbreviated new drug applications (ANDAs) for submission to FDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)). This guidance details the information that should be provided in each section of the common technical document (CTD) format for human pharmaceutical product applications and identifies supporting guidance documents and recommendations issued by FDA to assist applicants in preparing their ANDA submission. This guidance identifies the information that an applicant should include to ensure that a complete, high-quality application is submitted to FDA. FDA has previously published guidance documents on the filing process, including the guidance for industry about refuse-to-receive standards, and common, recurring deficiencies which should be reviewed thoroughly prior to submission of an ANDA. More information is available on the FDA’s website.

Quality requirements for drug-device combinations
The European Medicines Agency have published: Scientific guideline: Draft guideline on the quality requirements for drug-device combinations.

In recent years there has been an increase in the number of scientific advice requests and marketing authorisation applications (MAAs) where a medicinal product incorporates, either in an integral or non integral manner, a medical device/medical device component for the use of the medicine. The availability of commercialised devices with automated functions is increasing and this may benefit patients with regular and long-term dosing requirements in an outpatient setting, either by self administration or with the support of a professional or lay caregiver. This reduces the burden on patients and on healthcare systems. This guideline provides guidance on the documentation expected for Drug-Device Combinations (DDCs) in the quality part of the dossier for a marketing authorisation application or a variation application. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Developing drugs for treatment of nonalcoholic steatohepatitis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Nonalcoholic Steatohepatitis with Compensated Cirrhosis: Developing Drugs for Treatment.”

The purpose of this draft guidance is to provide the Agency’s current recommendations regarding the important components of a drug development program for nonalcoholic steatohepatitis (NASH) with compensated cirrhosis. This draft guidance focuses on the enrollment criteria, trial design, efficacy endpoints, and safety considerations for phase 3 trials. More information is available on the Federal Register’s website.

Consultation Deadline: 6th August, 2019

Enhancing the diversity of clinical trial popoulations
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Enhancing the Diversity of Clinical Trial Populations—Eligibility Criteria, Enrollment Practices, and Trial Designs.”

This draft guidance recommends approaches that sponsors of clinical trials to support a new drug application or a biologics license application can take to broaden eligibility criteria, when scientifically and clinically appropriate, and increase enrollment of underrepresented populations in their clinical trials. The draft guidance reflects FDA policy encouraging inclusion in clinical trials of participants representative of the broad population of patients who will be exposed to a marketed drug and is being issued to satisfy the FDA Reauthorization Act of 2017 (FDARA) mandate. More information is available on the Federal Register’s website.

Consultation Deadline: 6th August, 2019

Development of therapeutic protein biosimilars
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations.”

This draft guidance describes the Agency’s recommendations on the design and evaluation of comparative analytical studies intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product licensed under the Public Health Service Act (PHS Act). Additionally, this draft guidance is intended to provide recommendations to sponsors on the scientific and technical information for the chemistry, manufacturing, and controls (CMC) portion of a marketing application for a proposed product submitted under the PHS Act. This draft guidance revises the guidance entitled “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product” that was published on April 30, 2015. More information is available on the Federal Register’s website.

Consultation Deadline: 22nd July, 2019

Draft ICH guideline E8 (R1) on general considerations for clinical studies
The European Medicines Agency have published: Scientific guideline: ICH guideline E8 (R1) on general considerations for clinical studies – Step 2b, draft: consultation open.

Clinical studies of medical interventions are conducted to provide information that can ultimately improve access to safe and effective drugs with meaningful impact on patients, while protecting those participating in the studies. This document focuses on designing quality into clinical studies, considering the diversity of clinical study designs and data sources used to support regulatory and other health policy decisions. More information is available on the EMA’s website.

Consultation Deadline: 30th September, 2019

Considerations in demonstrating interchangeability with a reference product
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Considerations in Demonstrating Interchangeability With a Reference Product.”

This guidance is intended to assist sponsors in demonstrating that a proposed therapeutic protein product is interchangeable with a reference product for the purposes of submitting a marketing application or supplement under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)). The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) amends the PHS Act and other statutes to create an abbreviated licensure pathway in section 351(k) of the PHS Act for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological reference product (see sections 7001 through 7003 of the Patient Protection and Affordable Care Act (Affordable Care Act) (Public Law 111-148)). Although the 351(k) pathway applies generally to biological products, this guidance focuses on therapeutic protein products and gives an overview of important scientific considerations in demonstrating interchangeability of a proposed therapeutic protein product (proposed interchangeable biosimilar or proposed interchangeable product) with a reference product. More information is available on the FDA’s website.

Determining whether to submit an ANDA or a 505(b)(2) application
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Determining Whether to Submit an ANDA or a 505(b)(2) Application.”

This guidance is intended to serve as a foundational guidance to assist applicants in determining which one of the abbreviated approval pathways under the Federal Food, Drug, and Cosmetic Act (FD&C Act) is appropriate for the submission of a marketing application to FDA. Many potential drug product developers are not familiar with the different abbreviated approval pathways for drug products under the FD&C Act — the abbreviated approval pathways described in section 505(j) and 505(b)(2) of the FD&C Act (21 U.S.C. 355(j) and 21 U.S.C. 355(b)(2), respectively) — or the types of data and information that are permitted to support approval under those pathways. In order to familiarize potential drug product developers with these abbreviated pathways, this guidance highlights criteria for submitting applications under the abbreviated approval pathways described in section 505(j) and 505(b)(2), identifies considerations to help potential applicants determine whether an application would be more appropriately submitted under section 505(j) or pursuant to section 505(b)(2) of the FD&C Act, and provides direction to potential applicants on requesting assistance from FDA in making this determination. More information is available on the FDA’s website.

Maximal usage trials for topically applied active ingredients in OTC monographs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Maximal Usage Trials for Topically Applied Active Ingredients Being Considered for Inclusion in an Over-The -Counter Monograph: Study Elements and Considerations.”

This guidance provides recommendations for the conduct of in vivo absorption trials for topically applied active ingredients that are under consideration for inclusion in an over-the-counter (OTC) drug monograph. A Maximal Usage Trial (MUsT) is a standard approach to assess the in vivo bioavailability of topical drug products intended for local therapeutic effects. , The methodology described in this guidance adapts MUsT principles for active ingredients being considered for inclusion in an over-the-counter (OTC) monograph. Because information from a MUsT can help identify the potential for systemic exposure to a topically applied active ingredient, such information can help inform an FDA determination of whether additional safety data are needed to support a finding that a topical OTC drug containing that active ingredient is generally recognized as safe and effective (GRASE) for its intended use. This guidance outlines the FDA’s recommendations for designing and conducting a MUsT for this purpose, including critical study elements, data analysis, and considerations for special topic areas (e.g., pediatrics, geriatrics). This guidance also encourages study sponsors to seek feedback from the FDA on their overall approach and the design of a particular study. More information is available on the FDA’s website.

Reproductive toxicity testing and labeling recommendations for oncology pharmaceuticals
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations.”

The purpose of this guidance is to assist sponsors in evaluating reproductive toxicity (mainly for effects on embryo-fetal development (EFD)) for oncology pharmaceuticals and to provide recommendations for product labeling on duration of contraception following cessation of therapy to minimize potential risk to a developing embryo or fetus. This guidance is intended to facilitate the development of oncology pharmaceuticals while avoiding unnecessary use of animals, in accordance with the 3R (reduce, refine, replace) principles. More information is available on the FDA’s website.

Postapproval pregnancy safety studies
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Postapproval Pregnancy Safety Studies.”

When finalized, the purpose of this guidance will be to provide sponsors and investigators with recommendations on how to design investigations to assess the outcomes of pregnancies in women exposed to drugs and biological products regulated by FDA (i.e., pregnancy safety studies). This draft guidance, when finalized, will represent the current thinking of FDA on postapproval pregnancy safety studies. This draft guidance is intended to help industry develop more comprehensive and scientifically sound studies to assess the safety of drug and biological products during pregnancy in the postmarketing setting. The previous guidance for industry entitled “Establishing Pregnancy Exposure Registries,” issued on August 23, 2002, has been withdrawn. More information is available on the Federal Register’s website.

Consultation Deadline: 8th July, 2019

Real-world data and real-world evidence for drugs and biologics
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics.”

This draft guidance is intended to encourage sponsors and applicants who are using real-world data (RWD) to generate real-world evidence (RWE) as part of their regulatory submissions to provide certain information to FDA so that FDA can internally track the submissions. The purpose of this guidance is to provide instructions on how to document that a submission includes RWE. More information is available on the Federal Register’s website.

Consultation Deadline: 8th July, 2019

Considerations for design of clinical lactation studies
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Clinical Lactation Studies: Considerations for Study Design.”

This guidance reflects FDA’s current recommendations to sponsors regarding lactation studies during drug development. This guidance provides recommendations to facilitate the conduct of lactation studies. Such studies can inform breastfeeding with drug use recommendations included in the Lactation subsection of labeling. The recommendations in this guidance also reflect discussions from the 2007 Pediatric Advisory Committee meeting and the 2016 Lactation Workshop, which considered how data from clinical lactation studies can inform the safety of a drug when used during lactation. This guidance replaces the draft guidance for industry entitled “Clinical Lactation Studies—Study Design, Data Analysis, and Recommendations for Labeling” issued February 2005. More information is available on the Federal Register’s website.

Consultation Deadline: 8th July, 2019

Developing stimulant drugs for treatment of ADHD
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Attention Deficit Hyperactivity Disorder: Developing Stimulant Drugs for Treatment.”

The purpose of this draft guidance is to assist sponsors in the clinical development of stimulant drugs for treatment of attention deficit hyperactivity disorder (ADHD) in pediatric and adult patients. Specifically, this draft guidance addresses the Agency’s current recommendations regarding the development programs for methylphenidate and amphetamine products, as well as for novel (i.e., new molecular entity (NME)) stimulant drugs. More information is available on the Federal Register’s website.

Consultation Deadline: 5th July, 2019

European Commission Safety Features Q&A document updated
The European Commission has published an updated version, Version 14, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

Version 14 of the document, dated May 2019, supersedes Version 13. Q&A 5.9 was added, while Q&As 1.6, 1.28, 7.15 and 8.9 were revised.

More information is available on the Commission’s website.

Commission launches new version of the Union Register
The European Commission has launched a new version of its Union Register of medicinal products.

Available since 1995, the Union Register lists all medicinal products for human and veterinary use (over 1.300 medicines) authorised by the Commission through the centralised procedure. It also covers designation of orphan medicinal products, refused authorisations and reviews related to nationally authorised medicinal products. This update provides a whole range of additional features, including filtering and export functionalities, and aims at offering an improved experience for all users through simplified navigation and greater compatibility with mobile devices. More information is available on the Commission’s website.

Adjusting for covariates in randomized clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biologics with Continuous Outcomes.”

The draft guidance, when finalized, will represent the current thinking of FDA on adjusting for covariates in randomized clinical trials for drugs and biologics, focusing on randomized clinical trials with continuous endpoints. More information is available on the Federal Register’s website.

Consultation Deadline: 24th June, 2019

Initiation of voluntary recalls
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry and FDA staff entitled “Initiation of Voluntary Recalls Under 21 CFR part 7, subpart C.”

The draft guidance, if finalized, would establish guidance for industry and FDA staff regarding timely initiation of voluntary recalls of FDA-regulated products. The draft guidance discusses what preparations firms in a distribution chain, including manufacturers and distributors, should consider making to establish recall initiation procedures; to ensure timely identification of, and response to, product problems that might lead to a recall; and to promptly issue recall communications and press releases or other public notices. It also discusses preparations that firms in a distribution chain should consider making to ensure timely responses to a recall communication. In addition, it discusses how FDA assists firms with carrying out their recall responsibilities to protect the public health from distributed products in violation of the Federal Food, Drug, and Cosmetic Act and other laws administered by FDA. More information is available on the Federal Register’s website.

Consultation Deadline: 24th June, 2019

Determining when a REMS is necessary
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “REMS: FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary.”

This guidance is intended to clarify how the Food and Drug Administration (FDA or Agency) applies the factors set forth in section 505-1 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355-1) in determining whether a risk evaluation and mitigation strategy (REMS) is necessary to ensure that the benefits of a drug outweigh its risks. This guidance fulfills one of the performance goals that FDA agreed to satisfy in the reauthorization of the Prescription Drug User Fee Act (PDUFA) V. More information is available on the FDA’s website.

General approach to establish a microbiological ADI
The European Medicines Agency have published: Scientific guideline: VICH GL36(R2): Studies to evaluate the safety of residues of veterinary drugs in human food: general approach to establish a microbiological ADI, adopted.

A variety of toxicological evaluations are performed to establish the safety of veterinary drug residues in human food. An issue that needs to be addressed for veterinary antimicrobial drugs is the safety of their residues on the human intestinal flora. The objectives of this guideline are (1) to outline the steps in determining the need for establishing a microbiological acceptable daily intake (ADI); (2) to recommend test systems and methods for determining noobservable adverse effect concentrations (NOAECs) and no-observable adverse effect levels (NOAELs) for the endpoints of health concern; and (3) to recommend a procedure to derive a microbiological ADI. It is recognized that different tests may be useful. The experience gained with the recommended tests may result in future modifications to this guideline and its recommendations. More information is available on the EMA’s website.

Date for coming into effect: 1st August, 2019

Marker residue depletion studies to establish product withdrawal periods in aquatic species
The European Medicines Agency have published: Scientific guideline: VICH GL57 on Studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing species: marker residue depletion studies to establish product withdrawal periods in aquatic species, adopted.

This guidance is one of a series developed to facilitate the mutual acceptance of residue chemistry data for veterinary drugs used in food-producing animals by national/regional regulators. This guidance was prepared after consideration of the current national/regional requirements and recommendations for evaluating veterinary drug residues in the VICH regions. The objective of this guidance is to provide study design recommendations which will facilitate the universal acceptance of the generated residue depletion data to fulfill the national/regional requirements. This document is an extension to the parent residue guidance: VICH GL48, “Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-producing Animals: Marker Residue Depletion Studies to Establish Product Withdrawal Periods.” This guidance VICH GL57 provides recommendations on what should be included in a marker residue depletion study design for aquatic food-producing species. Metabolism studies based on VICH GL46, “Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food producing Animals: Metabolism Study to determine the Quantity and Identify the Nature of Residues” can be used in aquatic food-producing species to identify a marker residue. The use of this VICH guidance to support registration of a product for local distribution only is also encouraged, but is up to the discretion of the local regulatory authority. More information is available on the EMA’s website.

Date for coming into effect: 1st February, 2020

Revision 1 of ICH Q3D on elemental impurities
The European Medicines Agency have published: Scientific guideline: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q3D on elemental impurities – Step 5 – Revision 1, adopted.

Elemental impurities in drug products may arise from several sources; they may be residual catalysts that were added intentionally in synthesis or may be present as impurities (e.g., through interactions with processing equipment or container/closure systems or by being present in components of the drug product). Because elemental impurities do not provide any therapeutic benefit to the patient, their levels in the drug product should be controlled within acceptable limits. There are three parts of this guideline: the evaluation of the toxicity data for potential elemental impurities; the establishment of a Permitted Daily Exposure (PDE) for each element of toxicological concern; and application of a risk-based approach to control elemental impurities in drug products. An applicant is not expected to tighten the limits based on process capability, provided that the elemental impurities in drug products do not exceed the PDEs. The PDEs established in this guideline are considered to be protective of public health for all patient populations. In some cases, lower levels of elemental impurities may be warranted when levels below toxicity thresholds have been shown to have an impact on other quality attributes of the drug product (e.g., element catalyzed degradation of drug substances). In addition, for elements with high PDEs, other limits may have to be considered from a pharmaceutical quality perspective and other guidelines should be consulted (e.g., ICH Q3A). This guideline presents a process to assess and control elemental impurities in the drug product using the principles of risk management as described in ICH Q9. This process provides a platform for developing a risk-based control strategy to limit elemental impurities in the drug product. Version Q3D(R1) involves a revision of the Cadmium Inhalation PDE. More information is available on the EMA’s website.

Draft ICH guideline E19 on optimisation of safety data collection
The European Medicines Agency have published: Scientific guideline: Draft ICH guideline E19 on optimisation of safety data collection – Step 2b, draft: consultation open.

This Guideline is intended to provide internationally harmonised guidance on an optimised approach to safety data collection in some late-stage pre-approval or post-approval studies when the safety profile of a drug is sufficiently characterised. Optimisation of safety data collection using a selective approach may improve the efficiency of clinical studies while reducing the burden to study participants. Adoption of an internationally harmonised approach to selective safety data collection may facilitate global participation in clinical studies. More information is available on the EMA’s website.

Consultation Deadline: 29th September, 2019

Pediatric information incorporated into labelling
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Pediatric Information Incorporated Into Human Prescription Drug and Biological Product Labeling.”

This guidance is intended to assist applicants in determining the appropriate placement and content of pediatric information in human prescription drug and biological product labeling as described in the regulations for the content and format of labeling for human prescription drug and biological products. The goal of this guidance is to provide recommendations to help ensure that information on the use of prescription drugs in pediatric populations (whether positive, negative, or inconclusive) is consistently placed in the proper sections and subsections within labeling so that the information is clear and accessible to health care providers. More information is available on the FDA’s website.

Systemic drug products for pre-exposure prophylaxis of HIV-1 infection
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Human Immunodeficiency Virus-1 Infection: Developing Systemic Drug Products for Pre-Exposure Prophylaxis.”

The purpose of this guidance is to provide to sponsors nonclinical and clinical recommendations specific to the development of systemic drug products, with a focus on long-acting systemic drug products (including small molecules and monoclonal antibodies), regulated within the Center for Drug Evaluation and Research at the Food and Drug Administration (FDA) for the prevention of sexually acquired human immunodeficiency virus-1 (HIV-1) infection. Specifically, this guidance addresses FDA’s current thinking regarding the overall development program and clinical trial designs to support the development of systemic drug products for the prevention of HIV-1 infection. Investigational drug products for further development as pre-exposure prophylaxis (PrEP) can include the following: (1) an oral drug product approved for the treatment of HIV-1 infection that is subsequently developed as oral PrEP, (2) an oral drug product approved for the treatment of HIV-1 infection that is reformulated as a long-acting drug product or other delivery system (e.g., injectable, implantable device) for PrEP, or (3) a new investigational systemic drug product that is developed for treatment and/or prevention of HIV-1 infection. More information is available on the FDA’s website.

Drug product development for treatment of pediatric HIV infection
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Pediatric HIV Infection: Drug Product Development for Treatment.”

The purpose of this guidance is to provide general recommendations on the development of antiretroviral (ARV) drug products for the treatment of human immunodeficiency virus (HIV) infection in pediatric (birth to younger than 18 years of age) patients. This guidance is intended to help sponsors understand when it is appropriate to initiate pediatric formulation development and to begin pediatric studies. More information is available on the FDA’s website.

Draft ICH guideline M10 on bioanalytical method validation
The European Medicines Agency have published: Scientific guideline: Draft ICH guideline M10 on bioanalytical method validation – Step 2b, draft: consultation open.

This guideline is intended to provide recommendations for the validation of bioanalytical assays for chemical and biological drug quantification and their application in the analysis of study samples. Adherence to the principles presented in this guideline will improve the quality and consistency of the bioanalytical data in support of the development and market approval of both chemical and biological drugs. The objective of the validation of a bioanalytical assay is to demonstrate that it is suitable for its intended purpose. Changes from the recommendations in this guideline may be acceptable if appropriate scientific justification is provided. Applicants are encouraged to consult the regulatory authority(ies) regarding significant changes in method validation approaches when an alternate approach is proposed or taken. More information is available on the EMA’s website.

Consultation Deadline: 1st September, 2019

Nonclinical development of pharmaceuticals for severely debilitating or life-threatening hematologic disorders
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Severely Debilitating or Life-Threatening Hematologic Disorders: Nonclinical Development of Pharmaceuticals.”

The purpose of this guidance is to assist sponsors in the design of nonclinical studies for the development of pharmaceuticals used to treat patients with severely debilitating or lifethreatening hematologic disorders (SDLTHDs). This guidance is intended to streamline the development of pharmaceuticals used to treat patients with SDLTHDs, other than cancer, while still protecting patients’ safety and avoiding unnecessary use of animals, in accordance with the 3R (reduce, refine, replace) principles. This guidance applies to pharmaceuticals used both to treat the active disease and to prevent the recurrence of a life-threatening or debilitating event. More information is available on the FDA’s website.

Enrichment strategies for clinical trials to support determination of effectiveness
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs and Biological Products.”

The purpose of this guidance is to assist industry in developing enrichment strategies that can be used in clinical investigations intended to demonstrate the effectiveness of drug and biological products. Enrichment is the prospective use of any patient characteristic to select a study population in which detection of a drug effect (if one is in fact present) is more likely than it would be in an unselected population. Although this guidance focuses on enrichment directed at improving the ability of a study to detect a drug’s effectiveness, similar strategies can be used in safety assessments. The enrichment strategies described in this guidance are intended to increase the efficiency of drug development and support precision medicine, i.e., tailoring treatments to those patients who will benefit based on clinical laboratory, genomic, and proteomic factors. This guidance also discusses design options for enrichment strategies and discusses the interpretation of the results of studies that use enrichment strategies. More information is available on the FDA’s website.

Evaluation of bulk drug substances nominated for use in compounding
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act.”

This guidance sets forth FDA’s policy for evaluating bulk drug substances nominated for use in compounding by outsourcing facilities registered under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 353b).2 Section 503B of the FD&C Act directs FDA to develop a list of bulk drug substances for which there is a clinical need (the 503B Bulks List). Drug products compounded using bulk drug substances on the 503B Bulks List qualify for certain exemptions from the FD&C Act provided the other conditions in section 503B are met. This guidance addresses FDA policies for developing the 503B Bulks List, including the Agency’s interpretation of the phrase bulk drug substances for which there is a clinical need, as it is used in section 503B. This guidance also addresses the factors and processes by which the Agency intends to evaluate and list bulk drug substances. More information is available on the FDA’s website.

Investigational advanced therapy medicinal products in clinical trials
The European Medicines Agency have published: Scientific guideline: Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials, draft: consultation open.

The guideline provides guidance on the structure and data requirements for a clinical trial application for exploratory and confirmatory trials with advanced therapy investigational medicinal products (ATIMPs). The guideline is multidisciplinary and addresses development, manufacturing and quality control as well as non-clinical and clinical development of ATIMPs. Considerations on genome editing tools are included. Throughout the guideline, requirements for exploratory trials (including First in Human studies) and confirmatory trials are described. The main focus is however on the requirements for exploratory trials. More information is available on the EMA’s website.

Consultation Deadline: 1st August, 2019

Clinical investigation of medicinal products for the treatment of gout
The European Medicines Agency have published: Scientific guideline: Guideline on clinical investigation of medicinal products for the treatment of gout, draft: consultation open.

The main aim of the guideline is to address general guidance on the development of medicinal products for the treatment of gout. Guidance is provided on the evaluation of drugs for the treatment of gout, including the prevention and treatment of acute arthritis flares or chronic tophaceous gouty arthropathy. Potential therapies could be urate lowering therapies or anti-inflammatory drugs. In the circumstance where products are primarily developed for the treatment of acute pain, and where acute gouty arthritis flares are included in the study programme as a model for acute nociceptive pain, reference is made to the EMA guideline on the clinical development of medicinal products intended for the treatment of pain. More information is available on the EMA’s website.

Consultation Deadline: 8th August, 2019

Public warning and notification of recalls
The Food and Drug Administration (FDA or we) is announcing the availability of a final guidance for industry and FDA staff entitled “Public Warning and Notification of Recalls.”

The guidance establishes guidance for industry and FDA staff regarding the use, content, and circumstances for issuance of public warnings and public notification of recalls under federal regulations. The intent of the guidance is to increase and expedite the appropriate and accurate use of public warnings and public notification and to increase public health protection by better informing the public about violative products being recalled. The guidance clarifies and supplements existing policy for industry and FDA staff regarding the use of public warnings and public notification. More information is available on the Federal Register’s website.

Electronic product information (ePI) for human medicines
The European Medicines Agency, the Heads of Medicines Agencies (HMA) and the European Commission (EC) are launching today a six-month public consultation on draft key principles which will form the basis on which the electronic product information (ePI) for human medicines will be developed and used in the European Union.

The product information (PI) of a medicine in the EU includes the package leaflet for patients and the summary of product characteristics (SmPC) for healthcare professionals. These documents accompany every single medicine authorised in the EU and explain how it should be used and prescribed. The package leaflet is currently provided in the medicine’s box and can also be found, mainly as a pdf document, on the regulators’ websites. However, digital platforms open additional possibilities to disseminate the PI electronically. This can address some of the current limitations and better meet patients’ and healthcare professionals’ needs for accessible, up-to-date information on medicines at the point of need. More information is available on the EMA’s website.

Consultation Deadline: 31st July, 2019

Planning for the effects of high absenteeism to ensure availability of medically necessary drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Products.”

This guidance is intended to encourage manufacturers of medically necessary drug products (MNPs) and any components of those products to develop contingency production plans to use during emergencies that result in high absenteeism at production facilities. The guidance provides considerations for the development and implementation of a plan for production of MNPs during a crisis, including specific elements that should be included in the plan. The guidance also discusses the Center for Drug Evaluation and Research’s (CDER’s) intended approach to helping to avoid drug product shortages that could have a negative impact on the national public health during such emergencies. More information is available on the FDA’s website.

Providing regulatory submissions in electronic format
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications.”

This guidance implements the electronic submission requirements of section 745A(a) of the FD&C Act for the electronic format of the content submitted in new drug applications (NDAs), abbreviated new drug applications (ANDAs), certain biologics license applications (BLAs), and certain investigational new drug applications (INDs) to the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). More information is available on the FDA’s website.

Immunogenicity testing of therapeutic protein products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Immunogenicity Testing of Therapeutic Protein Products — Developing and Validating Assays for Anti-Drug Antibody Detection.”

This guidance provides recommendations to facilitate industry’s development and validation of assays for assessment of the immunogenicity of therapeutic protein products during clinical trials. Specifically, this document includes guidance regarding the development and validation of screening assays, confirmatory assays, titration assays, and neutralization assays. For the purposes of this guidance, immunogenicity is defined as the propensity of a therapeutic protein product to generate immune responses to itself and to related proteins or to induce immunologically related adverse clinical events. The recommendations for assay development and validation provided in this document apply to assays for the detection of one or more anti-drug antibodies (ADAs). This guidance may also apply to some peptides, oligonucleotides, and combination products on a case-by-case basis. More information is available on the FDA’s website.

Member States Supervision of the NMVSs/NMVOs
The European Commission has published the Inspection report template for National Competent Authorities as part of the Member States Supervision of the National Medicines Verification Systems/National Medicines Verification Organisations.

More information is available on the Commission’s website.

Labeling for human prescription drug and biological products approved under the Accelerated Approval Regulatory Pathway
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Labeling for Human Prescription Drug and Biological Products Approved Under the Accelerated Approval Regulatory Pathway.”

This guidance is intended to assist applicants in developing the INDICATIONS AND USAGE section of labeling for human prescription drug and biological products that are approved under the accelerated approval regulatory pathway (hereafter accelerated approval) as defined in section 506(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR part 314, subpart H, or 21 CFR part 601, subpart E. More specifically, this guidance focuses on indications for drugs approved via accelerated approval on the basis of a surrogate endpoint or a clinical endpoint other than survival or irreversible morbidity. This guidance also addresses labeling considerations for indications that were approved under accelerated approval and for which clinical benefit subsequently has been verified and the FDA terminates the conditions of accelerated approval under 21 CFR 314.560 or 21 CFR 601.46. In addition, this guidance addresses labeling considerations when the FDA withdraws approval of an indication that had been approved through the accelerated approval pathway while other indications for the drug remain approved. More information is available on the FDA’s website.

Evaluation of medicinal products indicated for treatment of bacterial infections
The European Medicines Agency have published: Scientific guideline: Guideline on the evaluation of medicinal products indicated for treatment of bacterial infections – Revision 3, draft: consultation open.

This guideline merges, revises and adds to the guidance previously included in the Guideline on the evaluation of medicinal products indicated for treatment of bacterial infections (CPMP/EWP/558/95 Rev.2) and the Addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections (EMA/CHMP/351889/2013). The revisions reflect scientific advice given on the development of antibacterial agents, decisions taken during regulatory procedures and alignments on clinical trial requirements that have resulted from discussions between regulators in the EU, United States and Japan, including revised recommendations for primary endpoints, primary analysis populations and non-inferiority margins in trials to support certain infection site-specific indications for use. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Multi-strain dossiers for inactivated vaccines against avian influenza, bluetongue and foot-and-mouth disease
The European Medicines Agency have published: Scientific guideline: Revised guideline on data requirements for multi-strain dossiers for inactivated vaccines against avian influenza (AI), Bluetongue (BT) and Foot-and-Mouth disease (FMD), adopted.

This guideline applies to new applications for authorisation of vaccines defined in multi-strain dossiers and variations to such dossiers concerning the addition or replacement of strains of inactivated vaccines intended for use against AI, BT and FMD diseases. It describes the requirements that should be presented in the analytical, safety and efficacy parts of the multi-strain dossier. It is envisaged that submission of a multi-strain dossier would not be appropriate in response to an emergency situation. The minimum data requirements for an authorisation under exceptional circumstances for vaccines for emergency use are therefore not considered within the scope of this guideline. More information is available on the EMA’s website.

Date for coming into effect: 1st July, 2019

DNA reactive (mutagenic) impurities in veterinary medicinal products
The European Medicines Agency have published: Scientific guideline: Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products, adopted.

The synthesis of drug substances involves the use of reactive chemicals, reagents, solvents, catalysts, and other processing aids. As a result of chemical synthesis or subsequent degradation, impurities reside in all drug substances and associated veterinary medicinal products (VMPs). While VICH GL10: Impurities in New Veterinary Drug Substances (Ref. 1) and VICH GL11 (Ref. 2): Impurities in New Veterinary Medicinal Products provide guidance for qualification and control for the majority of the impurities, limited guidance is provided for those impurities that are DNA reactive. The purpose of this guideline is to provide a practical framework that is applicable to the identification, categorisation, qualification, and control of these mutagenic impurities, to limit potential carcinogenic risk associated with the exposure to potentially mutagenic impurities. This guideline is intended to complement VICH GL10 and VICH GL11. This guideline considers both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that remain or are reasonably expected to remain in the final drug substance or VMP. The approach of this guideline is based on that of ICH guideline M7 (Ref. 3) on assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk which was used as a template, with amendments introduced in order to cover the issues specific to VMPs. More information is available on the EMA’s website.

Date for coming into effect: 1st July, 2020

EMA Regulatory Science to 2025 – Strategic Reflection
The European Medicines Agency have published: EMA Regulatory Science to 2025 – Strategic Reflection, draft: consultation open.

“The Regulatory Science strategy to 2025 aims to build a more adaptive regulatory system that will encourage innovation in human and veterinary medicine,” said Guido Rasi, EMA’s Executive Director. “The strategy includes developments and challenges in medicines development that we together with the Commission and NCAs experts have identified in a thorough process of mapping and selection. Now we want to hear from our stakeholders whether they consider this strategy is ambitious enough.” More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Allergen products development in moderate to low-sized study populations
The European Medicines Agency have published: Scientific guideline: Concept paper on a guideline for allergen products development in moderate to low-sized study populations, draft: consultation open.

This concept paper proposes the development of a scientific guideline for allergen products where adequate data according to existing guidelines cannot be reasonably obtained because the number of patients available for the required clinical trials is too low and for which there is no distinct regulatory guidance currently available within the EU. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Demonstration of efficacy for veterinary medicinal products containing anticoccidial substances
The European Medicines Agency have published: Scientific guideline: Guideline for the demonstration of efficacy for veterinary medicinal products containing anticoccidial substances, draft: consultation open.

This guideline provides specific guidance in respect to the documentation required to demonstrate the efficacy of veterinary medicinal products (VMPs) generally developed for the prevention or reduction of clinical signs of coccidiosis, and the reduction of oocyst shedding. The previous NtA guideline on anticoccidial products (7AE15a) was limited to poultry. This guideline covers a wider range of mammalian and avian target species, containing now general data requirements for all target species, as well as specific requirements for poultry, ruminants, dogs and cats, pigs and rabbits. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Conduct of bioequivalence studies for veterinary medicinal products
The European Medicines Agency have published: Scientific guideline: Guideline on the conduct of bioequivalence studies for veterinary medicinal products, adopted.

The aim of this guideline is to provide guidance regarding study design, conduct and evaluation of bioequivalence studies for pharmaceutical forms with systemic action and in vitro dissolution tests. In addition, recommendations are given on when in-vivo studies are mandatory and when in vitro data are likely to be sufficient. If bioequivalence cannot be demonstrated using pharmacokinetic parameters as endpoints, pharmacodynamic or clinical endpoints may be used, in exceptional circumstances, to demonstrate similar efficacy and safety. However, this situation is outside the scope of this guideline and the reader is referred to therapeutic area specific guidelines, where available. Recommendations for modified release products are given in this guideline as there are specific issues to be addressed for these products. The scope is limited to chemical entities. More information is available on the EMA’s website.

Date for coming into effect: 1st July, 2019

Quality, safety and efficacy of allergen products for use in horses, dogs and cats
The European Medicines Agency have published: Scientific guideline: Guideline on requirements for the quality (production and control), safety and efficacy of allergen products for use in horses, dogs and cats, draft: consultation open.

This guideline lays down the quality recommendations for allergen products of biological origin, including allergen extracts derived from natural source material and allergens produced through recombinant DNA technology, used for treatment or specific immunotherapy (SIT) or in vivo diagnosis of immunoglobulin E (IgE)-mediated allergic diseases in horses, dogs and cats. In addition, guidance is given for the clinical testing regarding safety and efficacy of the products. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Clinical trial endpoints for the approval of cancer drugs and biologics
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics.”

This guidance provides recommendations to applicants on endpoints for cancer clinical trials submitted to the Food and Drug Administration (FDA) to support effectiveness claims in new drug applications (NDAs), biologics license applications (BLAs), or supplemental applications. It also provides background information and discusses general regulatory principles. The endpoints discussed in this guidance are for drugs to treat patients with an existing cancer. This guidance does not address endpoints for drugs to prevent or decrease the incidence of cancer. This guidance is a revision of the final guidance of the same title that published in May 2007. This guidance replaces the May 2007 guidance of the same title. More information is available on the FDA’s website.

Safety and residue data requirements for pharmaceutical veterinary medicinal products intended for minor use or minor species
The European Medicines Agency have published: Scientific guideline: Revised guideline on safety and residue data requirements for pharmaceutical veterinary medicinal products intended for minor use or minor species (MUMS)/limited market, draft: consultation open.

The update to this guideline introduces the extrapolation criteria to be considered by the CVMP when assessing applications for MRLs, and refers to Commission Regulation (EU) 2017/880 of 23 May 2017 laying down rules on the use of a maximum residue limit established for a pharmacologically active substance in a particular foodstuff for another foodstuff derived from the same species and a maximum residue limit established for a pharmacologically active substance in one or more species for other species, in accordance with Regulation (EC) No 470/2009 of the European Parliament and of the Council. These updated criteria should enable applicants to provide the minimum required data to increase the availability of medicines for both major and minor species, by allowing the CVMP to set MRLs for additional animal species and commodities. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

EMVS Master Data Guide
The European Medicines Verification Organisation EMVO has published an updated version, Version 3.0, of the EMVS Master Data Guide.

The guide contains added NHRN rules for Portugal and amended NHRN rules for Germany. Appendix 5 of the documented has been enhanced to provide more detailed guidance concerning the “Designated Wholesaler”, as well as templates for “Delegation of Designated Wholesaler Appointment” and “Delivery Note”. More information is available on the EMVO’s website.

Risk management requirements for elemental impurities in veterinary medicinal products
The European Medicines Agency have published: Scientific guideline: Reflection paper on risk management requirements for elemental impurities in veterinary medicinal products, draft: consultation open.

Revision of the European Pharmacopoeia General Monograph 2619: Pharmaceutical Preparations which came into effect in January 2018, requires manufacturers of products outside the scope of the General Chapter 5.20 to control the levels of elemental impurities in the products using the principles of risk management. These changes to the European Pharmacopoeia have been introduced to align with requirements of the ICH Q3D guideline for elemental impurities that came into effect for existing human medicinal products in December 2017. The document “implementation of risk assessment requirements to control elemental impurities in veterinary medicinal products” (EMA/CVMP/QWP/631010/2017-Rev.1) outlines the phased implementation of submission of risk assessments required by the European Pharmacopeia. By 2023, a risk assessment should be performed for all products for veterinary use that will be on the European Union market. As no guidance is currently available for marketing authorisation holders, active substance, medicinal product and excipient manufacturers for veterinary medicinal products, the purpose of this reflection paper is to provide information on how such risk management may be conducted for elemental impurities in products authorised or to be authorised in the European Union. It also highlights the expectations of regulators regarding the data to be submitted in the product dossier for those risk managements/assessments. In accordance with European Pharmacopoeia General Monograph 2619, the responsibility for the conduct of the risk management rests with the medicinal product manufacturer. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Classification of veterinary medicinal products indicated for minor use minor species
The European Medicines Agency have published: Scientific guideline: Guidance on the classification of veterinary medicinal products indicated for minor use minor species (MUMS) / limited market, adopted.

This guidance document relates to requests from applicants seeking to access incentives for MUMS/limited market products where a request for classification is made to the Committee for Medicinal Products for Veterinary Use (CVMP). Classification of products by CVMP is not necessary in the case of products intended for submission to national competent authorities where the recommendation on whether or not a product is indicated for a limited market lies with the authority concerned. However, potential applicants should note that the measures detailed in section 6, including scientific advice and MRL incentives, may be provided to products classified by CVMP as MUMS/limited market irrespective of the final authorisation route. Furthermore, it is expected that this procedure and the other related documents will assist authorities in terms of classifying indications at a national level as MUMS/limited market and a classification by the CVMP can be useful as guidance in particular for authorisations under decentralised or mutual recognition procedures. More information is available on the EMA’s website.

Quality and equivalence of topical products
The European Medicines Agency have published: Scientific guideline: Guideline on quality and equivalence of topical products, draft: consultation open.

The diversity of topical products is very wide given the complex nature of skin, the range of conditions to be treated and the variety of patients and their needs. The guideline relates to locally applied and locally acting medicinal products for cutaneous use and is also relevant for other medicines e.g. preparations for auricular or ocular use. The guideline cannot present a single procedure to address such diversity, instead general recommendations are provided. These can be applied to any given product on a case-by-case basis. The guideline elaborates existing regulatory guidance and is informed by current scientific knowledge. Annexes I and II of this guideline replace Annex 1 of the Guideline on Quality of Transdermal Patches (EMA/CHMP/QWP/608924/2014). The guideline replaces Questions and Answer on Guideline: Clinical Investigation of Corticosteroids Intended for Use on The Skin (CHMP/EWP/21441/2006). More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation
The European Medicines Agency have published: Scientific guideline: Guideline on the reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation, adopted.

A growing number of regulatory submissions include physiologically based pharmacokinetic (PBPK) models that require the use of specialised software platforms. While PBPK modelling is presently mentioned in several existing EMA guidelines, this is the first to specifically provide detailed advice on what to include in a PBPK modelling report including, in particular, details of the predictive performance of the drug model. If PBPK modelling is intended to support a regulatory decision, the PBPK platform needs to be qualified for the intended use. This document, therefore, also aims to clarify which supportive data are expected in order to qualify a PBPK platform, accordingly. More information is available on the EMA’s website.

Date for coming into effect: 1st July, 2019

Questions and answers on data integrity and compliance with drug CGMP
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Data Integrity and Compliance With Drug CGMP: Questions and Answers.”

The purpose of this guidance is to clarify the role of data integrity in current good manufacturing practice (CGMP) for drugs, as required in 21 CFR parts 210, 211, and 212. Unless otherwise noted, the term CGMP in this guidance refers to CGMPs for drugs (including biologics). FDA’s authority for CGMP comes from section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Part 210 covers Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General; part 211 covers Current Good Manufacturing Practice for Finished Pharmaceuticals; and part 212 covers Current Good Manufacturing Practice for Positron Emission Tomography (PET) Drugs. All citations to parts 211 and 212 in this document pertain to finished pharmaceuticals and PET drugs, but these requirements are also consistent with Agency guidance on CGMP for active pharmaceutical ingredients with respect to data integrity. This guidance provides the Agency’s current thinking on the creation and handling of data in accordance with CGMP requirements. More information is available on the FDA’s website.

“Deemed to be a License” provision of the Biologics Price Competition and Innovation Act of 2009
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Interpretation of the “Deemed to be a License” Provision of the Biologics Price Competition and Innovation Act of 2009.”

This guidance describes FDA’s interpretation of the provision of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) under which an application for a biological product approved under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355) as of March 23, 2020, will be deemed to be a license for the biological product under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262) on March 23, 2020. Specifically, this guidance describes FDA’s interpretation of the “deemed to be a license” provision in section 7002(e) of the BPCI Act for biological products that are approved under section 505 of the FD&C Act as of March 23, 2020 (the transition date). This guidance also provides recommendations to sponsors of proposed protein products intended for submission in an application that may not receive final approval under section 505 of the FD&C Act on or before March 23, 2020, to facilitate alignment of product development plans with FDA’s interpretation of section 7002(e) of the BPCI Act. More information is available on the FDA’s website.

Questions and answers on biosimilar development and the BPCI Act
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Questions and Answers on Biosimilar Development and the BPCI Act.”

This guidance document provides answers to common questions from prospective applicants and other interested parties regarding the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The question and answer (Q&A) format is intended to inform prospective applicants and facilitate the development of proposed biosimilars and interchangeable biosimilars, as well as to describe FDA’s interpretation of certain statutory requirements added by the BPCI Act. More information is available on the FDA’s website.

Best practice with regard to 3Rs in regulatory testing of medicinal products
The European Medicines Agency have published: Scientific guideline: Review and update of EMA guidelines to implement best practice with regard to 3Rs (replacement, reduction and refinement) in regulatory testing of medicinal products – report on actions taken, adopted.

In February 2014, CHMP and CVMP published a joint concept paper announcing a review and update of EMA guidelines to implement best practice with regard to 3Rs (replacement, reduction and refinement) in regulatory testing of medicinal products (EMA/CHMP/CVMP/JEG-3Rs/704685/2012). As background, it should be noted that the purpose of this review was not to reconsider established testing requirements but, rather, to ensure that EMA guidelines do not make reference to animal tests that are no longer considered appropriate. The purpose of the current document is to provide an update on the work undertaken and the guidelines that have been or will be updated as a result of this review. More information is available on the EMA’s website.

Post-complete response letter meetings between FDA and ANDA applicants under GDUFA
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Post-Complete Response Letter Meetings Between FDA and ANDA Applicants Under GDUFA.”

This guidance provides recommendations to industry on post-complete response letter (CRL) meetings between FDA and abbreviated new drug application (ANDA) applicants for the purpose of clarifying deficiencies identified in a CRL to an ANDA submitted under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)). For purposes of this guidance, a post-CRL meeting is a meeting that is requested in writing by an ANDA applicant pursuant to the procedures described in this guidance following receipt of a CRL. It is important that there are efficient, consistent procedures for the timely and effective conduct of post-CRL meetings. This guidance will assist applicants in generating and submitting a request for a post-CRL meeting and the associated meeting package to FDA as contemplated in the FDA Reauthorization Act of 2017, reauthorizing the Generic Drug User Fee Amendments (GDUFA II) for Fiscal Years 2018-2022. This guidance is intended to provide procedures that will promote well-managed post-CRL meetings and help ensure that such meetings are scheduled and conducted in accordance with the time frames set forth in the GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2018-2022 (GDUFA II Goals or Commitment Letter). More information is available on the FDA’s website.

Environmental risk assessment of medicinal products for human use
The European Medicines Agency have published: Scientific guideline: Guideline on the environmental risk assessment of medicinal products for human use – Revision 1, draft: consultation open.

The purpose of this guideline is to describe the assessment of the potential environmental risks and hazards of human medicinal products (HMP). It specifies the scope and legal basis for assessment. It outlines general considerations and the recommended step-wise procedure of assessment. The general outline of the Environmental Risk Assessment Report is included, and for products for which risks cannot be excluded, this guideline outlines the possible precautionary and safety measures. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Core SmPC for human plasma derived and recombinant coagulation factor IX products
The European Medicines Agency have published: Scientific guideline: Guideline on core SmPC for human plasma derived and recombinant coagulation factor IX products – Revision 3, draft: consultation open.

This guideline describes the information to be included in the Summary of Product Characteristics (SmPC) for human plasma derived and recombinant coagulation factor IX products, which are indicated for use in the treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency). More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Clinical investigation of recombinant and human plasma-derived factor IX products
The European Medicines Agency have published: Scientific guideline: Guideline on clinical investigation of recombinant and human plasma-derived factor IX products – Revision 2, draft: consultation open.

This guideline describes the information to be documented when an application for a marketing authorisation for recombinant or human plasma-derived factor IX products is made for use in the treatment and prevention of bleeding in patients with haemophilia B. The guideline covers clinical investigations to be conducted pre- and post-marketing authorisation. Guidance is also provided for authorised products where a significant change in the manufacturing process has been made. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Elemental impurities in veterinary medicinal products
The European Medicines Agency have published: Scientific guideline: Guideline on implementation of risk assessment requirements to control elemental impurities in veterinary medicinal products – Revision 1, adopted.

Revision of the European Pharmacopoeia General Monograph 2619 for Pharmaceutical Preparations which came into effect in January 2018, requires manufacturers of products outside the scope of the General Chapter 5.20 to control the levels of elemental impurities in the products using the principles of risk management. In the case of veterinary medicinal products, the scientific principles on which risk assessment/risk management should be based have not yet been elaborated as the permitted daily exposure (PDE) based approach detailed in General Chapter 5.20 and in ICH Q3D cannot be easily applied to veterinary products. In order to allow time for regulators to elaborate guidance on the appropriate approach for a risk assessment for a veterinary medicinal product, the CVMP has adopted the following measured approach to the implementation of the monograph to existing veterinary products. The phased-in implementation of the risk assessment of elemental impurities in veterinary medicinal products is to be in accordance with the decision tree indicated in this document. More information is available on the EMA’s website.

Qualification of non-genotoxic impurities
The European Medicines Agency have published: Scientific guideline: Reflection paper on the qualification of non-genotoxic impurities, draft: consultation open.

The core ICH quality guidelines addressing qualification of NGI are ICH Q3A and Q3B. These guidelines state that qualification is the process of acquiring and evaluating data that establishes the biological safety of an individual impurity or a given impurity profile at the level(s) specified. The applicant should provide a rationale for establishing impurity acceptance criteria that includes safety considerations. For DNA reactive (mutagenic) impurities, elemental impurities and residual solvents specific guidance is provided (ICH M7, Q3D and Q3C, respectively). However, for non-genotoxic impurities (NGI) little guidance is available on how these impurities should be qualified. This reflection paper considers the safety evaluation of NGI in chemically synthesised pharmaceuticals. More information is available on the EMA’s website.

Consultation Deadline: 30th September, 2019

Clinical investigation of medicinal products for the treatment and prophylaxis of venous thromboembolic disease
The European Medicines Agency have published: Scientific guideline: Paediatric addendum on the guidelines on clinical investigation of medicinal products for the treatment and prophylaxis of venous thromboembolic disease, draft: consultation open.

This is an addendum to the Guideline on clinical investigation of medicinal products for the treatment of venous thromboembolic disease (EMA/CHMP/41230/2015) [1] and the two guidelines for prophylaxis of venous thromboembolism (VTE) in surgical (EMA/CHMP/325170/2012 Rev.2) [2] and non-surgical (EMA/CPMP/EWP/6235/04 Rev. 1) [3] adult patients, and should be read in conjunction with these guidelines. This addendum includes guidance on paediatric clinical medicine development, highlighting paediatric specific issues and differences from the treatment and prophylaxis of venous thromboembolism in adults. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Non-clinical requirements for radiopharmaceuticals
The European Medicines Agency have published: Scientific guideline: Guideline on the non-clinical requirements for radiopharmaceuticals, draft: consultation open.

The need for a guidance paper focusing specifically on the non-clinical testing requirements for radiopharmaceuticals has emerged since currently there is no detailed guidance available. Therefore, in addition to the general non-clinical requirements described in e.g. ICH M3(R2), ICH S9 and ICH S6(R1), the principles for non-clinical data generation in support of the specific clinical uses of radiopharmaceuticals are laid down in this guideline. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Off-label use of antimicrobials in veterinary medicine
The European Medicines Agency have published: Scientific guideline: Reflection paper on off-label use of antimicrobials in veterinary medicine in the European Union – First version, adopted.

This document intends to define off-label use and provide relevant examples of off-label use of antimicrobials in animals and the underlying reasons for these practices. The circumstances when off-label use is compatible with responsible use of antimicrobials will be explored. The goal is to identify and focus on areas that may cause unacceptable public and animal health risks due to dissemination of antimicrobial resistance. Off-label antimicrobial use in companion animals and food-producing animals will be addressed. More information is available on the EMA’s website.

Antimicrobial resistance in the environment
The European Medicines Agency have published: Scientific guideline: Reflection paper on antimicrobial resistance in the environment: considerations for current and future risk assessment of veterinary medicinal products, draft: consultation open.

This reflection paper aims to review the potential impact(s) on ecosystems, animal and human health from the possible presence of antimicrobial residues (ARs) and/or antimicrobial resistance genes (ARGs) in the environment arising from the use of VMPs. This paper will differentiate the key exposure pathways and subsequently, consider the likely extent of accumulation and mobility in the environment of ARs and ARGs excreted from animals treated with VMPs. In addition, the potential effects on the functioning of bacterial communities and the overall impacts on ecosystems, as a consequence of either AMR or by changing the microbial diversity without selecting for acquired antibiotic resistance, are considered. Moreover, an evaluation and understanding of the degree to which the environment is altered by VMP use, how it may contribute to the cycling of resistance genes between different ecosystem compartments (e.g. soil, water, animals and/or humans), and the effect or consequences of this on animal and human health is performed. Furthermore, as VMPs are not the only source of antimicrobials that enter the environment, the consideration of any potential impacts from VMP use needs to be done within the context of the global use of antimicrobials giving consideration to the ‘One Health’ approach. This reflection paper also considers whether the current ERA for VMPs should or could be further developed to appropriately assess the potential risks posed by veterinary medicines, with antimicrobial properties, to drive environmental AMR. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Development of medicinal products for chronic non-infectious liver diseases
The European Medicines Agency have published: Scientific guideline: Reflection paper on regulatory requirements for the development of medicinal products for chronic non-infectious liver diseases (PBC, PSC, NASH), draft: consultation open.

Chronic, non-infectious liver diseases are a medical field of high unmet medical needs. At the same time, the specifics of the diseases create major challenges for the development of new medicinal products. This reflection paper restricts the current regulatory approach to 3 different disease entities primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and non-alcoholic steatohepatitis (NASH) for which recent efforts are undertaken to bring new medicinal products to the market. As a reflection paper, this guidance document provides a high level description of the requirements for drug development in the field. For all three disease entities dealt with in the paper, the regulatory experience with the licensing of new medicinal product is limited. Therefore, this paper aims at a preliminary definition of development strategies only, which, in the case of several successful MAAs occurring in the future, will have to be refined, and may finally be superseded by full guidance documents. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal products
The European Medicines Agency have published: Scientific guideline: CHMP position statement on Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal products – Revision 3, draft: consultation open.

This is the third revision of the CHMP Position Statement on “Creutzfeldt-Jakob disease and plasma-derived and urine-derived medicinal products”. It was originally published in February 2003 (EMEA/CPMP/BWP/2879/02), replacing the CPMP Position Statement on “New variant CJD and plasma-derived medicinal products” (CPMP/201/98) from February 1998. EMEA/CPMP/BWP/2879/02 was revised in June 2004 (EMEA/CPMP/BWP/2879/02 rev 1.) and in June 2011 (EMA/CHMP/BWP/303353/2010). The purpose of this revision is to account for scientific developments since the last revision in 2011. The scientific information has been updated. However, there is no change in the regulatory recommendations regarding exclusion, potential testing of donors, the need to evaluate the prion reduction capacity of the manufacturing process and batch recalls. More information is available on the EMA’s website.

Consultation Deadline: 31st October, 2019

Clinical investigation of medicinal products for the treatment of peripheral arterial occlusive disease
The European Medicines Agency have published: Scientific guideline: Concept paper on the need for revision of the Note for Guidance on Clinical Investigation of Medicinal Products for the Treatment of Peripheral Arterial Occlusive Disease (CHMP/EWP/714/98 rev 1), draft: consultation open.

In light of the developments in the field of PADs, the title/scope of the guideline needs to be re-discussed to decide if other locations in addition to the lower extremities need to be covered or the title adapted to reflect limiting the guidance on the lower extremity disease only. The Note for Guidance also excludes the peripheral vascular disorders of inflammatory or immunologic origin (e.g. thromboangiitis obliterans or Buerger’s disease and necrotic vasculitis). The general cardiovascular (CV) prevention is covered in other guidance documents and is not to be in the scope of this guideline. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Use of patient disease registries for regulatory purposes
The European Medicines Agency have published: Discussion paper: Use of patient disease registries for regulatory purposes – methodological and operational considerations, draft: consultation open.

This discussion paper has been prepared by the Cross-Committee Task Force on Registries established by the EMA Patient Registries Initiative. The main objective of this initiative is to facilitate use of patient registries to support regulatory decision-making. The paper discusses methodological and operational aspects of the use of patient disease registries and registry studies for regulatory purposes. It has been published to seek comments and suggestions from all the interested parties. All the responses will be considered for the finalisation of the document with the EMA Committees in Q4 2019. More information is available on the EMA’s website.

Consultation Deadline: 30th June, 2019

Quality documentation concerning biological investigational medicinal products in clinical trials
The European Medicines Agency have published: Scientific guideline: Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials – Revision 1, adopted.

This guideline addresses the specific documentation requirements on the biological, chemical and pharmaceutical quality of IMPs containing biological / biotechnology derived substances. Moreover, this guideline lists, as regards documentation on the biological, chemical and pharmaceutical quality of the IMP, examples of modifications which are typically considered as ‘substantial’. The guidance outlined in this document applies to proteins and polypeptides, their derivatives, and products of which they are components (e.g. conjugates). These proteins and polypeptides are produced from recombinant or non-recombinant cell-culture expression systems and can be highly purified and characterised using an appropriate set of analytical procedures. The guideline also applies to Auxiliary Medicinal Products containing these proteins and polypeptides as active substances. The requirements depend on the type of the product (authorised / not authorised / modified / non-modified medicinal product). The principles may also apply to other product types such as proteins and polypeptides isolated from tissues and body fluids. More information is available on the EMA’s website.

Date for coming into effect: 1st November, 2018

Regulatory testing requirements for medicinal products for human use and opportunities for implementation of the 3Rs
The European Medicines Agency have published: Scientific guideline: Reflection paper providing an overview of the current regulatory testing requirements for medicinal products for human use and opportunities for implementation of the 3Rs – First version, adopted.

In December 2016 the CHMP and CVMP published a guideline on regulatory acceptance of 3R (replacement, reduction, refinement) testing approaches (EMA/CHMP/CVMP/JEG-3Rs/450091/2012). The current reflection paper has been developed as a follow up to that guideline and provides an overview of the main animal tests required for the regulatory testing of medicinal products for human use (a parallel document has been developed in relation to veterinary medicinal products – EMA/CHMP/CVMP/JEG-3Rs/740772/2015). It includes information on opportunities for limiting animal testing that can already be implemented, where appropriate, as well as information on opportunities that may become available in the future. The latter comprises areas, which are currently under investigation and will necessitate data review and further discussion before a definite impact on 3Rs can be appraised. This document should encourage sponsors to develop new 3Rs methodologies and submit them for regulatory review and acceptance. More information is available on the EMA’s website.

Developing fixed-combination drug products the treatment of hypertension
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Hypertension: Developing Fixed-Combination Drug Products for Treatment.”

The purpose of this guidance is to assist sponsors in the clinical development of fixed-combination drug products for the treatment of hypertension. This guidance focuses on development of two-drug combinations of previously approved drugs, although the general approach is readily applicable to three or more drugs in combination. This guidance does not address combinations that include unapproved drug products. More information is available on the FDA’s website.

Use of extrapolation in the development of medicines for paediatrics
The European Medicines Agency have published: Scientific guideline: Reflection paper on the use of extrapolation in the development of medicines for paediatrics, adopted.

This reflection paper aims to provide guidance to applicants and assessors on the main regulatory requirements that are expected to be met for the use and the evaluation of extrapolation approaches in the development of medicines for children. The focus of the paper is on the use of extrapolation to address one or more specific research questions, related to either efficacy or safety, that are part of a broader paediatric development plan aimed at MA. The paper aims to promote the use of available evidence and objective criteria to support extrapolation. The principles outlined should encourage further exploration of potentially suitable methods for specific situations, and choice of strategies should be justified. The choice of quantitative methods to use in each step of the extrapolation exercise and methodological issues related to their application are appropriate topics for discussion through Scientific Advice. More information is available on the EMA’s website.

Evaluation of testicular toxicity during drug development
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Testicular Toxicity: Evaluation During Drug Development.”

The purpose of this guidance is to assist sponsors who are developing drug products that may have potential adverse effects on the testes, which we refer to as testicular toxicity, based on findings in nonclinical studies. This guidance discusses the following topics: nonclinical findings that suggest risk of clinical testicular toxicity, and further nonclinical assessments that may be necessary to evaluate the extent of this risk, linical monitoring that can be employed when these drug products are initially administered to men, the design of a clinical trial that has as its primary purpose the evaluation of drug-related testicular toxicity. The guidance provides general considerations for when clinical trials to assess the risk of testicular toxicity may be needed but does not cover all possible scenarios that would prompt such a trial. The guidance also does not discuss the regulatory actions that FDA might consider based on the results of the clinical trials. More information is available on the FDA’s website.

Developing targeted therapies in low-frequency molecular subsets of a disease
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease.”

Insights into the molecular basis of disease have led to the development of targeted therapies. Often, the pharmacological effect of a targeted therapy is related to a particular molecular alteration. Many clinically defined diseases are caused by a range of different molecular alterations, some of which may occur at low frequencies, that impact common proteins or pathways involved in the pathogenesis of diseases. In a population of patients with the same clinical disease, the heterogeneity in the molecular etiology may influence responsiveness to a particular targeted therapy. However, certain targeted therapies may be effective in multiple groups of patients who have different underlying molecular alterations because the functional effect of the molecular alterations may be similar. Therefore, the FDA is providing guidance on the type and quantity of evidence that can demonstrate efficacy across molecular subsets within a disease, particularly when one or more molecular subsets occur at a low frequency. More information is available on the FDA’s website.

Selection of appropriate package type terms and recommendations for labeling
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Selection of the Appropriate Package Type Terms and Recommendations for Labeling Injectable Medical Products Packaged in Multiple-Dose, Single-Dose, and Single-Patient-Use Containers for Human Use.”

This guidance provides industry with the Food and Drug Administration’s (FDA’s) recommendations on the selection of appropriate package type terms and selection of appropriate discard statements for injectable medical products for human use, packaged in multiple-dose, single-dose, and single-patient-use containers. Specifically, this guidance provides FDA’s revised definitions for single-dose and multiple-dose containers as well as for the new package type term single-patient-use container. These containers may be part of a drug, a biological product, or a combination product assigned to CDER, CBER, or certain combination products assigned to CDRH. Marketing applications for such products include: New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), Biologics License Applications (BLAs), Premarket Approval Applications (PMAs), Premarket Notifications under section 510(k) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and requests for classification submitted under section 513(f)(2) of the FD&C Act (De Novo request). More information is available on the FDA’s website.

Timing of pediatric studies during development of systemic drugs for atopic dermatitis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Atopic Dermatitis: Timing of Pediatric Studies During Development of Systemic Drugs.”

This guidance addresses FDA’s current thinking about the relevant age groups to study and how early in drug development applicants should incorporate pediatric patients for development of systemic drugs for atopic dermatitis (AD). The recommendations in this guidance are based on input received from the March 9, 2015, Dermatologic and Ophthalmic Drug Advisory Committee (DODAC) meeting on this topic and review of medical literature and relevant statutes and regulations. More information is available on the FDA’s website.

Adverse event reporting for outsourcing facilities Under Section 503B
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act.”

This guidance is intended for firms that have registered with the Food and Drug Administration (FDA) under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as human drug compounding outsourcing facilities (outsourcing facilities). Under section 503B(b)(5) of the FD&C Act, an outsourcing facility must submit adverse event reports to FDA “in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations).” More information is available on the FDA’s website.

Compounding and repackaging of radiopharmaceuticals by state-licensed nuclear pharmacies, federal facilities, and certain other entities
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies, Federal Facilities, and Certain Other Entities.”

This guidance sets forth the FDA’s policy regarding the compounding and repackaging of radiopharmaceuticals for human use by state-licensed nuclear pharmacies, Federal facilities, and other entities that hold a radioactive materials (RAM) license for medical use issued by the Nuclear Regulatory Commission (NRC) or by an Agreement State. More information is available on the FDA’s website.

Compounding and repackaging of radiopharmaceuticals by outsourcing facilities
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Compounding and Repackaging of Radiopharmaceuticals by Outsourcing Facilities.”

This guidance sets forth the FDA’s policy regarding compounding and repackaging of radiopharmaceuticals for human use by entities that are registered with FDA as outsourcing facilities under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act or the Act). This guidance describes how FDA generally intends to apply section 503B of the FD&C Act to radiopharmaceuticals compounded by outsourcing facilities. It also describes the conditions under which FDA generally does not intend to take action for violations of sections 505 and 502(f)(1) of the FD&C Act when an outsourcing facility repackages radiopharmaceuticals. More information is available on the FDA’s website.

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Resistance in ectoparasites
The European Medicines Agency have published: Scientific guideline: Reflection paper on resistance in ectoparasites, draft: consultation open.

The scope of this reflection paper is to give an overview of the currently known resistance situation in ectoparasites to active substances used in both veterinary medicinal products (and also biocides) with a special focus on Europe, and to provide a review of the current knowledge on resistance mechanisms. This information might be useful for guidance on prudent use or for future applications. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Summary of product characteristics for veterinary medicinal products containing antimicrobial substances
The European Medicines Agency have published: Regulatory and procedural guideline: Draft guideline on the summary of product characteristics (SPC) for veterinary medicinal products containing antimicrobial substances – Revision 1, draft: consultation open.

This second revision of the guideline on the Summary of Product Characteristics (SPC) for antimicrobial products provides updated guidance on the information to be included in the SPC of veterinary medicinal products (VMPs) containing antimicrobial substances. It replaces the first revision of the guideline on the SPC for antimicrobial products (EMEA/CVMP/SAGAM/383441/2005), which came into effect in May 2008. Since then there have been significant developments in principles of antimicrobial therapy in regards to antimicrobial resistance and various regulatory initiatives have been undertaken by CVMP, including publication of the CVMP’s strategy on antimicrobials to 2020. According to these initiatives, recommendations from other CVMP reflection papers and referral procedures, and based on experience gained from Marketing Authorisation procedures, further guidance is provided on information to be included in the SPC in order to encourage optimal use and to minimise selection of antimicrobial resistance. The second revision of the guideline should also serve to improve consistency of the SPCs for antimicrobial products in the EU Member States. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019

Article 31 non-pharmacovigilance referrals
The European Medicines Agency have published: Regulatory and procedural guideline: Questions and answers on Article 31 non-pharmacovigilance referrals.

This guidance document addresses a number of questions which stakeholders, in particular the marketing authorisation holders (MAHs)/applicants, may have on an Article 31 non-pharmacovigilance referral procedure. It provides an overview of the European Medicines Agency’s (the Agency) practical and operational aspects with regards to the handling of Article 31 non-pharmacovigilance referral procedures. More information is available on the EMA’s website.

Grandfathering policy for packages and homogenous cases of product without a product identifier
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Grandfathering Policy for Packages and Homogenous Cases of Product Without a Product Identifier.”

This guidance addresses product distribution security provisions in section 582 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360eee-1). Section 582 was added by the Drug Supply Chain Security Act (DSCSA) (Title II of Public Law 113-54) and facilitates the tracing of products through the pharmaceutical distribution supply chain by requiring trading partners (manufacturers, repackagers, wholesale distributors, and dispensers) to exchange transaction information, transaction history, and a transaction statement (product tracing information) when engaging in transactions involving certain prescription drug products. In addition, section 582 requires manufacturers and repackagers to start affixing or imprinting a product identifier to each package and homogenous case of product no later than November 27, 2017 (for manufacturers) and November 27, 2018 (for repackagers). More information is available on the FDA’s website.

Product identifier requirements under the Drug Supply Chain Security Act
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Product Identifier Requirements Under the Drug Supply Chain Security Act – Compliance Policy.”

This guidance describes FDA’s compliance policy with regard to a requirement related to product identifiers under the Drug Supply Chain Security Act. Specifically, this guidance addresses the requirement in section 582(b)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360eee-1(b)(2)) that manufacturers “affix or imprint a product identifier to each package and homogenous case of a product intended to be introduced in a transaction into commerce” beginning not later than November 27, 2017. More information is available on the FDA’s website.

Developing drug products for treatment of allergic rhinitis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Allergic Rhinitis: Developing Drug Products for Treatment.”

The purpose of this guidance is to assist sponsors in the development of drug products for the treatment of allergic rhinitis in children and adults. The guidance addresses issues of trial design, effectiveness, and safety for new products being developed for the treatment of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). The recommendations in this guidance are based on an assessment of important issues raised in the review of both adult and pediatric allergic rhinitis clinical trials and the Agency’s current understanding of the mechanism of the two related disorders of SAR and PAR. The pathophysiology of SAR and PAR are similar in terms of the chemical mediators produced and end-organ manifestations, with differences between the two entities primarily based on the causes and duration of disease. The trial design issues pertaining to SAR and PAR trials are also similar. Thus, these two categories are treated collectively in this guidance as allergic rhinitis, with differences in recommendations for the design of SAR and PAR trials indicated. Sponsors are encouraged to discuss details of trial design and specific issues relating to individual products with division review staff before conducting clinical trials. This guidance does not contain discussion of the general issues of statistical analysis or clinical trial design. Those topics are addressed in the ICH guidances for industry E9 Statistical Principles for Clinical Trials and E10 Choice of Control Group and Related Issues in Clinical Trials, respectively, as well as the draft ICH guidance for industry E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials. More information is available on the FDA’s website.

Developing drug products for treatment of nonallergic rhinitis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Nonallergic Rhinitis: Developing Drug Products for Treatment.”

The purpose of this guidance is to assist applicants of new drug applications and biologics license applications in developing drug products for the treatment of nonallergic rhinitis (NAR) in children and adults. The guidance discusses issues regarding the definition of a clinical phenotype, trial design, efficacy, and safety for new drug products under development. In particular, the guidance addresses development programs for the treatment of vasomotor rhinitis (VMR), which is a subtype of NAR. This guidance does not contain discussion of the general issues of statistical analysis or clinical trial design. Those topics are addressed in the ICH guidances for industry E9 Statistical Principles for Clinical Trials and E10 Choice of Control Group and Related Issues in Clinical Trials and the ICH draft guidance for industry E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analyses in Clinical Trials. More information is available on the FDA’s website.

Physiologically based pharmacokinetic analyses
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Physiologically Based Pharmacokinetic Analyses — Format and Content.”

This guidance outlines the recommended format and content for a sponsor or applicant to submit physiologically based pharmacokinetic (PBPK) analyses to the FDA to support applications including, but not limited to, investigational new drug applications (INDs), new drug applications (NDAs), biologics license applications (BLAs), or abbreviated new drug applications (ANDAs). This guidance does not address methodological considerations and best practices for the conduct of PBPK modeling and simulation or the appropriateness of PBPK analyses for a particular drug or a drug product. The decision to accept results from PBPK analyses in lieu of clinical pharmacokinetic (PK) data is made on a case-by-case basis, considering the intended uses, as well as the quality, relevance, and reliability of the results from the PBPK analyses. More information is available on the FDA’s website.

Quality attribute considerations for chewable tablets
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Quality Attribute Considerations for Chewable Tablets.”

This guidance provides manufacturers of chewable tablets for human use with the Center for Drug Evaluation and Research’s (CDER) current thinking on the critical quality attributes that should be assessed during the development of these drug products. This guidance also provides recommendations for sponsors/applicants regarding the submission of developmental, manufacturing, and labeling information for chewable tablets in applications. The recommendations in this guidance apply to new drug applications (NDAs), abbreviated new drug applications (ANDAs), and certain chemistry, manufacturing, and controls (CMC) supplements to these applications. Some of the recommendations about the submission of developmental information may also apply to investigational new drug applications (INDs). The recommendations about assessing critical quality attributes apply to all immediate release (IR) chewable tablets for human use, including non-application products. More information is available on the FDA’s website.

Nonclinical study recommendations for microdose radiopharmaceutical diagnostic drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Microdose Radiopharmaceutical Diagnostic Drugs: Nonclinical Study Recommendations.”

This guidance is intended to assist sponsors of microdose radiopharmaceutical diagnostic drugs on the nonclinical studies recommended to support human clinical trials and marketing applications. This guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding regulation of this class of drugs and provides complementary recommendations to the guidance for industry, investigators, and reviewers Exploratory IND (Investigational New Drug Application) Studies (exploratory IND guidance) and the ICH guidance for industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3(R2)). More information is available on the FDA’s website.

Dissolution testing for immediate-release solid oral dosage forms with high solubility drug substances
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances.”

This guidance is developed to provide manufacturers with recommendations for submission of new drug applications (NDAs), investigational new drug applications (INDs), or abbreviated new drug applications (ANDAs), as appropriate, for orally administered immediate-release (IR) drug products that contain highly soluble drug substances. The guidance is intended to describe when a standard release test and criteria may be used in lieu of extensive method development and acceptance criteria-setting exercises. This guidance finalizes the guidance for industry on Dissolution Testing and Specification Criteria for Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics Classification System Class 1 and 3 Drugs (August 2015). More information is available on the FDA’s website.

Elemental impurities in drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Elemental Impurities in Drug Products.”

This guidance provides recommendations regarding the control of elemental impurities of human drug products marketed in the United States consistent with implementation of International Council for Harmonisation (ICH) guidance for industry Q3D Elemental Impurities (ICH Q3D). This guidance will also assist manufacturers of compendial drug products in responding to the issuance of the United States Pharmacopeia (USP) requirement for the control of elemental impurities. More information is available on the FDA’s website.

Draft questions and answers on Data Monitoring Committees issues
The European Medicines Agency have published: Scientific guideline: Draft questions and answers on Data Monitoring Committees issues, draft: consultation open.

The aim of this question-and-answer document is to supplement the CHMP Data Monitoring Committee Guideline (Doc Ref. EMEA/CHMP/EWP/5872/03) by providing clarification on the role and necessity for a Data Monitoring Committee (DMC) in different phases of drug development and throughout the product lifecycle as well as with regard to the responsibilities for implementing DMC decisions. More information is available on the EMA’s website.

Consultation Deadline: 31st July, 2019

Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells
The European Medicines Agency have published: Scientific guideline: Draft guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells, draft: consultation open.

This guideline defines scientific principles and provides guidance for the development and evaluation of medicinal products containing genetically modified cells intended for use in humans and presented for marketing authorisation. Its focus is on the quality, nonclinical aspects and safety and efficacy requirements of genetically modified cells developed as medicinal products. More information is available on the EMA’s website.

Consultation Deadline: 31st July, 2019

Development of medicinal products to prevent and treat acute kidney injury
The European Medicines Agency have published: Scientific guideline: Concept paper on the need to develop a reflection paper on development of medicinal products to prevent and treat acute kidney injury, draft: consultation open.

The concept paper will include discussion of and recommendations for the requirements for evaluation and development of medicinal products for the prevention and/or treatment of acute kidney injury (AKI) and its long-term complications. Relevant topics for discussion include patient populations, endpoints, study methodology, and study duration. More information is available on the EMA’s website.

Consultation Deadline: 31st July, 2019

Data requirements for veterinary medicinal products for the prevention of transmission of vector-borne diseases in dogs and cats
The European Medicines Agency have published: Scientific guideline: Draft guideline on data requirements for veterinary medicinal products for the prevention of transmission of vector-borne diseases in dogs and cats, draft: consultation open.

This guideline provides recommendations for the design and conduct of studies to support the efficacy of veterinary medicinal products (VMPs) intended for the prevention of transmission of vector-borne pathogens (VBPs) in dogs and cats, which can be transferred by blood-feeding arthropods. The guideline outlines the requirements for laboratory and field studies. Prevention of transmission of vector-borne disease in the context of this guideline means the reduction of the risk of transmission of VBPs by killing or repellent effect against the vector prior to the transmission of the VBPs. This guideline, therefore, establishes criteria for the demonstration of efficacy of a VMP in order to be granted a claim for the reduction of the risk of transmission of VBPs. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2019