15/16 September 2020
The European Medicines Agency (EMA) recently released industry comments gathered during its public consultation for the International Council for Harmonization's (ICH) draft guideline on pharmaceutical product lifecycle management (ICH Q12). The ICH Q12 draft guideline entitled Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, and its Annexes were adopted by ICH and released for public consultation in November 2017. Last year, EMA and FDA published the guideline for comment with deadlines. The comment deadline for ICH Q12 for Europe was December 18, 2018.
Now, EMA published an overwiev of the received comments on the EMA website. Most of these comments express concern that two of the central aspects of the guideline, established conditions (ECs) and product lifecycle management (PLCM) documents, are incompatible with the legal frameworks of certain ICH regions. While the draft guideline notes the potential legal holdups, it lacks in addressing them until a legal review can be conducted.
EMA published the draft guideline (which applies to drug substances, drug products and drug-device combination products) in the original version released by ICH containing the statement: "These concepts will, however, be considered when the legal frameworks will be reviewed and, in the interim, to the extent possible under the existing regulation in these ICH regions". In contrast, the FDA published the document differently. They added the following note in their published Q12 draft: "In the United States, the ICH Q12 guidance is fully compatible with the established legal framework. Therefore, the concept of Established Conditions and supporting Product Lifecycle Management document are fully supported by the U.S. FDA as described in this guidance".
Several EU associations, including the European Federation of Pharmaceutical Industries and Associations (EFPIA), the European Biopharmaceutical Enterprises (EBE), Vaccines Europe and Medicines for Europe, emphasize that the guideline as written implies a "real risk of divergence across countries/regions" in how ECs and PACMPs are handled that could lead to a greater regulatory burden for industry. Both the ECs and PLCM documents are the core of the Q12 guideline. "Incompatibility of these concepts with the established legal framework is a matter of concern" is one of the comments.
Some comments contain concerns that finalizing the ICH Q12 guideline before there is a harmonized approach to ECs could "trigger confusion" between regulators and industry. Furthermore, clarification is needed on whether the guideline will apply to existing marketing applications and requests that regulators set clear compliance dates for updating those applications. Similarly, there is the demand to "better clarify the expectations for 'legacy products' … to overcome the uncertainty that was raised with ICH Q8-Q11."
In addition, more than a dozen API-manufacturers have offered comments on FDA´s draft guidance Postapproval Changes to Drug Substances, noting that FDA's guidance does not incorporate concepts from the ICH Q12 guideline meant to simplify the postapproval change process. It also remains unclear whether FDA plans to update this guidance once Q12 is finalized.
More information can be found in the EMA document Overview of comments received on ICH guideline Q12 on technical and regulatory considerations for pharmaceutical product lifecycle management.