Pharmaceutical Validation

Monday, August 18, 2008

Packaging Process Validation

Packaging process validation is often supplemented by 100% inspection online. Many firms take the approach that a 100% online inspection is the way to go. Even today, many companies have inspectors set up offline to sort out or rework unacceptably packaged product. Often, process variables are not adequately studied or the process is not observed to “nail it” through process validation. The following approach used by a large pharmaceutical company to validate the blister packaging process may shed some insights on how Design of Experiments (DOE)—prior to packaging validation—can help.

This case study is about an OTC product. The product launch date was set in stone; the marketing managers were even talking about pre-launching the product to select large-scale retailers. The operations team was under tremendous pressure to finish the process validation and pre-launch activities of this OTC product. The product was a coated tablets, the packaging put-up was a carton with three blister cards, each card with eight tablets per card, making it a pack of 24 tablets.

The team consisted of a Packaging Engineer, an Operations Engineer, a Production Manager, a Quality Engineer and a Project Manager. Traditionally, the company validated the packaging process by optimizing the packaging process variables and making three runs. A statistically valid sampling plan would be implemented and sample packages would be tested per the finished product specifications. In most cases, this approach worked. But this was not one of those usual projects.

Let us look into the specifics. The package design required the patient to peel the foil by holding on to a center tab. See Figure 1, which shows an example of the four-way notch at the center tab. Since the product was geared towards the elderly, the package design presented some unique challenges. A trial run was performed and some samples were shown to marketing. While the overall package quality in terms of appearance and integrity was fine, Marketing thought that the package was simply too hard to open.

View Full Article

Author(s):

Shamik Pandit

Journal:

CONTRACT PHARMA December 2004.

Validation of Spectrometry Software: Risk Analysis Methodologies for Commercial Spectrometer Softwa

In the last "Focus on Quality" column (1), I noted that the risk analysis methodology used in the GAMP Good Practices Guide for Validation of Laboratory Computerized Systems (GPG) (2), which was based upon failure mode effect analysis (FMEA), was too complicated. The rationale was that we purchase mostly commercial software in regulated laboratories that already has been tested by the respective vendor. Therefore, why do we need to potentially repeat work that has already been performed?

Before we begin this discussion, it is worth mentioning that I have written a paper on risk assessment at the system level, and determination of how much validation is required has been published recently by Advanstar Communications (3). This publication looked at the nature of the software used in the system and the impact of the records produced by the system to determine how much validation was required. The outcome if validation was required was one of two options: Full validation based upon a system implementation life cycle when the detailed steps to be undertaken are defined in a validation plan for the system. Lower-risk systems could be validated using a single integrated validation document that defined the intended use, security and access control, compliance issues, and preservation of the records produced by the system.

View Full Article

Author(s):

R.D. McDowall

Journal:

Spectroscopy, Jul 1, 2006

A Compliance Perspective on Dissolution Method Validation for Immediate-Release Solid Oral Dosage Fo

As the pace of product development accelerates, the approach to dissolution-method development must advance beyond a manual method and an assay. A natural progression of the method-development process must include the transfer of the manual method onto automated instrumentation.

Author(s):

David Fortunato

Journal:

Pharmaceutical Technology, Sep 2, 2006

Aseptic Process Validation

What are the regulatory pressures facing aseptic process validation today and what will they be like over the next few years? An inquiry into existing literature and with current industry personnel reveals a corner of the pharmaceuticals industry driven by a lattice of suggested improvements, a constant hum of activity and improvements that fight to keep pace with general industry trends and emerging technology. Those working in aseptic processing validation must consistently look five years ahead and five years behind, at rules and informative processes and market realities, all of which play off one another like so many strings on a musical instrument. With an important FDA guidance revision just now beginning its long fade into routine and a brand new one described as imminent, aseptic processing and its regulatory outlook is at the forefront of pharma and biopharma business plans.

Author(s):

Tom Spurgeon

Journal:

contractpharma November / December 2006 .

Validation & Compliance: Using Risk Analysis in Process Validation

Process validation is used to confirm that the resulting product from a specified process consistently conforms to product requirements. A risk-based approach to process validation provides a rational framework for developing an appropriate scope for validation activities, focusing on processes that have the greatest potential risk to product quality. This article presents a case study in which a risk-based approach was used to evaluate a typical mammalian cell culture and purification process. This risk assessment used a Failure Modes and Effects Analysis (FMEA) to evaluate the impact of potential failures and the likelihood of their occurrence for each unit operation. Unit operations included in the process validation required a risk priority number greater than or equal to a specified threshold value. Unit operations that fell below the threshold were evaluated for secondary criteria such as regulatory expectations or historical commitments.

Author(s):

Leslie Sidor, Paul Lewus

Journal:

BioPharm International, Feb 1, 2007