Last year was disappointing for new drug approvals as the United States Food and Drug Administration cleared only 22 new medications to be sold, the lowest number for the past six years and a sharp decrease from the 45 approved in 2015.

The European Medicines Agency approved 81 new products that require prescriptions against 93 during 2015. Unlike with the FDA, the EMA list includes approvals of generic drugs in the list.

The downturn in approvals suggests that the pharmaceutical industry might be going back to more normal levels of productivity after a spike in FDA approval during both 2014 and 2015, at a time when the new drugs approvals hit a high of 19 years.

A number of factors led to the drop in approvals during 2016, the director of new drugs at the FDA John Jenkins explained during a December conference.

Five new drugs scheduled to be approved in 2016 won approval during the latter part of 2015. There was a drop as well in pharmaceuticals filing for approvals and the FDA also delayed or rejected more drug application during 2016 than in 2014 and 2015.

Some of the drugs delayed might be approved during 2017, including a multiple sclerosis treatment from Roche and a rheumatoid arthritis treatment from Sanofi.

Most executives in the industry are upbeat over the hunt for more new medicines, given the recent advances against cancer and the improved understanding of genetic basis of other types of diseases, which resulted in complete development pipelines for many companies.

However, it is still challenging to have new drugs go through approval process as well as securing a reasonable financial return when they are finally launched due to a resistance from insurers and governments to the increasing costs of medical treatments.

Deloitte, a consultancy, says the returns on the investment of research and development at the top one dozen pharmaceuticals dropped to only 3.7% during 2016 from a 10.1% high during 2010.

More and more political pressure related to high prices of today’s medicines has become a huge challenge during a time when pharmaceutical and biotech companies are in the developing stage of more drugs that are targeted at niche populations of patients.

For example, the final drug winning approval in 2016 from the FDA was Spinraza from Ionis and Biogen Pharmaceuticals. It became the first medicine that treats patients that have spinal muscular atrophy, a genetic disease that is rare and often times fatal. The drug costs $125,000 per dose.