CPV:

Let’s Foster Quality

Nov 2020
 CPV: Let’s Foster Quality
With almost one decade already, the 2011 FDA Process Validation Guideline
marked a shift in the Process Validation scene.

The traditional, rather static and compartmentalized, approach was replaced

by a dynamic Product (and Process) lifecycle one comprised of 3 stages:
• Stage 1: Process Design
• Stage 2: Process Qualification
• Stage 3: Continued Process Verification (CPV)

From the beginning, and across the industry, the 3rd stage was often
interpreted simply as a renaming of the Annual Product Quality Report
(APQR). The two serve different purposes and one does not replace the
other!

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 CPV: Let’s Foster Quality
CPV consists in establishing a program to assure the state of control is maintained throughout the product life cycle with
an evaluation of the relevant tendencies in the process.
APQR on the other hand, is a complete quality periodic review of a product and process aiming to confirm the validate
status of it.
Unlike the APQR, the CPV requires a well establish system for detecting drifts promptly so one can anticipate a shift in
quality.

The CPV data and assessments can be used to complete the

A CPV program is about: applicable APQR report sections, thus avoiding duplication and
promoting real continuous improvement leading to higher quality.

Actions

Data
Analysis

Monitoring

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 CPV: Let’s Foster Quality

Establishing a CPV program

The basis for establishing a CVP Program depends on whether the CVP is to be performed for a new product/process or an
existing (legacy) one.
• For a new product, the CVP is based on the knowledge obtained during Process Design and PPQ/PV by evaluating the
variability in the different CQAs due to the CMAs and CPPs. The suitability of the control strategy defined in Phase 1 is
reviewed and the sampling level for each parameter/attribute (increased or decreased) is defined with respect to the
previous phases:
1. Monitoring: A monitoring program for the relevant parameters to be recorded must be defined, specifying frequency
and establishing how and with which system this data will be acquired. Knowledge of the process is key to determine
what to monitor and at what stage, to ensure process variability is detected which could increase risk for the patient.
The Monitoring Plan does not have to be the same for all products or for all measurements of a given product.
2. Data analysis: When, how and by whom it is to be carried out must be defined.
3. Actions: What actions will be carried out if any of the parameters do not meet or trend away from the established
criteria must be defined.

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 CPV: Let’s Foster Quality

Establishing a CPV program

• For legacy products where CVP will be established for the first time, it will be based on prior knowledge from the years
of commercial manufacturing including the initial PV prior to product launch. In some cases, the validation was carried out
before the new process validation requirements were established with a level of developing appropriate to the regulation
of the time, but in many cases, not sufficient for current regulatory expectations and industry standards. On many
situations a systematic classification of process parameters was not performed so to allow a proper CPV program
definition. The methodology used for this products shall be the same as in Phase I but replacing the knowledge acquired
when developing the process with the experience and knowledge gained during the product commercial history.

Conclusion
Stage 3 of validation is not only a regulatory requirement but essentially of interest of producers and patients.
The solid establishment of CPV promotes an enhanced knowledge gain on product and process which fosters Quality and
creates value for the manufacturer. The large amount of data but specially its adequate analysis and use allows to
proactively act on the process and assure reliable and compliant supply of excellence products.

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 CPV vs APQR: Let’s Foster Quality

References:

1. EudraLex Volume 4. “Good Manufacturing Practices for medicinal products for human and veterinary use. Annex 15. Qualification and Validation”. 2015.

2. EMA “Guideline on process validation for finished products – Information and data to be provided in regulatory submissions”. 2016.

3. FDA “Guidance for industry process validation: general principles and practices”. 2011.

4. ISPE “Good Practice Guide: Practical Implementation of the Lifecycle Approach to Process Validation”. 2019

5. Alves, Andreia F., et at, 2020 “Case study: Life Cycle in process validation. Continued Process Verification” in Azbil Telstar, available in https://www.telstar.com/wp-
content/uploads/2020/06/Case-Study.Continued-Process-Verification-3.pdf

6. J. Gampfer, “Principal Approach to CPV” in Baxalta, available at https://cdn.ymaws.com/casss.site-

ym.com/resource/resmgr/CMC_No_Am_Jul_Spkr_Slds/2015_CMCS_GampferJoerg.pdf

7. Pazhayattil, A. et al, 2020, “Put your Continued Process Verification (CPV) Data to Work” in Pharmaceutical Online available in https://www.pharmaceuticalonline.com/doc/put-your-
continued-process-verification-cpv-data-to-work-0001

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 Thank you
Nuno Santos
Business Unit Manager Pharma
nuno.santos@stepwiseengineering.com
www.stepwiseengineering.com