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Posted 14 July 2021 | By Joanne S. Eglovitch 

Upcoming ICH guidelines should ease post-approval changes for analytical methods

2855 Two forthcoming guidelines from the International Council on Harmonization (ICH) should make it easier to switch analytical methods for testing medicines post-approval and better manage lifecycle changes, said regulators and industry officials speaking Wednesday at the CMC Strategy Forum sponsored by the California Separation Science Society (CASSS).
At the meeting, an official from the European Medicines Agency (EMA) and industry representatives provided a glimpse of ICH Q14 and ICH Q2(R2), pointing out how these forthcoming guidelines will help industry better manage lifestyle changes by addressing  shortcomings of current approaches for analytical method development.
Companies are often reluctant to change analytical methods and continue to use outdated and inefficient methods because of the cost involved in applying for and implementing these changes worldwide, noted presenters.
The forthcoming ICH Q14 guidelines will harmonize scientific approaches to analytical procedure development to facilitate more efficient, sound scientific and risk-based approval, while Q2(R2) will update current analytical methods to include some of the newer analytical procedures.
Cristiana Campa, technical R&D advisor for GlaxoSmithKline Vaccines in Siena, Italy, told the meeting that the guidelines would be a welcome addition. She said that at GSK, 40% of the post-approval changes sought by the company are in the analytical space.
Changes Embraced

Speakers at the meeting embraced these upcoming changes. “Analytical procedures are very important. They are the eyes, the ears and the smell of our process and our product,” said Oliver Grosche, director of business operations and strategy in quality at Switzerland’s Seagen International GmBH. “Yet there is a lack of common understanding of analytical change risk.”
Grosche said that manufacturers are often reluctant to change methods because of the high cost involved in securing regulatory approval for changes in markets where products are approved.
He gave an example of a company that wanted to institute a method change for a chiral column used to separate optical isomers to increase its performance, as the pressure in the column was too high. Yet the cost of securing the regulatory approval to change the method worldwide was prohibitive: $250,000. So instead of changing the method, the company had to replace columns frequently, which Grosche called an ineffective solution.
It should be easier to make minor adjustments to increase analytical procedure performance within the company’s pharmaceutical quality system, added Grosche.
Outdated Q2 guideline

Robert Bream, EMA’s scientific administrator for quality of medicines, said that plans to replace ICH Q2(R1) with the Q2(R2) guideline and to add a new ICH Q14 guidance create a harmonized performance-based approach for allowing analytical method changes.
In 1995, when the ICH Q2(R1) guideline was developed, chromatographic techniques predominated, said Bream. Since then, newer “hyphenated” techniques such as gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry have largely supplanted chromatography alone. These newer methods require multivariate statistical analysis techniques that are not addressed by the current Q2(R1) guideline, he added.
The ICH Q14 guidance is meant to fill a void in analytical procedure development; currently, validation results are presented without development data.  This means there is a currently a “reduced opportunity to present scientific basis for flexible regulatory approaches to postapproval changes for analytical procedures,” said Bream.
The guideline will also incorporate an analytical target profile (ATP) to evaluate post-approval changes. This model looks at a method’s performance and allows manufacturers to adopt alternative analytical methods if they achieve the same performance as the original method. (RELATED: MHRA Consults on Analytical Quality by Design Principles. Regulatory Focus 4 June 2019).  
Bream said that an Annex A of the forthcoming ICH Q14 guideline will include examples of the ATP, while Annex D will give examples of change management of analytical procedures. He noted that these guidelines complement the ICH Q12 on postmarket changes and the ICH Q13 guideline on continuous manufacturing.
Using the ATP to switch from rabbit studies

Campa of GlaxoSmithKline described how the company used the ATP to secure regulatory approval while switching from a rabbit pyrogen test to a non-animal-based monocyte activation test (MAT) to test pyrogenicity of vaccines. The ATP model allowed the firm to secure approval for the change in method by demonstrating that the MAT method had the same performance as the rabbit test. The switch allowed GlaxoSmithKline to save 194 rabbits over the course of a year, said Campa.
Bream said that ICH plans to have a step 2 guideline for ICH Q14 and Q2 out for public consultation in December. They were originally slated to be out in May 2020, but the pandemic interrupted this timetable.
CASSS Summer Strategy Forum


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Tags: ATPP, ICH, Q14, Q2(R2)

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