Frequently, a significant portion of most pharma manufacturing facilities is the warehouse operations area. Under this “pharma” umbrella we would include chemical manufacturers, API manufacturers, finished pharmaceutical manufacturers and contract manufacturing organizations (CMO) providing niche products for sponsor clients. From my perspective, the primary concern in this area is generally associated with Materials Control. This would include the handling of materials with temperature and humidity requirements, cold storage requirements, handling of controlled substances or active pharmaceutical ingredients (APIs).
In this brief article, I will highlight several items that should be evaluated during audits of warehouse operation areas.
Facility Orientation and Conditions
The most common point of entry for materials into a manufacturing facility is some portion of the warehouse area. Materials are off-loaded through a receiving dock, staged in an initial inspection area, sampled (as needed) for incoming analysis and release, then transferred into storage racks pending Quality release and distribution to the manufacturing group. Finished goods are returned to the warehouse area for storage pending final Quality release of finished goods, then shipped to market or distributions centers through a shipping dock.
Although there are many variations on how this may be accomplished, my intent is to establish a simple “material flow” to highlight auditing issues/items.
Receiving dock housekeeping and conditions should be clean, organized, and configured in a manner to allow efficient material flow through receiving and inspection into the initial storage locations. Pest control elements, such as traps and bug lamps, should be evident as this is generally an open area into the facility. Shipping docks may be in the same location as the receiving area. This isn’t necessarily a major issue, however, there are some worldwide regulations that require separation between receiving and shipping areas to eliminate any potential mix of receiving materials and finished goods. This can be addressed by clearly identifying receiving docks and shipping docks, and ensuring that any staging areas are sufficiently separated.
Initial inspection should ensure proper documentation has been submitted for the received materials, that no container damage has been observed, and that the received material has been properly labeled with the incoming Lot Number by the receiving site. When needed, containers are identified for sampling and transferred to a sampling area or booth to pull samples for laboratory analysis. The primary concern during the sampling process is potential cross contamination between differing materials. Sampling area configurations are varied ranging from simple mobile booths with curtains to allow a laminar air flow during sampling, to a completely separated and environmentally controlled room. The sampling processes should be evaluated against the potential risk of cross contamination, and at minimum, ensure that proper air flow has been established and documented prior to starting sampling activities. It should be noted as well that all containers of API materials must be sampled, specifically to confirm identity of the API material.
Although the inspection staging area is not intended for long-term storage, special consideration must be given to material requiring cold conditions for shipping and storage. Most processes will ensure cold storage materials are moved directly to the cold box or cold storage room/facility.
Following completion of any required sampling activity, the entire lot of material can then be moved into storage racks, pending Quality release, and use in the manufacturing operations for finished goods. Storage locations can also be highly varied in their configuration, however, the primary items to evaluate include the ability to clean between racks or pallets; and the identification of the material on the pallet, the location identification, and the status of the materials. Methods to accomplish these needs may be manual, entailing an inventory card at the storage location providing material details, or highly sophisticated Warehouse Management Systems (WHS) which track this information via bar codes and readers.
Quarantined and/or Rejected Materials
Some of the initial requirements for complete separation of quarantined materials from released materials have eased a bit with the implementation of validated material control systems which prevent the use of quarantined materials. However, the expectation still remains that rejected material be physically separated from other materials in a locked reject cage. Access to the reject cage must be limited to selected individuals. An effective auditing technique is to walk to the reject cage and determine if access is secured. There have been many incidents in my previous experience where the cage door was open, or I could easily open and gain access to the rejected materials.
The evaluation of managing Controlled Substances is better covered by another article, however, if the entity does handle controlled substances, the following items should be noted. Storage of controlled substances is required in a “vault” unit, the design of which is much more stringent than a warehouse cage. Access to the vault must be tightly controlled and documented. Material movement into and out of the vault must also be tightly controlled and documented, including the amount of material removed and replaced into the storage unit.
A comprehensive list of effective procedures must be in place to provide specific instruction for all activities regarding the receipt, sampling, analysis, release, and storage of materials. Practices may run from a manual process using logbooks and inventory cards, to automated WMS programs tracking materials via bar codes and readers. Regardless of the manner or process utilized, the following data must be captured on material receipt:
- Material Name
- Supplier Control/Lot Number
- Supplier Name and Location (supplier manufacturing location is important with respect to ongoing auditing needs)
- Material weight/quantity per container
- Storage Conditions (if required)
- Receipt Lot Number (receiving site assigned lot number)
- Material Status
- Storage Location
Much of this information may be captured via original labeling on material containers, with added lot numbering labels (provided by incoming receipt group) and color-coded labels providing material status, i.e. sampled, quarantined, released, etc., applied by the Quality Assurance group. Each receipt of a supplier material lot must be identified by an independent lot number generated by the receiving site. Once the new labeling is applied and material completes initial sampling (when required), container skids may be moved into assigned storage locations. The use of an automated WMS generally will provide these controls through the use of bar code labels. Scanning the container bar code label should provide all data noted previously. Another good auditing technique is to walk through the warehouse area and check various container bar codes against the system data, including containers located in a reject cage.
Good examples of material storage include the segmentation of warehouse rack locations to specific material categories, to include raw materials/excipients, APIs, packaging components, and finished goods. Product labels and labeling (such as product cartons or trays) require more stringent controls for access, so these items are generally managed via separate rooms or areas. If product labels and labeling are stored in the general warehouse location, this area must be “locked” in such a manner as to limit access to these materials to specific individuals responsible for managing these items.
At times, there are materials with specific storage requirements associated with temperature or humidity conditions. Warehouse areas will need to be monitored and controlled to these specifications. Even when there are no specific storage environment needs, the regulatory expectation is that mapping studies are conducted for the warehouse areas. Generally, mapping studies for both warm and cold weather periods are completed. The primary outcome from these studies is to determine the associated hot and cold spots within the warehouse areas. These identified spots will then become the locations of monitoring probes and instrumentation to record temperature (and humidity when needed) and provide efficient control of the warehouse areas within specified storage requirements.
Cold storage units and storage locations will also need qualification and validation of control systems. Mapping studies should also be conducted with both empty and filled rack locations, specifically to determine warm spots and air flow capabilities of the unit in a “full” condition. As noted with the warehouse studies, the identified warm spots should be the location of the instruments monitoring and recording the temperature within the storage unit; and providing control of the environment to meet cold storage requirements.
Hopefully this article providde some insight on the auditing of warehouse operations. Previous experience has shown that many of the items highlighted have been sufficiently addressed by a wide variety of processes and procedures utilized by differing manufacturers.
Is your company or group responsible for auditing warehouse or distribution center operations?
Please give me a call and let’s discuss the potential support that The Catalyst Compliance Group can provide to your auditing needs.
Richard D. Schlabach is a Quality Assurance professional with over 37 years of pharmaceutical industry experience in Quality Assurance, Quality Control, and Validation functions for a wide variety of product categories. Richard’s technical competencies include extensive knowledge of worldwide regulatory requirements; equipment, utility, process, and cleaning validation; specialization in automation validation; compliance auditing and training; and preparation of SOPs and related documentation. He is currently the VP of The Catalyst Group’s QA Division.
Mr. Schlabach can be reached at the following contact information: