Documentation standards change control

Impurity analysis/identification/synthesis Reference standard characterization Change control documentation Stability protocols... 

As far as possible, systems existing in a production mode prior to the effective date of the GALP standards, as well as purchased systems, should be docmnented in the same way as systems developed in accordance with the EPA System Design and Development Guidance and Section 7.9.2 of the GALPs. Documentation relevant to certain phases of the system fife cycle, such as validation, change control, acceptance testing, and maintenance, should be similar for all systems. 

In addition to inspection and calibration of instrumentation carried out as part of an SAT, the need for recalibration of critical instruments prior to IQ, OQ, and PQ should be reviewed and the decision documented in the respective qualification report. All site calibration activity should be conducted in accordance with quality standards and the respective engineering procedures. Any remedial work should be undertaken under document control, and where necessary, evaluated under change control. 

Most firms today use a validation change control system, by which such documents as engineering work orders, revisions to standard operating procedures (SOPs), and proposed formulation order changes are reviewed by a committee of the same disciplines as those responsible for validation approvals. The objectives are to determine the potential impact on validation status before formally approving the change. This mechanism enables a firm to take immediate prospective action, obviating the need to revalidate the entire system. 

All stability studies on clinical trial materials must be carried out in full accordance with cGMPs, even if a research department carries out the studies. All studies must be carried out by adequately trained personnel under adequate work conditions. The personnel must use properly qualified and calibrated stability chambers, instruments, reagents, and standards. They must follow validated analytical methods and approved written procedures, and they must properly document all work. There must be proper sample and data traceability, change control, and go on. 

Computer validation should not be undertaken unless fundamental validation controls have been fully understood and implemented within the pharmaceutical or healthcare company s organization. Here we allude to properly qualified personnel, effective document management and change control systems, internal audit procedures, methods of managing the deviations from standard practice thereby exposed, and a culture of continuous improvement (see Chapter 4 for more details). Senior management must not fall into the trap of assuming through complacency or idleness that these controls have been fully instituted In most firms there is usually much that still needs to be done in these areas. Let us examine these controls a little more closely. 

Documentation standards should be defined so that there is consistent document layout, style, and reference numbering. Documents should be clearly marked as draft until they are formally released. Version control should be apparent. The version identifiers should distinguish documents under development (drafts) from those that have been issued formally. Documents should include a document history section to log the changes made in successive issued versions of the document. Individual documents should have the following controls ... 

Suppliers of materials and reagents should be expected to operate according to standards appropriate to their supply and use, and to provide relevant quality control documentation. The developer has the responsibility to confirm that critical materials detailed in the SOP(s) are suitable for their intended purposes. Furthermore, it is important to monitor different batches of materials with regard to changes or variations, which may affect their use. For certain reagents, such as serum, testing prior to use may be necessary. 

Individual protocols and reports can be written for each test to facilitate transfer of specific mefhods. This approach allows a discrepancy fo be investigated while not holding up unaffected method transfer activities. To facilitate internal and regulatory inspections, the method transfer protocols and reports should be compiled for easy review at the receiving site. The raw data should be readily accessible. Transfer of any relevant documentation such as methods, specifications, validation reports, reference standard information should be completed. From this point on, the change control process should assure that methods and specifications remain the same at the qualified fesfing sifes except perhaps for document format. 

Standards In order to ensure consistency, standards must be used, for example, GAMP [1] and in-house standards and procedures. These procedures will typically cover production of validation documentation, change control, contingency planning, and so on. 

Determination of the maintenance effort is again a difficult task. It will depend on factors such as the size of the system, the age since delivery, structure and type of system, quality of the documentation standards and the document update procedures in place, the number of reported bugs, the type and number of change requests that are mandatory and desirable, the use of change control procedures, the establishment of test procedures, the level of staff competence and training and staff turnover. 

On the middle level are the concrete specification documents for the operational level, which describe certain work processes and are also considered to be controlled documents, that is, they are subject to change control. Examples of documents on this level are, for example, standard operating procedures (SOPs), test instructions, manufacturing instructions, packaging instructions, specifications, calibration instructions, or maintenance instructions. 

NOTE A change in these standards/specifications requires an updated record of customer production part approval when these specifications are r erenced on the design record or if they affect documents of production part approval process, such as control plan, FMEAs, etc. 

The standard does not require you to document how you maintain your quality policy but the requirements of clause 4.5.1 place the quality policy into the category of documents which need to be governed by documented control procedures and hence all changes must be reviewed and approved. 

The standard also requires that the instructions be derived from appropriate sources, such as the quality plan, the control plan, and the product realization process, which means that all instructions should be traceable to one or more of these documents. They should form a set, so that there are no instructions used outside those that have been approved by the planning team. This is to ensure that no unauthorized practices are employed. Another important aspect to consider is the use of informal practices - practices known only to the particular operator. Process capability should be based on formal routines, otherwise repeatability cannot be assured when operators change. 

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