#FDA Tag

26 Jun

Posted at 10:58h in Blog

The draft document “Data Integrity for In Vivo Bioavailability and Bioequivalence Studies” was published on the US FDA website at the beginning of April 2024. The document aims to assist applicants and marketing authorisation holders on achieving and maintaining data integrity for the clinical and bioanalytical part of bioavailability (BA) and bioequivalence (BE) studies for INDs (investigational new drug applications) submission, NDAs (new drug applications), ANDAs (abbreviated new drug applications), for the bioanalytical part of the clinical studies of BLAs (biologic licence applications) as well as for supplements and amendments to these marketing authorisations.

In addition, the recommendations in this guidance apply to the bioanalytical portion of nonclinical studies. The FDA also encourages applicants and testing sites to take these recommendations into consideration when conducting in vitro, pharmacology and toxicology studies.

 

SOURCES:

https://www.fda.gov/media/177404/download

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26 Jun

Posted at 10:50h in Blog

The draft guidance document “Handling and Retention of Bioavailability and Bioequivalence Testing Samples” is being distributed at March 2024

The guidance is intended to provide recommendations for study sponsors and/or drug manufacturers, contract research organizations (CROs), site management organizations (SMOs), clinical investigators, and independent third parties regarding the procedure for handling reserve samples from relevant bioavailability (BA) and bioequivalence (BE) studies, as required by 21 CFR 320.38 and 320.63.

The guidance highlights

  1. how the test article and reference standard for BA and BE studies should be distributed to the testing facilities,
  2. how testing facilities should randomly select samples for testing and material to maintain as reserve samples,
  3. how the reserve samples should be retained
  4. addresses the requirement at 21 CFR 320.38 (c) to retain sufficient quantity of reserve samples to allow FDA to perform five times all the release tests required in an application or supplemental application
  5. describes the conditions under which the Agency does not generally intend to take enforcement action against an applicant or CRO for retaining less than the quantity of reserve samples of the test article and reference standard that were used in the BA or BE study as specified in 21 CFR 320.38(c)

The guidance also clarifies the points addressed in §§ 320.38 and 320.63.

 

SOURCES:

https://www.fda.gov/media/71393/download

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03 Apr

Posted at 10:37h in Blog
  • FDA has published the draft guidance “Conducting Remote Regulatory Assessments Questions and Answers Draft Guidance for Industry” to describe the Agency’s current thinking on the use of remote regulatory assessments (RRAs). FDA has used RRAs to conduct surveillance, reduce risk, meet critical public health needs, and help maximize compliance of FDA-regulated products. This draft guidance provides answers to frequently asked questions about what RRAs are, when and why FDA may use them, and how FDA may conduct them, among others.

    The term “RRA”, as defined in the Question and Answers section, include activities for which the FDA may use different terminologies, such as “remote interactive evaluations” and “remote record reviews“. RRAs were mainly used to support submissions or applications assessments of FDA-regulated products and to reduce delays.

    In the presence of travel restrictions during the COVID-19 pandemic, FDA utilized RRAs to assess establishments and their compliance with applicable FDA requirements.

    Based on this experience, FDA has noted the value of RRAs and concluded that, under certain circumstances, they should be retained for some scenarios outside the COVID-19 pandemic for all types of FDA-regulated products.

    The Agency is also issuing this guidance to promote greater consistency in the way RRAs are conducted, explaining the processes for responding to an RRA request and outlining the factors to consider in assessing whether an establishment has responded timely and appropriately to a mandatory request.

    SOURCES:

    https://www.fda.gov/media/160173/download

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19 Dec

Posted at 16:34h in Blog

The U.S. Food and Drug Administration (FDA) has organized a stakeholder call to discuss the DSCSA implementation, which took place on 29 November 2023.

The Drug Supply Chain Security Act (DSCSA) drug supply chain security requirements, ten years after its implementation, are intended to improve the FDA’s ability to detect and remove potentially dangerous drugs, whether: counterfeit, stolen, contaminated or otherwise, from the supply chain.

Among the topics covered:

  • 10-year anniversary of DSCSA implementation
  • Stabilization period and expectations for trading partners to achieve interoperable, electronic tracing of products at the package level
  • Recent key guidances for industry related to supply chain security requirements
  • Looking ahead

Also in late November, the FDA announced that the CDER NextGen Portal (CDER NextGen) includes a DSCSA portal that enables the FDA and trading partners to communicate when the FDA requests information related to investigations of suspect or illegitimate products or during a recall.

The DSCA portal is used to:

  • Confirm basic information and points of contact for trading partners
  • Notify trading partners when they have messages from the FDA
  • Enable trading partners to respond to FDA messages and upload documents

Additionally, the DSCSA enables to:

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04 Oct

Posted at 16:14h in Blog

After the FDA had already published an initial discussion paper addressing Artificial Intelligence (AI) in the manufacturing of medicinal products, in early 2023, the EMA issued a draft reflection paper outlining the current thinking on the use of artificial intelligence (AI) to support the safe and effective development, regulation and use of human and veterinary medicines, on 19 July 2023.

This paper reflects on principles relevant to the application of AI and machine learning (ML) at any step of a medicines’ lifecycle, from drug discovery to the post-authorisation setting and reports the experience of the EMA in this context, in which scientific knowledge is rapidly evolving.

Recently the success of ChatGPT and related reporting have made the topic of Artificial Intelligence accessible to a wide audience.

 

General considerations

In general, it is mentioned that AI and ML, if used correctly, can effectively support the acquisition, transformation, analysis and interpretation of data within the medicinal products lifecycle.

A risk-based approach to the development, implementation and performance monitoring of AI and ML tools should enable developers to proactively define the risks to be managed during the life cycle of AI and ML tools.

AI and ML tools, when used properly, can effectively support the acquisition, transformation, analysis and interpretation of data within the medicinal product lifecycle. Section 5 of the document lists some guidelines and documents that may provide useful recommendations for implementing AI/ML applications.

It is essential to highlight that the marketing authorisation applicant or MAH is responsible for ensuring that the algorithms, models, datasets, etc. used are fit for purpose and meet ethical, technical, scientific and regulatory standards.

 

Content of the document

The document addresses the following topics:

  • AI in the lifecycle of medicinal products
    • Drug discovery
    • Non-clinical development
    • Clinical trials
    • Precision medicine
    • Product information
    • Manufacturing
    • Post-authorisation phase
  • Regulatory interactions
  • Technical aspects
    • Data acquisition and augmentation
    • Training, validation, and test data
    • Model development
    • Performance assessment
    • Interpretability and explainability
    • Model deployment
  • Governance
  • Data protection
  • Integrity aspects
  • Ethical aspects and trustworthy AI

 

Conclusion

The quickly developing field of AI and ML shows great promise for enhancing all phases of the medicinal product lifecycle.

Finally, the use of AI in the lifecycle of medicines should always comply with existing legal requirements, considering ethics and its underlying principles, and with due respect for fundamental rights. A human-centred approach should be adopted in the development and use of AI and ML.

SOURCES:

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04 Oct

Posted at 16:08h in Blog

The Mutual Recognition Agreement (MRA) between Switzerland and the United States in Good Manufacturing Practice (GMP) for medicinal products has entered into force from 27 July 2023.

This agreement in principle establishes a mechanism whereby each country recognises GMP inspections carried out by the regulatory authority of the other, i.e. Swissmedic for Switzerland and the Food and Drug Administration (FDA) for the United States.

Both authorities are thus able to mutually use GMP inspections and their results in order to avoid duplicate inspections.

A significant aspect of this MRA is that it is not only limited to human medicines, but also includes veterinary medicines

In addition to the FDA and Swissmedic, the Office of the U.S. Trade Representative and the State Secretariat for Economic Affairs of Switzerland had also signed the agreement. These institutions play an important role in facilitating negotiations and cooperation between the two nations to ensure the proper implementation of the agreement.

The Mutual Recognition Agreement is based on the Food and Drug Administration Safety and Innovation Act, enacted in 2012, which allows the FDA to enter into agreements with other regulatory authorities to recognise inspections performed by them. This regulatory environment has created a favourable environment for international collaboration and mutual exchange of information.

SOURCES:

https://www.swissmedic.ch/swissmedic/en/home/news/mitteilungen/inkrafttreten-mra-swissmedic-fda.html

 

 

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19 Jun

Posted at 15:13h in Blog

This guidance, published in March, is aimed at all those involved in the regulatory submission of medicinal product data. It supports the development and implementation of the International Organization for Standardization (ISO) Identification of Medicinal Products (IDMP) standards for substances, terminologies and other information used throughout the medicinal product development lifecycle worldwide.

The purpose of these standards is to make the international exchange of medicines information between stakeholders more accurate, complete, and consistent.

The five IDMP standards and corresponding technical specifications, were developed within the ISO network member organizations. The standards, originally published in 2012 by ISO, provide a framework (data models, terms, definitions, etc.) to uniquely identify and describe medicinal products with consistent documentation and terminologies to enable reliable exchange of product information between global regulators, manufacturers, suppliers, and distributors.

The FDA supports these standards for the identification and description of marketed non-investigational medicinal products, with the goal of harmonizing the standards for the international exchange of medicinal product data.

This guidance serves as a guidance document made available by the FDA and contains helpful but nonbinding recommendations.

SOURCES:

FDA Guidance “Identification of Medicinal Products – Implementation and Use“.

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29 Jun

Posted at 16:28h in Blog

The U.S. Food and Drug Administration (FDA) has updated (Revision 1) its Guidance for Industry on Out-of-Specification (OOS) Results. The first version of the document was dated October 2006.

The guide follows a step-by-step approach consisting of three main phases for investigating OOS test results

  • LABORATORY INVESTIGATION
  • FULL-SCALE OOS INVESTIGATION
  • CONCLUDING THE INVESTIGATION

The process outlined in the text follows quite closely the requirements laid out in 21 CFR part 211.

Definition

The definition of “OOS” has not changed.

«the term “OOS results” includes all test results that fall outside the specifications or acceptance criteria established in drug applications, drug master files (DMFs), official compendia, or by the manufacturer.  The term also applies to all in-process laboratory tests that are outside of established specifications.»

Comparison with the 2006 version

The revision of the guideline contains some formal adjustments from the previous version, and also focuses on updating references to other FDA relevant guidelines and regulatory requirements (USP chapters, CFR paragraphs, etc.)

In addition, the new text contains some clarifications or rewordings from the 2006 edition, the following changes are worth mentioning:

  • section IV.C.2.: the wording on “Outlier Tests” has been amended as follows:
  • Version October 2006: “Occasionally, an outlier test may be of some value in estimating the probability that the OOS result is discordant from a data set, and this information can be used in an auxiliary fashion, along with all other data from the investigation, to evaluate the significance of the result.”
  • Version May 2022: “Occasionally, an outlier test may be of some value in understanding how discordant from a data set a result is, but can be used solely in an informational capacity in the course of an investigation to determine the distance of a result from the mean.”
  • Section V.B. – Cautions: has been divided into three subsections:
  1. Averaging results from multiple sample preparations from the original sample
  2. Averaging results from same final sample preparation
  3. Borderline results that are within specification

Both versions of the guideline can be downloaded from the FDA homepage.

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