Professional Documents
Culture Documents
Page 1 of 13
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 2 of 13
(monitoring, hygiene plans) must be taken into consideration. The CFR also requires complaints, recalls, returns, destructions and observations from the batch record reviews to be analysed. As there are no clear statements regarding the scope and content of an annual product review, it is important to set out company-internal regulations in the form of an SOP. A considerable amount of work is required for an annual product review in order for it to provide more than just general statements and recognise actual dependencies e.g. between manufacturing parameters (e.g. dependencies between the breaking strength and disintegration of a tablet - the influence of disintegration on dissolution). For this, process parameters and analysis results must be contrasted even down to the level of individual values. To keep the amount of work within acceptable limits during the annual product review, "for some kinds of data (e.g. analytical tests results, yields, environmental controls, etc.) it is recommended that records be kept in a manner permitting trend evaluation" in the current year of production (EU GMP Guideline, chapter 6.9). Storing the batch documentation systematically will also considerably reduce the amount of work for the annual product review. The "quick retrievability" of documents and raw data required by GMP is thus also checked during the annual product review. Weaknesses in the documentation system (e.g. too many, scattered storage locations, lack of labelling of originals and copies, lack of cross references to raw data, traceability of raw data, etc.), in the documentation (e.g. overwriting, blank fields, missing reasons for modified entries, transfer errors) or in the change control program (e.g. not all changes have been recorded or evaluated, deficiencies in the implementation of follow-up measures, etc.), which are uncovered by the annual product review should be immediately rectified by corrective measures, such as improved storage organisation (check of the SOP on which this is based) and training. Figure 15.F-2 gives as an example a few measures which a company could implement as the result of the findings of the annual product review. Figure 15.F-2 Examples of company-internal consequences of an annual product review Examples of company-internal consequences of an annual product review Process optimisation Revalidation Adaptation of manufacturing or control procedures Amendments or authorisation changes Improvement to batch documentation storage (retrievability) Continuous, systematic gathering of specific process data and analysis values for
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 3 of 13
permanent validation or statistical process control (SPC) Strict change control programs Monitoring of implementation measures for approved changes Improvement of discipline for managing protocols Improvement of complaint processing Recording of conclusions as a training topic
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 4 of 13
complaints and recalls Cause analysis and follow-up Stability data Changes to packaging material Process changes Recipe changes Does the current data support the stability declared in the submission file for marketing authorisation?
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 5 of 13
An annual product review report must also satisfy the formal requirements for GMP conforming documents (see chapter 15.B GMP-conforming documentation). The information given in the header (see figure 15.F-4), a well-defined structure, clearly laid-out contents and a summary of the most important statements and conclusions all contribute to the readability of the report. Figure 15.F-4 Header data in an annual product review report Header data in an annual product review report Name of the preparation Material number of the preparation Batch designation of the evaluated batches Calendar year Date of creation Version number Ultimately, the annual product review report should not only serve to fulfil legal requirements, but should also be used as a useful internal status report ("validation barometer"). The annual product review report must not only be signed and authorised by the author, but also by the responsible persons, in this case specifically the Heads of Production and Quality Control as well as the Head of Quality Assurance.
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 6 of 13
Preparation: Material number: Batch designation: from to Version: Created on: Author: Objective: The annual product review records and evaluates all batches of the "sample tablets" preparation during the calendar year 2004. The evaluation includes the in-process data, the analytical results for the final product, the physical results and the general production data. The procedural changes implemented and changes in the starting material manufacturers are reviewed with regard to their effects on the final product. Deviations from the process are recorded and evaluated. There is a summary of all batches and any deviations from specifications and of all batches for which external complaints were received. Authorisation of the annual product review Head of Production: Date/signature Head of Quality Control: Date/signature Quality assurance: Date/signature Development: Date/signature Client authorisation: Date/signature Figure 15.F-7 Contents of an annual product review
Annual product review for calendar year 2004
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 7 of 13
Created on: Author: Contents 1.0 Overview of batches 2004 2.0 Analysis of the physical and chemical results Tablet cores 2.1 Dimensions 2.2 Breaking strengths 2.3 Disintegration 2.4 Friability 2.5 Loss on drying 2.6 Determination of content Coated tablets 2.7 Average weights 2.8 Dimensions 2.9 Breaking strength 2.10 Disintegration 2.11 Determination of content 3.0 Analysis of the production data 4.0 Analysis of the process changes 5.0 Deviations from the manufacturing specifications 6.0 Analysis of the batches that do not conform to the specifications 7.0 Recommended measures for the year 2005 8.0 Diagrams Figure 15.F-8 Example 1 for graphical presentation
Annual product review for calendar year 2004
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 8 of 13
cores It is useful to analyse the batches and to use a graph to show the various average weights of all manufactured batches. The batch production records or the certificates of analysis form the basis of the analysis. Figure 15.F-9 Example 2 for graphical presentation Annual product review for calendar year 2004 Preparation: Material number: Batch designation: from to Version: Created on: Author: Presentation of the average breaking strength of the
cores: It is also advisable to show the relationships between the breaking strengths of the individual batches as a graph. Additional inspections should be used to check the influence of the breaking strength on disintegration or on release. Figure 15.F-10 Example 3 for graphical presentation
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 9 of 13
Annual product review for calendar year 2004 Preparation: Material number: Batch designation: from to Version: Created on: Author:
Example of the presentation of yields: The total yield or the yields at the individual manufacturing stages can be used to show the yields. Where there is a collaboration between contract giver and contract acceptor, consideration of the yields does not only concern GMP, because the number of items supplied forms the basis for invoicing.
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 10 of 13
Quality control Quality assurance Engineering For information to created by checked by approved Change index - New compilation 1. Introduction 1.1 Background/objectives The annual product review looks back at production and quality control data to assess changes, trends and weaknesses. The SOP sets out the requirements for compiling the annual product review. It describes the scope and content, responsibilities, time specifications, important key words and authorisation procedures. 1.2 Relatedness to other regulatory information EU GMP Guideline, chapter 6.9 21 CFR 211.180 (e) 1.3 Definition Annual product review Examination of the history of the manufacture and testing of a product over a manufacturing year. 1.4 Scope and responsibilities The annual product review includes all medicinal products manufactured in the pharmaceutical company, including contract manufacturing. The Heads of Production, Quality Control and Engineering arrange that all relevant data and documents for their area of responsibility are made available. develop recommendations and corrective measures based on the existing data and reports. evaluate and authorise the results together with Quality Assurance. Quality assurance
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 11 of 13
collects and evaluates the necessary data and information in accordance with the SOP, compiles the summary report and makes it available. ensures authorisations and scheduling for necessary remedial action. is responsible for the annual compilation of the annual product review in accordance with the SOP. 2 Implementation 2.1 Data collection, responsibilities Quality Assurance compiles a list of all the products manufactured in the period concerned and distributes it to all the areas responsible for collecting the data. These complete the list in the time specified by Quality Assurance. The following individual data for all manufactured, rejected or destroyed batches must be determined and consolidated ( specialist function responsible): Yield Production and engineering Analytical and physical data Quality control Environmental monitoring Quality control In-process controls Production, Quality control, Engineering Stability studies Quality control Deviations and their follow-up measures Quality assurance Changes and their follow-up measures Quality assurance Out of Specification Quality control Results, trends and summaries Change of supplier and Quality assurance and material resulting measures characteristics Reworking Quality assurance Returns Quality assurance and material characteristics Recalls Quality assurance Complaints, trends and summaries Quality assurance All data must be prepared in tables and/or graphs so that results, deviations and trends are immediately recognisable. The following reports must be compiled by Quality Assurance: Detailed summaries with references to available interim reports and single value data List of all quality-relevant data and deviations with references to interim reports and any existing single value data Records of necessary measures, as well as action plans, responsibilities for these and their scheduling Measures status with regard to previous annual product reviews 2.2 Inspection, evaluation and authorisation
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 12 of 13
The annual product review, including the interim reports and recommendations, is inspected and authorised by the head of the specialist function concerned and those responsible for the required corrections, the Head of Production the Head of Quality Control the Head of Quality Assurancwe The annual product review contains a further concluding evaluation of the following points: Process is in order, GMP compliant That is, the reported data does not demonstrate anything unusual, the process functions and is valid. Measures are required The review has shown that some measures are required. The process functions as it is and is valid. Immediate measures are required The review has shown that significant corrections are required. The process is out of control, an inspection is required including an assessment of the products that are already on the market. 2.3 Archiving Archiving is carried out by Quality Assurance. 2.4 Distribution The specialist functions concerned and those responsible for the required correction should receive copies of all authorised annual product reviews. Summary The annual product review is a structured procedure in which all information, changes and dependencies that have arisen during a calendar year with regard to the manufacture and control of a preparation are detected, evaluated and documented and in which suggestions for improvements are formulated. Although a large amount of time is required to compile an annual product review, its significance will also be high due to the generally large number of batches analysed in comparison to the three validation batches. At the same time, the annual product review offers the opportunity to critically examine the functions of internal systems, such as change controls, documentation, storage, investigation of deviations, OOS procedures and the processing of complaints.
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011
Page 13 of 13
http://www.gmpua.com/World/GMPManual/daten/autorenteil/kapitel_15/15_f.htm
15/12/2011