Annual Product Review FDA (APR)
How to conduct an effective annual product review?
Before starting I want to go back to an idea mentioned above and which I suppose you have heard many times and in different places: the APR is more than a regulatory requirement, it is a review that allows the developer to understand more about their process and take improvement actions.
CGMPs need an annual evaluation of product quality standards to determine the need to adjust their specifications and the manufacturing and control procedures.
The guidelines emphasize the importance of the analysis of the investigations or deviations conducted and the complaints of products received, while the APR report must explore, in depth, the causes of recalls and product returns, if any.
In general, the mandate of the Regulatory Agencies (eg FDA) is to look through and systematically through all areas of improvement and consistently align processes to the development of quality products.
For these same general reasons, GMPs require processors to analyze after review, examine the results of the analysis of finished products and controls in critical processes and review: failed lots, diversions, CAPAs, exchange controls, stability studies, returns, claims, qualifications in critical equipment and quality agreements.
The CAPAs of the annual product review need to be communicated to Senior Management and completed effectively and on time, their effectiveness must be checked through internal audits.
Structure of an APR report:
It can vary depending on the company, or even the product. The idea of following a template or model ensures that all the required aspects are evaluated.
But an APR is an evolving type of document.
Changes and fixes
The Review of changes can be broken down into: raw material changes, packaging components, specifications and master documents. The non-conformities and deviations section needs to be reviewed, especially considering the corrective actions and their effectiveness. Any overdue or ineffective CAPA needs to be discussed in the report. This is one of the fundamental aspects.
Any observed trend needs to be addressed, not just the ones that are OOS.
Rationalization of APR source and management data
Compiling raw data is always a team effort, but the QA department must take the lead and be ultimately responsible for program administration.
An APR committee could typically include a representative for QA, QC, validations, operations, stability, engineering, and logistics. A draft report is completed on the critical analysis of the raw data, then discussed at an APR committee meeting to determine the effective CAPAs.
Another challenge for the APR administrator is data recovery for the purpose of the review.
Companies with qualified data acquisition systems can use their databases, while paper-based processors may have to review batch documents individually to see process parameters, in-process controls, final analyzes , yields, etc. In either way, the raw data used for the analysis must be accurate in order to complete an effective analysis / evaluation. If deviations from the process are observed during the review, it may be required to collect additional information to justify such findings.
The data should be available to the APR administrator in a timely manner. All of them must be verified by a second person if they are collected manually.
If spreadsheets are used, they must be validated prior to use.
Conclusions
Making an APR is a requirement for regulated markets. But more than that, the review helps the developer better understand and understand their processes and gather additional information for further improvements.
It is a tremendous help in determining if a product still meets specifications, if you need a formulation change, packaging modification, specification revision, or a more robust process. An APR conclusion is a step prior to future product development and should therefore be accurate and supported by adequate data.
The FDA Process Validation Guides call for continuous verification of the process. Thus, an APR program can serve as an on going system (step 3: continuous process verification) to collect and analyze product / process data that relates to product quality.
The APR needs are part of the risk mitigation plan according to the ICH Q9 recommendations.
The information gathered and the trends observed can assist in the development of a new product as such and so this is essential to distribute the report to all relevant and interested parties. The effort can also be reviewed and shared with continuous improvement teams (lean process) while developing CAPAs of an APR are critical in avoiding potential risks to a product in the future.
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Also if you need it we can offer you to carry out the annual review of your products, contact us here .
Structure of an APR report
We have already talked a lot on the subject of the Annual Product Review, but today I want to leave you with an idea or APR model, of course it may vary depending on the company, or even the product. The idea of following a template or model ensures that all the required aspects are evaluated.
It may be a few sections with minimum requirements or a document prepared with annexures containing information or data relevant to the product (eg Revision of retention samples). Each numbered subsection is typically followed by a summary. Having graphs or tables will help to understand the data and detect trends if they exist.
A list of content is shown below:
Objective / Scope
Review of processed batches, BR and yields
CC Review (consider label and gear / artwork changes)
Review of analytical data
Stability data review
Validation and qualification review
Review of nonconformities / deviations
Review of rejected lots
Review of reprocessed batches
Claims review
Recall review
Counter-sample review
Quality agreements
Review of previous APRs
Conclusions and recommendations
References
Approval
Tables and graphs:
Bulk Batch Enumeration Summary
Summary of finished product batch enumeration
Batch Yield Summary
Summary of analytical results
Summary of control results in process (IPC)
Exchange Controls Summary
Description of deviations and non-conformities
Lots introduced to the stability program during the review period
Stability batches introduced before the APR period
I hope you find it useful.
APR: Annual Product Review
On the other hand, the preparation of APRs is a regulatory requirement, the Good Manufacturing Practices (cGMP), establish the following:
(a) Written records must be maintained to evaluate, at least annually, the quality standards of each pharmaceutical product and determine the need for changes in product specifications or manufacturing or control procedures.
(b) There must be written procedures for the execution of the APR, which must include:
• The review of a representative number of lots, whether approved or rejected, and the records associated with said lots.
• The review of exchange controls, claims, market recalls (Recall), the return of products, and the investigations carried out in said period of time.
When done correctly, an APR provides many benefits, including the potential for quality improvements.
