NSF-DBA News & Tech Talk

EXCiPACT™ AUDITOR TRAINING COURSES

Wed, 16 May 2012 13:42:32 +0000

Dear Pharmaceutical Excipient Suppliers’ Auditors and Auditees,

You are cordially invited to attend one of the next 2-day EXCiPACT™ AUDITOR TRAINING COURSES in BRUSSELS on either 16/17 July, 2012 or 18/19 July, 2012.

Course Objective: Working knowledge of the EXCiPACT™ GMP and GDP standards

Who should attend: Pharmaceutical excipient suppliers’ auditors and auditees
Course Programme: Please see attached
Location: Fecc Offices, Rue du Luxembourg, 16B, Brussels, Belgium (www.fecc.org)

Booking conditions:
1. 20 places available on each course to be filled on a first-to-pay basis
2. Registrants should complete the attached form for either 16/17 July or for 18/19 July, 2012
3. Full payment of €1500.00 is necessary to secure a place; to be paid by bank transfer only to ING Bank, Brussels IBAN: 54 3630 8931 3697; SWIFT/BIC: BBRUBEBB
4. Successful registrants will be confirmed by e-mail when the bank transfer has been received
5. Should you cancel your registration, no refund will be given but you may transfer your place to
a colleague from the same company
6. The course cost does not cover personal costs, e.g., travel, accommodation, see “Cost” above.
7. By registering for the event, it is assumed that you accept these booking conditions.

All correspondence should be addressed to:
EXCiPACT Secretariat, info@excipact.org
T: 32 (0) 2 736 53 54

NSF-DBA cherche un ou plusieurs Consultants associés

Sat, 05 May 2012 05:57:48 +0000

NSF-DBA cherche un ou plusieurs Consultants associés indépendants pour proposer nos services en conseil pharmaceutique, en audit et en formation pour nos clients francophones.

Les candidats choisis, seront indépendants, avec de l’expérience professionnelle pharmaceutique, peut-être même avec leur propre société de conseil, mais qui seraient heureux de travailler chez NSF-DBA afin d’aider à développer l’entreprise en France, Belgique et en Suisse.

Les candidats doivent avoir un minimum de dix années d’expérience de travail dans l’industrie pharmaceutique ou dans l’organisme de réglementation et devrait avoir une excellente connaissance de la législation pharmaceutique, gestion de qualité et de bonnes expériences de fabrication. Il faut avoir un fort intérêt dans la formation et un désir de transmettre vos connaissances et votre expérience aux autres. Une bonne maîtrise de l’anglais est également importante. En retour, nous pouvons vous offrir un tarif professionnel et compétitif et la possibilité de participer au succès de l’un des consultants pharmaceutiques les plus respectés et les plus dynamiques dans le monde.

Si vous êtes intéressé à travailler chez NSF-DBA, veuillez envoyer s’il vous plaît votre lettre de candidature et CV en anglais au nom de NSF-DBA Managing Partner Dr. Bob Pietrowski à rap@nsf-dba.com

ICH Q11 Receives Step Four Approval

Fri, 27 Apr 2012 11:53:12 +0000

Please be aware that Q11 received step 4 approvals from the ICH steering committee on 24 April. The final step 5 is implementation by the national/regional authorities and this is expected to occur within the next 6 months.

The step 4 version has not yet been published on the ICH website.

Best regards,

Peter Gough, Partner
NSF-DBA Ltd.

Final CHMP Guidance on 'Real Time Release Testing'

Thu, 26 Apr 2012 15:49:01 +0000

In late March 2012 the EMA issued the final version of CHMP note for guidance (NfG) on Guideline on Real Time Release Testing (RTRT). This is new guidance replaces the previous guidance on parametric release (CPMP/QWP/3015/99) from 1 October 2012. The previous guidance only applied to the release of terminally sterilised products without performing a sterility test. The new guidance retains the previous guidance, as section 7, but extends the concept to other sorts of product along the lines described in ICH Q8, 9 & 10.

This guideline states in its introduction:

“Enhanced product knowledge and process understanding, the use of quality risk management principles and the application of an appropriate pharmaceutical quality system, as defined within ICH Q8,Q9 and Q10, provides the platform for establishing RTRT mechanisms for other applications, for new products as well as established marketed products. Release of a product can be a combination of a RTR approach for certain critical quality attributes (CQAs) and a more conventional evaluation for other CQAs (partial RTR).”

The scope of the guidance includes testing for active substances, intermediates and finished products. It does not include investigational medicinal products.

The guidance states that “The introduction of RTRT requires pre-authorization by the competent authority”; i.e. it must be submitted and approved as part of either a new Marketing Authorisation application or a type 2 Variation.

Even if RTRT is approved for routine use, a product specification has to be established and each batch of a product should comply with it if tested. This specification is also needed for stability testing.

A key point made in this guidance is that when RTR testing has been approved this should be routinely used for batch release and if the RTR testing fails or results are trending toward failure, RTR testing may not be substituted by end-product testing.

Attributes that are indirectly controlled by approved RTRT should still appear in the Certificate of Analysis for batches. The approved method for end-product testing should be mentioned and the results given as “Complies if tested” with a footnote: “Controlled by approved Real Time Release testing”.

If RTRT is registered but you have an equipment breakdown that means you are unable to use this for a period of time you will need a contingency plan for alternative testing. This contingency plan has to be included in your RTRT submission.

With respect to re-testing of products imported into the EU from ‘third’ countries the draft guidance states the following:

“For products coming from third countries into the EU, it is a requirement in Directive 2001/83/EC “that each production batch has undergone in a Member State a full qualitative analysis, a quantitative analysis of at least the active substances and all the other tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the marketing authorisation”. This normally means a complete re-analysis of the product according to the approved specifications. When a company has got approval for RTR testing for one or more tests in the specifications, these tests would not be considered a “necessary test or check to ensure the quality of the medicinal product in accordance with the requirements of the marketing authorisation”. Therefore a relief from this testing will be accepted.

The guidance gives the requirements for regulatory submissions in section 6.

Best regards,

Peter Gough, Partner
NSF-DBA Ltd.

New draft CHMP Guidance on Process Validation

Wed, 18 Apr 2012 08:12:24 +0000

Peter Gough reviews:

Dear All,

In late March 2012 the EMA published a draft CHMP Guideline on Process validation that proposes to replace the existing CHMP Guidance’s on this topic (CPM/QWP/848/96 and EMEA/CVMP/598/99). Comments on this proposal are due to EMA by 31 October 2012. Unlike the 2011 FDA Guidance on process validation this draft states that it does not introduce new requirements for medicinal products already authorised and on the market.

The changes are being proposed to bring EU guidance in line with ICH Q8, 9 & 10 and to also to better align with the 2011 FDA Guidance for Industry on Process Validation.

The scope of this draft revision is both human and veterinary medicinal products. It is also applicable to biological products but these should be considered on a case-by-case basis in view of the complex nature and inherent variability of biological substances. Unlike the FDA Guidance, it is NOT applicable to APIs.

There are several significant changes to the requirements for process validation (PV) in this new draft. One of these is the introduction of what is called “Continuous Process Verification” as an alternative to the traditional approach to PV. It is also important to note the philosophical change to a lifecycle approach to PV, which ever approach is followed, that is contained within this draft where it states:

“Process validation should not be viewed as a one-off event. A lifecycle approach should be applied linking product and process development, validation of the commercial manufacturing process and maintenance of the process in a state of control during routine commercial production.”

“Process validation should confirm that the control strategy is sufficient to support the process design and the quality of the product.”

The draft allows different approaches to process validation; the traditional approach, what it calls “Continuous Process Verification” or a combination of the two. The guidance on the traditional approach is largely the same as in the previous guidance. The main requirements are set out in Appendix 1 of the guide and are almost identical to the earlier text but where it originally said “usually 3 consecutive batches” the new draft says “the number of batches used would depend on the variability of the process, the complexity of the process / product and the experience of the manufacturer, but would usually be a minimum of 3 consecutive batches”. This does not go as far as the 2011 FDA guidance but by emphasising the link to process variability it does further undermine the former “three batches and you are done” mind-set even where the traditional approach is adopted.

The new approach given in section 5.2 of the draft is called “Continuous Process Verification” and is essentially what has become more generally known as the “Quality by Design (QbD)” approach, following the implementation of ICH Q8. As there is a later section, 5.4, in the draft on “Continued Process Verification during the lifecycle” (the same terminology as is used for stage 3 in the FDA guidance) there must be the opportunity for considerable confusion between these two different but linked concepts. It would be better if the approach given in section 5.2 were called something like the QbD approach.
Section 5.2 seems to be saying approximately the same as stages 1.2 and 2.2 of the 2011 FDA guidance. It says “Process analytical technology applications … and multivariate statistical process control can be viewed as enablers for continuous process verification.” However, this approach appears to be restricted to cases where the control strategy is based on continuous monitoring.

There is no mention in this draft of the qualification of facilities, utilities and equipment as there is in stage 2.1 of the FDA guidance. It appears that this is being left to a revision of Annex 15 of the EU GMP Guide, which is being initiated at a PIC/S meeting in September 2012.

If the continuous process verification approach is utilised, Annex 1 adds the requirement to conduct additional monitoring of the first commercial batches. It states that “The process validation scheme should provide details on the number of batches for which additional monitoring is proposed, the type of testing / monitoring to be performed, the acceptance criteria to be applied and how the data will be evaluated. Any statistical models or tools used should be described. … the stage where the commercial process is considered to be validated should be stated based on the complexity of the process, expected variability and manufacturing experience of the company.”

Section 5.3 is titled “Hybrid approach” and allows for the use of the traditional approach for some steps in a manufacturing process and the continuous process verification approach in others. It states that “A justification for using this hybrid approach should be presented in the dossier and it should be clear which approach to validation has been taken for which part of the manufacturing process.”

Section 5.4 “Continued Process Verification during the lifecycle”, is similar to stage 3 of the 2011 FDA guidance. It would appear to be a new requirement that applies whichever process verification approach is adopted. This section requires that “Subsequent to process validation and during commercial manufacture, companies should monitor product quality to ensure a state of control is maintained throughout the commercial part of the product lifecycle.”

There is also a new section 8 titled “Standard vs. non-standard methods of manufacture”. This section is only relevant for processes which have not been validated using continuous process verification. The section gives examples of several non-standard products and processes that may require non-standard approaches to process validation on a case-by-case basis.

The publication of this draft revision to the EU CHMP Guide to Process Validation marks a convergence with the 2011 FDA Guidance on the same topic but it falls a long way short of complete harmony; e.g. the traditional 3 batch approach is still acceptable. If you follow the FDA Guidance then you should meet these new draft EU expectations but not the other way round. A final version of this guide is not expected until late 2013.

Best regards,

Peter Gough, Partner

For information on our ‘Modern Approaches to Process Validation’ Course in May follow this link