PAT Guidance Will Draw From Existing Electronic Records Guidances

FDA plans to draw from existing guidances to clarify 21 CFR Part 11 electronic record/electronic signature requirements in its planned PAT guidance.

"We plan to adopt and/or refer to some of these in the [process analytical technologies] guidance," FDA Office of Pharmaceutical Science Deputy Director Ajaz Hussain, PhD, told the agency's Pharmaceutical Science/PAT Subcommittee Oct. 23.

The Process Analytical Technologies Subcommittee met to discuss FDA's planned draft guidance on PAT and Part 11 issues. It was the subcommittee's third and final meeting before it is replaced by a new manufacturing subcommittee that will address broader manufacturing issues.

Hussain noted that several guidances for computer systems validation exist. Guidances within the Center for Devices & Radiological Health include "General Principles of Software Validation," "Guidance for Off-the-Shelf Software Use in Medical Devices" and "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices."

The International Society for Pharmaceutical Engineering has also issued "Good Automated Manufacturing Practice" guidances to help FDA-regulated companies achieve Part 11 compliance.

"I think clearly the consensus was that we should draw on existing guidances for Part 11," committee member Arthur Kibbe, PhD, Wilkes University, said. "I think that's well-founded and well-accepted criteria."

FDA is expected to issue the PAT draft guidance by the end of the year. The guidance, which is expected to be five to six pages long, will address how data points are compiled and validated and will provide a "conceptual framework" for industry, Hussain said.

The draft guidance is expected to include a "safe harbor" research exemption provision to ensure that firms will not be penalized if they observe variances in their data using PAT.

"The protocol would simply be that they are collecting the data as research data and all regulatory decisions will only be based on the established regulatory methods so they won't have an impact," Hussain said.

Committee guest Kenneth Morris, PhD, Purdue University, added "with the research exemption and the fact that there are other compendia test on the release, we should embrace these variances as other methods of getting the information and clearly we would like to have [it] in order to control the processes."

"What underlies all of this is that in the development stage, or at least at some point, the process critical control points have to be identified, as well as how you're going to monitor those" points, Morris said.

Companies also are concerned about the amount of data they will be required to archive under Part 11. PAT allows continuous monitoring of manufacturing processes, and if raw data are collected, companies will need to maintain it.

"We are collecting relatively large amounts of data," Bristol-Myers Squibb Associate Director-Quality Glenn Thompson said. "There are certainly expectations around that, not just to hold it but to reprocess it...over time."

Pfizer Manager-Process Analytical Support Group Steve Hammond noted "PAT will take significant resources to implement and if validation is not handled very carefully, it will slow it down, it will stop it."

"Compliance with Part 11 will probably become a way of life....[Currently] it is a serious anchor that we're dragging along with development of PAT. This is not just an FDA issue, it is a problem within our internal regulatory groups," Hammond said.

Attendees at the Consumer Healthcare Products Association Manufacturing Controls Seminar voiced similar concerns and asked FDA to carefully consider what must be validated under Part 11 (¹ (Also see "FDA Risk-Based Part 11 Proposal Expected By February 2003" - Pink Sheet, 21 Oct, 2002.), p. 4)

The agency also is in the process of training its PAT inspection teams. Three universities are concurrently developing a training curriculum for PAT inspectors (² (Also see "FDA PAT Inspection Teams Being Formed: Further Training Set For Fall" - Pink Sheet, 22 Apr, 2002.), p. 23).

Kibbe suggested the agency "cross-train internal review staff and external inspectors, so...the inspectors know what [the reviewers] have written about, and the inspectors [who] see things - the reviewers will know what they have seen."