Reference standards qualification process

The critical parameter in the discussion of reference standards is the process of qualification. FDA guidance on this topic states that A non-compendial standard should be thoroughly characterized to assure its identity, strength, quality and purity. 3 It is therefore left to the pharmaceutical firm to establish thorough characterization for the ARS of each NCE. The overall qualification process for an ARS includes characterization of the material, proper form selection, and assignment of purity. Some general considerations in this process include... 

The term approval can be taken to mean certification or qualification, the difference being that certification is performed each time the equipment is repaired and qualification only when the equipment is introduced into service. The standard only refers to the term qualification in connection with special processes, but this clause does not distinguish between special and ordinary processes and equipment. However, there are two levels of approval that apply to processes and equipment initial qualification approval and periodic setting-up approval. 

This chapter defines the terms, responsibilities, requirements and recommended procedures involved in pre-installation, installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ), which are all part of a typical HPLC system validation process. As the FDA does not publish a definitive reference or cookbook for these procedures, the suggestions herein are only recommendations. These have been successfully incorporated into formal standard operating procedures (SOPs) that have been implemented at a number of larger pharmaceutical establishments. As long as proper SOPs... 

In step 5, the qualification stage, the critical issue is that the protocol for IQ/OQ of the equipment and the facility include the established method and acceptance criteria. The IQ/OQ report should include the maintenance program to keep the equipment in good condition for reproducibility of the product. For qualification of the equipment and process for terminal sterilization, the following standards should be referred to ISO 13408-1 [6] and 11138-1 [7] for general issues, ISO 11134 [8] and 11138-3 [9] for moist heat sterilization, ISO 11135 [10] and 11138-2 [11] for ethylene oxide sterilization, and ISO 11137 [12] for radiation sterilization. 

The reference model system method can be combined with the internal standard method. In this instance, the model system contains known amounts of the compound under determination and a calibration standard, a known amount of the standard is added to the system to be analysed and both systems are processed in the same way and under the same conditions. With this combination there obviously apply exactly the same qualifications as specified with the plain reference model system method described above. The... 

IV.55. Processes affecting the finished product/service quality, where the required quality cannot be verified by post-process examination alone, and where pre-qualification of the process is necessary, e.g. welding or heat treatment, should be controlled in accordance with documented procedures. Such procedures should refer to relevant codes, standards, specifications or dedicated requirements. Where specified, measures should be taken to ensure that these processes are accomplished by qualified personnel, procedures and equipment. 

An overview of the system development process - describing key phases, tools, techniques, programming languages used - and a justification of appropriateness for the allocated SILs and risk classes (e.g. references to tool qualifications, compliance with recommendations in the standards) etc. are given. 

---