Asessing Risk in Biopharma Raw Materials: Actuaries Wanted?

Adventitious agents—from viruses and Mycoplasmas to bacteria and fungi—require serious risk assessment on the part of the biopharmaceutical manufacturer. And yet “often people who do the risk assessment don’t have a background in adventitious agents," says Barbara Potts, PhD, senior consultant with Potts and Nelson Consulting and also the head of PDA’s Mycoplasma task force. Potts was presenting on “Risk Assessment and Management for Adventitious Agents in Raw Materials Used in the Biopharmaceutical Industry,” at the recent Biopharmaceutical Development & Production Week in San Diego.

To work around this dilemma, Potts proposes to develop something similar to the actuarial tables used by the insurance industry, to allow manufacturers to more thoroughly and accurately conduct risk assessments based on hard data and mathematical calculations.

“You could then locate a problem in the tables and identify risk.” She adds: “Then you can go to CFO and say, we need the money to build this type of facility.”

To help her in her work, Potts is looking for “volunteers who know nothing about virology but no how to develop and use actuarial tables.”

In the meantime, during her San Diego presentation Potts offered up some best practices in minimizing risks of adventitious agents:

Minimizing Risks of Transmission of Viruses
• Use raw materials that can withstand heat treatment, gamma irradiation or low pH.
• If using raw materials of animal origin:
  o use only animals designated for human consumption
  o a QA system must be in place for monitoring the production process and for batch delineation of animal raw materials
  o enhance traceability, self-auditing of supplies
• Put procedures in place to audit supplies of raw/starting materials
  o Audit for mouse presence at facilities, shipping, and storage—“Mice carry a lot of viruses, especially for MDM, and they always urinate,” she said.
  o Detect rodent urine with fluorescent light: Take UV lights to facility audits and shine them in corners. “If you see a trail you know there have been mice,” she said. “It’s such a cheap thing to do.”

Minimizing Risks of Transmission of Mycoplasma
• Use raw materials that can be heat treated, gamma irradiated or low pH treated.
• Assume that plant or fish sourced raw materials have a Mycoplasma risk.
  o Plants are a common host for Mycoplasma.
  o There are many Mycoplasma that infect fish.
• Do not assume sterilizing filtration for Mycoplasma with 0.1 micron or 0.2 micron filters is sufficient.
• Remember that Mycoplasma are very stable in a dried state (such as a lyophilized state). One QC lab that Potts worked with had dried Mycoplasma in pipetters, something it never thought possible.
• Remember that Mycoplasma are not detected in the traditional culture methods.
• Implement a rapid detection system to limit the impact of a Mycoplasma contamination.

Minimizing Risk of Transmission of Bacteria

• Use raw materials that can withstand heat treatment.
• Use validated sterilizing filtration
• Establish bioburden limits for unprocessed (peptones) raw materials to aid in monitoring the raw material process.

Minimizing Risk of TSE
• Use no raw materials of animal origin.
• If you must use animal raw materials, use porcine or equine sources.
• If using bovine raw materials, source from a country with negligible BSE risk (i.e., Australia and NZ).
  o Use only animals designated for human consumption.
  o Use tissues with no detectable TSE infectivity.
• Source from young animals.
• A QA system must be in place for monitoring the production process and for batch delineation of bovine raw materials
• Improve traceability and self-auditing of suppliers.
• Put procedures in place to monitor raw materials.

Finally, Potts advised the audience to never get too confident about outcomes or set in its ways. “Dogma is dangerous,” she said.

--Paul Thomas (@PaulThomasPharm)