When the FDA issued its draft process validation guidance document last November, I applauded the revision. "Old-style process
validation has finally died," I said in my December editorial. After reviewing some of the 45 comments that members of industry
have submitted on the draft, however, I now see that one important gap relates precisely to old validation—for products now
in commercial production.
In particular, several companies asked whether legacy products will require revalidation or increased process verification
during routine production. "It may be burdensome and unwarranted to apply some of the new expectations to legacy products
with a successful history of commercial production," Baxter noted in its submitted comments.
AstraZeneca also raised concern. "The [new] thinking is different and relies heavily on data generated early in the lifecycle
of the product which may not always be available for older products," the company's comment says. "This is particularly important
in light of the fact that retrospective validation is not recognised in the new guideline; it only references prospective
and rarely permits concurrent [validation]."
Indeed, industry should not be expected to revalidate processes for existing products.
Other comments submitted raise additional concerns that the agency should consider. An important one relates to the burden
of ongoing process monitoring. In particular, several companies said that the document's recommendation that sampling during
commercial production be conducted at the same level as during validation would be an unnecessary burden. "As more confidence
is obtained in the robustness and capability of the process, reduced testing should be allowed, if justified by the ever increasing
process knowledge obtained for the product," the Pfizer comments say.
Wyeth voiced similar concerns, saying that the recommendation to continue the same sampling and testing regimen after process
qualification is inconsistent with the application of quality risk management and scientific methods. "While heightened sampling
and testing may be appropriate, based on a risk assessment, it may not be necessary to conduct the same level as established
during qualification," the company said.
In spite of these concerns, the companies and organizations that submitted comments said they welcomed the revised guidance
and its reflection of the concepts outlined in the International Conference on Harmonization (ICH) Q8, Q9, and Q10 documents.
Several noted that the terminology, however, needs to be better aligned with that used in ICH Q8–Q10, and backed up by a glossary
to avoid confusion.
A much broader concern about consistency, however, was voiced by the Biotechnology Industry Organization (BIO). "We ask FDA
to ensure alignment within the inspectorate and review groups and between the review and inspectorate groups." Too many companies
can cite examples of being chastised by one branch of the agency for following recommendations issued by another. It may not
be possible to capture intra-agency alignment in the guidance document itself, but ensuring consistency in practice may be
the most critical factor in determining the success of the new guidance.
If the agency can achieve that, and also make revisions to address key industry concerns, it will truly usher in a new era
of process validation.
Laura Bush is the editor in chief of BioPharm International, firstname.lastname@example.org