Industry wants clarity on scope of ICH stability testing guideline, timing of studies
Pharmaceutical companies in the US are requesting additional information on how to conduct stability testing for both new and existing drugs in response to the International Council for Harmonisation’s (ICH) recent Q1 guideline. They have raised questions regarding the scope of the guideline and the appropriate timing for stability testing of drugs in development.These comments were in response to the US Food and Drug Administration’s (FDA) call for responses on the Q1 guideline. The draft ICH Q1 stability guideline for consultation in April 2025. (RELATED: ICH releases overhauled stability guideline for consultation, Regulatory Focus 17 April 2025)
The new guideline is a major reworking of ICH’s earlier guidelines. It consolidates the existing five stability guidelines into one document and addresses new topics such as stability considerations for advanced therapies, bracketing and matrixing, stability modeling, and stability considerations for reference materials and novel excipients.
Twelve stakeholders responded to the draft guidelines. The deadline for submitting responses was 25 August.
Guideline applauded by some groups
Two groups, the International Society for Pharmaceutical Engineering (ISPE) and Biocom California, expressed support for the guideline.
“ISPE considers that the ICH Q1 revision draft document, Stability Testing of Drug Substances and Drug Product is very well written and comprehensive document, fulfilling the consolidation of the various ICH Q1 guidelines into one guideline. It is repetitive at times, but that is expected as many readers will 'jump' to the section that they believe is applicable to their application.”
Biocom expressed similar thoughts on the guideline. The group said it “appreciates that this draft guidance has consolidated multiple stability guidances into one document and includes additional stability-related information for product categories which were not previously covered in past guidances (i.e., advanced therapy medicinal products, vaccines, and complex biological products including combination products).”
AAM wants clarification on shelf-life data
The Association for Accessible Medicines (AAM) requested clearer guidance on the shelf-life data for biological drug substances and products to provide to regulators.
The guideline specifies that for biological drug substances and drug products, data from three primary batches covering the entire duration of the proposed shelf life must be submitted, unless a valid alternative approach is justified. If these primary batches are not at production scale, a minimum of six months of data from production batches should also be included to support the evaluation of the regulatory submission.
AAM stated that “clarification is needed to determine when primary batches must cover the entire shelf life and when primary batches covering at least six months will be sufficient. The guidance should better define the circumstances in which the health authorities will require data covering the full duration of the shelf life and when they will accept at least 6 months of data.”
The group said that “even saying ‘a minimum of 6 months stability data’ is vague because it does not explain when 6 months will be adequate or when more than 6 months will be needed, and how much more than 6 months’ worth of data should be provided in those circumstances.”
Expanding the scope
The American Association of Pharmaceutical Scientists (AAPS) proposed expanding the guideline's scope to include botanicals and live bacterial products.
AAPS said that “overall the scope statements are very good, however, some specific product types are not included/identifiable in the scope statements including: Botanicals, live bacterial products such as oral products to treat C Difficile infections and Fecal Matter Transplantation Products, and bacteriophage products such as products to treat gut infections, UTIs.”
The Parenteral Drug Association (PDA) suggested that the guideline include radiopharmaceuticals. “While the shelf-life of radiopharmaceuticals is typically in the range of hours to days rather than months or years, the same principles apply. Moreover, the stability of the precursor (the molecule to be combined with the radionuclide) should be in the scope of this guidance.”
PDA also recommended that the guideline should provide more detail on stability testing for advanced therapy medicinal products (ATMPs).
The group stated that “the current text provides general principles for stability programs but does not sufficiently address the unique stability challenges associated with DNA/RNA-based ATMPs. These products are particularly susceptible to degradation via hydrolysis, oxidation, and enzymatic activity, which differ significantly from the degradation pathways of small molecule impurities.”
ISPE suggests deleting references to GMPs
ISPE suggested that references to Good Manufacturing Practice (GMP) topics should be removed from this guideline. The group wrote that “ICH Q1 should be focused on scientific and technical guidance on stability testing. Inclusion of GMP-related content may lead to confusion regarding the scope and regulatory expectations, and such topics are more appropriately addressed in GMP-specific guidelines.”
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