In an extraordinary move, the FDA has withdrawn the draft guidance, “Statistical Approaches to Evaluate Analytical Similarity,” after receiving public comments and one citizen petition (FDA-2018-P-1876). The goal of the guidance was to provide an action plan for evaluation of similarity between proposed biosimilars and the original products. FDA Commissioner Dr. Scott Gottlieb, ordering the withdrawal of the guidance, expressed disappointment with the current pace of biosimilar development. “As the cost to develop a single biosimilar product can reach hundreds of millions of dollars, it’s important that we advance policies that help make the development of biosimilar products more efficient, and patient and provider acceptance more certain,” he said.

But what makes the FDA about-face on biosimilar evaluation so monumental, is that it was the direct result of the citizen petition. Filed by one man: Dr. Sarfaraz Niazi, Adjunct Professor at the University of Illinois at Chicago and CEO of Pharmaceutical Scientist, Inc. When asked about his success in influencing the FDA, the man I once wrote about as the most interesting man revolutionizing the health world, commented, “The idea of making biosimilars accessible has not worked out well to date primarily because of the complexity and redundancy in the regulatory pathway. After I pointed out the complexities and errors in the regulatory guidance and offered alternative approaches, the FDA Commissioner became motivated to make changes. This is the first time that the FDA has simply withdrawn one of its guidance.”

So, what makes the opinions of Dr. Niazi so influential? In 2003, he established Therapeutic Proteins Inc., later named Adello Biologics, with the goal of manufacturing biological drugs and supply them, “at any cost affordable by anyone across the globe.” He then went on to write the largest number of books on biosimilars and worked with the White House in developing the details of the Affordable Care Act that included the Biologics Price Competition and Innovation Act (BPCIA). And is currently listed as the largest solo holder of bioprocessing patents in the world.

Challenging Biosimilar Development Plans

Although there have been barriers to biosimilar uptake in the U.S. that range from lack of provider education to therapeutic interchangeability, the FDA and non-big pharma supporters have high hopes for the future of biosimilars. So, when Dr. Niazi contacted the FDA and told them there was a dire need to re-evaluate the scientific rationale behind the current methods of testing biosimilarity – with aim to reduce barriers including redundant analytical testing and testing in humans without compromising the quality to save significant amounts of time and money – they listened.

His basic premise is built around the FDA’s commitment to engaging scientific methods that reduce testing; in line with US 21 CFR 320.25(a), which codifies the universal belief that, “No unnecessary human testing should be performed.” In the case of biosimilars, testing in healthy subjects is unethical because of their potential of making the study subjects immunoreactive for the rest of their lives. The second premise proposed by Dr. Niazi is to invoke new technologies to establish similarity between biosimilars and reference products to remove any “residual uncertainty,” to allow faster approval of biosimilars. Dr. Niazi argues the use of “thermodynamic equivalence,” a process he created that he claims removes the need for blood-level studies to determine differences between products, can do this.

Dr. Sarfaraz K. Niazi

Niazi.com

Other ideas presented included eliminating bridge testing when a non-U.S. reference is used in certain conditions (reducing the number of reference product batches required), creating a mechanism to make reference samples freely available (allowing more ethical in-vitro immunogenicity testing), minimizing non-inferiority testing in patients because of their lack of utility, and changing the pharmacokinetic testing to disposition-related parameters and allowing testing in more homogenous populations. Dr. Niazi also suggested that the FDA promote substitution of biosimilars for new patients through educational programs.

What’s Next?

Within days of the FDA withdrawing the guidance on biosimilars, Dr. Janet Woodcock, Director of Center for Drug Evaluation and Research (CDER) and the FDA Commissioner issued a July 1, 2018 Biosimilar Action Plan that considers most of the recommendations made by Dr. Niazi.

The FDA also committed to establishing an Office of Therapeutic Biologics and Biosimilars (OTTB) to expedite review process, and to invite modern scientific approaches to demonstrate biosimilarity.

In the 1980s, the Hatch-Waxman Act created a new class of drugs – generic – that has saved American patients over a trillion dollars. If successful, biosimilars, like generics, can save a lot more by making biological drugs more affordable. The FDA has demonstrated that it listens to scientific and creative suggestions. And Dr. Niazi may finally be able to reach his dream of making healthcare more affordable. “Now that FDA is open to scientific approaches to proving biosimilarity, the burden lies on developers to design their plan more creatively. I anticipate a wave of approvals by FDA that will bring price drop of more than 50% – a threshold required to disrupt the markets by taking the decision-making from the hands of prescribers to payers. Eventually I see biosimilars becoming biogenerics, which I had predicted in my first book on the subject,” he said.