The drug component and finished product CGMP guidances and regulations emphasize prevention of problems and avoidance of contamination rather than final testing or examination alone. In other words, control strategies that prevent contamination are central to CGMP, while control strategies based on testing alone do not comply with CGMPs. Raw materials from animals can have microbial pathogen health risks based on country of origin, LPE processing, transportation, and manufacturing processing. Under the right circumstances, raw material from animals can provide a suitable (e.g., nutrient-rich) environment for bacteria and mold to proliferate, or for viruses and other pathogenic agents to remain infective. If undetected contaminated raw material enters the manufacturing process, it can remain pathogenic in the product and a hazard to the consumer. The manufacturing conditions used in most ingredient manufacturing processes are often insufficient to eliminate all pathogenic agents from the ingredient. Methods of minimizing contamination of raw material with pathogenic agents may include the following:

Animal source
When animal-derived material is used, it is important that it be derived from healthy, disease-free animals. The occurrence of pathogens can vary greatly among different animal species. Ingredient manufacturers should understand the pathogenic risks associated with different animal species and with different organs, glands, or tissues within species. Drug ingredient manufacturers should be aware that even healthy animals can be reservoirs for pathogenic agents and improper handling can spread contamination. If improperly handled, microbial contamination can transfer to uncontaminated tissues and cause contamination.

Ensuring the health of U.S. livestock is the responsibility of many Federal agencies, most of which are part of the U.S. Department of Agriculture (USDA). Animal-health and food-safety regulations are detailed in titles 9 and 21 of the Code of Federal Regulations. Animal health authorities in each State develop regulations that are consistent with the Federal agencies and are responsible for monitoring and controlling diseases in the State’s domestic livestock and poultry. State inspectors ensure compliance by companies with individual State standards as well as with Federal meat and poultry inspection statutes. States assist in controlling diseases through inspections, testing, vaccinations, treatments, quarantines, and other activities.

Awareness of the conditions of control and monitoring of source animals will aid in determining which animals and animal parts are appropriate for drug product manufacturing.

LPE
Ingredient manufacturers should consider auditing the LPEs supplying raw materials to them and ensure their compliance with all Federal and State government regulations. It is recommended that manufacturers develop standard operating procedures and define sanitation requirements of raw materials immediately after butchering, including, for example, the following:

Chilling requirements, if indicated, including temperature ranges and how soon after butchering chilling should begin Chemical preservation methods, if indicated, including types and concentrations of chemical preservatives used Storage processes, including sanitization of containers and container type/material (e.g., stainless steel vs. food-grade plastics)
Transportation criteria, including sanitization of containers, if different from storage and temperature ranges the overall contamination of carcasses with pathogens depends on not only the prevalence and numbers of the pathogens on the hair, skin, and in the intestinal tract of the animal, but is significantly affected by the degree of cross-contamination occurring from these sources during slaughter and processing (see USDA references, below, for additional information). FDA expects that manufacturers will establish appropriate specifications for bioburden in their incoming raw materials. References:

USDA Animal and Plant Health Inspection Service
USDA Animal and Plant Health Inspection Service, Import and Export
USDA Food Safety and Inspection Service, Parasites and Foodborne Illness Fact Sheet