Master Plans vs. Policies

Aug 2007

While not a regulatory requirement, it is prudent (and practical) to have a high level document that describes how cleaning validation is performed in your facility. The rationale for this is the FDA’s “new” investigation program, which that states that the first thing to be evaluated is high level documents to see if a facility’s policies are appropriate.

Different companies will call this high level document by different names. Sometimes it is called a “Cleaning Validation Master Plan”, sometimes a “Cleaning Validation Policy”, sometime a “Cleaning Validation Quality Standard” and sometimes a “Cleaning Validation Directive”. There may be other names that are also used, depending on the document hierarchy of the company.

In all cases, these higher level documents are designed to define and limit the cleaning validation program for that facility. For example, the higher level document might specify that residue limits be calculated using a certain formula. In other cases, it might give parameters for certain strategies if those strategies are employed. For example, the higher level document might not require product grouping, but it will specify conditions to be met if product grouping is employed.

The level of detail in these higher level documents will vary depending on the topic. For cases like residue limits, a statement that residue limits should be “practical, achievable, and verifiable” (essentially a quotation from the 1993 FDA cleaning validation guidance document) without further qualification is probably not very useful. While it is a valid requirement (who would argue with that requirement?), it is not very useful in helping one to establish residue limits in a specific situation. For this reason, higher level documents typically will have more detail about setting residue limits. In contrast, there may be very little detail about sampling procedures in these higher level documents. Some general principles may be used for sampling, such as “Sampling methods may include both rinse and swab sampling, and such methods should be appropriate for the equipment and residue being evaluated”. One might go on to say things like “swab samples shall include worst case locations”, but the specific locations for various pieces of equipment are probably best left to a lower level document.

Where does this leave us with the supposed topic of this Cleaning Memo, which is “master plans vs. policies”? Is there a difference? Well, one possible difference is that a master plan may include a schedule. This schedule may include planned activities for the next year or so. The level of detail in the schedule should be such that it doesn’t necessarily tie one down to a specific timeline for detailed tasks. In other words, there would not be something that stated that analytical method validation for a certain protocol was going to be completed in September 2007. One might specify that it would be completed in a certain quarter, or one might be silent about the analytical method validation in the “master plan”, and only specify completion of the cleaning validation by the end of a certain quarter. Detail on the tasks to achieve that goal could be in lower level documents.

In addition to plans for the coming year, the master plan might also have the completed status of the cleaning validation effort covered by that master plan. This essentially gives the company (or an auditor or investigator) a snapshot of the current status of the program.

Note that the master plan doesn’t have to contain such a schedule and status summary. It may just refer to the fact that one exists and is maintained apart from (but obviously related to) the master plan. This may enable the status report and the schedule to be updated more regularly, without having to modify the master plan.

If the higher level document is more of a policy statement, then it typically will not have a schedule or status report attached to it. However, it may require that such a schedule and/or status report be maintained for the cleaning validation efforts in the facility.

Note that what I am saying is that strictly speaking, a plan has a schedule associated with it, while a policy document does not. However, as a practical matter, terminology and practice within the pharmaceutical industry varies considerably. Whatever the higher level document is called, the important issue is that it be a useful, practical document that defines and clarifies cleaning validation practices for that facility (or facilities). This means that it generally must be written with input from the scientists and their managers at the facility; global higher level documents (those covering many facilities in a multinational company, for example) can be written. But, without input from the specific facilities, inappropriate constraints may be placed on the individual facilities. This is one reason that such global documents need to be more like policy documents, focusing on principles (but not being shy about giving specific practices where justified). Certainly the documents for a facility may deviate from the global document with justification; however, it is best to make any difference explicit, and provide that justification.

One last word on these higher level documents, whether they are called master plans, policies, directives, or whatever. It is important that lower level documents be consistent with these higher level documents, including such things as definitions. In no cases should definitions in lower level documents be in any way different from definitions of the same term in higher level documents. This usually means that either a reference is made to the definition in the higher level document, or that the definition in the lower level document is “word for word” identical. Certainly just as with differences between a multinational’s global policy and a specific facility’s practices, there can be differences for that facility provided those differences are explicit and justified. Needless to say, such differences should be the exception rather than the practice; otherwise the higher level document requires some serious modification.

The purpose of this Cleaning Memo is not to specify what you call these higher level documents, nor to specify content. Acceptable practices can include a wide variety of terms for describing the document, as well as the content of the document. However, the purpose of the document should be clear, and this is usually to prescribe certain acceptable practices that must be followed (such as how residue limits are set), and allow certain practices under defined conditions where appropriate (such as grouping strategies). High level documents that just list platitudes and generalities that any facility could follow can be used (particularly as a global document for a multinational or multi-facility company); however, such general documents require more carefully and narrowly defined master plans or policies for the individual facility.

Take me to the memos

from the year: