Packaging is the art of science and technology of preparing products for sale in a cost effective manner. With respect to pharmaceuticals, packaging is a key component of the product and must preserve the product from environmental degradation or contamination, contain the product securely in order to avoid leakage, identify the product from its pack and thereby provide traceability, provide security against tampering and counterfeiting of the product, provide to the patient the information on use for compliance, provide convenience in use of the product for medical staff or patient. All these things must be ensured for the life of the product and achieved within a complex regulatory environment. To carry out a meaningful packaging validation following are key areas which have impact on the robustness of a packaging process.
Packaging Validation in Pharmaceuticals
- Packaging validation is establishing documented evidence, which provides a high degree of assurance that a specific packaging process performed, will consistently produce a pack, which meets predetermined specification.
- Packaging process validation is performed when new product is being packed for the first time on existing packaging line, using current or new packaging material. Packaging process validation should start with preparation of protocol called Validation protocol.
1. Validation Protocol
Short description of the process with a summary of the critical processing steps or critical parameters to be monitored during validation. Additional testing intended to be carried out e.g. with proposed acceptance criteria and analytical validation as appropriate. Sampling plan: where, when, how and how many samples will be taken. Details for recording and evaluation of results.
2. Types of Testing
- Toluidine Blue Test: for detecting seal leaks in porous medical packaging by dye penetration.
- Visual Inspection Test: for determining integrity of seals packaging by visual inspection e.g. of defects: unsealed areas, non-homogeneous area,
- Immersion Test: sample is placed in a container filled with water for 20 sec., it is verified that no air bubbles escape from the sealing or the packaging.
- Accelerated Aging: packaging samples are placed in the thermo-regulated chamber at 55°C for accelerated aging. During the whole aging time, temperature of the chamber is monitored. After aging, the packaging are tested.
ALSO READ: SOP for Concurrent Process Validation
3. Film Delivery (PVC Sheet)
Heat treatment to PVC sheet Blister forming from PVC sheet Filler- Tablet filling to blister Sealing of blister by alluminium foil Cutting of blister Rejection system Secondary Packaging Printing labeling details on Alluminium foil Alluminium foil Delivery.
4. Blister Packaging Operation
Critical Parameters: Optimization of temperature, Packaging machine speed optimization , Verification of film forming and sealing temperature, Verification of packaging machine speed, Efficiency of tablet feeder , Blister formation inspection system efficiency, Printing efficiency, Blister cutting efficiency, Blister counting efficiency
5. Secondary Packaging:
Primary packaging Delivery Cartonner Closure / Sticking Outside labeling, Product passed Carton, Delivery Leaflet Insert, Delivery Visual checking system, Visual checking system
6. Check Weighing & Check Weigher
Primary and/ or Secondary Packaging delivery , Product weight verification
Packaging Process Overview
- The product must be clearly understood and defined
- The product maybe the drug product or the drug package that protects the drug product from damage, contamination or spoilage
- Packaging implications must be evaluated for risk to both the drug product & drug package
- E.g in what way can a secondary operation packaging operation cause potential damage to the secondary package and/or the primary package inside? Is a drug package defect cosmetic? Which may lead to customer complaints (Business Risk), or does the defect introduce risk to the drug product (Consumer Risk?)
- Success or failure of a packaging process is determined by, the drugs package defects( tears, holes, smudges, or leaks)
- Two approaches: Equipment Validation lifecycle approach to packaging & Process Validation Lifecycle approach.
ALSO READ: Process Validation Protocol for Parenteral
Developing a Product Matrix
- Understand the breadth of formats the Validation will cover
- Format: combination of different drug/Package attributes and equipment/Process parameters, that combined form a packing process
- Packaging formats are Bracketed to improve efficiency of validation, not good to use method if theres limited knowledge on the product or process
Number of Batches
A risk analysis should be used to determine the number of batches required. Some of the factors that a Risk Analysis should focus on:
- Experience and understanding of the product and process
- Complexity
- Impact to patient
- Level and Length of PQ
- Knowledge of similar line/Equipment/processes
- Evaluation of exposed product hold time studies
- Good packages are produced, and primary dosage unit is preserved( i.e unit not damaged during packaging)
Since the aim of the packaging process validation is to demonstrate a robust process, the control strategy should detail and manage the level of variation from product and process inputs, including, for example, the number of operators, different shifts, and different sources, batches of input materials. The potential variation in these examples could be controlled, by a robust operator training program, and the material variation controlled with tight tolerances detailed in controlled and approved material specifications.
A low risk product/process may need only one batch validation, if very similar to an existing packaging process is used, whereas, a product/process with a high residual risk may need several batches.
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