‘Advanced manufacturing’ is a term for an innovative pharmaceutical manufacturing technology or approach that has the potential to improve the reliability and robustness of the manufacturing process and increase timely access to quality medicines.
The document can be found here: https://www.fda.gov/media/184825/download
Microbiological quality - botanical origin
The United States Pharmacopeia (USP) has issued a draft chapter for comment entitled ‘Ensuring Microbiological Quality of Articles of Botanical Origin’.
This general chapter provides information on practices to prevent, as well as methods to treat, the microbial contamination of articles of botanical origin. The general chapter ‘Manufacturing Practices for Dietary Ingredients’ 〈2740〉 defines contamination as ‘the undesired introduction of a substance of a biological (including allergenic), chemical (including radiological), or microbiological nature, or foreign matter, into or onto a raw material, another ingredient, in-process material, or dietary ingredient during production, sampling, packaging, repackaging, storage or transport’.
The information is not limited by the regulatory framework - microbiological quality is relevant to articles of botanical origin, whether components of conventional food products, dietary supplement products, or over the counter (OTC) drug products.
The chapter can be viewed via the Pharmacopeial Forum (requires registration).
In vitro diagnostics performance evaluation.
The British Standards Institute (BSI) has issued a document to assist those involved with in vitro diagnostics.
Performance evaluation is a critical part of the verification and validation of product performance and is recorded in the supporting technical documentation required to place an in vitro diagnostic device (IVD) on the EU market. The requirements for performance evaluation are described within Chapter VI of the Regulation on in vitro diagnostic medical devices (EU 2017/746) (IVDR) and supported by Annexes I, II, III and XIII.
The guidance document aims to aid users through the regulations (registration required): https://pages.bsigroup.com/l/35972/2023-12-11/3t7656n
Requests for expedited review of new drug application
The U.S. FDA’s Office of Pharmaceutical Quality (OPQ) has published a revised Manual of Policies and Procedures (MAPP) entitled ‘Requests for Expedited Review of New Drug Application and Biologics License Application Prior Approval Supplements Submitted for Chemistry, Manufacturing, and Controls Changes’.
To access: https://www.fda.gov/media/72405/download?source=email&utm_source=substack&utm_medium=email
Medical device regulations
The BSI has issued a document to assist those involved with medical devices, focusing on the quality system.
Both ISO 9001:2015 and ISO 13485:2016 have gone through their first standard review period to be reconfirmed for another five-years. These two standards for Quality Management Systems (QMS) have different structures and differences in the definition of risk and other terms.
There are many different requirements with which in vitro diagnostic manufacturers must comply to place products on the market. At the core of most of these requirements is a fundamental need to have a good QMS in place.
In the paper, the BSI considers how these standards co-exist and what developments are being discussed. The intent of this document is to provide insight into some of the differences and similarities between the standards, to allow organisations to understand how they can continue to work together without undue burden to their systems.
The guidance document aims to aid users through the regulations (registration required): https://pages.bsigroup.com/l/35972/2023-12-08/3t75yk8
A second paper looks at how the quality system can be developed: https://pages.bsigroup.com/l/35972/2023-12-07/3t75vhg
Volumetric analysis
The USP is revising the chapter 〈31〉 Volumetric Apparatus. This proposal is based on the version of the chapter official as of November 1, 2020. The potential changes are:
1. The clarification that a calibration temperature of 27° C is also performed in other countries that have adopted that reference temperature. Temperature correction might be required when ambient temperature differs from the reference temperature
2. The calibration of volumetric apparatus to ensure the degree of precision required. Frequency of calibration is risk-based and defined in the user’s manual quality management system
3. The incorporation of reference to the new chapter ‘Use and Calibration of Volumetric Apparatus’ 〈1331〉 to provide a theoretical basis for calibration and examples
4. The provision of alternatives when the limits of error are not met or not suitable at the conditions of use
5. Adding a new Table 1 to categorise the volumetric apparatus accuracy classes and the applicable external updated references
6. Updating terminology to the ‘International Vocabulary of Metrology’ [VIM; (Joint Committee for Guides in Metrology, JCGM) 200] for consistency with equivalent public standards. For example, the section ‘Standards of Accuracy’ formerly containing ‘capacity tolerances’ is proposed to be changed to ‘Limits of Error’ (or maximum permissible errors). Limits of error have been defined
7. The introduction of considerations for Piston-Operated Volumetric Apparatus (POVA) in several paragraphs where appropriate. The limits of error for POVAs are included in new columns added to pipettes in Table 3 (0.5 mL) and burettes in Table 4 (5 mL)
8. For plastic volumetric apparatuses, the introduction of temperature correction and equilibration, as well as limits of error
9. Specific references to applicable ISO and American Society for Testing and Materials (ASTM) standards introduced in the tables for limits of error
In addition, the USP is proposing 〈1331〉 Use and Calibration of Volumetric Apparatus, as a new chapter, to provide guidelines on methods validating the original calibration of volumetric apparatus described in Volumetric Apparatus 〈31〉, their appropriate usage and for periodic recalibrations as needed.
FDA Global Unique Device Identification Database
The U.S. Food and Drug Administration (FDA) issued minor updates to this final guidance ‘Global Unique Device Identification Database (GUDID) - Guidance for Industry and Food and Drug Administration Staff’.
This update reflects upcoming changes to the Global Medical Device Nomenclature (GMDN) field in GUDID and other minor clarifications. The FDA will be removing FDA Preferred Term (PT) Codes from GUDID. These are no longer necessary as GMDN Codes can now be accessed and used for free.
The FDA will let users know when the changes to GUDID are implemented. Once the FDA PT Codes are removed, GUDID users will only be able to use GMDN Codes.
To view: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/global-unique-device-identification-database-gudid
AI in medical devices and in vitro diagnostics
The BSI has issued a document to assist those involved with medical devices and in vitro diagnostics, focusing on artificial intelligence (AI).
As AI methods have already been implemented in different industries, such as in the automotive sector through the use of AI Computer Vision and consumer products that harvest Natural Language Processing (NLP) algorithms, considerations are raised on the ethical and trustworthy aspects of AI.
The BSI has witnessed the rapid growth of the implementation of AI in medical devices and in vitro diagnostics. Although strict regulatory frameworks, as well as standards, exist for such industries, they were not designed to address AI specific challenges.
This is the basis for the new paper (registration required): https://pages.bsigroup.com/l/35972/2023-12-08/3t75yrv
Marketing application content
The U.S. FDA has issued a new guidance document titled ‘Standardized Format for Electronic Submission of Marketing Application Content for the Planning of Bioresearch Monitoring [BIMO] Inspections for Center for Drug Evaluation and Research (CDER) Submissions.’ The guidance outlines how companies should submit standardised data to the FDA to assist in planning and conducting BIMO inspections.
See: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/standardized-format-electronic-submission-nda-and-bla-content-planning-bioresearch-monitoring-bimo?source=email&utm_source=substack&utm_medium=email
Quality management
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has published an updated Q9(R1) Annex 1- Q8/Q9/Q10 Questions & Answers (R5) related to ICH Q9(R1) Quality Risk Management (QRM).
The Q&As have been updated by removing outdated text and rephrasing in view of the implementation of ICH Q8, Q9 and Q10, with minor additions to address content gaps in the document. Furthermore, slight edits have been made to improve the readability of the document.
This revised document clarifies key aspects of quality system implementation to help manufacturers ensure consistent product quality throughout the drug development and manufacturing process.
See: https://database.ich.org/sites/default/files/ICH_Q9%28R1%29_Annex_1_Q8Q9Q10_QAs%28R5%29_1030.pdf
In addition, ICH has updated its Q9(R1) training materials: https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Fadmin.ich.org%2Fsites%2Fdefault%2Ffiles%2Finline-files%2FICH_Updated_Q8Q9Q10_Training_Materials_2024_0804_0.pptx&wdOrigin=BROWSELINK
FDA – Real World Evidence
The U.S. FDA (via CDER) has announced the creation of the CDER Center for Real-World Evidence Innovation (CCRI). The new centre is tasked with coordinating, advancing, and promoting the use of real-world data (RWD) and real-world evidence (RWE) in regulatory decision-making within CDER.
For details, see: https://www.fda.gov/drugs/drug-safety-and-availability/cder-establishes-new-center-real-world-evidence-innovation?source=email&utm_source=substack&utm_medium=email
EU GMP Annex 1
The Australian Therapeutic Goods Administration (TGA) is to incorporate EU GMP Annex 1 during quarter 1 of 2025.
Bioanalytical Method Validation for Biomarkers
The US FDA has released a final guidance document ‘Bioanalytical Method Validation for Biomarkers’.
This guidance helps sponsors of Investigational New Drug (IND) applications and applicants of New Drug Applications (NDAs) (and others) to validate bioanalytical methods used to evaluate biomarker concentrations. This guidance can also inform the development of bioanalytical methods used for the analysis of biomarker concentrations in nonclinical study samples.
For details see: https://www.fda.gov/media/185276/download
Developing Drugs for Optical Imaging
The US FDA has announced the availability of a draft guidance for industry entitled ‘Developing Drugs for Optical Imaging’. The purpose of this guidance is to provide recommendations regarding clinical trial design features that support the development and approval of optical imaging drugs that are used in conjunction with imaging devices and intended as intraoperative aids for the detection of pathology (such as tumours or to enhance the conspicuity of normal anatomical structures).
The guidance can be found here: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/developing-drugs-optical-imaging
