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.

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, adopted.

The main aim of the guideline is to address general guidance on the development of medicinal products for the treatment of gout. This guideline should be read in conjunction with other EMA and ICH guidelines, which may apply to these conditions and patient populations. In this document, guidance is provided on the clinical development of new ULT and anti-inflammatory treatment options. The study design, inclusion criteria, primary endpoints and trial duration largely depend on the treatment goal and mode of action of the new drug. More information is available on the EMA’s website.

Date for coming into effect: 1st June, 2020

Developing drugs for treatment of chronic hepatitis D virus infection
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Chronic Hepatitis D Virus Infection: Developing Drugs for Treatment.”

The purpose of this draft guidance is to assist sponsors in all phases of development of antiviral drugs for the treatment of chronic hepatitis D virus (HDV) infection. This guidance is intended to provide consistent FDA advice to stakeholders regarding HDV drug development strategies. More information is available on the Federal Register’s website.

Consultation Deadline: 31st December, 2019

Providing regulatory Submissions in Electronic Format
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Providing Regulatory Submissions in Electronic Format: IND Safety Reports.”

The draft guidance describes the electronic format sponsors will be required to use when they electronically submit to FDA investigational new drug (IND) safety reports to the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER) for serious and unexpected suspected adverse reactions that are required under the Agency’s regulations. FDA is establishing the electronic format requirements described in this guidance under the Federal Food, Drug, and Cosmetic Act (FD&C Act). The draft guidance, once finalized and effective, will require sponsors submitting the specified IND safety reports electronically to submit the reports to FDA using the FDA Adverse Event Reporting System (FAERS) as structured data elements and will provide sponsors with a reporting format that is consistent with the International Council for Harmonisation (ICH) E2B(R2) format guidelines and reporting requirements to other regulatory agencies. More information is available on the Federal Register’s website.

Consultation Deadline: 30th December, 2019

Electronic submission of IND safety reports
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Electronic Submission of IND Safety Reports Technical Conformance Guide.”

This Technical Conformance Guide (Guide) provides specifications, recommendations, and general considerations on how to submit electronic investigational new drug application (IND) safety reports to the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). The Guide supplements the draft guidance for industry Providing Regulatory Submissions in Electronic Format: IND Safety Reports (October 2019), which implements the electronic submission requirements of section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) with respect to electronic submissions for certain IND safety reports submitted to CDER or CBER. More information is available on the FDA’s website.

Postmarketing studies and clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Postmarketing Studies and Clinical Trials—Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act.”

This draft guidance revises the guidance for industry of the same name issued April 1, 2011. The draft guidance is being revised to describe the multiple factors that FDA considers, before requiring a postmarketing study or clinical trial for the purposes described in the Federal Food, Drug, and Cosmetic Act (FD&C Act), when determining the sufficiency of the reports under the FD&C Act and the active postmarket risk identification and analysis (ARIA) system available under the FD&C Act to meet these purposes. The draft guidance is also being revised to reflect certain provisions enacted under the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act as they relate to postmarketing studies and clinical trials. More information is available on the Federal Register’s website.

Consultation Deadline: 24th December, 2019

Drug products labeled as homeopathic
The Food and Drug Administration (FDA or Agency) is announcing the availability of a revised draft guidance for FDA staff and industry entitled “Drug Products Labeled as Homeopathic.”

The revised draft guidance, like the original version, describes how FDA intends to prioritize enforcement and regulatory action with regard to drug products, including biological products, labeled as homeopathic and marketed in the United States without the required FDA approval that potentially pose higher risk to public health. In response to comments received, we have revised the draft guidance and are reissuing it in draft form to enable the public to review and comment before it is finalized. More information is available on the Federal Register’s website.

Consultation Deadline: 23rd January, 2020

Identification of manufacturing establishments in applications submitted to CBER and CDER
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final question and answer document entitled “Identification of Manufacturing Establishments in Applications Submitted to CBER and CDER: Questions and Answers.”

This guidance is intended to clarify Agency expectations regarding facility information that should be included in original new drug application(s) (NDA); abbreviated new drug application(s) (ANDA); original biologics license application(s) (BLA); amendments; supplements; chemistry, manufacturing, and controls (CMC) supplements; and resubmissions to these submission types. Submission of Form FDA 356h fulfills the requirement for applicants to submit an application form (21 CFR 314.50(a) and 314.94(a)(1); 601.2(a)). Form FDA 356h serves as both a summary of administrative information, as well as a repository of complete information on the locations of all manufacturing, packaging, and control sites for both drug substance and drug product facilities associated with the application. This guidance addresses questions related to the inclusion and withdrawal of proposed commercial facilities and development facilities, the appropriate location within an application for facility information, and the type of facility information that should be included in applications. Applications that include appropriate and complete facility information in the establishment information section of Form FDA 356h will reduce the frequency of Information Request (IR), Refusal to File (RTF), and Refuse to Receive (RTR) actions and increase the efficiency of the application assessment process. This guidance describes the recommended placement of all facility information for both original and supplement applications. More information is available on the FDA’s website.

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.

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