Pharma/Biotech – USA, Europe Regulatory News, April 2023 Vol. 1

USA

FDA Issues Guidance on ISO Data Standards for Medicinal Products

As part of its efforts to harmonize with international standards for exchange of medicinal product data, the FDA has issued a final guidance on the use of five International Organization for Standardization (ISO) Identification of Medicinal Products (IDMP) standards.

ICH Finalizes S12 Guideline Covering Gene Therapy Products

The International Council for Harmonization (ICH) has finalized a new guideline covering nonclinical considerations for gene therapies, setting the stage for individual ICH member nations to accept and release their own versions of the guideline.

FDA Guidance Advises RCTs for Oncology Drugs Seeking Accelerated Approval

Sponsors of new oncology drugs and biologics that aim to apply for Accelerated Approval (AA) should use a randomized controlled trial (RCT) design rather than a single-arm trial in most cases, the FDA advises in new draft guidance issued last week.

Guidance details review process for pediatric research not approvable by an IRB

The US Food and Drug Administration (FDA) last week issued draft guidance offering insights to sponsors and institutional review boards (IRBs) on the process for referring research involving children in cases where such research would not normally be approvable by an IRB. In such cases, an IRB may refer the study to FDA or the Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP). Conducting pediatric clinical trials is a sensitive matter, and researchers and regulators must be even more cautious when they are involved in clinical trials or other regulated human subjects research. Typically, if a trial puts a patient at any significant risk, an IRB must oversee the study to ensure the interests of patients are addressed.

FDA Publishes Final Guidance on Meaning of ‘Suspect’ and ‘Illegitimate’ in DSCSA

The FDA clarified the agency’s interpretations of what is meant by “suspect” and “illegitimate” products in the Drug Supply Chain Security Act (DSCSA) in a final guidance.

FDA Shares Latest Thinking on Electronic Systems, Signatures and Records in Trials

The FDA offers recommendations for using electronic systems, records and signatures in clinical trials, including advice on validation, in a draft guidance

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 Offers Guidance on Potency Assays for Antibodies That Target Viral Proteins

A new draft guidance from the FDA offers drug sponsors recommendations for developing potency assays for every stage of the lifecycle of monoclonal antibodies (mAbs) that directly target viral proteins.

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.

Industry requests more information from FDA on dosage and administration labeling

While the US Food and Drug Administration’s (FDA) latest draft guidance on improving the consistency of information in the dosage and administration section of prescription drug labeling is significantly larger than an earlier guidance issued in 2010, industry stakeholders said they wanted more information from the agency on how labeling of specific cases should be handled. FDA’s draft guidance on improving development of the dosage and administration section of drug labeling is written to inform industry on required and recommended information that is “particularly critical to the safe and effective use of the drug,” such as the dosage range, starting or loading dose, dosage, titration schedule, maximum recommended dosage and duration, effectiveness, and concomitant therapy information, the agency said.

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.

EUROPE

EMA Highlights Trial Innovation, Real-World Data Advances

The European Medicines Agency (EMA) reported “remarkable” progress despite the pandemic in a mid-point assessment of its “Regulatory Science Strategy to 2025” to build a more adaptive regulatory system that will encourage innovation including advances in clinical trials and a new real-world data (RWD) network. The 65-page report, which looks at progress made from March 2020 to December 2022, notes the launch of the EU’s Clinical Trials Information System, which went live as a searchable public website in January 2022. The agency also launched the Accelerating Clinical Trials initiative to help develop the EU as a center for innovative clinical research.

Rules for the implementation of Council Regulation (EC) No 297/95 on fees payable to the European Medicines Agency and other measures

EMA published Revised implementing rules to the Fee Regulation as of 1 April 2023. This includes marketing authorization, variation, annual fee, inspection fee.

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).

Explanatory note on general fees payable to the European Medicines Agency

This explanatory note is meant as a guidance note only. Changes introduced in this version: Increase in the level of fees other than administrative fees to adjust for an inflation rate of +10.4% and rounding off to the nearest EUR 100, Increase in the level of all administrative fees to adjust for an inflation rate of +10.4% and rounding off to the nearest EUR 10.

EMA Q&A addresses submission of data elements for raw data pilot

The European Medicines Agency (EMA) this week issued a question-and-answer guidance to address sponsors’ questions on its pilot testing the review of raw clinical trial data for marketing authorization applications (MAAs) and post-authorization applications. EMA issued an updated guidance on the pilot in October. The purpose of the pilot is to “investigate the benefits of having access to raw data from regulatory submissions to support the scientific assessment of medicinal products and to identify the associated operational, resource and technological needs.”

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.