Is Temperature Mapping All I Need to be Regulatory Compliant?

It’s the chicken and egg scenario. Often a company conducts a temperature mapping of pharmaceutical storage space to be compliant. If it’s a new facility – you map it. If HVAC modifications are made, extensions to facilities or warehouse layout changes made – you re-map it.

But what and when is a full Qualification or Validation required? Well, technically… always.

Quality assurance during pharmaceutical manufacturing, storage, and distribution is essential for product quality and an integral part of GMP/GDP regulations. To comply with regulatory standards, facilities must be fully qualified and documented. However, putting together plans and reports for URS, QRA, DQ, IA, OQ, PQ and a Validation Master Plan is a time-consuming task.

What is the difference between Qualification and Validation?

Well, it depends on who you ask. The various national regulations in Europe and US, use both terms, interchangeably. The only bottom-line regulatory requirements are performing DQ/IQ/OQ/PQ as needed. In conversation, in the US, practitioners most often use the term validation. In most major markets its correct to say there are several qualifying steps (DQ/IQ/OQ/PQ); if completed successfully, the space is considered validated.

What needs to be qualified?

• Warehouses

• Transport vehicles

• Shipping/Cargo containers

• Standalone Refrigerators

• Standalone Freezers

• Incubators

• Stability chambers

• Walk in Coolers/Freezers

Where to start? The URS and Quality Risk Analysis

Taking a risk based approach is outlined and recommended in most regulatory guidelines. FDA Process Validation Guidelines are nearly synonymous with EU PIC/S Annex 15 and both recommend an ICH Q9 risk analysis for all GxP regulated environments.

In the so-called User Requirement Specifications (URS) you first should write down what is required from your equipment or your warehouse, to identify your risk. You may already have a sufficient tool in the form of a quality manual or quality guide. As long as you have a document that defines what your facility requirements are (i.e. storage, security, pest control, fire suppression, etc.). The purpose of the URS is to provide a full description of the required system performance, as well as define performance criteria, critical parameters, and operating range. The URS should also include cleaning, maintenance, training, documentation, and security requirements.

Then you draw up your processes, run a FMEA type quality risk analysis. As shown on ICH 9 graph, you will identify your risks for each process step, and define CAPAs as needed. These CAPA will be the basis for your validation master plan and the rest of your qualification.

Components of a Validation Master Plan

The VMP is generally one of the first documents an auditor will ask to review. In general, purpose of a VMP is to outline the qualification strategy, define rooms or equipment that are within the scope of the qualification project, how to implement change control, and define organizational responsibilities.

There are extremely important decisions to make when writing a VMP. The VMP must be expertly tailored to ensure all planned qualification steps meet both URS and regulatory requirements. The VMP also considers points that were identified during risk analysis and plans the qualification activities in order to address and satisfy any CAPA requirements. At this point, each requirement is matched with its corresponding qualification step. All plans and protocols for the subsequent qualification steps are written to ensure they comply with the VMP. After the VMP is written and released, the rest of the qualification steps (DQ/IQ/OQ/PQ) can be planned and executed.

Let’s look at each a bit closer.

Design Qualification
The intent of DQ is to provide documented assurance that the design of the facility/equipment meets both user requirements (defined in the URS) as well as regulatory requirements. During DQ engineering documents, site/factory acceptance tests, relevant SOPs, facility and equipment schematics, and vendor documents are reviewed and given an “as found” status. The purpose is to introduce all aspects of the facility design into change control.

Installation Qualification
The Installation Qualification (IQ) verifies and documents that the facility and equipment, have been installed according to the manufacturer’s specifications and meets URS and regulatory requirements. Relevant action items from the risk analysis pertaining to IQ are also assessed during the execution of IQ.

Operation Qualification
The purpose of OQ is to assess the worst case scenario of a facility (warehouse) or equipment (standalone or walk in). OQ is typically performed when a facility is unloaded (no product), with all ancillary systems installed and operational (i.e. racking, HVAC) and at rest (no personnel or activity). In other words, the facility should have everything ready to begin operations.

OQ is where the first temperature mapping will take place. The system is usually put under a series of stress tests during OQ. Again, these challenges are designed to simulate a worst case scenario.

Common stress tests include:

• Power failure (how long will facility/equipment maintain required temperature in the event of a power failure?)

• Backup generator (does the backup system start automatically in the event of a power failure?)

• Open door/recovery (what is the thermal impact of door openings?)

Performance Qualification
Performance qualification (PQ) is intended to assess the thermal influence of normal working conditions on a facility. A PQ mapping is typically performed when a facility is at least 50% loaded during active, daily operations. In most cases there are two PQ mappings; one during summer and one during winter.

Validation Summary Report
After all qualification steps are complete and all CAPAs have been implemented, a validation summary report is written that summarizes all the qualification steps that were taken and releases the facility for normal daily operations.

Conclusion

Time consuming qualification projects require heavy resources. First the ground work conducting FMEAs and risk assessment takes experience and understanding how to rate certain risk factors and how they can affect the end to end environmental monitoring project. Working with a partner like ELPRO can help you to do the heavy lifting, create the necessary validation plans and reports, and carry out the thermal mappings and stress tests on your critical GMP storage spaces.

ELPRO’s qualification services are designed in a modular way, allowing customers to choose the activities where they need assistance most. Contact ELPRO's GxP-experts to discuss your pharmaceutical storage space qualification requirements.

If you have already GMP qualified your spaces, and looking for updated mappings, read the customer story of Express Scripts, who carried out a mapping exercise at their facility because the medication they distribute has storage requirements of +20 °C..+25 °C (+68 °F..+77 °F). «We needed to ensure that we were meeting this requirement at each pallet location in the warehouse that the medication was stored,» Keith Konya, Sr. Manager of Facilities said. Read the full story Warehouse Mapping of GxP Storage Facilities: Why it’s Not an Option