The U.S. Food and Drug Administration (FDA) has issued a final guidance entitled ‘Evaluation of Therapeutic Equivalence’. This document explains the FDA’s thinking on therapeutic equivalence evaluations and therapeutic equivalence codes. The FDA’s therapeutic equivalence evaluations are listed for multisource prescription drug products approved under the Federal Food, Drug and Cosmetic Act (FD&C Act) in the active section of the ‘Approved Drug Products with Therapeutic Equivalence Evaluations’ (commonly known as the Orange Book). The FDA's message is that drug substitution should be based on demonstrated therapeutic equivalence, supported by robust manufacturing controls, rather than simply matching active ingredients.These therapeutic equivalence evaluations have been prepared to serve as public information and advice to state health agencies, prescribers and pharmacists to promote public education in drug product selection and to foster containment of health care costs.
This guidance finalises the draft guidance of the same title issued in July 2022. To access see: https://www.fda.gov/media/160054/download
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In a second document, currently at draft stage, expands on and clarifies the Agency’s recommendations and expectations regarding the development of delivery devices and container closure systems described in Q.I.4 of the guidance for industry entitled ‘Questions and Answers on Biosimilar Development and the BPCI Act’ as well as the guidance entitled ‘Considerations in Demonstrating Interchangeability with a Reference Product’ for biosimilar and interchangeable biosimilar products.
Here, the FDA is signalling that for biosimilars and interchangeable biosimilars, the delivery system, container closure system and user interface are integral parts of the comparability assessment and must be shown not to adversely affect safety, performance, usability or interchangeability.
This document is titled ‘Biosimilar and Interchangeable Biosimilar Products: Considerations for Container Closure Systems and Device Constituent Parts’. It can be accessed here: https://www.fda.gov/media/193917/download
RSSL can support biosimilar and biologic development with analytical characterisation, comparability, potency and stability testing, alongside specialist technical, GMP and regulatory consultancy.
Life Science & Pharmaceuticals | Training & Consultancy
The guidance is intended to provide industry with answers to frequently asked questions and commonly faced issues that arise during the development of Cellular and Gene Therapy (CGT) products and is intended to help facilitate the development of safe, effective and high-quality CGT products. The document represents common questions directed to the Agency and spans multiple disciplines, including regulatory review, Chemistry, Manufacturing and Controls (CMC), Pharmacology / Toxicology (PT), clinical and clinical pharmacology.
The guidance signals that successful Cell and Gene Therapy development depends on early FDA engagement, strong CMC/manufacturing control and a scientifically justified, risk-based development strategy from Investigational New Drug (IND) through to Biologics License Application (BLA) submission.
The document can be found here: https://www.fda.gov/media/183631/download
RSSL supports cell and gene therapy development with analytical characterisation, method development, validation and testing. Our experts can also provide GMP and regulatory consultancy to help teams navigate development and submission requirements.
Life Science & Pharmaceuticals | Training & Consultancy
The FDA has issued a draft guidance titled ‘Potency Assessment of Active Immunotherapy Products’. This guidance document provides recommendations for developing assays to assess potency as a part of a potency assurance strategy for Active Immunotherapy Products (ACTIMPs). Active immunotherapies aim to treat a pre-existing disease or condition by inducing, stimulating or modulating immune effector cells through the introduction of an antigen (or antigens) associated with that disease or condition to the immune system.
The FDA is signalling that for Active Immunotherapy Products, potency is a critical quality attribute that must be measured using scientifically justified, mechanism-based assays that remain relevant throughout the product lifecycle and support product consistency, comparability and clinical performance.
This guidance does not apply to preventive vaccines for infectious disease indications, bacteriophage products for infectious diseases, live biotherapeutic products, Faecal Microbiota for Transplantation (FMT) products or allergenic products. Considerations related to potential safety concerns associated with ACTIMP product design are outside the scope of this guidance. Sponsors are therefore encouraged to consult with the appropriate product office regarding such matters.
When finalised, this guidance will describe the FDA’s current thinking regarding design, validation and evaluation of potency tests for ACTIMPs. This guidance is intended to supplement the guidance for industry, on Potency Assurance for Cellular and Gene Therapy Products (Ref. 1) with additional advice and considerations specifically for ACTIMPs, including peptide- and-protein based ACTIMPs that are not Cellular or Gene Therapy products (Ref. 2).
The draft is located here: https://www.fda.gov/media/194324/download
RSSL develops and validates bespoke cell-based bioassays to assess biological activity and potency, with expert support available for assay strategy, validation and regulatory expectations.
Life Science & Pharmaceuticals | Training & Consultancy
The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a document titled ‘UK Position Paper on Microbiome-Based Medicinal Products (MBMPs)’.
MBMPs represent an emerging class of therapeutics with the potential to address areas of significant unmet clinical need. The purpose of this position paper is to encourage the development and licensing of these products in the UK.
For pharmaceutical quality professionals, this paper signals that live biotherapeutic and microbiome products will receive the same level of scrutiny applied to other biologics.
The document can be found here: https://www.gov.uk/government/publications/uk-position-paper-on-microbiome-based-medicinal-products-mbmps/uk-position-paper-on-microbiome-based-medicinal-products-mbmps
The FDA has issued a draft guidance for industry entitled ‘Container Closure Systems for Human Drugs and Biological Products’. This document provides guiding principles for evaluating the quality of Container Closure Systems (CCSs) used to package drugs and biological products, for human use. This includes CCSs that are also device constituent parts of combination products and CCSs used to package the drug or biological product constituent parts of combination products.
The FDA is reinforcing that CCSs are critical quality elements that must be scientifically qualified, risk assessed, continuously controlled and demonstrated to protect the product throughout manufacture, storage, distribution and use.
View the draft here: https://www.fda.gov/media/194220/download
RSSL provides container closure integrity, extractables and leachables and packaging assessment to help demonstrate the suitability and performance of packaging systems throughout the product lifecycle.
Life Science & Pharmaceuticals
The Ph. Eur. is updating chapter 3.2.1 ‘Glass Containers for Pharmaceutical Use’.
This chapter establishes the requirements for glass containers used for pharmaceutical products, including vials, bottles, ampoules, syringes and cartridges. It classifies pharmaceutical glass into Type I (borosilicate/neutral glass), Type II (surface-treated soda-lime glass) and Type III (soda-lime glass) according to hydrolytic resistance and provides recommendations on their suitability for different dosage forms.
The revision comes into force during April 2027.
RSSL supports pharmaceutical packaging assessment through material characterisation, pharmacopeial testing, extractables and leachables and container closure integrity testing.
Primary Packaging Testing
Prior to approving an antimicrobial new animal drug application, the FDA must determine that the drug is safe and effective for its intended use in the animal (section 512(d)(1) of the Federal Food, Drug and Cosmetic Act [‘the FD&C Act’]). The Agency must also determine that the antimicrobial drug intended for use in food-producing animals is safe in regard to human health (21 CFR 514.1(b)(8); sections 512(d)(1)(B) and 512(d)(2)(A) of the FD&C Act).
The FDA considers an antimicrobial new animal drug to be ‘safe’ if it concludes that there is reasonable certainty of no harm to human health from the proposed use of the drug in food-producing animals. This document provides guidance for industry to evaluate potential microbiological effects of antimicrobial new animal drugs on bacteria of human health concern as part of the new animal drug application process.
The document outlines a risk assessment approach to evaluate the microbial food safety risks posed by antimicrobial new animal drugs. Within the context of risk assessment, many possible mechanisms to address the development of antimicrobial resistance resulting from the use of antimicrobial new animal drugs in food-producing animals are available to the sponsor. Alternative processes that may be more appropriate to a sponsor’s drug and its intended conditions of use may be used to characterise the microbial food safety of that drug.
With this document, the FDA is reinforcing that approval of antimicrobial products for food-producing animals requires a robust assessment of antimicrobial-resistance risks to human health, supported by high-quality scientific data and a structured risk-based evaluation process.
The document can be accessed here: https://www.fda.gov/media/69949/download
In a new guidance document, the FDA has made recommendations to assist industry in following appropriate human factors and usability engineering processes to maximise the likelihood that new medical devices will be safe and effective for the intended users, uses and use environments. The recommendations in this guidance document are intended to support manufacturers in improving the design of devices to minimise potential use errors and resulting harm. The FDA believes that these recommendations will enable manufacturers to assess and reduce risks associated with medical device use.
With the guidance, the FDA is reinforcing that device safety depends not only on technical performance but also on how real users interact with the device, making human factors engineering, usability testing and use-related risk management essential elements of device development and regulatory submissions.
Read the document here: https://www.fda.gov/media/80481/download
RSSL can support medical device development with specialist technical testing and expertise, alongside training and consultancy to help teams address regulatory, quality and risk-management requirements.
Medical Devices | Training & Consultancy
The European Medicines Agency (EMA) has issued a document titled ‘Guidance and template for industry on implementing: Shortage Prevention Plans’.
The document indicates the relevant type and detail of information for shortage prevention plans, according to the different level of risk, including descriptions of the relevant shortage management measures. The degree of effort, formalisation and documentation for each Shortage Prevention Plan (SPP) - and consequent proposal of shortage mitigating measures - should be proportionate to the identified level of risk for each medicine.
This guidance effectively extends pharmaceutical quality risk management principles beyond product quality and into supply continuity. Inspectors are increasingly likely to examine whether supply chain vulnerabilities have been identified, formally assessed and mitigated using a documented, risk-based approach
The document can be accessed here: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guidance-template-industry-implementing-shortage-prevention-plans-spp_en.pdf
RSSL can support supply resilience through analytical testing, stability studies and technical support, while our consultants can help strengthen quality systems, supplier oversight and risk-based approaches to supply continuity.
GMP & CMC Laboratory Testing | Training & Consultancy
The US Pharmacopeia (USP) will no longer publish and maintain the description and solubility information for drug substances. This information is typically included as a part of the FDA-approved labels of the products, in the ‘Description’ section of the drug label information.
RSSL provides pharmacopeial and analytical testing to support pharmaceutical quality control and evolving compendial requirements.
Pharmacopeial Testing Services
The USP has updated the following chapter: 〈162〉 ‘Diphtheria Antitoxin Potency Testing for Human Immune Globulins’.
USP <162> describes an in vitro cell-based assay for determining the potency of diphtheria antitoxin in plasma-derived human immune globulin products. The method measures the ability of antitoxin antibodies to neutralise the cytotoxic effects of diphtheria toxin on cultured Vero cells. Diphtheria toxin inhibits protein synthesis and causes cell death - however, when neutralised by antitoxin, cell viability is maintained. Cell survival is quantified using an MTT assay, where metabolically active cells convert MTT into a coloured formazan product measured spectrophotometrically at 540 nm. Potency is determined by comparison with a suitable diphtheria antitoxin reference standard and calculation of relative activity using dilution-based analysis.
In a second document, currently at draft stage, expands on and clarifies the Agency’s recommendations and expectations regarding the development of delivery devices and container closure systems described in Q.I.4 of the guidance for industry entitled ‘Questions and Answers on Biosimilar Development and the BPCI Act’ as well as the guidance entitled ‘Considerations in Demonstrating Interchangeability with a Reference Product’ for biosimilar and interchangeable biosimilar products.
Here, the FDA is signalling that for biosimilars and interchangeable biosimilars, the delivery system, container closure system and user interface are integral parts of the comparability assessment and must be shown not to adversely affect safety, performance, usability or interchangeability.
This document is titled ‘Biosimilar and Interchangeable Biosimilar Products: Considerations for Container Closure Systems and Device Constituent Parts’. It can be accessed here: https://www.fda.gov/media/193917/download
RSSL supports biological potency testing and assay development for biopharmaceutical products.
Biopharmaceuticals.
The USP is revising chapter: 〈1030〉 ‘An Introduction to the Biological Assay Chapters -Overview and Glossary’.
USP <1030> provides an overview of biological assays and their role in measuring potency and bioactivity of biologics, vaccines and advanced therapies. It introduces a lifecycle approach encompassing assay development, validation, analysis and ongoing performance verification, while defining key statistical, design and bioassay terminology used throughout the USP bioassay chapter series.
RSSL supports biological assay development, validation and lifecycle testing, including bespoke potency and functional assays.
Biopharmaceuticals.
The European Pharmacopeia (Ph. Eur.) is introducing a new chapter: 2.2.62. ‘Evaporative Light-Scattering Detection’.
Evaporative Light-Scattering detection (ELS detection) is a recognition mode used in liquid chromatography (2.2.29). It allows the detection of substances regardless of whether they contain a chromophore in their structure, provided that they are less volatile than the mobile phase and thermally stable under the analytical conditions employed.
The update appears to modernise and expand the chapter rather than introduce a fundamentally new technique.
The chapter comes into effect in April 2027.
RSSL's analytical scientists can support method development, optimisation, transfer and validation using a broad range of chromatographic techniques.
GMP & CMC laboratory testing.
The Ph. Eur. is updating the chapter 2.2.23. ‘Atomic absorption spectrometry’.
This chapter describes Atomic Absorption Spectrometry (AAS), an elemental analysis technique used to quantify metals and other elements by measuring the absorption of element-specific radiation by free atoms in the gas phase. The chapter covers the scientific principles of AAS and the three main atomisation approaches: flame atomisation, electrothermal atomisation (graphite furnace) and cold vapour/hydride generation techniques for elements such as mercury and hydride-forming elements.
The chapter now provides detailed coverage of flame AAS, graphite furnace (electrothermal) AAS, cold vapour mercury analysis and hydride generation techniques within a single harmonised chapter.
The revised chapter is due to be implemented in April 2027.
2.2.22. ‘Atomic emission spectrometry’ is also under revision.
This chapter describes Atomic Emission Spectrometry (AES) - an analytical technique used to identify and quantify elements by measuring the light emitted by excited atoms and ions in a flame. The chapter focuses on flame-based AES, while ICP-AES (ICP-OES) is covered separately in Ph. Eur. 2.2.57. AES is particularly suitable for determining alkali and alkaline earth metals such as sodium, potassium, calcium, lithium, barium and caesium, typically at milligram-per-litre concentrations.
RSSL provides elemental and impurity testing using specialist analytical techniques to support pharmaceutical quality control and regulatory requirements.
Pharmacopeial Testing Services.
The European Pharmacopeia also has chapter 5.1.4. ‘Microbiological Quality of Non-Sterile Pharmaceutical Preparations and Substances for Pharmaceutical Use’ in revision, along with the test method chapters 2.6.12 and 2.6.13.
RSSL provides GMP microbiology testing for pharmaceutical raw materials and products, alongside method verification.
Microbiological analysis.
The Ph. Eur. is introducing a new chapter 2.7.38 ‘Bacteriophage potency determination’.
This general chapter describes an assay for the determination of potency as a quality attribute of a replicative bacteriophage (phage)-containing preparation, i.e. a seed lot, in-process sample, active substance or final product according to general chapter 5.31. ‘Phage therapy medicinal products’. The provisions of this chapter do not exclude the use of other approaches for potency determination acceptable to the competent authority.
The chapter comes into effect in April 2027.
RSSL can support emerging biopharmaceutical products with analytical method development, validation and microbiological testing tailored to product requirements.
Biopharmaceuticals.
As we reported last month, the European Pharmacopoeia Commission has issued a new revised general chapter on alternative microbiological methods, supporting advancement of the field by modernising quality standards. The revised chapter 5.1.6. ‘Alternative Methods for Control of Microbiological Quality’ was published in Issue 13.2 of the Ph. Eur.
Since the earlier announcement, further details have emerged.
The Commission has updated the description of technologies to include modern approaches, removing outdated quality control methods. It means the framework offers a clearer definition of the responsibilities of suppliers and those using the chapter.
This change aligns with an earlier publication from the Eur. Ph. In January, it published a new general chapter on quality of data 5.38. The framework aids stakeholders with digitalisation during pharmaceutical quality decision-making.
As demand increases for alternative microbiological methods, especially for those that can provide rapid, simultaneous viable quantitation and microbial identification, among other technologies, AI offers potential to accelerate the field. Yet upfront cost, as well as the limited pool of qualified operators, are among the main factors limiting its widespread use.
Moreover, in the current revised chapter, multiple validation strategies, based on a risk assessment, have been added to enhance its implementation. For example, leveraging relevant existing data and enabling multiple implementation activities to be assessed simultaneously.
This revised general chapter comes into force on 1 April 2027.
The USP is issuing a new chapter: <1059> ‘Excipient Performance’.
The purpose of this chapter is to explain how excipients may be used in formulations and how they relate to compendial specifications, Performance-Related Properties (PRPs), Critical Material Attributes (CMAs), Critical Quality Attributes (CQAs) of the drug product, and Quality by Design (QbD) principles that aid in their selection and control.
Excipients are used in virtually all drug products and are essential for drug product manufacturing and performance. To ensure drug products are with consistent quality, the excipients must be appropriately specified. Excipients used in drug products are typically manufactured and supplied in compliance with compendial standards.
However, the impact of excipient properties on the quality and performance of a drug product may be unique for each formulation and process and could depend on properties of excipients that are not evaluated in USP or NF monographs and which may vary from supplier to supplier and batch to batch.
The chapter comes into force on 1 December 2026. Access to this chapter requires a subscription.
RSSL provides raw material and analytical testing to assess excipient quality and variability, with expert consultancy available to support risk-based material and supplier qualification strategies.
GMP & CMC Laboratory Testing | Training & Consultancy
The USP is updating chapter 〈561〉 ‘Articles of Botanical Origin’. The chapter is open for comments.
USP <561> provides guidance for the sampling, testing and quality assessment of botanical materials used in medicines and supplements. It describes procedures for representative sampling, foreign matter assessment, ash values, extractives, starch, volatile oils, water content, aflatoxins, pesticide residues and elemental impurities. A significant update is the addition of a new Polycyclic Aromatic Hydrocarbons (PAHs) section, introducing limits for benzo[a]pyrene and PAH4 contaminants and a validated GC-MS method for their determination. The chapter aims to ensure the identity, purity, safety and quality of botanical materials throughout their lifecycle.
The chapter has undergone a major rewrite.
RSSL provides specialist analytical testing for pharmaceutical materials and contaminants using a range of analytical techniques.
GMP & CMC laboratory testing.
While this Regulatory Round-up gives you a broad snapshot of changes across the pharmaceutical landscape, our quarterly Key GMP Regulatory Updates webinar offers the chance to go deeper on what matters most for your quality systems.
