Supplement GMPs Focus On Process Controls Urged By CHPA, NNFA

Dietary supplement good manufacturing practices should rely more on improved process controls rather than exhaustive testing standards, CHPA and NNFA agree in comments submitted to FDA.

"The requirement to test every batch of finished product is overly burdensome, costly and not needed if the process is properly validated," the Consumer Healthcare Product Association asserts in Aug. 8 comments on FDA's proposed regulation to establish supplement GMPs.

The trade group argues for a "principle-based approach," in which "industry would be responsible for developing and defining written procedures for each stage of the process...and a written plan for qualifying this process."

This type of approach "focuses on the critical quality steps in the process and would be a more effective and efficient system for testing," CHPA says.

The National Nutritional Foods Association expresses similar sentiments in comments submitted Aug. 7. It contends that "an effective process control system reduces the need for the type of exhaustive and duplicative finished product testing scheme set forth in the proposal and justifies the use of a more flexible testing scheme."

A system that "strikes a more appropriate balance" between process controls and testing is more cost efficient and could reduce GMPs financial burden on industry, NNFA stresses.

The group focuses on the process/testing balance and increased flexibility for companies in its recommended changes to the proposed rule, which are based on the objective to reduce the cost of implementation "without compromising the legitimate goals of [current] GMPs."

The comment period for FDA's dietary supplement good manufacturing practices proposed rule closed Aug. 11. The proposal was issued in March.

Testing obligations of different links in the supply/manufacturing chain should be clarified, NNFA says, urging that the final reg should "make it clear that testing obligations fall primarily on the raw material supplier and the manufacturer of the finished product."

The scope of the supplement GMPs should include raw material suppliers and foreign firms, it recommends. NNFA notes that some suppliers have argued the regs should not apply to them, because "as suppliers of food and dietary supplement ingredients around the world it may not be feasible to make significant changes in their process to supply to the dietary supplement industry in the U.S."

The association argues that such suppliers would encounter less burden if FDA allows greater flexibility, "ensures a level playing field...by enforcing the final rule against foreign suppliers," and works with foreign regulators on international standards and enforcement.

NNFA suggests that FDA's own burden in implementing the GMPs could be reduced by allowing the use of qualified third-party facility inspectors.

Certification inspections conducted by accredited inspectors would both help reduce the costs to the government and "result in quicker widespread compliance," the group adds.

Use of third-party inspectors would save money in an era when obtaining additional funds from Congress "will be difficult, if not impossible to achieve," it says.

CHPA and NNFA strike a shared theme of calling for greater flexibilty throughout the rule. In addition to the area of testing, companies "need flexibility to design manufacturing facilities to suit their operation," NNFA stated, remarking, for example, that "ceiling surface is irrelevant to manufacturing processes which are completely enclosed."

CHPA suggests companies be afforded flexibility in the area of "generally recognized as safe" recognition for ingredients. Firms should be permitted to use as surrogates for GRAS listing a listing in the United States Pharmacopoeia, Food Chemical Codex, or American Pharmaceutical Association's Handbook of Pharmaceutical Excipients.

The two trade groups concur that some provisions in the proposed rule reflect or even exceed drug GMPs, rather than being modeled on food GMPs, as mandated by Congress. For example, CHPA contends that the rule's record retention requirements, which call for firms to retain written records for three years beyond the date of manufacture of the last product batch associated with the record, are too onerous.

NNFA suggests this section be modified to give companies the option of retaining records for one year past product expiration date.

Abbott Labs, in July 23 comments, recommends that some GMP language should be consistent with existing drug manufacturing terminology in appropriate areas.

The firm cites several instances where language should be modified for consistency with drug GMP terminology.

For example, FDA proposes that a quality control unit must not "approve and release for distribution any batch of dietary ingredient or dietary supplement that does not meet all specifications." There also is a requirement for evaluation and disposition if "a batch deviates" from specifications.

Abbott says this language "does not allow for investigation into the failure" and should be "reworded to be consistent with drug regulations."

The reworded section would read: "Any batch of dietary ingredient or dietary supplement shall be reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Any unexplained discrepancy, or the failure of a batch, or any of its components to meet any of its specifications shall be thoroughly investigated."

Abbott also suggests reconsideration of the proposal to require manufacturers to reserve samples for three years from the date of manufacture.

"We agree with the collection of samples for the purposes of testing, however to require samples from components or dietary ingredients to be maintained as reserve samples is an excessive requirement creating a burden for storage of materials and with no value added."

When applicable, the proposed GMPs should be specific to the ingredient source, Abbott says, suggesting that ingredients that are plant- or animal-derived or chemically synthesized may have different criteria for evaluating quality and purity.

For example, "testing for microbial load for botanicals must be tested each time, others can be tested as appropriate."

Regarding industry compliance costs, both CHPA and NNFA maintain that FDA significantly underestimated the cost burden of the proposed GMP regs.

The proposal "appears to dramatically underestimate the financial impact on firms - large, small, or in between - of the extensive requirements envisioned," CHPA states.

"We estimate initial costs to industry at $675 mil. - five times greater than FDA's estimate," NNFA says, "and that the ongoing costs will be nearly $1.2 bil. per year - 15 times greater than FDA's estimate." NNFA bases its estimates on a survey of members.

"Most adversely affected will be very small and small" companies, NNFA notes. The agency defined small companies as those with fewer than 500 employees, and very small as firms with fewer than 20 employees (¹ (Also see "FTC's Proposed Green Guides Point In Different Directions To AHPA, NPA" - Pink Sheet, 10 Jan, 2011.), p. 7).

"We believe 50 to 60% of small or very small companies could or will go out of business," NNFA continues.

The group also estimates product prices could increase by approximately 35% to 50% due to GMP compliance costs.

FDA's underestimate is due primarily to miscalculations of testing costs, NNFA states. According to the comments, the agency underestimated the number of analytical tests conducted, the numbers of batches produced, and total laboratory and testing costs.

For example, FDA estimated that batches produced annually by small establishments total 554, while NNFA's survey found "a mean of 1,600 batches are produced by small companies."

Further, FDA estimated average cost per test at $60, while NNFA found an average of $302, five times FDA's figure.

NNFA maintains that its recommended rule changes "will ease the economic impact and unnecessary burdens of the proposed rule to an acceptable level."

NNFA does voice support for FDA's proposed compliance timeline, which would allow very small and small firms three years for compliance "as long as the final rule includes appropriate flexibility and a balanced and achievable testing regime."