Final inspection is an essential element in controlling the quality of pharmaceutical preparations. In the first place, the final control comprises of the control of the batch documentation. In a larger organisation, such as a hospital, this is often the task of the production pharmacist.

The Quality Control (QC) department has to operate according to Good Quality Control Laboratory Practice (GQCLP) standards [2]. All QC methods have to be validated and verified before application. The instruments used for QC are qualified and calibrated before QC testing is performed. There is a procedure in place for the investigation of Out Of Specification (OOS) and Out Of Trend (OOT) results. The reference standards used should be certified, qualified and verified. Documentation and traceability are important such as in production. All raw data should be retained.

During quality control the laboratory checks whether the product meets all specifications. The control of the end product includes a number of non-destructive tests, such as checking the yield or the weight distribution or a visual control of packaging and labelling. Subsequently the required analytical and microbiological tests are carried out. The assessment of the finished product includes production conditions, the results of IPC testing, the documentation review and compliance of the final product with the specifications.

An important part of the quality control is the sampling policy (number of samples, method of sampling, select or random samples or both see Sect. 20.​4). The selected samples must be taken in those places where the risk of deviations is greatest (worst case procedure, see for instance 11.5 for sampling suspension-type suppositories after serial filling). In addition, samples are taken for stability testing (reference and retention samples) and validation.

QC is not restricted to laboratory operations, but should be involved in all decisions related to product quality (see Sect. 35.​6). As an example, QC participates in the investigation of complaints about product quality. QC is involved in the assessment and the monitoring of the stability of the products as well. The QC department has to approve the IPC methods used in production. In all situations, the independency of QC from the production department is fundamental.

When the pharmacy doesn´t have own facilities for conducting pharmaceutical analysis, these QC activities can be outsourced [4].

The final release of products comprises a major responsibility, which must be independent of production. In pharmaceutical industry release is performed by a qualified person (QP), in pharmacies often by a pharmacist. Investigational medicinal products (IMPs) always have to be released by a notified QP (Sect. 25.​3.​4).

The extent of the final inspection and release policy depends on the type of preparation. Thus, for extemporaneous preparations an independent control of the preparation record and a few non-destructive inspections of the product will suffice. If no abnormalities are observed, an authorised pharmacist can perform the product release. In some countries a delegated person may release the extemporaneous product conditionally; afterwards, within a defined time frame, the authorised pharmacist releases the product formally.

In some situations, for example with very short-lived radiopharmaceuticals, conditional release before all QC tests are performed is necessary. As a consequence, process validation is important. An immediate recall procedure must take place, when product quality is found to be insufficient.

Stock preparations usually undergo an extensive analytical control (see Sect. 34.9.2) and remain in quarantine until the QC is fully completed (see Sect. 34.9). The release is based on the assessment of the document control in combination with the analytical quality controls. During release, final reconciliation takes place. For certain preparations (e.g. aseptic preparations) also the results of monitoring of production conditions are included.

The GMP (Annex 15) requires that the producer controls the critical properties of the product and of the critical steps in the process [3]. This means that the quality of the design of the product, the preparation or manufacturing process, the equipment and automated systems used have to be assured. The organisation must demonstrate that processes, equipment, systems, installations and analysis perform reliably and reproducibly under all possible conditions. This is usually called validation.

According to GMP, validation is the action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, activity or system actually leads to the expected results. Qualification is the action of proving that any equipment works correctly and actually leads to the expected results. The word validation is sometimes widened to incorporate the concept of qualification.

Because of these somewhat vague and overlapping definitions, in this chapter the term qualification is used in the case of equipment and persons and the term validation when assessing processes or methods.

As a rule, qualification of equipment and building-related installations takes place before putting into operation (= prospective). Validation of preparation and manufacturing processes is done preferably prospective as well, when designing a new process. However, in some situations qualification or validation has to be performed simultaneously with the application of the equipment or process; this is called concurrent qualification or validation. Concurrent qualification or validation should only be applied to simple equipment or processes, where there is very little chance that the outcome would be negative and products would have to be destroyed.

It is also possible to perform a qualification of equipment or validation of a production process that is already operational, but has not been previously validated. This so-called retrospective validation consists of collecting, evaluating and assessing data from the past. Retrospective validation is only possible if no significant changes in the method of preparation or equipment have occurred during the measuring period, and if sufficient, reliable data are available. If that is not the case, additional prospective validations have to be performed.

When changes occur, it has to be ascertained that the product still meets the specifications and whether re-validation is necessary to prove this. Therefore, an effective change control procedure has to be in place.

A one-time validation or qualification does not exist whether regarding equipment or process. The minimum requirement is that the status of validation and qualification has to be evaluated on a regularly basis. The evaluation frequency has to be pre-defined in accordance with a risk-based approach. The evaluation has to include a systematic going through any changes, deviations or trends in performance e.g. as indicated from test results. If the evaluation leads to the conclusion that the “validated state” is changed a targeted re-validation has to be done. If there is no indication or need for re-validation the evaluation is documented in a report, which has to be approved by the same functions as the initial validation or qualification. For sterilisation processes re-validation is mandatory every year. Beyond the regular re-validation an important reason for re-validation is an essential change in the equipment, the process or the product range.

All proposed changes must go through the change control procedure (see Sect. 35.​6.​10) to determine the impact of the proposed change on all related equipment, systems and processes. A standardised risk assessment procedure may be helpful to determine the extent of re-validation activities. It is usually not necessary to entirely repeat the initial validation. Guided by the quality requirements of the product and the nature of the changes a decision is made which parts of the initial validation have to be repeated.

In general, the head of the production department and the head of the QC department have management responsibility for the validation program. Quality staff may play a significant supporting role in supporting validation activities. The final responsibility for validation is described in the validation master plan (see Sect. 34.11). Validation activities should only be performed by suitably trained personnel who follow approved validation procedures.

Despite its complexity, validation provides benefits. Besides the increased control of processes, validation provides more insight into the critical factors, which can result in increased patient safety, fewer errors and less rejections. The PIC/S has published a recommendation regarding validation, which may be used as reference material [5]. However, the latest version is from 2007 and recent developments are not included.

In the following sections the principles and different forms of validation and qualification are elaborated.