EMA tells companies to declare peptone use in biologics fermentation
Peptones, partial hydrolysates of protein created through digestion with acid or enzymes, are used in culture media due to their ability to promote and sustain the growth of organisms, including those used in the production of biologic medicines and vaccines. Human insulin is among the medicines made using peptones.
The suitability of peptones for this role is underpinned by their status as good natural sources of amino acids, peptides and proteins.
However, as peptones are derived from materials including animal tissues and put into contact with organisms that take up components from growth media, they are also a potential source of contamination.
The EMA and other European bodies have discussed that risk in publications in the past but until now peptones were absent from the agency’s question and answer document about the quality of human medicines.
In addressing the gap in the Q&A, EMA has posed and responded to two questions relating to the use of peptones in biopharma manufacturing.
The EMA’s response to the first question clarifies that it is necessary for dossiers including marketing authorization filings to state the source of any peptone used in the fermentation process for active substances.
Manufacturers must disclose whether the peptone is animal or vegetable in origin and provide the name and address of the supplier. If there is a change to the information, the company should file the appropriate variation and immediately inform any finished product manufacturers that use the active substance.
The EMA position reflects its view that peptone is a critical raw material.
That view informs the EMA’s response to the second question. In the response, the EMA explains that the use of fish peptone must be declared in the active substance specifications as the material could be contaminated with high levels of histamine that pose a threat to public health.
Declaring the use of fish peptones in the specifications ensures histamine is a specified impurity that is controlled to an acceptable limit.
Elevated histamine levels stemming from the use of fish peptones has caused problems for producers of the antibiotic gentamicin in the past. Last year, the EMA detailed some of the problems in a report that described how inadequate storage had accelerated the decomposition of fish, thereby resulting in elevated histamine levels that were linked to adverse events including death.