Let Me Qualify That for You

by Jim Lassiter

The Food and Drug Administration (FDA) issued a proposed rule concerning theestablishment of good manufacturing practices (GMPs) for dietary supplements onMarch 13, 2003. This proposed rule--six-plus years in development--contains ahost of issues the dietary supplement industry needs to pay attention to. Someof the issues are open and obvious while others are subtle yet no less onerousand odious.

Let's look at the matter of personnel qualifications, for example. There area couple of issues that will have a great impact businesses once the GMPs arefinalized. The first is a simple word change and the second is the matter ofissuing a regulation that cannot be adequately enforced.

The simple word change was from "or" to "and." The changein a conjunctive is often important in English grammar. The interesting thingabout this change is where the word change occurs. Historically, both indiscussions and in other GMP documents concerning the manufacture of differentclasses of goods, personnel requirements are identified. The wording for thisrequirement includes the phrase:

". . . qualified by a combination of education, training orexperience."

This allows for a broad approach in determining who is allowed to performwhat task while further allowing companies to make determinations as to whatqualifications from these choices apply to any particular position. With theissuance of the GMP proposal, FDA wishes to change the requirement to be:

". . . qualified by a combination of education, training andexperience."

The upshot of this new mandate is companies would need to consider carefullythe training and education aspects of personnel in their employ. FDA issufficiently concerned as to discuss the matter at great length within thepreamble to the proposed rule. The agency seems a bit ambivalent about thesubject. On the one hand:

". . . the proposed rule uses the conjunction 'and' because, whilesome might consider 'experience' to be a form of 'training,' most consider'experience' to be knowledge that a person gains over time as he or she becomesincreasingly familiar with a particular action or piece of equipment."[68 Federal Register, 49:12183]

While it is unclear who FDA interviewed to make the determination that"most" hold a particular definition, the fact remains there is clearrequirement that all three items be considered when making personneldeterminations. The training aspect is more interesting now since it isconjoined by the word "and" to experience. FDA attempts to assist inthis regard:

"Training, however, may not just include on-the-job training, but mayinclude some type of educational experience derived from attending classes orlectures or some other formal instruction on a particular subject."[Ibid.]

This appears to fold the matter back into the word "education."Regardless, companies are now required to carefully scrutinize and demonstrateto FDA upon inspection that the personnel are sufficiently qualified. FDA alsois asking companies make personnel records available to FDA inspectors to copyin order to determine if personnel were appropriately screened. This is thesubject of a whole different debate.

Regardless of the presentation of personnel records to FDA, the matter trulyrests with the change in conjunction. It is possible that a diligent FDAinspector may decide a staff member lacks the formal education to besufficiently qualified (which equates to "competent," according to FDAin its GMP preamble). Without the opportunity to use the combination of any twoof the three choices, people who have performed successfully for years in aposition could be removed from future performance based on the word of a companyoutsider.

Having qualified personnel in place is only the tip of the iceberg. Thesecond issue is more specific. Later in the proposed rule, companies aremandated to have an individual who is part of the quality control (QC) unit toperform the task of addressing "consumer complaints." Now, FDA wouldnot have us confuse the term "consumer complaints" with adverse eventreports (AERs), since that would require the issuance of another, differentregulation. No, consumer complaints are negative reports companies receive thatare the result of some manufacturing issue. Discussion of the whole concept ofconsumer complaints is also the subject of a very different article. The issuehere is who gets to decide if the report is a consumer complaint or an AER?

"A qualified person." [Proposed 21CFR Section 111.95(a)]

Manufacturers' QC units must investigate all such complaints and document theresults. Thus, it is logical to have the person who receives the complaint bethe same person who makes the determination as to whether the complaint ismanufacturing-related or product-related. This logic is derived from FDA'sassertion that there is no need to significantly increase staff in order tocomply with this proposed rule. As it is written, the GMPs require a company tohave one person responsible for performing the sorting and investigation. Thelevel of education, training and experience for this person must be high, sincehe is likely to receive consumer complaints ranging from broken tablets to thepresence of mycotoxin in the product. Just how the average consumer of dietarysupplements is going to determine the presence of mycotoxin in her productremains to be seen, but FDA specifically identifies it as a likely consumercomplaint. Nonetheless, the person who takes the complaint has to sort throughwhether it fits into the consumer complaint bucket or the AER bucket. This isnot a simple task.

When asked if FDA had given any consideration as to what the qualificationsout of the combination of education, training and experience might be toadequately perform such a task, the answer was obvious and anticipated: FDAintends to issue guidance documents and other materials that would cover thisaspect at some future date. Thus, when the final rule goes into effect therewill be no tool for enforcement of this aspect since the determination of whatqualifications are necessary won't be defined.

The implementation of a rule that is not enforceable speaks volumes aboutwhat FDA is really trying to accomplish. In more than one instance, FDA isattempting to leverage additional rulemaking into this single regulationconcerning the manufacture, packaging, holding and distribution of dietarysupplements. In this case, FDA is attempting to fit what amounts to AERregulations into a document that is supposed to cover the making of product.This effort specifically belongs elsewhere.

The concept of having a valid AER system for dietary supplements is sound andsupportable. Attempting to fit it in with regulations concerning the manufactureof dietary supplements is not. Industry should comment on this matter whileinquiring as to how FDA intends to determine what qualifications from the poolof education, training and experience are sufficient to determine competence.Manufacturers would be surrendering the right to determine the competence ofemployees to FDA inspectors since the inspectors would be charged with assessingthe qualifications. Just keep those personnel records handy though, since FDAwants to see them, copy them and take them out of your facility.

Jim Lassiter has more than 25 years of experience in regulatory affairsand is currently director of consulting and regulatory services at ChromaDexInc., a global provider of high purity reference standards and research,regulatory and product consulting services. Lassiter can be contacted at [email protected].