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ICH Q12 is here. What Does it Mean for Pharma?

The International Council for Harmonisation (ICH) is an organization which brings together the pharmaceutical industry and regulatory authorities to improve the synchronization of industry regulations. The organization’s ultimate goal is to ensure the development, production and registration of safe, effective and high quality medicines.

In November 2019 the ICH held its assembly in Singapore, where they formally adopted several guidelines:

  • Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management
  • E9(R1): Addendum to Defining the Appropriate Estimand for a Clinical Trial/Sensitivity Analyses
  • M9: Biopharmaceutics Classification System-Based Biowaivers.

The objective of ICH Q12 is to promote innovation and continual improvement in the pharmaceutical sector, and strengthen quality assurance and reliable supply of product, including proactive planning of global supply chain adjustments.

Some Challenges With Q12 Rollout
Q12’s approval and rollout, however, have met with some pushback. Among the concerns which have been aired, it has been termed “another quasi-management-based regulatory guideline” which could yield “additional confusion and more work from a vaguely defined, potentially duplicative system that will likely further inhibit the industry from achieving excellence.”

In an ironic twist, one chief concern regarding Q12 has been the potential loss of harmonization it might create. As things stand, ICH Q12 is complementary to ICH Quality Guidelines Q8 through Q11. The FDA has also indicated that Q12 is fully-harmonized with existing regulations & frameworks, while in the EU “revision of local regulations (e.g. the EU Variations Regulation) will have to be performed to fully implement the concepts of Q12.”

The article at GMP News (EMA Publishes Comments on ICH Q12) discussed the cross-Atlantic discrepancy, pointing out that when the EMA published ICH’s original version of the draft guideline, they included 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.” The FDA, meanwhile, simply noted that “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.

Earlier in 2019, Lachman Consultants mentioned at a meeting on The Future of Post-Approval Changes is Coming – Are You Ready for ICH Q12?: “Speakers from CBER were skeptical about the applicability of the enhanced approach (as defined in the Q12 guideline)” to their applicable CBER products, while “CDER’s outlook was a bit more positive and it has received the nine applications and supplements that it solicited” from a pilot program.” But the meeting report also noted:

“Among the concerns raised were the complexities of managing multiple applications in a global regulatory environment if each regulatory body approves a different set of ECs [editor’s note: Established Conditions. See ‘What is the Purpose of ICH Q12?’ below], challenges in knowledge management elated to justification of ECs and non-ECs, the need for efficient IT systems to track ECs for different applications in different countries, the need to establish standards within the company for justifying ECs and non-ECs and how to document them in applications, and how to utilize ECs in Accelerated Development situations.”

So Q12 may or may not be a problem, presumably depending on where you are, what markets you serve, and who is regulating you.

But what, exactly, is Q12? What does it mean for pharma companies, and how will it impact current manufacturing & compliance practices?

What is the Purpose of ICH Q12?
Q12 aims to improve management of post-approval chemistry, manufacturing and controls (CMC) changes, with the goal of making it a more efficient & predictable process across a product’s lifecycle.

According to the FDA, various sections of Q12 “focus on the categorization of post-approval CMC changes, established conditions, post-approval change management protocols, product lifecycle management, pharmaceutical quality system and change management, the relationship between the regulatory assessment and inspection and post-approval changes for marketed products.”

The FDA has discussed how Q12 could potentially improve product & process knowledge, ultimately leading to fewer regulatory submissions and lower costs. They also feel it may help decrease product variability and potential CMC- & quality-related shortages.

The International Council for Harmonisation also focuses on potential quality and supply chain benefits, stating ICH Q12 will “strengthen quality assurance and reliable supply of product, including proactive planning of supply chain adjustments.”

What Are Some of the Expected Benefits of ICH Q12?
One of the key potential benefits of ICH Q12 is reduced costs – for both regulators and industry. Others include standardization of ‘supportive information’ for regulatory submissions and “the greater application of innovative technologies in manufacturing and control (i.e. analytical methods) in a timely manner.”

For companies, one big benefit will be increased clarity and process transparency, making it easier to categorize CMC changes to determine whether supplemental regulatory filings are necessary.

What Steps Are Companies Taking? What About Regulators?
Companies are at nearly every stage in terms of Q12 preparations. Some have opted to wait and see what local regulators will do (e.g., Europe), while others have embraced the framework and are moving ahead with preparations prior to its implementation.

At a minimum, most companies are establishing teams to address the various impacts of Q12 (e.g., Established Conditions).

At Neuland Labs, we’ve begun providing training on ICH Q12 at all locations to ensure straightforward, seamless implementation of the new guidelines. The FDA is likewise making preparations, and has begun training staff on some of Q12’s key principles.


Interested in learning more? You can read the Q12 guideline here, or review the annexes.

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