Wood Pallet and pharmaceutical industries working together
The U.S. Food & Drug Administration provides easy access to safety alerts, market withdrawals and enforcement reports, including all recent recall information by product area, including food, drugs, biological products, devices and cosmetics. Search with keywords such as mold, musty, odor, pallet, fungicide, tribromoanisole (TBA), tricholoranisole (TCA)
By David Ulrich, Jorgelina González and Dr. Brad Gething
This is the fourth and final article meant to further the conversation and cooperative efforts between the pharmaceutical industry and wood packaging suppliers. Specifically, this fourth article will give an overview of the issue (general pallet control specific to the issue of 2,4,6 TBA and 2,4,6 TCA taints) by summarizing the first three articles and giving an update on recent events that have occurred regarding wood pallets and anisole taints.
This effort was initiated due to the numerous prescription pharmaceutical and OTC (over the counter) products that were being recalled, starting in 2009, to determine if these recalls were truly a wood pallet issue (i.e. inherent to wood pallets) or a supply chain pallet management issue (i.e. would appropriate controls mitigate this issue). The goal of these initial discussions was to determine the root cause of the taints. The first three articles published by NWPCA focus on the following:
- The first article gave background on the recalls and what is 2,4,6 TBA or 2,4,6 TCA, where do they come from and why wood pallets were originally thought to be the culprit of the taints and therefore the recalls. It also gave a non-pharma history of these taints related to the food and beverage industry, established from the Australian Food and Grocery Association booklet on taints.
The conclusion was that (1) taints have been identified in the food and beverage industry (milk, beer, wines, etc.) for decades, and that (2) controls were needed by pharmaceutical manufacturers regarding pallet source, moisture control and storage. The term for these controls is GDP (Good Distribution Practices)
- The second article focused heavily on controls needed at the sawmill and the pallet manufacturing site to eliminate the risk of taints in their products. It also focused on types of wood species, cleaning, and how pallet manufacturers can be proactive in mitigating the risk of these taints in their supply chain and manufacturing process, and how the pallet industry can partner with the pharma industries to educate on wood pallets.
The conclusion was that pallet manufacturers and other industries that are susceptible to taints (food, beverage, pharma) need to work together with their suppliers so that consistent levels of controls are implemented and sustained.
- The third article focused on controls needed by pharma manufacturers, and recommended that the “pallet management controls” that were in article #2 be integrated into their GDPs and part of their Supply Chain Integrity (SCI) plan.
The conclusion was that these GDP controls are an extension of the pharma manufacturer’s GMP (Good Manufacturing practices) and that (1) knowing the pallet manufacturer (and the source of their wood) and their controls, (2) implementing controls for storage and inspection (e.g. household clean) are adequate controls to mitigate this issue.
Starting in 2009 the pharmaceutical industry began receiving complaints from customers (patients) about “musty/moldy odor products.” In the pharmaceutical industry, complaints are categorized into the three distinct categories (1) quality assurance complaints (e.g. tablet is cracked) (2) medical complaints/adverse events (AE) (e.g. I developed a rash at my injection site) and (3) service complaint (e.g. wholesaler might state that they received shipment 1 day late). These initial complaints came in on a branded OTC product in the U.S. (packaged in U.S. and in Puerto Rico), but soon spread to greater than a dozen products both OTC and prescription drugs, and to Canada and western EU. Since some of the complaints resulted in patients vomiting and a few going to the hospital, these were initially classified as medical complaints AE. During the development of this issue, many MoH (Ministry of Health) officials started to get involved, initially the U.S. FDA then other countries’ MoHs.
So What Caused the Odor?
The complaint samples were returned to the manufacturers and tested for mold contamination (a logical response due to the product’s odor), but no mold was found, which led to the investigation of the packaging process where the “taint” (odor) was found. Basically lumber received for pallet manufacturing was pre-treated with a fungicide called 2,4,6 Tribromophenol (2,4,6 TBP), or 2,4,6, Trichlorophenol (2,4,6, TCP) both of which are used commonly in hot humid regions like Brazil and southeast Asia to impede the growth of mold on the newly cut wood and new wood pallets. Neither TBP nor TCP are registered in the U.S. by the EPA or USDA.
Since this “taint” issue spread to many companies and multiple products, a multi-pharma group under the PDA (Parenteral Drug Association) was formed to collectively work with U.S. FDA guidance on the RCA (root cause analysis) of this issue. With this initial investigation pointing to wood pallets, many pharma companies investigated switching their whole supply chain from wood to plastic or possibly even stainless steel pallets, and quickly realized this was not a near term feasible option. Then controls for wood pallet manufacturers (article #2) and the pharma supply chain (article #3) were investigated. But the fundamental questions to be asked were 1) what is 2,4,6 TBP/TCP and 2) is this a new issue?
What are “Taints”?
By far, the best educational document available is authored by the Australia Food and Grocery Association (AFGA). In this booklet, the AFGA chronicles five decades of taints due to 2,4,6, TCA and 2,4,6, TBA in the food and beverage supply chain. The musty odor caused by TBA and TCA have resulted in complaints and recalls on food and beverages (see table #1) for decades despite their ubiquitous nature (e.g. they naturally occur in potable water system). TBA and TCA (substances called anisoles) are converted via a process called biomethylation from 2,4,6, TBP and 2,4,6 TCP (parent phenol compound), respectively. TBP and TCP are phenol-based compounds commonly used as a fungicide in some countries. (See Figure 1).
| Figure 1. Conversion of fungicide into taints
> 2, 4, 6, tribromophenol (TBP) and 2, 4, 6 trichlorophenol (TCP) are common fungicides used in hot/humid climates to control mold growth on freshly cut wood
> Through biomethlylation (a naturally occurring process and ubiquitous in nature) the phenol is converted to an anisole resulting in 2,4,6, tribromoanisole (TBA) and 2,4,6, tricholoranisole (TCA)
> The anisole have a low odor threshold and smell musty moldy
The Australian Food and Grocery Council published “Organohalogen Taints in Foods” which documented taints detected in food, beverages (e.g. canned beer), water, etc. from the 1960s to 2010 (see Table 1). A number of sources were found to be the root cause of taints including fiberboard and wood floors of shipping containers. The very low odor threshold of various organohalogens was also included in the report.
This authoritative document confirmed that the taint problem is not a pallet issue, but more of a pallet management and supply chain issue.
What about Moisture - is that an issue?
ISPM 15, which mandates the treatment of solid wood pallets and wood packaging to control invasive insects from freely moving around the world, approves of two methods for treating wood:
- Methylene Bromide (MB) fumigation – treated to a specific temperature-time based schedule outlined in ISPM 15.
- Standard heat treatment (HT) – the wood material is heated to achieve a minimum core temperature of 56ºC for a minimum of 30 minutes. A drawback is that treatment can increase surface moisture, hence increasing the likelihood of mold.
- The kiln drying heat treatment (KD-HT) – this treatment process meets the standard HT process with the additional step of reducing the average wood moisture content below the fiber saturation point (19% or 15% moisture content is typical).
Initially the pharmaceutical industry thought heat treatment was an answer to control taints. However the pharma industry learned (as the pallet industry learned in 2001) that heat treating was not intended for mold control but for control of invasive species. Furthermore, HT can induce mold growth if the surface moisture remains without taking necessary action through drying or chemical treatment; therefore, it is logical for a lumber company in a country with a tropical climate (e.g. Brazil) to control mold growth with a fungicide, resulting in the use of the phenol-based TBP and TCP.
The problem arises when these very effective fungicides are applied to lumber used to manufacture pallets, and if the pallets are not properly stored (i.e. pallet management program) by either the pallet manufacturer or the supply chain that uses them, the phenol can convert to the anisole, which once again smells like mold. Moreover the anisoles have a very low odor threshold (i.e. at parts per million many people can smell TBA/TCA). Understanding the pallet manufacturing process and not allowing TCP or TBP on wood or pallets is a first step towards controlling these taints in the pharma supply chain, but that is not the only CAPA (corrective action/preventive action). Proper pallet storage away from weather elements with adequate ventilation is just as important.
The Ubiquitous Nature of Anisoles (and what about bleach)
For example, a shipping container used to transport pineapples or bananas or any “organic” product may experience some juice leakage onto the container floor. If the transport container has wood runners (see Australian booklet) and the container is washed out with bleach (an acceptable procedure), but the bleach is allowed to sit and soak into the wood, this can naturally produce an anisole (note bleach is hypochloric acid (HOCl)). These containers that are washed with bleach (but not rinsed), are the cause of a great many of the taints found in food products.
The following recommendations were discussed in great detail in articles #2 and #3. General recommended corrective actions/best practices/standard operating procedures (SOP) for effective pallet management are:
- Pharma manufacturers need to know their pallet supplier, and make them part of their supplier program as an approved vendor (with agreed upon specifications).
- Make pallet management part of audit program for third party manufactures (TPMs) including packaging supplier and commodity (e.g. plastic bottles).
- Specification - Don’t apply any halogenated fungicides on wood pallets.
- ISPM 15 compliance is necessary, however does not mitigate taints and the need to know what method your pallet manufacturer uses.
- Pallets should be inspected for “household cleanliness.”
- Pallets should be stored high and dry.
Pallet Manufacturer Controls
Since the “root cause” was determined to be indirectly related to wood pallets, the next step was to look at how pallet manufacturers source their wood and control their processes so that fungicides can be avoided when possible. While controls used in the wood pallet industry were extensive, they were by and largely unknown to the pharma industry. Part Two of this series played an integral part in communicating those control. KD HT (or air drying if feasible) is the most effective process (vs. MB or standard HT) to control for ISPM 15 and prevent the need for fungicides.
Finally, Pharma Manufacturer Controls
Now that we have an understanding of 1) the life cycle of a pallet 2) what are anisoles, 3) where they come from and 4) how to control them, the final step is pallet management by the pharma manufacturer. Pharma manufacturers have numerous controls based on government regulations on their very complex manufacturing processes, termed GMPs (good manufacturing practices). Recently these GMP controls are expanding out of necessity and by government regulations into supply chain control, termed GDPs (Good Distribution Practices). Treating a pallet manufacturer with the appropriate level of supplier controls AND developing a pallet management program is a relatively simple and effective way to mitigate the risk of TBA/TCA in the pharma supply chain. The following is a summary from Article #3:
Develop a SOP for pallet management. This can be stand alone or integrated into the material control program:
- Store pallets properly
- Pallets should be stored high and dry with adequate airflow.
- Pallets should be “house-hold” clean, meaning they look clean and are free of debris and foreign substances.
- Pallets must be structurally sound.
- Don’t apply any halogenated fungicides on wood pallet.s
- Bleach may be used following proper rinsing and drying procedures.
- Free of odor
ISPM 15 compliance: This is necessary but does not mitigate taints, and the method of treatment by the pallet manufacturer must be known.
- This specification is required to ship pallets across international borders.
- HT is typically preferred by most countries.
Pharma manufacturers need to know their pallet supplier and make them part of their supplier program as an approved vendor with agreed upon specifications.
Make pallet management part of audit program for third-party manufacturers (TPMs) including packaging supplier and commodity (e.g. plastic bottles).
Has progress been made?
The timing of this article provides the opportunity to 1) revisit this issue that was a primary focus of the pharma industry for about four years and 2) allow both the pallet manufacturer and pharma (and food/beverage, etc.) manufacturers to review the controls put in place and assure themselves that they haven’t been undone.
As noted above, the impetus behind this collaboration between the wood packaging and pharma industry was the recall of OTC products in 2009. Since then, and the writing of the previous articles in 2012, several other recalls relating to TBA/ TCA taints have occurred (summarized in Table 2).
The positive takeaway from this information is that there hasn’t been a reported recall due to a TBA/TCA taint since May of 2013, which may indicate that precautions being taken by both industries are working to prevent the anisole contamination.
The issue of TCA/TBA taints hasn’t been completely resolved, considering that U.S. FDA recalls have occurred as recently as 2013. Nonetheless, education on and implementation of best practices (within both the pharmaceutical and wood packaging industries) will help control or even eliminate taints from the pharmaceutical supply chain.
(Article published in PalletCentral Magazine, March-April, 2015)
David Ulrich holds the title of QA director Pharma Supply Chain at Abbott Laboratory. Jorgelina González is the technical lead at Paleteras Unidas & Caribe Recycling. Dr. Brad Gething is technical and PDS manager at NWPCA.