Search This Blog

Saturday, April 14, 2012

Significant Changes in HPLC System Suitability: New USP Provisions Planned

A revision of General Chapter <621> on Chromatography is proposed in the Pharmacopeial Forum (volume 38, edition 2). This new chapter has a major impact on system suitability tests (SST).

In the current USP 35, adjustments in the mobile phase in gradient conditions are not recommended. Now, adjustments should be possible but as they may cause changes in selectivity, they should be made with caution.

The revised USP chapter now defines for each variable of the SST whether this variable applies for isocratic separations only or for gradient separations, too. In the future, the following parameters of the SST will be possible for gradient separations:

pH of the mobile phase (± 0.2)
Concentration of salts in buffer (± 10 %)
Injection volumes
Column temperature (± 10%)

Different length, internal diameter, and/or particle size in the stationary phase in gradient separations are not allowed.

Also the formula for calculating the flow rate will be modified. A new table will also be created to show the interaction between the variables length, internal diameter, particle size, and flow rates for a few significant column configurations. The objective of this is to maintain the performance of the separation system when modifying the SST parameter.

On the contrary, changes in the chemical characteristics of the stationary phase will be considered a modification to the method and will require full validation.

Comments to the draft of the new USP chapter on Chromatography can be sent until 31 May 2012.

Friday, January 28, 2011

FDA Publishes Revised Process - Validation Guidance

Guidance on Process validation is published by the USFDA which was awaited for quite a long time i.e from May 1987 and the draft from November 2008.The newly published guidance revises and replaces the 1987 guidance with the title "Guideline on General Principles of Process Validation"

It covers the process validation for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients (APIs or drug substances).
This guidance aligns process validation activities with a product lifecycle concept and with existing FDA guidance, including the FDA/International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.

This guidance describes process validation activities in three stages.
Stage 1 – Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.
The goal of this stage is to design a process suitable for routine commercial manufacturing that can consistently deliver a product that meets its quality attributes.

Stage 2 – Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.
This stage has two elements: (1) design of the facility and qualification of the equipment and utilities and (2) process performance qualification (PPQ). During Stage 2, CGMP-compliant procedures must be followed. Successful completion of Stage 2 is necessary before commercial distribution.15 Products manufactured during this stage, if acceptable, can be released for distribution.

Stage 3 – Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.
The goal of the third validation stage is continual assurance that the process remains in a state of control (the validated state) during commercial manufacture. A system or systems for detecting unplanned departures from the process as designed is essential to accomplish this goal. Adherence to the CGMP requirements, specifically, the collection and evaluation of information and data about the performance of the process, will allow detection of undesired process variability.

During this stage, a company should establish an ongoing program to collect and analyze product and process data that relate to product quality. Trained personnel should statistically trend and review the data, and the information collected should verify that the quality attributes are appropriately controlled throughout the process, according to the guidance.

You can find the Guidance at :

Tuesday, November 2, 2010

DCGI becoming more and more vigilent and making the laws stringent in Pharma

it is well known by every personnel in pharma sector the recent updates of implementation of Certification of all the pharma bodies acording to Schedule-M and certifications w.r.t WHO are not beiong provided for every industry but basing in the requirement only these are being audited which was a daily process earlier to the recent implementation from 01 Nov. 2010 as mandatory for Schedule L (For GLP)leaving behind the industry plea to extend the timeline as it is 2 years from its release and again it is now concentrating on the formulation of Good distribution practices which might also become a mandatory guideline in future.

Monday, November 1, 2010

Draft Guidance for Qualifying Drug-Development Tools by USFDA

The US FDA issued draft guidance on the Qualification Process for Drug Development Tools.As per the document drug-development tools (DDTs) include biomarkers and patient-reported outcome instruments, among other things. The draft guidance also offers a mechanism for formal review by CDER to qualify the DDT.
“Qualification” means “a conclusion that within the stated context of use, the results of assessment with a DDT can be relied upon to have a specific interpretation and application in drug development and regulatory decision-making.”
In the draft guidance, FDA proposes stages for the qualification process, including consultation and advice with CDER (e.g., letter of intent, briefing, meeting, investigation), and review for the qualification decision. The agency intends to make public its information regarding qualified DDTs.

Tuesday, October 19, 2010

Chinese State Food and Drug Administration Proposed Route of Registration for APIs, Excipients and Auxiliary Materials

State Food and Drug Administration (SFDA) of China recently published a draft document describing their proposed route of registration of API, excipients and auxiliary material manufacture and quality assurance. The registration route is based on their analysis of the Drug Master File (DMF) content and process used in the US and EU. Of particular interest:

· The drug product manufacturer is the entity responsible for the quality of component materials used in the drug

· Scope covers drugs registered for sale in China, apparently not APIs or excipients which are made for export only

· Clinical investigational materials are not addressed in this document

· Audit reports from the drug product manufacturer audit of their suppliers mentioned in this document must be submitted in the filing

Sunday, October 10, 2010

Regulators are sharing more and more information through the agreements between them

As per the two recently signed confidentiality agreements we can know how the regulators are thinking on the future aspects. In both agreements, the partners have provided assurance that they can effectively protect this non-public information.

On September 15, 2010 EMA and FDA formally extended their existing confidentiality agreements for an indefinite period. This agreement allows sharing of inspection reports and other non-public information between the agencies.

On September 24, 2010, FDA and ANVISA signed a confidentiality agreement that permits sharing of non-public information. This is the first confidentiality agreement between the two regulatory agencies, and acknowledges Brazil’s rising importance as a pharmaceutical market and supplier and ANVISAs rise as a regulatory agency.

To read the agreements between agencies write to me i will be sending you the same agreements