Between 85 and 90 percent of people with CF are pancreatic insufficient. This occurs when thick, sticky pancreatic secretions block the release of enzymes needed to break down food for digestion. With no enzymes to break down food, much of the protein, fat and carbohydrate in food is not absorbed. This can result in poor growth, gastrointestinal symptoms like gas and bloating, and malnutrition.

To make up for this lack of enzymes, people with CF who are pancreatic insufficient should take pancreatic enzyme replacement therapy before they eat the majority of foods. Synspira's potential enzyme therapy SNSP003 contains three non-animal derived enzymes designed to break down fats, proteins, and carbohydrates (lipase, protease, and amylase, respectively).

Despite the approval of new treatments for the underlying cause of CF, many people with CF will continue to need treatments for complications such as malabsorption. The CF Foundation is dedicated to funding research into potential treatments for complications of CF, spending $62.5 million in 2018. There are more than 15 drugs in the pipeline, including potential anti-infectives, anti-inflammatories, mucociliary clearance therapies, and nutritional agents.