[Stability Testing related News – vol.56]

◆  Analytical Procedure Life Cycle – New USP Chapter <1220> published (13-Oct-21 ECA)

While in Europe the drafting or revision of ICH Guidance Q14 and Q2(R1) is at a standstill, the USP published an advance notice of its new chapter <1220> Analytical Life Cycle on 24 September. The chapter will be included in USP-NF 2022, Issue 1 on 1 November 2021, just over a year after the draft was published in September 2020, and will officially come into force on 1 May 2022.

Aim of the chapter
The new chapter focuses on a holistic approach to the life cycle of an analytical procedure and the associated validation activities. It also takes into account consistency with the Quality by Design concepts as described in the ICH guidelines. As in many new regulatory guidance documents and pharmacopoeial chapters, scientific approach and sound risk management are emphasised in the development and definition as well as in the control and application of analytical methods and procedures. The “total error” principle can be applied or the measurement uncertainty can be used. The principle is applicable to all analytical procedures, whereby complexity and criticality should be the measure of effort. Relevant elements of this life cycle concept are already known from the Guidance for Industry Analytical Procedures and Methods Validation for Drugs and Biologics of the FDA.

The 3-stage concept, which was already known from the draft, will be retained in the final version

Stage 1: Procedure planning covers procedure development, which consists of analytical technique and sample preparation. It includes knowledge gained through knowledge gathering, systematic process development experiments, and risk assessments and associated laboratory experiments.

Stage 2: Qualification of process performance consists of investigations to demonstrate that the process is fit for purpose. This includes confirmation that the reportable values generated by the use of the analytical procedure meet the ATP criteria and confirmation of the performance characteristics of the procedure through the traditional validation, verification or transfer studies. The data generated in stage 1 may be used if available and appropriate. At the end of stage 2, the replication strategy and the performance of the procedure are confirmed to meet the ATP and other criteria.

Stage 3: Ongoing review of the performance of the procedure involves monitoring the analytical procedure during routine use and confirming that performance continues to meet the ATP criteria. Monitoring ensures that the performance of the procedure is maintained at an acceptable level throughout the life of the procedure. It can also provide an early indication of potential performance problems or unfavourable trends and help identify necessary changes to the analytical procedure. Confirmation of process performance after modifications ensures that the modified process provides reportable values equivalent to those defined in the ATP. Further details on the life cycle of the procedure are described in the following sections.
◆  In 2021 again Numerous FDA 483s due to Deficiencies in the Stability Program (17-Nov-21 ECA)

Observations made by the inspector during an FDA inspection are listed on the FDA Form 483. Spreadsheets summarizing the areas of regulation cited on FDA’s system-generated 483s are available by fiscal year on the FDA’s homepage in the subsection on “Inspection Observations”. These spreadsheets represent the area of regulation and the number of times it was cited as an observation on a Form FDA 483.The FDA has now published the data for the fiscal year 2021 (October 2020 to September 2021). 215 FDA 483s were issued in the area of “Drugs”.

Typical deficiencies related to stability testing in the fiscal year 2021 are “Lack of written stability program”,  “Written program not followed”  and “Valid stability test methods”.

Looking at the ratio of 483s in stability relative to the total number of 483s in the area of Drugs, the percentage in fiscal year 2021 (20%) is at the same level as in 2019 (19%).

◆  Q13 CONTINUOUS MANUFACTURING OF DRUG SUBSTANCES AND DRUG PRODUCTS (October-21 FDA)

Docket Number: FDA-2021-D-1047
Issued by: Center for Drug Evaluation and Research

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has the mission of achieving greater regulatory harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed, registered, and maintained in the most resource-efficient manner. By harmonizing the regulatory expectations in regions around the world, ICH guidelines have substantially reduced duplicative clinical studies, prevented unnecessary animal studies, standardized safety reporting and marketing application submissions, and contributed to many other improvements in the quality of global drug development and manufacturing and the products available to patients.

ICH is a consensus-driven process that involves technical experts from regulatory authorities and industry parties in detailed technical and science-based harmonization work that results in the development of ICH guidelines. The commitment to consistent adoption of these consensus-based guidelines by regulators around the globe is critical to realizing the benefits of safe, effective, and high-quality medicines for patients as well as for industry. As a Founding Regulatory Member of ICH, the Food and Drug Administration (FDA) plays a major role in the development of each of the ICH guidelines, which FDA then adopts and issues as guidance to industry.