Shortlyafter the entry into force of the Good Manufacturing Guide for Active Pharmaceutical IngredientsICH Q7 in the year 2000 the Active Pharmaceutical Ingredients CommitteeAPIC wrote the "How to do" document which clarifies the requirementsof the guideline on the basis of experience gained from operational practice.The present document aims at providing practical advice for the implementationand maintenance of GMP standards during the production of active pharmaceuticalingredients concerning those provisions of ICH Q7 that require furtherinterpretation. The "How to do" document is a "living" documentas it is revised in irregular intervals in order to keep pace with theconstantly changing state of scientific and technical knowledge.

The recentlyrevised version of the document was published as "Version 8" on the APIC publicationswebsite in August 2015. As compared to the last revision (August 2012) thechapters 10 "Storage and Distribution", 11 "LaboratoryControls", 12 "Validation" and 15 "Complaints andRecalls" were revised. The following is a selection of the most importantchanges:

Chapter10 Storage and Distribution

• This     chapter points out the importance of controlling the temperature     distribution in warehouses taking into account seasonal temperature     changes. The document indicates sets of rules that describe concretely how     to perform a temperature mapping (section 10.10.). 


• It  stresses the necessity of physical separation between released and     returned material, preferably by storing them in different rooms. Storage     conditions for intermediates are based on development data and knowledge     (section 10.11). 


• The     document points out that logistics companies should be qualified (quality     agreement). The shipping conditions records should be reviewed. If     deviations occurred an investigation should be initiated and appropriate     measures be carried out and documented (section 10.21).

Chapter11 Laboratory Controls

• This     chapter expressly points out that analytical methods have to be validated     and that the integrity of analytical data has to be ensured by means of     controls (section 11.11). 


• Rounding rules and the process used for averaging should be described in a SOP     (section 11.11.). 


• In     chapter 11.13 ICH M7 and ICH Q3D have been added to the list of ICH     guidelines. Furthermore, it is pointed out that the design of experiments     approach can also be used within the framework of design space when     defining specifications. 


• Chapter     11.15 contains detailed guidance on the FDA requirements for active     pharmaceutical ingredients that are exported to the USA and sold there,     especially on the handling of OOS results.

Chapter12 Validation

• Chapter     12.11 explains more in detail the handling of critical parameters and     quality attributes referring to the actual ICH guidelines ICH Q8 and Q11     as well as to FDA and EMA guidelines. 


• It     indicates that the 3 consecutive validation batches should be considered     as an orientation. The actual number of validation batches has to be     pre-defined and to be justified (section 12.50). 


• The     process validation report has to contain all critical quality attributes     compared to the reference batches. These attributes should be comparable     to or better than the reference batches. The rationale for selecting the     reference batches must be justified (section 12.52).

Chapter15 Complaints and Recalls

• This     chapter refers to the necessity to include other batches potentially     connected with the batch affected by the complaint or recall in the     complaint investigation and to define a period to close complaint     investigations (section 15.10). 


• It     points out that a recall cannot be carried out by the API manufacturer     himself. This is the responsibility of the finished dosage form     manufacturer. The notification of the authorities (such as public health     departments) can also only be carried out in close cooperation with the     finished dosage form manufacturer (section 15.10).

As awhole the revised "How to do" document is a valuable aid for the implementationof the Good Manufacturing Practice in the production of active pharmaceuticalingredients. Due to the thorough revision of many sections it offers anup-to-date practice-oriented assistance every API manufacturing site can profitfrom.

APIC How to do document on ICH Q7