Keywords: Antitrypsin; Cirrhosis; Consequences; Hemorrhage; Peritonitis

Pharmaceutical laboratories operate under strict regulatory environments and provide vital services to their customers who expect accurate and reliable results produced within stipulated times and at reasonable cost. Adoption of the quality management system (QMS) by a laboratory in compliance with the ISO 17025 standard is the best way to achieve, maintain and improve accuracy, timeliness and reliability of the test results. The present article summarizes the QMS principles, steps for the QMS implementation and the practical benefits of accreditation according to ISO 17025. Focus is given to key aspects such as quality documentation, document control, control of records, internal audit, corrective and preventive action, management review and continual improvement. The strategies described herein may be adopted as a guide to implement the QMS in a pharmaceutical testing laboratory for assuring the quality of their results and services.

Keywords: Audit; Corrective and preventive action; ISO 17025; Management review; Pharmaceutical laboratory; QMS

Pharmaceutical laboratories carry out tests and assays for the confirmation of active pharmaceutical ingredients, pharmaceutical products and excipients to meet predefined specifications and thus play an important role in clinical or public health setting. Pharmaceutical regulation is heavily dependent on the analytical results generated by pharmaceutical testing laboratories to describe accurately about the quality of each drug. For these reasons, the results produced by pharmaceutical laboratories must be as accurate as possible, all aspects of the laboratory operations must be reliable and reporting must be timely in order to be useful. Implementation of the QMS by testing laboratories is considered as the best approach to achieve these goals and attain accreditation status for their services leading to the validity of the test results.

ISO has developed an standard, known as ISO 17025: 2005 ‘General requirements for the competence of testing and calibration laboratories’, for the accreditation of testing laboratories to a wide range of testing environments [1]. Compliance with ISO 17025 standard requires that the laboratory shall establish and maintain a systematic way to ensure and improve its performance. Implementing an ISO 17025 based laboratory management system is a means to ensuring efficiency and technical competency in testing laboratories. In this article we summarize the recommendations and strategies for implementation of the QMS in pharmaceutical testing laboratories.

Establishment of the QMS is primarily driven by proper documentation of laboratory policies, processes and procedures. Documentation is the mechanism for defining the quality system so that there is a consistent and secure basis for monitoring the system. Documentation used in the quality system must be communicated and available to, understood and implemented by, all laboratory personnel. The hierarchy of essential documentation for establishing the QMS is illustrated in a pyramidal form in (Figure 3). The key piece of quality documentation is quality manual which constitute the apex of pyramid. Quality manual describes the road map to the whole documentation of the laboratory and contains the quality policy, organization structure of the laboratory, responsibilities of laboratory staff for management of the QMS and technical operations, QMS procedures, and management responsibilities. The quality policy of the pharmaceutical laboratory shall describe the laboratory management’s intentions with respect to the purpose of the quality system and quality of testing, commitment to continual improvement in the performance of laboratory, statement that laboratory work will withstand scientific and legal requirements and statement on the commitment by the laboratory staff in ensuring compliance with ISO 17025. All personnel of the laboratory are responsible for adherence to the quality policy. The quality policy may be subject to periodic review but is unlikely to change significantly unless the primary purpose of the laboratory is to change.

Figure 3: Hierarchy of quality documentation.

Quality manual also describes the procedures, commonly known as SOPs, for effective implementation of the QMS. SOPs are defined as ‘detailed written instructions to achieve uniformity of the performance of a specific function’ [2] and constitute the second level in the hierarchy of documentation. In simple terms SOPs specify in writing the responsibilities of the personnel along with the way to carry out the activity. SOPs establish a systematic way of doing laboratory activities and ensure that activities are performed consistently by all laboratory staff.

The practical day-to-day work instructions are prepared for ready reference at the site of actual work. This becomes the third level of documentation hierarchy. Instructions are required to perform a section of a procedure and can be part of a procedure or can be referred to in a procedure and published separately. The advantage of having them separate is that any changes to instructions do not require a change to the procedure.

The final level in the hierarchy of documentation is the forms. These forms and the records created using them are a crucial part of the QMS as they are the evidence that a procedure and related instructions have been carried out.

In this section the most important technical requirements for compliance with the ISO 17025 standard are briefly discussed. Personnel are considered important as they probably have the highest impact on the quality of test results. Each pharmaceutical laboratory should ensure that all laboratory personnel are adequately qualified and competent for performing the testing and other laboratory activities. Authorize personnel should carry out specific tasks such as operation of equipments, testing of sample, issuing test reports, to interpret specific test results and to train other personnel. Based on required skills and available qualifications, a training program should be developed and implemented for each personnel and the effectiveness of the training should be evaluated.

Selection and validation of appropriate test methods is also important for obtaining accurate results. The laboratory should have written procedures on the use of test methods. If standard methods are available for a specific sample test, the most recent edition should be used. When using standard methods, the laboratory should verify its competence to successfully run the standard method. For validation of test methods standard guidelines may be followed [4]. Pharmaceutical laboratories should also ensure the quality of their results on an ongoing basis through regular analysis of quality control samples or participation in proficiency testing programs. Other critical quality control checks can include the regular use of certified reference materials, replicate tests using the same or different methods, and retesting of retained samples. Other key requirements for implementing the QMS in compliance with ISO 17025 are: uncertainty of measurement, equipment, sampling, sample integrity and reporting. Detailed description of these requirements is beyond the scope of present article.