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.

Good Clinical Practice specific to Advanced Therapy Medicinal Products
The European Commission has published: Guidelines on Good Clinical Practice specific to Advanced Therapy Medicinal Products.

Compliance with good clinical practice (“GCP”) is mandatory for clinical trials that are conducted in the EU. Article 4 of Regulation (EC) No 1394/20072 mandates the Commission to draw up guidelines on good clinical practice specific to advanced therapy medicinal products (“ATMPs”). These Guidelines develop the GCP requirements that are specific to clinical trials conducted with ATMPs. These Guidelines are to be read in conjunction with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines on good clinical practice,3 which are also applicable to ATMPs. To the extent that there is a difference in the requirements, the content of these Guidelines prevails. These Guidelines do not apply to clinical trials with medicinal products other than ATMPs. More information is available on the Commission’s website.

Promoting the authorisation of alternatives to antimicrobials in the EU
The European Medicines Agency have published: Scientific guideline: CVMP reflection paper on promoting the authorisation of alternatives to antimicrobials in the EU, draft: consultation open.

This reflection paper performs a gap analysis by reviewing the measures currently in place to support the authorisation of alternatives to antimicrobials (ATAm) in veterinary medicine, with particular emphasis given to alternatives to antibiotics, and identifying where and how these could be improved. More information is available on the EMA’s website.

Consultation Deadline: 30th April, 2020

Drug Master Files
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Drug Master Files.”

Once finalized, this guidance will provide FDA’s current thinking on drug master files (DMFs), which are submissions to FDA that may be used to provide confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products. DMFs are submitted solely at the discretion of their holders and are not required by statute or regulation. This draft guidance, when finalized, will revise the guidance for industry “Drug Master Files: Guidelines” that published in September 1989. More information is available on the Federal Register’s website.

Consultation Deadline: 20th December, 2019

Prescription drug user fee act waivers, reductions, and refunds for drug and biological products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Prescription Drug User Fee Act Waivers, Reductions, and Refunds for Drug and Biological Products.”

This guidance provides recommendations to applicants planning to request a waiver or reduction in user fees. This guidance finalizes the draft guidance for industry of the same title issued in June 2018. More information is available on the Federal Register’s website.

Manufacture of ATMPs and biological medicinal substances and products for human use
The Pharmaceutical Inspection Co-operation Scheme (PIC/S) is seeking comments on revisions to two parts of its GMP Guide (Annex 2A and Annex 2B) that deal with the manufacture of advanced therapy medicinal products (ATMPs) and biological medicinal substances and products for human use.

Draft Annex 2A (Manufacture of Advanced Therapy Medicinal Products for Human Use) takes into account the international development in the regulation of Advanced Therapy Medicinal Products (ATMP) with particular attention to the European Commission guideline on GMP for ATMP which has been published since the latest revision of the EU Annex 2, while addressing at the same time concerns of PIC/S Participating Authorities with regard to patient safety and proportionate regulation for ATMPs. Draft Annex 2B (Manufacture of Biological Medicinal Substances and Products for Human Use) is the revised version of EU Annex 2 for biologics (excluding ATMPs). This consultation will also allow PIC/S to collect feedback from stakeholders to help PIC/S develop its thinking in this area. More information is available on the PIC/S’s website.

Consultation Deadline: 20th December, 2019

Patient-focused drug development
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry, FDA staff, and other stakeholders entitled “Patient-Focused Drug Development: Methods To Identify What Is Important to Patients.”

This guidance (Guidance 2) is the second in a series of four methodological patient-focused drug development (PFDD) guidance documents that FDA is developing to describe in a stepwise manner how stakeholders (patients, researchers, medical product developers and others) can collect and submit patient experience data and other relevant information from patients and caregivers to be used for medical product development and regulatory decision-making. More information is available on the Federal Register’s website.

Consultation Deadline: 30th December, 2019

Nonclinical assessment of investigational enzyme replacement therapy products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Investigational Enzyme Replacement Therapy Products: Nonclinical Assessment.”

The purpose of this guidance is to help sponsors design and conduct nonclinical studies during development of investigational enzyme replacement therapy (ERT) products. Specifically, this guidance describes the Food and Drug Administration’s (FDA’s) current thinking about the substance and scope of nonclinical information needed to support initiation of clinical trials, ongoing clinical development, and marketing approval for investigational ERT products. More information is available on the Federal Register’s website.

European Commission Safety Features Q&A document updated
The European Commission has published an updated version, Version 16, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

Version 16 of the document, dated September 2019, supersedes Version 15. Q&As 2.23 and 7.20 were added, while Q&As 2.3, 2.12, 4.5 and 7.17 were revised.

More information is available on the Commission’s website.

Wholesale distributor verification requirement for saleable returned drug product
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Wholesale Distributor Verification Requirement for Saleable Returned Drug Product—Compliance Policy Guidance for Industry.”

This guidance is intended for wholesale distributors who must verify the product identifier upon receipt of a returned product that the wholesale distributor intends to further distribute as required under section 582(c)(4)(D) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360eee-1(c)(4)(D)). This guidance addresses the readiness of wholesale distributors to comply with the provisions in section 582 of the FD&C Act related to the verification of saleable returned drug products. The requirement under section 582(c)(4)(D) for wholesale distributors to verify saleable returned drug products prior to redistribution goes into effect on November 27, 2019. More information is available on the Federal Register’s website.

Developing drugs for treatment of amyotrophic lateral sclerosis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry.”

The purpose of this guidance is to assist sponsors in the clinical development of drugs and biological products for the treatment of amyotrophic lateral sclerosis (ALS). Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the clinical development program and clinical trial designs for drugs to support an indication for the treatment of ALS. More information is available on the Federal Register’s website.

Extrapolation of efficacy from adults to pediatric patients in drugs for treatment of partial onset seizures
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Drugs for Treatment of Partial Onset Seizures: Full Extrapolation of Efficacy from Adults to Pediatric Patients 2 Years of Age and Older.”

This guidance provides recommendations to sponsors on the clinical development of drugs for the treatment of partial onset seizures (POS) in pediatric patients. Specifically, this guidance addresses FDA’s current thinking regarding clinical development programs that can support extrapolation of the efficacy of drugs approved for the treatment of POS in adults to pediatric patients 2 years of age and older. This guidance does not address clinical development programs for the treatment of POS in pediatric patients younger than 2 years of age. This guidance does not address the development of drugs to treat other types of seizures. More information is available on the Federal Register’s website.

Evaluation of internal standard responses during chromatographic bioanalysis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Questions and Answers.”

This guidance provides recommendations to sponsors, applicants, and contract research organizations regarding internal standard (IS) response variability in chromatographic analytical data submitted in investigational new drug applications, new drug applications, abbreviated new drug applications, biologics license applications, and supplements. Chromatographic analytical methods are commonly used to quantitate analyte concentrations in samples from nonclinical and clinical studies to support regulatory submissions. Depending upon its source, IS response variability may impact the accuracy of analyte concentration measurements. This question and answer (Q&A) document provides the Agency’s current thinking on IS response variability and its potential impact on the accuracy of analyte concentration measurements. This Q&A also suggests approaches to determine whether observed IS response variability is likely to impact the accuracy of the data such that further investigation into the root cause(s) is warranted. More information is available on the FDA’s website.

Updates to EudraLex Volumes 6A and 6C
The European Commission is announcing the availability of an updated version of EudraLex “Volume 6A – Procedures for marketing authorisation: Chapter 1 Marketing Authorisation”, “Volume 6C – Regulatory Guidelines: Guideline on the categorisation of Extension Applications (EA) versus Variations Applications (V)” and “Volume 6C – Guideline on the packaging information of veterinary medicinal products authorised by the Union”.

More information is available on the European Commission’s website.

Placebos and blinding in randomized controlled cancer clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug and Biological Products.”

This guidance provides recommendations to industry about using placebos and blinding in randomized controlled clinical trials in development programs for drug or biological products to treat hematologic malignancies and oncologic diseases regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). This guidance finalizes the draft guidance entitled “Hematologic Malignancy and Oncologic Disease: Considerations for Use of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development” issued August 24, 2018. More information is available on the Federal Register’s website.

Nonclinical evaluation of drugs intended for treatment of osteoporosis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Osteoporosis: Nonclinical Evaluation of Drugs Intended for Treatment.”

The purpose of this guidance is to provide recommendations to industry for designing nonclinical bone quality studies to support the approval of drugs and biologics (e.g., recombinant proteins and monoclonal antibodies regulated by the Center for Drug Evaluation and Research) intended for the treatment of osteoporosis. More information is available on the Federal Register’s website.

Child-resistant packaging statements in drug product labeling
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Child-Resistant Packaging Statements in Drug Product Labeling.”

This guidance is intended to assist applicants, manufacturers, packagers, and distributors who choose to include child-resistant packaging (CRP) statements in prescription and over-the-counter human drug product labeling. The guidance discusses what information should be included to support CRP statements and to help ensure that such labeling is clear, useful, informative, and, to the extent possible, consistent in content and format. More information is available on the Federal Register’s website.

Developing drugs for treatment of Fabry Disease
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Fabry Disease: Developing Drugs for Treatment.”

This draft guidance describes the Agency’s current recommendations regarding eligibility criteria, trial design considerations, and efficacy endpoints to be used in clinical development programs of investigational drugs to treat Fabry disease. Through this draft guidance, the Agency provides clear and specific guidance to foster greater efficiency in drug development in this rare disease with the goal of enhancing clinical trial data quality and supporting the development of treatments for Fabry disease. More information is available on the Federal Register’s website.

Consultation Deadline: 6th November, 2019

Clinical pharmacology considerations for neonatal studies for drugs and biological products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products.”

This draft guidance is intended to assist sponsors of new drug applications (NDAs), biologics license applications (BLAs) for therapeutic biologics, and supplements who are planning to conduct clinical studies in neonatal populations. The issuance of this draft guidance on clinical pharmacology considerations for neonatal studies for drugs and biological products is stipulated under the FDA Reauthorization Act of 2017 (FDARA). More information is available on the Federal Register’s website.

Consultation Deadline: 30th October, 2019

Nonclinical studies and labeling recommendations for oncology therapeutic radiopharmaceuticals
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations.”

The purpose of this guidance is to provide information to assist sponsors in the design of an appropriate nonclinical program for the development of radiopharmaceuticals to treat cancer — also known as oncology therapeutic radiopharmaceuticals — and to provide recommendations for certain aspects of product labeling. For the purpose of this guidance, a therapeutic radiopharmaceutical is a product that contains a radionuclide and is used in patients with cancer to treat the disease or palliate tumor-related symptoms (e.g., pain). Recommendations in this guidance are applicable to products that are administered systemically and undergo alpha, beta, and/or gamma decay. More information is available on the FDA’s website.

Developing drugs for treatment of uncomplicated urinary tract infections
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Uncomplicated Urinary Tract Infections: Developing Drugs for Treatment.”

The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of uncomplicated urinary tract infections (uUTIs). Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the overall development program and clinical trial designs for drugs to support an indication for the treatment of uUTIs. More information is available on the FDA’s website.

Developing drugs for treatment of bacterial candidiasis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Bacterial Vaginosis: Developing Drugs for Treatment.”

The purpose of this guidance is to assist sponsors in the overall development program and clinical trial designs to support development of topical and systemic drugs and biological products for the treatment of bacterial vaginosis (BV). This guidance focuses on considerations that are specific to BV drug development. 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 (September 1998) and E10 Choice of Control Group and Related Issues in Clinical Trials (May 2001), respectively. More information is available on the FDA’s website.

Developing drugs for treatment of vulvovaginal candidiasis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Vulvovaginal Candidiasis: Developing Drugs for Treatment.”

The purpose of this guidance is to assist sponsors in the overall clinical development program and clinical trial designs to support drugs for treating vulvovaginal candidiasis (VVC). In general, this guidance focuses only on treating VVC. This guidance does not discuss clinical development programs focused on preventing or reducing the recurrence of VVC. Sponsors should discuss the clinical development of such programs with FDA. More information is available on the FDA’s website.

Developing drugs for prevention of delayed graft function
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Delayed Graft Function in Kidney Transplantation: Developing Drugs for Prevention.”

The purpose of this guidance is to assist sponsors in the clinical development of drugs for the prevention of delayed graft function (DGF) in kidney transplantation. Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the overall development program and clinical trial designs for systemic drugs administered to the kidney transplant recipient to support an indication of prevention of DGF. More information is available on the FDA’s website.

Batch testing of medicinal products in the context of Brexit
The European Commission has released information on batch testing of medicinal products in the context of withdrawal of the United Kingdom from the Union. In particular, the European Commission has reminded that it is essential that marketing authorisation holders complete their preparations so that by 1 January 2020 all batch testing facilities are fully transferred to the EU27/EEA and the necessary regulatory submissions are completed.

More information is available on the European Commission’s website.

Updates to EudraLex Volumes 2A and 2C
The European Commission is announcing the availability of an updated version of EudraLex “Volume 2A – Procedures for marketing authorisation: Chapter 1 Marketing Authorisation” and “Volume 2C – Regulatory Guideline: Guideline on the categorisation of New Applications (NA) versus Variations Applications (V)”.

More information is available on the European Commission’s website.

Submitting next generation sequencing data
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Submitting Next Generation Sequencing Data to the Division of Antiviral Products Guidance for Industry Technical Specifications Document.”

The purpose of this technical specifications document is to provide the current thinking of FDA’s Division of Antiviral Products (the Division) in regard to the submission of next generation nucleotide sequence analysis procedures and data in support of resistance assessments for the development of antiviral drug products. The Division performs independent analyses of all resistance data associated with antiviral drug products being developed to ensure that the emergence of resistance is carefully characterized and explained in the label of newly approved antiviral drug products. Providing accurate resistance information is imperative for protecting public health to prevent the emergence of novel resistant and cross-resistant viral variants that have the potential to infect others and cause major outbreaks of disease that cannot be controlled by approved drug products. In addition, the resistance information provides important guidance for health care professionals who oversee the use of antiviral drug products and is included in the drug product information approved by the Division. Moreover, the Division can request data for nucleotide sequence analysis of host-targeted genes for polymorphism analysis to determine if different population-based alleles have an effect on efficacy. More information is available on the FDA’s website.

European Commission Safety Features Q&A document updated
The European Commission has published an updated version, Version 15, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

Version 15 of the document, dated July 2019, supersedes Version 14. Q&As 3.7, 5.10 and 8.10 were added, while Q&A 1.6 was revised.

More information is available on the Commission’s website.

Risk evaluation and mitigation strategies
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Risk Evaluation and Mitigation Strategies: Modifications and Revisions Guidance for Industry.”

This guidance provides information on how the FDA defines the types of changes to approved risk evaluation and mitigation strategies (REMS), how application holders should submit changes to an approved REMS, and how the FDA will process submissions from application holders for changes to REMS. Specifically, this guidance provides information, as described in section 505-1(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), on what types of changes to REMS will be considered modifications of the REMS and what types of changes will be considered revisions of the REMS (changes that may be implemented following notification to the FDA). This guidance is issued pursuant to section 505-1(h)(2)(A)(ii), (iii), and (iv) of the FD&C Act and section 1132(c) of Public Law 112-144. More information is available on the FDA’s website.

Reporting and communication of medicines shortages
The European Union task force set up to address problems with medicines supply has published two documents: Guidance for marketing authorisation holders on reporting of shortages in the EU, and Good practice guidance for communication to the public on medicines’ availability issues.

Both documents lay the foundations for an improved and harmonised EU approach in reporting of and communication on medicines’ shortages and availability issues, a key public health priority for the EU network.

The first document provides guidance to the pharmaceutical industry, a key player in addressing shortages, to facilitate the detection and early notification to competent authorities. The guidance is based on a common definition of the term ‘shortages’, which should enable a more harmonised and timely approach in the detection and management of issues with the supply of medicines. A proposed template for shortage notification by companies is included in the guidance. The guidance and template will be implemented in a pilot phase, which is currently planned to start in the last quarter of 2019. Further information will be provided nearer the time.

The second document, addressed to EU national competent authorities and EMA, lays out principles and examples of good practices for communication on shortages to the public, including patients and healthcare professionals. These groups require timely, accurate and up-to-date information on availability issues to ensure continuity of care. The guidance is based on a survey carried out by the task force in all EU Member States to collect information on how issues related to shortages and availability of medicines are measured and communicated to the public.

More information is available on the EMA’s website.

Revision of the guideline on the investigation of medicinal products in the term and preterm neonate
The European Medicines Agency have published: Scientific guideline: Concept paper on the need for revision of the guideline on the investigation of medicinal products in the term and preterm neonate, adopted.

The current guideline includes more general principles for conducting clinical studies in neonates. Considerable experience has been gained from the assessment of PIPs involving development of medicinal products for neonates indicating that there is a need to reflect this in updated and more specific recommendations regarding non-clinical models of neonatal conditions, models for the demonstration of efficacy of medicinal products in term and preterm neonates, evaluation of short and long term safety as well as use of available tools and biomarkers. Furthermore, over recent years there have been an increasing awareness and discussions about neonatal research trends and standards, suggesting that the current guidance could benefit from an update in several areas to better address issues concerned with the development and investigation of products in term and preterm neonates. A review of the guideline in order to consider new clinical developments in neonatology, to improve the quality and consistency of neonatal research, as well as avoid unnecessary studies in this highly vulnerable population seems appropriate. More information is available on the EMA’s website.

Developing drugs for treatment of cutaneous manifestations of epidermolysis bullosa
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Epidermolysis Bullosa: developing drugs for treatment of cutaneous manifestations.”

The purpose of this guidance is to assist sponsors with the development of drugs for treatment or prevention of the serious cutaneous manifestations of the heterogeneous group of disorders collectively known as epidermolysis bullosa (EB). The paucity of effective treatment options for EB represents an important unmet medical need. This guidance focuses on drug development and trial design issues specific to the treatment of EB, including FDA’s current thinking on trial endpoints. There is not yet sufficient clinical trial experience to establish definitive endpoints. More information is available on the FDA’s website.

Falsified medicines GMP inspection aide memoire
The European Commission has published an aide memoire for GMP inspection of manufacturers’ compliance with Commission Delegated Regulation (EU) 2016/161 for safety features. More information is available on the Commission’s website.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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