ICH clarifies Q7 guidance on API GMP manufacturing

In response to a flood of requests over uncertainties regarding ICH Q7 guidance, the international consortium recently released a question and answer (Q&A) document intended help companies implement appropriate GMPs (good manufacturing practices) at all stages of the API supply chain.

The Q7 guidance, initially developed in 2000, aims to help API manufacturers ensure that their APIs meet the requirements for quality and purity that they purport or are represented to possess.

The Q&A on the guidance focuses on 20 different sections, including its scope, quality management, personnel, manufacturing facilities, cleaning process equipment, documentation and records, and the use of contract manufacturers and other parties involved in the supply chain.

Quality

The ICH further clarifies that product quality review “is generally expected annually,” though review timeframes can be adjusted based on manufacturing and campaign duration with adequate justification. “Even if no manufacturing has occurred in the review period, the quality review should be conducted as per section [ICH Q7, Section 2.50] and include stability, returns, complaints, and recalls,” the group says.

In terms of the quality management, the ICH specifies that when it calls quality units “independent from production,” it means to ensure “unbiased decision making regarding quality-related decisions in the organisation structure. The person in the quality unit who is responsible for final decision-making (e.g., batch release decision) should not have responsibilities for production activities.”

Facilities/Containment

The ICH offers specific examples of when dedicated production areas are expected, noting that they should be included for “highly sensitising materials such as penicillins and cephalosporins because of the patient risk (e.g., anaphylactic shock to penicillin-allergic patients) from trace amounts of these compounds in other medicines.”

The conference also calls for a risk-based approach in determining which materials are of an infectious nature or high pharmacological activity or toxicity in order to determine appropriate containment measures, which may include validated inactivation, cleaning and/or dedicated production areas.

Storage/Distribution

In terms of when APIs and intermediates can be transferred “under quarantine” to another unit under the company’s control, including a contract manufacturer, the ICH limits that to cases meant to allow for parallel testing. “Material that is transferred under quarantine is not to be used for further processing until all testing and quality review is complete and the material is released by the quality unit,” the ICH says.

Examples of circumstances where transfer under quarantine may be needed include extraordinary supply chain requirements, such as short shelf-life, and materials with a lengthy timeframe for required tests, for example some microbiological tests, ICH says.