Month: September 2016
Analytical Lifecycle: USP “Statistical Tools”, Analytical Target Profile and Analytical Control Strategy
Analytical Lifecycle: USP <1210> “Statistical Tools”, Analytical Target Profile and Analytical Control Strategy
The United States Pharmacopeia (USP) is currently undertaking further steps towards a comprehensive analytical lifecycle approach by publishing a draft of a new General Chapter <1210> Statistical Tools for Procedure Validation and two Stimuli Articles regarding Analytical Target Profile and Analytical Control Strategy in Pharmacopeial Forum. Read more about the life cycle concept for analytical procedures.
Following the recently announced elaboration of a new general chapter <1220> “The Analytical Procedure Lifecycle” the United States pharmacopeia (USP) is now proceeding in its approach for a comprehensive analytical lifecycle concept. A further step towards this approach is the draft of a new USP General Chapter <1210> Statistical Tools for Procedure Validation which has been published in Pharmacopeial Forum (PF) 42(5) in September 2016. Comment deadline is November 30, 2016.
Additionally, two Stimuli Articles regarding “Analytical Control Strategy” and “Analytical Target Profile: Structure and Application Throughout The Analytical Lifecycle” appeared in the same issue of the PF.
In the draft chapter <1210> Statistical Tools for Procedure Validation, the USP Statistics Expert Committee presents a revision to the proposal of <1210> published in PF 40(5) [Sept.–Oct. 2014]. On the basis of the comments and feedback given by stakeholders, the committee has addressed their concerns about the narrow scope and details on methodology to be used. The chapter is proposed as a companion to general chapter <1225> Validation of Compendial Procedures with the purpose of providing statistical methods that can be used in the validation of analytical procedures. A revision of general chapter <1225>, including a new section on Lifecycle Management of Analytical Procedures, has been published for comment in PF 42(2) in March 2016.
Specifically, the revision clarifies the accuracy and precision calculations while removing specific linearity requirements. Linearity may be inferred from accuracy or other statistical methods as deemed appropriate. The chapter discusses all of the following analytical performance characteristics from a statistical perspective:
- detection limit,
- quantitation limit,
- and linearity.
Additional related topics that are discussed in the draft include statistical power, two one-sided tests of statistical equivalence, tolerance intervals, and prediction intervals.
Furthermore, up to now, four Stimuli Articles regarding the analytical lifecycle have been published:
- “Lifecycle Management of Analytical Procedures: Method Development, Procedure Performance Qualification, and Procedure Performance Verification” in PF 39(5),
- “Fitness for Use: Decision Rules and Target Measurement Uncertainty” in PF 42(2),
and new in PF 42(5)
- “Analytical Control Strategy”, and
- “Analytical Target Profile: Structure and Application Throughout The Analytical Lifecycle”.
The Analytical Target Profile (ATP) is the focal point of the lifecycle approach. It is comparable to the Quality Target Product Profile (QTPP) which is defined in ICH Q8. The Stimuli Article emphasizes “that the current approach to development, validation, verification, and transfer of analytical procedures has served the industry well.” The lifecycle approach – comprised of the development (design, stage 1), qualification (stage 2), and monitoring of the performance of analytical procedures (control strategy, stage 3) – is an extension of the current guidance, taking advantage of the learnings from ICH Q8 – quality by design (QbD) concepts. The Article considers in particular the following questions (and provides examples):
- What is an ATP, and why is it useful?
- How can the ATP criteria be established?
- How can an ATP be applied during the three stages of the procedure lifecycle?
According to the article, “an additional advantage of using an ATP is that it can drive the development of a robust control strategy, resulting in better, more consistent performance of an analytical procedure throughout its lifecycle.”
In the Stimuli Article on the Analytical Control Strategy (ACS), the following questions are discussed:
- What is the ACS?
- What is the relationship between the ACS and the ATP?
- What is the quality risk management (QRM) process and how can it be applied to an analytical procedure?
- How does the ACS apply to the product lifecycle?
Additionally, examples of the following are provided:
- How to develop an ACS using the QRM process, and
- How to develop and apply a risk-based replicate strategy to minimize variability.
The USP Expert Panel would appreciate any feedback on the suggested approaches, as well as any alternative approaches for consideration.
Following your registration on the USP Pharmacopeial Forum website you can get to the proposal for general chapter <1210> and the complete stimuli articles. Because of the importance of the new USP chapter <1220>, ECA and USP join forces and organise the first joint event “Lifecycle Approach of Analytical Procedures“, in Prague, Czech Republic, from 8 to 9 November 2016.
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All participants of the GMP training course “Product Transfer” will receive a special version of the Guideline Manager CD including documents and templates useable for site change projects.
According to the European GMP-Rules, written procedures for tranfser activities and their documentation are required. For example, a Transfer SOP, a transfer plan and a report are now mandatory and will be checked during inspections.
As participant of the GMP education course “Product Transfer” in Berlin, from 25-27 October 2016 you will receive a special version of the Guideline Manager CD with a special section concerning product transfers. This section contains, amongst others, a Transfer SOP and a template for a Transfer Plan. Both documents are in Word format and can immediately be used after adoption to your own situation.
Regulatory Guidance Documents like the WHO guideline on transfer of technology in pharmaceutical manufacturing and the EU/US Variation Guidelines, are also part of the Guideline Manager CD. Due to copyright reasons, this CD is not available for purchase and can only be handed out to participants of the Product Transfer course.
New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach
The current work outlines the application of an up-to-date and regulatory-based pharmaceutical quality management method, applied as a new development concept in the process of formulating dry powder inhalation systems (DPIs). According to the Quality by Design (QbD) methodology and Risk Assessment (RA) thinking, a mannitol based co-spray dried formula was produced as a model dosage form with meloxicam as the model active agent.
The concept and the elements of the QbD approach (regarding its systemic, scientific, risk-based, holistic, and proactive nature with defined steps for pharmaceutical development), as well as the experimental drug formulation (including the technological parameters assessed and the methods and processes applied) are described in the current paper.
Findings of the QbD based theoretical prediction and the results of the experimental development are compared and presented. Characteristics of the developed end-product were in correlation with the predictions, and all data were confirmed by the relevant results of the in vitro investigations. These results support the importance of using the QbD approach in new drug formulation, and prove its good usability in the early development process of DPIs. This innovative formulation technology and product appear to have a great potential in pulmonary drug delivery.
“By identifying the critical process parameters, the practical development was more effective, with reduced development time and efforts.”
Edina Pallagi, our QbD evangelist from Hungary shares her team’s experience applying QbD to Dry Powder Inhalation Formulation.
The paper covers:
- QbD methodology the researchers applied
- Formulation of dry powder inhalation – API and excipients
- QTPP, CQA and CPPs identified for pulmonary use along with target, justification and explanation
- Characterization test methods
- Knowledge Space development
- QbD software used
New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach
- a Institute of Drug Regulatory Affairs, University of Szeged, Faculty of Pharmacy, Szeged, Hungary
- b Department of Pharmaceutical Technology, University of Szeged, Faculty of Pharmacy, Szeged, Hungary
Volume 511, Issue 1, 10 September 2016, Pages 151–160
Data Integrity has become one of the most frequently observed GMP deviations at FDA and EU Inspections. For that reason the ECA Foundation decided to set up a Task Force on Data Integrity in December 2015 – with the goal to provide Guidance for the implementation in practice. Read more about the ECA Guidance on Data Integrity.
Data Integrity has become one of the most frequently observed GMP deviations at FDA and EU Inspections. This is why the topic is currently in the centre of attention of both regulators and industry. And for that reason the ECA Foundation decided to set up a Task Force on Data Integrity in December 2015 – with the goal to provide Guidance for the implementation in practice.
– Dr. Wolfgang Schumacher, Hoffmann-La Roche, Switzerland
– Dr. Chris Burgess, Qualified Person and Consultant, UK
– Dr. Bob McDowall, Consultant, UK
– Ms. Margarita Sabater, ALK-Abelló A/S, Denmark
The Task Force decided to develop a Guidance entitled: “Data Governance and Data Integrity for GMP Regulated Facilities“. The ECA Guidance Document will cover – among others – the Roles and Responsibilities of Corporate and Senior Management in Data Governance as well as the necessary Policies, Procedures and Processes. Further information is provided on establishing criteria for Data Integrity and security of records based on ALCOA+Principles and on Auditing for Data Integrity and security of records.
The Guide will contain a Glossary as well as some illustrative appendices for further information.
Margarita Sabater, Member of the ECA Task Force, will present the Draft Version of the ECA Data Integrity Guidance Document during the Lab Data Integrity Conference on 20-21 October 2016 in Vienna, Austria. Every participant will receive a copy of the Draft Document – and is also invited to provide feedback to the Guidance Document.
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