Based on the WHO Good Trade and Distribution Practice for Pharmaceutical Starting Materials (GTDP) guideline, which APIC calls “the only guideline taking care of GDP for APIs,” APIC’s guidance calls on API manufacturers and distributors to institute a quality management system that lays out specific procedures and principles for interacting with suppliers.
“The Quality Management System should also include a procedure to verify that any supplier of APIs, packaging materials or services has the capability to consistently meet previously agreed requirements,” APIC says. The responsibilities of independent quality units within this system also should be written out in the form of a contract or agreement.
The committee also calls for an independent quality unit to ensure quality assurance (QA) responsibilities, such as documentation and traceability of the API distribution activities.
If the API is shipped in the originally sealed containers from the manufacturer, “no additional testing and batch release are required,” APIC notes, adding that there should still be inspection of the integrity of the packaging (including labeling) and seals.
Personnel should be trained in the handling of the material according to requirement of the product safety data sheet, which should also cover hygiene procedures.
As far as the storage of APIs, APIC recommends that they should be stored in a way that protects from degradation, contamination or cross-contamination – preferably in storage boxes, drums or bags off of the floor.
“Material should be stored in such a manner that there should be ample space for cleaning and inspection,” APIC cautions.
For longer-term storage, APIC recommends setting alarm limits on temperature and humidity limits, as well as procedures to manage such situations. In case of temperature excursions during storage, companies can use stability studies, cycling studies, as well as other risk assessments to gauge the impact on the API.
“Procedures should describe operation and maintenance of equipment used in the holding, transfer or sampling of the API,” APIC adds, noting that it recommends equipment devoted to the handling of APIs. Cleaning procedures and schedules will be necessary if non-dedicated equipment comes into contact with APIs.
In addition to the GDP document, APIC also released guidance on the aspects of cleaning validation for API manufacturing facilities.
Though APIC cautions that the guidance should “not be considered a technical standard,” the committee says it should be used as a starting point for internal discussions.
The guidance document addresses six areas:
• Acceptance criteria;
• Levels of cleaning;
• Control of the cleaning process;
• Bracketing and worst case rating;
• Determination of the amount of residue; and
• Cleaning validation protocol.