Upstream Validation

Multivariate Data-Driven Modeling for Continued Process Verification

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Continued process verification (CPV) is an integral part of process validation for the manufacture of human and animal drugs and biological products (1). It is designed to meet three primary goals: maintain a validated state of products, their processes, and related systems; enable continuous process improvements; and meet regulatory requirements for life-cycle validation. A CPV program for a biologic product entails regular collection of data related to critical process parameters (CPPs) and critical quality attributes (CQAs) and the preprocessing, analysis,…

October 28, 2021

Bioprocess Development and Qualification: PAT-Based Stage 1 and 2 Acceleration Strategies

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Well-established process analytical technology (PAT) strategies, such as those based on spectroscopy, bring with them several challenges related to the nature of those tools themselves (1–3). Such tools are multiparametric by design — in the sense that most spectroscopies capture multiple attributes sometimes different in nature (e.g., near-infrared, NIR, captures chemical and physical attributes simultaneously). Often a reference method is required; at other times, indirect calibrations are based on the correlation of one culture attribute with another for which a…

February 6, 2020

Taking Your Molecule Through Process Validation

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The dynamics of the biopharmaceutical industry to get innovative products to the client has evolved over the years. Studies have shown that by 2021, biologics and biosimilar products are projected to have higher growth than other pharmaceutical products. Following the industry trend, Avid Bioservices as a Contract Development Manufacturing Organization (CDMO) has helped numerous clients complete their process validations campaigns. Between 2016 to 2019, Avid has successfully completed six. This custom report will share some key factors to consider for…

June 26, 2019

Points to Consider in Quality Control Method Validation and Transfer

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The concept of an analytical lifecycle has been well received in the biopharmaceutical industry. In 2016, the US Pharmacopeia (USP) advocated for lifecycle management of analytical procedures (1) and defined its three stages: method design development and understanding, qualification of the method procedure, and procedure performance verification. The US Food and Drug Administration (FDA) has published guidance on process validation with a similar division into three stages: process design, process performance qualification, and process performance verification (2). For a manufacturing…

March 14, 2019

Multitiered Automation for Improved Efficiency of Bioprocess Analytics

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The first biopharmaceutical, human insulin, was approved for use in 1982 (1). The biopharmaceutical market continues to exhibit healthy growth now, with the number of yearly patent applications increasing by 25% annually since 1995 (2). The total pharmaceutical R&D pipeline has more than doubled since the beginning of the century (Figure 1), much of that attributable to the biologics industry segment. As this industry has matured, new platform methods have emerged, and competition has increased. Consequently, the pressures of speed,…

December 5, 2018

Methods on the Move: Addressing Method Transfer Challenges for the Biopharmaceutical Industry

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Analytical method transfers are essential components of the current global biotechnology environment. Analytical method transfer can be defined as “a documented process that qualifies a laboratory (the receiving laboratory) to use a validated analytical test procedure that originated in another laboratory (sending laboratory), thus ensuring that the receiving laboratory has the procedural knowledge and ability to perform the transferred analytical procedure as intended†(1). The goal is to ensure that a method continues to perform in the validated state regardless…

June 20, 2018

The Relationship Between R2 and Precision in Bioassay Validation

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Analytical linearity along with assessments of precision and accuracy determine the range for bioassays (1). Practitioners can include coefficient of determination (R2) criteria from a linearity study in the bioassay validation protocol. Herein I illustrate the relationship of R2 to study design and analytical method variation. Overview of the Simple Linear Regression Model Dilutional linearity assesses the “ability (within a given range) of a bioassay to obtain measured relative potencies that are directly proportional to the true relative potency of the…

April 20, 2018

Antibody Higher Order Structure Stability: Polymorphism Revealed By Protein Conformational Array

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For protein therapeutics and other biologics, the importance of the molecule’s structure to its efficacy and safety is well established (1–5). In particular, their tertiary and quaternary structures play very important roles in product quality and have been monitored extensively in comparability studies (6–12). However, because of both the large molecular size and rotational property of amino acid α carbons, a protein can assume an enormous number of different conformations (13). For antibody-based biologics such as monoclonal antibodies (MAbs), fusion…

November 16, 2017

A Statistical Approach to Assess and Justify Potential Product Specifications

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As stated in ICH Q6B, specifications are critical quality standards that are both proposed and justified by drug product manufacturers. Xiaoyu et al. provide information on several statistically based strategies to establish specification acceptance criteria (SAC) (1). Here we address an alternative approach to relate proposed SAC for quantitative data to relevant lot history. In particular, proposed SAC can be derived in part by using calculated limits for which the lower bound of an approximate 95% confidence interval for the…

February 13, 2017

CMC Forum: Evolution of Biopharmaceutical Control Strategy Through Continued Process Verification

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As defined in the ICH Q10 guideline, a control strategy is “a planned set of controls, derived from current product and process understanding, that assures process performance and product quality†(1). Every biopharmaceutical manufacturing process has an associated control strategy. FDA’s 2011 guidance for process validation (2) describes process validation activities in three stages (Figure 1). A primary goal of stage 1 is to establish a strategy for process control that ensures a commercial process consistently produces acceptable quality products.…

January 19, 2017