Documentation validation reports

B. Richter, J. EzzeU, and D. Felix, Single Laboratory Method Validation Report Extraction of Organo-phosphorus Agrochemicals, Chlorinated Herbicides and Polychlorinated Biphenyls Using Accelerated Solvent Extraction (ASE) with Analytical Validation by GC/NPD and GC/ECD, Document 101124, Dionex Sunnyvale, CA (1994). 

Part II Part II is the report concerning chemical, pharmaceutical, and biological documentation. The report details the composition, method of development of formulation, manufacturing processes under GMP, analytical test procedures, bioavailability, and bioequivalence. It should be noted that all analytical test procedures need to be validated, and the validation studies must be provided. 

In addition to these newly proposed test guidehnes, suggestions are being considered for new parameters to be included in the present repeated dose oral toxicity test (OECD TG 407) with more emphasis to be placed on detection of endocrine effects. The vahdation of the enhanced OECD TG 407 is now being reviewed by an international panel of reviewers. The peer review package, submitted to the panel and available at the OECD Web site for endocrine dismpters (OECD 2007b), includes the validation report, the draft and the current test guidelines, and a Secretariat document to support the peer review panel. 

A concurrent intensive monitoring of air, surface, and personnel hygiene should be performed during all validation procedures within the aseptic area. For documentation use Attachment No. 1700.100(A). For template validation/ report refer to Attachment No. 1700.100(B). 

A validation report is a written document that cross-references the validation protocol, summarizes the results obtained, describes any deviations observed, and draws the necessary conclusions, including recommending changes required to correct deficiencies for the qualification and validation performed [5]. In this report it is required to present both the results and conclusions and the secure approval of the study. The report should include a summary of the procedures used to clean, sample, and test as well as the physical and analytical test results or references for the same. The conclusions regarding the acceptability of the results should also be included. Other information would be the status of the procedures being validated, any recommendations based on the results, or any relevant information obtained during the study. These include, re validation practices (if applicable), the approved conclusions, and any deviations of the protocol that might have occurred. In cases where it is unlikely that further batches of the product will be manufactured for a period... 

In the present chapter, the pharmaceutical industry validation system has been reviewed. To have an appropriate validation system it is first required to define which equipment, facilities, and processes will be validated, when they will be validated, and by whom this must be performed. This definition is based on a risk assessment priority and is written in a specific document, the so-called MVP. In order to generate an adequate validation report, all the validation activities should be described in the validation protocols, SOPs, and specific procedures. 

The validation work should be carefully documented in an expert validation report in which it is unambiguously stated for which matrices and analyte levels the method has been found to perform in a satisfactory manner. 

Although a thorough validation cannot rule out all potential problems, the process of method development and validation would address the most common ones. Examples of typical problems that can be minimized or avoided include interferences that coelute with the analyte in liquid chromatography (LC), a particular type of column that no longer produces the separation needed because the supplier of the column has changed the manufacturing process, an assay method that is unable to achieve the same detection limit after a few weeks, or a quality assurance audit of a validation report that finds no documentation on how the validation was performed. 

Validation reports are written at the conclusion of the equipment IQ and OQ and when process validation is completed. The reports should be stand-alone documents containing all pertinent information because they will serve as primary documentation for later FDA regulatory inspections and as reference documents when changes to the system are planned and the need for revalidation is under consideration. 

Documentation—This section of the protocol specifies what documentation must be included in the final validation report. Some potential documents are... 

Document validation experiments and results in the validation report. 

On satisfactory completion of the computer system qualifications, with PQ conducted in conjunction with a successful process validation, a final report must be prepared by the pharmaceutical manufacturer s validation team. This is normally referred to as the validation report. The objective of the report is to give an overview of the results of the execution of the validation program for the computerized operation and to draw a conclusion as to the suitability of the computerized operation for pharmaceutical manufacturing. This may be unconditional use or there may be restrictions. In the latter case the proposed remedial ac-tion(s) must be approved and, as applicable, considered under change control. A schedule to complete any outstanding actions must be documented and progress formally reported. 

The validation report is a comprehensive summary that documents how the project validation plan has been satisfied. With reference to the qualification summary reports, the validation report serves as the approval document for all life-cycle activities and is the mechanism for releasing the computerized operation for pharmaceutical manufacturing use. Recommendations may be made for any follow-up audit or additional testing. 

The report should also preview the validation file documentation, control procedures, and support programs that are vital to the ongoing validation program and must be used as the basis for maintaining the validation status of the computer system. At this time a review of the GMP risk assessment should be undertaken and included as a section in the validation report. 

When the validation report is being assembled, most of the work of the team will in fact be completed, and the task only consists of adding supportive documents to the executed protocol. Basically a standard format can be developed for packaging validation at a given facility. The following suggestions could be included in the report, but this is subject to individual variations ... 

The final validation report or summary is prepared after careful review of the data gathered during execution of the protocols. These data should be compared with approved acceptance criteria. The appropriate representatives of the validation team are usually those who approved the protocol and review and sign the final report and associated accompanying documents. 

Documentation of the IQ is important for QA so that the information will be available for future reviews by QA or the FDA inspector. There are three possible approaches that may be followed. First, the IQ information may be compiled as a stand-alone document to which other parts of the validation document would refer. The advantage of this approach is that the IQ doesn t get tied into a specific process or product validation. The second approach would have each validation document stand alone, which would mean that the IQ information on the equipment and facility would be repeated for every validation report. The third approach would combine the other two approaches namely, that the facility IQ would remain generic and the equipment IQ would be a part of the... 

The PV of a new facility [21] must be documented in such a way to ensure that the facility s design and the operations within it are fully covered. An outline of such activities is listed in Table 4. For example, the validation of a new facility makes it necessary to document the equipment performance under relevant conditions. All process (or facility) equipment will undergo IQ testing to make sure that each piece of equipment operates as it was designed to do. The technologist will determine how the equipment s performance will vary without the influence of the process material (OQ). This information will form the basis for the remainder of the validation report. From a QA viewpoint, it should also be noted that this information might be useful if it is compared against the parameter measurements under load conditions. Since this information is more properly included in the performance qualification (as process optimization), however, it should not become a part of the validation protocol... 

In the course of data validation, data qualifiers are attached to the data. Data qualifiers are the alphabetic symbols that indentify an undetected compound or a deviation from acceptance criteria. Data qualifiers are also called data flags. The findings of data validation are detailed in a data validation report, which documents the validation process and explains the reasons for attaching the qualifiers to the data. Laboratories also use data qualifiers for indicating deviations from laboratory acceptance criteria. These qualifiers are replaced with the validation qualifiers in the course of data validation. Qualifiers are rarely used in data review. 

This uncertainty budget must not only take into account the uncertainties of all the references used in connection with the analytical procedure, but also the uncertainties from the operation of the laboratory procedure as documented in the validation report. The uncertainty from the measurement procedure is frequently much larger than the uncertainties carried by the references. 

Formal documentation of the method-transfer results as addenda to the original validation report would further substantiate the overall validation process. Thus, each new laboratory setting would either confirm the original method validation, or indicate a possible need for method modification with revalidation. 

From a regulatory perspective, the most important document is the validation report. This is because the report is typically the first document that a regulatory agency will review. If the validation report is error-free and complete, the regulatory body has no need to investigate further. Awell-written validation report should include the following three essential items. 

The validation report should be a living document that reflects the dynamic validation process. Therefore, it should be updated using addenda to report method transfer results, ongoing system suitability and any revalidation efforts. 

History and rationale for the development of all major non-compendial methods for excipients and the finished product. List of all applicable reports supporting method development (e.g., method validation reports, technical support documents, etc.). 

List of all applicable reports supporting method development (e.g., method validation reports, technical support documents). 

All validation activities associated with producing a minimum of three validation batches of the API are drawn together in the form of a Validation Report. This report essentially documents company compliance with the NDA process, making it a vital document in the effort to gain FDA approval of the NDA. 

A method should be validated for its intended use with an acceptable protocol. All experiments conducted to make claims or draw conclusions about the validation of the method should be documented in a method validation report. 

One of the most important benefits that XML brought to CML is the existence of standard validation tools, which, equipped with definition of the language, can automatically check the formal structure of a CML document and report possible inconsistencies. For XML, there is a wide variety of generic software tools and libraries that enable checking, reading, and transformation of documents. Even though these tools are not directly focused on CML, they represent a good foundation for manipulation of the format. More about the benefits of XML and CML itself can be found in Chapter 6. 

Regardless of the level of sophistication, the exposure model(s) used for a given purpose/situation should be accompanied by sufficient documentation and reporting so that the assumptions, underlying mathematical and statistical procedures, data quality and transformations, input and output, validation procedures, minimally required data and intended use and limitations are transparent and clearly defined. These are essential components of good exposure modeling practices. Such practices ensure that an appropriate level of understanding can be achieved... 

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