Packaging Process Validation

I’m looking for a guidance document on Packaging Process Validation.
I’m also looking for requirements on Matrixing and/or Bracketing of Products

Has anyone done a Packaging Process Validation before?
What I am talking about is “Packaging Validation run that is representative of a typical packaging process and be of sufficient lenght such that the packaging validation run will exhibit normal packaging process variability such as equipment variability, operator and mechanic variability, start-ups, shut downs, shift changes and environmental conditions”.

I am looking to the same info.
I have performed several audits on packaging lines for different CMOs and most of them always did some form of bracketing of parameters.
The company i am currently at do not bracket and I believe bracketing to be a time saving, risk based, and lean practice, however I haven’t found any guidances to implement it. (as an auditor, i just agreed it was compliant, but now I have to design it and would like a little bit more info).

All I found at the moment is this:

Please let me know if you find anything else, and I will do the same.

Thanks Rina120 for the link. I’ve search the internet and I can’t find any article or regulation or guideline on this subject.


[b]Select appropriate package material and design, qualify equipment, validate sealing process, produce test samples

Perform burst test, peel strength creep test on both sterile and non-sterile:
non-accelerated aged product

Place an appropriate number of samples into accelerated aging for the
required period.

After aging, the packaging is tested for physical testing. Device samples
are tested for material problems and whether or not they meet product

A portion of the accelerated samples are culled for transportation simulation tests: ISTA /ASTM shipping tests.

Packaging samples are tested for physical parameters as above. A visual
exam is performed to look for holes caused by vibration testing. Device
samples are tested for specification requirements.[/b]

[COLOR=“black”]Combinatory products require strict adherence to ICH guidelines for stability of the drug/biologic throughout the shelf life of the product. For products that have a delivery system (such as needle-less injection systems), storage and shipping parameters are critical to maintaining required potency. For other products that have a drug coating or scaffolding application, the validation program requires a unique perspective into both medical device shelf life studies and ability of the drug/biologic formulation to maintain stability throughout all phases of the manufacturing and sterilization process. Formulation issues are very important prior to FDA filings, and these considerations will be a major portion of the final regulatory filing.

Packaging testing guidelines are listed in ISO 11607. This document describes the available ASTM packaging tests. It also brings together many other key aspects of packaging validation (i.e. material qualification, validation of seal process, whole package seal integrity).

Cell therapy products such as xenografts, allografts, and stem cell products create unusual challenges for the package validation engineer. The FDA offers very little guidance on these issues. Cells must be able to withstand shipment and storage during a finite, defined period. Evaluation of cell lines and tissue implants during a stability program is required prior to FDA submission.[/color]


[COLOR=“darkred”]• Bacterial /fungal/ mycoplasma sterility testing (USP sterility and FDA mycoplasma test)
• Viral sterility test (FDA virus assay)
• Particulate test (USP)
• Cytotoxicity (USP)
• Container integrity testing (MBD immersion test)
• pH analysis
• Buffering capacity (container) USP
• Leachate testing (container) GC/MS analysis[/color]

Thanks for this:

I will have a look.

ASTM guide lines :

[b][COLOR=“blue”]F 1980-07

D 737-04



T 437-OM-96


F34-02 (2007)

F392-93 (2004)

F2228-02 (2007)

D1434-82 (2003)

F1929-98 (2004)


T483 cm-02

F1608-00 (2004)

D726-94 (2003)


F1306-90 (2008)




Hi Durga Prasad, thanks for all the posts but can I ask that you provide me a link to the ASTM guide lines? It would be great to have a look at all those references you posted.

ISTA Guideline attached

ISTAGuidelines.pdf (144.4 KB)

May I ask Durga Prasad, have you written a protocol/report for Packaging Process Validation or executed a Packaging Process Validation?
Or have you reviewed or viewed a Packaging Process Validation Protocol or a Validation Plan for Packaging Process Validation?

I have written , reviewed and executed Packing validation protocol when I was working as an employee and as consultant.
If you have questions you can mail in to me in the blog mail or post it here. I can help you to the best possible I can and also take help from my friends who are working in various places across the globe having exposure to various documents and regulatory agencies.

Let me tell you one more aspect about this subject matter. The situation & complexity of protocol varies from pack to pack and type of product to other products.

What we need is a set of testing parameters, design specifications, packing specifications and exuction of them, retesting them both inline and offline as stability programme.

Most of the people often either ignore or forget validating a parameter called " Shortest time required for packing". This is based up on the scale what is transferred from pilot scale is done during the first 3 production runs. You can also write the packing problems encountered and execute the manipulations done in the document and really look how it reflects on to Packing Quality.

May I ask you one question.

Do you have Packing Specification Quality Manual in place? If its not there please start developing that before you start this validation process.



No Packing Specification Quality Manual in place, can you elaborate more on this as this subject matter is very interesting for me. I appreciate all the help I’m getting from you.
Would it be possible if you can email me an outline or headings that is in a Packaging Specification Quality Manual?

Scope Of Manual
Quality guidelines you follow
What regulatory Guides you follow-ASTM/ISTA/ISO/ISPE/MCA/MHRA/USFDA/EMEA-Anex15.?
Quality control checks you execute?
What are tests for packing material and release of packed materials
What should be the proper outcome of such packing
How do you handle inprocess packing checks
How do you handle packed materials during shipping
How do you take packing complaints?
What is packing flow of Raw materials and packed materials–Flow sheets
Approval processes- flow sheet
How do you recall if you have packing problem?Responsibility flow chart too must be added.
Who heads the packing Quality?

This is very latest development we have done for a EU based company making Biological products. You can effectively use this.
If you have enough faith show to Mr.Graham first-- Probably he can guide you on GAMP-5 inclusion in packing lines --this is very essential. Iam no expert on GAMP-- i BELIEVE ITS VERY ESSENTIAL AT THE MOMENT.


[COLOR=“black”]I. The Company Overview
II. Structure and Format of Quality Manual
III. Packing Quality Policy and Objectives
IV. Organizational Structure
1.0 Management Responsibility
2.0 Quality System
3.0 Regulatory Guidelines
4.0 Contract Review
5.0 Design Control
6.0 Document and Data Control
7.0 Purchasing Control Procedures
8.0 Control of Customer-Supplied Product
9.0 Product Identification and Traceability
10.0 Process Control & In-process Checks
11.0 Inspection and Testing
12.0 Control of Measuring and Test Equipment
13.0 Inspection and Test Status
14.0 Control of Nonconforming Product
15.0 Corrective and Preventive Action
16.0 Handling, Storage, Packaging, Preservation and Delivery
17.0 Control of Quality Records
18.0 Packing Complaint handling & Recalls
19.0 Packing responsibilities and Qualified staff
20.0 Lables & Inks ( Regulatory perspective)
21.0 Internal Quality Audits
22.0 Training
23.0 Statistical Techniques
Quality Manual Revision History
Appendix 1 - ISO 9001 & ISO 11607 [/color]

[b][COLOR=“deepskyblue”]Table of Contents
The following standard test methods, specifications, practices and guides are included in the Sterilization Packaging Manufacturers Council Standards.

Standard Test Methods
Average Peel Strength Value of Flexible Barrier Materials
Maximum Seal Strength Value of Flexible Barrier Materials
Burst and Creep Package Testing Using Internal Pressurization
Seal Integrity Dye Penetration Method
Detection of Leaks in Heat Seal Packages Internal Pressurization Method
Seal Integrity Visual Inspection Method
Determining Porosity of Flexible Packaging Materials: Gurley Densometer Method
Coating/Adhesive Weight Determination
Linear Measurement Using Precision Steel Rule
Thickness Measurement of Flexible Packaging Materials
Standard Specifications
Dimensional Tolerances of Sterilizable Pouches
Standard Practice
Preparation of Flat Bar Heat Seal Specimens of Flexible Packaging Materials
Evaluation of Chemical Resistance of Printed Inks and Coatings on Flexible Packaging Materials
Ink or Coating Adhesion to Flexible Materials Using Tape
Standard Guide
Guide for Design and Evaluation of Primary Packaging for Medical Products [/color][/b]

Please tell me,do the same machine have to be validated for different pack sizes?

I strongly believe and suggest that these should be validated.
The reason is pack size changes with weight, capacity and volume of packing material.
The final packing material either for tablets or capsules or powders gives the utmost stability to these products.
When you change the packing size this results in changes in certain settings as per standard packing dimensions.
This results in a way change control.
So as the settings changes it might attract a validation to prove the effectiveness of packing that makes product stable during transport and handling before it reaches the ultimate user.

There are many casses recently due to packing problems millions of dosages were recalled by FDA in US.
Packing is not just a cosmetic thing. It gives so much stability to product.


thanks for reply, i wanted to ask that can i proceed my packaging validation in the following way or should i have to add something else in it.please give me

  1. Qualification of Strip Sealing Machine
    Design Qualification
    Installation Qualification
    Operational Qualification
    Performance Qualification
    2… Product Packaging Operation Validation
    Product Detail
    Packaging Material Specification
    Risk Analysis
    Preparation of Packaging Validation Experimental Plan
    Performance of Plan

pls reply on project on packaging validation of pharmaceutical products on strip sealing machine