FDA may ask firms to mail in process data after approval.

U.S. companies that do not have process validation complete on three full-scale lots at the time of approval might be asked to submit the data to the local FDA field district and might be told in the approval letter not to sell the product until the validation is complete.

Such requirements, already in place for several years with foreign inspections, is being instituted by various districts in an effort to avoid expending resources for reinspections, said New Jersey District Director Douglas Ellsworth.

Addressing the Sept. 12 PDA-FDA joint science conference in Washington, Ellsworth was caught off guard when a representative of Pharmacia & Upjohn (P&U) said she got such a letter, but for an animal health product.

"I'm not aware of that being done now," he said, referring to human drugs. "We're discussing that. I don't know if you can start calling it new policy, but in light of our resource constraints, we may be doing that a lot more. "

Under current policy, Ellsworth explained, if validation is not completed before approval, "the district will send a letter and ask them to notify us when the validation is complete so we can send someone out to do another audit." Until three lots are validated, the firm is asked not to market the product or else FDA will declare it adulterated.

For new uses to existing products "where the process hasn't changed, you should have process validation already established," he said. If a firm is making a new dosage form, "we're going to evaluate some of that process validation data." He elaborated by saying: "This may be through requests for data, or maybe we'll just base it on the fact the firm has done a good job in the past and we don't need to look at it again."

If firms are requested by letter to submit their process validation data post-approval, Ellsworth said his district, at least, would welcome it in electronic format, so firms do not have to do a lot of photocopying.

In the case of P&U, the letter requesting data on process validation by mail came from the Center for Veterinary Medicine headquarters, not the Detroit district, said Julia Sytsma, director of QA operations for Pharmacia's Kalamazoo, MI, facility.

She said only one lot had been validated at the time of the drug's approval and also noted it was a sterile product.

But FDA could still visit

Ellsworth warned firms that FDA could still come in for a reinspection of process data even after reviewing it at the office.

He also said the Center for Devices is considering changing its policy to allow firms to conduct process validation for premarket approved Class III devices after approval instead of beforehand.

However, Betty Collins, chief of the in vitro diagnostics branch, Center for Devices Office of Compliance, said Sept. 21 that she knows of no plans to change the requirement that process validation be completed before approval of a PMA.

For licensed biologics, however, FDA will still require validation on three lots before a license is issued, said Christopher Joneckis, expert biologist, Center for Biologics Division of Cellular and Gene Therapy.

But he noted that for supplements, which do not involve licensure, but "approval," there could be some leeway on process validation after approval, depending on the change being proposed and whether such data is really needed. Ellsworth gave no indication when districts would begin requesting firms mail in their process data.