USA/Europe BioPharma Regulatory 2023 News/Updates recap

BELGIUM

Guideline: Labelling of medicinal products

The Federal Agency for Medicines and Health Products (FAMHP) published guideline, labelling of medicinal products. This document describes the requirements for labelling and mock-ups for medicinal products for human use.

CANADA

Validation rules for regulatory transactions provided to Health Canada in the electronic Common Technical Document (eCTD) format

Health Canada has updated the validation rules for regulatory transactions submitted in the electronic Common Technical Document (eCTD) format, to reflect recent and upcoming changes in the processes. The purpose of the validation rules is to help ensure Sponsors provide a valid electronic transaction to Health Canada, and reduce errors and follow-up with Sponsors. Sponsors are encouraged to use a commercially available tool to validate their regulatory transactions in eCTD format, prior to filing them to Health Canada.

Master File Application Form (Version 1.0.2)

TGA updated Master File Application Form which is of Version 1.0.2. How to load application form, regulatory info, contact details to be filled are included.

Master File Application Form (Version 1.0.0)

Health Canada published Master File Application Form (Version 1.0.0). This also includes instructions to be followed for the application form.

Guidance on procedures and administrative requirements for master files

The revised guidance document is administrative in nature. It was revised to include the change to an online web-based XML application process. This guidance document provides MF-related definitions, information on filing requirements, processing and assessment procedures for Type I to V MFs. It also outlines the registration requirements for new MFs, as well as other MF transactions including administrative changes, updates, withdrawals and closures.

CZECH REPUBLIC

PHV-4 Version 9 electronic reporting of adverse drug reactions

The Guideline is issued on the basis and in accordance with the provision of Section 91 paragraph 4 and Section 93a of Act no. 378/2007 Coll., on Pharmaceuticals. The Guideline concerns the reporting of suspected adverse reactions to medicinal products in their postauthorisation period, i.e. those sent to the EVPM module of the EudraVigilance database. The ADR reports from clinical trials (SUSARs) sent to the EVCTM module of the EudraVigilance database follow the relevant guidances of EMA and the Clinical Trials Department of SÚKL.

EUROPE

IRIS guide for applicants

EMA updated IRIS guide for applicants. This guide has been produced to show applicants how to use the IRIS platform to prepare and submit an application and/or data for a scientific procedure (orphan designation application, scientific advice, ITF briefing meeting requests, PRIME, marketing status reports, inspections and veterinary signal management) and related activities, or applications for Parallel Distribution procedures.

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure

EMA updated post-authorisation procedural advice for users of the centralised procedure. How shall I present and submit my Type IA/ IAIN Variation, what procedure number will be given to grouped variation applications were updated in this document.

Guide to information on human medicines evaluated by EMA

The European Medicines Agency (EMA) publishes information on human medicinal products at various stages of their life cycle, from the early developmental stages through to EMA’s evaluation of authorisation applications, post-authorisation changes, safety reviews and withdrawals of authorisation. This guide describes the different types of information the Agency currently publishes for both centrally and non-centrally authorised medicines, as well as publication times and location on EMA’s website. It aims to help stakeholders know what kind of information to expect on medicines undergoing evaluations and other regulatory procedures.

First electronic product information (ePI) published for selected human medicines

The Heads of Medicines Agencies (HMA), the European Commission (EC) and EMA have published for the first time electronic product information (ePI) for selected human medicines harmonised across the European Union (EU).  The product information of a medicine includes its summary of product characteristics, labelling and package leaflet. These documents accompany every medicine authorised in the EU and explain how they should be prescribed and used. They can all be found, often as a PDF document, on the websites of EU regulators, with a printed package leaflet also provided in the medicine’s box. Digital platforms open new possibilities to share this information electronically, keep it constantly updated and make it more accessible to end users such as healthcare professionals and patients.

How to create, submit and withdraw a CTA CTIS Training Programme – Module 10 is updated

The European Medicines Agency developed this training material to enhance public access to information on the Clinical Trial Information System (CTIS). This material describes a preliminary version of CTIS and may therefore not entirely describe the system as it is at the time of use of this material. The Agency does not warrant or accept any liability in relation to the use (in part or in whole) or the interpretation of the information contained in this training material by third parties.

Revised transparency rules for the EU Clinical Trials Information System (CTIS)

EMA has adopted PDF icon revised transparency rules for the publication of information on clinical trials submitted through the Clinical Trials Information System. The simplifications introduced will give access to clinical trial information to stakeholders including patients and healthcare professionals in a faster and more efficient way. One of the key changes of the revised rules is the removal of the deferral mechanism, which allowed sponsors to delay the publication of certain data and documents for up to seven years after the end of the trial to protect personal data and commercially confidential information (CCI).

Explanatory note on pharmacovigilance fees payable to the European Medicines Agency

This explanatory note concerns the fees related to pharmacovigilance activities (and the rules of payments) that apply to medicinal products for human use authorised in the Union under Regulation (EC) No 726/2004 and Directive 2001/83/EC. Increase in the level of fees (other than pharmacovigilance annual fees) to adjust for an inflation rate of 10.4% (related to 2022) and rounding off to the nearest EUR 10.  Increase in the level of pharmacovigilance annual fees to adjust for an inflation rate of 10.4% (related to 2022), with no rounding.

Update on human variations web-based electronic application form implementation on product lifecycle management portal

The web-based electronic Application Forms (eAF) in the new Product Lifecycle Management (PLM) portal will replace the current interactive PDF eAFs used for regulatory submissions. This is a first step towards making the form-filling and submission-handling process more efficient. The web-based Variations eAF for Human medicinal Centrally Authorised Products (CAPs) was released on 4 November 2022.

Frequently asked questions about parallel distribution

EMA updated Frequently asked questions about parallel distribution. What to do when my organisation details have changed? What is the validity of the notice for parallel distribution and can it be revoked, suspended or annulled? What is the scope of and how to submit a bulk change? Were updated.

How to prepare and review a summary of product characteristics

EMA updated How to prepare and review a summary of product characteristics. The committee for human medicines (CHMP) has adopted guidance for assessors to follow a consistent approach in the process of defining therapeutic indications during the assessment of centralised applications for new active substances or new indications. When is it relevant to include a bodyweight limit in the wording of a paediatric indication? is updated.

Guidance to applicants /Marketing Authorisation Holders (MAHs) on oral explanations at EMA

EMA updated Guidance to applicants /Marketing Authorisation Holders (MAHs) on oral explanations at EMA. This document is intended to provide practical guidance to companies on oral explanations/discussion meetings before Committees, Working Parties, Scientific Advisory Groups (SAGs) and Ad Hoc Expert Groups (AHEGs) (irrespective of the type of application / procedure under discussion).

EMA Revises Guidance for Its “PRIME Scheme” Drug Development Assistance Program

EMA has issued revised guidance for its PRIority MEdicines (PRIME) scheme that provides early consultation and scientific advice between applicants and regulators for medicines under development and not currently authorized in the EU.

Obtaining an EU marketing authorisation, step-by-step

The European Medicines Agency (EMA) is responsible for the scientific evaluation of applications for centralised marketing authorisations in the European Union (EU). This authorisation procedure allows pharmaceutical companies to submit a single marketing authorisation application to EMA and to market the medicine and make it available to patients and healthcare professionals throughout the European Economic Area on the basis of a single marketing authorisation. Applicants may apply in parallel for an EU marketing authorisation under the centralised procedure and an opinion for their medicine to be used outside the EU.

Changing the labelling and package leaflet (Article 61(3) notifications)

The page lists questions that marketing-authorisation holders (MAHs) may have on Article-61(3) notifications. It provides an overview of the European Medicines Agency’s position on issues that are typically addressed in discussions or meetings with MAHs in the post-authorisation phase. When can I submit my 61(3) Notification, What are Article 61(3) Notifications are updated.

Guidance on Parallel EMA/HTA body (HTAb) Scientific Advice for the Interim Period

This guidance highlights ideal timelines and actions for each party undertaking a Parallel EMA/HTAb Scientific Advice. This is a multi-stakeholder procedure with EMA and HTAbs being equal partners. As a multi-stakeholder procedure, collaboration and communication between all stakeholders are important to ensure agreement and clarity on the ownership of different actions, and to deliver on the objectives of the exercise.

Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol

This document was prepared in collaboration with the UK Medicines & Healthcare products Regulatory Agency (MHRA) and was available for public consultation between May and August 2017. To outline the practical arrangements for notification of serious breaches; this document does not cover notifications related to unexpected events, other reporting obligations related to the safety of trial participants or urgent safety measures, as defined in Articles 53 and 54 of the Regulation (EU) No 536/2014.

EU to Run Pilot to Test Real-Time Generated Human Medicine Product Information

The European Medicines Agency (EMA), along with the regulatory authorities of three member nations, is starting a one-year pilot to test the use of electronic product information (ePI) for human medicines in the EU.

EMA won’t delay drug approval of combo product if diagnostic part doesn’t have CE mark

European regulators will not prevent approval of a drug if the device part of the combination product is delayed in getting certification from a notified body, a European Medicines Agency (EMA) official assured delegates at RAPS Euro Convergence. During a town hall meeting on 12 May with European regulators and notified body representatives, Marina Belonogova, associate director for diagnostics and digital health at Janssen Pharmaceutical, asked that if companies are putting themselves at risk if their drug and device components are not reviewed in parallel when trying to gain market authorization in the EU.

EMA Adopts Final ICH S12 Covering Nonclinical BD Studies for Gene Therapies

The European Medicines Agency (EMA) has become the first regulator to accept the International Council for Harmonization (ICH) S12 guideline, laying out the council’s recommendations for how to conduct nonclinical biodistribution (BD) studies when developing gene therapy products.

EU patent reform proposal addresses compulsory licensing and SPCs

The European Commission on Thursday published a package of regulations that would establish an EU-wide compulsory licensing scheme allowing other companies to make drugs without the patent holder’s consent in emergency situations and establishes community-wide supplementary protection certificates (SPCs) that would extend the patent term for pharmaceutical products for up to five additional years. Currently, SPCs are only granted at the national level. The Commission said that these proposals “will create a more transparent, effective and futureproof intellectual property rights framework.”

 EU releases draft legislation that will reshape pharma regulation

The European Commission on Wednesday published the thrice-delayed draft of the contentious legislation that will reshape the regulation of the pharma sector and set the course of the industry for years to come. After a series of delays, the draft document is now available for public scrutiny. The draft is the product of a long, heated debate into the future of the European pharma industry that at various points has seen politicians disparagingly call the delays “a huge victory for the pharmaceutical lobby” and the trade group EFPIA warn that a leaked, earlier draft would “irretrievably sabotage” the industry and “send Europe to the back of the queue for healthcare treatments, clinical research, jobs and global investment.”

Guideline on computerized systems and electronic data in clinical trials

The European Medicines Agency (EMA) has offered recommendations for electronic data collection in clinical trials in a new final guidance. This guideline replaces the ‘Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials’ (EMA/INS/GCP/454280/2010).

Regulatory, industry panels address EU GMP Annex 1 implementation

Pharmaceutical manufacturers in the EU may have to approach the manufacturing of sterile drugs a little differently under the EU’s Annex 1 covering good manufacturing practices (GMPs), which goes into effect soon. For example, regulators may be asking to see whether firms have a documented contamination control strategy (CCS) and may require firms to conduct pre- and post-sterilization integrity testing (PUPSIT) on filters used in sterile drug manufacturing. In the meantime, regulators from the US Food and Drug Administration (FDA) said that while they will not be enforcing Annex 1, inspectors will be looking into similar areas as their counterparts in the EU.

EMA Clarifies Its Policy on Biosimilar Interchangeability

The European Medicines Agency’s (EMA) policy on interchangeability of biosimilars relates only to the active substance and formulated product, the agency said in a clarifying statement. Referring to an EMA policy statement issued last fall about biosimilar interchangeability, the agency moted that the statement “does not include potential issues related to the handling of different administration devices,” such as the need for patient training when using a new device, or “physician or patient perception of biosimilars.” “As for any biological medicinal product, traceability should also be ensured for biosimilars to allow for proper root cause analyses in case adverse drug reactions occur,” the clarifying statement said.

EMA Adopts ICH Q13 Guideline on Continuous Manufacturing

The European Medicines Agency (EMA) is the first regulator to adopt the International Council for Harmonization (ICH) new guideline Q13 on continuous manufacturing (CM) of drug substances and drug products, effective July 10, 2023.

EMA certificates of medicinal products – instructions on how to fill the application form

EMA has updated the document of instructions on how to fill the application form. This form is intended for requesting EMA certificates of medicinal products only. It can be used as of date of publication. Requests cannot be submitted on any other form. A complete request includes Part A and Part(s) B of the form and, if applicable, a statement of composition and permission from the marketing-authorisation holder (MAH) to obtain the certificates on their behalf.

Changes to the guidance document authorization of human medicinal products under Art. 13 TPA

Application of Art. 13 TPA for temporary authorization according to Art. 9a TPA was previously only possible for new authorization of human medicinal products with a new active substance. Subject to certain conditions, assessment is now also possible in application of Art. 13 TPA for temporary additional indications for human medicinal products with a new active substance as well as for human medicinal products with a known active substance where an application is being made for an indication that has not previously been authorized. The guidance document authorization of human medicinal products under Art. 13 TPA has been updated accordingly. Aspects of the document Questions and answers Art. 13 TPA have also been incorporated into the guidance document authorization of human medicinal products under Art. 13 TPA.

Changes to the guidance documents Fast-track authorization procedure and Temporary authorization for human medicinal products

The deadline for finalizing the decision minutes has been extended. The decision minutes can be finalized by the applicant following the Accelerated Application Hearing (AAA) and sent to Swissmedic on the next working day after the hearing. In addition, documentation for the AAA can now be exchanged via the eGov portal with immediate effect. The guidance documents Fast-track authorization procedure and Temporary authorization for human medicinal products have been revised accordingly and the new versions are valid with immediate effect.

GERMANY

Deactivation of the variation branch of the Pharmnet.Bund application “Änderungsanzeigen”

As of 26.10.2023, the previously recommended additional electronic submission of variations according to Regulation (EC) No 1234/2008 via the PharmNet.Bund portal will be discontinued. Due to internal BfArM developments, the submission via the PharmNet.Bund portal is no longer required and will be deactivated as of 26.10.2023. The sending of notifications of changes according to § 29 AMG and other notifications remains unaffected and is still required via the PharmNet.Bund portal. Variations are to be submitted exclusively via the CESP portal from 26.10.2023. Please note that variations that have already been created but not yet sent can no longer be submitted from this date.

ICELAND

Exemptions from Icelandic package labelling requirements

The Icelandic Medicines Agency has updated guidelines on applications for exemptions from package labelling requirements. In most cases an exemption is only granted on a temporary basis with the aim of protecting human or animal health.

IRELAND

Fee Application Form for Human Products in Ireland

HPRA published Fee Application Form for Human Products fin-f0018. This includes application form, fee codes, fee for different types.

SWITZERLAND

Update to the guidance document “RMP ICH E2E Information submission HMP”

The guidance document “RMP ICH E2E Information for submission HMP” has been fully revised.  The most important change concerns the obligation to submit RMPs, which now only applies to first authorisation applications for new active substances and their indication extensions. There is no RMP obligation for known active substances without/with innovation or for biosimilars. Other changes include clarifications regarding the submission of RMP updates and concerning the implementation of the RMP, as well as additional risk-minimisation measures.

Guidance document Formal requirements

Swissmedic published ZL000_00_020e_WL Guidance document Formal requirements version 13.5. Similar biological medicinal products (biosimilars) – human medicinal products only, Applications under Article 13 TPA, PVP / RMP / Pharmacovigilance planning documents (human medicinal products only) were revised due to RMP changes.

Directory Overview of documents to be submitted

Swissmedic published ZL000_00_006e_VZ Directory Overview of documents to be submitted for new authorization, extension, modification, renewal.

Variations and extensions form

Swissmedic published variations and extensions form ZL300_00_003, version 18.1. Basic procedures, addresses, special procedures, additional forms to be submitted should be filled in the form.

Modifications to guidance document Formal requirements

Submission of complete identical document sets for eDOK and eCTD has been clarified with regard to co-marketing medicinal products. In addition, the submission deadline for variations without assessment after implementation for VMPs has been extended from a maximum of 1 month to a maximum of 60 calendar days.

Changes to the guidance document Temporary authorisation of human medicinal products

Swissmedic clarified regarding authorised medicinal products, harmonised deadlines for applications before expiry of temporary authorisation and changes to terminology.

ZL000_00_006e_VZ Directory Overview of documents to be submitted

Swissmedic updated Directory Overview of documents to be submitted. It includes cover letter, forms, quality documents, product information, packaging texts, information about experts.

ZL300_00_003e_FO Form Variations and extensions

Swizzmedic published ZL300_00_003e_FO Form Variations and extensions, version 18. It includes basic information, procedures, addresses, additional forms to be submitted.

Software HOMANT Asia for the authorisation based on a notification (notification procedure) of Asian medicinal products without indication

The Complementary and Phytotherapeutic Products Ordinance (KPTPO; SR 812.212.24) provides for Asian medicinal products without indication a marketing authorisation based on a notification. The single notifications must be submitted in the form prescribed by Swissmedic according to article 41 of the KPTPO. Swissmedic provides a corresponding electronic form and has developed the HOMANT Asia software for this purpose.

Guidance document- Formal requirements ZL000_00_020

Swissmedic uses this guidance document first and foremost as a resource for applying the legal provisions in a uniform and equitable manner. The publication of this document provides transparency concerning how applications should be structured so that they can be processed efficiently and completed in accordance with Swissmedic’s practices and systems. This document also takes into account all publications on this subject in the Swissmedic Journal in recent years.

TURKEY

Regulation on the marketing authorization of medicinal products for human use

Turkish medicines and medical devices agency published Regulation on the marketing authorization of medicinal products for human use. This regulation shall comprise medicinal products for human use which are manufactured industrially or manufactured by a method that includes an industrial process and the real persons and legal entities who have applied for the marketing authorization and/or have been granted the marketing authorization of such products.

UK

UK Solicits Feedback on End of EU Regulatory Reciprocity Pathway

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is seeking public feedback on a plan that would end regulatory reciprocity between the UK and the EU for drug and device review and approvals.

International Recognition Procedure

The MHRA has created a new international recognition route for medicines utilising pre-existing approvals from Australia, Canada, the European Union, Japan, Switzerland, Singapore and the United States. This new framework will support patients in the UK with expedited access to safe and effective medicines that have been approved by trusted regulatory partners. From 1 January 2024, international recognition will sit alongside the MHRA’s current national procedures.

150-day assessment for national applications for medicines

The MHRA offers a 150-day assessment timeline for all high-quality marketing authorisation applications (MAAs), aiming at accelerating the availability of medicines for patients in the UK. Under this process, the MHRA will evaluate the application for a UK, Great Britain (England, Wales and Scotland) or Northern Ireland marketing authorisation and reach its opinion on approvability within 150 days of submission of a valid application. New active substances and biosimilar products applications section updated.

Advertise your medicines

How to comply with the requirements on promoting medicines to the public and to prescribers and suppliers of medicines. Updated ‘guidance for vetting of promotional material’ document. This document provides advice to companies who are submitting material for medicines to MHRA for vetting prior to issue. It covers various common issues and arrangements in relation to advertising in Great Britain and Northern Ireland and is designed to help ensure that the vetting exercise is carried out efficiently.

Medicines: apply for a parallel import licence

How to get a parallel import licence for your medicine in the UK, including pharmacovigilance requirements and submitting the application.MR-DC product list is updated in the guidance.

USA

Using Collaboration and AI to Repurpose Already-Approved Medications for New Indications

At first, the idea of repurposing a drug seems so logical. A reasonable person could be forgiven for thinking this is already common practice. Since safety and efficacy have been shown in order to gain FDA approval to use a drug for a specific disease, that logic goes, wouldn’t researchers check to see what other diseases might be treated using such a drug?

Prescription Drug Use-Related Software Output Reviewed in Draft Guidance

The FDA has released a draft guidance on how it intends to determine whether sponsor-provided prescription drug software output should be treated as FDA-required labeling or promotional labeling and how, or if, the corresponding software function should be described in the prescribing information (PI).

ICH Adopts Guideline on Viral Safety Evaluation of Biotechnology Products

The International Council for Harmonisation (ICH) has adopted its Q5A(R2) guideline on viral safety evaluation of biotechnology products.

Innovation in Cell and Gene Therapies Could Be Stifled From Draft Guidance Requirements, Commentors Say

An FDA draft guidance on reporting manufacturing changes in cellular and genetic therapy (CGT) products puts too much emphasis on clinical trials and neglects the benefits and efficacy of bridging studies, according to comments filed by 16 manufacturers and industry. The guidance, “Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products,” proposes to require manufacturers of all investigational and approved CGTs to notify the agency of any changes in manufacturing that might alter the therapy’s safety or efficacy.

Single Trial Can Support FDA Drug Approval, Says Draft Guidance

The FDA has offered greater direction on demonstrating substantial evidence of effectiveness for drugs and biologics, publishing draft guidance on whether a single trial plus confirmatory evidence will suffice for a development program.

FDA Final Guidance Tackles Human Factor Studies for Combination Products

The FDA’s latest final guidance features questions and answers on how to apply human factors (HF) engineering principles when developing combination products, clarifying how the uniqueness of these products affect HF engineering considerations for industry and agency staff. The 14-page document, “Application of Human Factors Engineering Principles for Combination Products: Questions and Answers,” finalizes a draft guidance from February 2016 and should be used alongside the guidances “Applying Human Factors and Usability Engineering to Medical Devices” and “Safety Considerations for Product Design to Minimize Medication Errors,” as well as other FDA product development guidances, advised the agency.

Cybersecurity Final Guidance Details System Considerations for Premarket Submissions

The frequent electronic exchange of health data through wireless, internet and networks along with the cybersecurity threats and vulnerabilities is driver for an FDA final guidance making recommendations for cybersecurity information to be submitted with premarket applications to CDRH and CBER.

Labeling of Ready-to-Use Prescription Drug Injectables Subject of FDA Guidance

Recommendations on labeling of injectable prescription drug product information submitted in an NDA or certain BLAs is the subject of an FDA guidance on dose banding.

FDA Issues Product-Specific Guidelines for Generic Drug Development

The FDA has issued multiple draft and revised product-specific guidances that provide recommendations on the design of bioequivalence studies to support ANDAs and facilitate generic drug product availability.

Untangling Combination Product Regulations Requires More FDA Guidance

The complex process of regulating combination products begins with the FDA’s determination of which center — CDRH, CBER or CDER — will take the lead role in overseeing a product’s development, but even after that determination is made, the way regulations are applied opens up another layer of complexity.“At a high level,” says Bradley Thompson, an attorney at Epstein Becker Green, “the biggest problem the industry faces is that there simply aren’t enough FDA guidance documents that explain the rules with regard to combination products.” Because of how much more labor-intensive it is to have the centers work together, he said, “they do not often come up with guidance to help combination product developers,” leaving combination product developers “guessing.”

FDA issues draft guidance on post-warning letter meetings under GDUFA III

The US Food and Drug Administration (FDA) has published a new draft guidance to help sponsors navigate the post-warning letter meeting process as specified under the latest round of the Generic Drug User Fee Amendments (GDUFA III). The guidance spells out the process for how an eligible facility may request a post-warning letter meeting with FDA, regarding what corrective action the facility is taking to address current good manufacturing practice (cGMP) deficiencies described in the warning letter, how to prepare and submit a complete meeting package and how FDA will conduct the post-warning letter meeting.

Breaking Down the Draft of ICH E6(R3)

In the third revision to its guideline on good clinical practice, ICH E6, the International Council on Harmonisation (ICH) is proposing a full-scale restructuring of the document that has provided a global standard for sponsors, sites and investigators since 1996. In this blog post from Avoca, a WCG company, Karen Harvey, senior director of the Avoca Quality Consortium, outlines the changes in the new ICH draft guideline.

Experts Say Combination Products Can Cause Unique Regulatory Headaches

Drug-device combination products can pose cumbersome regulatory challenges for companies, say regulatory experts, primarily because the product has to comply with two complicated regulatory systems that are not designed to work together. One office — the FDA’s Office of Combination Products (OCP) — has the job of determining which center — CDER, CDRH or CBER — will serve as the lead, applying its specific regulations and procedures, while the other(s) provide a consulting role.

CDER Finalizes Voluntary Consensus Standards for Pharmaceutical Quality Program

The FDA has issued a final guidance outlining a program that allows stakeholders to propose pharmaceutical quality standards for recognition by CDER, providing industry with additional resources for pharmaceutical development and manufacturing.

Dietary Management Critical in IEM Drug Trials, FDA Guidance Says

Optimizing dietary management during drug trials is critical to accurately assessing drug efficacy in clinical trials for inborn errors of metabolism (IEM), the FDA says in a new draft guidance. Dietary management is the core avenue of treatment for a number of IEMs in which specific enzyme mutations prevent the breakdown of dietary components and subsequently lead to toxic metabolites and organ damage. The new eight-page draft guidance says trials that don’t adequately consider and brace for the impact of dietary changes may jeopardize the interpretability of their findings.

Patient Preference, Safety Evaluation, Bioequivalence New Guidance Areas for ICH

The International Council for Harmonisation’s (ICH) governing group announced earlier this month it will begin work on new guidelines in three areas: patient preference, nonclinical safety evaluation for oligonucleotide-based therapies and bioequivalence for modified-release products.

Better Matching of Patients to Oncology Drugs is Goal of New FDA Pilot Project

To better understand the performance of the in vitro diagnostic tests used to identify the right treatment for cancer patients, the FDA has begun a pilot project for CDER-regulated oncology drugs and the corresponding clinical assays.

Form 483 Responses Must Include Adequate Corrective Actions, Says FDA Official

Though there is no regulation requiring they do so, companies that receive an FDA Form 483 should always provide a response in writing that is well-organized, comprehensive and includes adequate corrective actions to addresses deficiencies, says Rebecca Asente, an FDA compliance officer with the Office of Regulatory Affairs. “I’ve received responses that were out of order such that I had to contact the firm for a corrected, organized response package,” Asente remarked during an FDA webinar, What to Expect after an Inspection: 483s, Responses and Beyond, posted to the agency’s YouTube channel.

Drug Facility Remote Inspections is Focus of Draft Guidance

In a new draft guidance, the FDA describes how it requests and conducts voluntary remote regulatory assessments (RRA), an evaluation the agency says it may conduct in lieu of or in support of an inspection.

Expert Says Sample Sizes Need to be Larger to Satisfy FDA Expectations

Manufacturers of drugs and medical devices make several common errors when choosing the sample size for their sampling plan, but selecting too few samples routinely tops the list, according to Steven Walfish, president of Statistical Outsourcing Services.“The most common error I see is the fact that the sample size is too small for the risks that you’re trying to get at,” he said in a recent webinar hosted by FDAnews, a WCG company.

FDA Guidance Shares Quality Considerations for Ophthalmic Drugs

The FDA’s newest draft guidance discusses quality considerations for ophthalmic drugs, including ways to assess impurities, evaluate visible contaminants, design containers and conduct stability studies. The 15-page draft guidance shares ways to evaluate visible particulate matter, extractables and leachables from closed container systems as well as the use of in vitro drug release and dissolution testing for quality control.

Data-Sharing, AI, Collaboration Prioritized in FDA IT Modernization Plan

The FDA’s plan to modernize its IT infrastructure features several improvements that will benefit clinical trials and sponsors, including upgrades to data-sharing and electronic submissions, support for responsible use of AI/machine learning (ML) and increased collaboration between the agency and industry. The strategy for FY 2024 to 2027 acknowledges the growing importance of technology in drug and device development, as well as the challenges that accompany fast-paced scientific progress and innovation. IT-focused upgrades will be needed to keep up with ever-evolving technology and therapeutics, says Vid Desai, chief information officer for the agency’s Office of Digital Transformation.

FDA Guidance Outlines GDUFA III Fee Program Changes

The FDA sketched out how it is implementing the fee structure of the Generic Drug User Fee Amendments of 2022 (GDUFA III) in a final guidance.

FDA Confirms Its Cover Letter Attachments for Generic Submissions Are Voluntary

The use of FDA’s checklist-like cover letter attachments for controlled correspondence and generic drug submissions are voluntary, the agency emphasized in a final guidance.

ICH paper calls for ‘stepwise’ harmonization of RWE

The International Council for Harmonisation (ICH) issued a Reflection Paper outlining a “stepwise” approach to harmonization of real-world data and evidence (RWD/RWE) that includes common operational definitions, general principles for assessment, and best practices for registration of study protocols and results. The ICH Assembly endorsed the Reflection Paper in June 2023, and it is under public consultation until 30 September 2023. Any comments received by that date will be considered for inclusion in the final Reflection Paper, anticipated to be adopted in June 2024.

FDA issues revised site selection model tying surveillance inspections to location

The US Food and Drug Administration (FDA) recently issued an internal Manual of Policies and Procedures (MAPP) for its staff outlining how it will prioritize inspections under its site selection model (SSM) for routine quality related surveillance inspections. The update adds a risk factor for establishments located in countries where there is a “history of violations” related to exports. The update revises a previous version issued in September 2018 to add a “risk factor for establishments related to the compliance history of establishments in the country or region in which an establishment is located.” This can include “the history of violations related to products exported from such country or region that are subject to such regulation.”

FDA Proposes Rule to Replace Medication Guides with Single-Page Info Sheets

The FDA has proposed a rule to require sponsors of all new — and already-approved — outpatient prescription drugs and blood products to create a single-page Prescription Medication Information (PMI) sheet explaining how to use the drug, its benefits and its potential risks in plain, easy-to-understand language.

FDA Requires Updates to ADHD Medication Labeling

Manufacturers of amphetamine and methylphenidate products, a class of stimulant medications used to treat ADHD and other disorders, must update their labeling and prescribing information to “clearly inform” patients, caregivers and healthcare professionals risks associated with these medications. Prescription stimulants can be important options for treating ADHD, binge-eating disorder, and uncontrollable episodes of deep sleep such as narcolepsy, however, even when prescribed to treat a specific condition, their use can lead to misuse or abuse.

User fee hiring: CBER on track while CDER lags

Quarterly data released by the US Food and Drug Administration (FDA) show discrepant hiring patterns for staff at the agency’s drug and biologics centers under the Prescription Drug User Fee Act (PDUFA VII) and Biosimilar User Fee Act (BsUFA III) for the first half of FY 2023. While the Center for Biologics Evaluation and Research (CBER) has achieved 57% of its full year hiring goal under PDUFA, the Center for Drug Evaluation and Research (CDER) is further behind and has filled 34% of the positions it aims to fill this year by the end of the second quarter. CBER’s goal is to hire 132 full time equivalents (FTEs) in FY 2023, while CDER’s goal is to hire 77 FTEs by the end of the fiscal year.

FDA ramps up for transition to QMSR

The US Food and Drug Administration (FDA) is working to finalize its proposal to align its device Quality System Regulation (QSR) with the international standard ISO 13485:2016, creating the Quality Management System Regulation (QMSR). In preparation for the final rule, the agency is readying for the change internally by updating its technology systems, training staff and replacing the Quality System Inspection Technique (QSIT).

FDA Offers Formatting and Content Guidelines for OMORs in Draft Guidance

In a new draft guidance, the FDA offered advice on the format and content of an over-the-counter (OTC) monograph order request (OMOR) — which allows an OTC drug covered by a monograph to be marketed without an approved drug application. Sponsors submit an OMOR to request that the agency issue a final order on whether a drug already is generally recognized as safe and effective (GRASE) or whether a change to the use of a drug is GRASE. OMOR requirements include mandatory electronic submission for five modules — administrative information, summaries, quality, nonclinical study reports and clinical study reports.

New FDORA Provision Allows FDA to Conduct Some Inspections Based on Records Review

In a potentially “game-changing” legislative move, the Food and Drug Omnibus Reform Act of 2022 (FDORA) has given the FDA the option to rely on review of records and other information collected from a manufacturer in lieu of some types of on-site inspections.

FDA encourages RCTs in accelerated approval guidance for oncology

The US Food and Drug Administration (FDA) issued draft guidance on the design of oncology trials for accelerated approval, calling randomized controlled trials (RCTs) – rather than single-arm studies — the “preferred approach” to support accelerated approval.  Sponsors can conduct a single RCT to support accelerated approval and verify clinical benefit or run two trials, one that supports accelerated approval through the use of an early endpoint and one confirmatory trial that is powered to assess a longer-term clinical endpoint, according to the draft guidance.

FDA outlines plan for digital health technologies for clinical trials

The US Food and Drug Administration (FDA) plans to hold at least one public meeting and release several guidances on digital health technologies (DHT) to be used in drug clinical trials by the end of the year. While it has issued guidances on digital health products generally, there is still concern about whether such products are accurate and reliable enough to gather data for the drug development process

FDA issues guidance on submission of pharmacogenomic data

The US Food and Drug Administration (FDA) has issued draft guidance to clarify which pharmacogenomic study findings and data should be included in regulatory submissions for investigational new drug applications (INDs), new drug applications (NDAs) and biologics license applications (BLAs).   The guidance also provides recommendations to sponsors on the format and level of detail for reporting pharmacogenomic data submissions, which will vary based on how the genomic biomarkers are used and the potential risks. When finalized, this new guidance will replace final guidance for industry that FDA published in 2005.

FDA issues guidance on developing long-acting local anesthetics

The US Food and Drug Administration (FDA) has issued draft guidance on the development of local anesthetic products with a prolonged duration of effect that can last for days. The guidance, published is part of a larger effort to reduce the use of opioid analgesic drugs, according to FDA. “Although different local anesthetic drug products have different pharmacokinetic (PK) profiles, in general their effects last a few hours. However, the increasing interest in reducing or eliminating the use of opioid analgesic drug products is leading to development of dosage forms of local anesthetic drug products that prolong the duration of action of the drug product to a period of days rather than hours,” the agency wrote.

FDA Offers Advice on Macular Degeneration Drug Trials

The 8-page draft — which includes recommendations on trial eligibility criteria, efficacy endpoints and trial design considerations — recommends that sponsors consider parallel-group, double-masked trials randomized by patient that aim to show the investigational drug group’s superiority over the control group. Sponsors can also consider an alternative trial approach that uses the same design but shows the investigational drug’s noninferiority to either ranibizumab injection given intravitreally every four weeks, or to aflibercept given intravitreally either every four weeks or eight weeks (after three monthly injections), the agency says.

Industry groups call for changes in ICH M11 guideline on harmonized protocols

In comments to the US Food and Drug Administration (FDA), pharmaceutical industry groups called for revisions to the International Council for Harmonisation’s (ICH) M11 guidance establishing a harmonized template for clinical trial protocols. The groups said the document should be revised to broaden the definition of a protocol, recommended that the use of estimands be justified in the protocol and include more examples of real-world data (RWD). The guidance also includes a template for the format called the “Clinical Electronic Structured Harmonized Protocol (CeSHarP), as well as a set of specifications.

HHS prioritizing FDA labeling, DTC advertising, and compounded drug rules

The US Department of Health and Human Services (HHS) on Tuesday published a list of regulations its agencies will prioritize over the coming year. It includes several rules that the Food and Drug Administration (FDA) will work on to address issues such as patient labeling, conduct of clinical trials and drug compounding. On 22 February, HHS published its semiannual regulatory agenda, which included a number of rules either under development or set to be finalized by FDA, as well as a timetable for expected completion. Notably, several of the rules, including a rule on medication guides, have been listed in the regulatory agenda for multiple years.

CMS Will Require Drugmakers to Pay if Price Hikes Exceed Inflation

Newly released federal guidance details how the government will punish drug companies who hike prices faster than the rate of inflation for some prescription Medicare medicines. Administered by the Centers for Medicare and Medicaid Services (CMS), the Medicare Prescription Drug Inflation Rebate Program requires drug companies to pay Medicare a rebate if they raise their prices for certain Part B and Part D drugs faster than the rate of inflation. CMS will calculate the rebate and the money will be deposited in a supplementary medical insurance trust fund. For Part D drugs, rebates would be retroactive to Oct. 1, 2022. For Part B drugs, the price tracking began on Jan. 1.

FDA On Track with PDUFA VII Goals Centered on DHT-Related Submissions

By the end of March, the Center for Drug Evaluation and Research (CDER)’s Office of Strategic Programs (OSP) will have met its first Prescription Drug User Fee Act (PDUFA) VII goal: enhancing internal systems review of digital health technology (DHT)-related submissions — enabling the agency to better receive and digest submissions that contain reams of data from, for example, wearable devices.

FDA Releases Final guidances on Standardized Format for REMS Documents

Two final documents from the FDA outline a standardized structure and language for risk evaluation and mitigation strategy (REMS) documents to make them more clear and consistent and submissible in Structured Product Labeling (SPL) format.