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.

Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients: Questions and Answers.”

The ICH guidance Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess. Since the ICH Q7 Guidance was finalized, experience with implementing the guidance worldwide has given rise to requests for clarification of uncertainties due to the interpretation of certain sections. This question and answer (Q&A) document is intended to respond to those requests. More information is available on the FDA’s website.

Metered Dose Inhaler and Dry Powder Inhaler drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products—Quality Considerations.”

The purpose of this guidance is to provide recommendations to industry on the development and manufacture of inhalation aerosols (also known as metered dose inhalers, or MDIs) and inhalation powders (also known as dry powder inhalers, or DPIs). Although not explicitly discussed, some of the principles and recommendations provided in this guidance may be applicable to nasal delivery products, as well. The recommendations in this guidance can apply to MDI and DPI products intended for local or systemic effect. More information is available on the Federal Register’s website.

Consultation Deadline: 18th June, 2018

Special protocol assessment
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Special Protocol Assessment.”

This guidance provides information on the procedures and general policies adopted by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) for special protocol assessment (SPA). SPA is a process in which sponsors may ask to meet with FDA to reach agreement on the design and size of certain clinical trials, clinical studies, or animal studies to determine if they adequately address scientific and regulatory requirements for a study that could support marketing approval. More information is available on the FDA’s website.

Clinical investigation of medicinal products in the pediatric population
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “E11(R1) Addendum: Clinical Investigation of Medicinal Products in the Pediatric Population.”

Pediatric drug development has evolved since the original guidance E11 Clinical Investigation of Medicinal Products in the Pediatric Population (ICH E11 (2000)) published, requiring consideration of regulatory and scientific advances relevant to pediatric populations. This addendum does not alter the scope of the original guidance. ICH E11 (2000), including this addendum (R1); is not intended to be comprehensive; other ICH guidances, as well as documents from regulatory authorities worldwide, the World Health Organization (WHO), and pediatric societies, provide additional detail. The purpose of the addendum is to complement and provide clarification and current regulatory perspective on topics in pediatric drug development. More information is available on the FDA’s website.

Scientific and ethical considerations for inclusion of pregnant women in clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials.”

This draft guidance discusses the ethical and scientific issues when considering the inclusion of pregnant women in clinical trials of drugs and biological products. This draft guidance is intended to advance scientific research in pregnant women, and discusses issues that should be considered within the framework of human subject protection regulations. More information is available on the Federal Register’s website.

Consultation Deadline: 8th June, 2018

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

This draft guidance addresses FDA’s current thinking about the relevant age groups to study and how early in the drug development pediatric patients should be incorporated during development of systemic drugs for atopic dermatitis (AD). More information is available on the Federal Register’s website.

Consultation Deadline: 8th June, 2018

Evaluation of medicinal products indicated for treatment of bacterial infections
The European Medicines Agency have published: Scientific guideline: Draft addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections to address paediatric-specific clinical data requirements – First version, draft: consultation open.

This document proposes the development of an addendum to the Guideline on the evaluation of medicines indicated for treatment of bacterial infections (CPMP/EWP/558/95 rev 2), to provide specific guidance on paediatric clinical development programmes to support the authorisation of antibacterial agents for treating infectious diseases in children. More information is available on the EMA’s website.

Consultation Deadline: 30th August, 2018

Liposome drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation.”

This guidance discusses what types of information you, the applicant, should submit in your new drug application (NDA) or abbreviated new drug application (ANDA) for a liposome drug product reviewed by the Center for Drug Evaluation and Research (CDER). The discussion addresses the following topics for liposome drug products: (A) chemistry, manufacturing, and controls (CMC); (B) human pharmacokinetics and bioavailability or, in the case of an ANDA, bioequivalence; and (C) labeling in NDAs and ANDAs. It finalizes the revised draft guidance for industry Liposome Drug Products, Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation that published in October 2015. More information is available on the FDA’s website.

European Union template for GMP non-compliance statement
The European Medicines Agency have published: Scientific guideline: Public consultation concerning the European Union template for good manufacturing practice (GMP) non-compliance statement, draft: consultation open.

The aim of this public consultation is to collect relevant information from stakeholders to help the Good manufacturing practice (GMP)/Good distribution practice (GDP) Inspectors Working Group to develop an effective and harmonised risk-based approach for dealing with the supply of critical medicines in case of serious GMP non-compliance. This will amend the compilation of community procedures and exchange of information (CoCP). More information is available on the EMA’s website.

Consultation Deadline: 15th May, 2018

Elemental impurities in animal drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry (GFI) #255 entitled “Elemental Impurities in Animal Drug Products—Questions and Answers.”

This guidance is intended to assist sponsors of animal drug products in addressing changes in the United States Pharmacopeia (USP) requirements for the control of elemental impurities in drug products marketed in the United States. More information is available on the Federal Register’s website.

Consultation Deadline: 29th May, 2018

Protecting citizens against health threats
The European Commission has published the roadmap “Communication from the Commission on Improving Health Security in the EU – a one health approach to counteracting the threat from infectious diseases.”

The Roadmap aims to inform citizens and stakeholders about the Commission’s work in order to allow them to provide feedback and to participate effectively in future consultation activities. Citizens and stakeholders are in particular invited to provide views on the Commission’s understanding of the problem and possible solutions and to make available any relevant information that they may have. More information is available on the Commission’s website.

Consultation Deadline: 23rd April, 2018

Use of the St. George’s Respiratory Questionnaire in COPD
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Chronic Obstructive Pulmonary Disease: Use of the St. George’s Respiratory Questionnaire as a PRO Assessment Tool.”

This guidance emphasizes considerations of both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that reside or are reasonably expected to reside in final drug substance or product, taking into consideration the intended conditions of human use. 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 the Agency) is announcing the availability of a draft 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 draft guidance describes policies that FDA proposes to use in evaluating bulk drug substances nominated for use in compounding under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for inclusion on the list of bulk drug substances that can be used in compounding under section 503B. More information is available on the Federal Register’s website.

Consultation Deadline: 25th May, 2018

Postmarketing safety reporting for combination products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry and FDA staff entitled “Postmarketing Safety Reporting for Combination Products.”

This draft guidance addresses certain means by which applicants may comply with the final rule on postmarketing safety reporting (PMSR) requirements for combination products that FDA issued on December 20, 2016. Combination products are products composed of two or more different types of medical products (drug, device, and/or biological product). Although the PMSR regulations for drugs, devices, and biological products share many similarities, each set of regulations establishes distinct postmarketing reporting requirements, standards, and timeframes. The final rule provides clarity on the PMSR requirements for combination products to ensure consistent and complete reporting while avoiding duplication. This draft guidance is not final nor is it in effect at this time. More information is available on the Federal Register’s website.

Consultation Deadline: 19th June, 2018

Good pharmacogenomic practice
The European Medicines Agency have published: Scientific guideline: Guideline on good pharmacogenomic practice – First version, adopted.

This guideline provides recommendations for the conduct of genomic studies in relation to medical therapy in order to provide high quality information on the impact of genomic variability on drug response. Primary focus is on the analysis of genomic germline DNA. The analysis of somatic DNA and genomic biomarkers for cancer treatment is not being discussed and might be developed as an Annex or in separate guidance. More information is available on the EMA’s website.

Date for coming into effect: 1st September, 2018

Diethanolamine as an excipient in veterinary medicines for food-producing animals
The European Medicines Agency have published: Scientific guideline: Public consultation concerning a request for CVMP opinion under Article 30(3) of Regulation (EC) No 726/2004 on the risk for the consumer resulting from the use of diethanolamine as an excipient in veterinary medicinal products for food-producing species (EMEA/V/A/127), draft: consultation open.

The European Medicines Agency is seeking stakeholder input on any information or data that may help its Committee for Medicinal Products for Veterinary Use (CVMP) to reach an opinion on consumer risk from using diethanolamine as an excipient in veterinary medicines for food-producing animals. In addition, some editorial changes have been implemented. More information is available on the EMA’s website.

Consultation Deadline: 14th May, 2018

Assessment and control of DNA reactive impurities in pharmaceuticals
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk.”

This guidance emphasizes considerations of both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that reside or are reasonably expected to reside in final drug substance or product, taking into consideration the intended conditions of human use. More information is available on the FDA’s website.

Proprietary names for new animal drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry #240 entitled “Proprietary Names for New Animal Drugs.”

This draft guidance provides recommendations to help new animal drug sponsors develop proprietary names for new animal drugs that do not contribute to medication errors, negatively impact safe use of the drug, or misbrand the drug. This draft guidance proposes a framework for evaluating proposed proprietary names before submitting them for review by the Center for Veterinary Medicine (CVM or we). It also explains how new animal drug sponsors can request that CVM evaluate a proposed proprietary name. More information is available on the Federal Register’s website.

Consultation Deadline: 11th May, 2018

GxP data integrity guide
The MHRA has published its ‘GxP data integrity guide’

The guidance is intended to be a useful resource on the core elements of a compliant data governance system across all GxP sectors (good laboratory practice, good clinical practice, good manufacturing practice, good distribution practice and good pharmacovigilance practice). It addresses fundamental failures identified by MHRA and international regulatory partners during GLP, GCP, GMP and GDP inspections; many of which have resulted in regulatory action. More information is available on the MHRA’s website.

Standardization of data and documentation practices for product tracing
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Standardization of Data and Documentation Practices for Product Tracing.”

The draft guidance elaborates on the standards for the interoperable exchange of transaction information, transaction history, and transaction statements (product tracing information) provided under the drug supply chain security provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act). This guidance is intended to assist trading partners in standardizing the data contained in the product tracing information that trading partners must provide, capture, and maintain under the FD&C Act. In addition, this guidance includes recommendations for documentation practices that a trading partner can use to meet its product tracing obligations, including in situations where a trading partner is permitted by law to provide other trading partners with product tracing information that omits certain elements that would otherwise be required. More information is available on the Federal Register’s website.

Consultation Deadline: 1st May, 2018

Excipients in the labelling and package leaflet of medicinal products for human use
The European Commission has published a revised guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’

More information is available on the Commission’s website.

Clinical investigation of medicines for the treatment of Alzheimer’s disease
The European Medicines Agency have published: Scientific guideline: Guideline on the clinical investigation of medicines for the treatment of Alzheimer’s disease – Revision 2, adopted.

This guideline provides guidance for the development of medicines across all stages of Alzheimer’s disease. It covers the impact of new diagnostic criteria for Alzheimer’s, including early and even asymptomatic disease stages, factors to be considered when selecting parameters to measure clinical trial outcomes at the different disease stages in Alzheimer’s, the potential use of biomarkers in the various stages of medicine development and the design and analysis of efficacy and safety studies. This guideline replaces ‘Guideline on medicinal products for the treatment of Alzheimer’s disease and other dementias’ (CPMP/EWP/553/95 Rev. 1). More information is available on the EMA’s website.

Date for coming into effect: 1st September, 2018

Genomic sampling and management of genomic data
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “E18 Genomic Sampling and Management of Genomic Data.”

The main objective of this guidance is to provide harmonized principles of genomic sampling and management of genomic data in clinical studies. This guidance will facilitate the implementation of genomic studies by enabling a common understanding of critical parameters for the unbiased collection, storage, and optimal use of genomic samples and data. This guidance also intends to increase awareness and provide a reminder regarding subjects’ privacy, protection of the data generated, the need to obtain suitable informed consent, and the need to consider transparency of findings in line with local legislation and regulations. More information is available on the FDA’s website.

Instruments for baseline characterisation of older populations in clinical trials
The European Medicines Agency have published: Scientific guideline: Reflection paper on physical frailty: instruments for baseline characterisation of older populations in clinical trials – First version, adopted.

The scope of this document is to describe the recommended instruments to be applied for the baseline characterisation of physical frailty of patients aged 65 years and older enrolled in a clinical trial or other clinical investigation (e.g. registry). These instruments are proposed to supplement age, as delineated in ICH E7, as a demographic characterisation factor in order to support a better understanding of the benefit-risk of a medicine in the older population. More information is available on the EMA’s website.

Development and manufacture of drug substances
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) Questions and Answers.”

Since the ICH guidance Q11 Development and Manufacture of Drug Substances (ICH Q11) was finalized, worldwide experience with implementation of the recommendations on the development and manufacture of drug substances has given rise to requests for clarification relating to the selection and justification of starting materials. This question-and-answer (Q&A) document is intended to provide additional clarification and to promote convergence and improve harmonization of the considerations for the selection and justification of starting materials and of the information that should be provided in marketing authorization applications and/or Master Files. The focus of the Q&A document is on chemical entity drug substances. More information is available on the FDA’s website.

Measures in the veterinary field to promote 3Rs measures described in the European Pharmacopoeia, applicable to veterinary vaccines
The European Medicines Agency have published: Scientific guideline: Recommendation to marketing authorisation holders, highlighting recent measures in the veterinary field to promote reduction, refinement and replacement (3Rs) measures described in the European Pharmacopoeia – Applicable to veterinary vaccines from 01/01/2017, adopted.

In accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (Council of Europe), tests performed in animals must be carried out in such a way as to use the minimum number of animals and to cause the least pain, suffering, distress or lasting harm. The European Pharmacopeia (Ph. Eur.) has, over the years, applied these principles by implementing alternative tests and assays that reduce, refine and replace animal use. Therefore, in order to comply with the provisions of Directive 2010/63/EU and Ph.Eur and to secure an undisrupted supply of medicinal products to the European Market, MAHs should take all necessary actions to introduce 3Rs Ph. Eur. methods including submission of variations to marketing authorisations as appropriate. More information is available on the EMA’s website.

Measures in the veterinary field to promote 3Rs measures described in the European Pharmacopoeia, applicable to human vaccines
The European Medicines Agency have published: Scientific guideline: Recommendation to marketing authorisation holders, highlighting recent measures in the veterinary field to promote replacement, reduction, and refinement (3Rs) measures described in the European Pharmacopoeia – Applicable to human vaccines from 01/01/2018, adopted.

In accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (Council of Europe), tests performed in animals must be carried out in such a way as to use the minimum number of animals and to cause the least pain, suffering, distress or lasting harm. The European Pharmacopeia (Ph.Eur.) has, over the years, applied these principles by implementing alternative tests and assays that replace, reduce and refine animal use. Therefore, in order to comply with the provisions of Directive 2010/63/EU and Ph.Eur and to secure an undisrupted supply of medicinal products to the European Market, MAHs should take all necessary actions to introduce 3Rs Ph. Eur. methods including submission of variations to marketing authorisations as appropriate. More information is available on the EMA’s website.

Developing drugs for treatment of Duchenne muscular dystrophy and related dystrophinopathies
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment.”

This guidance addresses FDA’s current thinking regarding clinical development programs and trial designs for drugs to support an indication for the treatment of one or more dystrophinopathies: Duchenne muscular dystrophy (DMD) and related dystrophinopathies including Becker muscular dystrophy (BMD), DMD-associated dilated cardiomyopathy (DCM), and symptomatic carrier states in females. More information is available on the FDA’s website.

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

This guidance is intended to assist sponsors in the clinical development of drugs for the treatment of the stages of sporadic Alzheimer’s disease (AD) that occur before the onset of overt dementia. This guidance revises the draft guidance for industry entitled “Alzheimer’s Disease: Developing Drugs for the Treatment of Early Stage Disease” issued February 8, 2013. More information is available on the Federal Register’s website.

Consultation Deadline: 17th May, 2018

Regulatory classification of pharmaceutical co-crystals
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Regulatory Classification of Pharmaceutical Co-Crystals.”

This guidance provides applicants planning to submit new drug applications (NDAs) and abbreviated new drug applications (ANDAs) with information on the appropriate regulatory classification of pharmaceutical co-crystal solid-state forms. This guidance also provides information about the data that applicants should submit to support the appropriate classification of a co-crystal as well as the regulatory implications of the classification. 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 9, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

Version 9 of the document, dated February 2018, supersedes Version 8. Q&As 1.19, 2.17, 2.18, 2.19, 2.20, 2.21, 3.5, 4.4, 5.6, 5.7, 6.5, 6.6, 7.16, 7.17, 7.18, 7.19, 8.5, 8.6, 8.7, 11.2 and 12.1 were added to the document, while Q&As 2.3, 2.10, 5.5 and 7.4 were revised. Q&A 9.2 was renumbered 11.1 following addition of section 11. More information is available on the Commission’s website.

Expert Panel on Health publishes three opinions to help guide policy makers
The independent Expert Panel on Effective ways of Investing in Health has adopted three Opinions related to access to healthcare, innovative payment models for high-cost innovative medicines and performance of primary care.

The Opinion on innovative payment models for high-cost innovative medicines analyses how national pricing and reimbursement authorities could improve patients’ access to innovative medicines and foster innovation that matters whilst ensuring that health systems are financially sustainable. The Opinion on benchmarking access to healthcare in the EU responds to the request for quantitative and qualitative benchmarks to assess progress in reducing unmet need for healthcare. The Opinion on tools and methodologies for assessing the performance of primary care explores how to measure the performance of primary care. More information is available on the Commission’s website.

Developing drugs and biologics for BCG-unresponsive nonmuscle invasive bladder cancer
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment.”

The purpose of this guidance is to assist sponsors in the development of drugs, including biologics, for the treatment of patients who have bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC). This guidance is intended for pharmaceutical sponsors, the academic community, and the public and provides a framework, based on current Food and Drug Administration (FDA) thinking, to facilitate the development of drugs to treat this patient population. This guidance discusses pathological diagnosis and staging, risk stratification, and trial design, including assessment of appropriate clinical endpoints. More information is available on the FDA’s website.

Clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus
The European Medicines Agency have published: Scientific guideline: Draft guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus – Revision 2, draft: consultation open.

This guideline intends to address the EU regulatory position on the main topics of the clinical development of new medicinal products in the treatment or delay in onset / prevention of diabetes. The current revision refers mainly to an update of the safety section with respect to cardiovascular safety, but also updated guidance concerning e.g. treatment effects on diabetes complications, requirements for first line indications, high strength insulin preparations, definitions of hypoglycaemia and development of oral treatments for patients with type 1 diabetes. In addition, some editorial changes have been implemented. More information is available on the EMA’s website.

Consultation Deadline: 15th August, 2018

Microbiology data for systemic antibacterial drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Microbiology Data for Systemic Antibacterial Drugs — Development, Analysis, and Presentation.”

The purpose of this guidance is to assist sponsors in the development, analysis, and presentation of microbiology data during antibacterial drug development. Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the overall microbiology development program needed to support clinical development and approval of antibacterial drugs administered systemically as well as microbiology information collected after approval. This guidance replaces the guidance for industry Microbiology Data for Systemic Antibacterial Drugs — Development, Analysis, and Presentation issued in August 2016. More information is available on the FDA’s website.

Safety and efficacy follow-up and risk management of advanced therapy medicinal products
The European Medicines Agency have published: Scientific guideline: Draft guideline on safety and efficacy follow-up and risk management of advanced therapy medicinal products – Rev. 1, draft: consultation open.

The aim of this guideline is to provide the guidance for the Safety and Efficacy (S&E) follow-up and risk management for advanced therapy medicinal products (ATMPs) according to Article 14(4) of Regulation (EC) No 1394/2007. This regulation requires the European Medicines Agency (EMA) to develop a detailed guideline relating to the post-authorisation follow-up of efficacy and adverse reactions, and risk management for these products. This is the 1st revision of the original ATMP guideline on safety and efficacy follow-up and risk management; the guideline has been revised to take into consideration the experience gained with the authorisation of these products and to define their risks and their risk minimisations measures. In addition, guidance on methodology in order to design post-authorisation S&E follow-up studies is provided. More information is available on the EMA’s website.

Consultation Deadline: 30th April, 2018

Evaluation of advanced therapy medicinal products
The European Medicines Agency have published: Regulatory and procedural guideline: Procedural advice on the evaluation of advanced therapy medicinal product in accordance with Article 8 of Regulation (EC) No 1394/2007, adopted.

This document describes the procedure for the evaluation of marketing authorisation applications for ATMPs. This procedure is put in place to establish timely and effective interactions between the EMA and the different committees (CAT, CHMP and the Pharmacovigilance Risk Assessment Committee (PRAC)) in conjunction with the Applicant during the centralised evaluation of an ATMP. The CAT is also responsible for post-authorisation activities of ATMPs. Though not described in this document, the same principles as outlined for the MAA evaluation procedure applies to postauthorisation activities (e.g. variations, renewals, etc.) according to the established timetables for the relevant procedure. More information is available on the EMA’s website.

Commission report on Member State penalties for the falsification of medicines
The European Commission has published a Report from the Commission to the European Parliament and the Council on the Member States’ transposition of Article 118a of Directive 2001/83/EC of the European Parliament and the Council of 6 November 2001 on the Community code relating to medicinal products for human use as amended by Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011.

The Falsified Medicines Directive (2011/62/EU) (FMD) requires all EU countries to put in place proportionate, effective and dissuasive penalties for those involved in the production and circulation of falsified medicines. The report on how this requirement has been met shows a wide variation in penalties across the EU. More information is available on the Commission’s website.

Marker residue depletion studies to establish product withdrawal periods in aquatic species
The European Medicines Agency have published: Scientific guideline: Draft 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, draft: consultation open.

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. More information is available on the EMA’s website.

Consultation Deadline: 15th June, 2018

Reduction, refinement and replacement (3Rs) measures in the veterinary vaccines field described in the European Pharmacopoeia
The European Medicines Agency have published: Scientific guideline: Recommendation to marketing authorisation holders, highlighting recent measures in the veterinary field to promote reduction, refinement and replacement (3Rs) measures described in the European Pharmacopoeia – Applicable to veterinary vaccines from 01/01/2017, adopted.

In accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (Council of Europe), tests performed in animals must be carried out in such a way as to use the minimum number of animals and to cause the least pain, suffering, distress or lasting harm. The European Pharmacopeia (Ph. Eur.) has, over the years, applied these principles by implementing alternative tests and assays that reduce, refine and replace animal use. The European Pharmacopoeia has introduced a number of measures via new or revised texts in the veterinary field to promote 3Rs. These requirements are published in the 9th edition and are in force from 01/01/2017. More information is available on the EMA’s website.

Transfer of quality control methods validated in collaborative trials with a view to implementing 3Rs
The European Medicines Agency have published: Scientific guideline: Guidance for individual laboratories for transfer of quality control methods validated in collaborative trials with a view to implementing 3Rs, adopted.

In accordance with Directive 2010/63/EU, the principle of the 3Rs (Replacement, Reduction and Refinement) needs to be considered when selecting approaches for validating quality control tests in laboratories for regulatory testing of human and veterinary medicinal products. Collaborative studies between laboratories may be carried out to introduce new 3Rs methods for regulatory purposes where animal tests have been traditionally used. This guidance aims to facilitate transfer and acceptance of the new methods validated in such trials with a view to implementing 3Rs for testing in a product specific context in laboratories originally involved in the collaborative trial or in new laboratories. More information is available on the EMA’s website.

Reduction, refinement and replacement (3Rs) measures in the human vaccines field described in the European Pharmacopoeia
The European Medicines Agency have published: Scientific guideline: Recommendation to marketing authorisation holders, highlighting recent measures in the veterinary field to promote replacement, reduction, and refinement (3Rs) measures described in the European Pharmacopoeia – Applicable to human vaccines from 01/01/2018, adopted.

In accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (Council of Europe), tests performed in animals must be carried out in such a way as to use the minimum number of animals and to cause the least pain, suffering, distress or lasting harm. The European Pharmacopeia (Ph.Eur.) has, over the years, applied these principles by implementing alternative tests and assays that replace, reduce and refine animal use. The European Pharmacopoeia has introduced a number of measures via new or revised texts in the human field to promote 3Rs. These requirements are published in Supplement 9.3 and are in force from 01/01/2018. More information is available on the EMA’s website.

Chemistry of active substances for veterinary medicinal products
The European Medicines Agency have published: Scientific guideline: Guideline on the chemistry of active substances for veterinary medicinal products, adopted.

Guideline concerning the application of Directive 2001/82/EC with a view to the granting of a marketing authorisation for a veterinary medicinal product. This guideline replaces the ‘Note for guidance on chemistry of new active substances’ (EMEA/CVMP/541/03/Final) and ‘Chemistry of active substances’ (3AQ5a). It has been revised to cover new and existing active substances in one guideline. More information is available on the EMA’s website.

Date for coming into effect: 19th July, 2018

Mixing, diluting, or repackaging biological products outside the scope of an approved BLA
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application.”

This guidance sets forth FDA’s policy regarding the mixing, diluting, and repackaging of certain types of biological products that have been licensed under section 351 of the Public Health Service Act (PHS Act) when such activities are not within the scope of the product’s approved biologics license application (BLA) as described in the approved labeling for the product. This guidance describes the conditions under which FDA does not intend to take action for violations of section 351 of the PHS Act and section 502(f)(1), section 582, and, where specified, section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 352(f)(1), 21 U.S.C. 360eee-1, and 21 U.S.C. 351(a)(2)(B), respectively), when a state-licensed pharmacy, a federal facility, or an outsourcing facility dilutes, mixes, or repackages certain biological products outside the scope of an approved BLA. More information is available on the FDA’s website.

Compounded drug products that are essentially copies of a commercially available drug product
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act .”

To qualify for exemptions under section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), a drug product must be compounded by a licensed pharmacist or physician who does not compound regularly or in inordinate amounts any drug products that are essentially copies of a commercially available drug product, among other conditions. This guidance sets forth FDA’s policies regarding this provision of section 503A, including the terms commercially available, essentially a copy of a commercially available drug product, and regularly or in inordinate amounts. More information is available on the FDA’s website.

Compounded drug products that are essentially copies of approved drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act.”

For a drug product compounded by an outsourcing facility to qualify for the exemptions under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act), it must not be “essentially a copy of one or more approved drug products,” and must meet the other conditions in section 503B. This guidance sets forth FDA’s policies concerning the essentially a copy provision of section 503B. More information is available on the FDA’s website.

Clinical investigation of medicinal products for the treatment of rheumatoid arthritis
The European Medicines Agency have published: Scientific guideline: Guideline on clinical investigation of medicinal products for the treatment of rheumatoid arthritis, adopted.

The scope of this guideline is to provide a European common position on pertinent issues relating to the clinical evaluation of medicinal products (synthetic as well as biological DMARDs) for the treatment of RA classified according to international criteria, e.g. ACR-EULAR 2010. Intra-articular products are beyond the scope of this guideline. This document gives guidance on the performance of studies involving drug treatment for RA only. Separate guidance is available for other rheumatic diseases such as osteoarthritis, juvenile idiopathic arthritis, ankylosing spondylitis and psoriatic arthritis, in view of their different pathogenesis and natural histories. More information is available on the EMA’s website.

Date for coming into effect: 1st July, 2018

Best practices for communication between IND sponsors and FDA during drug development
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry and review staff entitled “Best Practices for Communication Between IND Sponsors and FDA During Drug Development.”

The purpose of this guidance is to describe best practices and procedures for timely, transparent, and effective communications between investigational new drug application (IND) sponsors and FDA at critical junctures in drug development, which may facilitate earlier availability of safe and effective drugs to the American public. This guidance applies to communications between IND sponsors and FDA during the IND phase of drug development, including biosimilar biological product development (BPD). More information is available on the FDA’s website.

ICH guideline Q12 on technical and regulatory considerations for pharmaceutical product lifecycle management
The European Medicines Agency have published: Scientific guideline: Draft ICH guideline Q12 on technical and regulatory considerations for pharmaceutical product lifecycle management – Step 2b – First version, draft: consultation open.

This new guideline is proposed to provide guidance on a framework to facilitate the management of post-approval chemistry, manufacturing and controls (CMC) changes in a more predictable and efficient manner across the product lifecycle. This guideline aims to promote innovation and continual improvement, and strengthen quality assurance and reliable supply of product, including proactive planning of supply chain adjustments. The guideline strives to promote, for regulators (assessors and inspectors), an improved understanding of the Applicants’ pharmaceutical quality systems (PQSs) for management of post-approval CMC changes. This new guideline is intended to complement the existing ICH Q8 to Q11 guidelines. More information is available on the EMA’s website.

Consultation Deadline: 18th December, 2018

ICH guideline E17 on general principles for planning and design of multi-regional clinical trials
The European Medicines Agency have published: Scientific guideline: ICH guideline E17 on general principles for planning and design of multi-regional clinical trials – Step 5 – First version, adopted.

The purpose of this document is to outline general principles for the planning and design of multiregional clinical trials with the aim of increasing their acceptability in global regulatory submissions. The document addresses some strategic programme issues as well as aspects specific to the planning and design of confirmatory MRCTs and should be used together with other ICH efficacy guidelines, including E2, E3, E4, E5, E6, E8, E9, E10 and E18. More information is available on the EMA’s website.

Date for coming into effect: 14th June, 2018

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

This draft guidance 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. More information is available on the Federal Register’s website.

Consultation Deadline: 21st May, 2018

Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System.”

This guidance provides recommendations for sponsors of investigational new drug applications (INDs), and applicants who submit new drug applications (NDAs), abbreviated new drug applications (ANDAs), and supplements to these applications for immediate-release (IR) solid oral dosage forms, and who wish to request a waiver of an in vivo bioavailability (BA) and/or bioequivalence (BE) study requirement. These recommendations are intended to apply to waivers requested during the IND period and the NDA stage or for ANDAs, i.e., (1) subsequent in vivo BA or BE studies of formulations after the initial establishment of the in vivo BA of IR solid oral dosage forms during the IND period, and (2) in vivo BE studies of IR solid oral dosage forms in NDAs, ANDAs, and supplements to these applications. More information is available on the FDA’s website.

ICH Guideline S3A: Note for guidance on toxicokinetics: the assessment of systemic exposure in toxicity studies
The European Medicines Agency have published: Scientific guideline: ICH Guideline S3A: Note for guidance on toxicokinetics: the assessment of systemic exposure in toxicity studies – Questions and answers – Step 5 – First version, adopted.

The S3A guideline was successfully implemented in 1994. However, in recent years, analytical method sensitivity has improved, allowing microsampling techniques to be widely used in toxicokinetic (TK) assessment. This Q&A document focuses on points to consider before incorporating the microsampling method in TK studies, acknowledges its benefits, and some limitations, for assessment of TKs in main study animals and its overall important contribution to the 3Rs benefits (Replacement, Reduction and Refinement) by reducing or eliminating the need for TK satellite animals. More information is available on the EMA’s website.

Systemic antibacterial and antifungal drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Systemic Antibacterial and Antifungal Drugs: Susceptibility Test Interpretive Criteria Labeling for NDAs and ANDAs.”

This guidance provides recommendations on fulfilling the new labeling requirements for susceptibility test interpretive criteria for prescription systemic antibacterial and antifungal drugs as established by section 3044 of the 21st Century Cures Act (Cures Act) (Public Law 114-255). It describes FDA’s recommendations on (1) how to make these labeling changes for antimicrobial drugs with approved new drug applications (NDAs) or abbreviated new drug applications (ANDAs), (2) language to remove from the labeling of such drugs, and (3) labeling language to use for all antimicrobial drugs to reference the FDA’s Susceptibility Test Interpretive Criteria web page. More information is available on the FDA’s website.

Monoclonal antibodies for veterinary use
The European Medicines Agency have published: Scientific guideline: Questions and answers on monoclonal antibodies for veterinary use, adopted.

The range of clinical indications with potential for treatment with mAbs is very wide. Currently, in human medicine, a number are authorised for use as anti-cancer medicines and in medicines against diseases affecting the immune system, such as rheumatoid arthritis. To date, the CVMP and its Scientific Advice Working Party (SAWP-V) have addressed a limited number of scientific advice requests concerning mAb products. This activity indicates that a number of mAbs for use as veterinary medicinal products are in development. Indeed, in February 2017, the CVMP recommended the granting of a marketing authorisation for Cytopoint (lokivetmab), the first monoclonal antibody in a veterinary medicine in the EU, intended for the treatment of dogs with atopic dermatitis. Following a review of the scientific information relating to mAbs, a number of areas (in the form of questions) were identified that would benefit from consideration by relevant experts and the elaboration of specific guidance in the form of questions and answers (Q&A). information is available on the EMA’s website.

QRD guidance on the use of approved pictograms on the packaging of veterinary medicinal products
The European Medicines Agency have published: Regulatory and procedural guideline: Quality review of documents (QRD) guidance on the use of approved pictograms on the packaging of veterinary medicinal products authorised via the centralised (CP), mutual recognition (MRP) and decentralised procedures (DCP), adopted.

The need for a harmonised, approved ‘catalogue’ of pictograms was identified and this draft guidance was developed as a collaboration between the QRD (vet) group, the CMDv, CVMP and industry stakeholders. The use of pictograms from Annex 1 of this guidance will apply to the national authorisation procedures, including MRP and DCP and to the centralised procedure (EMA). The aim of the guidance is to outline the approval requirements and processes where pictograms from Annex 1 are used on the product literature. More information is available on the EMA’s website.

Product name placement, size, and prominence in promotional labeling and advertisements
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Product Name Placement, Size, and Prominence in Promotional Labeling and Advertisements.”

This guidance clarifies the requirements for product name placement, size, prominence, and frequency in promotional labeling and advertisements for prescription drugs. The disclosure of the product name in promotional labeling and advertisements is important for proper identification and to ensure safe and effective use. This guidance also articulates the circumstances under which FDA intends to refrain from taking enforcement action regarding these requirements. More information is available on the FDA’s website.

Drug development in pediatric rare diseases
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Pediatric Rare Diseases—A Collaborative Approach for Drug Development Using Gaucher Disease as a Model.”

This draft guidance focuses on drug development for pediatric patients with Gaucher disease. In particular, it proposes for consideration a novel approach to improve the efficiency of drug development in pediatric rare diseases using Gaucher disease as an example. The emergence of concomitant trials for multiple investigational drug products for the treatment of rare diseases can pose significant challenges to effective drug development, because there are limited numbers of patients for any given rare condition worldwide. This approach discusses the feasibility of the development of multiple drug products in a time-efficient manner while minimizing the number of patients necessary to be treated with placebo. More information is available on the Federal Register’s website.

Consultation Deadline: 5th February, 2018

Juvenile animal studies and impact on anti-cancer medicine development and use in children
The European Medicines Agency have published: Scientific guideline: Results of juvenile animal studies (JAS) and impact on anti-cancer medicine development and use in children, adopted.

This project was aimed to assess the impact and the utility of JAS on paediatric medicinal product development, and the example of anti-cancer medicines was chosen as they are expected to show toxicity that most likely affects developing tissues and organs, in both humans and animals. More information is available on the EMA’s website.

Preparation of EU herbal monographs for well-established and traditional herbal medicinal products
The European Medicines Agency have published: Scientific guideline: Guideline on the assessment of clinical safety and efficacy in the preparation of EU herbal monographs for well-established and traditional herbal medicinal products – Revision 1, adopted.

This guideline describes the legal background and recommendations for the assessment of data that are used to prepare European Union herbal monographs (formerly called Community herbal monographs) on herbal medicinal products and the European Union list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products. The areas of herbal medicinal products with well-established medicinal use and traditional herbal medicinal products
are addressed.

Revision 1 pertains to an update of the document to current standards taking into account advances over the last 10 years and established practice and legal interpretations. Developments and details in the assessment methodology have so far been mainly reflected in template revisions (such as Assessment report template), but also other documents such as the public statement EMA/HMPC/473587/2011. In addition to the alignment with other documents the revision aimed for improved clarity and transparency by shortening some sections or providing more detail on some particular aspects of the assessment process, e.g. as regards specific population groups.

More information is available on the EMA’s website.

GMP specific to advanced therapy medicinal products
The European Commission has published a set of guidelines on good manufacturing practice (GMP) specific to advanced therapy medicinal products (ATMPs).

The new guidelines adapt the European Union GMP requirements to the specific characteristics of ATMPs and address the novel and complex manufacturing scenarios utilised for these products. The guidelines foster a risk based approach to manufacture and testing of such products. The guidelines ensure that these novel medicinal products are consistently produced and controlled according to high quality standards, for the benefit and the safety of patients. This initiative is part of the joint action plan launched by the Directorate General for Health and Food Safety (DG SANTE)External link icon and the European Medicines Agency (EMA) in October 2017 to foster the development of ATMPs. More information is available on the Commission’s website.

European Commission Safety Features Q&A document updated
The European Commission has published an updated version, Version 8, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

Version 8 of the document, dated November 2017, supersedes Version 7. Q&As 1.17, 1.18, 7.13, 7.14, 7.15, 8.4 and 10.1 were added were added to the document, while Q&As 1.2, 2.12 and 3.3 were revised. More information is available on the Commission’s website.

Conduct of pharmacokinetic studies in target animal species
The European Medicines Agency have published: Scientific guideline: Draft guideline on conduct of pharmacokinetic studies in target animal species – Revision 1, draft: consultation open.

The objectives of this guidance are to specify the pharmacokinetic factors to be investigated, acknowledging that this will depend on the active substance and its use, and to provide recommendations for the conduct of pharmacokinetic studies for the purpose of supporting the clinical part of the dossier for a veterinary pharmaceutical product. In addition, general guidance is given on pharmacokinetic-pharmacodynamic modelling and population pharmacokinetics, should applicants opt to pursue these approaches. More information is available on the EMA’s website.

Consultation Deadline: 31st May, 2018

Clinical development of medicinal products for the treatment of Autism Spectrum Disorder
The European Medicines Agency have published: Scientific guideline: Guideline on the clinical development of medicinal products for the treatment of Autism Spectrum Disorder (ASD), adopted.

Autism Spectrum Disorder (ASD) is amongst the most common and varied disorders in paediatric psychiatry. It impacts significantly on social, occupational and other important areas of functioning. It is a lifelong condition and although various therapies and interventions are available few are supported by scientific studies. Pharmacotherapies approved to date for the management of ASD have been nonspecific for the condition (e.g. atypical antipsychotics for the control of behavioural disturbances) and do not target the core symptoms. This document is intended to provide guidance on the evaluation of new products in ASD; it should be read in conjunction with other EMA and ICH guidelines, which may apply to similar conditions and patient populations. More information is available on the EMA’s website.

Date for coming into effect: 1st June, 2018

Evaluating the abuse deterrence of generic solid oral opioid drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products.”

This guidance is intended to assist a person who plans to develop and submit an abbreviated new drug application (ANDA) (hereinafter potential ANDA applicant) to seek approval of a generic version of a solid oral opioid drug product that references an opioid drug product with abuse-deterrent properties described in its labeling. The guidance recommends studies, including comparative in vitro and pharmacokinetic (PK) studies, that the potential ANDA applicant should conduct and submit to FDA in an ANDA to demonstrate that a generic solid oral opioid drug product is no less abuse deterrent than its reference listed drug (RLD) with respect to all potential routes of abuse. More information is available on the FDA’s website.

Comments received on ‘Draft Guideline on manufacture of the finished dosage form’
The European Medicines Agency have published: Scientific guideline: Overview of comments received on ‘Draft Guideline on manufacture of the finished dosage form’ (EMA/CHMP/QWP/245074) – Revision 1.

More information is available on the EMA’s website.

Evaluating drug effects on the ability to operate a motor vehicle
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Evaluating Drug Effects on the Ability to Operate a Motor Vehicle.”

The purpose of this guidance is to assist pharmaceutical sponsors in the evaluation of the effects of psychoactive drugs on the ability to operate a motor vehicle. More information is available on the FDA’s website.

Developing drugs for treatment and prevention of recurrent herpes labialis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Recurrent Herpes Labialis: Developing Drugs for Treatment and Prevention.”

The purpose of this guidance is to assist sponsors in the development of drugs for the treatment and prevention of recurrent herpes labialis (RHL). Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the overall development program and clinical trial designs to support the development of drug products with an antiviral mechanism of action used to prevent and/or treat RHL caused by either herpes simplex virus type 1 or 2 (HSV-1 or HSV-2) in immunocompetent subjects. More information is available on the FDA’s website.

Recommended statement for OTC aspirin-containing drug products labeled with cardiovascular related imagery
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Recommended Statement for Over-the-Counter Aspirin-Containing Drug Products Labeled With Cardiovascular Related Imagery.”

This guidance is intended to promote the safe use of OTC aspirin drug products by encouraging drug manufacturers, packagers, and labelers marketing aspirin drug products with cardiovascular related imagery to include a statement that reminds consumers to talk to their doctor or other healthcare provider before using aspirin for the professional indication of secondary prevention of cardiovascular events. More information is available on the FDA’s website.

Developing direct-acting antiviral drugs for treatment of chronic hepatitis C virus
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment.”

The purpose of this guidance is to assist sponsors in the clinical development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC) from the preinvestigational new drug application (pre-IND) stage through the new drug application (NDA) and postmarketing stages. More information is available on the FDA’s website.

Formal dispute resolution for sponsor appeals
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry and review staff entitled “Formal Dispute Resolution: Sponsor Appeals Above the Division Level.”

This guidance provides recommendations for industry and review staff on the procedures in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) for resolving scientific and/or medical disputes between CDER or CBER and sponsors that cannot be resolved at the division level. This guidance describes the formal dispute resolution (FDR) procedures for sponsors that wish to appeal a scientific and/or medical issue to the office or center level and provides a structured process for resolving disputes. More information is available on the FDA’s website.

New analytical methods/technologies in the quality control of herbal medicinal products
The European Medicines Agency have published: Scientific guideline: Concept paper on the development of a reflection paper on new analytical methods/technologies in the quality control of herbal medicinal products, draft: consultation open.

Quality control is a prerequisite to assure safe and effective use of (traditional) herbal medicinal products, which are complex mixtures of numerous phytochemical constituents. For the majority of herbal substances, herbal preparations and (traditional) herbal medicinal products the active constituents are not known or are only partly understood. Requirements on quality control are based on Directive 2001/82/EC and Directive 2001/83/EC and specified in detail in Annex I (Directive 2003/63/EC) and relevant guidelines published by EMA (see references). Binding quality standards are also described in the relevant monographs of the European Pharmacopeia. There is an established set of methods (such as HPLC, TLC, GC, etc.) which is currently used in quality control of (traditional) herbal medicinal products (HMPs). In total, the system established cannot exactly measure all features or constituents in parallel, but is an appropriate and generally applied convention. When considering introduction of new methodology, this will usually be complementary to the existing methodology. Although some new techniques offer the option to create a type of “holistic” fingerprint, it is necessary to consider if such approaches offer added value in terms of quality control. More information is available on the EMA’s website.

Consultation Deadline: 30th April, 2018

Clinical investigation of medicinal products for the treatment of axial spondyloarthritis
The European Medicines Agency have published: Scientific guideline: Guideline on the clinical investigation of medicinal products for the treatment of axial spondyloarthritis – Revision 1, adopted.

This document is a revision of the Guideline on clinical investigation of medicinal products for the treatment of ankylosing spondylitis (CPMP/EWP/4891/03) which came into effect in May 2009. It should be considered as general guidance on the development of medicinal products for the treatment of axial spondyloarthritis and should be read in conjunction with other European and ICH guidelines which may apply to this disease area and patient population. The current revision has taken into account that clinical practice has evolved since publication of the previous guideline and acknowledges that patients with axial spondyloarthritis (axial SpA) who do not fulfill the modified New York (mNY) criteria of ankylosing spondylitis (AS) can present with disease activity and functional impairment similar to those observed in patients with AS. These patients, captured under the term non-radiographic axial SpA, are considered in this revised CHMP guideline. The new guideline also reviews relevant treatment goals, new outcome measures for the treatment as well as the design of confirmatory trials in the light of the currently available treatment options. More information is available on the EMA’s website.

Date for coming into effect: 1st May, 2018

Statistical principles for clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance entitled “E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials.”

The draft guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The draft guidance clarifies, updates, and extends the earlier “E9 Statistical Principles for Clinical Trials” in two main areas. Concerning estimands, it provides a framework for discussion of how the aims of a trial relate to the proposed statistical analysis. Concerning sensitivity analysis, it discusses how to use additional analyses to address concerns about the validity of assumptions underlying the main analysis. The draft guidance is intended to better align the choice of statistical methods with questions of regulatory importance and to improve the reliability of decisions about and representations of the effects of medical products. More information is available on the Federal Register’s website.

Consultation Deadline: 30th April, 2018

Prophylaxis or treatment of respiratory syncytial virus (RSV) disease
The European Medicines Agency have published: Scientific guideline: Draft guideline on the clinical evaluation of medicinal products indicated for the prophylaxis or treatment of respiratory syncytial virus (RSV) disease, draft: consultation open.

The guideline covers the clinical development of vaccines and monoclonal antibodies for the prevention of RSV disease and direct acting antiviral agents for the treatment of RSV disease. The focus is on the assessment of safety and efficacy in populations most likely to develop RSV lower respiratory tract infection and severe RSV disease, including (newborn) infants and toddlers, older children predisposed to develop severe RSV disease and the elderly. The guideline also addresses vaccination of pregnant women with the aim of preventing RSV disease in their infants.
The draft guideline proposes some considerations on nonclinical investigations of efficacy and risk of vaccine-associated enhanced disease to support clinical trials with preventive or therapeutic products directed at RSV. More information is available on the EMA’s website.

Consultation Deadline: 30th April, 2018

State of children’s medicines in the EU
The European Commission has presented a report to the European Parliament and the Council, on progress made in children’s medicines since the Paediatric Regulation came into force 10 years ago.

This report is an essential intermediate step in the debate on a joint vision about the future parameters for paediatric and orphan medicines. Before proposing any amendments, the Commission will evaluate – in consultation with stakeholders and experts, how the combined effects of the Orphan and Paediatric Regulation can support medicine development in subpopulations of particular need, e.g. children with cancer. Results of this reflection will be presented by 2019 to allow the next Commission to take informed decision about possible policy options. More information is available on the Commission’s website.

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

This guideline addresses the specific documentation requirements on the biological, chemical and pharmaceutical quality of IMPs containing biological / biotechnology derived substances. Moreover, this guideline lists, as regards documentation on the biological, chemical and pharmaceutical quality of the IMP, examples of modifications which are typically considered as ‘substantial’. More information is available on the EMA’s website.

Evaluation of new active substance status of chemical substances – veterinary
The European Medicines Agency have published: Scientific guideline: Reflection paper on the chemical structure and properties criteria to be considered for the evaluation of new active substance (NAS) status of chemical substances – Veterinary, adopted.

This reflection paper is intended to reflect the current experience of the Quality Working Party (QWP), of the Committee for Medicinal Products for Veterinary Use (CVMP) and the Co-ordination Group for Mutual Recognition and Decentralised Procedures-Veterinary (CMDv) concerning the definition of a New Active Substance (NAS) in the context of preparation of dossiers and submissions of applications for Marketing Authorisation (MAA) in the Centralised Procedure (CP), the Mutual Recognition Procedure (MRP)/Decentralised Procedure (DCP) and purely national procedures for chemical medicinal products for veterinary use under Article 12(3) of Directive 2001/82/EC as amended. The paper describes the chemical structure and properties criteria to be taken into account by the competent authorities to qualify a chemical active substance as NAS, as well as the required elements to be submitted by applicants to substantiate their claims. More information is available on the EMA’s website.

Excipients in the labelling and package leaflet of medicinal products for human use
The European Medicines Agency (EMA) and the European Commission have updated the annex to the European Commission guideline on excipients in the labelling and package leaflet of medicinal products for human use.

The updated annex contains all excipients that must be declared in a medicine’s labelling and package leaflet and their agreed safety warnings. The main aim of this update is to take into account safety concerns which are not currently addressed in the existing annex to the guideline. More information is available on the EMA’s website.

Classification of veterinary medicinal products indicated for minor use minor species (MUMS) / limited market
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 – Revision 1, adopted.

This guideline is based on the Revised Policy for classification and incentives for veterinary medicinal products indicated for minor use minor species (MUMS)/limited market (EMA/308411/2014).
This revision (Rev.1) is an administrative update to ensure that the document corresponds with the revised guidelines on data requirements for veterinary medicinal products intended for MUMS/limited market that were adopted by CVMP in 2017. The opportunity has been taken to simplify the request process for applicants and to introduce a small number of textual changes aiming to improve the clarity of the document without changing the meaning or intention. More information is available on the EMA’s website.

Companies requesting classification as minor uses minor species (MUMS) / limited markets
The European Medicines Agency have published: Regulatory and procedural guideline: Q&A – European Medicines Agency guidance for companies requesting classification as minor uses minor species (MUMS) / limited markets, adopted.

This guidance document addresses a number of questions that applicants requesting classification of products/indications for minor use or minor species (MUMS)/ limited market may have. More information is available on the EMA’s website.

Completeness assessments for Type II API DMFs under GDUFA
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Completeness Assessments for Type II API DMFs Under GDUFA Guidance for Industry.”

This guidance is intended for holders of Type II active pharmaceutical ingredient (API) drug master files (DMFs) that are or will be referenced in an abbreviated new drug application (ANDA), an amendment to an ANDA, a prior approval supplement (PAS) to an ANDA, or an amendment to a PAS (generic drug submissions). More information is available on the FDA’s website.

ANDA submissions – prior approval supplements under GDUFA
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “ANDA Submissions – Prior Approval Supplements Under GDUFA.”

This guidance is intended to assist applicants preparing to submit to FDA prior approval supplements (PASs) and amendments to PASs for abbreviated new drug applications (ANDAs) under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)). More information is available on the FDA’s website.

Advancement of emerging technology applications for pharmaceutical innovation and modernization
The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled “Advancement of Emerging Technology Applications for Pharmaceutical Innovation and Modernization.”

This guidance finalizes the draft guidance issued December 23, 2015, which provides recommendations to pharmaceutical companies interested in participating in a program involving the submission of emerging manufacturing technology. The program is open to companies that intend to include the technology as part of a regulatory submission including an investigational new drug application (IND), original or supplemental new drug application (NDA), abbreviated new drug application (ANDA) or biologic license application (BLA), or application-associated Drug Master File (DMF) reviewed by the Center for Drug Evaluation and Research (CDER), and where that technology meets other criteria described in this guidance. More information is available on the Federal Register’s website.

Expedited programs for serious conditions – drugs and biologics
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Expedited Programs for Serious Conditions – Drugs and Biologics.”

The following four FDA programs are intended to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious or lifethreatening condition: fast track designation, breakthrough therapy designation, accelerated approval, and priority review designation (see section IV for an overview of the programs). The purpose of this guidance for industry is to provide a single resource for information on FDA’s policies and procedures for these four programs as well as threshold criteria generally applicable to concluding that a drug is a candidate for these expedited development and review programs. More information is available on the FDA’s website.

European Commission adopts acts on Good Manufacturing Practices for medicines
The European Commission has adopted two legal acts aimed at improving patient safety in the EU through good manufacturing practices (GMP) that ensure the highest quality of medicines for human use.

The first act is an implementing directive that sets out principles and guidelines of GMP in medicines where the manufacture or import is subject to a manufacturing authorization, as per Article 40 of the Community code Directive (2001/83/EC).

The second act is a delegated regulation that sets out GMP for investigational medicinal products, as required by the Clinical Trials Regulation (536/2014/EU), and detailed arrangements for inspections. This legal act ensures the highest quality of medicinal products used in clinical trials and prepares the smooth entry into force of this Regulation.

The principles and guidelines for GMP set out in these acts take into account recent updates to the well-established EU rules on the safety of medicines. Whether a medicinal product is already on the market, or still undergoing a clinical trial, the newly adopted acts aim to ensure the highest level of quality for medicines for the benefit of the patients as well as consistency between the GMP requirements for both types of medicinal products.

More information is available on the Commission’s website.

Medicinal products intended exclusively for markets outside the Community under Article 58 of Regulation (EC) No 726/2004
The European Medicines Agency have published: Regulatory and procedural guideline: European Medicines Agency procedural advice on medicinal products intended exclusively for markets outside the Community under Article 58 of Regulation (EC) No 726/2004 in the context of cooperation with the World Health Organization.

This document addresses a number of questions that users of Article 58 of Regulation (EC) No 726/2004 may have. It provides an overview of the EMA’s position on issues that are typically addressed in pre-submission meetings.
More information is available on the EMA’s website.

Dissolution specification for generic solid oral immediate release products with systemic action
The European Medicines Agency have published: Scientific guideline: Reflection paper on the dissolution specification for generic solid oral immediate release products with systemic action – First version.

This paper discusses the suitability of the dissolution method and the specifications for in vitro dissolution of orally administered generic drug products with immediate release characteristics. Where applicable, this reflection paper should be read in connection with the principles of relevant guidelines listed as references. More information is available on the EMA’s website.

Comments on dissolution specification for generic solid oral immediate release products with systemic action
The European Medicines Agency have published: Scientific guideline: Overview of comments received on ‘Draft reflection paper on the dissolution specification for generic solid oral immediate release products with systemic action’ – First version.

This document lists the comments submitted by interested parties (organisations or individuals) on the draft document as released for consultation, together with the responses of the EMA. More information is available on the EMA’s website.

Antibacterial therapies for patients with an unmet medical need for the treatment of serious bacterial diseases
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases.”

This guidance is intended to assist sponsors in the clinical development of new antibacterial drugs. Specifically, the guidance explains the FDA’s current thinking about possible streamlined development programs and clinical trial designs for antibacterial drugs to treat serious bacterial diseases in patients with an unmet medical need, including patients who have a serious bacterial disease for which effective antibacterial drugs are limited or lacking. More information is available on the FDA’s website.

Data elements for transmission of individual case safety reports
The European Medicines Agency have published: Scientific guideline: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use topic E 2 B (R3): Questions and answers: Data elements for transmission of individual case safety reports – Step 5, adopted.

This Q&A document provides clarifications for the harmonized interpretation of the E2B(R3) IG package and should be reviewed in conjunction with the IG package. This will facilitate the implementation of the electronic transmission of Individual Case Safety Reports (ICSRs) in the ICH regions. The sections of this Q&A document corresponds to the organization of the E2B(R3) IG. More information is available on the EMA’s website.

Allogenic stem cell-based products for veterinary use
The European Medicines Agency have published: Scientific guideline: Questions and Answers on allogenic stem cell-based products for veterinary use: Specific questions on extraneous agents, adopted.

Freedom from extraneous agents is a crucial aspect of quality evaluation of stem cell-based preparations. Therefore, appropriate acceptance criteria for starting and raw materials of human or animal origin need to be established. Following a review of the scientific information relating to stem cells, a number of areas have been identified that would benefit from further consideration by relevant experts and, where appropriate, the elaboration of specific guidance in the form of question and answer document (Q&A). Three specific questions for further consideration have been identified relating to freedom from extraneous agents aspects. More information is available on the EMA’s website.

Promotion of pharmacovigilance reporting
The European Medicines Agency have published: Scientific guideline: Reflection paper on promotion of pharmacovigilance reporting, adopted.

Experience to date within the regulatory network suggests that there may be an issue relating to under-reporting of adverse events associated with the use of veterinary medicinal products (VMPs) particularly with regard to use in food producing animals. This document will provide an overview of the different tools used by national competent authorities (NCAs) and the European Medicines Agency (EMA or the ‘Agency’) to date to promote pharmacovigilance (PhV) reporting. In addition, further activities that may be beneficial in increasing PhV reporting in general and particularly with regard to food producing animals will be examined. More information is available on the EMA’s website.

Generic Drug User Fee Amendments of 2012
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Generic Drug User Fee Amendments of 2012: Questions and Answers Related to Self-Identification of Facilities, Review of Generic Drug Submissions, and Inspections and Compliance.”

This guidance provides answers to questions arising from the implementation of the Generic Drug User Fee Amendments of 2012 (GDUFA) (Public Law 112-144, Title III), commonly referred to as GDUFA. The questions and answers (Q&A) format is intended to promote transparency and facilitate compliance by the generic drug industry. The first draft of this document was issued pursuant to 21 CFR 10.115 in August 2012 and a revised draft was issued in September 2013. FDA is issuing the final guidance as two separate guidances. This guidance includes questions and answers related to self-identification, review of generic drug submissions, and inspections and compliance. This final guidance clarifies some of the questions and answers included in the previous versions based on FDA’s experience in implementing GDUFA. More information is available on the FDA’s website.

Involvement of young patients/consumers within EMA activities
The European Medicines Agency have published: Regulatory and procedural guideline: Principles on the involvement of young patients/consumers within EMA activities, adopted.

The purpose of this document is to establish the principles for the involvement of young patients, consumers, and their carers, in the activities of the Agency’s scientific committees and working parties in a consistent and efficient manner, whenever such involvement is appropriate in the interest of the ongoing scientific assessment within a particular (scientific) committee. More information is available on the EMA’s website.

NORs, PARs, DSp and normal variability of process parameters
The European Medicines Agency have published: Scientific guideline: Questions and answers: improving the understanding of normal operating range (NOR), proven acceptable range (PAR), design space (DSp) and normal variability of process parameters.

This question and answer document is aimed at improving the understanding of NORs, PARs, DSp and normal variability of process parameters. More information is available on the EMA’s website.

European Union individual case safety report (ICSR) implementation guide
The European Medicines Agency have published: Regulatory and procedural guideline: European Union individual case safety report (ICSR) implementation guide, adopted.

This guidance specifies the technical requirements and the process of transmission of individual case safety reports (ICSRs) and is applicable to all stakeholders, which are exchanging ICSRs electronically within the European Economic Area. More information is available on the EMA’s website.

Selection and justification of starting materials for the manufacture of chemical active substances
The European Medicines Agency have published: Scientific guideline: Reflection paper on the requirements for selection and justification of starting materials for the manufacture of chemical active substances, adopted.

This reflection paper aims to clarify some of the expectations of EU competent authorities arising from the guidance found in ICH Q11 (Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) regarding the information to be submitted in marketing authorisation dossiers to justify the selection of starting materials. Whilst ICH Q11 is not generally applicable to veterinary products, the principles outlined in this document should apply equally for active substances destined to treat both humans and animals. More information is available on the EMA’s website.

Development of non-substantially manipulated cell-based ATMPs
The European Medicines Agency have published: Regulatory and procedural guideline: Development of non-substantially manipulated cell-based advanced therapy medicinal products: flexibility introduced via the application of the risk-based approach.

This document aims to illustrate some of the possibilities and limitations of the risk-based approach using the example of an ATMP based on cells that have not been subjected to substantial manipulation and that are not intended for the same essential function: a de-novo development of autologous bone marrow or peripheral blood CD34+ cells for treatment of acute myocardial infarction. More information is available on the EMA’s website.

Gaucher disease: a strategic collaborative approach from the EMA and FDA
The European Medicines Agency have published: Scientific guideline: Gaucher disease: a strategic collaborative approach from the European Medicines Agency and Food and Drug Administration, adopted.

This Strategic Collaborative Approach document is not a formal guidance; the purpose of this document is to facilitate paediatric drug development particularly in the field of Gaucher disease. The general principles presented should be viewed as suggestions only. More information is available on the EMA’s website.

Criteria to waive target animal batch safety testing for inactivated vaccines for veterinary use
The European Medicines Agency have published: Scientific guideline: VICH GL50: Harmonisation of criteria to waive target animal batch safety testing for inactivated vaccines for veterinary use – Revision 1, adopted.

The objective of this guideline is to provide internationally harmonized recommendations for criteria on data requirements to waive target animal batch safety testing of inactivated veterinary vaccines in regions where it is required. More information is available on the EMA’s website.

Date for coming into effect: 1st May, 2018

Criteria to waive target animal batch safety testing for live vaccines for veterinary use
The European Medicines Agency have published: Scientific guideline: VICH GL55: Harmonization of criteria to waive target animal batch safety testing for live vaccines for veterinary use – First version, adopted.

The objective of this guideline is to provide internationally harmonized recommendations for criteria on data requirements to waive target animal batch safety testing of live veterinary vaccines in regions where it is required. More information is available on the EMA’s website.

Date for coming into effect: 1st May, 2018

Safety features on the packaging of medicinal products for human use
The European Commission has published: Commission Delegated Regulation EU) 2016/161 of 2 October 2015 supplementing Directive 2001/83/EC of the European Parliament and of the Council by laying down detailed rules for the safety features appearing on the packaging of medicinal products for human use.

The delegated act detailing the characteristics of the safety features, how medicine authenticity should be verified, and by whom, was adopted on 2nd October 2015 and published, after scrutiny by the European Parliament and the Council, on 9th February 2016. To facilitate the implementation of the delegated Regulation, the Commission has also prepared a “Questions and Answers” document.

In addition, the regulatory requirements to be followed to notify the EMA of the placing of the unique identifier and/or the anti-tampering device on centrally authorised products are detailed in an implementation plan developed by the EMA and the European Commission and published in the “product information templates” section of the EMA website.

More information is available on the Commission’s website.

Date for coming into effect: 9th February, 2019