Animal pharmaceutical development proves challenging, costly for industry
Use of antibiotics in the animal agriculture industry is continually under fire, with calls from the public and Congress to significantly slow use of antibiotics in food animals.
“I represent the industry, and I’ve seen a lot through my experience in my vet practice and now in the industry,” commented Animal Health Institute Vice President of Regulatory, Scientific and International Affairs Richard Carnevale. “While the regulatory environment going forward affects antibiotic use and development, there is a component to the discovery and development of new products and the public perception of what is happening.”
Carnevale noted that the public takes issue in the use of medically important antibiotics in food animas and marks it as contributing to antibiotic resistance. As a result, the discovery and development of new products is important.
Discovery and development
“In scientific discovery, it is difficult to find a new compound that is successful,” Carnevale explained. “Only one in 20,000 compounds are successful.”
Once a compound is developed, it first goes through preliminary trials including bacterial test and chemical screens. After passing those trials, drugs are introduced to pre-clinical trials, usually in the form of general lab animal acute, chronic studies and dose ranging studies.
“If it goes that far, the antibiotic goes into full blown clinical trials with the target animal or humans,” he continued. “It goes into controlled field trials, and if it is a food animal, residue studies and the regulatory review.”
Once approved by the Food and Drug Administration (FDA), Carnevale noted that animal drug approvals are then published in the Federal Register and ongoing monitoring continues.
On top of a limited chance of success, he added that the expense of developing new drugs is monumental.
“The process takes seven to 10 years,” he said, “and can cost $100 million.”
Each new pharmaceutical product costs an average of $38.8 million, but most companies agree that developing products for beef cattle costs closer to $100 million or more.
Rigorous approval process
The FDA approval process is extensive and rigorous, including quality, safety and efficacy trials.
“Quality deals with how well it is manufactured,” explained Carnevale. “With regard to safety, there are several components.”
Not only are animal drugs required to be safe to the animal and the environment, FDA also conducts human food safety trials to ensure residues in food aren’t present.
“FDA spends time related to toxicology, residue depletion, tolerance levels and withdrawal times,” Carnevale said. “With antimicrobials, there are additional requirements, including the impact of food residue on human gut flora.”
Additionally, guidance documents also require FDA to look for the potential for antibiotic or antimicrobial resistance selection and the impact to human health through food.
“The process is more complicated for animal drugs than it is for humans,” Carnevale mentioned, “which leads to added complications in getting animal antibiotics approved.”
“All new antibiotics approved in recent times have been approved for short duration, by prescription or by veterinary feed directive (VFD),” commented Carnevale. “There have been no new products for herd or flock administration.”
Since 2003 when FDA implemented Guidance 152, Carnevale said that drug approval has been limited to very targeted drugs distributed under prescription.
“Guidance 152 is portrayed as a qualitative risk assessment, but it is about risk management,” explained Carnevale. “They look at the antibiotic resistance in the animal, exposure in food and the consequence to human health.”
He noted that critically important human medical products would likely be very restricted, as a result.
FDA categorizes new drugs as low, medium or high risk, and all recent products have been rated medium to high risk, or categories one and two.
For future development, Carnevale marked that companies will prefer to research products with no human use or unique analogs will be preferred.
“It is highly unlikely that new antibiotics will be available over the counter,” he said, “and it is likely that administration will be very focused to individual injections and individual animal application.”
Additionally, future developments will focus on world food production needs.
“In development of novel antibiotics that meet animal health, food safety and human health needs, the challenge lies in whether the regulatory agencies are going to cooperate,” Carnevale commented. “If it is a risk-only equation, we aren’t going to get very far.”