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.

Quality of water for pharmaceutical use
The European Medicines Agency have published: Scientific guideline: Draft guideline on the quality of water for pharmaceutical use, draft: consultation open.

This guideline replaces the Note for Guidance on quality of water for pharmaceutical use (CPMP/QWP/158/01, EMEA/CVMP/115/01) originally adopted in May 2002, and the CPMP Position Statement on the Quality of Water used in the production of Vaccines for parenteral use (EMEA/CPMP/BWP/1571/02 rev.1). The note for guidance has been updated to reflect the following changes in the European Pharmacopoeia: a revised monograph for Water for Injections (0169) allowing the possibility to use methods other than distillation for producing water of injectable quality, a new monograph for Water for preparation of extracts (2249), and a suppression of the monograph for Water, highly purified (1927). More information is available on the EMA’s website.

Consultation Deadline: 15th May, 2019

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

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

Consultation Deadline: 30th June, 2019

Metastasis-free survival endpoint in clinical trials for nonmetastatic, castration-resistant prostate cancer
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Nonmetastatic, Castration-Resistant Prostate Cancer: Considerations for Metastasis-Free Survival Endpoint in Clinical Trials.”

This draft guidance provides recommendations to sponsors regarding the use of metastasis-free survival (MFS) as an endpoint in clinical trials for nonmetastatic, castration-resistant prostate cancer (nmCRPC) development programs for drug or biological products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). More information is available on the Federal Register’s website.

Consultation Deadline: 14th January, 2019

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

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

Consultation Deadline: 30th June, 2019

Quality aspects included in the product information for vaccines for human use
The European Medicines Agency have published: Scientific guideline: Guideline on quality aspects included in the product information for vaccines for human use – Revision 1, adopted.

The purpose of this document is to provide applicants and regulators with harmonised guidance on the quality aspects to be included in the summary of product characteristics (SmPC), package leaflet (PL) and labelling for vaccines for human use. This guideline should be read in conjunction with the other guidelines and documents which are referenced in this document. Applicants are advised to take this guideline into account when submitting new applications for Marketing Authorisation (MA) for vaccines, and may consider it when applying for renewal of, or variations to, existing MAs for vaccines for human use, where the product information is already approved. More information is available on the EMA’s website.

Date for coming into effect: 1st May, 2019

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

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

Date for coming into effect: 1st November, 2018

Demonstration of therapeutic equivalence for locally acting products in the GIT
The European Medicines Agency have published: Scientific guideline: Guideline on equivalence studies for the demonstration of therapeutic equivalence for locally acting products in the gastrointestinal tract – Revision 1, adopted.

This guideline defines the requirements that need to be fulfilled to waive clinical trials with clinical or pharmacodynamic endpoints in the demonstration of therapeutic equivalence for locally applied, locally acting gastrointestinal products. It also defines the in vivo bioequivalence studies and in vitro equivalence tests that are necessary. More information is available on the EMA’s website.

Date for coming into effect: 1st May, 2019

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

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

Clinical evaluation of medicinal products indicated for the prophylaxis or treatment of RSV disease
The European Medicines Agency have published: Scientific guideline: Guideline on the clinical evaluation of medicinal products indicated for the prophylaxis or treatment of respiratory syncytial virus (RSV) disease – First version, adopted.

This guideline addresses clinical development programmes for medicinal products intended for the pre-exposure prophylaxis or treatment of disease due to respiratory syncytial virus (RSV). The guidance covers the development of vaccines and monoclonal antibodies for the prevention of RSV disease and direct acting antiviral agents (DAAs) for the treatment of RSV disease. More information is available on the EMA’s website.

Date for coming into effect: 1st May, 2019

Meta-analyses of randomized controlled clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products.”

This document, when finalized, will provide guidance to applicants submitting investigational new drug applications, new drug applications, biologics license applications, or supplemental applications on the use of meta-analyses of randomized controlled clinical trials (RCTs) to evaluate the safety of human drugs or biological products within the framework of regulatory decision-making. (1) This draft guidance is also intended for FDA reviewers and for third-party entities that prepare or evaluate meta-analyses assessing the safety of drug products. Specifically, this guidance describes the factors FDA intends to consider when evaluating the strength of evidence provided by a meta-analysis studying the safety of drugs. More information is available on the Federal Register’s website.

Consultation Deadline: 7th January, 2019

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

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

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

The purpose of this guidance is to assist sponsors in the clinical development of drugs and biologics for the treatment of chronic hepatitis B virus (HBV) infection from the initial investigational new drug application (IND) through the new drug application (NDA)/biologics license application (BLA) and postmarketing phases. More information is available on the Federal Register’s website.

Consultation Deadline: 2nd January, 2019

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

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

Biopharmaceutics Classification System-based biowaivers
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Biopharmaceutics Classification System-Based Biowaivers.”

The draft guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The draft guidance will provide recommendations to support the biopharmaceutics classification of drug substances and the Biopharmaceutics Classification System (BCS)-based waiver of in vivo bioequivalence (BE) studies for drug products. In vivo BE studies are needed to demonstrate lack of impact of significant formulation changes on a drug’s bioavailability during its development, for post-approval line extensions, and when developing a generic product. Utilizing the critical properties of the drug substance and the drug product, and applying the BCS framework, assurance of in vivo BE findings can be obtained using extensive in vitro studies. The draft guidance is intended to avoid unnecessary human BE trials based on extensive in vitro characterization of the drug substance and drug product properties. More information is available on the Federal Register’s website.

Consultation Deadline: 24th January, 2019

Verification systems under the Drug Supply Chain Security Act
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs.”

The draft guidance addresses the verification systems that manufacturers, repackagers, wholesale distributors, and dispensers must have in place to comply with the Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by the Drug Supply Chain Security Act (DSCSA). Specifically, this draft guidance covers the statutory verification system requirements that include quarantine and investigation of a product determined to be suspect and quarantine and disposition of a product determined to be illegitimate. The draft guidance also addresses the statutory requirement for notification to the Agency of a product that has been cleared by a manufacturer, repackager, wholesale distributor, or dispenser after a suspect product investigation because it is determined that the product is not an illegitimate product. More information is available on the Federal Register’s website.

Consultation Deadline: 24th December, 2018

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

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

Medicines for children and rare diseases
The European Commission has launched a public consultation on an evaluation of the legislation on medicines for children and rare diseases (medicines for special populations).

This joint evaluation covers the legislation on medicines for special purposes, in particular medicines for children and medicines to treat rare diseases. The evaluation will assess to which extent the EU legislation is efficient and effective and considers whether it is fit for purpose in the light of developments in the area of pharmaceuticals. It will look in particular in the impact of the incentives introduced for research, development and marketing, for these specific medicines. More information is available on the Commission’s website.

Consultation Deadline: 4th January, 2019

Quantitative efficacy and risk information in direct-to-consumer promotional labeling and advertisements
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements.”

This draft guidance provides recommendations for presenting quantitative efficacy and risk information in direct-to-consumer (DTC) promotional labeling and advertisements for prescription human drugs and biological products and prescription animal drugs and in DTC promotional labeling for over-the-counter (OTC) animal drugs (collectively promotional materials). FDA is issuing this draft guidance to describe the Agency’s recommendations for how manufacturers, distributers, and packers (collectively firms) that include quantitative efficacy or risk information about their drugs in DTC promotional materials can make the language and presentation more consumer-friendly. More information is available on the Federal Register’s website.

Consultation Deadline: 17th December, 2018

Development of drug and biological products for treatment of hematologic malignancies
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease in Development of Drug and Biological Products for Treatment.”

This draft guidance is intended to assist sponsors planning to use minimal residual disease (MRD) as a biomarker in clinical trials conducted under an investigational new drug application (IND) or to support marketing approval of drugs and biological products for the treatment of specific hematologic malignancies. More information is available on the Federal Register’s website.

Consultation Deadline: 17th December, 2018

Early drug development and the role of pre-investigational New Drug Application meetings for rare diseases
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Rare Diseases: Early Drug Development and the Role of Pre-Investigational New Drug Application Meetings.”

The purpose of this draft guidance is to assist sponsors of drug and biological products for the treatment of rare diseases in planning and conducting more efficient and productive pre-investigational new drug application (pre-IND) meetings. Drug development for rare diseases has many challenges related to the nature of these diseases. This draft guidance is intended to advance and facilitate the development of drugs and biological products for the treatment of rare diseases. More information is available on the Federal Register’s website.

Consultation Deadline: 17th December, 2018

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

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

Irritation and sensitization potential of transdermal and topical delivery systems
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Assessing the Irritation and Sensitization Potential of Transdermal and Topical Delivery Systems for ANDAs.”

This draft guidance provides recommendations for the design and conduct of studies to evaluate the in vivo skin irritation and sensitization (I/S) potential of a proposed transdermal or topical delivery system (collectively referred to as TDS). The recommendations in this draft guidance relate exclusively to studies submitted in support of an abbreviated new drug application (ANDA). More information is available on the Federal Register’s website.

Consultation Deadline: 10th December, 2018

Adhesion with transdermal and topical delivery systems
The Food and Drug Administration (FDA or Agency) is announcing the availability of a revised draft guidance for industry entitled “Assessing Adhesion With Transdermal and Topical Delivery Systems for ANDAs.”

This revised draft guidance supersedes the draft guidance entitled “Assessing Adhesion with Transdermal Delivery Systems and Topical Patches for ANDAs,” which was announced in the Federal Register on June 1, 2016. This revised draft guidance provides recommendations for the design and conduct of studies evaluating the adhesive performance of a transdermal or a topical delivery system (collectively referred to as TDS). Depending on the objectives of a TDS product development program, applicants may choose to evaluate TDS adhesion in clinical studies performed to evaluate TDS adhesion only or in clinical studies performed with a combined purpose (e.g., for the simultaneous evaluation of adhesion and bioequivalence (BE) with pharmacokinetic (PK) endpoints). The recommendations in this revised draft guidance relate exclusively to studies submitted in support of an abbreviated new drug application (ANDA). More information is available on the Federal Register’s website.

Consultation Deadline: 10th December, 2018

Citizen petitions and petitions for stay of action
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act.”

This draft guidance revises the guidance for industry entitled “Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act” issued in November 2014. This draft guidance updates the November 2014 guidance to account for recent regulatory changes and describes a change in FDA’s current thinking on what constitutes a 505(q) petition. In addition, FDA is revising this guidance to describe some of the considerations FDA will take into account in determining whether a petition is submitted with the primary purpose of delaying the approval of an application. More information is available on the Federal Register’s website.

Consultation Deadline: 3rd December, 2018

Contents of a complete submission for threshold analyses and human factors submissions
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Contents of a Complete Submission for Threshold Analyses and Human Factors Submissions to an IND, NDA, BLA, or ANDA.”

The draft guidance provides recommendations to industry and FDA staff regarding the content and submission procedures for use-related risk analyses, human factors validation study protocols and reports, threshold analyses, and comparative use human factors study protocols and reports. More information is available on the Federal Register’s website.

Consultation Deadline: 30th November, 2018

Efficient clinical trial design strategies to expedite development of oncology drugs and biologics
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics.”

This guidance provides advice to sponsors of drugs and biologics for cancer treatment regarding the design and conduct of clinical trials, other than first-in-human (FIH) trials, intended to simultaneously evaluate more than one investigational drug and/or more than one cancer type within the same overall trial structure (master protocols) in adult and pediatric cancers. In contrast to traditional trial designs, where a single drug is tested in a single disease population in one clinical trial, master protocols use a single infrastructure, trial design, and protocol to simultaneously evaluate multiple drugs and/or disease populations in multiple substudies, allowing for efficient and accelerated drug development. More information is available on the Federal Register’s website.

Consultation Deadline: 30th November, 2018

Adaptive designs for clinical trials of drugs and biologics
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Adaptive Designs for Clinical Trials of Drugs and Biologics.”

This document provides guidance to sponsors and applicants submitting investigational new drug applications (INDs), new drug applications (NDAs), biologics license applications (BLAs), or supplemental applications on the appropriate use of adaptive designs for clinical trials to provide evidence of the effectiveness and safety of a drug or biologic. The guidance describes the basic principles for designing, conducting, and reporting the results from an adaptive clinical trial. The draft guidance will replace the 2010 draft guidance for industry entitled “Adaptive Design Clinical Trials for Drugs and Biologics.” More information is available on the Federal Register’s website.

Consultation Deadline: 30th November, 2018

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

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

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

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

European Commission Safety Features Q&A document updated
The European Commission has published an updated version, Version 11, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

Version 11 of the document, dated September 2018, supersedes Version 10. Q&As 5.8, 6.8 and 8.8 were added to the document, and Q&As 1.23, 7.15, 8.4 and 8.7 were revised. More information is available on the Commission’s website.

Investigation of medicinal products in the term and preterm neonate
The European Medicines Agency have published: Scientific guideline: Concept paper on the need for revision of the guideline on the investigation of medicinal products in the term and preterm neonate – Revision 1: consultation open.

The Guideline on the investigation of medicinal products in the term and preterm neonates was prepared during the period from 2007 to 2009 and came into effect in 2010 (EMEA/536810/2008). Considerable experience of assessing PIP applications covering neonatal age subset has been gained since then and it has become apparent that some essential questions arise repeatedly during the assessment of Paediatric Investigation Plans (PIP) applications for products intended to be investigated and used in neonates. Furthermore, in recent years there has been increasing debate about neonatal research trends and standards, suggesting that the existing guidance even though approved only 5 years ago is not adequately addressing issues associated with the development and investigation of products in term and preterm neonates. Therefore it seems that there is a need to update currently available guidelines regarding the nonclinical and clinical development of medicinal products in neonates in accordance with current trends in neonatal terminology, and issues encountered and experience gained during assessment of several PIP applications involving neonatal population. Input will be sought from relevant working parties, committees and experts. More information is available on the EMA’s website.

Consultation Deadline: 16th December, 2018

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

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

Insanitary conditions at compounding facilities
The Food and Drug Administration (FDA or Agency) is announcing the availability of a revised draft guidance for industry entitled, “Insanitary Conditions at Compounding Facilities.”

Drug products compounded under insanitary conditions could become contaminated and cause serious adverse events, including death, in patients. FDA is issuing this revised draft guidance to help compounding facilities identify insanitary conditions so that they can implement appropriate corrective actions. This revised draft guidance is also intended to help state regulatory agencies understand some examples of what FDA considers to be insanitary conditions that could cause a drug to become contaminated or rendered injurious to health. This guidance revises the draft guidance entitled “Insanitary Conditions at Compounding Facilities” that was published on August 4, 2016. More information is available on the Federal Register’s website.

Consultation Deadline: 26th November, 2018

Good Review Management Principles and Practices for New Drug Applications and Biologics License Applications
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry and review staff entitled “Good Review Management Principles and Practices for New Drug Applications and Biologics License Applications.”

This draft guidance describes the fundamental values and operational principles that serve as the foundation for the review process. It also clarifies the roles and responsibilities of review staff and identifies ways in which applicants may support a robust and efficient review process. This draft guidance revises the guidance for review staff and industry entitled “Good Review Management Principles and Practices for PDUFA Products” issued April 2005. More information is available on the Federal Register’s website.

Consultation Deadline: 24th December, 2018

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

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

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

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

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

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

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

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

Consultation Deadline: 31st August, 2019

Use of aminopenicillins and their beta-lactamase inhibitor combinations in animals in the European Union
The European Medicines Agency have published: Scientific guideline: Reflection paper on the use of aminopenicillins and their beta-lactamase inhibitor combinations in animals in the European Union: development of resistance and impact on human and animal health, draft: consultation open.

The objective of this document is to review available information on the use of aminopenicillins and their beta-lactamase inhibitor combinations in veterinary medicines in the EU, their effect on the emergence of antimicrobial resistance (AMR) and the potential impact of resistance on human and animal health. The document provides information for the risk profiling, as recommended by the Antimicrobial Advice ad hoc Expert Group (AMEG) of the EMA. More information is available on the EMA’s website.

Consultation Deadline: 21st December, 2018

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

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

Consultation Deadline: 31st August, 2019

Stride velocity 95th centile as a secondary endpoint in Duchenne Muscular Dystrophy
The European Medicines Agency have published: Regulatory and procedural guideline: Draft qualification opinion on stride velocity 95th centile as a secondary endpoint in Duchenne Muscular Dystrophy measured by a valid and suitable wearable device, draft: consultation open.

This report provides a final agreed draft Context of Use for public consultation describing where Stride Velocity measured at the ankle 95th Centile is deemed by CHMP as an appropriate endpoint in studies to support regulatory decision making on medicines for the treatment of Duchenne Muscular Dystrophy (DMD), together with CHMP’s scientific consideration of the submission leading to the draft opinion. The document also includes the questions posed by the applicant and also raised by CHMP to the Applicant, and all the data provided by the applicant in support of the Application. More information is available on the EMA’s website.

Consultation Deadline: 30th November, 2018

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

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

Determination of withdrawal periods for edible tissues
The European Medicines Agency have published: Scientific guideline: Guideline on determination of withdrawal periods for edible tissues – Revision 1, adopted.

This document, originally published in 1997 as the CVMP Note for guidance: approach towards harmonisation of withdrawal periods, provides detailed guidance on how to establish withdrawal periods and was developed by the CVMP in order to provide a standardised approach for derivation of withdrawal periods within the European Union. Much of the document is focused on the statistical approach used by CVMP, but an alternative, for use in those cases where the data do not allow use of the statistical approach, is also described. The issue of withdrawal periods for substances with a ‘No MRL required’ classification is also addressed. More information is available on the EMA’s website.

Date for coming into effect: 1st April, 2019

Product identifiers under the Drug Supply Chain Security Act
The Food and Drug Administration FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Product Identifiers Under the Drug Supply Chain Security Act Questions and Answers.”

This draft guidance intends to clarify questions relating to product identifiers that are required by the Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by the Drug Supply Chain Security Act (DSCSA) for packages and homogenous cases of certain drug products. Sections of the FD&C Act require manufacturers and repackagers to affix or imprint a product identifier to each package and homogenous case of a product intended to be introduced in a transaction into commerce beginning November 27, 2017, and November 28, 2018, respectively. This draft guidance intends to clarify these requirements. More information is available on the Federal Register’s website.

Consultation Deadline: 19th November, 2018

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Clinical investigation of medicinal products in the treatment of epileptic disorders
The European Medicines Agency have published: Scientific guideline: Draft guideline on clinical investigation of medicinal products in the treatment of epileptic disorders – Revision 3, draft: consultation open.

The present document is a third revision of the existing guideline. It should be considered as general guidance on the development of medicinal products for the treatment of epileptic disorders and should be read in conjunction with other EMA and ICH guidelines, which may apply to these conditions and patient populations. The main changes to the existing guideline include incorporation of the new classification / definitions of seizure types and epilepsies, the acceptance of add-on studies in support of a monotherapy claim on a case-by-case basis, the inclusion of new sections on neonates and status epilepticus and other changes related to paediatric developments. This guideline provides assistance for the development and evaluation of medicinal products for the treatment of epilepsy in adults and children. The scope of this document is restricted to treatment of seizures in epileptic disorder although there are some remarks concerning non-seizure features of epilepsy syndromes. More information is available on the EMA’s website.

Consultation Deadline: 17th February, 2019

Quality of herbal medicinal products/traditional herbal medicinal products
The European Medicines Agency have published: Scientific guideline: Draft guideline on quality of herbal medicinal products/traditional herbal medicinal products – Revision 3 , draft: consultation open.

This document intends to cover the general quality aspects of herbal medicinal products for human and veterinary use, including traditional herbal medicinal products for human use. It describes the special problems of herbal medicinal products and the differences between medicinal products containing chemically defined active substances. The third revision of the ‘Guideline on quality of herbal medicinal products/traditional herbal medicinal products’ (EMA/CPMP/QWP/2819/00, EMA/CVMP/814/00, EMA/HMPC/201116/2005) takes into account new and revised guidelines, questions and answers and the European Pharmacopoeia revised general monograph ‘Herbal Drug Extracts’ as well as experiences gained over the years with the application of the guideline. Further clarifications on quality data requirements are provided via improved wording, structure and reference to updated related guidelines as outlined in the concept paper EMA/HMPC/217631/2015. Particular attention has been paid to adjustment with the in parallel revised Guideline on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations and HMPs/THMPs (CPMP/QWP/2820/00; EMEA/CVMP/815/00, EMA/HMPC/162241/2005). More information is available on the EMA’s website.

Consultation Deadline: 30th November, 2018

Test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products/traditional herbal medicinal products
The European Medicines Agency have published: Scientific guideline: Draft guideline on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products/traditional herbal medicinal products – Revision 3 , draft: consultation open.

This document addresses specifications, i.e. those tests, procedures, and acceptance criteria used to assure the quality of the herbal substances/preparations and herbal medicinal products at release and during the shelf-life. The third revision of the ‘Guideline on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations and herbal medicinal products/traditional herbal medicinal products’ takes into account new and revised guidance documents such as the updated ‘Questions & Answers on quality of HMPs/THMPs’ (EMA/HMPC/41500/2010), the European Pharmacopoeia revised general text on the ‘Microbiological Quality of HMPs for Oral Use and Extracts used in their preparation’ (5.1.8), the revised general Ph. Eur. monograph ‘Herbal Drug Extracts’ and the new information chapter on this monograph, the ‘Guideline on quality on combination HMPs/THMPs’ (MA/HMPC/CHMP/CVMP/214869/2006) and the ‘Reflection paper on markers used for quantitative and qualitative analysis of HMPs/THMPs’ (EMEA/HMPC/253629/2007) as outlined in the Concept paper EMA/HMPC/217753/2015. Particular attention has been paid to adjustment with the in parallel revised Guideline on quality of herbal medicinal products /traditional herbal medicinal products (EMA/CPMP/QWP/2819/00, EMA/CVMP/814/00, EMA/HMPC/201116/2005). More information is available on the EMA’s website.

Consultation Deadline: 30th November, 2018

Similar biological medicinal products containing recombinant granulocyte-colony stimulating factor
The European Medicines Agency have published: Scientific guideline: Draft guideline on similar biological medicinal products containing recombinant granulocyte-colony stimulating factor (rG-CSF) – Revision 1, draft: consultation open.

This guideline lays down the EU regulatory position on the non-clinical and clinical development of recombinant granulocyte colony stimulation factor (rG-CSF) containing medicinal products claimed to be biosimilar to an originator product approved in the Economic European Area (EEA). It is a revision of the Guideline on Similar biological medicinal products containing recombinant granulocyte-colony stimulating factor. The proposed guideline will replace annex to guideline on similar medicinal products containing biotechnology-derived proteins as active substance: Non-Clinical and Clinical Issues – Guidance on similar medicinal products containing recombinant granulocyte-colony stimulating factor, EMEA/CHMP/BMWP/31329/2005. More information is available on the EMA’s website.

Consultation Deadline: 15th February, 2019

Core summary for product characteristics for human albumin solution
The European Medicines Agency have published: Scientific guideline: Guideline on core summary for product characteristics for human albumin solution – Revision 3, adopted.

The purpose of this core SmPC is to provide applicants and regulators with harmonised guidance on the information to be included in the Summary of Product Characteristics (SmPC) for human albumin solution. Revision 3 deletes the text preceding the Core SmPC, Section 4.1. Therapeutic indications is amended by deleting the wording “The choice of albumin rather than artificial colloid will depend on the clinical situation of the individual patient, based on official recommendations”. More information is available on the EMA’s website.

Date for coming into effect: 1st February, 2019

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

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

Date for coming into effect: 1st February, 2019

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

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

Date for coming into effect: 1st February, 2019

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

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

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

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

Biopharmaceutics classification system based biowaivers
The European Medicines Agency have published: Scientific guideline: ICH M9 on biopharmaceutics classification system based biowaivers – Step 2b – First version, draft: consultation open.

This new multidisciplinary guideline is proposed to address biopharmaceutics classification system (BCS)-based biowaivers. BCS-based biowaivers may be applicable to BCS Class I and III drugs, however BCS-based biowaivers for these two classes are not recognized worldwide. This means that pharmaceutical companies have to follow different approaches in the different regions. This guideline will provide recommendations to support the biopharmaceutics classification of medicinal products and will provide recommendations to support the waiver of bioequivalence studies. This will result in the harmonisation of current regional guidelines/guidance and support streamlined global drug development. More information is available on the EMA’s website.

Consultation Deadline: 6th February, 2019

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

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

Consultation Deadline: 31st July, 2019

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

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

Consultation Deadline: 31st July, 2019

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

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

Consultation Deadline: 31st July, 2019

Stability testing of new veterinary drug substances and medicinal products in climatic zones III and IV
The European Medicines Agency have published: Scientific guideline: Draft VICH GL58 Stability testing of new veterinary drug substances and medicinal products in climatic zones III and IV – First version, draft: consultation open.

The guideline is an annex to the VICH parent stability guideline, stability testing of new veterinary drug substances and medicinal products (VICH GL3 (R)), and provides guidance regarding the stability data package for a new veterinary drug substance and medicinal product to be included in a registration application submitted within the regions in the climatic zones III and IV. More information is available on the EMA’s website.

Consultation Deadline: 31st December, 2018

Dose optimisation of established veterinary antibiotics in the context of SPC harmonisation
The European Medicines Agency have published: Scientific guideline: Reflection paper on dose optimisation of established veterinary antibiotics in the context of SPC harmonisation, draft: consultation open.

The Committee for Medicinal Products for Veterinary Use (CVMP) started a pilot project on dose optimisation of established veterinary antibiotics to which AnimalhealthEurope (formerly IFAH Europe), and the European Group for Generic Veterinary Products (EGGVP) were invited to provide anonymised data. The results of this project are for consideration by the CVMP for possible future work on the subject. More information is available on the EMA’s website.

Consultation Deadline: 31st January, 2019

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

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

Consultation Deadline: 31st August, 2019

Residue studies in honey for establishing MRLs and withdrawal periods
The European Medicines Agency have published: Scientific guideline: VICH GL56 on studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing species: study design recommendations for residue studies in honey for establishing MRLs and withdrawal periods – First version, adopted.

The objective of this guidance is to provide study design recommendations which will facilitate the universal acceptance of the generated residue depletion data to fulfill the national/regional requirements in order to establish appropriate Maximum Residue Limits (MRLs) or other safe limits in honey following the treatment of honeybees with veterinary drug products, or to justify withdrawal periods in honey for registration purposes when an MRL already exists. More information is available on the EMA’s website.

Date for coming into effect: 1st June, 2019

Development of new medicinal products for the treatment of Ulcerative Colitis
The European Medicines Agency have published: Scientific guideline: Guideline on the development of new medicinal products for the treatment of Ulcerative Colitis – Revision 1, adopted.

This is the 1st revision of the Guideline on the development of new medicinal products for the treatment of UC. The main aim of this 1st revision is to update the guidance on the design of studies in adult patients, especially on potential claims, primary and secondary endpoints and comparators. It is also intended to give further guidance with regards the possibility for extrapolation from adults, or the need to generate separate data in children and to give recommendations regarding the exploration of PK/PD in paediatric drug development. Possible targets of estimation that define treatment effects of interest in UC are also considered. More information is available on the EMA’s website.

Date for coming into effect: 1st January, 2019

Development of new medicinal products for the treatment of Crohn’s Disease
The European Medicines Agency have published: Scientific guideline: Guideline on the development of new medicinal products for the treatment of Crohn’s Disease – Revision 2, adopted.

This is the 2nd revision of the Guideline on the development of new medicinal products for the treatment of Crohn’s Disease (CD). The main aim of this 2nd revision was to update the guidance on the design of studies in adult patients, especially on potential claims, primary and secondary endpoints, and comparators. It is also intended to give further guidance regarding the possibility for extrapolation from adults, or the need to generate separate data in children and to give recommendations regarding the exploration of PK/PD in paediatric drug development. More information is available on the EMA’s website.

Date for coming into effect: 1st January, 2019

Development of similar biological medicinal products containing recombinant erythropoietins
The European Medicines Agency have published: Scientific guideline: Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant erythropoietins – Revision 1, adopted.

The main aim of the guideline is to address the non-clinical and clinical requirements for recombinant human erythropoietin (epoetin)-containing medicinal products claiming to be similar to another one already marketed. The non-clinical section addresses the pharmaco-toxicological assessment and the clinical section the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as the risk management plan. Criteria for extrapolation of clinical data to other indications approved for the reference medicinal product are discussed. More information is available on the EMA’s website.

Date for coming into effect: 1st January, 2019

Annex to guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance
The European Medicines Agency have published: Scientific guideline: Annex to Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues – Guideline on similar medicinal products containing somatropin – Rev. 1, adopted.

The main aim of the guideline is to address the non-clinical and clinical requirements for somatropin-containing medicinal products claiming to be similar to another one already marketed. The non-clinical section addresses the pharmaco-toxicological assessment. The clinical section addresses the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as the risk management plan. Criteria for extrapolation of clinical data to other indications approved for the reference medicinal product are discussed. More information is available on the EMA’s website.

Date for coming into effect: 1st January, 2019

Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration
The European Medicines Agency have published: Scientific guideline: Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg) – Rev. 3, adopted.

This guideline describes the information to be documented when an application is made for a marketing authorisation for a human normal immunoglobulin for intravenous use (IVIg). The guidance covers biological data, clinical trials and patient follow-up. Quality aspects are outside the scope of this guideline. Guidance is also provided for authorised products where a significant change in the manufacturing process has been made. More information is available on the EMA’s website.

Date for coming into effect: 1st January, 2019

Guideline on core SmPC for human normal immunoglobulin for intravenous administration
The European Medicines Agency have published: Scientific guideline: Guideline on core SmPC for human normal immunoglobulin for intravenous administration (IVIg) – Rev. 5, adopted.

The purpose of this core SmPC is to provide applicants and regulators with harmonised guidance on the information to be included in the summary of product characteristics (SmPC) for a human normal immunoglobulin for intravenous administration (IVIg). This guideline should be read in conjunction with the Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg) (EMA/CHMP/BPWP/94033/2007 rev. 2). More information is available on the EMA’s website.

Date for coming into effect: 1st January, 2019

General principles for planning and design of multiregional clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “E17 General Principles for Planning and Design of Multiregional Clinical Trials.”

With the increasing globalization of drug development, it has become important that data from multiregional clinical trials (MRCTs) can be accepted by regulatory authorities across regions and countries as the primary source of evidence to support marketing approval of drugs (medicinal products). The purpose of this guidance is to describe general principles for the planning and design of MRCTs with the aim of increasing the acceptability of MRCTs in global regulatory submissions. More information is available on the FDA’s website.

Use of electronic health record data in clinical investigations
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Use of Electronic Health Record Data in Clinical Investigations.”

This guidance is intended to assist sponsors, clinical investigators, contract research organizations, institutional review boards (IRBs), and other interested parties on the use of electronic health record data in FDA-regulated clinical investigations. More information is available on the FDA’s website.

Labeling for biosimilar products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Labeling for Biosimilar Products.”

This guidance is intended to help applicants develop draft labeling for proposed biosimilar products for submission in an application under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)). The recommendations for prescription drug labeling in this guidance pertain only to the prescribing information (commonly referred to as the package insert), except for certain recommendations in section V pertaining to FDA-approved patient labeling (e.g., Patient Information, Medication Guide, and Instructions for Use). This guidance does not provide specific labeling recommendations for interchangeable products (see section VIII of this guidance).
More information is available on the FDA’s website.

Use of adjuvanted veterinary vaccines
The European Medicines Agency have published: Scientific guideline: Draft guideline on the use of adjuvanted veterinary vaccines, draft: consultation open.

The main aim of the guideline is to outline the information which should be included for the adjuvant in the marketing authorisation application (MAA) of an immunological veterinary medicinal product (IVMP). This guideline replaces the ‘Note for Guidance on the use of adjuvanted veterinary vaccines’. The guideline discusses the important aspects to consider for the adjuvant in an IVMP and provides guidance on the information on the adjuvant which should be included in Parts 2, 3 and 4 of the MAA. The details on the adjuvant which should be referred to in the SPC of the IVMP is also addressed in this guideline. More information is available on the EMA’s website.

Consultation Deadline: 15th January, 2019

Real time release testing and parametric release
The European Commission has published: EudraLex Volume 4 Annex 17: Real Time Release Testing and Parametric Release.

The previous guideline only focused on the application of Parametric Release for the routine release of terminally sterilised products waiving the performance of a test for sterility on the basis of successful demonstration that predetermined and validated sterilising conditions have been achieved. Moreover, advances in the application of process analytical technology (PAT), quality by design (QbD) and quality risk management (QRM) principles to pharmaceutical development and manufacturing have shown that an appropriate combination of process controls together with timely monitoring and verification of pre-established material attributes provides greater assurance of product quality than finished product testing (conventionally regarded as the end-product testing) alone. This revision to Annex 17 takes into account changes to other sections of the EudraLex, Volume 4, Part I, Chapter 1, Annex 1 and 15, ICH Q8, Q9, Q10 and Q11, QWP Guideline on Real Time Release Testing, and changes in manufacturing and analytical technology. More information is available on the Commission’s website.

Date for coming into effect: 26th December, 2018

Amendments to Abbreviated New Drug Applications under GDUFA
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “ANDA Submissions — Amendments to Abbreviated New Drug Applications Under GDUFA.”

This guidance is intended to explain to applicants how the review goals established as part of the Generic Drug User Fee Amendments Reauthorization of 2017 (GDUFA II) apply to amendments to either abbreviated new drug applications (ANDAs) or prior approval supplements (PASs) submitted to the Food and Drug Administration under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)). This guidance describes amendment classifications and categories and explains how amendment submissions may affect an application’s review goal dates. The guidance also describes how FDA should assess amendments submitted to ANDAs and PASs received prior to October 1, 2017, which is the GDUFA II review goals effective date. More information is available on the FDA’s website.

Assessing user fees under the Biosimilar User Fee Amendments of 2017
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Assessing User Fees Under the Biosimilar User Fee Amendments of 2017.”

This guidance provides stakeholders information regarding FDA’s implementation of the Biosimilar User Fee Amendments of 2017 (BsUFA II) under Title IV of the FDA Reauthorization Act of 2017. Because BsUFA II created changes to the user fee program, this guidance serves to provide an explanation about the new fee structure and types of fees for which entities are responsible. More information is available on the FDA’s website.

Nonclinical evaluation for anticancer pharmaceuticals
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “S9 Nonclinical Evaluation for Anticancer Pharmaceuticals – Questions and Answers.”

Since the ICH guidance S9 Nonclinical Evaluation for Anticancer Pharmaceuticals was finalized (ICH S9 or ICH S9 guidance), all parties using the guidance have experienced some challenges with implementation of the recommendations on nonclinical evaluation for anticancer pharmaceuticals. This question-and-answer guidance is intended to facilitate the implementation of ICH S9, as well as to continue progress in the 3Rs of Reduction, Refinement, and Replacement in the use of animals. More information is available on the FDA’s website.

Medical product communications that are consistent with the FDA-required labeling
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers.”

This guidance provides information for firms about how FDA evaluates firms’ medical product communications that fall within the scope of FDA’s regulatory authority (product communications) and that present information not contained in the FDA-required labeling for the product but that may be consistent with the FDA-required labeling for the product. More information is available on the FDA’s website.

Drug and device manufacturer communications with payors
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry and review staff entitled “Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities — Questions and Answers.”

This guidance provides answers to common questions regarding firms’ communication of health care economic information (HCEI) regarding their prescription drugs and medical devices to payors, formulary committees, or other similar entities6 with knowledge and expertise in the area of health care economic analysis (collectively referred to as payors). This guidance also addresses common questions relating to dissemination to payors of information about medical products that are not yet approved or cleared for any use and dissemination to payors of information about unapproved uses of approved/cleared medical products. More information is available on the FDA’s website.

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

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

Economic impact of supplementary protection certificates, pharmaceutical incentives and rewards in Europe
The European Commission has published: Study on the economic impact of supplementary protection certificates, pharmaceutical incentives and rewards in Europe.

In this study, the Commission utilises a unique, new dataset to assess the economic impact of supplementary protection certificates (SPC’s) and the pharmaceutical incentives and rewards in the EU, develops a measure called the ‘Effective protection period’. It reflects the time that elapses from a medicinal product obtains a marketing authorisation until the last measure of protection on it expires; this could be the original patent, an SPC or one of the other incentives and rewards in the pharmaceutical legislation. 45% of the medicinal products in the dataset obtained an SPC in at least one of the European countries. The SPC added years to the effective protection period for those innovator products where the SPC is the last measure of protection to expire. While the protection for medicinal products in the EU is amongst the strongest in the world, for the medicinal products in the dataset the average effective protection period decreased by approximately two years from 15 to 13 years since 1996 (with variations in individual cases). A longer effective protection period stimulates research and development into new medicinal products. It also delays an average price drop of approximately 50 pct. following the entry of generics. Companies choose to launch more medicinal products faster in larger and wealthier countries. Hence, not all new products are made available in all European countries and not at the same time. More information is available on the European Commission’s website.

Pharmaceutical product lifecycle management
The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance entitled “Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management; International Council for Harmonisation.”

The draft guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The draft guidance, which consists of a Core Guideline and an Annex, provides a framework to facilitate the management of post-approval chemistry, manufacturing, and controls changes for new and marketed pharmaceutical drug substances and drug products, including marketed chemical and biotechnological/biological products. More information is available on the Federal Register’s website.

Consultation Deadline: 15th December, 2018

Developing drugs for complicated intraabdominal infections
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Complicated IntraAbdominal Infections: Developing Drugs for Treatment.”

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

Supplementary protection certificate manufacturing waiver
The European Commission has published: Proposal for a Regulation of the European Parliament and of the Council amending Regulation (EC) No 469/2009 concerning the supplementary protection certificate for medicinal products.

The European Parliament’s Resolution on the Single Market Strategy endorsed the need for actions on the EU SPC regime and ‘urge[d] the Commission to introduce and implement before 2019 an SPC manufacturing waiver’, so as to boost the competitiveness of the generics and biosimilars sector, but ‘without undermining the market exclusivity granted under the SPC regime in protected markets’. This initiative delivers on the first of these above-mentioned issues and, to that end, proposes an amendment to the Union’s legislation on Supplementary Protection Certificates for medicinal products, namely Regulation (EC) No 469/20095. It aims to introduce a so-called manufacturing exemption for export purposes (also known as a manufacturing waiver) during the term of an SPC. This would take the form of an ‘exception’, in other words, a restriction, to the protection conferred to the certificate, which would aim at removing the competitive disadvantages EU-based manufacturers of generics and biosimilars are currently facing. It will allow them to manufacture, in the territory of a Member State during the term of an SPC, for the exclusive purpose of exporting their products to non-EU markets where patent or SPC protection has expired or never existed. The objective is to boost investment and job creation in the manufacturing of generics and biosimilars in the Union by restoring a level playing field between EU-based manufacturing and manufacturing in non-EU countries. This exception should not affect the exclusive rights of certificate holders in relation to the Union market. EU-based small and medium-sized enterprises (SMEs) in particular will benefit from the proposal, as they are often engaged in the production of generics and biosimilars. More information is available on the European Commission’s website.

Developing drugs for prophylaxis of inhalational anthrax
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Anthrax: Developing Drugs for Prophylaxis of Inhalational Anthrax.”

The purpose of this guidance is to assist sponsors in the development of drugs for the indication of prophylaxis of inhalational anthrax in persons who have or may have inhaled aerosolized Bacillus anthracis spores but who have not yet manifested clinical evidence of disease. The indication also applies to persons with anticipated exposure to B. anthracis spores (e.g., first responders for anthrax incidents); in such cases, initiation of antibacterial therapy would begin immediately before entering the B. anthracis-contaminated environment. More information is available on the FDA’s website.

OTC sunscreen drug products marketed without an approved application
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Enforcement Policy — OTC Sunscreen Drug Products Marketed Without an Approved Application.”

This guidance describes FDA’s enforcement approach with respect to over-the-counter (OTC) sunscreen products marketed without approved applications during the period before a final sunscreen monograph becomes effective. It is intended for manufacturers who market OTC sunscreen drug products without an approved application. OTC sunscreens are not yet the subject of an effective final monograph, and we continue to evaluate information relevant to defining conditions under which such products are generally recognized as safe and effective (GRASE) and not misbranded. However, OTC sunscreens marketed without approved applications and containing specified active ingredients (see section II., Background) are subject to labeling and testing requirements located at 21 CFR 201.327. Several other ongoing and planned rulemaking proceedings will also address these products. More information is available on the FDA’s website.

Bioanalytical method validation
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Bioanalytical Method Validation.”

This guidance helps sponsors of investigational new drug applications (INDs) or applicants of new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologic license applications (BLAs), and supplements validate bioanalytical methods used in human clinical pharmacology, bioavailability (BA), and bioequivalence (BE) studies that require pharmacokinetic, toxicokinetic, or biomarker concentration evaluation. This guidance can also inform the development of bioanalytical methods used for nonclinical studies that require toxicokinetic or biomarker concentration data. For studies related to the veterinary drug approval process such as investigational new animal drug applications (INADs), new animal drug applications (NADAs), and abbreviated new animal drug applications (ANADAs), this guidance may apply to blood and urine BA, BE, and pharmacokinetic studies. The information in this guidance applies to bioanalytical procedures such as chromatographic assays (CCs) and ligand binding assays (LBAs) that quantitatively determine the levels of drugs, their metabolites, therapeutic proteins, and biomarkers in biological matrices such as blood, serum, plasma, urine, and tissue such as skin. More information is available on the FDA’s website.

Establishing effectiveness for drugs intended to acne vulgaris
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Acne Vulgaris: Establishing Effectiveness of Drugs Intended for Treatment.”

The purpose of this guidance is to provide recommendations to industry for establishing clinical effectiveness of drugs for the treatment of acne vulgaris (acne). The recommendations in this guidance are based on the FDA’s assessment of issues raised in the review of clinical trials for acne. More information is available on the FDA’s website.

Establishing effectiveness for drugs intended to treat male hypogonadotropic hypogonadism attributed to nonstructural disorders
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Establishing Effectiveness for Drugs Intended to Treat Male Hypogonadotropic Hypogonadism Attributed to Nonstructural Disorders.”

This guidance provides recommendations for establishing clinical effectiveness for drugs intended to treat male hypogonadotropic hypogonadism associated with obesity and other conditions that do not cause structural disorders of the hypothalamus or pituitary gland. These drugs should both increase serum testosterone concentrations and improve how patients feel, function, or survive. This guidance incorporates advice the FDA received at a December 2014 advisory committee meeting on the appropriate indicated population for testosterone therapy and a December 2016 advisory committee meeting on hypogonadotropic hypogonadism. More information is available on the FDA’s website.

ICH S9 guideline on nonclinical evaluation for anticancer pharmaceuticals Q&A
The European Medicines Agency have published: Scientific guideline: ICH S9 guideline on nonclinical evaluation for anticancer pharmaceuticals – questions and answers – Step 5, adopted.

The ICH S9 Guideline: Nonclinical Evaluation for Anticancer Pharmaceuticals reached Step 4 in November 2009 and the guideline was a significant advance in promoting anticancer drug development. Since reaching Step 4, all the parties using the guideline have experienced some challenges around implementation. Implementation of the guideline has revealed areas that are open to broad and divergent interpretation by both regulatory authorities and industry. For this reason, an Implementation Working Group (IWG) was formed in October, 2014, by the International Council for Harmonization (ICH), formerly the International Conference on Harmonisation, to develop Questions and Answers to provide additional clarity around anticancer pharmaceutical development. The Questions and Answers developed by the IWG are intended to facilitate the implementation of the S9 Guideline and, of additional benefit, to continue progress in the 3Rs of Reduction, Refinement, and Replacement in use of animals. More information is available on the EMA’s website.

Date for coming into effect: 16th November, 2018

Facility definition under Section 503B of the Federal Food, Drug, and Cosmetic Act
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Facility Definition Under Section 503B of the Federal Food, Drug, and Cosmetic Act.”

This guidance is intended for entities that are registered or are considering registering with FDA as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 353b). Section 503B defines an outsourcing facility, in part, as “a facility at one geographic location or address.” FDA has received questions from outsourcing facilities and other stakeholders about the meaning of this term, such as whether multiple suites used for compounding human drugs at a single street address constitute one or multiple facilities, or whether a single location where human drugs are compounded can be subdivided into separate operations compounding under different standards. FDA is issuing this guidance to provide the agency’s current thinking on these issues, and related issues regarding how to ensure that the compounding of drugs in an outsourcing facility occurs only in accordance with section 503B. More information is available on the FDA’s website.

S3A Guidance: Note for guidance on toxicokinetics
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies: Focus on Microsampling.”

The guideline for industry S3A Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies (S3A guidance) has been successfully implemented since 1994, and in recent years, analytical method sensitivity has improved, allowing microsampling techniques to be used in toxicokinetic (TK) assessment. This question-and-answer (Q&A) document focuses on points to consider before incorporating the microsampling method in TK studies, acknowledges the benefits (and some limitations) of using microsampling to assess toxicokinetics in main study animals, and acknowledges the overall important contribution of microsampling to the 3Rs benefits (replacement, reduction and refinement) by reducing or eliminating the need for TK satellite animals. More information is available on the FDA’s website.

Enhanced early dialogue to facilitate accelerated assessment of PRIority MEdicines (PRIME)
The European Medicines Agency have published: Regulatory and procedural guideline: Enhanced early dialogue to facilitate accelerated assessment of PRIority MEdicines (PRIME), adopted.

In December 2014, a group composed of members of the Committee for Medicinal Products for Human Use (CHMP) and EMA representatives was established to explore ways, within the current regulatory framework, to further support the development of new medicines addressing major public health needs. As a result of that work, a scheme has been developed to reinforce early dialogue and regulatory support to stimulate innovation, optimise development and enable accelerated assessment of PRIority MEdicines (referred to as PRIME). An overview of the PRIME scheme is provided in this document. The present document is being revised further to initial experience since launch in March 2016. More information is available on the EMA’s website.

User fees under the Prescription Drug User Fee Amendments
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Assessing User Fees Under the Prescription Drug User Fee Amendments of 2017.”

This guidance provides stakeholders information regarding FDA’s implementation of the Prescription Drug User Fee Amendments of 2017 (PDUFA VI) under Title I of the FDA Reauthorization Act of 2017. Because PDUFA VI created changes to the user fee program, this guidance explains the new fee structure created by the statute, and the types of fees for which entities are responsible. More information is available on the FDA’s website.

Clinical trial imaging endpoint process standards
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Clinical Trial Imaging Endpoint Process Standards.”

The purpose of this guidance is to assist sponsors in optimizing the quality of imaging data obtained in clinical trials intended to support approval of drugs and biological products. This guidance focuses on imaging acquisition, display, archiving, and interpretation process standards that we regard as important when imaging is used to assess a trial’s primary endpoint or a component of that endpoint. More information is available on the FDA’s website.

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.

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.

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.

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.

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

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