The design and construction of facilities must afford a clean environment. Surfaces must be impervious and able to withstand regular cleaning. Activities must be segregated with interlocking doors to prevent cross-contamination. There must be a cascade of filtered air pressure from the cleanest area to the exterior to minimise the ingress of particles. This is achieved by heating, ventilation and air conditioning system (HVAC) with high-efficiency particulate air (HEPA) filters. Similarly, there must be a regimen of gowning up to prevent staff from carrying contaminants into the clean areas. Materials are sanitised and then transferred in via hatches with interlocking doors. Aseptic processes must be carried out within an appropriate environment of filtered air. Generally, radiosynthesis can be carried out in Grade C, but sterile filtration and dispensing must be carried out in Grade A. These are generally achieved with a hot cell, pharmaceutical isolator or laminar airflow cabinet. All equipment must be kept in good working order with regular checks of performance and records of maintenance undertaken. Proper operation of the facility must be documented by routine environmental and microbiological monitoring. This includes a combination of measurements of air flows and air change rates, active air sampling and particle counting and routine microbiological monitoring including agar settle plates, contact plates and finger dab plates. All of this is covered by the site master file (SMF).

Personnel must be adequately trained in any procedures they carry out, with a training record. The training record must indicate that the member of staff has read the SOP and has demonstrated competence with evidence of a certain number of monitored activities. The responsibilities and authorities of each grade of staff must be specified. Persons who perform aseptic procedures must undergo periodic revalidation of their competence. If production facilities are shared with a research institution, the research personnel must be adequately trained in GMP regulations, and the quality controller (see below) must review and approve the research activities to ensure that they do not pose any hazard to the manufacturing of radiopharmaceuticals.

There must be a person designated as production manager, sometimes called responsible person. This person is responsible for the routine operation of the facility to ensure that the radiopharmaceuticals are produced to GMP standards. This includes ensuring that there are sufficient numbers of suitably trained staff available on a daily basis. This person makes sure that all documentation is complete before products are passed on to the quality assurance department.

There must be another independent person designated as quality controller. This person takes ultimate responsibility for the quality of the radiopharmaceuticals produced, though the act of release may be delegated to a suitable trained person. In some situations the quality controller might also be a qualified person.

All Standard Operating Procedures (SOPs) must be written down, approved and reviewed at regular intervals. There must be contemporaneous manufacturing records which document the adherence to SOPs and record the identities and quantities of all materials used and any in-process checks, all of which must be initialled or signed by the operator and checker. Quality assurance results must include evidence that the analytical equipment had been properly calibrated. There must be a Validation Master Plan (VMP).

One of the underpinning features of GMP is the quality of starting materials. Precursors must be obtained from approved vendors. There must be a process for auditing or inspecting vendors. It may be possible for a single such audit to be performed on behalf of a number of PET centres in the same country. All chemicals which remain in the final formulation must be obtained from certified pharmaceutical suppliers. In particular, active pharmaceutical ingredients (API) must be obtained from a certified GMP source.

In recent years, inspectors have placed increasing emphasis on the quality management system [30]. Indeed, this chapter was revised in 2013. Quality management is a wide-ranging concept, encompassing all matters which individually or collectively influence the quality of a product. The components of a QMS include the following. Product and process knowledge is managed throughout all life cycle stages. Managerial responsibilities are clearly specified. Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials, the selection and monitoring of suppliers and verifying that each delivery is from the approved supply chain. Processes are in place to assure the management of outsourced activities. The results of product and process monitoring are taken into account in batch release, in the investigation of deviations and with a view of taking preventive action to avoid potential deviations occurring in the future. All necessary controls on intermediate products and any other in-process controls and validations are carried out. Where the true root cause (s) of the issue cannot be determined, consideration should be given to identifying the most likely root cause (s) and to addressing those in order to assess which might be responsible. Where human error is suspected or identified as the cause, this should be justified having taken care to ensure that process, procedural or system-based errors or problems have not been overlooked. Appropriate corrective actions and/or preventative actions (CAPAs) should be identified and taken in response to investigations in a timely manner. The effectiveness of such actions should be monitored and assessed, in line with quality risk management principles. There is a process for self-inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the pharmaceutical QMS.