Month: November 2015
Pfizer’s PF 04991532 a Hepatoselective Glucokinase Activator Clinical Candidate for Treating Type 2 Diabetes Mellitus
MW 396.36, MF C18 H19 F3 N4 O3
3-Pyridinecarboxylic acid, 6-[[(2S)-3-cyclopentyl-1-oxo-2-[4-(trifluoromethyl)-1H-imidazol-1-yl]propyl]amino]-
Type 2 diabetes mellitus (T2DM) is a rapidly expanding public epidemic affecting over 300 million people worldwide. This disease is characterized by elevated fasting plasma glucose (FPG), insulin resistance, abnormally elevated hepatic glucose production (HGP), and reduced glucose-stimulated insulin secretion (GSIS). Moreover, long-term lack of glycemic control increases risk of complications from neuropathic, microvascular, and macrovascular diseases.
The standard of care for T2DM is metformin followed by sulfonylureas, dipeptidyl peptidase-4 (DPP-IV) inhibitors, and thiazolidinediones (TZD) as second line oral therapies. As disease progression continues, patients typically require injectable agents such as glucagon-like peptide-1 (GLP-1) analogues and, ultimately, insulin to help maintain glycemic control. Despite these current therapies, many patients still remain unable…
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After the long-awaited Chapter <1790> on visual inspection of injections was first published in the PF 41(1) as a draft the USP has now submitted a revised draft in the PF41 (6). Read more about the revised draft of the USP Chapter <1790>.
After the long-awaited Chapter <1790> Visual Inspection of Injections was first published in the Pharmacopeial Forum 41(1) as a draft the USP has now submitted a revised draft in the PF41 (6). Through its number >1000, the monograph <1790> is not binding but rather offers an explanation to Chapter <790> Visible Particulates in Injections.
With regard to the content, several comments recommended by the industry have been included. The new Chapter 9 represents the biggest change and describes the evaluation of marketed products where anomalies had been observed regarding particles. The test procedure for it is described in Chapter <790>. Yet, this topic was missing in the original draft of Chapter <1790>. Thus, in total there is one more chapter. In addition, the underlying test statistics contained in the chapter on inspection of lyophilised product have been detailed. The requirements on the premises for manual inspection have also been added in more detail. Moreover, a clear statement can be found on the validation of a fully automatic system which should be based on the comparison with the compendial manual inspection.
The draft document is available for free on the website of the USP Pharmacopeial Forum. You only need to register for free. The deadline for comments is 31 Januar 2016. The new chapter could be published in the USP 40 in November 2016 and becomes effective as of May 2017. A document comparing the original and the second draft can be found on the website ofECA’s Visual Inspection Group, under useful links.
Changes to the fundamental monograph on pharmaceutical water <1231> Water for Pharmaceutical Purposes from the US-American Pharmacopeia have been published for comments in the Pharmacopeial Forum 41(5). The revision presented in the current draft mainly has a structural nature. The content of the monograph has been reorganised in 9 new chapters which aim at improving readibility and searchability of the content searched:
2. SOURCE WATER CONSIDERATIONS
3. WATERS USED FOR PHARMACEUTICAL MANUFACTURING AND TESTING PURPOSES
4. VALIDATION AND QUALIFICATION OF WATER PURIFICATION, STORAGE, AND DISTRIBUTION SYSTEMS
5. DESIGN AND OPERATION OF PURIFIED WATER AND WATER FOR INJECTION SYSTEMS
7. CHEMICAL EVALUATIONS
8. MICROBIAL EVALUATIONS
9. ALERT AND ACTION LEVELS AND SPECIFICATIONS
The draft document is available for free on the website of the USP Pharmacopeial Forum. You only need to register for free. The deadline for comments is 20 November 2015.
After the FDA moved towards a life cycle approach with its Process Validation Guidance in 2011, the EU GMP Guide now followed with the revision of Annex 15, also moving to modern process aspects (e.g. life cycle approach). But how can the industry implement the new process validation requirements? The ECA’s Good Practice Guide on Validation does provide answers.
Since the publication of FDA´s Process Validation Guidance in 2011, validation has become a life cycle approach with focus on process knowledge and process understanding based on scientific sound principles. In addition, with the revision of Annex 15 of the EU GMP Guide, the EU has also been moving to modern process aspects (e.g. life cycle approach).
The question is how to implement these new requirements – in the USA and in Europe?
To answer this question, an ECA Working Group has revised the Version 1 of ECA´s Good Practice Guide on Validation. With the revision the group wants to provide support to both regulators and industry. On one hand, the guide contains the main elements of the new approach (“what to do”). On the other hand, it also serves as a supporting guide for the implementation (“how to do”).
The revised version comprises 174 pages divided in 5 chapters and 5 annexes (with detailed analyses of the regulatory guidances).
The topics covered are e.g.:
- risk based qualification and validation
- legacy products
- case study about process validation
- case study about continued/ongoing process verification in biopharmaceutical manufacturing
The ECA Good Practice Guide on Validation will be officially launched at ECA´s Annex 15 Conference on 25/26 November 2015 in Berlin. All participants will receive a free copy of the document.
ECA´s Annex 15 Conference on 25/26 November 2015 in Berlin. All participants will receive a free copy of the document.
Course No 9379
25-26 November 2015, Berlin, Germany
Since 2001 the Annex 15 has been state of the art for Validation Master Plan, Qualification, Validation, Cleaning Validation and Change Control within the EU. In the meantime ICH
Q 8-11 has been published. The FDA has implemented most of these ICH guidelines and introduced a Validation Process Life Cycle in its Process Validation Guidance from 2011. The EMA has published a revision of its Note for Guidance on Process Validation to implement this new aspects too. This is also the reason why the Annex 15 has to be revised. The first thoughts have been provided in a concept paper. In February 2014 was a draft published and now the final version of the revision is available.
ECA Annex 15 Survey
Industry view on Annex 15
Overview of the new Annex 15 revision view of an EU GMP Inspector
History of validation guidelines in the EU
The Annex 15 revision
The EMA Process Validation revision
What´s really new?
Organisation and Planning for Qualification and Validation
Integration of outsourced data in a validation
What is an “appropriate validation oversight” ?
New requirements in the Validation Master Plan
Requirements regarding the qualification of suppliers
Requirements regarding Risk Management
Good Documentation Practice – what does that mean for validation?
How to support knowledge management
Content of validation protocols and reports
Conditional approvals – a challenge
Qualification – Annex 15 revision vs FDA Process Validation Guidance
The new first step(s) URS/FDS
How to use FAT and SAT?
Combinations of qualification stages IOQ/OPQ
Interface PQ/Process Validation
Is the requirement to qualify utilities really new?
How to handle the qualification of established equipment (in-use) in the future?
What´s about alternatives (ASTM E 2500)?
Are there differences to the FDA Process Validation Guidance?
Process Validation in the new Annex 15 revision – in the light of modern
life cycle thinking
The Process Validation Life Cycle
Modern vs. traditional approach
What is a hybrid approach?
How is bracketing possible?
Are the three magic runs still applicable?
Clarification of the terms continuous process verification, continued process verification, ongoing process verification
Is the Annex 15 revision in line with the FDA Process Validation Guidance?
Cleaning validation in the new Annex 15 – how to implement the PDE concept?
Grouping of equipment – a new possibility?
How to validate manual cleaning operations`
The new acceptance criteria: PDE – how to implement?
Choice of worst case products taking account of toxicity PDE values and solubility
How to determine the cleaning validation batches?
Cleaning verification – what´s that?
Transport verification – solutions for future challenges
Requirements of Annex 15
Qualification, Verification, Validation
Lean Verification Approach
Actual status, future challenges
Packaging Validation – from fill to finish
Requirements of Annex 15
Qualification of packaging lines
The validation of primary vs secondary packaging processes
October 31, 2015 — 2:22 AM IST,
The Pfizer Ltd. research and development plant in Dalian, China.
Bernardo De Niz/Bloomberg
A Pfizer Inc. plant in China that was being inspected by Food and Drug Administration regulators in order to ship drugs to the U.S. kept a second set of quality and manufacturing records that didn’t match official ones, according to an FDA review of the facility.