BioPharm

32 BioPharm International eBook March 2018 www.biopharminternational.com Outsourcing Resources Analyzing Biologics Catalent has turned to automation of both cell-based assays as well as molecular binding assays to provide additional capacity. We are now planning to apply additional auto- mation to the manufacture of ana- lytical cell banks for bioassays. NEW TECHNOLOGIES AND REGULATORY REQUIREMENTS BioPharm: Are there new analytical technologies being developed? If yes, how will these impact the industry? Kapetan (Eurofins): New analytical technologies are being developed in order to perform testing on fin- ished products that incorporate drugs with microchips. QC testing will not only be required to assess the drug performance and specifica- tions but will also need to determine if the microchip is functioning as intended. This will require modifi- cations to existing standard equip- ment for certain tests and will require new regulations and stan- dards to keep pace with this new technology. Pan and Merges (Catalent): Yes, there are many new technologies being developed. Some have been rolled out and acquired by Catalent such as the automation mentioned above, mass spectrometers for exten- sive deep characterization of biolog- ics, extractables and leachables and trace metals, and automated data acquisition software technologies. In [the] small-molecule area, the appli- cation of existing non-traditional techniques such as evaporative light- scattering detection (ELSD), charged aerosol detection (CAD), electro- chemical, conductivity, [and] refrac- tive index coupled with multi-angle light-scattering (MALS) detection are on the rise with the increasing number of either poorly soluble or difficult-to-detect compounds enter- ing the development phase. BioPharm: What are the top things companies should be doing when it comes to analytical method devel- opment? Pan and Merges (Catalent): It is critical for companies to establish a strategy and partnership with the CDMO to provide continuous assur- ance that the methods developed remains fit for its intended purpose during the lifecycle of the prod- uct. As the development programs advance from Phase I, Phase II, Phase III, and commercialization, a comprehensive review must be done for each stage to evaluate the need to optimize the analytical procedure or to revalidate all or a part of the analytical procedure. Even after a product recieves FDA approval and becomes a commercial product, FDA still requires a trend analysis on method performance be performed at regular intervals. Kapetan (Eurofins): The current t rend in met hod development is to utilize a quality-by-design (QbD) principle. This is defined in ICH [Inter national Council for Harmonization] Q8 (R2) but i s gea re d towa rd ma nu fac t u r- ing processes. However, the same principles can be applied toward analytical method development. Following a QbD approach stresses a thorough understanding of the method requirements, enforces that the method is fit for purpose and robust, and supports evaluation of the method throughout its life- cycle. Defining expectations for a method prior to initiating develop- ment guides the science of method establishment. Once initial method conditions are established, they must be thoroughly evaluated to ensure that the method is both rugged and robust. Ensuring so during method development increases confidence in the method prior to perform- ing method validation. Evaluation of the method does not stop after successful validation. Monitoring of method performance should con- tinue throughout the lifecycle of the method and should result in optimi- zation of method conditions should performance change. Another best practice for method development is to establish the robustness of the method by using a design of experi- ments. In the past, robustness would be evaluated by altering individual parameters to observe impact on method performance. Using a design of experiments approach allows for multiple parameters to be statisti- cally assessed simultaneously. BioPharm: Have there been recent changes in regulatory requirements, either in the United States or inter- nationally, that have impacted how you perform analytical testing and/ or method development? K a p e t a n (E u r o f i n s): W h i le t he QbD approach discussed above is not specifically written for analyti- cal methods, the major regulatory agencies expect this approach to be applied to the method develop- ment arena. Pan and Merges (Catalent): T he United States Pharmacopeia (USP) introduced new General Chapters <1032>, <1033>, and <1034> [that] address the design, validation, and analysis of bioassays, respectively. ICH Q3D Elemental Impurities dis- claimer icon guidance, and USP General Chapters <232> Elemental I mpu r it ie s — L i m it s a nd < 2 33> Elemental Impurities—Procedures reached their official implemen- tation date for new and existing human drug products. Starting Jan. 1, 2018, all new [new drug appli- cations] NDAs and [abbreviated new drug applications] ANDAs for drug products with an official USP monograph are required to meet t he requ irements desc r ibed in <232> and <233>, and applicants submitting new NDAs and ANDAs for non-compendial drug products are expected to follow the recom- mendations in ICH Q3D. BP

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