Contract Services

Product & Process Transfer of Low Solubility Compound with 6 year OTIF>95%

Summary

Alkermes, through the merger with Elan Drug Technologies, to form Alkermes plc, has been developing and manufacturing commercial scale solid oral dosage products for over 40 years.  This case study demonstrates the successful transfer of a low solubility compound into one of our manufacturing sites and achieving as a result, an OTIF (On-Time-In-Full) consistently over 95%.

Product History

Donor site closure required transfer to be completed in a short time frame. During this entire process, the product had to remain commercially available for the partner.

Why was Alkermes Contract Pharma Services Chosen?

The manufacturing capabilities at Alkermes were chosen as they met the donor site’s requirements of experience and expertise in working with low solubility compounds developed using the company’s proprietary NanoCrystal Colloidal Dispersion^® (NCD) technology. The manufacturing capacity afforded by the Athlone Ireland facility, together with its excellent compliance record supplying product from an FDA/EMA inspected site, fulfilled all the criteria required to successfully tech-transfer this product into the facility. 26 products have been manufactured at the Athlone site since the 1970s, the majority of which are solid oral dosage forms.

The Challenge

Specific challenges to the project, which was the first commercial launch using the NCD technology from Athlone, included:

• Setting up of on-site commercial systems for the NCD process as, prior to this project, only clinical batches had been manufactured
• Training of manufacturing staff as, although the site had previously used milling equipment required to manufacture the product, site knowledge was limited on this commercial system
• Introduction of new commercial technology across site functions
• Establishing new test methods at site and training of associated laboratory staff
• Transferring the process to predominantly like-for-like manufacturing equipment in order to minimize regulatory impact
• Set-up of required low bio-burden processing practices and systems
• Minimizing number of transfer runs using API due to material cost constraints.

Alkermes’ Athlone Site

Located on a 40-acre site, with over 220,000 ft² of dedicated cGMP grade facilities, this site has a proven manufacturing track-record with many products optimized and manufactured for partners in multiple territories. The facility has an equipped annual capacity of two billion solid oral doses. The Athlone site is an FDA/EMA inspected facility.

The Result

A number of significant achievements resulted from our involvement with this project. A robust technology and process transfer was achieved in 18 months.  Training of staff was successfully managed which was a key component to achieve the successful manufacture of this product at commercial scale.  The commercial partner was kept involved at all stages of the project which was critical in ensuring un-interrupted customer supply during the transfer process and minimization of regulatory changes.

Key activities in successful execution of this project included:

• US (donor) to Ireland (recipient) site : site transfer
• Systematic Tech Transfer process with defined work flow applied
• Initial technical review focusing on donor : recipient process assessment, aimed at identifying gaps at recipient site through comparison matrix
• Joint transfer team convened and transfer program agreed
• Ongoing project management executed through combined site and partner project team
• Technology implemented at site - Primary areas: process equipment, manufacturing systems and analytical methods
• Process characterization and engineering runs executed at site for comparison assessment
• Demonstration batch executed against pre-defined acceptance criteria for confirmation of successful transfer
• Registration batch manufactured within 6 months of transfer initiation
• Successful FDA PAI executed and validation batches initiated within 12 months of transfer initiation.

As a result of the successful tech transfer, the partner’s product was manufactured at full capacity for more than six years, consistently delivering OTIF in excess of 95%.  This transfer brought the site to a more competent place allowing the site to confidently take on further commercial NCD tech transfer projects.

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