This paper discusses background information related to RM regulatory requirements and industry challenges, and then highlights key principles to consider in setting up a risk-based RM management approach and control strategy. This paper then provides an example of how to translate those key principles into a detailed RM risk assessment methodology, and how to apply this methodology to specific raw materials. To better illustrate the diversity and nuance in applying a corresponding RM control strategy, a number of case studies with raw materials typically utilized in the manufacture of biological medicinal products have been included as well as discussion on phase-based mitigations.European Biopharmaceutical Enterprises (2018) “Management and Control of Raw Materials Used in the Manufacture of Biological Medicinal Products and ATMPs“
Good foundation document for how to build a risk management program for managing raw materials.
Significantly, your firm failed to perform identification testing for all incoming glycerin lots to verify identity and determine whether diethylene glycol (DEG) or ethylene glycol (EG) was present. Because you did not test each lot and container of glycerin using the USP identification test that detects these hazardous impurities, you failed to ensure the acceptability of component lots used in drug product manufacture. DEG contamination in pharmaceutical products has caused lethal poisoning incidents in humans worldwide. FDA Warning Letter of 02-Nov-2018 to Product Packaging West, Inc.
First of all, ouch. This brings to mind an old investigation that drew a lot of attention a few years back. It involved a tanker truck and a hurricane, but still, lots of memories.
This Warning Letter brings to mind questions about receipt of materials. So here are some top level thoughts.
Choosing tests should be a risk based approach evaluating what the material is, what it is used for, supplier qualification level and history of test results. A critical raw material with custom chemistry from a supplier that has had issues is a different matter than an off-the-shelf component that hasn’t had a problem in 10 years. But there always should some basic identity testing, especially if that is listed in an pharmacopeia. This should be done through a formal process, with periodic review.
Have a process in place for delivery of material to ensure that each container or grouping of containers of material are examined visually for correct labeling (including correlation between the name used by the supplier and the in-house name/code, if these are different), container damage, broken seals, and evidence of tampering or contamination. A good in-coming receipt inspection includes:
- Each lot within a shipment of material or components is assigned a distinctive code and an unique internal number so material or component can be traced through manufacturing and distribution
- A check to guarantee the origin of materials from approved manufacturers and approved distributors
- Start inspection with visual examination of each shipping container for appropriate labelling, signs of damage, or contamination
- Use a predefined checklist for inspection
Incoming material should be quarantined prior to approval for use. I recommend a separate quarantine area for incoming versus material segregated for investigations or issues.
Supplier qualification deserves a post of it’s own.