This section of the U.S. Code of Federal Regulations was revoked by the FDA in August 2020. It previously prescribed specific culture-based and indicator-cell assays for mycoplasma detection in live virus vaccines.
It ensures that each batch of a drug product labeled as sterile or pyrogen-free is confirmed free from microbial contamination and endotoxins before it reaches patients.
In practice, §610.13 serves as a fundamental purity safeguard in biologics regulation, requiring manufacturers to demonstrate that licensed products are essentially free of extraneous material..
Under 21 CFR § 610.13(b), each lot of a licensed biological product intended for injection must be tested for pyrogenicity
21 CFR Part 11 sets the criteria under which the FDA accepts electronic records and electronic signatures as equivalent to paper records..
21 CFR Part 211 establishes the minimum CGMP requirements for the preparation of finished pharmaceutical products for human use.
ASTM E2834 is a standard guide that provides recommended practices for nanoparticle tracking analysis (NTA). It does not prescribe mandatory acceptance criteria or serve as a compendial test method.
Provides the core scientific and regulatory guidance for biosimilar development in the EU, complementing the legislative framework for authorizing biosimilars
EMA Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products (GTMPs) (EMA/CAT/80183/2014) sets EU expectations across the full lifecycle for GTMPs under the ATMP framework.
Ph. Eur. 2.2.3 Potentiometric determination of pH is the official European Pharmacopoeia method used when a monograph requires pH testing.
Ph. Eur. 2.2.35 Osmolality defines the official European Pharmacopoeia procedure for determining the osmolality
This chapter describes the harmonized compendial method for verifying that the volume of liquid that can be withdrawn from a parenteral container meets or exceeds the nominal volume stated on the label under practical conditions of use.
This is an informational, non-mandatory chapter that provides a framework for validating and implementing alternative microbiological methods.
https://www.who.int/publications/m/item/annex-3-mRNA-vaccines-trs-no-1039
This final guidance provides recommendations for the development of human gene therapy (GT) products for rare diseases
This FDA guidance provides a framework for predicting, detecting, and managing the risk of unwanted immune responses to therapeutic protein products.
Explains how FDA determines whether two human gene therapy products are the “same drug” for purposes of orphan-drug designation and the 7-year orphan-drug exclusivity.
It introduces the Potency Assurance Strategy (PAS), a comprehensive, lifecycle-based approach grounded in quality risk management.
This 2011 final guidance (still in effect) provides recommendations for developing, implementing, and validating potency assays for cellular and gene therapy (CGT) products.
This FDA guidance describes how to demonstrate that a proposed biological product is biosimilar to a licensed reference product.
This final guidance outlines FDA’s expectations for aseptic manufacturing of sterile drug products, providing recommendations on facility design, environmental controls, personnel practices, equipment qualification, and process validation.
The FDA Guidance for Industry, Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice, is a foundational document that outlines the agency’s current thinking and cGMP expectations for manufacturing sterile drugs.
This U.S. Food and Drug Administration (FDA) guidance provides recommendations for testing for Replication-Competent Retrovirus (RCR) in retroviral vector-based gene therapy products.
Final guidance stating FDA’s current thinking on developing and regulating human drug products (including biologics) when a nanomaterial is present in the finished dosage form.
This guidance, issued by the U.S. Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER), outlines the Chemistry, Manufacturing, and Control (CMC) information required for a human gene therapy Investigational New Drug Application (IND).
ICH Q14 is a harmonized guideline providing a comprehensive, science- and risk-based framework for developing analytical procedures.
ICH Q2(R2) is the modernized harmonized guideline for validating analytical procedures, finalized in parallel with its companion guideline, ICH Q14.
ICH Q4B Annex 14 formally declares that the Bacterial Endotoxins Test (BET) procedures in the European Pharmacopoeia (EP), Japanese Pharmacopoeia (JP), and United States Pharmacopeia (USP) are scientifically equivalent and interchangeable in the ICH regions.
ICH Q5C is the harmonized guideline for stability testing of biotechnological and biological products.
ICH Q5E provides the scientific framework for assessing whether a biotechnological or biological product remains highly similar before and after a manufacturing process change.
ICH Q6B is a harmonized framework for establishing and justifying specifications for biological/biotechnological products.
ICH Q8(R2) sets out harmonized principles for the pharmaceutical development section of regulatory submissions, with an emphasis on Quality by Design (QbD)
ISO 22412:2025 (Edition 3) modernizes the ISO standard for DLS, expanding the 2017 framework to include multi-angle and imaging DLS methods, enhanced treatment of concentrated suspensions, cross-correlation and new backscatter/ polarisation modes, and incorporation of “good practice” material previously in ISO TR 22814.
The BET detects or quantifies endotoxins from Gram-negative bacteria in parenteral pharmaceuticals and other materials where endotoxin control is required.
JP 6.06 is harmonized with USP <790> and Ph. Eur. 2.9.20 under the Pharmacopoeial Discussion Group (PDG), ensuring globally aligned requirements for visible particle testing in parenteral preparations.
The Minimum Information for Publication of Quantitative Digital PCR Experiments (dMIQE) guidelines, first published in 2013 and revised as dMIQE2020, are community-developed best practice standards for reporting digital PCR (dPCR) studies.
Ph. Eur. Chapter 2.2.1 describes the official visual test for assessing clarity and opalescence of pharmaceutical liquids.
European Pharmacopoeia (Ph. Eur.) Chapter 2.2.25, Absorption Spectrophotometry, Ultraviolet and Visible, defines the principles, instrumentation, and qualification requirements for UV–Vis spectrophotometry.
Ph. Eur. 2.2.29 (Liquid Chromatography) defines LC principles, apparatus, and general procedural elements used by monographs for assay, identification, and related substances testing.
Ph. Eur. 2.6.1 Sterility is the compendial sterility test required when a European Pharmacopoeia monograph specifies that an article must be sterile.
Ph. Eur. 2.6.12 – Microbiological examination of non-sterile products: microbial enumeration tests provides harmonized, quantitative methods.
This chapter sets general requirements, to be applied when NAT is specified in a monograph or agreed with regulators (e.g., plasma pool testing, virus safety).
This harmonized chapter establishes official methods and acceptance criteria for controlling sub-visible particulate matter in parenteral injections and infusions.
European Pharmacopoeia (Ph. Eur.) chapter 2.9.20, Particulate Contamination: Visible Particles, outlines the official method for the visual inspection of parenteral preparations to ensure they are “essentially free” from visible particulate matter.
Ph. Eur. 5.14 – Gene transfer medicinal products for human use sets quality expectations for products that deliver genetic material to human cells.
The European Pharmacopoeia (Ph. Eur.) Chapter 2.6.14, (harmonized with USP <85> and JP 4.01 under ICH Q4B Annex 14) “Bacterial Endotoxins,” provides methods for detecting and quantifying endotoxins from gram-negative bacteria.
USP General Chapter 〈1032〉 is an informational chapter on the design and development of biological assays (bioassays).
USP General Chapter <1033> Biological Assay Validation is an informational general chapter that provides specific guidance for validating biological (relative-potency) assays.
USP General Chapter ⟨1047⟩, Gene Therapy Products, provides an advisory, risk-based framework for controlling the five critical quality attributes (CQAs): identity, strength, purity, potency, and safety.
USP General Chapter <1057> provides an informational, non-enforceable framework for selecting, developing, and validating assays used to measure Total Protein in biotechnology-derived products.
USP General Chapter <1058> provides a science- and risk-based framework for the lifecycle management of analytical instruments.
USP <1058> provides a scientific, risk-based framework to generate documented evidence that an analytical instrument (or system) is fit for its intended use.
This is the corresponding informational chapter providing detailed guidance on validation, troubleshooting, and best practices.
USP General Chapter <1132> provides a comprehensive, informational framework for controlling residual host cell proteins (HCPs)—process-related impurities from the production cell line (e.g., CHO, E. coli).
USP General Chapter <1207> provides a modern framework for ensuring the container-closure integrity (CCI) of sterile products.
USP General Chapter <1220>, The Analytical Procedure Lifecycle, establishes a science- and risk-based framework for the entire lifecycle management of analytical procedures.
USP General Chapter <1223> Validation of Alternative Microbiological Methods provides the official framework for validating non-compendial (alternative) testing strategies for microbiological control.
USP General Chapter <1227> Validation of Microbial Recovery from Pharmacopeial Articles is an informational chapter that explains the scientific rationale and procedures for demonstrating that a compendial microbiological test can detect and recover microorganisms in the presence of a specific product matrix.
USP chapters <1787> and <1788> provide critical context for measuring and interpreting subvisible particulate matter in parenterals.
USP General Chapter <1790> Visual Inspection of Injections is an informational chapter that provides a modern, life-cycle framework for preventing, detecting, and controlling visible particulates in injectable drug products.
USP General Chapter <621> is an enforceable, harmonized standard that defines the principles, calculations, performance requirements, and allowable adjustments for liquid chromatography (LC) and gas chromatography (GC) procedures in USP monographs.
USP General Chapter <63> Mycoplasma Tests establishes the harmonized compendial methods for detecting mycoplasma contamination in cell substrates, viral seed stocks, and unprocessed bulk harvest of biotechnology products.
USP General Chapter <71> provides the harmonized procedures for sterility testing of articles required to be sterile.
United States Pharmacopeia (USP) General Chapter <785> Osmolality and Osmolarity provides the official definitions of the two terms and prescribes the method for determination of osmotic concentration when required by a specific USP monograph or selected in a validated QC procedure.
USP General Chapter <787> establishes an enforceable compendial test for subvisible particles specifically tailored to therapeutic protein injections.
USP General Chapter <788> is the primary, enforceable standard for controlling subvisible particulate matter in injectable drug products in the United States.
USP General Chapter <791> pH establishes the mandatory potentiometric method for measuring the pH of pharmaceutical articles.
USP General Chapter <85> Bacterial Endotoxins Test (BET) is an official, harmonized compendial chapter (USP/Ph. Eur./JP) that provides validated methods to detect and quantify Gram-negative bacterial endotoxins in articles where an endotoxin limit applies
USP <855> is a general test chapter but not harmonized under the PDG process
In practice, <857> ensures UV–Vis instruments are reliable and fit for compendial use, forming the foundation for accurate identity, assay, impurity, and dissolution tests across USP–NF.
In practice, meeting the USP Poloxamer monograph ensures excipient quality, safety, and regulatory compliance..
USP <1> sets the enforceable quality standards for injections and implanted parenteral products.
USP 〈1151〉 Pharmaceutical Dosage Forms is a General Information chapter that provides guidance on standardized dosage-form terminology and descriptions.
USP <631> Color and Achromicity is to assess the color or colorlessness of liquid samples
USP General Chapter <790> is an enforceable compendial standard that establishes requirements for visible particulate control in parenteral injections and infusions in their final containers.
TRS 878 should be referenced only for historical perspective; WHO TRS 978 (2013) provides the applicable expectations.