ICH seeks harmony on quality

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) recently closed consultation on its draft guidance, ICH Q10 Pharmaceutical Quality System. If all goes to plan, adoption could come as soon as Spring 2008.

The ICH began its work on formulating Q10 when it set the ICH Quality Vision in 2003. The ambition was to create a regulatory framework based on a harmonized pharmaceutical quality system that would be applicable across the life cycle of the product, with an emphasis on an integrated approach to quality risk management and science.

A key point about ICH Q10 is the desire to apply the ICH vision to the entire product life cycle (i.e., pharmaceutical development, technology transfer, manufacturing, product discontinuation). It is proposed that firms that employ quality by design (ICH Q8 Pharmaceutical Development)¹ and risk-management principles (ICH Q9 Quality Risk Management)² will have a robust quality system to manage change and continual improvement. This should reduce the requirement for post-approval filings and give manufacturers more control over their own destiny, reducing the obstructions that regional variation to regulation can sometimes place over innovation, process improvement and new product launches.

As the draft guidance itself states: "Implementation of ICH Q10 throughout the product life cycle should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities."

ICH Q10 — an overview

By creating ICH Q10, the ICH openly admits that, in one sense, it has created nothing new. Rather, ICH Q10 describes an approach to an effective pharmaceutical quality system that is based on ISO concepts, includes applicable GMP regulations, and complements ICH Q8 "Pharmaceutical Development" and ICH Q9 "Quality Risk Management".

ICH Q10 is a model for a pharmaceutical quality system, and much of the content applicable to manufacturing sites is already specified by regional GMP requirements. The draft guidance specifically states that "ICH Q10 is not intended to create any new expectations beyond current regulatory requirements", and anything within ICH Q10 that is additional to current GMP requirements is "optional" rather than obligatory. Though not specifically referenced in ICH Q10, it should come as no surprise that there are elements of other quality systems mirrored within it.

From our perspective as a contract laboratory, our quality systems are based on the International Standard ISO/IEC 17025 for the General Requirements for the Competence of Testing and Calibration Laboratories. The management system requirements in ISO/IEC 17025 are written in language relevant to laboratory operations and meet the principles of ISO 9001:2000 Quality Management Systems Requirements. They are also aligned with its pertinent requirements.

Table 1 demonstrates the common themes between ISO 9001, ICH Q10, ISO/IEC 17025 and what could, no doubt, appear in other quality management system (QMS) standards.

Table 1 Correlation between QMSs

The adoption of ISO/IEC 17025 is a relatively unique position for a pharmaceutical testing laboratory. However, RSSL comes from a background as a food testing laboratory (accredited to ISO/IEC 17025) and therefore used the fundamentals of that system as the foundation of its GMP system. Most pharmaceutical labs will only have GMP, but as stated above, there are similarities between all QMSs.

ICH Q10 — a business case

One of the main rationales behind Q10 is the idea that a modern quality system, coupled with the manufacturing process, product knowledge and the application of effective risk-management practices, can help manufacturers change facilities, equipment and processes without the need for prior approval or regulatory submissions. There is also an assumption that using an effective quality system to lower the risk of manufacturing problems should result in shorter and fewer regulatory inspections.

From a purely financial perspective, some have argued that savings will come from improved process performance, a reduction in cost of internal failures, a reduction in the costs that might otherwise be incurred from delayed implementation of improvements, and a reduction in the cost of preparing and reviewing post-approval submissions.⁵

There may be expenditures involved with implementation, but there can be few manufacturers that do not already have many, if not all, of the elements on ICH Q10 in place via existing QMSs.

Potential pitfalls?

A potential complication for ICH Q10 is the use of subcontractors for any part of the manufacturing process that can be outsourced. If an activity is outsourced, it will be necessary to ensure that the subcontractor follows the required elements of Q10 to a sufficient standard.

There are two main approaches to this conundrum. The first is to have a formal contract with the subcontractor, which would be agreed between the two parties and detail the responsibilities the subcontractor must meet. This is already a requirement of European GMP, and is also the approach detailed in ICH Q10. An alternative approach would be an audit of the subcontract, where the subcontractor's approach to the requirements of Q10 are reviewed in person. Again, the right to audit a subcontractor is already permitted by GMP regulations.

That said, adopting a unified approach to QMSs across the regions could prove to be very beneficial. We can envisage best practice discussions with common outcomes, regardless of the continent in which the company is based. Rationalized outcomes to the requirements of Q10 could cause regulatory agencies to have similar expectations, which would stop the possibility of various approaches to the same quality requirement.

Key points

What's next for ICH Q10?

The deadline for public comment on ICH Q10 has now passed and the comments will be delivered to the ICH meeting in Spring 2008 in Brussels. Step 2 of the ICH process is for the ICH Steering Committee to agree that there is sufficient scientific consensus on the technical issues for the draft guideline, or recommendation, to proceed to step 3 — the next stage of regulatory consultation. Step 4 will be the adoption of the ICH guideline, which is reached when the ICH Steering Committee agrees, on the basis of the report from the regulatory Rapporteur of the Expert Working Group, that there is sufficient scientific consensus on the technical issues. This will shortly be followed by implementation or Step 5.

References

1. International Conference on Harmonisation, ICH Q8: Pharmaceutical Development, November 2005. www.ich.org

2. International Conference on Harmonisation, ICH Q9: Quality Risk Management, November 2005. www.ich.org

3. International Conference on Harmonisation, Draft Consensus Guideline, ICH Q10: Pharmaceutical Quality System, May 2007. www.ich.org

4. Joint ISO-ILAC-IAF Communiqué on the Management Systems Requirements of ISO/IEC 17025:2005, General requirements for the competence of testing and calibration laboratories, (2005).www.ukas.org

5. International Conference on Harmonisation, Quality Systems, Gerry Migliaccio Pfizer Inc, AAPS Workshop — Pharmaceutical Quality Assessment, October 2005. www.aapspharmaceutica.com

6. FDA, Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations, September 2006. www.fda.gov