Salvaged/Returned Goods and Destruction
Good manufacturing practices (GMP) regulations were designed to ensure that pharmaceutical products that are manufactured and released for distribution are safe, pure, and effective, and that they have a level of quality commensurate with their use in humans or animals. This level of quality needs to be maintained throughout the distribution network to ensure that products are not negatively impacted during transit and subsequent storage. When pharmaceutical products are returned to the company, or salvaged after a natural disaster, it is imperative that appropriate measures are taken to verify the quality of the product before reconditioning or releasing the product back into the supply chain. It is critical that returned or salvaged product that is ultimately rejected is disposed of appropriately.
RETURNED DRUG PRODUCTS
Drug products that are returned to the pharmaceutical company, for whatever reason, need to be identified during the receiving process and segregated from other saleable product until an appropriate disposition is made. Documentation of the receipt of returned goods, including the product name, strength, lot number, reason for the return, and quantity returned, must be recorded. If the reason for the drug product return implicates other batches, an investigation should be conducted to determine the extent of the issue.
After receipt, returned goods need to be evaluated to determine an appropriate disposition (for example, return to stock, reprocessing, or rejection). This evaluation should take into account the length of time outside the control of the pharmaceutical company, the likely conditions under which the product was distributed or held before return, and the condition of the drug product, its container, carton, or labeling. In the case of an error in shipment, or if the drug products have been in the distribution channel for a brief time, this evaluation may be limited to a physical examination of the returned product. In this case, if the physical examination demonstrates that the product was not damaged during the short period of time that it was outside the control of the company, it can be returned to stock as saleable product.
In situations where the product has been in the distribution channels for some time, or there is a question about how the product was stored, additional testing may be necessary to ensure that the product meets appropriate standards of safety, identity, strength, quality, and purity. In general, products that have been outside the control of the pharmaceutical manufacturer for some time should not be returned to saleable stock unless:
• Products are in their original unopened containers and are in good condition
• Products appear to have been stored and handled appropriately
• Remaining shelf life is suitable for continued distribution
• Products have been tested to ensure that they meet the appropriate quality standards
European regulations require that returned goods be examined and assessed by a person authorized to do so. The company needs to weigh the benefit of returning the product to stock against the cost of additional verification testing to ensure that the product has not been negatively impacted. In addition, the pharmaceutical company should look closely at the labeling of the returned drug product before returning it to stock to ensure that the product labeling includes the latest safety information. Reprocessing of returned drug product is allowed provided that the subsequent drug product meets the appropriate standards, specifications, and characteristics of the original drug product. Reprocessing is a viable option where an update to the labeling is warranted to ensure that the latest safety information is available for patient use.
In all cases, the holding, evaluation, inspection, and testing, if necessary, to disposition a returned product should be documented. Release of returned product back into the supply chain should be done only after review of all of the relevant information by the quality unit (QU) or qualified person (QP). The activities surrounding returned goods, and the functional areas involved in the process, need to be outlined in a formal procedure, and records of the returns process need to be maintained.
Finally, returned drug products may serve as an indication of quality problems related to the product itself or how the product was handled during the distribution process. As a result, it is imperative that the root cause for the return be identified and documented so that the returns data can be reviewed as part of the annual product review process.
SALVAGED DRUG PRODUCTS
When it is clear that pharmaceutical products have been subjected to improper storage conditions (for example, extremes in temperature or humidity) or exposed to atypical conditions (for example, smoke or chemical fumes) due to natural disasters, fires, accidents, or equipment failures, they should not be salvaged and returned to the marketplace. Whenever it is unclear, or there is some level of doubt regarding whether the drug products have been subjected to these types of conditions, salvaging operations may be conducted, but only when it is evident from analytical testing that the drug products meet all applicable standards of identity, strength, quality, and purity, and it is evident from an inspection of the facility where the salvaged drug products were held that the drug products were not subjected to improper conditions as a result of the natural disaster or accident.
In the case of salvaged drug products, a preponderance of evidence that demonstrates the acceptability of these types of products is required. Without a substantial body of evidence, salvaged drug products should be rejected and disposed of appropriately. The outcome of the evaluation of salvaged drugs should be documented.
Reverse logistics is the term used to describe the process of returning products back through the distribution network for reimbursement, product assessment, and appropriate disposal. Recognizing that the effective management of the reverse logistics process is essential for the company and the environment, some pharmaceutical firms have turned to third-party reverse logistics companies to handle all aspects of the returned goods process. In general, the product that flows through these processors will ultimately be rejected, and therefore no evaluation of the product is deemed necessary.
Like any third-party service provider that conducts a GMP operation on behalf of the pharmaceutical company, these providers must be assessed to ensure that they are capable of doing the work, providing adequate data back to the pharmaceutical company for quality evaluation, and that they are disposing of product in compliance with the appropriate laws and regulations.
DISPOSAL OF DRUG PRODUCTS
Public awareness and concern are growing over the disposal of pharmaceutical products and the potential for adverse impact on the environment. An article (“Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999–2000: A National Reconnaissance,” published in 2002 by the US Geological Survey) outlined the presence of pharmaceuticals and other organic wastewater contaminants in streams across the country. This report highlighted the need for improving the handling and disposal of pharmaceutical waste. Proper disposal of potentially dangerous pharmaceutical products is now of critical importance not just in the United States but around the world.
All drug products that are rejected by the pharmaceutical company need to be disposed of in accordance with applicable laws and in a manner that protects consumers as well as the environment. Many drug products are considered hazardous waste and must be disposed of by companies that are licensed to handle these types of materials. In the United States, the Environmental Protection Agency (EPA) is responsible for defining hazardous chemicals and the procedures to be followed to properly dispose of these materials. Drug formulations are considered hazardous waste if they fall into one of two primary categories: listed hazardous waste or characteristic hazardous waste. It is critical to understand the EPA (or other relevant environmental regulatory agency) requirements as they pertain to a company’s specific products, that
the products are assessed to determine the appropriate category for disposal and, ultimately, that they are disposed of in accordance with the laws and regulations that govern the operations in the area. The complexity of the laws has increased the use of third-party vendors by pharmaceutical companies, but it is important to understand that these vendors need to be adequately assessed and qualified by the pharmaceutical company to ensure that they are abiding by the laws for handling and disposal of returned drug products.
Controlled substance drug products are another special category that requires very tight control on the inventory and destruction of these products. The destruction of controlled substance products requires specific documentation (Form 41) for the Drug Enforcement Agency (DEA) in addition to the documentation that is required to be maintained for GMP purposes. The disposal of controlled substances often requires witnessing the actual disposal to ensure that the product does not inadvertently reenter the supply chain.
The processing of pharmaceutical product returns and salvaged drug products can be a daunting task and requires knowledge of laws and regulations outside the GMP regulations. Proper disposition and disposal of pharmaceutical products ensures that consumers receive drugs that have the required quality, and that they, and the environment, are not inadvertently harmed by inadequate disposal of rejected or expired drug products.