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3.92.466.318.845.567 1.135.744.29.179.677.36 1.16.546.483.186.933.278 1.35.278h.026c.417 0 .867-.092 1.35-.278.483-.186.87-.367 1.16-.546.29-.177.67-.426 1.136-.744 1.39-.932 3.429-2.239 6.113-3.92z"></path></g></g></g></svg></a></li></ul></div></div><div class="w-full lg:w-2/3 px-4"><div class="articles"><h1 style="color:#ef373e">Challenges to Process Validation for Viral Vectors</h1><div class="my-4"><p><span class="text-orange-500 font-bold cursor-pointer italic"><span href="/articles/topics/aav">AAV</span></span><span class="text-navy"> | </span><span class="text-orange-500 font-bold cursor-pointer italic"><span href="/articles/topics/cell-and-gene-therapy">Cell and Gene Therapy</span></span><span class="text-navy"> | </span><span class="text-orange-500 font-bold cursor-pointer italic"><span href="/articles/topics/q1-2020">Q1-2020</span></span><span class="text-navy"> | </span><span class="text-orange-500 font-bold cursor-pointer italic"><span href="/articles/topics/thermo-fisher-scientific">Thermo Fisher Scientific</span></span><span class="text-navy"> | </span><span class="text-orange-500 font-bold cursor-pointer italic"><span href="/articles/topics/validation">Validation</span></span><span class="text-navy"> | </span><span class="text-orange-500 font-bold cursor-pointer italic"><span href="/articles/topics/viral-vector">Viral Vector</span></span></p></div><div></div></div></div><div class="w-full lg:w-1/4 px-4 flex flex-col"><ul class="px-8"><li class="mb-8"><div><div class="flex justify-center mb-4"><a href="/authors/kyle-zingaro-ph-d"><span style="box-sizing:border-box;display:inline-block;overflow:hidden;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0;position:relative;max-width:100%"><span style="box-sizing:border-box;display:block;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0;max-width:100%"><img style="display:block;max-width:100%;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0" alt="" aria-hidden="true" src="data:image/svg+xml,%3csvg%20xmlns=%27http://www.w3.org/2000/svg%27%20version=%271.1%27%20width=%27211%27%20height=%27266%27/%3e"/></span><img alt="Kyle Zingaro, Ph.D. Headshot" src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" decoding="async" data-nimg="intrinsic" style="position:absolute;top:0;left:0;bottom:0;right:0;box-sizing:border-box;padding:0;border:none;margin:auto;display:block;width:0;height:0;min-width:100%;max-width:100%;min-height:100%;max-height:100%"/><noscript><img alt="Kyle Zingaro, Ph.D. Headshot" srcSet="/_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FK_Zingaro_ThermoFisherScientific.png&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FK_Zingaro_ThermoFisherScientific.png&w=640&q=75 2x" src="/_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FK_Zingaro_ThermoFisherScientific.png&w=640&q=75" decoding="async" data-nimg="intrinsic" style="position:absolute;top:0;left:0;bottom:0;right:0;box-sizing:border-box;padding:0;border:none;margin:auto;display:block;width:0;height:0;min-width:100%;max-width:100%;min-height:100%;max-height:100%" loading="lazy"/></noscript></span></a></div><p class="text-navy font-bold cursor-pointer hover:text-orange-500">Kyle Zingaro, Ph.D.</p><p>Head of Process Sciences, Viral Vector Services<!-- -->,<!-- --> <span class="text-navy font-bold cursor-pointer hover:text-orange-500">Thermo Fisher Scientific</span></p><div class="flex justify-end mt-4 -mx-2"><a href="https://www.linkedin.com/in/kylezingaro/" target="_blank" class="px-2 grayscale hover:grayscale-0 transition"><svg xmlns="http://www.w3.org/2000/svg" width="44" height="44" viewBox="0 0 44 44"><g fill="none" fill-rule="evenodd" stroke="none" stroke-width="1"><g 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style="box-sizing:border-box;display:block;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0;max-width:100%"><img style="display:block;max-width:100%;width:initial;height:initial;background:none;opacity:1;border:0;margin:0;padding:0" alt="" aria-hidden="true" src="data:image/svg+xml,%3csvg%20xmlns=%27http://www.w3.org/2000/svg%27%20version=%271.1%27%20width=%27211%27%20height=%27266%27/%3e"/></span><img alt="Deborah Mar Begos Headshot" src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" decoding="async" data-nimg="intrinsic" style="position:absolute;top:0;left:0;bottom:0;right:0;box-sizing:border-box;padding:0;border:none;margin:auto;display:block;width:0;height:0;min-width:100%;max-width:100%;min-height:100%;max-height:100%"/><noscript><img alt="Deborah Mar Begos Headshot" srcSet="/_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FD_Mar_Begos_ThermoFisherScientific.png&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FD_Mar_Begos_ThermoFisherScientific.png&w=640&q=75 2x" src="/_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FD_Mar_Begos_ThermoFisherScientific.png&w=640&q=75" decoding="async" data-nimg="intrinsic" style="position:absolute;top:0;left:0;bottom:0;right:0;box-sizing:border-box;padding:0;border:none;margin:auto;display:block;width:0;height:0;min-width:100%;max-width:100%;min-height:100%;max-height:100%" loading="lazy"/></noscript></span></a></div><p class="text-navy font-bold cursor-pointer hover:text-orange-500">Deborah Mar Begos</p><p>Senior Manager Upstream MST, Viral Vector Services<!-- -->,<!-- --> <span class="text-navy font-bold cursor-pointer hover:text-orange-500">Thermo Fisher Scientific</span></p><div class="flex justify-end mt-4 -mx-2"><a href="https://www.linkedin.com/in/deborah-mar-begos/" target="_blank" class="px-2 grayscale hover:grayscale-0 transition"><svg 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alt="Todd Miller Headshot" srcSet="/_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FT_Miller_ThermoFisherScientific.png&w=256&q=75 1x, /_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FT_Miller_ThermoFisherScientific.png&w=640&q=75 2x" src="/_next/image?url=https%3A%2F%2Fthatsnice-testing3.com%2Fwp-content%2Fuploads%2FT_Miller_ThermoFisherScientific.png&w=640&q=75" decoding="async" data-nimg="intrinsic" style="position:absolute;top:0;left:0;bottom:0;right:0;box-sizing:border-box;padding:0;border:none;margin:auto;display:block;width:0;height:0;min-width:100%;max-width:100%;min-height:100%;max-height:100%" loading="lazy"/></noscript></span></a></div><p class="text-navy font-bold cursor-pointer hover:text-orange-500">Todd Miller</p><p>MST Manager, Viral Vector Services<!-- -->,<!-- --> <span class="text-navy font-bold cursor-pointer hover:text-orange-500">Thermo Fisher Scientific</span></p><div class="flex justify-end mt-4 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#0091d6\"\u003eProcess validation is essential for ensuring robust, reliable processes that can produce high-quality viral vector products. Many challenges remain in implementing effective process validation strategies for these highly complex biomolecules.\u003c/span\u003e\u003c/h3\u003e\n\u003ch4 class=\"p1\" style=\"font-weight: normal\"\u003e\u003cspan class=\"s1\" style=\"color: #ef373e\"\u003eThe Process is the Product\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003e\u003cspan class=\"s2\"\u003eOwing to the complexity of viral vector products, which comprise multiple proteins and nucleic acids, it is not possible to directly compare batches of the final drug product in the same manner used for conventional biologics. While we generally have a good understanding of a given virus, including the protein structure and nucleic acid sequence, other factors that can influence the efficacy and safety of viral vectors are less well understood. Post-translational modifications (PTMs) can be introduced enzymatically or chemically (deamination, methylation) on proteins, increasing the complexity of the vector. An adeno-associated virus (AAV) has 60 protein subunits; any protein may have PTMs that may influence efficacy. Further complicating this issue is the lack of analytical tools available for this type of evaluation. Validating the production process is, therefore, even more critical than it might be for conventional biologics.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003c!--more--\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eA second factor to consider is still-evolving platform systems in use for the production of viral vectors, including the baculovirus approach, which generates viral vectors via infection and replication, and multi-plasmid transfection-based processes. In both cases, there are minimal historical published or platform data on process conditions and viral vector product performance, and empirical data must be leveraged as they are collected to generate a better understanding of those very important connections.\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eProcess characterization in this evolving industry is critical for generating the data necessary to support process validation. Conducting relevant studies to develop the information required to adequately define the optimal process design space is essential, especially given that the analytical tools required are either unavailable or insufficiently sensitive. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eParameters of interest during process characterization are dependent on the process itself, including the nature of the cell line, the specific viral vector product, and the operations involved (e.g., infection, transfection, chromatography). The overall goal is to develop process knowledge around consistency of the process and potential sources of process and material variability. This knowledge serves to develop a robust control strategy that can ensure consistent production of safe and efficacious therapies.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 class=\"p1\"\u003e\u003cspan class=\"s1\" style=\"color: #ef373e\"\u003eValidation Scope\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003e\u003cspan class=\"s2\"\u003eProcess validation involves documentation that production processes are robust and can reliably and repeatedly generate a high-quality product that meets a predetermined set of specifications.\u003csup\u003e1\u003c/sup\u003e It is performed in three stages: process characterization, process evaluation (EMA)\u003csup\u003e2\u003c/sup\u003e or process qualification (FDA),\u003csup\u003e3\u003c/sup\u003e and process verification, which is an ongoing process intended to ensure continued performance during commercial production.\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eWith viral vectors, there are no specific requirements for process validation inputs and outputs, because they are highly dependent on the product and its intended application. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eCritical quality attributes (CQAs) of the product are identified and used to determine the critical process parameters (CPPs) that will impact the CQAs. A risk-based approach is essential to identify the most impactful process parameters, including those for which a robust understanding or obvious means of control is lacking. During the process evaluation or characterization stage, a series of design-of-experiment (DoE) studies is performed according to ICH Q11 guidelines to identify a robust operating space wherein the quality attributes of the product are well controlled.\u003csup\u003e4\u003c/sup\u003e This information is used to establish an appropriate control strategy, which includes the material controls, process controls, and control of the drug substance. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003eProcess qualification is the stage at which the ability of the process to repeatedly produce viral vector product that meets the determined specifications at commercial scale and the ability to execute that process within those control ranges are verified through the execution of the process performance qualification (PPQ) protocols. The approach is similar to that used for conventional biologics, as outlined in ICH Q7 and the FDA guidance\u003ci\u003e \u003c/i\u003e\u003ci\u003eProcess Validation: General Principles and Practices.\u003c/i\u003e\u003csup\u003e1\u003c/sup\u003e The manufacturing processes are performed by trained operators as expected to be implemented for commercial production, and all associated aspects, including the facilities, equipment, systems, and utilities, must be validated. All raw material used in the PPQ \u003cspan class=\"s2\"\u003emust have predefined specifications and must be sampled, inspected, tested, and released prior to use in the validation.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 class=\"p1\" style=\"font-weight: normal\"\u003e\u003cspan class=\"s1\" style=\"color: #ef373e\"\u003eTransfection vs. Infection\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003e\u003cspan class=\"s2\"\u003eThe two leading scalable production platforms for AAV production are transient transfection of suspension-adapted mammalian HEK293 cells and the infection of \u003ci\u003eSpodoptera frugiperda\u003c/i\u003e (Sf9) insect cells using the baculovirus expression vector system (BEVS).\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eFrom an operational standpoint, infection processes — and the associated controls — are generally simpler than transfection processes, which involve packaging plasmids (or sets of plasmids) and transferring them into cells. For infection processes, the added mass and the ratio of virus to cell are values that can be quantified with existing technologies. There is more of a challenge on the raw material side, because, in addition to the working cell bank, a viral cell bank is also needed, which introduces a measure of potential process variability as a complex starting material. \u003cbr /\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eThe impact of different parameters on product quality is not always clear, making characterizing of process parameters for PPQ challenging. Often, we know that a parameter may be impactful to process consistency or product quality attributes, but we may not have a strong understanding of how sensitive the process is to perturbations in that parameter or how that parameter may interact with others in the process. In particular, there are many delicate cell lines used for transfection for which cell health can be affected by even minor manipulations. While these changes in cell health may not be apparent, they could potentially impact the transfection performance and product quality. \u003c/span\u003e\u003c/p\u003e\n\u003ch4 class=\"p1\" style=\"font-weight: normal\"\u003e\u003cspan class=\"s1\" style=\"color: #ef373e\"\u003eSeparation of Full/Empty Capsids\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003eOne of the current challenges in developing AAV manufacturing processes is the generation of empty capsids, viral capsids that do not contain the nucleic acid cargo that is clinically active. The technologies in use today provide a mixture of full, partly full, and empty capsids, leveraging both the upstream production process and the downstream purification to maximize the percentage of full capsids. Production of high concentrations of full capsids in a scalable manufacturing pro\u003cspan class=\"s2\"\u003ecess is highly challenging. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eDue to the similarity of the physicochemical properties of all three types of capsids, a very limited number of tools are available to separate full capsids. These processes operate within very tight design spaces and require continuous maintenance of control, creating challenges for process validation.\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eThermo Fisher Scientific has unique experience in developing and characterizing a wide array of viral vector products and processes and developing equipment and reagents required for robust viral vector therapeutic programs. This experience allows for development of robust customer processes that can meet the regulatory and scientific requirements for commercialization of these complex products. \u003c/span\u003e\u003c/p\u003e\n\u003ch4 class=\"p1\" style=\"font-weight: normal\"\u003e\u003cspan class=\"s2\" style=\"color: #ef373e\"\u003eNeed for Analytical Tools\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003e\u003cspan class=\"s2\"\u003eSuccessful process validation requires a connection between process parameter inputs, biological and physiochemical assessment of the product via quality attributes, and clinical outcomes from administration of the product in patients. Access to appropriate analytical tools that can provide the data essential for making decisions about the process design space and evaluating ongoing process performance is needed. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eThe lack of robust analytical tools supporting the biological and physiochemical characterization of viral vector products remains a considerable challenge for process validation. In some cases, methods do not yet exist. In others, the available techniques lack the sensitivity and granularity required to provide the necessary level of detailed understanding. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eMost of the analytical tools used in the viral vector space have been adapted from tools developed for conventional biologics. Significant innovation is needed to enable the optimal application of these methodologies to viral vectors and to evolve the tool set to address the tremendous complexity of these products. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eThe key assays focus on safety, potency, and purity. Titer measurements indicate the number of viral genomes per milliliter, which is useful for dosing of the product but does not tell us how much of the product is active. Quantitative PCR (qPCR) provides a relative result, which can carry a lot of noise if the analysis is transferred from one laboratory to another. Droplet digital PCR (ddPCR) provides an absolute value, but still only tells how much virus is present, not how much is potent. Direct measures of potency are typically cell-based and noisy. \u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eA variety of analytical methods can interrogate aspects of the vector structure that might impact potency, including mass spectrometric methods, HPLC, and others. These assays will be critical to the understanding of process performance and product quality but are currently limited in their implementation and still require considerable development across the industry. Additionally, knowledge of connections between these structural and chemical differences and clinical efficacy is extremely limited, which creates a significant barrier to developing robust control strategies.\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eThere are some assays for determining the full/empty capsid ratio for AAV products, but very few exist for measuring this ratio for lentiviral and retroviral vectors. Methods for the detection of host-cell protein and DNA need greater sensitivity.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 class=\"p1\" style=\"font-weight: normal\"\u003e\u003cspan class=\"s1\" style=\"color: #ef373e\"\u003eThe Raw Material Factor\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003e\u003cspan class=\"s2\"\u003eRegulatory authorities have been encouraging companies to better understand their raw material suppliers and where their raw materials are coming from, how they are processed, and the practices used for their release, to enhance the security of pharmaceutical manufacturing supply chains.\u003cspan class=\"Apple-converted-space\"\u003e\u0026nbsp; \u003c/span\u003eThis understanding is needed not just for cell lines, plasmids, media, and buffers, but also for single-use equipment components and consumables, from bags to tubing. An understanding of the raw material supply chain, including traceability and knowledge of the methodologies used, can enable a proper assessment of any risks the materials may pose with respect to impacting the quality, safety, and efficacy of viral vector products.\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eAt Thermo Fisher Scientific, we have a catalog of consumables and raw materials utilized throughout the cell and gene therapy manufacturing space and can provide a more robust understanding of where our materials for viral vector manufacturing have come from and how they have been produced. When issues do arise, we have direct access to the raw material team and can collaborate with them to rapidly identify and address the root causes.\u003c/span\u003e\u003c/p\u003e\n\u003cdiv class=\"callout\"\u003e\n\u003ch4 class=\"callout-title\"\u003e\u003cspan style=\"color: #0091d6\"\u003eProcess characterization in this evolving industry is critical for generating the data necessary to support process validation.\u003c/span\u003e\u003c/h4\u003e\n\u003c/div\u003e\n\u003ch4 class=\"p1\" style=\"font-weight: normal\"\u003e\u003cspan class=\"s1\" style=\"color: #ef373e\"\u003eAccelerated Development\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003e\u003cspan class=\"s2\"\u003eMost viral vectors developed for cell and gene therapy applications garner orphan drug and/or breakthrough therapy, priority review, or other accelerated approval designations. The development timelines for these products are significantly shorter, translating to a compression of CMC activities. There is a drive not only to build robust processes, but to do so under compressed schedules. With projects moving at greater speeds, PPQ and process validation efforts can move forward with fewer runs performed at scale before starting process characterization or PPQ, leading to the generation of much smaller data sets. These smaller data sets highlight the need for a solid risk-based approach to the process characterization and validation being driven through earlier stage operations to help increase the guidance and understanding moving into process characterization.\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eThe third phase of process validation is particularly impacted by the smaller data sets due to increased risk.\u003cspan class=\"Apple-converted-space\"\u003e\u0026nbsp; \u003c/span\u003eStandard statistical models that are often used at this point are generally not viable given the limited historical data and expected manufacturing run rate in some processes. These models must continue to evolve through the life cycle of these therapies as additional CMC data is collected.\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eIn most cases, these issues are addressed by working closely with the health authorities, preferably through face-to-face meetings, but at least via written coordination and communication between the company and the agency. Regulatory experts can assist with everything from CMC requirements to clinical trial design and provide guidance on what is appropriate across the entire validation timeline. \u003cbr /\u003eOften, alternative approaches to validation are developed by leveraging this interaction with the authorities. This can include the concurrent release of PPQ batches, among others. The key to success here is the use of a risk-based approach. In Europe, for instance, the EMA has established the PRIME initiative to enhance support for the development of medicines that target unmet medical needs. Through PRIME, the agency offers early and proactive support to drug developers to optimize the generation of robust data on a medicine’s benefits and risks and to enable accelerated assessment.\u003csup\u003e8\u003c/sup\u003e For orphan drugs in this program, the EMA is often flexible regarding the number of PPQ batches and tailors requirements to the individual products considering the indication and other relevant factors.\u003c/span\u003e\u003c/p\u003e\n\u003ch4 class=\"p1\" style=\"font-weight: normal\"\u003e\u003cspan class=\"s1\" style=\"color: #ef373e\"\u003eEvolving Regulatory Guidance\u003c/span\u003e\u003c/h4\u003e\n\u003cp class=\"p2\"\u003e\u003cspan class=\"s2\"\u003eThe regulations for advanced therapy medicinal products (ATMPs) are evolving along with the expectations from health authorities for these products. The EMA published its \u003ci\u003eGuideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products\u003c/i\u003e in March 2018,\u003csup\u003e5\u003c/sup\u003e while the U.S. FDA issued the draft guidance \u003ci\u003eChemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) \u003c/i\u003ein July 2018.\u003csup\u003e6\u003c/sup\u003e The FDA has indicated that it is working on several additional guidances covering clinical development through manufacturing.\u003csup\u003e7\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp class=\"p3\"\u003e\u003cspan class=\"s2\"\u003eBecause the regulations are not locked and have the ability to shift, the best approach is to expect similar progress within the viral vector field as has been observed over the past 20 years in the biologics space, but at an accelerated pace. Adopting a risk-based approach and establishing processes with robust controls are fundamental to effective process validation. By doing so, viral vector manufacturers can help set the standards upon which the health authorities will base new regulations.\u003cbr /\u003eThermo Fisher is uniquely positioned to drive the highly accelerated development of these advanced therapeutic products. Across process and analytical tools and technologies, viral vector manufacturing capabilities, and a rich history of development experience in viral vectors and other biologics products, Thermo Fisher can help deliver these products to patients and meet the evolving needs of the cell and gene therapy industry.\u003c/span\u003e\u003c/p\u003e\n\u003ch4\u003eReferences\u003c/h4\u003e\n\u003col\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003cspan class=\"s1\"\u003e\u003ci\u003eICH Harmonized Tripartite Guideline on good manufacturing practice for active pharmaceutical ingredients Q7.\u003c/i\u003e International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2000. Web. \u003c/span\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003cspan class=\"s1\" style=\"font-size: 1em;letter-spacing: -0.1px\"\u003e\u003ci\u003eGuideline on process validation for the manufacture of biotechnology-derived active substances and data to be provided in the regulatory submission.\u003c/i\u003e EMA. Committee for \u003c/span\u003e\u003cspan class=\"s1\" style=\"font-size: 1em;letter-spacing: -0.1px\"\u003eMedicinal Products for Human Use (CHMP). EMA /CHMP/BWP/187338/2014. Apr. 2016. Web. \u003c/span\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003cspan style=\"font-size: 1em;letter-spacing: -0.1px\"\u003e“Process Validation: General Principles and Practices. cGMP.” U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Center for Biologics Evaluation and Research (CBER). Center for Veterinary Medicine (CVM).\u0026nbsp;\u003c/span\u003eJan. 2011. Web.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003cspan class=\"s1\"\u003e\u003ci\u003eICH Harmonized Tripartite Guideline on Pharmaceutical Development Q8 (R2).\u003c/i\u003e International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2006. Web.\u003c/span\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003ci\u003eGuideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products.\u003c/i\u003e EMA. Committee for Advanced Therapies (CAT). EMA/CAT/80183/2014. Mar. 2018. Web.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003cspan class=\"s1\"\u003e\u003ci\u003eDraft Guidance for Industry: Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs).\u003c/i\u003e U.S. FDA. Jul. 2018. Web. \u003c/span\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003cspan class=\"s1\"\u003e\u003cstrong\u003eMacdonald, Gareth.\u003c/strong\u003e “FDA pledges to support cell and gene therapy manufacturing innovation.” \u003ci\u003eBioprocess International.\u003c/i\u003e 3 May 2019. Web. \u003c/span\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp class=\"p1\"\u003e\u003cspan class=\"s1\"\u003e“PRIME: priority medicines.” EMA. 21 Nov. 2019. Web.\u003c/span\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ol\u003e\n","date":"2020-03-19T17:26:01","dateGmt":"2020-03-19T21:26:01","roundtable":{"topic":null,"question":null,"roundtable":null},"featuredImage":{"node":{"sourceUrl":"https://thatsnice-testing3.com/wp-content/uploads/PA_Q120_ThermoFisher_Digital.jpg"}},"articleTags":{"edges":[{"node":{"name":"AAV","slug":"aav","id":"dGVybToxMTc2MA=="}},{"node":{"name":"Cell and Gene Therapy","slug":"cell-and-gene-therapy","id":"dGVybTo5MTcx"}},{"node":{"name":"Q1-2020","slug":"q1-2020","id":"dGVybToxMTk0Ng=="}},{"node":{"name":"Thermo Fisher Scientific","slug":"thermo-fisher-scientific","id":"dGVybTo5MjMz"}},{"node":{"name":"Validation","slug":"validation","id":"dGVybTo5Mjg1"}},{"node":{"name":"Viral Vector","slug":"viral-vector","id":"dGVybTo5MTg1"}}]},"mainTopic":{"mainTopic":"AAV Vector Production"},"articleFields":{"articleId":"PAP-Q1-20-CL-002","accentColor":"#ef373e","vimeoId":null,"associatedCompanies":[{"company":{"id":"cG9zdDo3NjM1OA==","title":"Thermo Fisher Scientific","slug":"thermo-fisher-scientific"}}],"authors":[{"author":{"id":"cG9zdDo4MDI2Mw==","title":"Kyle Zingaro, Ph.D.","slug":"kyle-zingaro-ph-d","featuredImage":{"node":{"sourceUrl":"https://thatsnice-testing3.com/wp-content/uploads/K_Zingaro_ThermoFisherScientific.png"}},"authorFields":{"bio":"\u003cp\u003eDr. Zingaro is the Head of Process Sciences at Thermo Fisher Scientific\u003cbr /\u003e\nViral Vector Services (formerly Brammer Bio) and is responsible for leading late-phase process development, commercial tech transfer, and process characterization for all viral vector products. Prior to Thermo Fisher, he was responsible for cell line development and process development at Alexion Pharmaceuticals. He holds a BS in biochemistry from Virginia Tech and a Ph.D. in chemical engineering from University of Delaware. \u003c/p\u003e\n","email":null,"linkedin":"https://www.linkedin.com/in/kylezingaro/","title":"Head of Process Sciences, Viral Vector Services","company":{"id":"cG9zdDo3NjM1OA==","title":"Thermo Fisher Scientific","slug":"thermo-fisher-scientific"}}}},{"author":{"id":"cG9zdDo4MDI1OQ==","title":"Deborah Mar Begos","slug":"deborah-mar-begos","featuredImage":{"node":{"sourceUrl":"https://thatsnice-testing3.com/wp-content/uploads/D_Mar_Begos_ThermoFisherScientific.png"}},"authorFields":{"bio":"\u003cp\u003eDeborah Mar Begos is a MST Senior Manager at Thermo Fisher Scientific Viral Vector Services (formerly Brammer Bio) and is responsible for leading the Upstream Manufacturing Sciences and Technology Team at the Cambridge location. Prior to Thermo Fisher, she held roles of increasing responsibility in process engineering, manufacturing sciences, and technology and manufacturing. She holds a BS in chemical engineering from the University of Rochester.\u003c/p\u003e\n","email":null,"linkedin":"https://www.linkedin.com/in/deborah-mar-begos/","title":"Senior Manager Upstream MST, Viral Vector Services","company":{"id":"cG9zdDo3NjM1OA==","title":"Thermo Fisher Scientific","slug":"thermo-fisher-scientific"}}}},{"author":{"id":"cG9zdDo4MDI2Ng==","title":"Todd Miller","slug":"todd-miller","featuredImage":{"node":{"sourceUrl":"https://thatsnice-testing3.com/wp-content/uploads/T_Miller_ThermoFisherScientific.png"}},"authorFields":{"bio":"\u003cp\u003eTodd Miller is an MST Manager at Thermo Fisher Scientific Viral Vector Services (formerly Brammer Bio) and is responsible for leading the process validation system for Viral Vector Services. Prior to Thermo Fisher, he held roles of increasing responsibility in downstream process development, manufacturing sciences, and technology and manufacturing. He holds a BS in chemical engineering from Syracuse University.\u003c/p\u003e\n","email":null,"linkedin":"https://www.linkedin.com/in/todd-miller-7478a55/","title":"MST Manager, Viral Vector Services","company":{"id":"cG9zdDo3NjM1OA==","title":"Thermo Fisher Scientific","slug":"thermo-fisher-scientific"}}}}]}},"vimeoThumb":false},"__N_SSG":true},"page":"/articles/[slug]","query":{"slug":"articles-challenges-to-process-validation-for-viral-vectors"},"buildId":"3j1kwQFJR4bAVxAE0sM1B","isFallback":false,"gsp":true,"scriptLoader":[]}</script></body></html>