The US Food and Drug Administration announced plans to revise CGMP regulations.

By: Angie Drakulich. This story is courtesy of ePT–the Electronic Newsletter of Pharmaceutical Technology.

The US Food and Drug Administration announced plans to revise the current good manufacturing practice (GMP) regulations at a conference held jointly by the agency and Xavier University in Cincinati, Ohio, June 13-16. Brian Hasselbalch, representing the Office of Compliance’s Division for Manufacturing and Drug Product Quality within FDA’s Center for Drug Evaluation and Research, was speaking as part of the first joint annual Global Outsourcing Conference at the school.

According to Haselbalch’s presentation, which is available on the Xavier website, a draft of new CGMP regulations focusing on component controls is expected before the year’s end. Potential revisions include requiring pharmaceutical manufacturers to physically audit their suppliers (i.e., no more paper audits), test containers in each shipment received, implement tamper-evident packaging and security features, notify FDA of contaminated shipments and lots, and to use only those components recognized as safe for their intended use or listed in an already approved application.

In addition to increased enforcement and information-sharing, FDA also plans to play a stronger “guiding role” in corporate responsibility. Hasselbalch offered some recent guidance documents as examples of FDA’s role in encouraging corporate responsibility: process validation, pharmaceutical quality systems, and testing of glycerin for diethylene glycol. It seems the agency will go even further by issuing a second phase of revised CGMP regulations that focus specifically on corporate responsibility. These revisions might include requirements that management assures compliance, performs self-inspections, evaluates and investigates problems, implements change control, and documents training and effectiveness, according to the presentation.

What’s behind the proposed changes? Hasselbalch’s presentation noted growing gaps in quality control caused by factors such as globalization, new technologies and processes, distribution challenges, and increased outsourcing of production. Between 2001 and 2007, he pointed out, the number of products manufactured outside the United States and the number of manufacturing sites abroad doubled. Some of the new products being imported into the US come from countries with “less developed regulatory systems,” according to the presentation. Along with these more complex supply chains, there has been an increase in pharmaceutical cargo thefts and in drug counterfeiting. More preventative measures are therefore needed.

Industry will have a chance to comment on the proposed revisions once they are issued.

Note: On June 24, 2010, an FDA press officer clarified that the agency is “considering requiring finished pharmaceutical manufacturers to conduct on-site audits of the original manufacturers for components (i.e., ingredients) that they use in manufacturing.”

The End.

Digest Break – Quotes To Make You Think.

“When everything seems to be going against you, remember that the airplane takes off against the wind, not with it.” — Henry Ford

“Make crime pay. Become a Lawyer.” — Will Rogers

“Few things are more satisfying than seeing your own children have teenagers of their own.” — Doug Larson

Question. Do I have to notify FDA before I start to use covert markings or materials in my labels?

Answer. The current labeling requirements for pharmaceuticals are part of 21 CFR Parts 210 and 211 – Current Good Manufacturing Practice In Manufacturing, Processing, Packing or Holding of Drugs; General and Current Good Manufacturing Practice For Finished Pharmaceuticals. These are the cGMP’s (Current Good Manufacturing Practices).

The cGMP’s deal mainly with overt labeling features. These include, but are not limited to:
Written procedures designed to assure that correct labels, labeling, and packaging materials are used for drug products. These written procedures must be followed. These procedures incorporate the following features:
(a) Prevention of mixups and cross-contamination by physical or spatial separation from operations on other drug products.
(b) Identification and handling of filled drug product containers that are set aside and held in unlabeled condition for future labeling operations to preclude mislabeling of individual containers, lots, or portions of lots. Identification need not be applied to each individual container but shall be sufficient to determine name, strength, quantity of contents, and lot or control number of each container.
(c) Identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch.
(d) Examination of packaging and labeling materials for suitability and correctness before packaging operations, and documentation of such examination in the batch production record.
(e) Inspection of the packaging and labeling facilities immediately before use to assure that all drug products have been removed from previous operations. Inspection shall also be made to assure that packaging and labeling materials not suitable for subsequent operations have been removed. Results of inspection shall be documented in the batch production records.

As for pharmaceuticals and tamper-evident packaging: Each manufacturer who packages an OTC drug product (except a dermatological, dentifrice, insulin, or lozenge product) for retail sale must package the product in a tamper-evident package, if this product is accessible to the public while held for sale. A tamper-evident package is one having one or more indicators or barriers to entry which, if breached or missing, can reasonably be expected to provide visible evidence to consumers that tampering has occurred. To reduce the likelihood of successful tampering and to increase the likelihood that consumers will discover if a product has been tampered with, the package is required to be distinctive by design or by the use of one or more indicators or barriers to entry that employ an identifying characteristic (e.g., a pattern, name, registered trademark, logo, or picture).

The term “distinctive by design” means the packaging cannot be duplicated with commonly available materials or through commonly available processes.

Photos Below: “Distinctive By Design” examples from August 13, 1776. This New York ten dollar bill had a distinctive pattern on the back. Please note the penalty that was printed on the bill: “Tis Death To Counterfeit”.

A tamper-evident package may involve an immediate-container and closure system or secondary-container or carton system or any combination of systems intended to provide a visual indication of package integrity. The tamper-evident feature must be designed to and must remain intact when handled in a reasonable manner during manufacture, distribution, and retail display.

Covert features lack the standardization that you would find in cGMP’s. To my knowledge, the FDA supports covert features, but there are no standards that are mandated. This is why “The International Organization of Standardization” (ISO) has approved the creation of a new Technical Committee (TC) on fraud countermeasures and controls to help address development of standards related to combating fraud. The TC, proposed by the American National Standards Institute (ANSI) in conjunction with the North American Security Products Organization (NASPO), focuses on the development of standards in the areas of brand and intellectual property protection, identity management, and financial fraud.

The proposal, identified as ISO/TS/P 206, hopes to bring together fraud experts, law enforcement, government agencies, criminologists, brand owners, and solution providers to develop relevant security standards for the use of private industries and governments worldwide. ISO recognition and support from other international standards organizations will help to counter the rising financial and social cost of worldwide fraud activity.
The new committee provides a framework to engage international fraud experts with existing ISO technical committees to create solutions to complex issues. Standards will affect parties concerned with brand protection, intellectual property, drug counterfeiting, supply chains for products of value, authentication of goods, food supply chains, identity credentials, identity management, identity theft, customs and immigration enforcement, and financial fraud. Although the scope may appear broad, it effectively addresses the wide variety of fraud throughout industry segments.

So, for now, the FDA is concerned with 21 CFR 210 and 211. These standards do not encompass covert features.

Notable & Quotable: “Your true value depends entirely on what you are compared with.” — Bob Wells