How do you establish a reference standard for release of your first GMP lot?

There are some different approaches depending on situation, but here is one general approach that many people use:

* Preclinical material that was used to support IND-enabling tox studies is characterized and used as an interim reference standard. This doesn't have to be manufactured by GMP; could even be research grade material. Characterization tests should be performed and include methods to determine content, primary structure, bioactivity, tentative release tests, etc. Important to have a good handle on content from this standard (i.e., for a protein drug you might look at total protein content by elemental analysis.) Potency units could be defined here as well.
* Use this interim reference standard as a comparator to release your initial GMP material.
* Use material from the first GMP campaign to create a primary reference standard. Again, this material will need to be subjected to a panel of characterization tests in addition to the release tests (typically at least or more in-depth than the characterization done on initial reference standard).
* The primary reference standard supercedes the interim reference standard after it is created and qualified. This typically happens during or immediately after the first GMP campaign.

From an assay validation standpoint, you will always have to start with some initial standard (typically, the interim reference standard, which is all you may have available before GMP manufacture), and you can get into some circularity with accuracy (i.e., assaying the standard against itself). So for your initial standard and assay validation you rely somewhat on orthogonal methods of analysis. Also, as per ICH Q2, accuracy can be inferred from precision, linearity and specificity.

By Lori Nixon, RMC Pharmaceutical Solutions, Inc.

Find out more at www.rmcpharma.com

RMC Pharma is 5!

RMC Pharmaceutical Solutions celebrated its 5 year anniversary today. We have grown from a couple people looking for their first consulting opportunity each in our spare bedrooms or kitchen tables to an integrated team capable of taking almost any health care product from conception to commercialization. Today, we are 10 regular employees, with 6000 square feet of office and lab space in Longmont, CO. We've helped 40 clients on three continents with projects ranging from producing pre-clinical proof of concept materials to overseeing pre-approval inspections and quality audits from the biggest pharmaceutical companies in the world. Our capabilities have expanded beyond those of a typical consulting group, to include specialized software such as Slimstat, Minitab, Omnisign, SuperPro and DPL decision modeling software, to laboratory capabilities, including zetasizing, HPLC and Akta based process development. Still, our most valuable resource is our people and the relationships that we've built in our five years. The experience has been very rewarding for me personally, and I hope that my partners, associates and clients have benefited from it as I have.

RMC Expands Board of Directors

FOR IMMEDIATE RELEASE May 04, 2009
Contact: Kathy Rudge
RMC Pharmaceutical Solutions, Incorporated
info@rmcpharma.com
303 776 5200

Longmont, CO. Shareholders of RMC Pharmaceuticals Solutions, Inc. recently approved the expansion of its Board of Directors and appointed Dr. Mark Young and W. Todd Myers as additional members to the Board. The move brings outside directors to the company’s leadership, and adds invaluable expertise and experience as RMC Pharmaceuticals, Inc. continues to build its brand and business. In a related action, the shareholders unanimously elected Dr. Scott Rudge to the position of Chairman of the Board of Directors.
“I’m pleased to welcome Dr. Young and Mr. Myers to our leadership team at RMC Pharmaceutical Solutions,” said Dr. Rudge. “These gentlemen are very highly regarded in the biotechnology and entrepreneurial pharmaceutical business space. Their advice and guidance will help us to leverage and promote our “Bolt-on CMC” services as we continue to grow and expand our capabilities.” Timothy Joy, RMC Pharmaceutical Solutions’ President and CEO said, “Our collaborations with Mark and Todd have been very positive over the years. It made sense to formalize these relationships and take full advantage of their talents. Our clients will derive extended benefits from their addition to our team.”
Dr. Young is an experienced executive specializing in process development and manufacturing of biopharmaceutical products. He started his career as a process development scientist with large international pharmaceutical companies (Hoffmann LaRoche and Upjohn), and then joined the biotech industry in 1985. He has served as a Senior Vice President of three biotech companies (Synergen, Protein Design Labs, ZymoGenetics) and as Chief Operating Officer of Biomira. Dr. Young received degrees at the University of Nebraska, Columbia University, and The University of Michigan, all in Chemical Engineering. He is currently a consultant, specializing in bioprocess development and manufacturing issues.
W. Todd Myers, C.P.A., is a veteran financial executive with significant management experience in both public and private drug discovery/development companies. Mr. Myers is currently a member of the Board of Advisors of BioLaurus, Inc., a contract research organization specializing in cutting edge molecular imaging and high content analysis services for the biotechnology and pharmaceutical industry. He also provides coaching and guidance to start-up life science companies as an Entrepreneur-in-Residence at CONNECT, a non-profit organization dedicated to creating and sustaining the growth of innovative technology and life science businesses in San Diego. Most recently, Mr. Myers was the Chief Financial Officer of SGX Pharmaceuticals, Inc., a publicly-traded biotechnology company focused on the discovery, development and commercialization of innovative cancer therapeutics, and was instrumental in the sale of SGX to Eli Lilly & Company at a premium of 119% to its then-current trading price. Prior to SGX, as the Director of Finance at CombiChem, Inc, a publicly-traded computational drug discovery company, Mr. Myers managed all financial operations and was the senior financial representative on the team responsible for the sale of the company to DuPont Pharmaceuticals. He was also the Chief Financial Officer of FeRx Incorporated, a privately-held, clinical stage company dedicated to the development of oncology products, and has held positions with Premier Inc. and with Ernst & Young LLP. Mr. Myers received his B.S. in Accounting from the University of Illinois.

About RMC Pharmaceutical Solutions, Inc.
RMC Pharmaceutical Solutions, Inc. is a privately-held provider of expert services to the pharmaceutical, biotechnology, medical device and food industries. The company was founded by Timothy Joy and Scott Rudge in 2004 to provide comprehensive services to companies developing products for the health care industry. Since its inception, RMC Pharmaceutical Solutions has served more than 50 different clients in North America, Europe and Asia. More recently, RMC has rolled out its “Bolt-on CMC” service offering. Bolt-on CMC support provides an experienced integrated team to support Chemistry, Manufacturing and Control areas such as process, analytical and formulation development; quality control/quality assurance; and oversight of GMP manufacturing. As part of this service, clients can access both the considerable expertise of the RMC team, as well as physical assets, such as an analytical and process development laboratory; document management and storage; and advanced software tools. For more information, please visit www.rmcpharma.com.