17/18 September 2019
Already in October 2012 the International Conference on Harmonisation (ICH) has started to develop the ICH Q7 Q&As. At this time a Final Concept Paper was published.
Now the ICH has published the ICH Q7 Questions and Answers on GMP for Active Pharmaceutical Ingredients. It is the intension of the guideline to clarify uncertainties due to different interpretations of requirements laid down in the ICH Q7 Guideline. The Q&A provides a table which aims to show the link between each Q&A and the relevant Sections of ICH Q7 and other ICH Quality guidance. Very much of the content of the new Guideline has been provided by the Pharmaceutical Inspection Co-operation Scheme (PIC/S). The PIC/s has been involved by selecting and reviewing relevant Q&As. In addition questions were developed based on responses from an ICH survey. The preface of the Q&A document states that ICH Q7 should be applied in combination with the principles laid down for development and manufacturing in ICH Q11 (see definition of API starting material; see also ICH Q8(R2) Part II), Quality Risk Management (ICH Q9), and Pharmaceutical Quality Systems (ICH Q10).
The document is structured according to the chapter of ICH Q7. Already for the scope of the ICH Q7 the Question and Answer Guide provides a very frequently asked question:
Should GMP according to ICH Q7 be applied for manufacturing Steps before the defined ‘API starting material' i.e., Steps not identified in grey in Table 1?
ICH Q7 does not apply to Steps prior to the introduction of the API starting material. However, there is an expectation that an appropriate level of controls suitable for the production of the API starting material should be applied [ICH Q7, Section 1.3]. Normally, the ‘API-starting material’ is defined in the regulatory filing by the applicant and approved in the regulatory reviewing process. Additional guidance is provided to define and justify ‘API starting material’ derived from various sources [ICH Q11, Section 5]; for master cell banks, see [ICH Q5B; ICH Q5D].
Clarification is provided to nearly all additional chapters such as Quality Management, Personnel, Buildings and Facilities (Containment), Process Equipment (Cleaning), Documentation and Records, Material Management, Production and In-Process Controls, Storage and Distributions, Laboratory Controls, Validation, Change Control, Rejection and Reuse of Materials, Complaints and Recall, Contract Manufacturing (including Laboratories), Agents, Brokers, Traders, Distributors, Repackers and Relabellers. Also questions on specific manufacturing steps such as APIs manufactured by Cell Culture and Fermentation and APIs used in Clinical Trials are covered.
Among the many interesting Q&As here is one regarding Building and Facilities:
When are dedicated production areas expected?
ICH Q7 expects dedicated production areas 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 [ICH Q7, Section 4.40]. For materials of an infectious nature or high pharmacological activity or toxicity, a risk-based approach should be used to determine appropriate containment measures, which may include validated inactivation, cleaning and/or dedicated production areas [ICH Q7, Section 4.41]. While ICH Q7 does not define high pharmacological activity or toxicity, these are generally determined by evaluating relevant animal and human data collected during research and development. Important considerations in this evaluation of pharmacological activity or toxicity may include Occupational Exposure Limit (OEL), Permitted Daily Exposure (PDE), Acceptable Daily Exposure (ADE), Threshold for Toxicological Concerns (TTC), No Observed Adverse Effect Level (NOAEL) [ICH S Guidelines, ICH E2E, Section 2.1.1], and the consequences of cross-contamination [ICH Q9, Section 4.3].
The Question and Answer Guideline on ICH Q7 will be covered by a session at the 18th European API Conference organised by APIC/CEFIC on 4-6 November in Amsterdam. APICs President Anthony Storey (Pfizer) and Francois Vandeweyer, Janssen Pharmaceutica, Belgium, will lead the session. For more information please visit the API Conference website.