IDBS Blog | 24th June 2019

The Approval Minefield Laid Out – Why Biotherapeutic Drugs Stumble

Getting a product to market has always been a challenge. Discovering something new is just the beginning.

After that, there’s the issue of securing the funding to bring the idea to life – the research, manufacturing processes, and pushing it out to customers. Achieving these milestones is worth celebrating, especially getting your product the regulatory stamp of approval.

In the last blog post, we explored biologics and biosimilars with the potential to become big hits. We also touched upon the differences in regulations between the US and EU. In this issue, we’ll investigate why there’s such a huge gap in geographical biopharma approvals and some of the difficulties faced at the regulatory level.

Achieving regulatory approval is tough, yet vital

Medications take the challenging journey of product conception to distribution to the next level. And rightly so, considering the severity of the consequences if something goes wrong – patients’ lives are on the line. Demonstrating safety and efficacy is important, otherwise the very medications produced to help patient health could end up harming them. That’s why it should come as no surprise that regulatory bodies overseeing the lifecycle of medicines are so strict.

Back in 2006, the European Medicines Agency (EMA) approved its first biosimilar and has since given its blessing to 58 biosimilars to be marketed in the EU. By contrast, the US is far behind: the FDA has only approved 18, of which just seven are available to the public. Could the US be waiting to see how drugs will fare in the EU market and build upon the available data?

Trust and public confidence go a long way

Over the years, many treatments were added to the pharmacy shelves, but almost double that amount never made it past the regulatory phase – canceled or delayed for some reason or the other.

While biosimilars and generic pharmaceutical medicines are often put into the same bucket, there is a major difference (other than the chemical vs biological make-up), which is public perception. Generics have been on the market for many years and have gained patients’ confidence. There are decades of studies available to back up pharmaceutical generics, compared to just a few years for biosimilars.

The bar has been set even higher by biologic manufacturers, who disseminate misleading information to increase the competition and sow doubt into stakeholder’s minds about the efficacy and safety of biosimilars. To prove that biosimilars are safe to treat patients, regulators set more guidelines and rules to be met.

The regulatory process in action

Let’s take Mylan’s Ogivri – a treatment for breast and gastric cancer – as an example to showcase the complexities of the regulatory process surrounding medications. The drug was developed as a biosimilar, modelled from the biological medicine marketed in the EU as Herceptin. That is, they contain the same active ingredient, trastuzumab.

In 2017, Ogivri was ready to join the growing list of biosimilars in the market. Mylan presented the results of multiple studies on quality, effectiveness and safety of the drug. The first two studies involved healthy volunteers to explore if Ogivri produces the same amount of the active ingredient as Herceptin. This would prove it has the same effect as its reference medicine, a key point for regulatory scrutiny.

The third study measured the number of patients with breast cancer with an overexpression of HER2 responding to combination treatment of Ogivri and taxane, again compared to a similar combination of the model drug.

The Committee for Medicinal Products for Human Use (CHMP) reviewed the documentation and drew up a list of questions about Ogivri. But Mylan was not able to answer all the questions put forward, and towards the middle of the year, Mylan withdrew its application for marketing authorization. Why?

The CHMP reviewed the data and documents surrounding the product and concluded that there was not enough evidence to support Ogivri’s application. The main concern in this case was that Mylan lacked a valid certificate from the manufacturer showing the product met good manufacturing practice (GMP) requirements.

Whether the production of Ogivri observed GMP or not, Mylan was not able to obtain the certificate from the product’s manufacturer in time before the application deadline. The drug may have not gotten approval at that time, but the ongoing clinical trials were not impacted. It was later given authorization in late 2018, closely followed by Prestige BioPharma’s biosimilar of the same kind, Tuzune.

Biopharma organizations have equal responsibility

Studies and medicines are not the only ones to stumble – sometimes, the entire plant can come crashing down for regulatory reasons. Aurobindo Pharma, an Indian generic pharma company, is a prime example of this. The company revealed one failure after another, bringing the quality of the medications they produce into question.

In a series of site visits, the FDA busted the quality control team for allowing their drugs to be affected by ‘objectionable conditions’. The agency found data reports written in loose notebooks and sterile operations reports left unsigned. Data was missing or incomplete in certain cases, leading to data integrity issues and unresolved investigations into data discrepancies.

And there was more! The report went on to describe unsecured computers, cleaning protocols ignored, and unsanitary conditions in the lab. In the past, it has had to recall drugs due to suspected cancerous impurities found in losartan or valsartan.

Reading this article might give the impression that a minimal amount of medicines is being approved. In reality, more drugs are being approved than ever before. The FDA gave the green light to more new drug approvals in 2018 than previous years – a record high of 21 new biologics and 7 biosimilars! The regulatory landscape might be complex, but it means patients can be sure medicines are safe treatments.


Our software can help you navigate the regulatory landscape. Find out how here, or contact our team of experts.

Sobre a IDBSEntre em contato conosco

More news