Purpose An overview of Good Manufacturing Practices, targeted to those participating in research and development, is essential to the process of late-stage development of any critical material that is intended for use in an in vitro diagnostic, a pharmaceutical, a medical device, or any of an entire host of other applications that are regulated by the U.
S.
Food and Drug Administration (FDA).
While most of the Code of Federal Regulations (CFR) and the Points to Consider provide guidance for the finished diagnostic kit (or finished pharmaceutical, etc.
), it is necessary to begin detailed record-keeping and other practices in the latter stage of research and development in order to meet the increasingly strict regulations for historical development information and traceability to the source of such critical materials.
This document is not intended to be a comprehensive discussion of the requirements, but rather to highlight those practices necessary to ensure that, on an ongoing basis, the level of control and record-keeping that will be needed for licensure of such products begins during the research phase for critical materials.
Key Points Controls must be in place for process and production.
These controls help to prevent any errors that threaten the product's integrity.
Error prevention must be built into the procedures which support manufacturing.
A section of the GMPs is devoted to these controls and states: specifications and processing procedures must be in writing and must be controlled such that the product (or material) being made conforms to its original design or any approved changes in that design.
Record-keeping The first and most basic form of control is recording what is done such that it can be read and understood well into the future.
Documentation, when properly done, will show exactly what was done, when and by whom, should questions arise.
It cannot be stressed enough that this is the cornerstone to any and all work that is undertaken, whether it is in support of production or laboratory work not governed by the GMPs.
Each and every entry on a log, each lab notebook page, or any document used in production should be dated and signed (or initialed), reviewed by a senior person knowledgeable in the subject matter and his/her signature (and date) added.
This ensures adequate traceability and accountability for the work undertaken.
If an error is made during record-keeping, you must line through the error (with a single line), date and initial the error, and then record the accurate information.
You must not obliterate the error by scratching it out, writing over it, or using correction fluid (white-out).
When using reagents, buffers, materials that will contact the product, and testing kits to assure activity, sterility, physical parameters, and other pertinent information to the critical material, it is essential that the vendor name, catalog number, lot number and expiration date be recorded, along with the experimental design and results of such testing.
This enables third-party review of work conducted with assurance that the parameters are in control and that the work can be, or has been, reproduced.
This document is in no way intended to be a comprehensive checklist of the controls that must be place during late-stage research and development of critical raw materials that will eventually find their way into finished diagnostics, devices, or pharmaceuticals.
It is, rather, a starting point toward understanding that regulatory requirements for control are being pushed further and further back up the "pipeline" toward the research and development phase.
Client requirements have become increasingly stringent because the FDA has required that when the finished device or pharmaceutical is licensed, these historical references to developmental work are in place and under control.