Lessons from the food and beverage industries
TBA and TCA taints are long and well recognized in the food, wine, and beverage industries (2). The technical literature from
these industries is useful to the pharmaceutical industry regarding the origin of these odors and taints, analytical methods
developed, and risk-management strategies that may be employed.
It is widely recognized that TBA and TCA taints can migrate into packaging materials, ingredients, and products by leaching
or diffusion. Literature examples from the food and beverage industries indicate that chemically porous polymeric materials,
such as wood, corrugate, and plastic, are susceptible to contamination with these taints (see Table II). Likewise, food and beverage products are quite porous and can readily absorb these taints from contaminated materials.
Consumers having sensory expectations are more likely to notice contamination of food, beer, and wine because these taints
can also produce unpleasant tastes that would more likely be noted during consumption.
Table II: Representative literature references to Organohalogen taints in the food, beverage, consumer healthcare, and pharmaceutical
industries (1966 to 2010).
PDA TBA/TCA benchmarking survey
The PDA task force prepared a survey to benchmark knowledge of TBA/TCA odors and taints and actions taken within the bio/pharmaceutical
industry to mitigate the risks of these musty/moldy odors and taints. PDA distributed the survey in May 2011 to 27 pharmaceutical,
consumer healthcare, and biotechnology manufacturers, as well as packaging suppliers represented on the Task Force, to collect
definitive feedback (3). The survey was sent to specific experts within these companies, and it was requested that the responses
reflect the current position of the organization regarding how issues with these taints are handled.
The responses from 19 companies (70% of those polled) were used to help benchmark industry practice and conduct a gap analysis.
The 32-question survey covered the following areas: complaint-handling system, analytical methods, supply-chain controls,
and regulatory issues. The full results from this survey are available through PDA (3).
Vulnerabilities in the supply chain
One outcome of the PDA Technical Report is that each company should review its supply chain to ensure that proper good distribution
practices (GDPs) and controls are implemented to mitigate the risk associated with TBP, TCP, TBA, and TCA contamination. To
date, the primary focus in industry has been on the use of heat-treated (HT) wood pallets that are certified to be TBP/TCP-free
to prevent risks of TBA/TCA odors and taints from entering into the supply chain. Other potential sources through which TBP/TCP
can enter the supply chain should also be considered and are addressed in the PDA TBA Technical Report. For example, TBP/TCP
can come from recycled materials and disinfectants. In addition, because fungi perform the biomethylation of TBP (or TCP)
to TBA (or TCA), ventilation and moisture controls should be implemented to minimize fungal growth on pallets.
Figure 1: Halophenol to haloanisole biomethylation conversions (adapted from Ref. 2). (FIGURE COURTESY OF AUTHORS)
The primary root cause for TBA-tainted product recalls in the bio/pharmaceutical industry was that wood treated with TBP (or
TCP) was used to construct pallets that were then used to ship and or store plastic packaging components. In this supply chain,
the TBP (or TCP) from the pallets was biomethylated to TBA (or TCA) which then contaminated plastic packaging components before
product filling and, ultimately, the drug products stored in these components. The ability of TBP/TCP and the more volatile
TBA/TCA, formed by biomethylation, to readily migrate from one material to another also makes the taint distribution uneven.
It also makes determining the ultimate root cause of the contamination challenging.
According to the International Plant Protection Convention (IPPC), most pallets shipped across national borders must be made
of materials that are free of invasive insects and plant diseases. The standards for these pallets are specified in the International
Standards for Phytosanitary Measures (ISPM) No. 15. Regulation of Wood Packaging Material in International Trade (2009 Revision).
In accordance with ISPM 15, wood pallets intended for international trade should be constructed of either heat-dried or methyl
bromide-treated lumber. Therefore, tainting could be associated with imported TBP/TCP-treated wood or treated wood pallets
from outside the US.
There are approximately 1–2 billion wood pallets in circulation in the US, and an estimated 500 million pallets are replaced
annually. Total control of TBP-impregnated wood pallets entering into US commerce, therefore, may be difficult, if not impossible.
A unique challenge may be the control of wood pallets constructed from TBP-treated lumber entering Puerto Rico from neighboring
South America, where TBP is registered for use as a wood preservative. It is known that TBP is used as a wood preservative
in other regions of the world, including Northern Asia and Eastern Europe. In addition, multiple examples in the literature
from the food and beverage industries highlight that TBA tainting has been an issue in other regions of the world, including
Australia. Based on the available literature, goods are more susceptible to TBA tainting if exposed to TBP-treated wood when
moving from higher to lower temperatures under high humidity because the risk of condensation increases. Higher moisture levels
increase the risk for fungal growth and, ultimately, for biomethylation of TBP (TCP) to TBA (TCA). The PDA Technical Report
provides more details about these specific risks.
The report addresses controls that can be employed to mitigate the possibility of TBA/TCA formation and tainting for pallets,
shipping containers, corrugate, and plastics. The main approaches include:
- Eliminate use of TBP/TCP in the supply chain
- Minimize risk of fungal growth in the supply chain
- Use appropriate humidity control and ventilation in warehouses
- Monitor wood materials, such as pallets, shipping containers and corrugate, for mold growth
- Train personnel to be on alert for musty, moldy odor characteristics of TBA/TCA.