The objective of any pharmaceutical manufacturing firm is to manufacture a product which fulfils all the requirements of being a product of quality and is also safe and efficacious. The quality of material shall be maintained not only during the production but also during the distribution and subsequent storage. Accordingly, Good Distribution Practices are always considered as an important aspect of Good Manufacturing Practices.

Although sales of materials are always considered as uniflow i.e. from manufacturing unit to the consumers, but sometimes the products have to be recalled for various reasons and sometimes are returned and are sometimes salvaged due to exposure to some obnoxious chemicals, gases, temperatures, floods or may be due to improper storage etc.

The primary question here arises what is the difference between returned goods and salvaged goods?

Returned Goods: Drugs products returned back to the manufacturing company for any reason namely failing to meet the acceptance criteria or may be returned due to breakage, packaging error, damaged packaging or any other issues.

Salvaged Goods: The complete or a part of a consignment that is returned to the plant when it has been exposed to improper storage conditions (for example, extremes in temperature or humidity) or exposed to atypical condition (for example, smoke or chemical fumes) due to natural disasters, fires, accidents or equipment failures.

When drug products are returned to the company, or salvaged after a natural disaster, it is important to assess the products completely w.r.t. their quality, safety and efficacy before a decision to remarket or destruction is taken.

The secondary question is how to handle the returned and salvaged goods? Are they to be handled in a similar way and the same yardstick is to be employed? Let us understand the basic difference in handling these two types of products.

RETURNED DRUG PRDUCTS

Drug products that are returned to a pharma company shall be properly identified and shall be stored in a completely segregated location/ area. On receipt of the returned drug products, special attention shall be paid for proper documentation of the returned material which shall include but not limited to recording, product name, strength, Batch No., reason for return, quantity returned, physical condition of returned material, date of disposition, and ultimate disposition of the returned drug product etc.

The returned drug products shall be thoroughly evaluated by the cross-functional team including QA, QC, Stores, Management Representative etc. The team thus formed shall clearly and impartially evaluate all the documents associated with the distribution and storage of the drug product before and during their return. The evaluation shall also consider the duration for which the product was outside the control of the manufacturing unit.

If the conditions under which returned drug products have been held, stored, or shipped before or during their return, or if the condition of the drug product, its container, carton, or labeling, as a result of storage or shipping, casts doubt on the safety, identity, strength, quality or purity of the drug product, the returned drug product shall be destroyed unless examination, testing, or other investigations prove the drug product meets appropriate standards of safety, identity, strength, quality, or purity.

However, in case the evaluation reveals that the:

  • 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.

Then, the cross functional team can take appropriate decision to remarket the product. Procedures for the holding, testing, and reprocessing of returned drug products shall be in writing and shall be followed.

Reprocessing of returned drug product is allowed provided that subsequent drug product meets the appropriate standards, specifications and characteristics of the original drug product. Reprocessing is viable option where an update to the labelling is warranted to ensure that the latest safety information is available for patient use.

If the reason for a drug product being returned implicates associated batches, an appropriate investigation shall be conducted to determine the extent of the issue. The team shall thoroughly investigate and find the root cause so that the associated risks w.r.t. distribution and further storage may be identified, assessed and management accordingly.

SALVAGED DRUG PRDUCTS

Drug products that have been subjected to improper storage conditions including extremes in temperature, humidity, smoke, fumes, pressure, age, or radiation due to natural disasters, fires, accidents, or equipment failures shall not be salvaged and returned to the marketplace. Such exposure can pose a serious risk to a drug’s identity, strength, quality, purity or safety. This fundamental CGMP principle applies to any component, in-process material, or finished drug product subjected to such conditions.

Whenever there is a doubt regarding whether the drug product have been subjected to be this type of conditions, salvaging operations may be conducted. Salvaging may be carried out only if there is :

  1. an evidence from laboratory tests and assays (including animal feeding studies where applicable) that the drug products meet all applicable standards of identity, strength, quality, and purity;
  2. an evidence from inspection of the premises that the drug products and their associated packaging were not subjected to improper storage conditions as a result of the disaster or accident.

In case of salvaged drug products, a preponderance of evidence that demonstrates the acceptability of the 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 drug should be documented.

When determining whether drugs have been subjected to such improper conditions, a firm’s actions should include but not be limited to:

  1. Obtaining supply chain information, including knowing the names and addresses of all suppliers and distributors of a drug (including components and packaging) to determine if there is a reasonable possibility that such materials were stored under improper conditions.
  2. Determining details such as the time frame, duration, nature, scope, and location of exposure as well as identity of all lots potentially subjected to the improper conditions (e.g., ramifications of a natural disaster such as power disruptions should be considered to ensure a complete risk assessment).
  • Obtaining certification (either on the certificate of analysis or as a separate statement) declaring that drug lots, including components and packaging, were not subjected to improper storage conditions.

References:

  1. 21 Code of Federal Regulations, Part 211
  2. USFDA – Questions and Answers on Current Good Manufacturing Practices—Returned and Salvaged Drug Products