Key Points to consider in performing a Suppler cGMP Audit. The Perils of not paying attention!

Part 1. The Warehouse.

Like most things in life, starting with good preparation is the best way to ensure a good endpoint. In the case of identifying competent and reliable compliant suppliers, this means making sure they have the right skills to do the job. It also means that they can be a reliable on time supplier of the correct quantities of materials required and with the correct specification. Often forgotten by some that are looking for a Contract Manufacturing Organization, is whether they have a solid business financial base to handle the production capacity you require. This can often be a “death nail” for some situations. For example, if the material becomes part of the critical production technology (such as a chromatography resin), for a clinical stage product candidate, then a failure to be able to supply this at commercial scale would cause significant delays in the licensing and product launch. This would more than likely require clinical trials to be repeated to establish outcomes with the new manufacturing process because changing the resin would be a significant process change. Reducing risk and exposure during this process is possible by implementing the use of a detailed questionnaire in which the client company can request essentially a dossier of information to establish the health of the company/supplier. This upfront data collection can be invaluable in de-risking the process and in the medium-term will save the need for costly site audits to qualify unsuitable suppliers. For those prospective vendors that meet your basic requirements, the site audit should be planned out to be a detailed affair that kicks the tires of the whole process. They should include the facility, equipment, processes personnel and documentation.

Usually at the site, to start the process, it’s important to get a good overview presentation of the company. This is often done by the head of QA or the Site Manager and it should provide information about the layout, capacity, equipment, personnel and the size of their business. For the personnel description, as should be a complete current organizational structure which highlights all the job functions and demonstrates a separation of Operations and Quality. This is most important! Once this is completed, the next important thing is to start the facility tour, starting with the loading dock and the warehouse. It’s important that the vendor can demonstrate a good process for receiving, handling, sample sampling and disposition of the material upon arriving at the facility. Highlight include checking the packing documents against the purchase order, assessing if the material and its packaging has not been damaged or affected in transit and whether the material is the appropriate grade, quantity and overall condition ordered. Usually at this point the pallets handling the material are cordoned off with a chain fence and for manually based processes, the boxes drums etc. on the pallets are labeled with a quarantine label. Next, the material needs to be sampled for ID testing. Usually the company has an SOP that explains this, and it often conforms to a statistical formula. This should be noted and checked later to see whether the practice conforms to their SOP that describes the process. In some cases where the number of boxes/drums/bottles is small, all units are sampled. Material is usually sampled in a HEPA’d booth fitted with dust collectors to prevent plumes of powder spreading. Samples are usually taken with either as stainless-steel implement such as a thief, or disposable versions of the same. If the stainless steel version is used, you’ll need to check what procedures they have for cleaning this. Experience teaches some firms are sloppy about issues like this, so it needs to be checked to prevent cross contamination. Samples are labeled and sent with transit documentation and a request for the tests to be performed by the QC laboratory. Once the material is sampled, the labeled raw material pallets are moved to the quarantine section of the warehouse and stored. For electronic facilities it’s usual to have these testing samples and raw material pallets barcoded rather than labeled with quarantine stickers, and this would allow the material to be randomly stored within the warehouse facility racking as designated with a unique location barcode. In the case of manually operated warehouses, once the test is complete, the quarantine stickers are changed for approval stickers (often green), and the material is moved to a released or approved section of the warehouse.

The benefits of the electronic system are obvious, as it avoids the unnecessary movement of material and replacing stickers, both of which are wasteful and potentially prone to cause mistakes. For manual systems is helpful to test the system with a raw material and then to trace its movements and assure that things are working. Similarly, tracing raw material in a bar code system through the interrogation of the ERP system is a good way to assure that the CMO has control over their operation. Another useful exercise is to check the reconciliation, either manually using record cards, or electronically (via transactions performed), to show that the company has control over the disposition and use of the materials it’s ordering and using.