In biopharmaceutical manufacturing, buffer preparation is traditionally performed manually by dissolving solid salts in water for injection (WFI) followed by offline mixing and specification testing. This method requires large buffer volumes, extensive infrastructure, and significant labor, often creating bottlenecks in production. To address these limitations and support process intensification, inline buffer preparation technologies have emerged…
Tag: <span>biologics</span>
The number of cellular therapies in clinical trials and on the market has continued to rise significantly in recent years—and so does the need to maintain strict control over all manufacturing steps in order to reduce batch-to-batch variability. One potential source of product variability is the manual thawing of cryopreserved cells in a water bath, which can differ between operators. Additionally, water baths pose a significant contamination risk, making them less suitable for GMP environments. To overcome these challenges, several companies have developed water-free thawing devices that offer better control of the thawing process. However, these devices either accommodate only one vial at a time or lack U.S.
FDA 21 CFR 11 compliance in producing a computer-generated audit trail. Hence, we have developed a novel, water-free and dry-heat-based, fully programmable thawing device that is capable of thawing up to ten vials simultaneously and complies with 21 CFR11 requirements…
The Leahy-Smith America Invents Act (AIA) and the Biologics Price Competition and Innovation Act (BPCIA) are dramatically reshaping business strategies designed to protect intellectual property and regulatory exclusivity rights granted by the United States Patent and Trademark Office (PTO) and the Federal Drug Administration (FDA) to the sponsors of new and follow-on versions of many biopharmaceutical products. The AIA alters many provisions in the U.S. patent statutes, most notably long-standing policies and practices relating to the conditions for patentability of an invention, particularly 35 USC §§ 102 and 103 relating to novelty and non-obviousness, respectively, and introduces new provisions relating to post-grant review proceedings and prioritized examination that will affect the business plans of academic and corporate institutions seeking to discover and develop health care products that serve unmet medical needs or provide consumers with safe sources of drug products at a low cost. The BPCIA implements many new provisions relating to the abbreviated review and approval of follow-on biopharmaceutical products. Important aspects of the BPCIA, particularly issues identified in draft guidance documents that were released by the FDA in February 2012 concerning the characterization, comparison, and evaluation of reference and follow-on macromolecules, will be discussed in this article. Political issues that may jeopardize the BPCIA, economic considerations faced by drug product sponsors, and public reaction to the guidance documents are also discussed in this final article of a three-part series describing key provisions of the AIA and the BPCIA that affect intellectual property and regulatory exclusivity rights of institutions having an interest in developing novel or follow-on versions of biopharmaceutical drug products…
The Patient Protection and Affordable Care Act (PPACA), which was passed in 2010, included the Biologics Price Competition and Innovation Act (BPCIA) authorizing the United States Food and Drug Administration (FDA) to establish an abbreviated regulatory approval pathway for complex macromolecules produced in living cells or organisms. The BPCIA implements many new provisions relating to the abbreviated review and approval of follow-on biopharmaceutical products. These include: (1) evaluating the biochemical properties of reference and follow-on macromolecules; (2) establishing procedures for the exchange of information between product sponsors, regulatory agencies, and the federal court system; and (3) establishing periods of regulatory exclusivity which complement patent rights typically awarded to the sponsor of a reference molecule. Important aspects of the BPCIA, particularly issues relating to the exchange of information between product sponsors and the establishment of periods of regulatory exclusivity protecting a novel or follow-on macromolecule are discussed in this article. This is the second in a series of three articles describing key provisions of the Leahy-Smith America Invents Act (AIA) and the BPCIA that affect intellectual property rights of academic and corporate institutions having an interest in the life sciences…
The expansion of stem cells, including mesenchymal stem cells (MSCs), has been successfully demonstrated using microcarrier-based small bioreactors such as spinner flasks. In this study, we explored a simple alternative for microcarrier-based MSC expansion using conventional shake flasks. This method relies on a new type of shaker with built-in CO2 gas control capability, the New Brunswick™ S41i incubator shaker. The expansion of adipose-derived mesenchymal stem cells (AdMSCs) was compared between shake and spinner flasks containing microcarriers. The AdMSCs were seeded at a density of 3 × 103 cells/cm2 in both setups, each containing 0.5 g of plastic microcarriers and 50 mL of stem cell growth medium. The cell culture experiments were conducted over 12 days with samples collected daily for cell growth, biochemistry, and metabolite analysis. The study revealed that AdMSCs cultured under shake flask conditions achieved excellent growth under 12-day batch-culture conditions. Finally, the AdMSCs expanded using the shake flask method retained high quality stem cell characteristics, as indicated by CD44 and CD90 stem cell marker assays, and the ability of these cells to differentiate into either adipocytes or osteocytes…
This paper places the “Quality by Design” (QbD) in an overall context and provides the following straightforward definition so that QbD can be effectively used to solve a wide variety of important problems:
Quality by Design–During the design stage, to achieve a well-defined goal, iteratively apply science and engineering methods to anticipate, identify, understand, resolve, and control problems that will be encountered during testing, operating, and verifying the goal over its lifecycle.
The viewpoint of the paper is to view QbD as “Success by Design.” The definition is based on answering the following question: What will be required to provide assurance that the enabler developed during the design stage will successfully reach the goal over the entire lifecycle before leaving the design stage? The paper argues that QbD should not be implemented as a program, but used as a tool. To provide understanding, the paper explores underlying concepts, the history of QbD, develops a working definition, and then applies it to biopharmaceutical development and manufacturing…
As the institutionalized collection, storage, and distribution of bio-samples becomes more commonplace, the attention and adherence to strict and systematic sample handling practices is paramount. An important component of such efforts is the maintenance of bio-samples in a safe and controllable state (e.g., –80°C storage) apart from any downstream processes the samples could be subjected to in the future. CryoXtract Instruments’ CXT 750 Frozen Aliquotter provides repeated and reproducible access to a variety of frozen bio-fluid samples by maintaining samples at –80°C, thus eliminating undesirable freeze-thaw cycles during sample handling processes. The following study was performed by the Cincinnati Biobank Core Facility and the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children’s Hospital Medical Center, in order to assess the feasibility of frozen aliquotting in conjunction with DNA extraction services provided by the Cincinnati Biobank. The Cincinnati Biobank planned and independently executed the experiment while CryoXtract’s role was to provide technical guidance running the CXT 750. Both groups participated in preparation of the manuscript…