EMA/ FDA Mutual Recognition Agreement on drug facility inspections moving forward

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EMA/ FDA Mutual Recognition Agreement moving forward
A possible agreement between the EMA and the US FDA on mutual recognition agreement on drug facility inspections could already be signed in January 2017.

http://www.gmp-compliance.org/enews_05650_EMA–FDA-Mutual-Recognition-Agreement-moving-forward_15642,15660,15656,Z-QAMPP_n.html

A possible agreement between the European Medicines Agency EMA and the US Food and Drug Administration FDA on mutual recognition of drug facility inspections could already be signed in January 2017. This is noted in a report of the EU Commission: “The state-of-play and the organisation of the evaluation of the US and the EU GMP inspectorates were discussed. In light of the progress achieved, the conclusion of a mutual recognition agreement of Good Manufacturing Practices (GMPs) inspections by January 2017 is under consideration.”

But, according to the Commission, some issues are still not resolved – like, for example, the exchange of confidential information and the inclusion of veterinary products in the scope of the text.

The “Report of the 15th Round of Negotations for the Transatlantic Trade and Invesment Partnership” summaries the 15th round of negotiations for the Transatlantic Trade and Investment Partnership (TTIP) from 3rd to 7th October 2016 in New York.

////////EMA, FDA,  Mutual Recognition Agreement, drug facility inspections

Opportunities for Reducing Sampling and Testing of Starting Materials

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Chapter 5 of the EC GMP Guide for the area of production was updated last year. This chapter contains concrete information about the conditions when testing and sampling of APIs and excipients can be reduced. Read more here about the sections 5.35 and 5.36 of the EU GMP Guide.

http://www.gmp-compliance.org/enews_05655_Opportunities-for-Reducing-Sampling-and-Testing-of-Starting-Materials_15461,15911,15462,Z-QCM_n.html

Chapter 5 of the EC GMP Guide for the area of production was already updated last year. However, not everybody really knows that it contains concrete information about the conditions when testing and sampling of APIs and excipients can be reduced. Particularly sections 5.35 and  5.36 include requirements and thus show possibilities for a reduction.

Basically, the manufacturers of finished products are responsible for every testing of starting materials as described in the marketing authorisation dossier. Yet, part of or complete test results from the approved starting material manufacturer can be used, but at least their identity has to be tested – as described in the in the marketing authorisation dossier.

If one chooses to outsource the testing activity to the supplier, this has to be justified and documented. Moreover, a few additional measures have to be fulfilled, like:

  • Particular attention should be paid to the distribution controls (transport, wholesaling, storage, delivery) to ensure that ultimately the test results are still applicable to the delivered material.
  • Performance of risk-based audits at the sites executing the testing and sampling of starting materials to verify the GMP compliance and to ensure that the specifications and testing methods are used as described in the marketing authorisation dossier.
  • The certificate of analysis of the manufacturer/supplier of the starting material should be signed by a designated person with appropriate qualifications and experience. The signature confirms the compliance with the agreed product specification.
  • The medicinal product manufacturer should have adequate experience in dealing with the starting material manufacturer – including assessment of batches previously received and the history of compliance before reducing own, internal testing.
  • At appropriate intervals, the medicinal product manufacturer or another approved contract laboratory has to carry out a full analysis to compare the test results with the results of the certificate of analysis of the material manufacturer or supplier, and thus to check their reliability. In case of discrepancy, an investigation has to be performed and appropriate measures taken. The certificates of analysis cannot be accepted until those measures are completed.

You can access the complete Chapter 5 “Production” of the EU GMP Guide here.
////////Opportunities,  Reducing,  Sampling, Testing, Starting Materials, EC GMP Guide

New EDQM’s Public Document informs about the Details required in a New CEP Application for already Referenced Substances

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A Policy Document recently published by the EDQM describes regulations for referencing already existing CEPs in an application for a new CEP. Read more about how the certificates of an intermediate or starting material have to be used in new applications for a CEP.

http://www.gmp-compliance.org/enews_05624_New-EDQM-s-Public-Document-informs-about-the-Details-required-in-a-New-CEP-Application-for-already-Referenced-Substances_15429,15332,15982,15721,S-WKS_n.html

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When applying for a Certificate of Suitability (CEP) for an API, detailed information has to be provided regarding the synthesis stages, the starting material and the intermediates. In the event that the starting materials or the intermediates are already covered by a CEP, the EDQM has recently published a “Public Document” entitled “Use of a CEP to describe a material used in an application for another CEP”. The document contains regulations on how to reference the “CEP X” of a starting material or an intermediate in the application for the “CEP Y” of an API. The requirements for both scenarios are described as follows:

  • CEP X belongs to an intermediate or a starting material within the synthesis route of a substance Y for which a CEP is submitted.
    1. The submission must make clear that X is really an intermediate or a starting material and is covered by a valid CEP (“CEP X”). A copy of this CEP X has to be attached.
    2. The complete specification described in the CEP X must be the basis for the release of the intermediate or the starting materials X for use in the synthesis of Y.
    3. The lifecycle of CEP X is directly coupled with the lifecycle of CEP Y. For example, a revision of CEP X also triggers a revision of CEP Y so that the revised CEP X has to be included to the revision application of CEP Y.
    4. If the CEP X looses its validity (e.g. due to expiry or withdrawal) the application for CEP Y has to be updated, for example the CEP of a substance from an alternative source has to be submitted.
    5. The application for CEP Y has to include complete details about the supply chain and/ or about all the manufacturing sites involved in the process described on CEP X.

Details about all manufacturing sites involved in the process described in the CEP X will also be mentioned in the annex 1 of the new CEP Y when X is an intermediate for the synthesis of Y. However, this doesn’t apply when X is the starting material for the synthesis of Y.

Please see the Public Document “Use of a CEP to describe a material used in an application for another CEP” for further details.

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////////// EDQM,  Public Document,  New CEP Application, already Referenced Substances

Now online – Stimuli article on the proposed USP General Chapter “The Analytical Procedure Lifecycle “

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Now online – Stimuli article on the proposed USP General Chapter “The Analytical Procedure Lifecycle <1220>”
A Stimuli Article to the Revision Process regarding the proposed New USP General Chapter “The Analytical Procedure Lifecycle <1220>” has been published. Read more about the new concept for the lifecycle managment of analytical methods.

http://www.gmp-compliance.org/enews_05629_Now-online—Stimuli-article-on-the-proposed-USP-General-Chapter-%22The-Analytical-Procedure-Lifecycle–1220-%22_15438,Z-PDM_n.html

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The General Chapters—Chemical Analysis Expert Committee is currently developing a new general chapter <1220> The Analytical Procedure Lifecycle. The purpose of this new chapter will be to more fully address the entire procedure lifecycle and define concepts that may be useful.

A Stimuli article on the proposed General Chapter <1220> has been approved for publication in Pharmacopeial Forum 43(1) [Jan.-Feb. 2017]. USP is providing this Stimuli article in advance of its publication to provide additional time for comments.

In addition to offering a preview of the proposed general chapter, the General Chapters—Chemical Analysis Expert Committee and the Validation and Verification Expert Panel are seeking specific input from users in the pharmaceutical industry regarding the following questions:

  • Would a general chapter on the lifecycle approach be valuable?
  • Is the information presented herein sufficient for implementation of an analytical procedure under the quality by design (QbD) approach?
  • Would incorporation of references to statistical tools, either in this chapter or in another chapter, be valuable?
  • Can you provide input or approaches that would improve this proposed general chapter?

The content and scope of the proposed general chapter will be refined on the basis of responses to this Stimuli article. Because stakeholders may have differing views, the objective of this Stimuli article is to identify and build areas of consensus that may be included in <1220>.

The approach is consistent with the concept of quality by design (QbD) as described in International Council for Harmonisation (ICH) Q8-R2, Q9, Q10, and Q11.

In order to provide a holistic approach to controlling an analytical procedure throughout its lifecycle, one can use a three-stage concept that is aligned with current process validation terminology:

  • Stage 1: Procedure Design and Development (Knowledge Gathering, Risk Assessment, Analytical Control Strategy, Knowledge Management, Preparing for Qualification)
  • Stage 2: Procedure Performance Qualification
  • Stage 3: Continued Procedure Performance Verification (Routine Monitoring, Changes to an Analytical Procedure)

A fundamental component of the lifecycle approach to analytical procedures is having a predefined objective that stipulates the performance requirements for the analytical procedure. These requirements are described in the analytical target profile (ATP) which can be considered as analogous to the quality target product profile (QTPP).

The Download Stimuli Article is available on the USP website since October 14, 2016: Proposed New USP General Chapter: The Analytical Procedure Lifecycle <1220>.

Comments will be accepted until March 31, 2017, the end of the comment period for Pharmacopeial Forum 43(1). This Stimuli article provides the framework for the proposed general chapter “The Analytical Procedure Lifecycle <1220>” and describes the current thinking of the USP Validation and Verification Expert Panel which advises the General Chapters—Chemical Analysis Expert Committee with regard to future trends in analytical procedures development, qualification, and continued monitoring.

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/////////////Stimuli article, proposed USP General Chapter, The Analytical Procedure Lifecycle,  <1220>