The First Planning Focus of VMPs: The Systems Inventory

Hello again! Welcome back to my blog, which focuses on the validation in the Pharmaceutical, Biotech, and Medical Device communities. As I mentioned at the end of my last post, validation master plans have three main planning focuses, one of which is the systems inventory.

The VMP contains a plan for the systems inventory. The systems inventory lists everything requiring validation. It also captures the required level of validation for each system. Refer to Figure 3 for an example systems inventory.

Figure 3. Example systems inventory in a VMP

There are many systems that can be listed in a systems inventory depending on the scope of validation. Some examples of systems included in the systems inventory are:

• Equipment (e.g., freezers and incubators)
• Manufacturing processes (e.g., manufacture of arterial stents)
• Cleaning processes (e.g., CIP processes)
• Analytical methods (e.g., UV assays)
• Computer systems (e.g., electronic batch records and document repositories)
• Utilities (e.g., WFI and nitrogen gas)
• Facilities (e.g., ISO Class 7 cleanroom)
• Materials (e.g., syringes for injecting drug product)
• Critical Operator Processes (e.g., operators performing the aseptic gowning technique for entry into an aseptic filling suite)

The systems inventory is a living document. The systems inventory should be attached as a reference in the VMP rather than reside within the VMP. The systems inventory must be updated as often as needed based on validation scheduling and scope changes. It must be an accurate representation of the validated systems. The VMP will be viewed by inspectors who will expect the attached systems inventory to be a comprehensive list of the validated systems.

The systems inventory is a very useful component of a VMP. It provides a clear picture of the systems to be validated and outlines the level of validation required for each system. A general understanding of the process is required when creating the systems inventory to ensure that over-qualification or under-qualification of the systems does not occur. Appropriate qualification levels for each system, along with an adequate sampling strategy, will save time and resource requirements during validation.

As previously mentioned, the systems inventory identifies the required level of validation for each system. There are several levels of validation that can be performed. The most common levels of validation are:

• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
• Method Validation (MV)
• Process (Product) Validation (PV)
• Cleaning Validation (CV)
• Computer System Validation (CSV)

The terms for the various validation levels may vary even though the concepts are generally the same. For example, a recent draft of FDA guidance on process validation lists “process qualification” as a stage of process validation in the product lifecycle (1). Terminology in the industry is constantly evolving. As a result, different companies may use different terminology. Be sure to use the terminology specific to the company to avoid confusion and ensure there are no validation gaps due to misuse or misunderstanding of terminologies.

Another item to note with regard to the validation levels involves Process (Product) Validation (PV) and Cleaning Validation (CV). Although PV and CV are listed separately, CV is a specific type or subset of PV. When creating the systems inventory and determining the required level of validation, it is perfectly acceptable to include CV under PV or keep CV separate.

There are several regulatory guidance documents that can be used when performing either Method Validations or Computer System Validations. Most current Method Validations are performed by following ICH Q2(R1), Validation of Analytical Procedures: Text and Methodology (2), USP <1225> (3), or the Global Harmonization Task Force (GHTF) (www.ghtf.org) guidance (4). For Microbiological Assays, the following USP chapters can be used for guidance:

• USP <85> for Endotoxin Inhibition/Enhancement (5)
• USP <71> for Sterility - Bacteriostasis/Fungistasis (6)
• USP <61> (7) and USP <1227> (8) for Bioburden - Bacteriostasis/Fungistasis

Nowadays, Computer System Validation is typically performed by following GAMP® 5 guidance (9) from the International Society for Pharmaceutical Engineering (ISPE) in conjunction with the minimum validation language addressed in the drug and device GMPs. Both Method Validation and Computer System Validation may require more regulatory guidance due to the increased complexity of the tested systems, and the above references are a good place to start.

My next post will continue the discussion of the systems inventory and focus on determining the appropriate level of validation for each system. Please feel free to contact me with any questions or comments you have regarding this blog. Thanks!

Best regards,

Megan K Gladfelter

References:

1. FDA, Process Validation: General Principles and Practices, Guidance for Industry (Draft), United States Food and Drug Administration, November 2008.
2. ICH, Validation of Analytical Procedures: Text and Methodology Q2(R1), International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use November 2005.
3. United States Pharmacopeia, USP <1225>
4. Quality Management Systems - Process Validation Guidance, Document Number GHTF/SG3/N99-10:2004 (Edition 2) January 2004.
5. United States Pharmacopeia, USP <85>
6. United States Pharmacopeia, USP <71>
7. United States Pharmacopeia, USP <61>
8. United States Pharmacopeia, USP <1227>
9. ISPE GAMP® 5: A Risk-Based Approach to Compliant GxP Computerized Systems. International Society for Pharmaceutical Engineering 28 February 2008.