eBooks

eBook: Alternative Delivery of Biologics — Underdogs Pursue Roads Less Traveled

A number of failures in development of noninjectable delivery methods for therapeutic proteins have caused numerous development programs to crash and burn along with investors’ hopes, dreams, and cash. Most everyone reading BioProcess International is familiar with the issues and challenges: Needles hurt and involve risks to both caregivers and patients. Injections often require administration by trained personnel in specialized settings. But alternative delivery methods are fraught with greater challenges related to dosing, bioavailability (particularly for oral dosing), and inherent…

eBook: Development of a Representative Scale-Down UF/DF Model: Overcoming Equipment Limitations and Associated Process Challenges

Scale-down models (SDM) are physical, small-scale models of commercial-scale unit operations or processes that are used throughout the biopharmaceutical industry for validation studies, commercial deviation investigations, and postapproval process improvements. To support these studies, regulatory guidelines state that SDMs should be representative of the commercial process. For some downstream unit operations such as column chromatography, developing a representative SDM is straightforward because a linear scale-down approach can be used. However, developing a representative SDM for other downstream unit operations such…

eBook: Addressing Quality in Cell-Line Development — Direct Analysis of Bioreactor Harvest for Clone Selection and Process Optimization

Using Direct Analysis of Bioreactor Harvest for Clone Selection and Process Optimization Therapeutic monoclonal antibodies (MAbs) mostly are manufactured using bioengineered mammalian cells cultured in a bioreactor for two to three weeks. High temperatures and an altered redox environment may compromise the quality of MAbs produced (e.g., fragmentation, truncation), as can the presence of proteases, reductases, and other chemicals released from dead cells. Thus, it would be valuable to establish analytical methods that can help cell culture groups monitor immunoglobulin…

eBook: Of Microbrews and Medicines — Understanding Their Similarities and Differences in Bioprocessing Can Help Improve Yields and Quality While Reducing Cost

Meeting a biopharmaceutical scientist or engineer who proclaims a love for brewing is not surprising. Perhaps it’s because of the challenge of mixing raw ingredients together and waiting patiently for the final product, maybe it’s the hands-on nature of the equipment or the data analytics entertainment, or it just might be the simple joy of creating something. Whatever attracts a scientist or engineer to making medicines and/or craft brews, a surprising number of principles hold true for both bioprocesses despite…

eBook: Bioinks for Bioprinting — Three-Dimensional Printing in Research and Medicine

Three-dimensional (3D) printing is one method of digital biomanufacturing for both basic biological research and translational, clinical applications. The medical field has used it to create such constructions as 3D surgical models for preoperative planning, to assist surgeons in their procedure preparations, which improves postsurgical outcomes. Examples here include generation of cleft-palate models (1), orthopedic applications (2), and cardiovascular surgical planning (3). Other forms of 3D printing for biological applications — such as 3D bioprinting — go beyond such surgical…

Postapproval CMC Changes: Increasingly a Fact of Biopharmaceutical Life

The manufacture of vaccines and therapeutic proteins has suffered from a reputation of being part art and part science, with heavy doses of regulatory uncertainty thrown in. Postapproval changes (PACs) to chemistry, manufacturing, and controls (CMC) were initiated reluctantly and carefully in the era of “the process is the product.” Today, CMC PACs are a normal part of the biopharmaceutical industry business. Emma Ramnarine (head of global biologics quality control at Hoffmann-La Roche in South San Francisco, CA) notes that…

eBook: Challenges Facing Biosimilar Entries into US Markets

Since the 2009 enactment of the Biologics Price Competition and Innovation Act (BPCIA) (1), the US Food and Drug Administration (FDA) has licensed six biosimilar products under PHS 351(k) and approved one product under FD&C 505 (b)(2). It also provided complete response letters (CRLs) to four biologics license application (BLA) filings (Table 1) (2). By comparison, the European Medicines Agency (EMA) has approved 31 biosimilar products (3) and refused or withdrawn about five. There is no doubt that US market…

High-Throughput Technologies: Accelerating Process Development

One of the key elements of any biopharmaceutical drug development project is the timeline from identification of the appropriate DNA sequence to investigational new drug (IND) application filing and the start of clinical trials. Typically, this timeline ranges from 18 to 20 months, depending on the type of molecule being developed and the extent and requirements of the chemistry, manufacturing, and controls (CMC) packages supporting the nonclinical and clinical parts of a development program. There is constant pressure to shorten…

U.S. Approval of Three Rapid Microbiological Methods for MACI Product Release

Short time frames are a major challenge in developing alternative microbiological methods for autologous cell therapy products. Ideally, results are made available in under a day. Obtaining regulatory acceptance also can be a challenge, but it is made easier if methods are included in an application (e.g., a biologics license application, BLA) rather than changing a method that is already part of an approved process. Comparing different detection platforms can be a challenge if they have different readouts, and validation…

Comparing Adherent-Cell Technologies: Amplification of Virus Stocks and Viral Vectors

FUJIFILM Diosynth Biotechnology (FDB) is a multifunctional commercial development manufacturing organization (CDMO) that manufactures virus-based therapeutics. Its site in Texas specializes in both adherent and suspension cell culture for production of virus vectors and for development of analytical assays to support production and expression of our clients’ therapeutics. We work with a number of cell lines such as human embryonic kidney (HEK293) and human retinal cells (Johnson & Johnson/Crucell’s proprietary PER.C6 line), which can grow in suspension. However, many of…