Developing a Master Plan for Complex Validation Projects

An overview of validation can show FDA that a process is under control.

by Erik Swain, Senior Editor

When validating a complex healthcare packaging line, a master plan can be an essential tool. Not only is it a valuable internal resource, but a correctly prepared plan can help win FDA's confidence that the process in question is under control.

Mark Celeste, validation project leader at O'Neal Inc. (Raleigh, NC), addressed the master plan's importance at a seminar sponsored by the Institute of Packaging Professionals' (IoPP; Herndon, VA) Eastern Equipment Committee Conference, held March 9 in Secaucus, NJ, as well as during an interview with Pharmaceutical & Medical Packaging News.

The master plan is not the same thing as the validation protocol. The master plan is an overview of the process to be used to validate the project. The validation protocol is the specific set of test procedures and acceptance criteria for each system being validated. The master plan is much less detailed, although the information included in the two should be consistent. Celeste says the master plan requires senior management's approval—the absence of which can cause serious doubts in the minds of FDA inspectors as to the company's commitment to the project. "The overall objective is to set out the philosophy for how you will handle the project," Celeste says. If there is no indication that senior management agrees with the objective, then the philosophy loses credibility with FDA, and so may the entire project.

THE PLAN'S CONTENTS

According to Celeste, the master plan should include the following:

• A discussion of the scope of the project.

• A physical description of the equipment.

• A rationale for each validation decision. Explain which machines are being validated and which machines are not, and explain the reasons for each decision. Celeste's advice is to validate what is defined as critical, and not to validate what is defined as noncritical, as long as the rationale justifying each decision is documented and the decisions are consistent with current practices. For the strict purposes of validation, a critical item, he says, is something that "directly affects the quality of the product being produced." That includes anything that contacts the product and anything that can cause a corrective action (such as computer systems). Some items are ambiguous. In these cases, a company must make policy decisions and attempt to maintain consistency. A lack of consistency may demonstrate a need to revisit the criticality of the system involved. It is normal to reevaluate what is critical and what is not critical, but once a decision to change a definition is made, the reasons must be documented.

• A methodology for each validation. Product qualifications document the performance of the processing and packaging equipment. Process qualifications can be used to document performances of continuous processes or of utility systems. For example, Celeste says, if a line is to run three packages for 15 products, the full product performance qualification may not have to be conducted for 15 different products for the complete line. For a drug, product performance qualifications might be conducted on each of the 15 different tablet fills, while the qualifications for the capper might be done on just the different cap-bottle combinations. A corresponding analysis of the different aspects of packaging for a medical device might be instituted, but how so would depend on the specific product.

• Identities and responsibilities of each member of the validation team.

• General acceptance criteria. Matrices are a good tool to use here. Do not describe the criteria in detail—that is for the protocol.

• Any related programs that have been conducted, such as calibration and lab testing. "List the sort of programs that will in fact support the project," Celeste says. "Many [engineers] use the finished product testing from the labs."

• A schedule tied into construction or installation schedules.

Not only should upper management have access to this document, but so should every member of the validation team and anyone who is developing the protocols, Celeste says.

The master plan may also be revised as required. Each change must be logged and explained as to why the change was made. Previous revisions of the plan should be kept on file for reference.

Sample table of contents for a master plan for a packaging line. Source: O'Neal Inc.

1. Table of Contents 2. Approval Page 3. Project Introduction 4. Scope 5. Definitions 5.1 Critical Items 5.2 Noncritical Items 6. Facility Considerations 7. Utility, Process, and Descriptions 7.1 Utility Systems 7.2 Equipment 8. Document Requirements 9. Required Protocol Matrix 10. Standard Operating Procedure Matrix 11. Support Programs 12. Responsibilities 12.1 Master Plan 12.2 Validation Protocols—Prior to Execution 12.3 Validation Protocols—Postexecution 13. Schedule 14. Acceptance Criteria

ASKED FOR BY FDA

While the master plan may not be specifically noted in any FDA regulations, its use has become common practice in the industry. "It is usually one of the first things FDA asks for" during an inspection, Celeste says. "Therefore, it can serve to limit their digging into other things. If you demonstrate you have followed the master plan, that shows preparedness and control. Without one, I would expect them to start digging from there."

It may not be necessary for simple validations, such as for a single machine. In those cases, the information that would go into a master plan may be able to be covered in the change control documents, Celeste says.

Planning can help in other ways, Celeste says. If a company has its validation people present when the machine is installed, the tests can also double as the installation qualification and the operational qualification, saving money.

FOCUS ON RESULTS

Some companies may choose to focus on specific products during validation, while others on an overall process—it will depend upon what the line is running.

But, Celeste says, what is most important is showing that "the specific products and process you're running meet predetermined acceptance criteria," which is part of a predetermined test protocol.

If the actual results do not match the predetermined criteria, "you must investigate what happened, come to a conclusion, and determine how much it affects the validation effort," Celeste says.

A serious problem likely signals a problem that should have been corrected before validation got under way, not a problem in the validation process. "In process validation, you shouldn't be solving problems," he says. "Troubleshooting should be done during development and technology transfer. It should be completed before FDA comes in—or else you must present what you've got and say how you plan to correct it."

CONCLUSION

Validation is likely to be a topic of any FDA inspection or audit. As with any system, it is important to demonstrate that the validation process is under control. A master plan is an excellent way to demonstrate that that is the case for your system.

"If a master plan is well laid out—if you describe what you're doing and the protocols are consistent with it—then FDA has more confidence that you have control over what you're doing," Celeste says. "It is definitely a document to take very seriously."