APQR | Annual Product Quality Review Know Hows
Purpose
To lay down the procedure for preparation of APQR / Annual
Product Quality Review for the products to enhance the consistency of
manufacturing process and overall quality of the product.
Procedure
Definition: APQR
is an evaluation conducted annually to assess the quality standard of each drug
product with a view to verify the consistency of existing process and to check
the appropriateness of current specifications and to highlight any trend in
order to determine the need to change any product specifications or the
manufacturing processes or control procedures.
Significance of APQR
- Verify the consistency of the existing manufacturing process and minimize the risks to develop their products consistently of best quality on yearly basis.
- It determines the quality and process defects of the products. It also determines possible improvements of the analytical methods and manufacturing process.
- Trend of yield, analytical results, manufacturing parameters of the product are also highlighted. It is helpful to identify the process and product defects.
- It reviews the quality of the raw material and packaging material which is used for the product. Mainly it indicates the quality of material.
- In-process and the finished product results are reviewed to determine the consistency of the product quality.
- Verifies the appropriateness of current specifications for both starting materials and finished product to highlight any trends and to identify product and process improvements.
- Out of Specification parameter helps to determine the product defects and the prospective actions are defensing the product from possible risks.
- If any of the batches is failed, then it is also included in the APQR to determine reasons for the batch rejection.
- The review of the stability study results of any long term and on-going stability of the bulk product and the marketed product should be done.
APQR Preparation
- APQR shall be prepared for the drug products (generic name) manufactured in the calendar year from January to December.
- APQR of calendar year shall be completed as per requirement till 31st march of the next calendar year. If APQR not completed within time frame then deviation shall be raised.
- APQR shall be prepared for at least 5 batches manufactured in that year. If less than 05 batches manufactured during the define review period, APQR for that product shall be prepared next year considering the batches of both years.
- Graphical trends shall be prepared for critical process parameter and critical quality attributes to easily exhibit the results & deviations.
- APQR shall include the following information, but not limited to:
Title, identification number,
General Product information,
Product details including batch no, batch size, details
of customers, pack size etc.
Product specification,
Review and trend of starting material/ packing
material,
Review of water system,
Critical process parameters,
In-process checks,
Analytical data for in-process bulk and finished
product,
Yield data (in-process stages/ Finished products),
Staging period of the batches,
Environmental conditions during manufacturing and
filling,
Change control/ Deviation/ Incidences/ Market
complaints / CAPA
Returned batches/ Product recalls
Product failure/ Related investigations
Regulatory changes (Pharmacopoeial changes RM/ PM/ IP/
FG)
OOS/ OOT
Vendor details and addition of new vendor
Number of rejected batches,
Control sample review,
Batch reworking/ re-processing details,
Stability profile,
Details of equipment/ instruments/ utility support and
qualification state
Review of environment condition
Validation status,
New Marketing authorizations and quality related
variations to marketing authorization
Review of technical agreements,
Review of previous year recommendation and
implementation closure
Review of Self inspection/ Regulatory/ Customer audit
report to ensure the CAPA for observations related to product quality are
closed
Capability index,
Summary,
Recommendations,
Conclusions,
Approval.
- QA Personnel shall generate an overall APQR summary, comprising of the following:
Narrative summary of each
sections or reference to individual section summary.
Listing
of quality issues or deviations identified by the section summaries.
Listing
of corrective and preventive actions to address the issues.
Status
of any action plans from previous APQRs for the specific product.
Individuals
responsible and target dates for completion of each action plan.
A
statement indicating the conclusion of the individual APQR as defined by one of
the following:
Process in control - It
indicates no abnormalities within sets of data and confirms that the process
continues to function as validated.
Action recommendations - It
indicates the recommended corrective and preventive actions.
Corrective actions required - It
indicates the need for immediate actions or corrections.
The completed APQR shall include each section summary
and the overall APQR summary with recommendation.
APQR shall identify the weakness and strength of
process and operations based on complaints in-process failure and product
distribution.
Process capability Cp and
Process capability index [Cpk]:
Cp stands for process capability and Cpk stands for
process capability index. Both are used for the measure of a potential
capability of a process.
Process Capability, Cp: A
process is said to be capable if the spread of the natural variations fits in
the spread of the specified limits.
Process capability index (Cpk): is the
measure of process capability. It shows how closely a process is able to
produce the output to its overall specifications.
Calculation of Cpk value
Cp =(USL–LSL)/6S
Cpl =(Mean–LSL)/3S
Cpu = (USL – Mean)/3S
Cpk= min [Cpl, Cpu]
If the value of Cpk=1, the process can be considered
barely capable. In this case, there is a risk to fall down capability below 1,
hence process may produce defective product.
If the value of Cpk>1, the process is capable. It
means process is capable to meet or exceed customer’s expectations.
If the value of Cpk<1, the process is Less capable.
In this case, improvement of process or revision of specification is required.
Where,
USL = Upper specification limit
LSL = Lower specification limit
S = Standard deviation
- Mean shall be calculated as per the following equation:
Mean (m) = (∑Xn)/N
Where,
∑Xn indicate total sum of observations made
for individual batch
N is the total number of the batches.
- Standard deviation shall be calculated as per the following equation:
S = √(∑Xn – m)2/ N - 1
Mean, Standard deviation and Process capability index
shall be calculated with the help of validated excel sheet.
Trend shall be prepared with the help of validated
excel sheet.
List of products manufactured in the company shall be prepared.
Summary of APQR shall be discussed in management review
meeting.
Any adverse observation made in APQR, proposed CAPA and
action plan shall also be discussed in MRM.