Review Argues That Same Safety, Efficacy Can Be Expected From Biologics, Biosimilars

Despite their size, complexity, and heterogeneity, biopharmaceuticals and their biosimilars can be expected to be safe and effective irrespective of batch or production history, according to a recent review in Expert Opinion on Biological Therapy, published online January 10, 2018, by William C. Lamanna, PhD, and colleagues.

The researchers, all employees and shareholders of Sandoz/Novartis, conclude that modern analytic methods, manufacturing quality systems, and comparability requirements for the evaluation of manufacturing changes help to ensure the consistent quality and clinical performance of biologics throughout their product lifecycles. More than a decade of real-world experience with biosimilars in Europe and the demonstrated success and safety of biosimilars have not done away with skepticism—particularly in the United States—about product regulation and quality. In this expert review, the authors provide transparency about biosimilar production, approvals, risk, and benefits to help improve confidence that the same safety and efficacy can be expected from biologics and their biosimilars.

Biologic therapies have a demonstrably long track record of consistent safety and effectiveness over the entire course of their often decades-long lifecycles. There have been only rare historical instances where clinically relevant changes have occurred—a situation defined as “clinical drift.” The review analyzes these cases and discusses modern tools in place to prevent them, including improved analytics, quality systems, and regulatory frameworks. Variability resulting in clinical differences is extremely rare, with only a single verifiable case resulting in adverse events in over 35 years and over 260 products, the reviewers note.

Despite this history, as the number of biosimilars increase, concerns regarding the ability of biosimilars to maintain equivalent clinical performance with their reference products have been disseminated. At the center of these concerns is the misconception that the sheer complexity and heterogeneity of biologic products precludes effective monitoring and control of relevant quality attributes. But, the reviewers point out, biosimilars employ the same post-approval regulatory framework and quality systems as their respective originator products to maintain quality and clinical performance. “Effective strategies for maintaining product quality and clinical performance are a pivotal regulatory requirement for the production of biopharmaceuticals, including biosimilars,” the review states.

To this end, production quality systems based around the central concepts of Good Manufacturing Practices (GMP) and the Pharmaceutical Quality System (PQS) have been developed to help ensure consistent production of safe and efficacious products over time and worldwide, irrespective of manufacturing process changes.

GMP was established in the 1990s to set up international requirements for a huge array of quality control measures, ranging from personnel and equipment to laboratory controls. In addition to GMP, the Pharmaceutical Quality System (PQS) was established, which has as its core objectives consistently achieving a realization of safe and effective medicines, establishing and maintaining product control, and continually improving products and processes to mitigate quality risks. Analytical capabilities and modern quality systems are always evolving to ensure consistent biopharmaceutical quality.

The review discusses recent improvements in manufacturing quality systems including:

• Implementation of quality-by-design strategies to leverage extensive product and manufacturing knowledge to mitigate risk and maintain product consistency
• Use of continued process verification strategies to track data and allow early response to risk associated trends
• Implementation of 2-tiered reference standards to ensure the maintenance of consistent acceptance criteria and specifications over time

Finally, quality systems must be continually evaluated and improved for robust maintenance of product quality, and to improve confidence in the safety and efficacy of reference biologics and their biosimilar products.