COMPONENTS OF THE PACKAGE
The P&A-TP should define a process as it is to take place under GMP conditions at the scale desired. Written from pre-GMP
batch records and other documentation, it should fully describe process parameters. Further, it should be updated throughout
the process of the transfer until successful GMP manufacturing is achieved and, in the case of transfers for commercialization,
the process is validated.
Regardless of which party writes the final P&A-TP, or whether both parties create it together, the P&A-TP should include the
Process Description: Based on molecule and process knowledge accumulated during research and development, this description includes the sequence
of operations for the process, the rationale for each process unit operation, initial operating ranges for process parameters,
in-process controls, and initial acceptance criteria for the product. As the receiver conducts experiments and manufactures
test batches, the description will be revised to characterize the process in light of new knowledge. Companies often generate
a schematic representation of the process, generally referred to as a process flow diagram, that provides a snapshot of how
the process will be executed during manufacturing.
Equipment List: This includes details of the equipment that will be used at the receiver site to manufacture the product. Such a list is
always important, but it is even more important if the receiver's equipment differs from that of the donor and if scale-up
is desired. Changes in the equipment can be addressed during the execution of transfer protocols to ensure that product quality
is not affected by equipment change.
Bill of Materials (BOM): The BOM typically lists all raw materials and process consumables that will be used to manufacture the product. This helps
in identifying key attributes such as long lead-times for procuring the materials and consumables, amounts that are needed
for the specific manufacturing campaign, and special tests, if any, that need to be performed for acceptance.
Analytical Package: The analytical transfer is a separate exercise that occurs either in parallel or before the process being transferred. The
state of analytical method development at the donor site can severely impact the transfer and successful execution at the
receiving site. Typically, in early development, release assays (used to monitor product safety, identity, strength, purity,
and quality); stability-indicating assays are qualified and subsequently validated at a later stage (before process validation).
Although it is important to ensure that assays for release and stability are appropriately qualified, you should also make
sure that in-process assays (especially those that monitor titer) are appropriately developed and qualified.
Along with the process and analytical transfer package, it is essential to have a list of samples that will be pulled at different
process steps to be tested (for in-process, release, characterization, and stability), or stored as retains to support potential
investigations. As this list is compiled, it often turns out that the final amount of product available for preclinical or
clinical use may be much less than had been anticipated.
The P&A-TP should also be accompanied by other relevant documentation from the donor. This list should include development
batch records, process and analytical development reports, assay qualification reports, and test methods. Guidance from the
donor on process ranges and operating parameters as well as initial specifications are very helpful in compiling the development
of transfer protocols and batch records at the receiving site. Any information that is inadvertently not included in the initial
documentation may be obtained by interviewing the appropriate personnel at the donor site, documenting the interviews, and
adding appropriate information to the transfer documentation. Further, throughout the transfer process, both sides should
not only communicate fully and often, but also meet face to face. The personnel from the receiving site should become process
experts by visiting the donor site and, conversely, donor personnel should be present for initial runs at the recipient site.