ICH Q5C Stability Testing of Biotechnological/Biological Products

Davies, John G.; Gao, Di; Kim, Yoen Joo; Harris, Richard; Cash, Patricia; Schofield, Timothy L.; Zhang, Roujian; Qu, Qiang

doi:10.1002/9781118971147.ch12

Cited by 11 publications

(10 citation statements)

References 33 publications

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“…When developing analysis protocols, it is crucial to take the drug substance degradation products into account (Davies et al, 2017). For this purpose, the developed analytical assay is validated in compliance with the ICH Q2 (R1) guideline (International Conference on Harmonization, 2017).…”

Section: Calibration and Validationmentioning

confidence: 99%

Stability assessment of FDA‐approved ramucirumab monoclonal antibody; validated SE‐HPLC method for degradation pattern evaluation

Abdelghaffar

Hegazy

Eltanany

2021

Biomedical Chromatography

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Ramucirumab (RAMU) is a recently US Food and Drug Administration-approved monoclonal antibody that is included in various anticancer protocols. It has a structural complexity and high degradation risk that have a significant effect on its safety and effectiveness. The major aim of this work was to assess the degradation pattern of RAMU based on physicochemical characterization. Mechanical agitation, repeated freeze-thaw cycles, pH and temperature were the selected stress conditions to which RAMU samples were subjected. The SE-HPLC method was applied and validated to monitor the RAMU monomer along with its aggregates and/or fragments.The purity of the separated peaks together with system suitability parameters were determined through the calculation of percentage purity and percentage drop in RAMU concentration. The results were interpreted by correlating them with those of dynamic light scattering and reducing and non-reducing sodium dodecyl sulfatepolyacrylamide gel electrophoresis. Samples incubated at pH 2.0-10.0 and 37 C for up to 4 weeks were analysed, recording detection of reversed phase (RP) aggregates and low molecular weight peptide fragments. Similarly, samples under short-term storage conditions of 4 weeks at different temperatures (À20, 2-8, 25, 37 and 50 C) showed low molecular weight peptide fragments but to a lesser extent. These results highlight the alarming effect on RAMU multidose vial efficacy and safety.

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Section: Calibration and Validationmentioning

confidence: 99%

Stability assessment of FDA‐approved ramucirumab monoclonal antibody; validated SE‐HPLC method for degradation pattern evaluation

Abdelghaffar

Hegazy

Eltanany

2021

Biomedical Chromatography

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“…There is a global requirement for meningococcal conjugate vaccines to meet ICH Guidelines Q5C, which outlines the stability requirements for the drug substances and drug product to establish shelf life [ 23 ]. Three consistency Phase 3 clinical trial NmCV-5 batches were fully evaluated by SIIPL, with independent confirmatory testing of key quality attributes being performed by the National Institute for Biological Standards and Control (NIBSC), U.K. Official lot release was performed by the Central Drug Laboratory, India’s National Control Laboratory.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

et al. 2021

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Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.

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“…Although biosimilars have reached the EU and US markets, the uptake and acceptance of biosimilars in clinical practice varies within the European countries and is still low in the US. This variance has been attributed to, among others, budget and reimbursement factors and a lack of understanding, acceptance, or trust in the science behind the biosimilar approval that heavily relies on the comparability of QAs [65,66]. Previous research on the comparability of QAs by Halim et al focused on comparing filgrastim and epoetin products and found that certain QAs for products (copies) from less regulated markets differed significantly from the reference products and biosimilars available on the EU market.…”

Section: Comparability Exercisementioning

confidence: 99%

“…Biopharmaceuticals, whether reference products or biosimilars, must have consistent and comparable QAs throughout their life cycle to ensure that patients can use safe and effective treatments. Previous research and PhD theses on biosimilars have focused on requirements for developing regulatory guidelines for biosimilar approval [108], analysis of a selection of QAs to compare the reference product and biosimilars of filgrastim and epoetin obtained from the EU market with copies from emerging markets [109], market access to biosimilars [65], barriers to sustainable biosimilar competition and uptake in clinical practice [66], scientific, legal, and regulatory hurdles for biosimilar development, and interchangeability of biosimilars [110].…”

Section: Knowledge Gap and The Rationale Behind This Phd Thesismentioning

confidence: 99%

“…As EPARs are considered an unbiased information source, there is great value in providing insight into the biosimilarity assessment of QAs for various stakeholders involved in biosimilar development, adoption, and regulation. The pharmaceutical industry can use EPARs to learn from past successes and failures and predict the regulatory process, and EPARs as such may contribute to reducing the time and cost of biosimilar development [65]. Healthcare professionals (HCPs) can use EPARs to understand the QA assessment's crucial role during the regulatory approval of biosimilars [66,67].…”

Section: 3mentioning

confidence: 99%

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Quality of biopharmaceuticals: Comparability exercise and post-approval surveillance

Alsamil¹

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Kwaliteit van biologische geneesmiddelen: aantonen van gelijkwaardigheid en surveillance na toelating (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof. dr. H.R.B.M Kummeling, ingevolge het besluit van het College voor Promoties in het openbaar te verdedigen op woensdag 3 november 2022 des middags te 2.15 uur door

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ICH Q5C Stability Testing of Biotechnological/Biological Products

Cited by 11 publications

References 33 publications

Stability assessment of FDA‐approved ramucirumab monoclonal antibody; validated SE‐HPLC method for degradation pattern evaluation

Stability assessment of FDA‐approved ramucirumab monoclonal antibody; validated SE‐HPLC method for degradation pattern evaluation

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Quality of biopharmaceuticals: Comparability exercise and post-approval surveillance

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