GMP for APIs practically applied - the revised APIC "How to do" guideline

The provisions of guideline ICH Q7 published in 2007 regulate the GMP-compliant manufacture of active pharmaceutical ingredients. It was supplemented by a question and answer document in 2015, establishing a link to the ICH guidelines Q8-Q11, which have been published in the meantime.

Shortly after the publication of ICH Q7, APIC developed a "How to do" document, giving practical advice on the implementation of the API GMP regulations. This document was updated regularly. APIC has recently published version 10 of the "How to do" document. This new version includes updated implementation recommendations for the requirements of the ICH Q7 question and answer document.

The following are some examples of the highlights from the updated chapters of the "How to do" document.

Process Equipment - Computerized Systems

The validation scope of computerized systems should be based on a risk assessment considering every individual part of the system.

Packaging and Identification Labelling of APIs and Intermediates - Packaging Materials

Packaging material coming into direct contact with the API should at least comply with the food standard. If another primary packaging material is being used, its compatibility with the product must be ensured. Suppliers of packaging materials should be part of the supplier qualification program. Components of the packaging material which could migrate into the product (Extractables and Leachables) should be identified and classified in a risk assessment.

Rejection and Re-use of Materials

If API batches are reprocessed regularly due to non-compliance with the specifications, that is a sign for an inadequate manufacturing process or deficiencies in the quality assurance system, especially if the root cause for the deviations is usually the same. More and more companies are moving away from reprocessing API batches in compliance with their specifications but having reached their retest period. It is recommended that this practice, if continued, should be supported by stability data, at least.

How returned goods are to be processed - reworking, reprocessing, release, destruction, etc. - must be defined in a standard operating procedure (SOP), in which the processes are described in detail. The following points should be taken into account: state of the original seal, damage to the primary packaging and condition of the labelling, information about the storage conditions of the customer who returned the product as well as the need for further tests. If the product was returned due to quality concerns from the market environment, it must be evaluated (risk assessment!) whether the quality deficiency has any effect on goods which had already been distributed or are still in storage. In any case, the whole procedure from the receipt of a return to the last process step must be seamlessly documented and traceable.

Overall, the revised "How to do" document contains many recommendations and links to other guidances and position papers from the APIC as well as other organisations and authorities (ISPE, USP, EMA, ICH, etc.). An annex including a table, giving an overview of the correlation between the questions and answers from the ICH Q7 Q&A document and the corresponding chapters from ICH Q7, completes the "How to do" document.