Example Annual Product Review Report Format

PURPOSE:

SCOPE:

1.

To evaluate the performance of manufactured product versus the approved specifications and expected quality attributes.

2.

To identify trends in product quality or changes in Active Raw Material(s), In-Process, or  Finished Goods performance.

3.

To propose the need for changes in product specifications or manufacturing processes or  control procedures.

4.

Comply with 21 CFR Part 211.180 (e).

This procedure is intended to describe the minimum requirements of 21 CFR Part 211.180 (e) regarding evaluation of the batches and the batch records on an annual basis in order to assure the quality standard requirements of the product. This procedure covers the approved marketed products manufactured for commercial distribution.

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RESPONSIBILITY

ACTION

QA

1.0

During the beginning of each calendar year, QA will obtain a list of approved products from Regulatory Affairs (RA). Refer to Attachment I - APR Flow Chart for  reference.

2.0

Based on this list, QA will generate a schedule of the Annual Product Reviews (APR) due for the year. 2.1

The schedule will include, as a minimum: product, strengths, product codes, the review period and approval due date.

2.2

The review period is determined by each product’s approval date. For  example, a product whose approval date is June 15, 2002 will contain data from batches manufactured/dispositioned within the June 15, 2002 to June 14, 2003 reporting period. The review period encompasses 1 year of data from manufactured/dispositioned lots. APRs for different strengths of the same product with similar approval dates may be combined.

2.3

APR packages will not be compiled for products for which there were no lots manufactured or products that have been discontinued during the review period. Although those products were not manufactured, product quality will be monitored and documented throughout their shelf life through the following systems: stability study programs, customer complaints, and retention samples review.

3.0

QA will coordinate preparation of the APR report, which consists of two parts: the Executive Summary and the Data File.

4.0

The Executive Summary consists of the following sections. See section 7.0 for  detailed information that will be included in the Executive Summary. 4.1

Cover Page

4.2

Approval Page

4.3

Abstract

4.4

Active Raw Materials

4.5

Product Review

4.6

Change Control

4.7

Deviations/Planned Variances

4.8

Laboratory Investigation Reports (OOS/OOT)

4.9

Stability

4.10

Complaints

4.11

Field Alerts/Recalls/Returned Goods

4.12

Retention Samples

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RESPONSIBILITY

ACTION

QA

4.13

Corrective Actions

4.14

Attachments

5.0

The Data File consists of the supporting documentation, such as raw data, charts, graphs, Specification sheets, Certificates of Analyses, etc. The Data File will be retained in QA until the Executive Summary is approved.

6.0

Compilation Requirements

7.0

6.1

Charts/Graphs generated for the Executive Summary must have the following in the header: product name, strength, product code, and review period. In addition, charts/graphs must have “Prepared By/Date:” and “Verified By/Date:” as a footer and be initialed and dated by the preparer  and the verifier. Charts/graphs will be generated if there are five or more lots/entries available, otherwise no charts/graphs are required. This does not apply to the Data File.

6.2

100% of the manufactured lots within the review period will be reviewed.

6.3

For Deviations/Planned Variances, LIRs and Stability investigations addressing product with multiple actives, specify which active is involved.

6.4

List the Stability lots and the purpose of study.

6.5

Ensure a statistical analysis is conducted to determine trends.

Compile the Executive Summary. The summary will include the following sections with the indicated requirements. 7.1

7.2

Cover Page 7.1.1

Product name and strength

7.1.2

Application number 

7.1.3

Application approval date

7.1.4

Review Period

Approval Page 7.2.1

Product name, strength, and product code

7.2.2

Review Period

7.2.3

Compiled By and Date

7.2.4

Assessment of Manufacturing Process Changes

7.2.5

Product Review

7.2.6

Approval Signatures and Dates

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RESPONSIBILITY

ACTION

QA

7.2.7 7.3

7.4

7.5

Total Number of Pages

Abstract 7.3.1

A brief overview of product performance during the review period.

7.3.2

Report any trends or changes to ( Title of escalation responsible  party) and identify any corrective actions.

Active Raw Material(s) 7.4.1

Evaluation of the active raw material(s) used in the manufacturing of the drug product. Characteristics to be evaluated include, as applicable, but are not limited to: Assay, Specific Rotation, LOD, pH, Particle size, Bulk Density, and Impurities. Explain any out of  specification results and outliers.

7.4.2

Name of manufacturer.

7.4.3

Number of active raw materials lots utilized.

7.4.4

Number of active raw materials lots rejected.

7.4.5

Compare full tested active raw material lot(s) results to their  respective Certificate of Analysis.

7.4.6

Evaluate data for trends, shifts, and outliers.

Product Review 7.5.1

Evaluation of in-process attributes. This includes, as applicable: packaging yield, blending, theoretical and total accounted yields, weight, thickness, hardness, disintegration time, friability, compression theoretical and total accounted yields, and film coating theoretical and total accounted yields.

7.5.2

Evaluation of finished product data: Assay, Content Uniformity, and Dissolution. Report Chromatographic Purities.

7.5.3

Number of lots manufactured. For multiple strength APRs, state if  any product codes had no manufactured lots.

7.5.4

Number of lots released.

7.5.5

Number of lots not dispositioned.

7.5.6

Number of lots rejected, lot corrective/preventive action taken.

number,

cause,

and

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any

RESPONSIBILITY

ACTION

QA

7.6

7.7

7.8

7.5.7

Identify any experimental lots converted from rejected finished good lots.

7.5.8

Identify the lots not yet dispositioned. These lots will be carried over to the next review cycle, if applicable.

7.5. 9

Generate Control Charts for in-process attributes and finished product data, if applicable, as an attachment. Address any control parameters that are visually verified but cannot be graphed (Examples: hardness may be a range; impurities may be a < value or a NMT value).

7.5.10

Evaluate Control Charts for trends, shifts, and outliers.

7.5.11

Identify, review, and summarize the results of any process and method validation/re-validation, if applicable.

Change Control 7.6.1

Review Change Controls issued during the review period.

7.6.2

Report the change controls, including but not limited to, Specifications (Active Raw Materials and Finished Goods), Batch Records, Test Methods, Packaging Components, Bills of Material and Labeling.

7.6.3

Verify that any changes in the manufacturing process, formulation, batch size and/or equipment for the lots manufactured during the review period have been approved, validated, and qualified.

7.6.4

Generate a Pareto chart.

7.6.5

Details of the manufacturing process change(s) affecting validated processes will be in the Data File.

Deviations and/or Planned Variances 7.7.1

Review and report the deviations and/or planned variances generated within the review period and determine if there are any developing trends.

7.7.2

Compare the product related deviations and/or planned variances initiated during the review period to previous year’s APR.

7.7.3

Generate a Pareto chart.

OOS/OOT 7.8.1

Review and report the OOS/OOT generated within the review period and determine if there are any developing trends.

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RESPONSIBILITY

7.8.2

Compare the product related OOS/OOT initiated during the review period to previous year’s APR.

7.8.3

Generate a Pareto chart.

ACTION

QA 7.9

7.10

7.11

7.12

Stability 7.9.1

Evaluate the annual stability data for product lots in the stability program. The Stability Results Summary shall include any Stability Study Termination/Modification Request documents.

7.9.2

Data (assay, dissolution, hardness and impurities, as applicable) from the stability studies will be entered into regression data tables. Stability regression analyses will only be generated when there are four or more time points.

7.9.3

Generate graphs for regression profiles using Statistical software. If the data is non-continuous, a data table will be provided in place of regression graphs. Include confidence interval on charts if the pvalue is