Approval of biosimilars: a review of unsuccessful regulatory filings

Rathore, Anurag S.; Chhabra, Hemlata; Bhargava, Ankita

doi:10.1080/14712598.2020.1793954

Cited by 10 publications

(10 citation statements)

References 14 publications

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“…Validation, documentation, and quality control have been identified as the major CGMP violations as per the warning letters. Also, in our previous study with biosimilar regulatory applications, process validation and GMP compliance were among the top five reasons for denying the approval of product by regulatory authorities [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

FDA Warning Letters: A Retrospective Analysis of Letters Issued to Pharmaceutical Companies from 2010–2020

Rathore

Chhabra

et al. 2022

J Pharm Innov

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Purpose To launch a pharmaceutical product in the US market, approval from the FDA is required. Pharmaceutical companies undergo FDA pre-approval inspection (PAI for small molecule products) or pre-license approval (PLI for biological products) at their manufacturing sites (including contract development and manufacturing organization, testing laboratories, and packaging labelling facilities) prior to approval. After the products are approved by the FDA, surveillance inspections are performed by the FDA which are risk based as which company and which site will be inspected. The present study examines the causes of warning letters issued by the Center for Drug Evaluation and Research (CDER), FDA to the pharmaceutical companies after post-approval inspections. Methods Warning letters issued from the time period 2010 to 2020 were obtained from the FDA website, and information about date of issuance, company, and type of violations was extracted for the study. Results Poor compliance to CGMP and misbranding were the most common reasons for the warning letters. Detailed analysis of CGMP warning letters elucidated three major types of violations, namely deficiencies in process validation, documentation practices (data integrity), and quality control corresponding to 26%, 21%, and 15% warning letters, respectively. Conclusion Review of the analysed letters demonstrates that the FDA’s major concern is over CGMP compliance. To avoid these warning letters, pharmaceutical manufacturers need to improve their quality compliance and focus on creating effective quality management systems that govern the entire manufacturing process, quality control, employee training, and documentation practice. Companies should develop an internal compliance check list and also be ready for corrective measures as and when required. Supplementary Information The online version contains supplementary material available at 10.1007/s12247-022-09678-2.

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Section: Discussionmentioning

confidence: 99%

FDA Warning Letters: A Retrospective Analysis of Letters Issued to Pharmaceutical Companies from 2010–2020

Rathore

Chhabra

et al. 2022

J Pharm Innov

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“…Because of this, a process must be well defined to make the glycosylation patterns reproducible between multiple batches 15 . Additional complexity is further added if the mAb product of interest is a biosimilar that has stricter tolerances for CQAs to match the originator or innovator drug product 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Automated Workflow for Instant Labeling and Real-Time Monitoring of Monoclonal Antibody N-Glycosylation

Gyorgypal

Potter

Chaturvedi

et al. 2022

Preprint

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With the transition toward continuous bioprocessing, process analytical technology (PAT) is becoming necessary for rapid and reliable in-process monitoring during biotherapeutics manufacturing. Bioprocess 4.0 is looking to build an end-to-end bioprocesses that includes PAT-enabled real-time process control. This is especially important for drug product quality attributes that can change during bioprocessing, such as protein N-glycosylation, a critical quality attribute for most monoclonal antibody (mAb) therapeutics. Glycosylation of mAbs is known to influence their efficacy as therapeutics and is regulated for a majority of mAb products on the market today. Currently, there is no method to truly measure N-glycosylation using on-line PAT, hence making it impractical to design upstream process control strategies. We recently described the N-GLYcanyzer: an integrated PAT unit that measures mAb N-glycosylation within 3 hours of automated sampling from a bioreactor. Here, we integrated Agilents Instant PC (IPC) based chemistry workflow into the N-GLYcanzyer PAT unit to allow for nearly 10x faster mAb glycoforms analysis. Our methodology is explained in detail to allow for replication of the PAT workflow as well as present a case study demonstrating use of this PAT to autonomously monitor a mammalian cell perfusion process at the bench-scale to gain increased knowledge of mAb glycosylation dynamics during continuous biomanufacturing of biologics using Chinese Hamster Ovary (CHO) cells.

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“…Additionally, as the patents of many biologicals have expired or are on the verge of expiration, there has been a recent emergence of the biosimilar industry [17]. Biosimilars are biopharmaceuticals that have demonstrated similarity in their structure, function, quality, safety, and efficacy to the innovator product [21]. Since biosimilars are also produced by living organisms, extensive analytical characterization is necessary to prove their similarity to the reference product as minor alterations during manufacturing may lead to significant implications on the quality of the product.…”

Section: Introductionmentioning

confidence: 99%

Applications of capillary electrophoresis for biopharmaceutical product characterization

2021

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Capillary electrophoresis (CE), after being introduced several decades ago, has carved out a niche for itself in the field of analytical characterization of biopharmaceutical products. It does not only offer fast separation, high resolution in miniaturized format, but equally importantly represents an orthogonal separation mechanism to high‐performance liquid chromatography. Therefore, it is not surprising that CE‐based methods can be found in all major pharmacopoeias and are recommended for the analysis of biopharmaceutical products during process development, characterization, quality control, and release testing. Different separation formats of CE, such as capillary gel electrophoresis, capillary isoelectric focusing, and capillary zone electrophoresis are widely used for size and charge heterogeneity characterization as well as purity and stability testing of therapeutic proteins. Hyphenation of CE with MS is emerging as a promising bioanalytical tool to assess the primary structure of therapeutic proteins along with any impurities. In this review, we confer the latest developments in capillary electrophoresis, used for the characterization of critical quality attributes of biopharmaceutical products covering the past 6 years (2015–2021). Monoclonal antibodies, due to their significant share in the market, have been given prioritized coverage.

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Approval of biosimilars: a review of unsuccessful regulatory filings

Cited by 10 publications

References 14 publications

FDA Warning Letters: A Retrospective Analysis of Letters Issued to Pharmaceutical Companies from 2010–2020

FDA Warning Letters: A Retrospective Analysis of Letters Issued to Pharmaceutical Companies from 2010–2020

Automated Workflow for Instant Labeling and Real-Time Monitoring of Monoclonal Antibody N-Glycosylation

Applications of capillary electrophoresis for biopharmaceutical product characterization

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