FDA publishes good manufacturing practices guidance for small businesses making dietary supplements nearly six months after the deadline for compliance with the GMP final rule.

The agency's completion of its long-awaited GMP small entity compliance guide likely marks an end to a safety net FDA allowed industry during the three-year implementation of the final rule. FDA announced it would provide the guidance after it published the GMP final rule in June 2007.

The guidance made available in a Dec. 16 Federal Register notice could help nudge struggling firms over the GMP hump, stakeholders say.

Supplement GMPs Through The Years

June 2007: FDA publishes GMP final rule
Compliance deadlines:
- o June 2008: Large firms
- o June 2009: Medium-sized firms
- o June 2010: Small firms
December 2010: FDA publishes supplement GMPs small entity compliance guide

"This is the CliffsNotes version of the rather long and difficult-to-read preface to the GMP reg and the reg itself," said Loren Israelsen, executive director of the United Natural Products Alliance.

The Center for Food Safety and Applied Nutrition laid out the guidance in a question-and-answer format to illuminate certain portions of 21 CFR 111, the regulation FDA finalized in the GMP rule.

For example, the guide walks a manager step-by-step through determining whether a sick employee should be allowed to work, how to evaluate the water supply used in manufacturing and what product specifications must be established.

"Assuming small companies actually read it – now that has to happen first – it gets rid of some ignorance in these areas as an excuse," said Council for Responsible Nutrition executive Andrew Shao.

A Helpful Reference

The guidance offers select clarification regarding the GMP final rule, such as specifying when certain components of 21 CFR 110 – the GMP rule for foods – apply to supplement manufacturers.

Shao, CRN's senior VP of scientific and regulatory affairs, said FDA's guidance appears more explicit about when the agency will or will not exercise enforcement discretion with complementary and alternative medicine practitioners selling herbals and other supplements.

While the guidance should prove a helpful reference, it does not alleviate problems for small companies with little capital to invest in GMPs, Shao said.

"This is short and simplified, but if you look … through all these subparts, it's still a lot of stuff to do, and very resource-intensive."

Perplexity Persists, Emord Says

GMP compliance came first for supplement manufacturers with 500 or more employees, in June 2008, and firms with more than 20 employees had a June 2009 deadline.

As the largest group of firms – those with fewer than 20 full-time employees – became subject to the regulation in June 2010, stakeholders said many struggled to grasp the enormity of implementation (Also see "As Supplement GMP Implementation Hits Zero Hour, Small Firms Still Struggle" - Pink Sheet, 28 June, 2010.).

Beyond resource issues, firms face too many ambiguities in the GMPs that FDA's guidance fails to clear up, according to attorney and frequent agency critic Jonathan Emord.

"Supplement companies are perplexed by the absence of any clear guidance concerning what will or will not be deemed satisfactory compliance," said Emord, of Emord & Associates in Clifton, Va., in an e-mail.

He refers to a facility's number of hand-washing stations and the background of a quality control supervisor as just a few of the many unknowns inherent in the GMP rule.

"The company does its best but cannot know if what it has done complies until the FDA inspector arrives and says, good enough or not good enough," Emord said.

In November 2009, an FDA official said the release of the small entity compliance guide was on hold following a lawsuit Emord filed against the agency, alleging the GMP rule was an unconstitutionally vague law (Also see "FDA's Frankos Grades GMP Complaint Recordkeeping "Needs Improvement"" - Pink Sheet, 23 November, 2009.).

Emord said the suit is briefed fully and pending. He expects a decision from the U.S. District Court for the District of Columbia within six months.

GMP Warnings Offer Additional Guidance

FDA Principal Deputy Commissioner Josh Sharfstein said in October about one-third of the agency's 90 supplement GMP inspections up to that point found major deviations (Also see "One-Third Of Supplement GMP Inspections Reveal "Serious Problems" - FDA" - Pink Sheet, 11 October, 2010.).

Although Sharfstein expressed a willingness to clarify to industry exactly what FDA wants to see, the agency is ramping up inspections, planning more than 400 in fiscal 2011.

For supplement makers yet to play host to an FDA inspector, the agency's growing cache of GMP warning letters is instructive and revealing.

On Nov. 8, FDA issued a warning to Soma Labs in Middlesex, N.J., detailing the firm's failure to establish product specifications and set up a sampling plan for testing finished product batches.

The agency produced another laundry list of its GMP concerns with a Nov. 10 warning letter to Kabco Pharmaceuticals. FDA alleged the Amityville, N.Y.-based contract manufacturer failed to verify the identities of dietary ingredients, omitted information from its batch production records and failed to adequately qualify ingredient suppliers.

Supplier Qualification Still Vague

Much like the GMP rule itself, FDA's small entity guidance does not outline steps firms should take in qualifying ingredient suppliers.

"I would've liked to have seen them emphasize that much more," said Shao, who hopes to shine a light on the black box of supplier qualification via the Standardized Information on Dietary Ingredients working group.

Despite the recent departure of two of its five founding trade associations, the SIDI coalition continues drafting supplier qualification guidelines and expects to launch a centralized website soon (Also see "SIDI Group Split Reflects Supplement Industry Disparate Interests" - Pink Sheet, 25 October, 2010.).

By Dan Schiff

FDA Publishes Small Entity Guide For Supplement GMPs

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