Regulatory Affairs

Fundamental Strategies for Viral Clearance – Part 1: Exploring the Regulatory Implications

Over the past several decades, biologics such as monoclonal antibodies (MAbs) and recombinant proteins have provided therapeutic benefits and efficacy for the treatment of human disease. Completion of the human genome project (launched in 1990) produced a draft of the genome in 2001. A full sequence was published on the 50th anniversary (2003) of the initial publication of Watson and Crick’s papers on the double-helical structure of DNA (1). That large volume of genetic information has been translated into usable…

The Single-Use Watering Hole: Where Innovation Needs Harmonization, Collaboration, and Standardization

Within the past few years, the single-use technology (SUT) arena of the biopharmaceutical industry has exploded in growth. Leading organizations have predictably and understandably stampeded to the “watering hole” of single-use to drink up the advantages that disposable components offer over traditional multiuse parts and technologies. The initial value and risk-reduction results are being realized — but not without the emergence of other trade-offs. End users continue to call for standardization in emerging areas of the industry while also recognizing…

Accelerated Product Development: Leveraging Industry and Regulator Knowledge to Bring Products to Patients Quickly

A Chemistry, Manufacturing and Controls (CMC) Strategy Forum titled “Accelerated Product Development: Leveraging Combined Industry and Regulator Knowledge to Bring Products to Patients More Quickly” was held in Washington, DC, on 27 January 2014. Biological therapeutics in development are demonstrating remarkable results in the clinic for many indications. So companies are seeking ways to accelerate the approval of these therapies and rapidly bring them to market. Many such products take the form of well-characterized proteins (e.g., IgG1 or IgG2 monoclonal…

The US Biosimilars Future Is Hard to Predict: Global Health Policy, Innovation, Prices, and Profits Are All at Stake

Enthusiasm in the United States over opportunities for biosimilars has waned since such products were first launched in Europe. The hesitation stems from confusion and uncertainty surrounding regulations. Manufacturers and suppliers are looking for guidance from the US Food and Drug Administration (FDA), which has promised guidelines that are still in process after five years. Even naming protocols for biosimilars are clogging the works. And in the absence of coherent FDA guidelines, many US states are haphazardly implementing laws concerning…

Guidance Is Lacking in the European Biosimilar Regulatory Framework: Considering the Dynamic of Quality Profiles in Development

Biopharmaceutical medicinal products (biologics) had an estimated global commercial market size of US$100 billion in 2013. Because they are more complex than small molecules — and defined by the uniqueness of their manufacturing processes — the generics approval process is not applicable for biologics. Article 10(4) of European Medicines Agency (EMA) directive 2001/83/EC was amended in 2004 in response to the industry’s desire for market access by launching a “similar” biologic abbreviated approval pathway. Leading the subsequent process, the EMA…

Process Challenges of Antibody–Drug Conjugates

With two products now on the market, and a host of others in clinical trials, antibody-drug conjugates (ADCs) are slowly becoming a big business. Designed to deliver extremely active cytotoxic drugs that are otherwise undosable, they take advantage of the targeting ability of a specifically designed monoclonal antibody (MAb) to “shield” a highly potent API (HPAPI) as it travels through a patient’s bloodstream after administration. Once the antibody reaches its target on the cancer cell, it will release the payload,…

Qualification of Scale-Down Bioreactors: Validation of Process Changes in Commercial Production of Animal-Cell-Derived Products, Part 2 — Application

Here we apply our approach to validation of animal cell culture process changes using qualified, scale-down bioreactors. As described in Part 1 (including Table 1, Figures 1 and 2, and References 1–23), the goal is to facilitate implementation for the benefit of both the patients and industry. “Qualification of Scale-Down Bioreactors: Validation of Process Changes in Commercial Production of Animal-Cell–Derived Products, Part 1 — Concept” appears on pages 38–45 of BioProcess International’s May 2014 issue. Process changes often entail validation,…

Cell Therapy Will Transform the Future of Medicine

The third annual IBC Cell Therapy Bioprocessing conference was held in Bethesda, MD, on 21–22 October 2013. It brought pioneers in the development of cell-based therapies together with companies that have enabling technologies, such as bioreactors, cell culture media, and advanced monitoring software. After the conference, I discussed the highlights and key themes coming out of the event with Dr. Phil Vanek, general manager of cell bioprocessing at GE Healthcare Life Sciences in Westborough, MA. Also an instructor for advanced…

Essentials in Quality By Design

Quality by design (QbD) is a systematic approach to drug development. It begins with predefined objectives and emphasizes product and process understanding and process control, all based on sound science, data-based decision making, and quality risk management (QRM). As introduced by the US Food and Drug Administration (FDA), QbD brings modern drug development methodologies to chemistry, manufacturing, and control (CMC) teams working on biologics, pharmaceuticals, and vaccines. The innovations associated with QbD are not so much the development concepts (which…

Cost-Effectiveness and Robustness Evaluation for Biomanufacturing

As the biotech sector has matured, it has come under increasing economic and regulatory pressures for continuous improvement in both drug development and manufacturing. As a result, assessing the value potential of alternative strategies has become critical to decision-making in areas such as bioprocess and facility design, capacity sourcing, and portfolio selection. Related decisions typically involve large cash expenditures and thus have a direct bearing on the feasibility of business units and whole companies. Figure 1:  () Making such decisions…