Rising COVID-19 cases impede progress of bioequivalence test

ahead drug pricing reevaluations

Difficult recruiting subjects, dropouts due to confirmed COVID-19 cases lead to additional recruitment, disrupting the test schedule

Unclear whether companies will be able to meet the drug re-evaluation deadline next February…companies request “deadline extensions.”

Pharmaceutical companies are having trouble conducting bioequivalence tests for the development of generics due to COVID-19.

 

The spread of COVID-19 has made it difficult for companies to recruit subjects, and even those recruited are dropping out after being confirmed with COVID-19, causing disruptions in the companies’ schedules.

 

With delays inevitable due to the unexpected pandemic, pharmaceutical companies have been asking authorities to extend the drug pricing reevaluation deadlines that were set for February next year.

 

According to industry sources on the 8th, several pharmaceutical companies have expressed their difficulties in progressing their ongoing bioequivalence tests due to the surge of COVID-19 cases.

 

With hundreds of thousands of people being confirmed with COVID-19 every day, recruiting patients for the bioequivalence test itself is difficult.

 

According to KDCA, 1,683,111 people were confirmed with COVID-19 over the past 1 week since the 6th.

 

With over a million people in self-isolation due to COVID-19, the companies are complaining of difficulties in recruiting necessary subjects.

 

With subject requirements are already stricter than before, difficulties in recruiting subjects for bioequivalent tests have been ongoing for some time.

 

In accordance with the revised Pharmaceutical Affairs Act passed by the National Assembly in November 2018, people who have no experience participating in a clinical trial within 6 months prior to the trial date should be selected as subjects for clinical trials.

 

With the restriction period extended from 3 months to 6 months.

 

the number of participants viable for the tests has also decreased significantly.

 

Also, even the registered subjects are frequently leaving trials to COVID-19.

 

This renders it difficult to conduct a normal bioequivalence test due to the lack of subjects.

 

The drug equivalence standards require 12 or more people in each group -the test group and control group for bioequivalence tests.

 

This means the bioequivalence tests cannot be conducted unless over 24 people register for the tests.

 

If subjects in the test group or control group are reduced to less than 12 due to COVID-19, the bioequivalence test itself may turn to waste.

 

The companies can increase the test group or control group can by recruiting additional subjects, but this would inevitably push back the schedule.

 

An official from a pharmaceutical company said, “We are planning to recruit more subjects than originally planned due to the rapid increase in the number of confirmed COVID-19 cases, but it isn’t easy.

 

Even those who already registered are leaving trials after being confirmed with COVID-19, so we’re having much difficulty conducting the required bioequivalence test” Also, if the fallouts are concentrated in a specific group, such as the control or test group, the test itself may not derive significant results.

 

For example, if 30 people were recruited for each group but 15 people from the test group leave due to COVID-19, the reliability of the test statistics may be undermined.

 

Pharmaceutical companies have also had difficulty conducting bioequivalence tests in the early stages of the COVID-19 pandemic.

 

In the early stages of the outbreak in 2020, the tests had been delayed with medical institutions discontinuing face-to-face work related to bioequivalence tests such as administration, screening, and monitoring.

 

The main reason why pharmaceutical companies are expressing concern over their difficulties is because of the pressing deadline of the drug pricing re-evaluations for generic drugs.

 

The Ministry of Health and Welfare announced a plan to re-evaluate the price ceiling of drugs, under which generics that do not meet the highest-price requirements in June 2020 are required to submit data on their ‘performance of bioequivalence tests’ and ‘use of registered APIs’ by February 28th, 2023 to maintain their previous drug price.

 

This is a follow-up measure to apply the new drug pricing system which took effect in July 2020 to registered generic products.

 

Under the revised drug pricing system, generic products can only be priced at the maximum price, which is 53.55% of the original drug’s price before patent expiry only when it satisfies both the requirements – directly-conducted bioequivalence tests and the use of registered raw materials.

 

If either of the requirements is not met, the price cap is lowered by 15%.

 

This means that a generic, which is approved by consigning the entire process to other companies without developing or producing it, will receive a drug price discount and be set at 72.25% of the previous price cap.

 

The requirement of using a registered raw material can be met by switching the API.

 

Due to the revised law, companies were left to decide between accepting the drug pricing discounts or maintaining the previous price by conducting bioequivalence tests.

 

This is why companies have been actively conducting bioequivalence tests on their registered generics.

 

According to the Ministry of Food and Drug Safety, a total of 768 plans for bioequivalence tests were approved in 1.8 years from July 2020 to February this year, which averages at 38 plans per month.

 

Compared to 445 (22 per month on average) that were approved during the 1.8 years prior to July 2020 (November 2018 to June 2020), this is a 72.6% increase.

 

Over half of the bioequivalence test plans approved recently are for registered generics.

 

Of the 51 bioequivalence test plans approved in February, 39 were already on sale as registered generic products.

 

Most of the bioequivalence tests are being conducted for ‘'in-house conversion' of the generics to manufacture in their own companies.

 

If the companies make generics through formulation research and conduct bioequivalence tests that demonstrate bioequivalence, the companies can avoid the price cuts by obtaining change approvals.

 

If companies convert consigned manufacturing to in-house manufacturing while applying for license changes, the companies can satisfy the ‘conducting bioequivalence test’ condition.

 

Whichever way, it is said that it takes up to six months or more for bioequivalence tests to be imitated and render results.

 

However, if the bioequivalence test data cannot be submitted by February next year due to a delay in the test schedules caused by the surge in confirmed COVID-19 cases, generic drugs will have no choice but to bear the drug price cuts.

 

This means that the price of generic drugs may be reduced by 15%, even after the companies spent a lot of money and effort to avoid such discounts.