Mr. Brian Hilton: Welcome. My name is Brian Hilton, Production Manager with Almac Clinical Services. Within this segment, we will evaluate the many challenges associated with blinding
Inhalers where physical differences are so extreme making blinding difficult to achieve, modifications of the inhalation device or using the same device for both treatments is not always feasible because the inhaler plays such a critical role in the disposal and subsequent action of the active ingredient into the airwaves
Just as there are many differences in the size and shape of solid oral dosages [sp], so too are there many variations in inhaler devices, as detailed here. It is these variations that present the pharmaceutical industry with so many challenges when needing to blind
Processing of inhalers may require the removal of labels, embossed details and/or ink markings
Additional blinding considerations focus on the need to closely mimic the canister pressure at time of actuation, the sound, the taste and the potential residue remaining around the mouth after inhalation
Blinding considerations may include delaying of an embossed print code, dismantling of the unit, including removal of all product labels to convert an active inhaler to a placebo inhaler. This may also include the breaking down and washing of inhalers under local exhaust ventilation
Accuhalers and Turbuhalers pose just as many challenges to the blinding process. During unit conversion, specific equipment and detailed processes may allow for the removal of the active product and reassembly of the unit now containing a matching placebo
Depending on your protocol design, blindness may not always need to be taken to the inhaler unit. Blindness may simply be maintained through the addition of study labels or assembly of units into sealed pouches or cartons
During unit conversion, modified blistering equipment is used to assemble matching placebo products. Each aspect of the unit conversion is monitored through in process and quality control checks to confirm seal, functionality and weight
Subsequent slides illustrate the unit conversion process
Blinding of Turbuhalers may require the overlay link of a printed component with blinding label or using an acetone to remove printed text
During the blinding process, contents of each inhaler are removed and weighed followed by a dismantling into each component part. The components go through several wash cycles using a series of methanol baths and Sonicators
To confirm the component wash removed all active residue, a sampling of the components is performed. Units may then be reassembled with placebo backfill matching the original weights
Continuing the trend, blinding of syringes, vials and patches provide significant challenges with even fewer viable solutions
Although it is feasible to disassemble a syringe to change out a portion of components from the original assembly, challenges still exist in regards to barrel style, product color and fill volumes
Similar challenges also hold true when working with vials and ampoules. Various sizes, shapes, fill contents, cap colors, embossings, vial wall densities, storage conditions each poses their set of blinding conflicts
A number of proven blinding methods would allow for the removal of the commercial label, removal of the print applied directly to the unit and/or a restriking [sp] of the print for complete obscurity. Additionally, application of a shrink wrap over the vial would allow for the fill content and color to be maxed
Variances in pouches include ink jet codes applied directly to the unit, tear notch assist, which is the opening feature of the pouch, as well as the seal area around the perimeter of the pouch
Pouches that are similar in size may be fully encased with any stud label for complete blinding of the units
Variance in tubes include tube size, any ink jet or embossed codes applied directly to the unit, the crimp thickness at the base of the tube as well as cap styles
Due to the limited options for blinding, it is recommended that you contact your packaging contractor for viable solutions
Within the labeling and compilation, we will explore the considerations needed during final packaging to maintain blindness
It would be pointless to have taken every precaution of maintaining blind with previous operations only to have variances in labels and/or general components on blinded study. Blinded study should provide consideration to variations in label stock, including the adhesives, the transparency of label if being used to urva [sp] label and existing label as well as label backing and/or color differences between the label stock
Considerations should also be provided to label profiles including the font style or size, the print boldness, the print indentation as well as any stray print marks
Ongoing challenges will often be present at any phase of the clinical packaging. It is the ability to recognize these differences and the precautions put in place to limit the chance of unblinding a clinical trial
Master samples are taken at the first receipt of any raw material type and are referenced as the blinded sample upon inspection of subsequent lots of that same material type
For blinded samples and first unit assemblies, a sample unit is created in the first operation of each campaign. The same unit will be used for direct comparison in subsequent operations
Packaging contractors may utilize design layouts and labeling templates to assist in providing consistency across all operations within a campaign
Routine inspections are performed by production and quality personnel, ensuring correctness of unit assembly, label placement, patient kit collations and blindness checks. Thank you.