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.

Postapproval changes to drug substances
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Postapproval Changes to Drug Substances.”

This draft guidance provides recommendations to holders of approved new drug applications, abbreviated new drug applications, new animal drug applications, abbreviated new animal drug applications, and holders of drug master files and veterinary master files who may want to make a change to the drug substance manufacturing process during the drug product application postapproval period. The draft guidance applies to synthetic drug substances and the synthetic steps involved in the preparation of semisynthetic drug substances. The draft guidance covers facility, scale, and equipment changes associated with all steps of drug substance manufacturing; specification changes to starting materials, raw materials, intermediates, and the unfinished and final drug substance; synthetic manufacturing process changes; changes in the source of drug substance; and change to container closure system of the drug substance. More information is available on the Federal Register’s website.

Consultation Deadline: 13th November, 2018

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.

Use of placebos and blinding in clinical trials for hematologic malignancy and oncologic disease
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Hematologic Malignancy and Oncologic Disease: Considerations for Use of Placebos and Blinding in Randomized Controlled Clinical Trials for Drug Product Development.”

This draft guidance provides recommendations to industry regarding the use of placebos and blinding in randomized controlled clinical trials in development programs for drug or biological products for the treatment of hematologic malignancies and oncologic diseases 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: 23rd October, 2018

Structural endpoints for the development of drugs for osteoarthritis
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Osteoarthritis: Structural Endpoints for the Development of Drugs, Devices, and Biological Products for Treatment.”

The purpose of this draft guidance is to assist sponsors who are developing drugs, devices, or biological products to treat the underlying pathophysiology and structural progression of osteoarthritis (OA). This draft guidance does not address improvement of symptoms of OA, such as pain or functional impairment, which will be addressed in future guidances. More information is available on the Federal Register’s website.

Consultation Deadline: 22nd October, 2018

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

Use of expansion cohorts in clinical trials for oncology drugs and biologics
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics.”

The purpose of this draft guidance is to provide advice to sponsors regarding the design and conduct of first-in-human (FIH) clinical trials intended to efficiently expedite the clinical development of cancer drugs, including biological products, through multiple expansion cohort study designs. More information is available on the Federal Register’s website.

Consultation Deadline: 12th October, 2018

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.

Demonstrating effectiveness of drugs for medication-assisted treatment of opioid use disorder
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Opioid Use Disorder: Endpoints for Demonstrating Effectiveness of Drugs for Medication-Assisted Treatment.”

This guidance addresses the clinical endpoints acceptable to demonstrate effectiveness of drugs for medication-assisted treatment of opioid use disorder. FDA is also requesting comments on when the use of placebo or active controls is most appropriate in clinical trials for such drugs. More information is available on the Federal Register’s website.

Consultation Deadline: 9th October, 2018

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.

Use of minimal residual disease as a clinical endpoint in multiple myeloma studies
The European Medicines Agency have published: Scientific guideline: Draft guideline on the use of minimal residual disease as a clinical endpoint in multiple myeloma studies, draft: consultation open.

The guideline aims to address the use of undetectable minimal residual disease (MRD) as an intermediate efficacy endpoint in controlled randomised clinical studies in patients with multiple myeloma (MM), adequately designed to demonstrate efficacy by relevant hard endpoints. MRD as an endpoint in this context would allow earlier approval of new drugs pending final confirmatory data. More information is available on the EMA’s website.

Consultation Deadline: 31st October, 2018

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

Nonclinical testing of orally inhaled nicotine-containing drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Nonclinical Testing of Orally Inhaled Nicotine-Containing Drug Products.”

The document provides guidance regarding the nonclinical information FDA recommends to support development and approval of orally inhaled nicotine-containing drug products, including electronic nicotine delivery systems intended for smoking cessation and other chronic uses. More information is available on the Federal Register’s website.

Consultation Deadline: 5th October, 2018

Guidelines on Good Clinical Practice for Advanced Therapy Medicinal Products
The European Commission has published: Targeted stakeholder consultation on the draft Guidelines on Good Clinical Practice for Advanced Therapy Medicinal Products.

Article 4 of Regulation 1394/2007 of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC requires the Commission to draw up guidelines on good clinical practice specific to advanced therapy medicinal products. Taking account the advances and experience in the field the Commission services have developed a new draft Guidelines on Good Clinical Practice specific to Advanced Therapy Medicinal Products with the European Medicines Agency and the expert group of the competent authorities of the Member States. The Guidelines will adapt good clinical practice requirements (“GCPs”) to ATMPs. It will be a document that focuses on ATMP specificities only and which applies in addition to the GCP Guidelines of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The Directorate General for Health and Food Safety wants to give an opportunity for concerned stakeholders to express their views on the GCP requirements that should apply to ATMPs. More information is available on the European Commission’s website.

Consultation Deadline: 31st October, 2018

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

Antimicrobial resistance due to the use of an antimicrobial veterinary medicinal product in food-producing animals
The European Medicines Agency have published: Scientific guideline: Second draft guideline on the assessment of the risk to public health from antimicrobial resistance due to the use of an antimicrobial veterinary medicinal product in food-producing animals, draft: consultation open.

This guideline provides advice in regards to applications for Marketing Authorisations for antimicrobial veterinary medicinal products (VMPs) on the data required and the methodology to be used for performing an assessment of the risk to public health from antimicrobial resistance (AMR) due to use of the product. The scope of the guidance extends to VMPs intended for food producing species and to the transmission of AMR by the foodborne route or through direct contact with treated animals. More information is available on the EMA’s website.

Consultation Deadline: 31st October, 2018

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

Rare diseases with substrate deposition that results from single enzyme defects
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Slowly Progressive, Low-Prevalence Rare Diseases with Substrate Deposition That Results from Single Enzyme Defects: Providing Evidence of Effectiveness for Replacement or Corrective Therapies.”

This document is intended to provide guidance to sponsors on the evidence necessary to demonstrate the effectiveness of new drugs, including biological drugs, or new drug uses intended for slowly progressive, low-prevalence rare diseases that are associated with substrate deposition and are caused by single enzyme defects. This guidance applies only to those low-prevalence rare diseases with a well-characterized pathophysiology and in which changes in substrate deposition can be readily measured in relevant tissue(s). More information is available on the Federal Register’s website.

Consultation Deadline: 25th September, 2018

Use of liquids and/or soft foods as vehicles for drug administration
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments.”

This draft guidance applies to orally administered drug products and provides recommendations to sponsors who will use or recommend use of liquids and/or soft foods as vehicles for drug administration in investigational new drug applications (INDs), new drug applications (NDAs), Biologics License Applications (BLAs), as applicable, and in supplements to these applications. More information is available on the Federal Register’s website.

Consultation Deadline: 24th September, 2018

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

Considerations for optimizing and standardizing diet in clinical trials for drug product development
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Inborn Errors of Metabolism That Use Dietary Management: Considerations for Optimizing and Standardizing Diet in Clinical Trials for Drug Product Development.”

This draft guidance describes FDA’s current recommendations regarding how to optimize and standardize dietary management in clinical trials for the development of drugs treating inborn errors of metabolism (IEM) for which dietary management is a key component of patients’ metabolic control. Optimizing dietary management in these patients before entry into and during the clinical trial(s) is essential to providing an accurate evaluation of the efficacy of new drug products. More information is available on the Federal Register’s website.

Consultation Deadline: 24th September, 2018

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.

Field alert report submission
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Field Alert Report Submission: Questions and Answers.”

This draft guidance, when finalized, will provide the Agency’s current thinking regarding the requirements for submission of field alert reports (FARs) by applicants of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) and will outline FDA’s recommendations for FAR submissions to help increase their consistency and relevancy. The draft guidance also addresses certain frequently asked questions about FARs. More information is available on the Federal Register’s website.

Consultation Deadline: 17th September, 2018

Innovative approaches for nonprescription drug products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Innovative Approaches for Nonprescription Drug Products.”

This draft guidance describes two innovative approaches that may be useful to consider for demonstrating safety and effectiveness for a nonprescription drug product in cases where the drug facts labeling (DFL) alone is not sufficient to ensure that the drug product can be used safely and effectively in a nonprescription setting: The development of labeling in addition to the DFL and the implementation of additional conditions so that consumers appropriately self-select and use the product. More information is available on the Federal Register’s website.

Consultation Deadline: 17th September, 2018

Implementing ‘safety features’ under the Falsified Medicines Directive
The Medicines and Healthcare products Regulatory Agency (MHRA) has published: Open consultation: Implementing ‘safety features’ under the Falsified Medicines Directive.

This consultation invites views on the proposed steps intended to be taken to make sure the UK meets its obligations to transpose the ‘safety features’ provisions of the Falsified Medicines Directive (FMD). More information is available on the UK Government website.

Consultation Deadline: 23rd September, 2018

Human gene therapy for retinal disorders
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft document entitled “Human Gene Therapy for Retinal Disorders; Draft Guidance for Industry.”

The draft guidance provides recommendations to stakeholders developing human gene therapy (GT) products for retinal disorders affecting adult and pediatric patients. The draft guidance focuses on issues specific to GT products for retinal disorders and provides recommendations related to product development, preclinical testing, and clinical trial design for such GT products. More information is available on the Federal Register’s website.

Consultation Deadline: 10th October, 2018

Long term follow-up after administration of human gene therapy products
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft document entitled “Long Term Follow-Up After Administration of Human Gene Therapy Products; Draft Guidance for Industry.”

The draft guidance provides sponsors, who are developing a human gene therapy (GT) product, recommendations regarding the design of long term follow-up (LTFU) observational studies for the collection of data on delayed adverse events following administration of a GT product. The draft guidance, when finalized, is intended to supersede the document entitled “Guidance for Industry: Gene Therapy Clinical Trials—Observing Participants for Delayed Adverse Events” dated November 2006. This draft guidance, when finalized, is also intended to supplement the guidance entitled “Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus during Product Manufacture and Patient Follow-up; Draft Guidance for Industry.” More information is available on the Federal Register’s website.

Consultation Deadline: 10th October, 2018

Human gene therapy for hemophilia
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft document entitled “Human Gene Therapy for Hemophilia; Draft Guidance for Industry.”

The draft guidance document provides recommendations to stakeholders developing human gene therapy (GT) products for the treatment of hemophilia. The draft guidance provides recommendations on the clinical trial design and related development of coagulation factor VIII (hemophilia A) and IX (hemophilia B) activity assays, including how to address discrepancies in factor VIII and factor IX activity assays. The draft guidance also includes recommendations regarding preclinical considerations to support development of GT products for the treatment of hemophilia. More information is available on the Federal Register’s website.

Consultation Deadline: 10th October, 2018

Human gene therapy for rare diseases
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft document entitled “Human Gene Therapy for Rare Diseases; Draft Guidance for Industry.”

The draft guidance document provides recommendations to stakeholders developing a human gene therapy (GT) product intended to treat a rare disease in adult and/or pediatric patients regarding the manufacturing, preclinical, and clinical trial design issues for all phases of the clinical development program. Such information is intended to assist sponsors in designing clinical development programs for such products, where there may be limited study population size and potential feasibility and safety issues as well as issues relating to the interpretability of bioactivity/efficacy outcomes that may be unique to rare diseases or to the nature of the GT product itself. More information is available on the Federal Register’s website.

Consultation Deadline: 10th October, 2018

Testing of retroviral vector-based human gene therapy products for replication competent retrovirus
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft document entitled “Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up; Draft Guidance for Industry.”

The draft guidance document provides sponsors of retroviral vector-based human gene therapy products recommendations regarding the testing for replication competent retrovirus (RCR) during the manufacture of retroviral vector-based products, and during follow-up monitoring of patients who have received retroviral vector-based products. Recommendations include the identification and amount of material to be tested, and general testing methods. In addition, recommendations are provided on monitoring patients for evidence of retroviral infection after administration of retroviral vector-based gene therapy products. The draft guidance, when finalized, is intended to supersede the document entitled “Guidance for Industry: Supplemental Guidance on Testing for Replication Competent Retrovirus in Retroviral Vector Based Gene Therapy Products and During Follow-up of Patients in Clinical Trials Using Retroviral Vectors,” dated November 2006. The draft guidance, when finalized, is also intended to supplement the documents entitled “Long Term Follow-Up After Administration of Human Gene Therapy Products; Draft Guidance for Industry” and “Chemistry, Manufacturing, and Control Information for Human Gene Therapy Investigational New Drug Applications; Draft Guidance for Industry,” when these draft guidance documents are finalized. More information is available on the Federal Register’s website.

Consultation Deadline: 10th October, 2018

CMC information for human gene therapy INDs
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs); Draft Guidance for Industry.”

The draft guidance document provides sponsors of a human gene therapy IND with recommendations regarding CMC information required to assure product safety, identity, quality, purity, and strength (including potency) of the investigational product. The draft guidance applies to human gene therapy products and to combination products that contain a human gene therapy in combination with a drug or device. The draft guidance, when finalized, is intended to supersede the document entitled “Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs),” dated April 2008 (April 2008 guidance). More information is available on the Federal Register’s website.

Consultation Deadline: 10th October, 2018

European Commission Safety Features Q&A document updated
The European Commission has published an updated version, Version 10, of the Questions and Answers document on the Safety Features for Medicinal Products for Human Use.

Version 10 of the document, dated July 2018, supersedes Version 9. Q&As 1.20, 1.21, 1.22, 1.23 and 6.7 were added to the document, and Q&As 1.19, 2.15, 2.18, 2.21, 3.5, 4.3, 5.3, 5.5, 6.6, 7.17, 8.7 and 12.1 were revised. More information is available on the Commission’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 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.

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

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