【讨论】Detailed Analysis of Annex 15 Draft

zhulikou431

In our News EMA published a concept paper on the revision of theAnnex 15 we reported about the planned revision of Annex 15. The draft EU GMP Annex 15 is nowavailable. Compared to the original 11 pages of Annex 15 the drafthas now 17 pages. The above-mentioned EMA Concept Paper is mentioned as areason for the revision, i.e. adjustments to:
Changes in Part 1 of the EU GMP Guide
Changes in Annex 11
ICH documents Q8-11
The EMA draft on Process Validation
Changes in manufacturing technologies
New points have been added to the table ofcontents like subparts of the Process Validation Chapter, topics on transportverification, packaging validation, qualification of utilities, and validationof test methods. The issue revalidation has been replaced byrequalification.
Principles: The root principles address aproduct / process lifecycle which should be accompanied by qualification andvalidation activities. In addition, it is now highlighted that changes shouldalso assess the influence on "control strategy". Furthermore,references have been made to validate computerised systems according to Annex11 and to consider the requirements of ICH Q8-11.
There is a brand new section("General") in which a "justified and documented" riskanalysis (as part of the quality risk management approach) should be the basisfor decision making regarding the scope and depth of the qualification/validation activities. In this chapter too, the principles of ICH Q8-11 (orothers if comparable or better) are mentioned as support for qualification/validation activities. According to the last section of this chapter "data supporting qualification and/orvalidation studies which were obtained from sources outside of themanufacturers own validation programme may be used provided that this approachhas been justified and that there is adequate assurance that controls were inplace throughout the acquisition of such data".
The name of the original first chapter"Validation planning" is now named "Organisation and Planningfor Qualification and Validation". There, importance is attached to theanalysis of the life cycles of equipment, processes and products, and to therespective training of validation employees according to approved validationSOPs. Report structures of the validation personnel should be based on theinternal quality system of the company; not necessary given to a QM or QSfunction. But an appropriate "oversight" over the whole validationlife cycle should be available. Later in the text, the validation master planis addressed. The requirements are very similar to the previous version ofAnnex 15. Nevertheless, the current validation status of facilities, systemsand processes, and that of the location has to be indicated now. Moreover, thedescription of deviation management in the validation master plan, the handlingof acceptance criteria, die evaluation of necessary resources and the"ongoing validation strategy" is now required. With regard to the"ongoing validation strategy", the term "revalidation" (aswell as "requalification") appears once more. In addition, aconfirmation should be provided "that the materials used for validation are of therequired quality and suppliers are qualified to the appropriate level". There is also an additional new requirement which refers toquality risk management. The "approach should be used for validation activities with risk assessmentsrepeated, as required, in light of increased knowledge and understanding fromany changes during the project phase or during commercial production. The wayin which risk assessments are used to support validation activity should beclearly documented".
The second chapter "Documentation"starts with the requirement with regard to the use of "good documentationpractices" to support "knowledge management" during thevalidation life cycle. All the validation documents have to be approved andauthorised according to the determinations of the quality system. In case ofcomplex validation projects, there should be clear references between thedocuments. Important and critical systems, attributes and parameters, as wellas their acceptance criteria should be listed in a validation protocol. Ifvalidation protocols are delivered by third parties, the manufacturer has toconfirm their suitability and compliance with the internal procedure before anyapproval. Each change to approved protocols should be documented as deviationand be scientifically evaluated. Results outside the acceptance criteria shouldalso be treated as deviation and investigated. Besides, the influences onvalidation should be discussed in the report. Regarding the content, therequirements on reporting haven't changed. A cross reference to the protocolisn't required any longer but the results should be opposed to the acceptancecriteria. The draft reveals to be flexible with regard to the releases ofvalidation steps which can be part of the release of the validation report, orcan be summarised on a document. Mentioning conditional approval to proceed tothe next stage is something new: this approval can be "given where certain acceptance criteria ordeviations have not been fully addressed and there is a documented assessmentthat there is no significant impact on the next activity."
Chapter 3 "Qualification stages forequipment, facilities and utilities" starts with underlining thefact that all stages from initial development of the user requirements shouldbe considered. Specifications for new facilities, systems or equipment shouldbe defined in a user requirements specification (URS) and/or a functionalspecification. This should help building in quality at this stage andminimising GMP risks. The URS should be "a point of reference"throughout the validation life cycle.
The design qualification (DQ) is now thesecond step of qualification. There haven't been many changes with regard tothe content; only the obligation to verify the user requirements during thedesign qualification has been added.
Factory acceptance tests (FAT) are new, andsite acceptance tests (SAT) have been included in the draft. For equipment withnovel or complex technology, the FAT is binding ("should beevaluated at the vendor prior delivery"). Documentation review and sometests could be performed at the FAT stage where appropriate and justified, butonly when transport has no influence on these functions. On the contrary, theuse of SAT is mentioned as "may be" option.
The requirements on installationqualification (IQ) have remained almost unchanged; but the listing is made of a"could" wording. There is a new sub item regarding the verificationof the correct installation against pre-defined acceptance criteria.
Regarding operational qualification (OQ)there is now the possibility to perform this task together with IQ and IOQdepending on the complexity of the equipment. The formal release requiredafter OQ has slipped.
It is now explicitly mentioned that it ispossible (in some cases) to perform performance qualification (PQ) inconjunction with process validation. The use of "worst case batchsizes" has been newly added. In addition the frequency of sampling in thePQ should be justified. The activities for IQ, OQ and PQ are "could"provisions according to the new draft Annex 15.
Generally, the section on the qualificationof established (in-use) facilities, systems and equipment has disappeared.

玻璃杯

求翻{:soso_e112:}

zyq2011

能有全文吗

彩虹

呵呵，英文看不懂啊