The industry (including FDA) has been going through a learning curve to comply with every cGMP(current good manufacturing practice) requirement. However, this has been challenging to many as FDA has not consistently provided guidance that is either clear or uniform in enforcement. FDA has the authority to decide what constitutes adequate or acceptable compliance, and many well-intentioned companies have been left confused and puzzled, especially when they receive an unexpected 483 or warning letter.

A company is subject to FDA dietary supplement cGMP rule (21 CFR 111) when it manufactures, packages, labels, holds or distributes a dietary supplement product for sale in the United States, including foreign manufacturers. Recently, FDA has extended its reach beyond just manufacturers to include companies that entirely outsource production. These types of sellers (own-label companies) that hold and distribute dietary supplement products need to be compliant with the regulations concerning their operations, and be able to confirm their contract manufacturers are in compliance. FDA expects these own-label companies to have qualified their outsourced products and have sufficient evidence to demonstrate and show GMP compliance.

During an FDA inspection, the area of focus for Part 111 cGMP compliance can be quite wide ranging, typically taking several days to complete. The inspection will include a thorough inspection and review of facility, operations, components, quality control (QC), quality assurance (QA), laboratory (testing/records), standard operating procedures (SOPs) and written procedures, documentation/record-keeping, batch records, training records, supplier qualification, etc.

The recent focus of FDA audits has been adequate documentation; the documentation/records required by the Part 111 rule are quite extensive. Do not ignore the importance of written procedures, documentation and record-keeping responsibilities. Remember, if you set a procedure, specification or SOP in writing, you are expected to follow it, and if something is not documented, then it does not exist.

Recent FDA action shows dietary supplement firms that fail to correct deficiencies in their GMPs do so at their own risk. Several companies have now experienced product recalls, seizures, consent decrees and shut downs. And even a few had executives facing criminal court action. FDA is also warning dietary supplement manufacturers they may face felony charges if undeclared (spiking/adulterated) ingredients are found in their products.

Independent, third-party certifiers and auditors can effectively assist firms in evaluating a contract manufacturers GMP compliance, which can help in assessing (or mitigating) risk. Additionally, the frequency of re-qualification of suppliers via on-site facility audits, certificate of analysis (COA) verification, change control/notification, documentation reviews, past performance, etc., can also help mitigate risk.

Next: The Future

The Future

FDA is increasingly requesting or strongly suggesting having quality and manufacturing (supply) agreements in place between manufacturers and own-label sellers. These agreements are intended to define who is responsible for different issues or points.

A quality agreement is a legally binding agreement that is mutually negotiated and concluded between the quality departments of the manufacturer and their customer. It is intended to define, in a formalized manner, the responsibilities relative to quality tasks to ensure the manufacture and supply of safe products. A quality agreement is based on the quality procedures in place at both the manufacturer and its customer.

A manufacturing agreement (also known as a supply agreement) documents the legal and business relationship between the manufacturer and its customer. Quality agreements are usually designed to complement the manufacturing agreements.

Clear quality and manufacturing agreements define roles and responsibilities, so double work" is not being performed. If a quality agreement has been agreed upon, it is best to avoid using any quality provisions in the manufacturing agreement. These documents define which agreement governs, in case of a conflict. Both quality and legal departments should review both agreements to ensure their provisions are aligned together.

Robin Koon, executive vice-president at Best Formulations, has more than 25 years of pharmaceutical experience in clinical pharmacy, as a drug chain executive overseeing operations and managed-care, and in retail mass market.

Additional information about GMP compliance is available in the on-demand video "The FDA Speaks on GMP Compliance" on the SupplySide Store.

Next: Bonus: GMP Basics

GMP Basics

The dietary supplement GMPs are similar to those of drugs. For dietary supplement manufacturers, they include minimally the following points: