Documentation

All procedures must be properly documented. It is assumed that any event did not occur if it is not documented. The different types of documen-tation include:

(a) Standard operation procedures — These are instructions for staff to carry out their tasks.

(b) Validation plans and records — These should describe the basics of validation work, how to perform the validation work, including detailed work instructions, staff responsibilities and timetables, as well as the results of each validation test.

(c) Batch records — These are records of the manufacture of each batch of products. The records should at least include the name of the product, lot number of the product, date of manufacture, staff carrying out the manufacturing, raw materials used, equipment used, facility where the manufacture took place, manufacturing method, monitoring of the manufacturing reaction, as well as monitoring of the manufacturing environment.

(d) Quality control records — These are records of the QC tests performed on each batch of product. The record should include at least the name of the product, lot number of the product, date of tests, staff carrying out QC tests, reagent used, equipment used, test method, results, acceptance limits and interpretation of the results. These records should be signed by

the person in charge of QC and include a statement confirming whether the product has passed the QC tests.

(e) Approved forms — There should be different forms for different purposes.

(f) Specifications — These refer to raw material requirements, final products, test reagents, manufacture and QC equipment, manufacturing facility, etc.

(g) Data sheets.

(h) Log books, etc.

6.3.1. Records

Proper records are helpful for reducing errors. Records must be completed in a timely and accurate manner. The objective of having records is not to find fault with staff, but to identify problems so that they can be avoided in future.

Supervisors and staff should periodically and routinely review records. By reviewing records, staff can monitor equipment performance and changes in environment, so that necessary actions such as maintenance, calibration or repairs can be carried out.

The following records should usually be kept:

(a) Production batch records — These are detailed records of how the product is manufactured. The records should include descriptions of the starting materials, manufacturing procedures, manufacturing environ-ments, manufacturing staff and labelling.

(b) Checklist records of release for supply — These are records of the final check of a product before it is released from the facility. A PET product, because of its ultra-short half-life, can be released without a completed release for the supply checklist records. These records provide assurance that the product and the manufacturing process have been cross-checked before it is released.

(c) Dispensing records — These are records of the dispensing of the product.

They should provide details of the time of release of a certain dose, the identity of the patient receiving the dose, dosage, time of dispensing, lot number of the product and the staff dispensing the dose.

(d) Quality control records — These are records of the QC tests of the product. The QC should be signed by the staff performing the QC, then reviewed and signed by the person in charge of QC.

(e) Equipment use records — These records track how equipment is used, calibrated and maintained. They also describe the functional status of the equipment and ensure that all equipment is functioning properly.

(f) Environment monitoring records — These records track the manufacturing environment to ensure that it is suitable for the manufacture of PET radiopharmaceuticals.

(g) Cleaning records of equipment and facility — These records monitor the cleanliness of the manufacturing equipment and facility according to SOPs. It is used to check that the facility and equipment are functioning within acceptable limits.

(h) Validation records of the equipment and facility — These records ensure that the manufacturing facility and equipment have been validated.

(i) Maintenance records of the equipment and facility.

(j) Calibration records of equipment.

(k) Staff training records — These records ensure that staff have been properly trained in certain procedures.

(l) Check-in records of raw materials — These records ensure that the raw materials received are acceptable according to the specification set. Each batch of raw materials received should be checked.

(m) Out of specification investigation records — These records ensure that a proper investigation has been carried out if a product has failed a QC test.

(n) Corrective and preventive action records — These records ensure that appropriate action has been taken in response to any problem outside normal specifications.

(o) Recall and complaints records — These records ensure that proper action has been taken in the case of a complaint or product failure.

6.3.2. Standard operating procedures

All procedures must be clearly written and reviewed, and all staff must be familiar with all SOPs. Standard operating procedures, which are properly written and adhered to, can prevent human error and individual variations, as well as maintain uniformity among batches.

Standard operating procedures must be constantly reviewed. Before an SOP is put into use, it should be tried or ‘field tested’. A well written SOP should include:

(a) Version number — To keep track of the revision history of the SOP. The SOP in use should be the one with the latest version number.

(b) Author — Usually the author who wrote the SOP is the one who will rewrite or update it.

(c) Signature, date of adoption of the SOP — All SOPs should be reviewed and approved by the person in charge. This means that the SOP has been tested and found to be suitable for use. An SOP is not official without the signature of the person responsible for approval.

(d) Objective of the SOP — This is a description of what the SOP is used for.

For every procedure, there should be a specific SOP. Staff should use the correct SOP.

(e) Persons responsible for carrying out the SOP — This must clearly identify the responsibility of the staff when performing a certain procedure, in order to avoid confusion and, subsequently, mistakes.

(f) An overview or flow diagram of the procedures — This is a summary of the procedures to be performed.

(g) Procedures in detail — Instructions should be as detailed as possible. The instructions should also be written clearly so that any new staff can follow them.

(h) Interpretation of results (if any).

(i) Actions to be taken if failures occur (if any).

(j) Affiliated documents.