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.

Developing drugs for treatment of major depressive disorder
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Major Depressive Disorder: Developing Drugs for Treatment.”

The purpose of this draft guidance is to assist sponsors in the clinical development of drugs for the monotherapeutic, combination, and adjunctive treatment of major depressive disorder (MDD). Specifically, this draft guidance addresses FDA’s current thinking regarding the overall development program and clinical trial designs for antidepressant drug products. This draft guidance is intended to serve as a focus for continued discussions among FDA, pharmaceutical sponsors, the academic community, and the public. This draft guidance revises the guidance for industry entitled “Guidelines for the Clinical Evaluation of Antidepressant Drugs” issued in September 1977. More information is available on the Federal Register’s website.

Consultation Deadline: 20th August, 2018

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The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Prescription Drug Act User Fee Waivers, Reductions, and Refunds for Drug and Biological Products.”

This revised draft guidance provides recommendations to applicants planning to request a waiver or reduction in user fees. This draft guidance is a revision of the guidance for industry entitled “User Fee Waivers, Reductions, and Refunds for Drug and Biological Products,” issued in September 2011. More information is available on the Federal Register’s website.

Consultation Deadline: 20th August, 2018

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The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Epidermolysis Bullosa: Developing Drugs for Treatment of Cutaneous Manifestations.”

The purpose of this draft guidance is to assist sponsors with the development of drugs for treatment or prevention of the serious cutaneous manifestations of the heterogeneous group of disorders collectively known as epidermolysis bullosa (EB). There is an unmet medical need for EB patients due to the paucity of effective treatment options. More information is available on the Federal Register’s website.

Consultation Deadline: 17th August, 2018

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.

Evaluation of medicinal products indicated for treatment of bacterial infections
The European Medicines Agency have published: Scientific guideline: Concept paper on preparation of a revised guideline on the evaluation of medicinal products indicated for treatment of bacterial infections, draft: consultation open.

This concept paper proposes the development of a single guideline on the clinical evaluation of medicinal products indicated for treatment of bacterial infections. The development of this single guideline is intended to merge, revise and add to the guidance that is currently included in two separate documents as follows: guideline on the evaluation of medicinal products indicated for treatment of bacterial infections (CPMP/EWP/558/95 Rev. 2), adopted in 2011 and in force since 2012 and the addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections (EMA/CHMP/351889/2013), adopted in 2013 and in force since 2014. More information is available on the EMA’s website.

Consultation Deadline: 13th September, 2018

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

This draft guidance provides nonclinical and clinical recommendations specific to the development of systemic drug products, with a focus on long-acting systemic drug products, regulated within the Center for Drug Evaluation and Research (CDER) at FDA for the prevention of sexually acquired human immunodeficiency virus-1 (HIV-1) infection. More information is available on the Federal Register’s website.

Consultation Deadline: 13th August, 2018

Limited population pathway for antibacterial and antifungal drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Limited Population Pathway for Antibacterial and Antifungal Drugs.”

This guidance provides information on the implementation of the limited population pathway provision of the 21st Century Cures Act (Cures Act), which established the limited population pathway for antibacterial and antifungal drugs (LPAD pathway). More information is available on the Federal Register’s website.

Consultation Deadline: 13th August, 2018

Patient-focused drug development
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry, FDA staff, and other stakeholders entitled “Patient-Focused Drug Development: Collecting Comprehensive and Representative Input.”

This guidance (Guidance 1) is the first of a series of four methodological guidance documents that FDA committed to develop to address in a stepwise manner how to collect and submit information from patients and caregivers for medical product development and regulatory decision making. More information is available on the Federal Register’s website.

Consultation Deadline: 11th September, 2018

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.

PDUFA waivers for fixed-combination antiretroviral drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Prescription Drug User Fee Act Waivers for Fixed-Combination Antiretroviral Drugs for the President’s Emergency Plan for AIDS Relief.”

This draft guidance describes circumstances under which an applicant may be eligible for a barrier-to-innovation waiver for some new drug applications (NDAs) for fixed-combination versions and single-entity versions of previously approved antiretroviral therapies for the treatment of human immunodeficiency virus (HIV). More information is available on the Federal Register’s website.

Consultation Deadline: 6th August, 2018

Formal meetings between the FDA and Sponsors or Applicants of BsUFA products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products.”

This draft guidance provides recommendations to industry on formal meetings between FDA and sponsors or applicants relating to the development and review of biosimilar or interchangeable biological products regulated by the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). The previous guidance for industry entitled “Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants,” issued on November 18, 2015, has been withdrawn. More information is available on the Federal Register’s website.

Consultation Deadline: 4th September, 2018

Considerations for the inclusion of adolescent patients in adult oncology clinical trials
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials.”

The purpose of this draft guidance is to provide the pharmaceutical industry, clinical investigators, and institutional review boards with information to facilitate the inclusion of adolescent patients (for purposes of this draft guidance defined as ages 12 to 17) in relevant adult oncology clinical trials. The draft guidance focuses on appropriate criteria for inclusion in adult trials at various stages of drug development, considerations for dosing and pharmacokinetic evaluations, safety monitoring, and ethical requirements. More information is available on the Federal Register’s website.

Consultation Deadline: 3rd August, 2018

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.

Development of a shared system REMS
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Development of a Shared System REMS.”

This draft guidance provides recommendations on the development of a shared system risk evaluation and mitigation strategy (REMS) for multiple prescription drug (including biological) products. This guidance describes some of the possible benefits of a shared system REMS, and provides general principles and recommendations to assist industry with the development of these programs. More information is available on the Federal Register’s website.

Consultation Deadline: 31st July, 2018

Waivers of the single, shared system REMS requirement
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Waivers of the Single, Shared System REMS Requirement.”

This guidance describes how FDA intends to consider granting a waiver of the requirement in the Federal Food, Drug, and Cosmetic Act (FD&C Act) that the applicant for an abbreviated new drug application (ANDA) and its reference listed drug (RLD) use a single, shared system (SSS) for a required risk evaluation and mitigation strategy (REMS) with elements to assure safe use (ETASU). More information is available on the Federal Register’s website.

Consultation Deadline: 31st July, 2018

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.

Assessment of pressor effects of drugs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Assessment of Pressor Effects of Drugs.”

This guidance is intended to advise sponsors on the premarketing assessment of a drug’s effect on blood pressure. Elevated blood pressure is known to increase the risk of stroke, heart attack, and death. The effect of a drug on blood pressure may therefore be an important consideration in benefit-risk assessment. More information is available on the Federal Register’s website.

Consultation Deadline: 30th July, 2018

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

Non-clinical bench performance testing in premarket submissions
The Food and Drug Administration (FDA or Agency) is announcing the availability of the draft guidance entitled “Recommended Content and Format of Complete Test Reports for Non-Clinical Bench Performance Testing in Premarket Submissions.”

FDA has developed this document to describe relevant information that should be included in complete test reports for non-clinical bench performance testing provided in a premarket submission (i.e., premarket approval (PMA) applications, humanitarian device exemption (HDE) applications, premarket notification (510(k)) submissions, investigational device exemption (IDE) applications, and De Novo classification requests). This draft guidance is not final nor is it in effect at this time. More information is available on the Federal Register’s website.

Consultation Deadline: 30th July, 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.

Handling and shipping of IMPs for human use in accordance with GCP and GMP
The European Medicines Agency have published: Scientific guideline: Draft guideline on the responsibilities of the sponsor with regard to handling and shipping of investigational medicinal products for human use in accordance with good clinical practice and good manufacturing practice, draft: consultation open.

The guideline lays down the principles for the two-step release and shipping of the investigational medicinal products by the qualified person and the sponsor. The guideline also describes the areas of interface between the manufacturer and the sponsor and the required contractual agreements. More information is available on the EMA’s website.

Consultation Deadline: 31st August, 2018

Maximal usage trials for topical active ingredients being considered for inclusion in an Over-the-Counter monograph
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Maximal Usage Trials for Topical Active Ingredients Being Considered for Inclusion in an Over-the-Counter Monograph: Study Elements and Considerations.”

This draft guidance addresses FDA’s current thinking on the conduct of in vivo absorption trials for topical active ingredients that are under consideration for inclusion in an over-the-counter (OTC) monograph. More information is available on the Federal Register’s website.

Consultation Deadline: 23rd July, 2018

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.

Duplicate marketing authorisations for biological medicinal products
The European Commission has published: Targeted stakeholder consultation on duplicate marketing authorisations for biological medicinal products.

Since the publication of the note on the handling of duplicate marketing authorisations in 2011, the Commission Services have identified potential issues related to the granting of duplicate marketing authorisations for biological medicinal products on the ground that they would be a “first generic”. These issues relate to the possible impact of such duplicate marketing authorisations on the biosimilar market (including potential anticompetitive effects) and the undermining of treatment options available to patients. The objective of the targeted stakeholder consultation is to seek the views of interested parties on the specific issue of the impact of duplicate marketing authorisations of biological medicinal products on the availability of biosimilars to healthcare professionals and patients. The results of the targeted stakeholders consultation will allow the Commission to take an informed decision as to whether there is a need to clarify the current wording of Annex I, Section 1 of the note on the handling of duplicate marketing authorisations applications on this particular matter. In the interim, requests for duplicate marketing authorisation applications in this specific case will be assessed on a case-by-case on the basis of the evidence provided by the applicant. More information is available on the European Commission’s website.

Consultation Deadline: 10th September, 2018

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 guideline Q3D (R1) on elemental impurities
The European Medicines Agency have published: Scientific guideline: ICH guideline Q3D (R1) on elemental impurities – Step 2b, draft: consultation open.

This guideline presents a process to assess and control elemental impurities in the drug product using the principles of risk management as described in ICH Q9. This process provides a platform for developing a risk-based control strategy to limit elemental impurities in the drug product. More information is available on the EMA’s website.

Consultation Deadline: 16th August, 2018

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

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

This guidance provides general recommendations on the development of drug products for the treatment of human immunodeficiency virus (HIV) infection in pediatric patients (birth to younger than 17 years of age). More information is available on the Federal Register’s website.

Consultation Deadline: 13th July, 2018

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

The purpose of this draft guidance is to assist sponsors in the development of new drugs for the treatment of uncomplicated urinary tract infections. More information is available on the Federal Register’s website.

Consultation Deadline: 8th August, 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.

Waivers, exceptions and exemptions from the FD&C Act
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Waivers, Exceptions, and Exemptions from the Requirements of Section 582 of the Federal Food, Drug, and Cosmetic Act.”

When finalized, this draft guidance will describe the process that trading partners and stakeholders should use to request a waiver, exception, or exemption from certain requirements of the Federal Food, Drug, and Cosmetic Act (FD&C Act), and describe how FDA intends to review and decide such requests and determine FDA-initiated exceptions and exemptions. Additionally, when finalized, this draft guidance will describe how FDA intends to biennially review and renew waivers, exceptions, and exemptions. More information is available on the Federal Register’s website.

Consultation Deadline: 9th July, 2018

Evaluation of the European Medicines Agency fee system
The European Commission has published: Public Consultation: Study supporting the Evaluation of the European Medicines Agency Fee System.

The European Medicines Agency (EMA) is the European Union’s (EU) central regulatory body operating centralised pre- and post-authorisation procedures for medicinal products for human and veterinary use across the EU and the European Economic Area (EEA). The EMA works in close collaboration with national competent authorities (NCAs) in the EU and EEA Member States. NCAs are represented in the EMA committees and working parties and in this setting they carry out assessments of medicinal products for human and veterinary use in the context of EU marketing authorisations. The EMA is funded by EU and EEA contributions as well as fees paid by entities for obtaining and maintaining marketing authorisations and for providing other services. NCAs receive remuneration from the EMA for activities for centralised procedures at the level of the EU. The relevant rules are laid down in the fee Regulation (Council Regulation (EC) No 297/95) and its implementing rules, as well as the pharmacovigilance fee Regulation (Regulation (EU) No 658/2014). Fee incentives are provided for specific types of products (including medicines for rare diseases, medicines for children, advanced therapies, and veterinary medicines for minor use/minor species) and specific applicants and marketing authorisation holders such as micro, small and medium-sized enterprises (SMEs). This public consultation is part of a study supporting the evaluation of the EMA fee system. The study, including the public consultation, is carried out by the consultant, RAND Europe. The consultation aims to elicit information, views and concerns of all groups having an interest in the EMA fee system and its implementation. More information is available on the European Commission’s website.

Consultation Deadline: 2nd August, 2018

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 safety of topically administered veterinary medicinal products
The European Medicines Agency have published: Scientific guideline: Guideline on user safety of topically administered veterinary medicinal products, adopted.

The guideline on user safety of topically administered products has been written to provide specific guidance and advice on how user risk assessments should be conducted for such products. This guideline should be used in conjunction with the ‘Guideline on user safety for pharmaceutical veterinary medicinal products’ (EMA/CVMP/543/03-Rev.1). More information is available on the EMA’s website.

Date for coming into effect: 1st November, 2018

Assessing the environmental and human health risks of veterinary medicinal products in groundwater
The European Medicines Agency have published: Scientific guideline: Guideline on assessing the environmental and human health risks of veterinary medicinal products in groundwater, adopted.

Groundwater is a source of drinking water and also provides a unique ecosystem with vulnerable aquatic communities. This guideline provides a methodology for performing a risk assessment of residues of veterinary medicinal products (VMPs) in groundwater, serving both as a source of drinking water and as an ecosystem. A risk assessment needs to be performed when the concentration of a VMP in groundwater is equal to or above 0.1 µg/l. In addition, this guideline highlights case studies where a risk assessment may be needed for highly toxic or persistent substances, when the predicted concentration in groundwater is lower than 0.1 µg/l. The guideline complements existing guidelines such as the CVMP guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL38, which provide a methodology for groundwater for exposure assessment. More information is available on the EMA’s website.

Date for coming into effect: 1st November, 2018

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.

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, draft: consultation open.

The guideline, which was developed to encourage optimal use and to minimise selection of antimicrobial resistance (AMR), was revised in order to improve consistency of the summary of product characteristics (SPCs) for antimicrobial products in the EU Member States. More information is available on the EMA’s website.

Consultation Deadline: 30th September, 2018

Clinical evaluation of vaccines
The European Medicines Agency have published: Scientific guideline: Draft guideline on clinical evaluation of vaccines – Revision 1, draft: consultation open.

This guideline addresses the clinical evaluation of vaccines intended for the prevention of infectious diseases. It includes considerations for trials intended to document the safety, immunogenicity and efficacy of new candidate vaccines and to support changes in the prescribing information of licensed vaccines. It also considers the need for and use of vaccine effectiveness studies. The draft guideline includes specific considerations for clinical trials with vaccines in special populations, such as pregnant women or the elderly. It also adds considerations to priming and boosting strategies, including the option of heterologous prime-boost, which entails administration of one type of vaccine first followed by a different type of vaccine for the same pathogen later. More information is available on the EMA’s website.

Consultation Deadline: 30th October, 2018

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.

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

The purpose of this guidance is to provide information to assist sponsors in the design of an appropriate program of nonclinical studies for the development of pharmaceuticals used to treat patients with severely debilitating or life-threatening hematologic disorders (SDLTHDs). While FDA has guidance for oncology indications (most of which are considered severely debilitating or life-threatening diseases) and for rare diseases (which include some SDLTHD conditions), FDA has no guidance to facilitate nonclinical development specifically for pharmaceuticals used to treat nononcology patients with SDLTHDs. A streamlined approach to drug development is necessary to allow patients with SDLTHDs earlier and continued access to new and potentially effective therapies. More information is available on the Federal Register’s website.

Consultation Deadline: 25th June, 2018

Manufacture of the veterinary finished dosage form
The European Medicines Agency have published: Scientific guideline: Draft guideline on manufacture of the veterinary finished dosage form – Revision 1, draft: consultation open.

This guideline replaces the veterinary note for guidance on the manufacture of the finished dosage form (EMEA/CVMP/126/95). The note for guidance has been updated to reflect the requirements as laid down in the current legislation (Directive 2001/82/EC, as amended and its Annex I). It also addresses current manufacturing practices in terms of complex supply chains and worldwide manufacture. In addition, applicants for EU marketing authorisations (MAs) of veterinary medicinal products may voluntarily choose to follow enhanced concepts in the manufacturing process of the final dosage forms as outlined in the ICH guidelines Q8, Q9 and Q10 (formally applicable to medicinal products for human use, refs 3, 4 and 5 respectively). The revised guideline takes this option into account although it is highlighted that the traditional approach is still acceptable. This guideline does not introduce new requirements for authorised medicinal products for veterinary use. However as stated in Article 27 of Directive 2001/82/EC as amended, after a marketing authorisation has been approved, the authorisation holder should, in respect of the methods of manufacture and control, take account of scientific and technical progress and introduce any changes that may be required to enable the medicinal product to be manufactured and controlled by means of generally accepted scientific methods. More information is available on the EMA’s website.

Consultation Deadline: 22nd October, 2018

Developing depot buprenorphine products for treatment of opioid dependence
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Opioid Dependence: Developing Depot Buprenorphine Products for Treatment.”

This draft guidance addresses drug development and trial design issues relevant to the study of depot buprenorphine products (i.e., modified-release products for injection or implantation). More information is available on the Federal Register’s website.

Consultation Deadline: 22nd June, 2018

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.

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

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

Consultation Deadline: 30th August, 2018

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

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

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.

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

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

Date for coming into effect: 1st September, 2018

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

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

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

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

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

More information is available on the Commission’s website.

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

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

Date for coming into effect: 1st September, 2018

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

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

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

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

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

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

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

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

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

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

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

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

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

This guidance provides applicants planning to submit new drug applications (NDAs) and abbreviated new drug applications (ANDAs) with information on the appropriate regulatory classification of pharmaceutical co-crystal solid-state forms. This guidance also provides information about the data that applicants should submit to support the appropriate classification of a co-crystal as well as the regulatory implications of the classification. More information is available on the FDA’s website.

European Commission Safety Features Q&A document updated
The European Commission has published an updated version, Version 9, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

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

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

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

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

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

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

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

Consultation Deadline: 15th August, 2018

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Date for coming into effect: 19th July, 2018

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

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

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

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

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

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

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

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

Date for coming into effect: 1st July, 2018

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

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

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

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

Consultation Deadline: 18th December, 2018

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