“When the EMA reviewed our biosimilar HD201, it neither considered the product drift of the original drug Herceptin nor applied consistent criteria for analytic equivalence comparison. As a scientist, I could not accept such an unscientific approach, which is why we applied for re-examination. Therefore, I will strongly appeal Prestige BioPharma’s stance to the EMA.”

So said Park So-yeon, CEO of Prestige BioPharma, a Singapore-based company, during an online interview with Korea Biomedical Review.

On Thursday, Prestige BioPharma received a negative opinion on the marketing authorization for HD201, a biosimilar referencing Herceptin, from the EMA’s Committee for Medicinal Products for Human Use (CHMP).

In a public filing and a letter to investors, the Kosdaq-listed company repeatedly said it could not accept the EMA’s review results.

“We have already applied for re-examination to the EMA,” Park said.

The company expressed its intention to apply for re-examination and plans to submit data for a new review within the next 30 to 60 days.

Then, the EMA has to bring new reviewers to re-evaluate the biosimilar and come up with a conclusion within 60 days, she explained.

According to Park, the EMA re-examination includes one month of coordinating opinions with the company. Thus, it will take about 120 days to get the final result of the re-evaluation, Park said.

Prestige BioPharma changed the manufacturing process of HD201 to reflect the product drift of Herceptin during the phase 3 trial.

However, the EMA did not consider all batches produced before and after the manufacturing change. Instead, it considered only the batch produced after the manufacturing change as the basis for analytical equivalence comparison, and this was irrational, Park argued.

“As the quality of the original drug changed, we expected that the EMA would review all batches produced before and after the manufacturing change. Moreover, we produced only a small batch after the manufacturing change, and the numerical range was narrower,” Park said. “Then, one examiner at the EMA argued that there should be only one clinical batch to compare with the commercial batch. This examiner’s claim ‘snowballed’ and led to the EMA’s conclusion.”

Park emphasized that the EMA had no rule to require a single production batch for analytical equivalence comparison. She criticized the EMA for setting too narrow criteria and making unreasonable demands.

“The ‘Afucose’ range required by the EMA was only one-tenth of that of Herceptin. Therefore, if the EMA reviews with such narrow criteria (hypothetically), Herceptin will be eliminated first,” Park said.

She added that EMA’s criteria were not adequate for an antibody-drug review.

Prestige BioPharma met with the FDA before applying for marketing approval and agreed to compare analytical equivalence based on a commercial batch, Park went on to say.

This signals that the EMA’s review criteria were exceptional, she said.

Also, Park said the EMA’s review of Prestige BioPharma’s biosimilar was unfair compared with biosimilars by other companies.

One biosimilar maker failed to prove equivalence because the drug candidate was out of the Herceptin’s range in a phase 3 trial. However, the EMA recognized Herceptin’s product drift and granted the permit to the biosimilar, she said.

Prestige Biologics, a CDMO subsidiary, was expected to produce HD201 once the biosimilar won the license in Europe.

“We are confident that we will obtain a European nod for HD201. So, the production at the CDMO subsidiary will be no problem but delayed only a little,” Park said.

During the preparation for the HD201 product, Prestige Biologics’ original technology was patented. A team for CDMO marketing will showcase Prestige Biologics’ technological power at the 2022 Bio USA in June, she said.

Prestige BioPharma has almost completed enrolling patients for a global phase 3 study of Avastin biosimilar, HD204. According to Park, it expects to apply for approval to the EMA and the FDA next year.

As for Humira biosimilar, HD1502, the company will start a phase 3 study within this year once it secures its safety in a phase 1 trial in Spain, she said, adding that Prestige Biologics completed preparations for clinical samples.