An increasing percentage of pharmaceutical industry revenue is derived from collaborations, copromotions, acquisitions, and
licensing arrangements. For example, one major pharmaceutical company recently reported that more than 64% of its 2010 revenue
was attributable to alliance products. Partnerships and alliance management are now considered essential to growth strategy.
Although the scope of this article is limited to in-licensed products, and focuses on development of chemistry, manufacturing,
and controls (CMC) and technology transfer, the principles described can be applied to any partnership and technology-transfer
activity between two or more companies. This article is written from the point of view of a US-centric company and development
of CMC for FDA submission, and assumes that the due diligence performed using multifunctional teams was comprehensive and
that gaps relating to CMC were identified properly. It does not delve into details of CMC requirements that can be found elsewhere,
such as FDA and International Conference on Harmonization (ICH) websites, but provides a high level view of partnership management
leading to successful technology transfer and CMC package development.
The technology transfer and CMC development of an in-licensed product can take several shapes with varing levels of complexity.
Some of these arrangements can be broken down as follows: codevelopment of CMC and manufacturing at licensor's facility; codevelopment
of CMC and manufacturing at licensee's facility; technology transfer of a developed product from licensor to licensee with
product being manufactured at licensee's facilities; and technology transfer of a developed product from licensor to licensee
with product being manufactured at a third party contract manufacturing organization (CMO). Although different, these arrangements
can be brought to successful fruition using similar management techniques. This article addresses the important aspects of
successful process management, common pitfalls, and recommended best practices in this regard.
For the purposes of this article, let's consider an aseptically filled liquid product. A typical CMC package includes critical
and noncritical components. Critical components are defined as those documents that require tangible laboratory data. Non-critical
components are defined as documents that are purely administrative in nature and do not require data generation in the laboratory.
Some components of a typical CMC package are below.
- Product development report
- Analytical method validation package for active pharmaceutical ingredient (API), excipients, and finished product
- Container-closure selection
- Master and executed batch records
- Exhibit batch stability reports
- Microbiological validation, including aseptic filters
- Aseptic-fill validation package
- Labeling information.
- Applicable FDA forms
- Drug master file (DMF) approval letters from API and excipient manufacturers
- DMF approval letters from component manufacturers
- Establishment information for drug substance and drug product manufacturers
- Establishment information for outside testing laboratories.
One of the most important and often ignored aspects for successful CMC package development is a well written and comprehensive
development agreement. The agreement defines the scope of a partnership, the legal framework, expectations and deliverables
of each party, and any monies involved. The agreement between parties is the most important document that defines the path
of the relationship. It should be well thought out with clearly defined objectives, deliverables, timelines, and responsibilities.
If possible, regulatory and manufacturing departments should be involved in the development of deliverables as they relate
to CMC, basing them on regulatory requirements. In addition to legal and financial information, a good agreement should contain
the following CMC development and management points:
- Licensing terms
- Technology-transfer process
- Detailed project deliverables
- Companies responsible for each of the deliverables
- Timelines for the deliverables (and corresponding payments)
- Risk-bearing responsibilities
- Termination procedures, which can occur for several reasons including successful outcomes.