Bulk Pharmaceuticals Task Force
- Introduction to BPTF: Drug Product and Drug Substance Supply Chain Safety
- Quality Agreement Template for API and API Intermediate Manufacturers
- Establishment and Product Listing Registration – FDA Electronic Submission Requirements
- Process Validation – FDA Draft Guidance for Industry
- U.S. Pharmacopeia – Revisions to Guidance and Standards
- BPTF Members
- Meeting Presentations
For more information or updates, please contact
In recent years there has been much concern over consumer food and drug safety, especially for products entering the U.S. market from foreign producers. SOCMA’s Bulk Pharmaceuticals Task Force (BPTF) has been active since 2006 in advocating for increased resources for the Food and Drug Administration (FDA) in order to conduct more good manufacturing practices (GMP) inspections of foreign drug ingredient manufacturers.
While the FDA conducts regular unannounced GMP inspections every two years for U.S. facilities, many foreign facilities are rarely or never inspected for general GMP compliance unless there is cause to do so. While the drug industry takes steps to ensure patient safety and security of the drug supply chain, industry self-regulation is not enough. The FDA has the authority to regulate any and all drug products and drug substances that enter the U.S. supply chain, but does not have the resources to appropriately staff a foreign inspectorate or maintain the necessary technology to track registered firms. Disproportionate regulatory oversight of drug firms supplying the U.S. market amounts to an unfair business advantage to foreign firms who might be enticed into sacrificing drug quality for market advantage.
SOCMA’s BPTF has been working closely with members of Congress, FDA staff, and industry leaders to address FDA’s lacking resources and the need for increased security for the U.S. drug supply chain. SOCMA is a strong advocate of increasing the number of FDA inspectors and foreign inspections through the implementation of an inspections fee schedule for drug and drug ingredient importers as needed to offset the costs to conduct such inspections. We also endorse the idea of certified third-party inspectors and mutual acceptance programs with other foreign governments to offset the needs of the FDA.
SOCMA is actively engaged in advocacy activities and monitoring legislative developments on Capitol Hill.
SOCMA’s Citizen Petition requesting FDA take action to mitigate risks to public health associated with the use of drugs manufactured or processed at foreign facilities.
Joint Position Statement between SOCMA and the European Fine Chemicals Group “Uneven Enforcement Leads to Sub-par Drugs and National Security Risk.”
SOCMA’s BPTF has developed a quality agreement template for use by the drug and custom chemical industries. The template is customized for APIs and API intermediates and can be used by manufacturers supplying customers or users of APIs and API intermediates with suppliers. The template has been developed in response to demand from the industry for guidance on industry ‘best practices’ on the development and negotiation of quality agreements.
Quality agreements are established between drug manufacturers outsourcing APIs and API intermediates from suppliers in order to ensure drug quality and compliance with current good manufacturing practices (cGMPs). Often times it can be a difficult and lengthy process when negotiating quality agreements, especially when negotiated in tandem with a supply agreement. The quality agreement template serves as a tool for helping parties on both sides of the negotiating table navigate the process in a more timely and efficient manner.
In July 2008, the FDA announced that it would no longer accept paper submissions for registrations of drug establishments and drug product listings. As of June 1, 2009, companies subject to 21 CFR Part 207 (Sec. 510 of 21 USC 360) must now submit annual FDA registrations and updates, due by December 31, by creating Structured Product Labeling (SPL) files for submission through FDA’s Electronic Submissions Gateway (ESG). In order to do this, companies must download XForms software from GlobalSubmit to create the SPL files. Drug ingredient manufacturers, re-packagers, and re-labelers are encouraged to begin the process of learning the new electronic submissions system now in order to avoid risking late submissions and possible FDA enforcement. The FDA is providing technical assistance through a series of free training webinars being offered over two module courses. The training modules are organized as follows:
- Module One: SPL Overview, NDC Labeler Code, Domestic & Foreign Establishment Registration (2 hours)
- Module Two: Content of Labeling, Product Data Elements & Submitting SPL Document via FDA Gateway (2 hours)
The new training module format will begin September 10. The FDA plans to host a training course specifically for bulk ingredient/bulk product manufacturers sometime in the mid-October timeframe. Other resources available include:
- FDA Structured Product Labeling Resources web page – for technical assistance on creating electronic submissions
- FDA Drug Registration and Listing and web page – for regulatory information on drug registration and product listing policy
- SLP Work Group Wikispace – a one-stop shop for updates on SPL technical information and a discussion support group
- SPL Release Four Training Sessions Schedule – for FDA training sessions updates and webinar registration information
SOCMA is working with industry and the FDA to help facilitate technical and regulatory assistance for companies encountering problems with the new system.
In November 2008, the FDA published a DRAFT guidance for industry entitled, “Process Validation: General Principles and Practices” for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients. This guidance represents FDA’s current thinking on principles and approaches to validating a manufacturing process and is intended to promote modern manufacturing principles, process improvement, innovation, and sound science.
The process validation guidance document was available for review and comment for 90 days after publication of the draft at which time SOCMA’s BPTF submitted comments. SOCMA supports the FDA’s emphasis on the use of statistical methods to calculate process variability and its directive to align process validation with the concept of maintaining the process in a state of control throughout the product lifecycle. However the BPTF expressed concerns regarding some of the specific recommendations expressed in the text of the guidance document and in other areas where the language is too vague and could lead to different and conflicting opinions being drawn by industry, CMC reviewers, and the FDA’s inspectorate.
The process validation guidance document could remain in draft form for an indefinite period of time until FDA has had a chance to review all comments received by industry for consideration in any future revisions. SOCMA is actively monitoring the practical application of the guidance within the drug ingredient manufacturing industry while watching for any other developments within the FDA.
In August 2008, FDA issued a DRAFT guidance for industry entitled, “Residual Solvents in Drug Products Marketed in the United States” to assist manufacturers in responding to the issuance of USP’s revised General Chapter <467> “Residual Solvents” test standards for the control of residual solvents in drug products which went into effect July 1, 2008. The purpose of the guidance document is to establish FDA’s expectations for complying with the new standard along with 21 CFR 314.70 and the Federal Food, Drug and Cosmetic Act.
SOCMA submitted comments on the draft guidance and collaborated on an additional set of comments submitted by an industry coalition developed specifically to respond to FDA’s guidance. Although the implementation of USP <467> had been anticipated by industry for a few years prior to the issuance of the final standard, manufacturers encountered many problems including deficiency letters from the FDA due to a lack of mutual understanding between the FDA and industry on how USP <467> should be applied. As a result, a FDA-industry dialogue was established in order to seek clarity and resolution to the problems that led to the deficiency letters. Those conversations were recorded and provided to the public through the respective members of the coalition.
While the bulk of the issues seem to have been addressed, the dialogue with the FDA remains open while SOCMA and other trade associations continue to monitor the practical application of USP <467>.
In October 2008, the U.S. Pharmacopeia announced plans to revise USP General Chapter <231> “Heavy Metals” in order to conform to ICH Q3A “Impurities in Drug Substances.” The test procedures and methods for the control of toxic metal impurities in pharmaceutical products currently described in USP <231> are outdated and lack the sensitivity to properly monitor the levels of these metals. The USP is proposing a new General Chapter to address inorganic impurities in drug and dietary supplement products which would contain more modern analytical methods and limits for selected metals.
Upon the development of a new General Chapter for metal impurities, it is likely the FDA will develop and publish a draft guidance document describing its expectations for complying with the new standard, much in the same way the Agency issued its draft guidance for residual solvents. In order to avoid the confusion encountered when the FDA issued its guidance on residual solvents, SOCMA’s BPTF will be fully engaged in the stakeholder process for the development of the heavy metals standard and subsequent FDA guidance. We will also work through an industry coalition made up of other drug industry stakeholders in order to ensure an ongoing dialogue with USP and FDA officials through the development process.
- Albemarle Corporation
- AMPAC Fine Chemicals
- Ash Stevens
- BASF Corporation
- Cambridge Major Laboratories
- Chattem Chemicals, Inc.
- Copperhead Chemical Company
- Polypeptide Laboratories
Click on the link below to download the presentation.